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April 8, 2021
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https://www.sciencedaily.com/releases/2021/04/210408152324.htm
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The tuberculosis pathogen releases its toxin by a novel protein transport system
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Six years ago, Michael Niederweis, Ph.D., described the first toxin ever found for the deadly pathogen Mycobacterium tuberculosis. This toxin, tuberculosis necrotizing toxin, or TNT, became the founding member of a novel class of previously unrecognized toxins present in more than 600 bacterial and fungal species, as determined by protein sequence similarity. The toxin is released as M. tuberculosis bacteria survive and grow inside their human macrophage host, killing the macrophage and allowing the escape and spread of the bacteria.
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For 132 years, the lack of an identified toxin in M. tuberculosis had contrasted with nearly all other pathogenic bacteria whose toxins contribute to illness or death. M. tuberculosis infects 9 million people a year and kills more than 1 million.Now, in another groundbreaking work, the University of Alabama at Birmingham researcher and colleagues describe how two small ESX proteins made by the M. tuberculosis bacteria mediate secretion of TNT by pore formation in the membranes that envelop the bacteria. This finding may have broad application because a distinctive three-amino acid motif found on EsxE and EsxF -- tryptophan/any-amino-acid/glycine, known in shorthand as WXG -- is also found on many other small mycobacterium proteins and on the large WXG100 superfamily of bacterial proteins that resemble EsxE and EsxF."Here, we show for the first time that small Esx proteins of the WXG100 family have an important molecular function inside the Mtb cell by mediating toxin secretion," said Niederweis, a professor in the UAB Department of Microbiology. "Our results suggest a dynamic mechanism of pore formation by small Esx proteins that might be applicable to other members of the large WXG100 protein family. Thus, our study not only represents a major advancement in our understanding of secretion of TNT and likely of other proteins in M. tuberculosis, but also describes a biological function for Esx-paralogs in M. tuberculosis and their homologs in the large WXG100 protein family in Gram-positive bacteria."TNT is one of two domains in the M. tuberculosis outer membrane protein CpnT; activity of the TNT domain of CpnT in the cytosol of the macrophage induces macrophage death by hydrolyzing NAD+. M. tuberculosis has an inner membrane and an outer membrane, and a protein needs to get through each layer to be secreted outside of the bacterium. How CpnT gets to the outer membrane was unknown.EsxE and EsxF are part of the same gene segment as CpnT, and the UAB researchers hypothesized that the two small proteins might be involved in secretion of the toxin.By creating different strains that lacked either EsxE or EsxF, they showed that both proteins were necessary for the translocation of CpnT to the cell surface of M. tuberculosis and for the secretion of TNT into the cytosol of macrophages infected with M. tuberculosis. Furthermore, EsxE and EsxF are surface-accessible proteins on M. tuberculosis as a membrane-associated complex.To learn more about the mechanism of that translocation, the UAB team made mutants of each Esx protein, where the tryptophan amino acid of the single WXG motif on each protein was replaced by the amino acid alanine. The mutants showed that an intact WXG motif on EsxE and on EsxF were required for efficient CpnT translocation to the outer membrane of M. tuberculosis and subsequent TNT secretion into the cytosol of infected macrophages.Purification of the water-soluble EsxE and EsxF proteins showed they formed EsxE-EsxF dimers, and five of these dimers assembled into star-shaped structures, as viewed by electron microscopy. Each was about 10 nanometers across, with a 3-nanometer central pore.Experiments with planar lipid bilayers were key to understanding the molecular function of EsxE-EsxF, as they showed that the EsxE-EsxF pores formed channels through lipid membranes.Finally, the researchers showed that the WXG motifs were required for pore formation and membrane disruption by the EsxE-EsxF complex, and the motifs mediated assembly of functional EsxE-EsxF oligomers. This now defines a biochemical role for the previously enigmatic WXG motif."EsxE and EsxF constitute the first known outer membrane components mediating protein secretion in M. tuberculosis," Niederweis said. "However, it is unlikely that EsxE and EsxF are sufficient for TNT secretion, since an energy source is required in all known bacterial protein secretion systems. Therefore, it is possible that EsxE-EsxF associate with other proteins or protein complexes to achieve CpnT export and TNT secretion."The UAB researchers propose two models for the transport of CpnT by EsxE and EsxF. In the first, the EsxE-EsxF heterodimers form a pore in the inner membrane, and then form another pore in the outer membrane to create transmembrane channels. "Alternatively," Niederweis said, "the inner membrane channel is extended to span the periplasm via filament formation, and connects to EsxE-EsxF pores in the outer membrane, exposing EsxF on the cell surface. In this model, the putative EsxE-EsxF channel tunnel enables export of the CpnT polypeptide to the outer membrane of M. tuberculosis, and subsequent secretion of TNT and EsxE-EsxF."Co-authors with Niederweis in the study, "Pore-forming Esx proteins mediate toxin secretion by Mycobacterium tuberculosis," published in "This work was a remarkable achievement of an outstanding graduate student, Uday Tak, who did almost all of these experiments by himself," Niederweis said. Uday Tak obtained his Ph.D. in November 2020 and is now a postdoctoral fellow at the University of Colorado-Boulder.
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Biology
| 2,021 |
April 8, 2021
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https://www.sciencedaily.com/releases/2021/04/210408131436.htm
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Where Siberian orchids thrive: New hotspot of orchids discovered near Novosibirsk
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Orchids of the Boreal zone are rare species. Most of the 28,000 species of the Orchid family actually live in the tropics. In the Boreal zone, ground orchids can hardly tolerate competition from other plants -- mainly forbs or grasses. So they are often pushed into ecotones -- border areas between meadows and forests, or between forests and swamps.
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Furthermore, there has been a decline in wild orchids all over North America and Eurasia, caused in part by human-induced destruction of their habitats, the transformation of ecosystems, and the harvesting of flowers from the wild.In the Novosibirsk region, 30 orchid species have been found, and about 40 in the entire Siberia.It is no coincidence that many orchids are included in regional and national Red Book lists, with dedicated protected areas created to preserve them. When specialists find high concentrations of orchid species in a small area, it is always a significant discovery, in terms of both science and ecology. A recent publication in the open-access, peer-reviewed scientific journal About 15 years ago, local biology teacher Yuri Panov found a place with mass growth of 13 orchid species in the Novosibirsk region. Together with his students, he studied the territory and took care of it, hanging birdhouses. The place was informally called School Orchid Zapovednik.In 2014, a wildfire from nearby farm fields broke out in the area. Fortunately, the orchid populations did not suffer much -- in fact, this disturbance partially contributed to their growth in some areas, reducing competition from grasses and shrubs. However, the danger of frequent fires prompted Panov to invite specialists for a thorough botanical survey of the territory.Researchers Alexander Dubynin, Inessa Selyutina and Alexandra Egorova of the Central Siberian Botanical Garden in Novosibirsk, and Mikhail Blinnikov of Kazan Federal University have been working in the area since 2017, registering the occurrences of orchids and photographing plants for the iNaturalist platform. There and in adjacent territories, they discovered a total of 14 orchid species, some of which were new to this territory and had never been registered before.The area in Novosibirsk region is truly unique. Here, researchers found one of the largest populations of large-flowered lady's-slipper (Cypripedium macranthos) in Northern Eurasia, with up to 5,000 individual plants. The Cypripedium calceolus Lady's-slipper orchid and the rare and beautiful bloated lady's slipper (Cypripedium ventricosum) were also plentiful. Some of the discovered orchids require further study, such as the hybrids between Dactylorhiza and Gymnadenia and some unusual forms of Platanthera.After an expert description of the territory, a new Important Plant Area was nominated for South Siberia. "Based on the analysis of plant species composition of protected areas in Novosibirsk Region," Alexander Dubynin resumes, "we conclude that in situ preservation of orchids in the region is overall insufficient. It is therefore necessary to organize a new protected area 'Orchid Zapovednik' in the category of 'botanical Zakaznik' on 335 hectares with an explicit floral diversity conservation mandate and long-term orchid population monitoring."Over the past three years, the territory has increasingly attracted the attention of researchers and educators, becoming a kind of a 'field laboratory' for the study of orchid communities in South Siberia.
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Biology
| 2,021 |
April 8, 2021
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https://www.sciencedaily.com/releases/2021/04/210408131431.htm
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Research shows cytonemes distribute Wnt proteins in vertebrate tissue
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Scientists have made a pivotal breakthrough in understanding the way in which cells communicate with each other.
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A team of international researchers, including experts from the University of Exeter's Living Systems Institute, has identified how signalling pathways of Wnt proteins -- which orchestrate and control many cell developmental processes -- operate on both molecular and cellular levels.Various mechanisms exist for cells to communicate with each other, and many are essential for development. This information exchange between cells is often based on signalling proteins that activate specific intracellular signalling cascades to control cell behaviour at a distance.Wnt proteins are produced by a relatively small group of cells and orchestrate cell proliferation and differentiation, but also cell movement and polarity of the neighbouring cells.However, one of the most crucial functions of the Wnt signalling is patterning of the body axis -- which essentially helps determine where the head and tail should form in in a developing tissue.Previous research led by Professor Steffen Scholpp, from the Living Systems Institute, highlighted that thin finger-like protrusions, known as cytonemes, carry Wnts from the source cells to recipient cells.However, the mechanism controlling Wnt cytonemes at the molecular level is currently unknown.In the new study, his team explored the role of a key component of the PCP signalling pathway Vangl2 in zebrafish embryos.In this project, Dr Lucy Brunt, identified that Wnt proteins activate the PCP pathway in a source cell in order to regulate cytoneme initiation and signal dissemination.By activating this pathway via Vangl2, she induced the formation of long and branched cytonemes which reinforced distant Wnt signalling in the neighbouring cells.Based on these data, fellow researcher Dr Kyle Wedgwood and his team developed a mathematical model to simulate this effect in a developing zebrafish egg, and predicted that the patterning of the body axis is massively altered."And the prediction was correct" explained Dr Brunt. " We found that the formation of longer cytonemes in zebrafish larvae led to a strongly reduced head, and strikingly the forebrain tissue was missing completely."Together with cell biologists from the National University of Singapore, the scientists showed that the mechanism they described in zebrafish embryogenesis, operates also in different tissues, including human cancer cells.Professor Scholpp said "The exciting results of this multidisciplinary, multiscale project provides a step change in understanding how the Wnt signalling pathway operates at the molecular and cellular level in a living vertebrate animal."The data from this project will help us to understand the mechanisms involved in controlling normal Wnt signalling, in the future," he added. "We believe that the outcome will have fundamental implications for how we could manipulate Wnt signalling during disease states."
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Biology
| 2,021 |
April 8, 2021
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https://www.sciencedaily.com/releases/2021/04/210408131420.htm
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Energy transmission by gold nanoparticles coupled to DNA structures
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Using DNA structures as scaffolds, Tim Liedl, a scientist of Ludwig-Maximilians-Universitaet (LMU) in Munich, has shown that precisely positioned gold nanoparticles can serve as efficient energy transmitters.
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Since the inception of the field in 2006, laboratories around the world have been exploring the use of 'DNA origami' for the assembly of complex nanostructures. The method is based on DNA strands with defined sequences that interact via localized base pairing. "With the aid of short strands with appropriate sequences, we can connect specific regions of long DNA molecules together, rather like forming three-dimensional structures by folding a flat sheet of paper in certain ways," as Professor Tim Liedl of the Faculty of Physics at LMU explains.Liedl has now used DNA origami to construct chiral objects, i.e. structures that cannot be superimposed by any combination of rotation and translation. Instead they possess 'handedness', and are mirror images of one another. Such pairs often differ in their physical properties, for example, in the degree to which they absorb polarized light. This effect can be exploited in many ways. For example, it is the basis for CD spectroscopy (the 'CD' here stands for 'circular dichroism'), a technique that is used to elucidate the overall spatial configuration of chemical compounds, and even whole proteins.With a view to assembling chiral metal structures, Liedl and his group synthesized complex DNA-origami structures that provide precisely positioned binding sites for the attachment of spherical and rod-shaped gold nanoparticles. The scaffold therefore serves as a template or mold for the placement of nanoparticles at predetermined positions and in a defined spatial orientation. "One can assemble a chiral object based solely on the arrangement of the gold nanoparticles," says LiedlGold is not only chemically robust, as a noble metal it exhibits what are known as surface plasmon resonances. Plasmons are coherent electron oscillations that are generated when light interacts with the surface of a metal structure. "One can picture these oscillations as being like the waves that are excited when a bottle of water is shaken either parallel or at right angles to its long axis," says Liedl.Oscillations excited in spatially contiguous gold particles can couple to one another, and the plasmons in Liedl's experiments behave as image and mirror image, thanks to their chiral disposition on the origami scaffold. "This is confirmed by our CD spectroscopic measurements," says Liedl. In the experiments, the chiral structures are irradiated with circularly polarized light and the level of absorption is measured as a percentage of the input. This enables right- and left-handed arrangements to be distinguished from one another.In principle, two gold nanorods should be sufficient for the construction of chiral object, as they can be arranged either in the form of an L or an inverted L. However, the rods used in the experiments were relatively far apart (on the nanoscale) and the plasmons excited in one had little effect on those generated in the other, i.e. the two hardly coupled to each other at all. But Liedl and his colleagues had a trick up their sleeves. By appropriate redesign of the origami structure, they were able to position a gold nanosphere between the pair of L-formed rods, which effectively amplified the coupling. CD spectroscopy revealed the presence of energy transitions, thus confirming the hypothesis which the team had derived from simulations.Liedl envisages two potential settings in which these nanostructures could find practical application. They could be used to detect viruses, since the binding of viral nucleic acids to a gold particle will amplify the CD signal. In addition, chiral plasmonic transmitters could serve as model switching devices in optical computers, in which optical elements replace the transistors that are the workhorses of electronic computers.
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Biology
| 2,021 |
April 8, 2021
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https://www.sciencedaily.com/releases/2021/04/210408131417.htm
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How birds defend against brood parasites
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Avian brood parasites lay their eggs in the nests of other bird species, forcing the hosts to do the hard work of raising the unrelated young. A team of scientists wanted to simulate the task of piercing an egg -- a tactic that only a minority of host birds use to help grasp and eject the foreign eggs. Their study offers insight into some of the physical challenges the discriminating host birds face.
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The new findings appear in the Take cowbirds, for example. Their eggs look nothing like the host birds' eggs, "yet most of their hosts do not reject the parasite eggs," said study co-author Mark Hauber, a professor of evolution, ecology and behavior at the U. of I. and a brood parasitism expert. "One explanation is that the cowbird eggshell is too thick and strong for a small host's beak to pierce."To determine whether the difficulty of piercing a brood parasite's egg played a role in whether the host bird tried to eject it, Daniel Clark, an undergraduate student working in Hauber's laboratory, teamed up with another professor in the same department, Philip Anderson, an expert in the biomechanics of piercing, slashing and stabbing. Anderson has previously studied the characteristics that contribute to the cutting and crushing ability of teeth and the piercing power of viper fangs and cactus spines.The team used chicken eggs in the experiments because collecting and destroying wild bird eggs would be ethically problematic and difficult to standardize. The researchers wanted to determine which elements influenced an egg's ability to withstand being pierced."The factors we specifically looked at in the paper were the presence of a nest, the sharpness of the bird's beak and the speed at which it struck the egg," Clark said.The team measured the energy required to pierce the eggs under different conditions: with and without a nest supporting the egg, with a piercing object approaching the eggs at high or low speeds, and with dull or sharp objects. The researchers used the sharp end of a nail to simulate a sharp beak, and the nail head as a proxy for a dull beak. The experiments involved either a fast-swinging pendulum-mounted nail or a materials-testing device that slowly pushed the nail into the egg.The researchers said they were surprised to find that the dull end of the nail did a better job of piercing the egg than the sharp end, particularly when striking the egg at a higher speed."My lab has done a lot of research on puncture and cutting mechanics, but we've always been looking at soft materials such as skin or muscle," Anderson said. "An eggshell is brittle -- more like ceramic than skin. If you're trying to break something brittle, like glass, it makes more sense to use a hammer than a knife, so this result is not as surprising at it seemed at first."The experiments also revealed that nests absorb some of the energy of the nail strike, particularly when the nail moves at slower speeds."In the slow-moving experiment, the nest mattered a lot, but the sharpness or dullness of the nail mattered less," Clark said. "In the fast-moving experiment, the nest mattered less but the sharpness of the nail ended up mattering a lot."The team also discovered that the act of repeatedly striking eggs dulled even the sharp end of a steel nail."This shows that biological surfaces are a lot more tough and durable than we think," Clark said.If pecking at a foreign egg rapidly in the bottom of a nest damages its beak, the host bird might reduce its ability to preen, weave its own nest or feed itself and its young. These findings offer clues to the factors that influence how -- and whether -- a host bird responds to the arrival of a foreign egg in its nest, the researchers said."Our experiments help us to understand the long-standing conundrum of why most hosts of the cowbird and its conspicuous egg have not evolved to eject the parasitic egg from the nest," Hauber said.The National Science Foundation and the Joseph B. Hawkes Research Award from the U. of I. supported this research.
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Biology
| 2,021 |
April 8, 2021
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https://www.sciencedaily.com/releases/2021/04/210408131411.htm
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How to tame a restless genome
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Short pieces of DNA -- jumping genes -- can bounce from one place to another in our genomes. When too many DNA fragments move around, cancer, infertility, and other problems can arise. Cold Spring Harbor Laboratory (CSHL) Professor & HHMI Investigator Leemor Joshua-Tor and a research investigator in her lab, Jonathan Ipsaro, study how cells safeguard the genome's integrity and immobilize these restless bits of DNA. They found that one of the jumping genes' most needed resources may also be their greatest vulnerability.
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The mammalian genome is full of genetic elements that have the potential to move from place to place. One type is an LTR retrotransposon (LTR). In normal cells, these elements don't move much. But if something happens to allow them to move, say during sexual reproduction or in cancerous cells Joshua-Tor says:"Sometimes they jump into very important spots, either genes themselves or in areas of the genome that is important for regulating genes."In this study, Joshua-Tor and Ipsaro examined a mouse protein called Asterix/Gtsf1 that immobilizes LTRs. To understand how this protein locks down LTRs, Ipsaro used several techniques, including cryo-EM, to take a closer look at the protein structure. Joshua-Tor says:"Structure just informs us in many ways, like how things work. If you can see something, you have a way better idea of how it works."Ipsaro found Asterix/Gtsf1 binds directly to a particular class of RNA called transfer RNA (tRNA). tRNAs normally are part of the cell's protein manufacturing machinery. LTRs have borrowed that part of the protein-making machinery to replicate their genetic material. Asterix/Gtsf1 overrides what the LTRs are trying to do by freezing the otherwise mobile element in place, shutting down their ability to move. Ipsaro says:"It's trying to copy and paste itself all over the genome. A part of it evolutionarily has depended on tRNA binding in order to replicate."Instead of freezing the entire genome, scientists think Asterix/Gtf1 is using tRNAs to suppress small specific regions, like LTRs. Researchers are trying to figure out how cells protect themselves against these and other types of mobile genetic elements. They hope that someday they might tame an overly restless genome, preventing new mutations in the germline and in tumors.
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Biology
| 2,021 |
April 8, 2021
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https://www.sciencedaily.com/releases/2021/04/210408112418.htm
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Biologists create better method to culture cells for testing drug toxicity
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When a new drug is being developed, the first question is, "Does it work?" The second question is, "Does it do harm?" No matter how effective a therapy is, if it harms the patient in the process, it has little value.
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Doctoral student Robert Skolik and Associate Professor Michael Menze, Ph.D., in the Department of Biology at the University of Louisville, have found a way to make cell cultures respond more closely to normal cells, allowing drugs to be screened for toxicity earlier in the research timeline.The vast majority of cells used for biomedical research are derived from cancer tissues stored in biorepositories. They are cheap to maintain, easy to grow and multiply quickly. Specifically, liver cancer cells are desirable for testing the toxicity of drugs for any number of diseases."You like to use liver cells because this is the organ that would detoxify whatever drug for whatever treatment you are testing," Menze said. "When new drugs are being developed for diabetes or another disease, one of the concerns is whether they are toxic to the liver."The cells do come with limitations, however. Since they are cancer cells, they may not be as sensitive to toxins as normal cells, so they may not reveal issues with toxicity that can appear much later in the drug testing process.Skolik and Menze have discovered that by changing two components of the media used to culture the cells, they can make liver cancer cells behave more like normal liver cells. Rather than using standard serum containing glucose, they used serum from which the glucose had been removed using dialysis and added galactose -- a different form of sugar -- to the media. The tumor cells metabolize galactose at a much slower rate than glucose. This changes the metabolism of the cells making them behave more like normal liver cells.By using cells cultured with this modified serum, drugs may effectively be screened for toxicity earlier in the research process, possibly saving millions of dollars."It started just as a way to sensitize cells to mitochondrial activity, the cellular powerhouse, but then we realized we had a way to investigate how we are shifting cancer metabolism," Skolik said. "In short, we have found a way to reprogram cancer cells to look -- and act -- more like a normal cell."The research is featured on the cover of the April issue of To fully realize the effect he reported, Skolik also cultured the cells for a longer period of time than usual."In the past, people would do a 12-hour adaptation to this new media. But what we showed is if you culture them for 4 to 5 weeks, you have a much more robust shift," Skolik said."When it comes to gene expression, you get much more bang for the buck when you adapt them for a longer period."Although the modified serum for the cultures requires the additional step of dialysis and longer culture time, it can yield benefits at later testing stages."You would reserve this process for key experiments or toxicity screening," Menze said. "However, if you go into a Phase 1 clinical trial and find toxicity there, it is way more expensive than using this method."
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Biology
| 2,021 |
April 8, 2021
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https://www.sciencedaily.com/releases/2021/04/210408112355.htm
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How did 500 species of a fish form in a lake? Dramatically different body clocks
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Animals are remarkably diverse in their sleep and activity patterns due to foraging strategies, social behavior and their desire to avoid predators. With more than 3,000 types of cichlids, these freshwater fish may just be one of the most diverse species in the world. Lake Malawi alone, which stretches 350 miles through eastern Africa, is home to more than 500 cichlid species. They evolved from a few species that likely entered the lake about 3 million years ago and now display very different behaviors and inhabit well-defined niches throughout the lake.
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So how is it possible that so many different species can coexist in this large tropical lake? Many factors have been considered including the multitude of ecological resources available, predation, and the ability of cichlid species to evolve highly specific courtship and feeding behavior. Despite the dramatic difference between day and nightlife, the way fish exploit different times of day has not been studied systematically.Lake Malawi's cichlids are presumed to be active during the daytime, most likely to avoid predation, although this has never been investigated scientifically. By examining alterations in the circadian timing of activity and the duration of rest-wake cycles, researchers from Florida Atlantic University in collaboration with the University of Massachusetts Amherst, are the first to identify a single nocturnal species of a Malawi cichlid -- the Tropheops sp. "red cheek."The study, published in the Lake Malawi cichlids in the study exhibited substantial and continuous variation in activity levels and patterns, and closely related species differed markedly in activity. Findings suggest that circadian regulation of activity may provide a mechanism for niche exploitation in African cichlids. Researchers also identified diversity of locomotor behavior, and together, these results provide a system for investigating the molecular and neural basis underlying variation in nocturnal activity.To examine the effects of ecological niche and evolutionary history on the regulation of locomotor activity and rest, researchers measured locomotor activity across the circadian cycle in 11 Lake Malawi cichlid species. The species were selected for diversity in habitat, behavior and lineage representation and included the near-shore rock-dwelling clade of Malawi cichlids (mbuna) as well as representative species from another major lineage within the lake. Prior to this study, the circadian regulation of activity and rest within a lineage that inhabits a shared environment was unknown."Given that Malawi cichlids exhibit an impressive magnitude of diversity in an array of anatomical and behavioral traits, we predicted that they may also exhibit high magnitudes and continuous variation in rest-activity patterns. We think these differences also extend to sleep and foraging behavior, providing a system to investigate how complex traits that are critical for survival evolve," said Alex Keene, Ph.D., lead author and a professor of biological sciences in FAU's Charles E. Schmidt College of Science, on the John D. MacArthur Campus at Jupiter. "Our finding that the timing and duration of rest and activity varies dramatically, and continuously, between populations of Lake Malawi cichlids raise the possibility that these differences play a critical role in the rapid speciation of this system."
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Biology
| 2,021 |
April 7, 2021
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https://www.sciencedaily.com/releases/2021/04/210407202848.htm
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PNA-based technique an essential part of the gene editing toolkit
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In an article published in the April 8 issue of
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Gene editing allows scientists to modify sections of an organism's DNA and is considered a promising treatment for a number of genetic diseases. There have been numerous advances in the laboratory over the last few decades, but there are still many challenges to overcome before gene editing can be widely used in the patient population. Launched in 2018, the Somatic Cell Gene Editing Consortium (SCGE) has brought together some of the leading researchers in the field to advance discovery and accelerate the translation of somatic gene editing advances in the lab to the clinical setting.Over six years, the NIH will allocate approximately $190 million to SCGE to realize gene editing's potential. The end result will be a freely available toolkit that will provide the biomedical research community with rigorously evaluated information about genome editors and methods for delivering and tracking gene editing molecules."NIH realized it was important for all of us who are investigating gene editing to work together toward a common goal," said Carnegie Mellon University Professor of Chemistry Danith Ly who joined the consortium in 2019. "We're designing molecules that can go into the cell and we're cataloging each and every one. What we'll end up with is a very valuable, rigorously evaluated resource for those who want to bring gene editing to patients."While much of the consortium's work focuses on CRISPER-Cas related systems, the SCGE points out that it's important to continue to develop other systems. They specifically single out the peptide nucleic acid-based gene editing technique developed by Carnegie Mellon's Ly and Yale University's Peter Glazer."Although there is a significant focus on CRISPR-Cas related systems within the SCGE, it is crucial to continue to explore alternate systems, in part because they may differ in both their potential for delivery and their biological or immunological responses," the consortium wrote in While CRISPR-Cas edits genes in cells that have been removed from the body, Ly and Glazer's peptide nucleic acid (PNA) system is administered intravenously and edits cells in vivo. Using nanoparticles, a PNA molecule paired with a donor strand of DNA is delivered directly to a malfunctioning gene. Ly, a leading researcher in synthetic nucleic acid technology, has programmed PNA molecules to open double stranded DNA at the site of a targeted mutation. The donor DNA from the complex binds to the cell's faulty DNA and triggers the DNA's innate repair mechanisms to edit the gene. The team has used the technique to cure beta thalassemia in adult mice and in fetal mice in utero.The PNA gene editing system doesn't have the high-yield of CRISPER-Cas systems, but it does have the advantage of being less likely to make off-target modifications. According to Ly, that means their technique might be better for genetic diseases that only need to have a small percentage of cells corrected to make a therapeutic difference. For example, in the beta thalassemia studies, Ly and Glazer found that editing only six to seven percent of cells was curative.Ly and Glazer plan to further refine and improve their technique through their participation in SCGE, and they look forward to sharing their results with the consortium and the greater biomedical community.
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Biology
| 2,021 |
April 7, 2021
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https://www.sciencedaily.com/releases/2021/04/210407174323.htm
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One of Africa's rarest primates protected by... speedbumps
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A new study revealed that a drastic reduction of deaths of one of Africa's rarest primates, the Zanzibar red colobus (Piliocolobus kirkii), followed the installation of four speedbumps along a stretch of road where the species frequently crossed.
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Zanzibar red colobus are found only in the Zanzibar archipelago and classified as Endangered by the IUCN Red List. Reliant on Unguja Island's forests for their survival, around half of the species population is found in Jozani-Chwaka Bay National Park.In the study, published in They found that historic data from the road traversing the national park showed that one colobus was killed on average every 2-3 weeks by traffic. After speedbumps were installed, this was reduced to one every six weeks.While great progress, this mortality rate is still a significant threat to the species -- especially given that natural predation tends to target weaker individuals, yet roadkill is indiscriminate, killing reproductively active adults as well as the very young and old.Bangor primatologist and Director of the Zanzibar Red Colobus Project, Dr. Alexander Georgiev, and senior author of this study, said: "Cars are not selective in the animals they kill. This means that while natural predators may target the very young and old more often, cars are equally likely to kill reproductively active young adults, who would contribute the most to population growth. And this may be a problem."Harry Olgun, now a PhD student at the University's School of Natural Sciences, led this study as part of his Masters research on the road ecology of the Zanzibar red colobus. Olgun said: "After the road at Jozani was surfaced but before the speedbumps were installed, a colobus was reported to have been killed every two to three weeks, resulting in perhaps about 12-17 percent annual mortality, according to one estimate. The recent data show that speedbumps have made a huge difference for the safety of the colobus. Adding more speedbumps would help reduce the risk further."Dr. Tim Davenport, Director of Species Conservation & Science in Africa at WCS, who led the first countrywide census of the Zanzibar red colobus a few years ago and is a coauthor of the study, said: "As tourism grows in Zanzibar and habitat continues to shrink, using science to quantify and solve conservation problems has never been so important. Understanding the impact of vehicles on wildlife within a park, and implementing practical solutions is exactly what we as conservationists should be doing."
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Biology
| 2,021 |
April 7, 2021
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https://www.sciencedaily.com/releases/2021/04/210407143759.htm
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U. S. socio-economic effects of harmful algal blooms
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Harmful algal blooms (HABs) occur in all 50 U.S. states and many produce toxins that cause illness or death in humans and commercially important species. However, attempts to place a more exact dollar value on the full range of these impacts often vary widely in their methods and level of detail, which hinders understanding of the scale of their socio-economic effects.
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In order to improve and harmonize estimates of HABs impacts nationwide, the National Oceanic and Atmospheric Administration (NOAA) National Center for Coastal Ocean Science (NCCOS) and the U.S. National Office for Harmful Algal Blooms at the Woods Hole Oceanographic Institution (WHOI) convened a workshop led by WHOI Oceanographer Emeritus Porter Hoagland and NCCOS Monitoring and Event Response (MERHAB) Program Manager Marc Suddleson. Participants focused on approaches to better assess the socio-economic effects of harmful algal blooms in the marine and freshwater (primarily Great Lakes) ecosystems of the United States. The workshop proceedings report describes the group's objectives, and presents recommendations developed by 40 participants, mostly economists and social scientists from a range of universities, agencies, and U.S. regions. Their recommendations fall under two broad categories: those intended to help establish a socio-economic assessment framework, and those to help create a national agenda for HABs research."This has been a goal of the research and response communities for a long time, but coming up with a robust national estimate has been difficult, for a number of reasons, mainly related to the diversity of algal species and the wide variety of ways they can affect how humans use the oceans and freshwater bodies," said Hoagland. "This gives us a strong base on which to build the insight that will vastly improve our estimates."Framework recommendations call for enhancing interagency coordination; improving research communications and coordination among research networks; integrating socioeconomic assessments into HAB forecasts and observing networks; using open-access databases to establish baselines and identify baseline departures; facilitating rapid response socio-economic studies; improving public health outcome reporting and visibility of HAB-related illnesses; fostering the use of local and traditional ecological knowledge to improve HAB responses; engaging affected communities in citizen science; and engaging graduate students in HAB socio-economic research.Research agenda recommendations include elements necessary for addressing gaps in our understanding of the social and economic effects of HABs. They include a suggested approach for obtaining an improved national estimate of the economic effects of HABs; supporting rapid ethnographic assessments and in depth assessments of social impacts from HABs; defining socioeconomic impact thresholds for triggering more detailed studies of impacts (such as in the case of designated HAB events of significance); sponsoring research on the value of scientific research leading to improved understanding of bloom ecology; assessing the value of HAB mitigation efforts, such as forecasts, and control approaches and their respective implementation costs; and supporting research to improve HAB risk communication and tracking and to better understand the incidence, severity, and costs of HAB-related human illnesses."These recommendations give us a strong series of next steps to increase focus on HAB-related socio-economic research," said Don Anderson, director of the U.S. National Office for Harmful Algal Blooms. "The report is certain to spur increased collaborations that will provide a better understanding of the many complex socio-economic effects of HABs and provide the tools to increase the effectiveness of efforts to minimize impacts on society and the environment."The detailed final proceedings report and more information about the workshop is available on the U.S. National HAB Office website.
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Biology
| 2,021 |
April 7, 2021
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https://www.sciencedaily.com/releases/2021/04/210407135749.htm
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New biosensor makes control hormone auxin visible in cells
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The hormone auxin is of central importance for the development of plants. Scientists at the University of Bayreuth and the Max Planck Institute for Developmental Biology in Tübingen have now developed a novel sensor that makes the spatial distribution of auxin in the cells of living plants visible in real time. The sensor opens up completely new insights into the inner workings of plants for researchers. Moreover, the influences of changing environmental conditions on growth can now also be quickly detected. The team presents its research results in the journal
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The effects of the plant hormone auxin were first described scientifically almost 100 years ago. Today we know that auxin controls countless processes in plant cells -- be it in the development of the embryo in the seed, the formation of the root system, or the orientation of growth to incident sunlight. In all cases, the hormone has the function of coordinating the plant's responses to external stimuli. To do this, it must always be present in the cell tissue where the response to an external stimulus needs to be triggered. Indeed, it is often the case that auxin is needed at very different places in the cell tissue within a very short space of time. This leads to rapid spatial redistribution. With the new biosensor, called AuxSen for short, the dynamics of these processes can be observed in real time for the first time. Light signals indicate where the auxin is located in the cell tissue. What is special about this sensor is that it is not a technical device that has to be introduced into the plants, but an artificial protein that the plants are engineered to produce themselves.The application of the biosensor has already led to some surprising findings. One example is the rapid redistribution of auxin when a plant is turned upside down. When the root tip no longer points downwards but diagonally upwards, the auxin molecules responsible for root growth collect on the new underside of the root tip within just one minute. And upon being placed right-side up, the old distribution of auxin is restored after just one minute.The development of the biosensor is the result of many years of interdisciplinary collaboration. A team led by Prof. Dr. Birte Höcker, Professor of Protein Design at the University of Bayreuth, and a team led by Prof. Dr. Gerd Jürgens at the Max Planck Institute for Developmental Biology, have combined their knowledge and many years of experience. "It is to be expected that the new biosensor will uncover many more unforeseen insights into the inner workings of plants and their reaction to external stimuli over the coming years. The development of the sensor has been a long process in which we have gained fundamental insights into how proteins can be selectively altered to bind specific small molecules," says Prof. Dr. Birte Höcker."There is already a great deal of interest in the new sensor, and it is to be expected that optimised variants of AuxSen will be developed over the next few years to enable even better analysis of the diverse auxin-regulated processes in plants. With our new publication in At the beginning of the biosensor's development was a protein in the bacterium E. coli, which binds to the amino acid tryptophan, but much more poorly to the chemically-related auxin. This protein was coupled with two proteins that fluoresce when excited with light of a certain wavelength. If these partner proteins come very close to each other, their fluorescence increases considerably. A fluorescence resonance energy transfer (FRET) then occurs. The next step was crucial: the initial protein was to be genetically modified so that it binds better to auxin and less well to tryptophan. At the same time, the FRET effect of the partner molecules should always occur when the protein binds to auxin, and only then. With this goal in mind, about 2,000 variants of the protein were created and tested until finally a molecule was found that fulfilled all requirements. Thus, the biosensor AuxSen was born: strong fluorescent signals indicating where in the cell tissue the vital hormone is located.Another challenge was to enable plants to produce AuxSen themselves. On the one hand, it had to be ensured that AuxSen would bind to the existing auxin molecules in as many cells as possible. This was the only way to map the spatial distribution of auxin in the cell completely and to produce high signal quality. On the other hand, however, the auxin molecules were not to be permanently prevented from fulfilling their original tasks in the plant organism because of binding to AuxSen. Nevertheless, the two research teams succeeded in finding a compromise solution. Plants were genetically modified in such a way as to produce a large amount of AuxSen throughout their cell tissue. But this would only happen when stimulated to do so by a special substance -- and then only for a short time. In this way, the biosensor provides precise snapshots of auxin distribution in cells without permanently affecting the processes controlled by auxin.
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Biology
| 2,021 |
April 7, 2021
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https://www.sciencedaily.com/releases/2021/04/210407135723.htm
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Junctions between three cells serve as gateways for the transport of substances
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Within multicellular organisms, cells build connections with each other forming cell layers that cover the surfaces of tissues and organs and separate structures in the body. For example, the skin forms a mantle around the entire organism, and the layer of cells lining the blood vessels creates a boundary between the bloodstream and tissues. Special connections between neighbouring cells ensure that these cellular barriers are, on the one hand, stable and tight -- thus protecting the body and organs against pathogens -- while, on the other hand, they remain permeable to specific substances or migrating cells. This is how the cells allow dissolved nutrients to be transported into organs, and how cells of the immune system are able to migrate from the blood across the blood vessel wall into inflamed tissue.
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Scientists at the University of Münster have now investigated a comparable process in the ovary of the fruit fly (Drosophila melanogaster). Here, the maturing egg cells are enclosed by a layer of epithelial cells through which the egg absorbs yolk-forming proteins. The researchers found that, at the points where three cells meet, the epithelial cells loosen their connections in a controlled manner and the yolk proteins are transported to the egg cell through the resulting gaps. At places where only two cells connect, the connections are maintained, thus keeping the tissue integrity intact. "Our findings contribute to a better understanding of how cellular barriers function and are restructured during development, which provides a basis for deciphering the mechanisms of certain pathological processes," explains Prof Dr Stefan Luschnig, a developmental biologist and leader of the research project. The study has now been published in the scientific journal Whenever substances are transported through a cell layer, the cells either take them up through the membrane on one side of the cell layer and then release them on the other side -- which requires a lot of energy -- or the substances diffuse through gaps between the cells. From studies of other insects, it was already known that yolk proteins are usually transported into egg cells via spaces between the epithelial cells that enclose the eggs. The new investigation confirmed that this is also the case for the fruit fly. However, it was not previously clear how the cells manage to transiently open up intercellular spaces while at the same time keeping the tissue intact.To visualize these cellular processes live and analyze the molecular mechanisms behind them, the scientists genetically labelled certain proteins of the fruit fly with fluorescent molecules, kept the ovaries in tissue cultures, and examined the living tissue using confocal laser scanning microscopy. They focused their attention on the proteins on the surface of the epithelial cells. These so-called adhesion proteins mechanically hold the cellular network together and seal the spaces between cells.The scientists found that the epithelial cells sequentially removed four different adhesion proteins from their membranes. "This process takes several hours, and only when the last protein is gone do the cell junctions open," explains biologist Jone Isasti-Sanchez, who is the first author of the study and a doctoral candidate in the Integrated Research Training Group within the Collaborative Research Center 1348 "Dynamic Cellular Interfaces" at the University of Münster. After the junctions have opened, the uptake of yolk proteins into the egg proceeds over about 16 hours and, subsequently, the process reverses -- the intercellular spaces close again. The researchers demonstrated that the cells open their contact sites by taking up adhesion proteins from the surface into the cell interior, using a basic cellular process called endocytosis. An important new finding is that endocytosis seems to take place to a greater extent at those points where three cells meet, and, as a result, the cell junctions only open up at these points. Where only two cells meet, the contact is maintained. "The fact that this process occurs selectively at the three-cell contact-points and, moreover, in such an orderly fashion, is probably important for preventing the tissue from falling apart," says Stefan Luschnig. In addition, he adds that the process presumably has to take place in a very controlled manner because the opening of gates in a tissue comes with the risk that pathogens will enter.In their experiments, the scientists also genetically increased or reduced the amount of the adhesion protein E-cadherin and were able to show that the amount of this protein determines how wide the intercellular spaces open. In addition, they found that the mechanical tension in the cytoskeleton plays a key role in the process. This tension is generated by a structure consisting of the proteins actin and myosin, which encircles the cell periphery and is able to contract, similar to a rubber band. When the researchers increased the activity of myosin in the cell, the cytoskeleton contracted more, which prevented the cell junctions from opening.
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Biology
| 2,021 |
April 7, 2021
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https://www.sciencedaily.com/releases/2021/04/210407135720.htm
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Coral predators exert a much larger influence on young coral than expected
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You might not think an animal made out of stone would have much to worry about in the way of predators, and that's largely what scientists had thought about coral. Although corallivores like parrotfish and pufferfish are well known to biologists, their impact on coral growth and survival was believed to be small compared to factors like heatwaves, ocean acidification and competition from algae.
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But researchers at UC Santa Barbara have found that young corals are quite vulnerable to these predators, regardless of whether a colony finds itself alone on the reef or surrounded by others of its kind. The research, led by doctoral student Kai Kopecky, appears in the journal Kopecky and his co-authors were curious how corals can reemerge following large disturbances like cyclones and marine heatwaves, which periodically devastate the reefs of Mo'orea, French Polynesia, where the research was conducted."Mo'orea is prone to big heat shocks, storm waves, cyclones and predatory sea star outbreaks," said co-author Adrian Stier, an associate professor in the Department of Ecology Evolution & Marine Biology and one of Kopecky's advisors. "It just wipes the slate clean in terms of coral death. And sometimes, just a few years later, you can swim around and see thriving life. We're still really curious about what allows these ecosystems to bounce back."Scientists had implicated predators in shaping coral population dynamics, but there hadn't really been many direct studies. "People who study coral reefs have thought a lot about the supply of new babies coming from elsewhere, or limitation by the amount of nutrients, or competition with algae as important drivers of coral recovery," Stier continued. "But there hasn't been as much done on the importance of predators as a limiting factor."After reviewing the literature on coral growth, mortality and predation, Kopecky decided to focus on the effects predation and density had on young coral colonies.He planted small nubbins of Pacific staghorn coral at various locations on the reef either alone, in a group of four, or in a group of eight. Some of these groups were protected by metal cages, while others were left exposed. For the unprotected coral, Kopecky sought to determine whether high density increased or decreased predation on the staghorn. For the protected groups, he was curious how density influenced coral growth.The researchers found that protection was key to these small corals' futures. After 30 days out on the reef, nearly all of the unprotected nubbins had been completely consumed. In fact, density had virtually no effect on this outcome.The researchers let the experiment run for an entire year. When they returned, virtually none of the unprotected specimens remained. On the other hand, the caged corals had outgrown their accommodations by year's end."The corals that were protected grew all the way into the upper corners of the cages and were poking little branches out," Kopecky recalled. "They formed a cube of coral inside the cages, whereas the ones that were exposed to predators were just barely hanging on."Coral are not typically fast-growing organisms, but staghorn coral grows quickly, giving it a competitive edge following disturbances that remove large amounts of coral. But according to Kai, staghorn coral are like the popcorn chicken of the reef: irresistible to a hungry corallivore.The protected corals grew so quickly that Kai had to adopt a different way to measure them, because at a certain point the nubbins fused, and he could no longer unscrew their base plates to measure them in the lab.So, if there's no protection in numbers for these tasty staghorns, how do they ever survive their infancy?The corals benefit from the protection of fish like the Dusky farmerfish, which farms algae on the reef. These farmer fish doggedly defend their territories, offering protection to any small coral that happens to settle in their range, Kopecky explained. And while algae and coral are often considered archenemies -- with the former able to outcompete the later -- by munching on their crops, the farmer fish keep the algae in check. This enables the coral to get through the stage where they're vulnerable to predation.In fact, researchers rarely see staghorn corals in large colonies absent the protection of these fishy farmers, Kopecky added.The authors thought density would have some effect on predation. "I think it just turns out that this coral is so tasty that predators simply mowed everything down," Stier remarked.The team is considering running a similar experiment with cauliflower coral, which is more robust and slower-growing than the staghorn. Hopefully it's also slightly less scrumptious, as well."When these pufferfish eat enough, you can see their bellies weighted down by the coral rocks that are in their stomachs," Stier said. "I mean, they're oddly shaped fish to begin with; they're already having a hard time swimming without that ballast, but this makes it extra tricky.""It really is a cartoonish dynamic," Kopecky added.Staghorn coral is widely used in reef restoration efforts, especially in the Caribbean where this and a related species (elkhorn coral) are endangered. In fact, before joining UC Santa Barbara, Kopecky spent several months working as a coral restoration technician on the U.S. Virgin Islands."I had an opportunity to see coral restoration in action, but also see some of the limitations associated with it," Kopecky said. "And then I was able to go and conduct research, like this experiment, that can feed back into and inform how restoration might be improved."Getting out-planted coral nubbins through this vulnerable life stage presents a major bottleneck to restoration efforts, Kopecky explained. He has already received feedback on the study from people engaged in coral reef restoration expressing how relevant his findings are to their work."When you protect these young, vulnerable corals from predators, the amount of growth is substantially higher than when they're not protected," Kopecky said. "It's clear that coral predators can really shape whether young corals actually reach the size where they're no longer vulnerable to predation."
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Biology
| 2,021 |
April 7, 2021
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https://www.sciencedaily.com/releases/2021/04/210407083624.htm
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The incredible bacterial 'homing missiles' that scientists want to harness
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Imagine there are arrows that are lethal when fired on your enemies yet harmless if they fall on your friends. It's easy to see how these would be an amazing advantage in warfare, if they were real. However, something just like these arrows does indeed exist, and they are used in warfare ... just on a different scale.
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These weapons are called tailocins, and the reality is almost stranger than fiction."Tailocins are extremely strong protein nanomachines made by bacteria," explained Vivek Mutalik, a research scientist at Lawrence Berkeley National Laboratory (Berkeley Lab) who studies tailocins and phages, the bacteria-infecting viruses that tailocins appear to be remnants of. "They look like phages but they don't have the capsid, which is the 'head' of the phage that contains the viral DNA and replication machinery. So, they're like a spring-powered needle that goes and sits on the target cell, then appears to poke all the way through the cell membrane making a hole to the cytoplasm, so the cell loses its ions and contents and collapses."A wide variety of bacteria are capable of producing tailocins, and seem to do so under stress conditions. Because the tailocins are only lethal to specific strains -- so specific, in fact, that they have earned the nickname "bacterial homing missiles" -- tailocins appear to be a tool used by bacteria to compete with their rivals. Due to their similarity with phages, scientists believe that the tailocins are produced by DNA that was originally inserted into bacterial genomes during viral infections (viruses give their hosts instructions to make more of themselves), and over evolutionary time, the bacteria discarded the parts of the phage DNA that weren't beneficial but kept the parts that could be co-opted for their own benefit.But, unlike most abilities that are selected through evolution, tailocins do not save the individual. According to Mutalik, bacteria are killed if they produce tailocins, just as they would be if they were infected by true phage virus, because the pointed nanomachines erupt through the membrane to exit the producing cell much like replicated viral particles. But once released, the tailocins only target certain strains, sparing the other cells of the host lineage."They benefit kin but the individual is sacrificed, which is a type of altruistic behavior. But we don't yet understand how this phenomenon happens in nature," said Mutalik. Scientists also don't know precisely how the stabbing needle plunger of the tailocin functions.These topics, and tailocins as a whole, are an area of hot research due to the many possible applications. Mutalik and his colleagues in Berkeley Lab's Biosciences Area along with collaborators at UC Berkeley are interested in harnessing tailocins to better study microbiomes. Other groups are keen to use tailocins as an alternative to traditional antibiotics -which indiscriminately wipe out beneficial strains alongside the bad and are increasingly ineffective due to the evolution of drug-resistance traits.In their most recent paper, the collaborative Berkeley team explored the genetic basis and physical mechanisms governing how tailocins attack specific strains, and looked at genetic similarities and differences between tailocin producers and their target strains.After examining 12 strains of soil bacteria known to use tailocins, the biologists found evidence that differences in the lipopolysaccharides -- fat- and sugar-based molecules -- attached to the outer membranes could determine whether or not a strain is targeted by a particular tailocin."The bacteria we studied live in a challenging, resource-poor environment, so we're interested to see how they might be using tailocins to fight for survival," said Adam Arkin, co-lead author and a senior faculty scientist in the Biosciences Area and technical co-manager of the Ecosystems and Networks Integrated with Genes and Molecular Assemblies (ENIGMA) Scientific Focus Area. Arkin noted that although scientists can easily induce bacteria to produce tailocins in the lab (and can easily insert the genes into culturable strains for mass production, which will be handy if we want to make tailocins into medicines) there are still a lot of unanswered questions about how bacteria deploy tailocins in their natural environment, as well as how -- and why -- particular strains are targeted with an assassin's precision."Once we understand the targeting mechanisms, we can start using these tailocins ourselves," Arkin added. "The potential for medicine is obviously huge, but it would also be incredible for the kind of science we do, which is studying how environmental microbes interact and the roles of these interactions in important ecological processes, like carbon sequestration and nitrogen processing."Currently, it's very difficult to figure out what each microbe in a community is doing, as scientists can't easily add and subtract strains and observe the outcome. With properly harnessed tailocins, these experiments could be done easily.Mutalik, Arkin, and their colleagues are also conducting follow-up studies aiming to reveal tailocins' mechanisms of action. They plan to use the advanced imaging facilities at Berkeley Lab to take atomic-level snapshots of the entire process, from the moment the tailocin binds to the target cell all the way to cell deflation. Essentially, they'll be filming frames of a microscopic slasher movie.
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Biology
| 2,021 |
April 7, 2021
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https://www.sciencedaily.com/releases/2021/04/210407110417.htm
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Grass rings: How the spinifex got its hole
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Anyone who has visited the Australian outback would be familiar with spinifex grasses, which cover almost a fifth of our continent.
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Like many scientists, they may have also wondered why this iconic arid grass grows in striking ring shapes.Previous studies have tested whether spinifex rings could be caused by termites, water availability or nutrient depletion, but none has provided a convincing explanation.Now scientists from UNSW Sydney have found that pathogenic soil microbes play a role in how the spinifex got its hole.Their study, the first of its kind in an arid ecosystem, has been published in the Professor Angela Moles and Neil Ross from The Evolution & Ecology Research Centre tested the idea that an accumulation of pathogenic soil microbes might impede seedling emergence and subsequent growth in the centre of spinifex rings.They collected soil from inside and outside naturally occurring spinifex rings and compared plants grown in soil with live microbes to plants grown in sterilised soil."Consistent with our hypothesis, we found that sterilising soil from the inside of spinifex rings significantly increased spinifex seedling emergence," Prof. Moles said."We also found that seedings had significantly higher seedling emergence in unsterilised soil from outside the rings than in unsterilised soil from inside the rings."Their results suggest that die-back in the centre of spinifex plants might be explained by older parts of the plant succumbing to a build-up of pathogenic soil microbes through time, where as new seedlings tend to establish more at the outside edge of the rings where there are fewer pathogens in the soil."Most people tend to think of the beneficial effects of microbes on plant growth," co-author and director of UNSW Science's Evolution & Ecology Research Centre, Professor Angela Moles said."However, sterilising soil actually makes most plants grow better. That is, the negative effects of the pathogenic microbes tend to outweigh the positive effects of the beneficial microbes.""Overall, these results suggest that soil pathogens are quietly shaping the way the plants around us grow."Prof. Moles said this new information helps scientists further understand the unique ecology of Australia's arid grasslands, and adds to the growing recognition of the crucial function that soil microbes play in terrestrial ecosystem processes worldwide.The scientists have recommended further study to identify the types of soil microbes involved in the establishment of arid-zone plants, as well as the different types of microbes that are most important for seedlings at different times or under different germination conditions.
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Biology
| 2,021 |
April 6, 2021
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https://www.sciencedaily.com/releases/2021/04/210406164209.htm
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Fossil discovery deepens snakefly mystery
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Fossil discoveries often help answer long-standing questions about how our modern world came to be. However, sometimes they only deepen the mystery -- as a recent discovery of four new species of ancient insects in British Columbia and Washington state is proving.
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The fossil species, recently discovered by paleontologists Bruce Archibald of Simon Fraser University and Vladimir Makarkin of the Russian Academy of Sciences, are from a group of insects known as snakeflies, now shown to have lived in the region some 50 million years ago. The findings, published in Snakeflies are slender, predatory insects that are native to the Northern Hemisphere and noticeably absent from tropical regions. Scientists have traditionally believed that they require cold winters to trigger development into adults, restricting them almost exclusively to regions that experience winter frost days or colder. However, the fossil sites where the ancient species were found experienced a climate that doesn't fit with this explanation."The average yearly climate was moderate like Vancouver or Seattle today, but importantly, with very mild winters of few or no frost days," says Archibald. "We can see this by the presence of frost intolerant plants like palms living in these forests along with more northerly plants like spruce."The fossil sites where the ancient species were discovered span 1,000 kilometers of an ancient upland from Driftwood Canyon in northwest B.C. to the McAbee fossil site in southern B.C., and all the way to the city of Republic in northern Washington.According to Archibald, the paleontologists found species of two families of snakeflies in these fossil sites, both of which had previously been thought to require cold winters to survive. Each family appears to have independently adapted to cold winters after these fossil species lived."Now we know that earlier in their evolutionary history, snakeflies were living in climates with very mild winters and so the question becomes why didn't they keep their ability to live in such regions? Why aren't snakeflies found in the tropics today?"Pervious fossil insect discoveries in these sites have shown connections with Europe, Pacific coastal Russia, and even Australia.Archibald emphasizes that understanding how life adapts to climate by looking deep into the past helps explain why species are distributed across the globe today, and can perhaps help foresee how further change in climate may affect that pattern."Such discoveries are coming out of these fossil sites all the time," says Archibald. "They're an important part of our heritage."
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Biology
| 2,021 |
April 6, 2021
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https://www.sciencedaily.com/releases/2021/04/210406131957.htm
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A novel form of cellular logistics
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Biophysicists from Ludwig-Maximilians-Universitaet (LMU) in Munich have shown that a phenomenon known as diffusiophoresis, which can lead to a directed particle transport, can occur in biological systems.
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In order to perform their biological functions, cells must ensure that their logistical schedules are implemented smoothly, such that the necessary molecular cargoes are delivered to their intended destinations on time. Most of the known transport mechanisms in cells are based on specific interactions between the cargo to be transported and the energy-consuming motor proteins that convey the load to its destination. A group of researchers led by LMU physicist Erwin Frey (Chair of Statistical and Biological Physics) and Petra Schwille of the Max Planck Institute for Biochemistry has now shown for the first time that a form of directed transport of particles can take place in cells, even in the absence of molecular motors. Furthermore, this mechanism can sort the transported particles according to their size, as the team reports in the latest issue of The study focuses on the MinDE system from the bacterium E. coli, which is an established and important model for biological pattern formation. The two proteins MinD and MinE oscillate between the poles of the rod-shaped cell and their mutual interaction on the cell membrane ultimately restricts the plane of cell division to the center of the cell. In this case, the researchers reconstructed the pattern forming MinDE system in the test-tube, using the purified Min proteins and artificial membranes. As expected from previous experiments, when the energy-rich molecule ATP was added to this system, the Min proteins recapitulated the oscillatory behavior seen in bacterial cells. More importantly, the experimenters went on to demonstrate that many different kinds of molecules could be caught up in the oscillatory waves as they traversed the membranes -- even molecules that have nothing to do with pattern formation and are not found in cells at all.In order to analyze the transport mechanism in greater detail, the team turned to cargoes that consisted of DNA origami, and could be anchored to the membrane. This strategy allows one to create molecular structures of varying sizes and shapes, based on programmable base-pairing interactions between DNA strands. "These experiments showed that this mode of transport depends on the size of the cargo, and that MinD can even sort structures on the basis of their size," says Beatrice Ramm, a postdoc in Petra Schwille's department and joint first author of the new study. With the aid of theoretical analyses, Frey's group went on to identify the underlying transport mechanism as diffusiophoresis -- the directed motion of particles along a concentration gradient. In the Min system, the friction between the cargo and the diffusing Min proteins is responsible for the transport of the freight. Thus, the crucial factor in this context is not a specific set of biochemical interactions -- as in the case of transport via motor proteins in biological cells -- but the effective sizes of the particles involved. "Particles that are more strongly affected by friction, owing to their large size, are also transported further -- that's what accounts for sorting on the basis of size," says Andriy Goychuk, also joint first author of the paper.With these results, the team has demonstrated the involvement of a purely physical (as opposed to a biological) form of transport based on diffusiophoresis in a biological pattern-forming system. "This process is so simple and fundamental that it seems likely that it also plays a role in other cellular processes, and might even have been employed in the earliest cells at the origin of life," says Frey. "And in the future, it might also be possible to make use of it to position molecules at specific sites within artificial minimal cells," he adds.
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Biology
| 2,021 |
April 6, 2021
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https://www.sciencedaily.com/releases/2021/04/210406131950.htm
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Scientists reveal elusive inner workings of antioxidant enzyme with therapeutic potential
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Mitochondria, known as the powerhouses within human cells, generate the energy needed for cell survival. However, as a byproduct of this process, mitochondria also produce reactive oxygen species (ROS). At high enough concentrations, ROS cause oxidative damage and can even kill cells. An overabundance of ROS has been connected to various health issues, including cancers, neurological disorders, and heart disease.
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An enzyme called manganese superoxide dismutase, or MnSOD, uses a mechanism involving electron and proton transfers to lower ROS levels in mitochondria, thus preventing oxidative damage and maintaining cell health. More than a quarter of known enzymes also rely on electron and proton transfers to facilitate cellular activities that are essential for human health. However, most of their mechanisms are unclear because of the difficulties in observing how protons move.Researchers from the University of Nebraska Medical Center (UNMC) and the Department of Energy's (DOE's) Oak Ridge National Laboratory (ORNL) have now observed the complete atomic structure of MnSOD, including its proton arrangements, with neutron scattering. The findings, published in "Using neutrons, we were able to see MnSOD features that were completely unexpected, and we believe this will revolutionize how people think this enzyme and other enzymes like it operate," said Gloria Borgstahl, a UNMC professor and corresponding author of the new study.MnSOD works by targeting superoxide, a reactive molecule that leaks from the mitochondrial energy production process and is the chemical precursor for other harmful ROS. The enzyme's active site turns superoxide into less toxic products by using its manganese ion to move electrons to and from the reactive molecule. The manganese ion is capable of stealing an electron from a superoxide molecule, converting it to oxygen. This stolen electron can then be given to another superoxide to make hydrogen peroxide.For this biochemical reaction to work, a series of proton movements need to take place between the enzyme's amino acids and other molecules at its active site. The protons act as instruments that enable the electrons to move. Until now, the enzyme's sequence of electron and proton transfers, also known as its catalytic mechanism, had not been defined at the atomic level because of challenges in tracking how protons are shuttled between molecules. A fundamental understanding of this catalytic process could inform therapeutic approaches that harness this enzyme's antioxidant abilities.Proton transfers are not easily seen because they occur in the form of atomic hydrogen, which x-rays and other techniques for observing atoms have difficulty detecting. Neutrons, on the other hand, are sensitive to lighter elements like hydrogen and thus can pinpoint proton movements. Neutrons are also well suited for this research because they do not interact with electrons, unlike other atom-visualizing techniques. Thus, they can be used to study the inner workings of electron-transfer enzymes without disturbing their electronic state."Because neutrons are particles that do not interact with charge, they don't interfere with the electronic properties of metals, which makes them an ideal probe for analyzing metal-containing enzymes, like MnSOD," said Leighton Coates, an ORNL neutron scattering scientist involved with this study. "Additionally, neutrons don't cause radiation damage to materials, allowing us to collect multiple snapshots of the same sample as it shifts between electronic states."Using MaNDi, the macromolecular neutron diffractometer at ORNL's Spallation Neutron Source (SNS), the research team was able to map out the entire atomic structure of MnSOD and track how the enzyme's protons change when it gains or loses an electron. By analyzing the neutron data, the scientists traced the pathways of protons as they moved around the active site. Using this information, the team built a model of a proposed catalytic mechanism, detailing how electron and proton transfers enable MnSOD to regulate superoxide levels.Their analysis suggests that catalysis involves two internal proton transfers between the enzyme's amino acids and two external proton transfers that originate from solvent molecules. While the results of this study confirm some past predictions of the enzyme's biochemical nature, several aspects were unexpected and challenge previously held beliefs.For example, the team uncovered cyclic proton transfers occurring between a glutamine amino acid and a manganese-bound solvent molecule. This interaction is a central part of the catalytic process, as it allows the enzyme to cycle between its two electronic states. The researchers also found the proton movements within the active site to be unusual, as several amino acids did not have a proton where they normally would. The study demonstrates the dramatic effects a metal has on the chemistry of the active site that is usually not accounted for."Our results suggest that this mechanism is more complex and atypical than what past studies had theorized," said Jahaun Azadmanesh, a researcher at UNMC and study co-author.As a next step in the project, the researchers are now planning to examine the enzyme's structure when it is bound to a superoxide substrate. They also aim to study mutated components of MnSOD to gain more details regarding how each amino acid influences catalysis. Another research goal is to expand their neutron analysis to other enzymes that rely on electron and proton transfers to carry out cellular tasks."Over a fourth of all known enzyme activities involve electron and proton transfers," said Azadmanesh. "MnSOD is just one enzyme in a sea of many others, and with neutrons, we can study their catalytic mechanisms to a level of detail that hasn't been possible before."
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Biology
| 2,021 |
April 6, 2021
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https://www.sciencedaily.com/releases/2021/04/210406120732.htm
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How the fly selects its reproductive male
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Even a well-characterized genome, such as that of the Drosophila the so-called fruit fly, still holds surprises. A team from the University of Geneva (UNIGE), Switzerland, in collaboration with Cornell University (USA) and the University of Groningen (Netherlands), has discovered an RNA coding for a micro-peptide -- a very small protein -- that plays a crucial role in the competition between spermatozoa from different males with which the female mates. In addition to shedding new light on this biological mechanism, this work, to be read in the journal
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In many species, including insects, mating induces physiological changes in the female aimed at the reproductive success of the couple. This response is induced by substances in the male's seminal fluid that interact with the female's reproductive system. These post-coital changes include increased ovulation and egg laying, semen storage and release, dietary changes and gut growth. A mated female also becomes less receptive to other males and can use the semen stored in her spermatheca from her first intercourse for many days. However, this behavior is counterbalanced by the "last male preference" phenomenon. Indeed, despite the decrease in libido normally induced by a first mating, females sometimes decide to mate with a new, healthier or stronger male, probably in order to have more robust offspring. In this case, the semen of the first male is expelled and only that of the last male is kept.The authors of this study have studied this phenomenon in Drosophila, the small fly that lingers around overripe or rotting fruit. This model organism, very popular with researchers for genetic and developmental studies, allows for easy observation and study of reproductive behavior. The biologists analyzed the proteins produced by the accessory functional gland, homolog of the human prostate. "Among the proteins we identified as essential for a normal response after mating is a micro-peptide, a very small protein that had never been studied before, as the RNA that codes for it was considered 'non-coding'," says Clément Immarigeon, first author of this study conducted in the Department of Genetics and Evolution of the Faculty of Science at UNIGE.In order to verify if this peptide finally played a determining role, the researchers created mutants that no longer possess it. In females first mated by a mutant male, the phenomenon of "last male preference" is no longer observed. Indeed, if they are then mated by another male, they lay eggs fertilized by the sperm of both males, and not exclusively by the last progenitor, which could reduce the robustness of their offspring. "To our surprise, we found that this micro-peptide -- encoded by a putative non-coding transcript -- performs important reproductive functions. Such micro-peptides were not previously recognized but are emerging as important players in complex biological processes," summarizes Robert Maeda, researcher in the Department of Genetics and Evolution at UNIGE and last author of the study.The study of these mating-induced phenomena is of particular interest in certain insect species responsible for sanitary, economic or environmental problems. A biological alternative to non-selective insecticides is the "sterile insect" method, which limits harmful populations by releasing millions of sterilized males into the wild to prevent females from mating with fertile wild males. A better understanding of the post-mating response will allow the development of even more effective biological control methods.
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Biology
| 2,021 |
April 6, 2021
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https://www.sciencedaily.com/releases/2021/04/210406120712.htm
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Radical attack on live cells
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Is there a way to chemically manipulate small, confined areas on cellular surfaces? Scientists have developed a microfluidic probe to send a flow of free radicals on live cells and track the outcome using fluorescence imaging. As outlined in the journal
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Free radicals are important stimulants for cells. When live cells are exposed to radicals, they develop intense reactions that can lead to cell injury or even death. Many anticancer drugs are based on the action of free radicals sending cancer cells to death.However, scientists find it difficult to perform research on the reactions of live cells to radicals in a truly controlled way. Free radicals are unstable and react with their environment before reaching their targets. A team of scientists led by Jin-Ming Lin from Tsinghua University, Beijing, has now developed a microfluidic approach to continuously generate a flow of free radicals for subcellular manipulation.To make the radicals, the researchers chose a microfluidic two-component system. In this setup, one microchannel harbored a solution of enzymes able to cleave hydrogen peroxide. Another channel contained a solution of hydrogen peroxide and an organic dye. Both channels were immersed with their ends in a nutrient solution where a live cell was placed just below the channel ends. A third channel with an upward flow ensured that the fluids leaving the microchannel ends would meet in the middle position, forming a confined reaction zone.According to the authors, this setup ensured that the reaction zone had the size of only a few micrometers. In this zone, the enzyme horseradish peroxidase would react with the hydrogen peroxide to form reactive enzyme intermediates, which then reacted with the organic dye to give an organic radical. Immediately after their generation, the dye radicals would then attack the cell placed directly below the reaction zone.After tens of seconds of component flow and radical attack, the researchers observed that a tiny spot emitting bright red fluorescence had emerged on the cellular membrane. Tracking this spot over time, the researchers found it slowly wandered around on the cellular surface.The authors say that the tiny fluorescent spot and its movement highlight the ability of the microfluidic method to manipulate small subareas on the cell surface. "By contrast with lipophilic tracers, which stain the whole cell, it is convincing that the free radicals generated only attack the target subcellular region of the single cell," they argue.One particular application fascinates the authors: they envision using the microfluidic probe as a "pen" for cells. "This will enable us to directly write text or draw graphics on single cells for personalized cell marking or artwork," they explain.
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Biology
| 2,021 |
April 6, 2021
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https://www.sciencedaily.com/releases/2021/04/210406120709.htm
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Source of Zika neurodevelopmental defects
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A study led by Edward Wojcik, PhD, Associate Professor of Biochemistry & Molecular Biology at LSU Health New Orleans School of Medicine, identified how microcephaly (abnormally small heads) and blindness may develop in Zika-infected fetuses, as well as a new way to potentially prevent these neurodevelopmental defects. The results are published online in
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The mechanism by which Zika virus disrupts neuronal development and results in congenital Zika syndrome was unknown. Because of similarities between Zika syndrome and a recognized congenital genetic disease (Kinesin-5) known to cause microcephaly and retinopathies in developing infants, the research team studied both, looking for similarities. They discovered a direct link, the first molecular and cellular evidence supporting a direct connection between the two."We had a hunch that the microcephaly and blindness that results from Kinesin-5 genetic disease could be linked to Zika infection, and the hunch paid off," notes Dr. Wojcik. "Our experiments identify a molecular motor as a target for degradation by an encoded Zika virus protein (Zika protease). The molecular motor is Kinesin-5, and it is required for cell division in humans. Our data identify Kinesin-5 as a target for the virus and links the infection to microcephaly."The researchers observed that Zika protease cuts Kinesin-5 during cell division, disrupting the process and causing a loss of function. They also suggest a way to prevent it.The Zika protease can degrade only a target protein it can reach. Since the protease is part of the endoplasmic reticulum (ER) membrane, only target proteins that come in direct contact with the ER can be degraded. In this way, the protease acts in a spatially restricted manner in the cell; target proteins are degraded only in certain regions of the cell volume and not in others. So, the research team proposes a drug that would affect only the Zika protease instead of drugs that would affect all target proteins in a cell."We predict and hope that potential drugs that inhibit Zika protease may be effective in preventing microcephaly and blindness from developing within Zika-infected fetuses," Dr. Wojcik concludes.
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Biology
| 2,021 |
April 6, 2021
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https://www.sciencedaily.com/releases/2021/04/210406092649.htm
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Glass nanopore pulls DNA like spaghetti through a needle
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DNA sequencing has become so common, few realize how hard it is to even extract a single molecule of DNA from a biological sample.
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Research led by UC Riverside is making it easier to detect and capture DNA from fluid samples such as blood using a tiny glass tube and electric current. The technique, described in the journal, DNA, a double-stranded, electrically charged molecule that contains all the information an organism needs to create and organize the building blocks of life, is tightly folded within the cell nucleus. Extracting the DNA from a single cell is time consuming and impractical for many medical and scientific purposes. Fortunately, as cells die naturally, their membranes burst, releasing the contents, including DNA. This means that a blood sample, for example, contains many strands of free-floating DNA that should, in theory, be easier to identify and extract in quantity.However, scavenger cells called macrophages that clean up cellular waste destroy most cell-free DNA, leaving it at low concentrations in the blood. Most approaches to capturing cell-free DNA require expensive techniques that first concentrate the molecules before using fluorescent dyes to help see the DNA.Corresponding author Kevin Freedman, an assistant professor of bioengineering at UC Riverside's Marlan and Rosemary Bourns College of Engineering, led an effort to improve detection and capture of DNA at lower concentrations by using an electric charge to direct a DNA sample directly into a glass tube with a tiny opening called a nanopore. Nanopore sensing has emerged as a fast, reliable, and cost-effective diagnosis tool in different medical and clinical applications."We know that if you apply voltage across a cell membrane, ions will move through pores in the cell membrane," Freedman said. "DNA also travels with the electric field, and we can use it to move the DNA."The researchers put a positive electrode inside a glass tube with an opening, or pore, 20 nanometers wide -- a bit bigger than a DNA molecule but too small to admit cells. They applied an electrical potential to the nanopore, which was dipped into a vial containing a DNA sample and a negative electrode. The cell-free DNA moved into the pore and blocked it. The change in electrical current as the DNA traveled through the pore allowed the researchers to detect it."It's like trying to pull spaghetti through a needle," Freedman said. "To go through the pore it has to be almost perfectly linear."The closer to the liquid surface the researchers held the pore, the more DNA it picked up."Amazingly, we found that DNA accumulates at the liquid-air interfaces. If there is a cooling layer, the DNA will try to go to the cooler location," Freedman said. "We hope the same is true for a blood sample, so the same mechanism can be used to concentrate DNA near the surface. Not only is this beneficial, but this nanopore-sensing strategy demonstrated a higher signal-to-noise ratio near the surface as well. It is really a win-win situation."With some refinements, the authors think their purely electric technique could help diagnose some kinds of cancer from a single blood sample. In addition to DNA, as tumors grow, vesicles are released into the blood stream. These mini lipid-based droplets can be thought of as mini-cells that are identical to the original cancer cells and could also be detected by nanopore sensing.Considering all the unique features of this purely electrical technique, the nanopore-sensing system has the potential to be utilized as a point-of-care diagnostic test evaluation in the future.
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Biology
| 2,021 |
April 6, 2021
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https://www.sciencedaily.com/releases/2021/04/210406092646.htm
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Origins of life could have started with DNA-like XNAs
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Nagoya University scientists in Japan have demonstrated how DNA-like molecules could have come together as a precursor to the origins of life. The findings, published in the journal
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"The RNA world is widely thought to be a stage in the origin of life," says Nagoya University biomolecular engineer Keiji Murayama. "Before this stage, the pre-RNA world may have been based on molecules called xeno nucleic acids (XNAs). Unlike RNA, however, XNA replication probably didn't require enzymes. We were able to synthesize an XNA without enzymes, strongly supporting the hypothesis that an XNA world might have existed before the RNA world."XNAs are formed of chains of linked nucleotides, similar to DNA and RNA but with a different sugar backbone. XNAs can carry genetic code very stably because the human body can't break them down. Some researchers have reported that XNAs containing specific sequences can act as enzymes and bind to proteins. This makes XNAs exciting in the field of synthetic genetics, with potential biotechnology and molecular medicine applications.Murayama, Hiroyuki Asanuma and colleagues wanted to find out if conditions likely present on early Earth could have led to XNA chain formation. They synthesized fragments of When placed together in a test tube under controlled temperature, the shorter L-"To the best of our knowledge, this is the first demonstration of template-driven, enzyme-free extension of The team also demonstrated that L-"Our strategy is an attractive system for experimenting with the construction of artificial life and the development of highly functional biological tools composed of The team plans to continue their investigations to clarify whether L-
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Biology
| 2,021 |
April 6, 2021
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https://www.sciencedaily.com/releases/2021/04/210406092643.htm
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Thinking with your stomach? The brain may have evolved to regulate digestion
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Many life forms use light as an important biological signal, including animals with visual and non-visual systems. But now, researchers from Japan have found that neuronal cells may have initially evolved to regulate digestion according to light information.
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In a study published this month in Light-dependent systems often rely on the activity of proteins in the Opsin family, and these are found across the animal kingdom, including in organisms with visual and non-visual systems. Understanding the function of Opsins in animals from different taxonomic groups may provide important clues regarding how visual/non-visual systems evolved in different creatures to use light as an external signal. The function of Opsins in the Ambulacraria groups of animals, which include sea urchins, has not been characterized, something the researchers aimed to address."The functions of eyes and visual systems have been well-characterized," says senior author of the study Professor Shunsuke Yaguchi. "However, the way in which light dependent systems were acquired and diversified throughout evolution is unclear especially in deuterostomes because of the lack of data regarding the signaling pathway in the Ambulacraria group."To address this, the researchers tested whether light exposure caused changes in digestive tract activity in sea urchins. They then conducted micro-surgical and genetic knockdown experiments to test whether Opsin cells in the sea urchin digestive system mediated the effect of light."The results provided new information about the role of Opsins in sea urchins," explains Professor Yaguchi. "Specifically, we found that stimulation of sea urchin larvae via light caused changes in digestive system function, even in the absence of food stimuli."Furthermore, the researchers identified brain serotonergic neurons near the Opsin-expressing cells that were essential for mediating the light-stimulated release of nitric oxide, which acts as a neurotransmitter."Our results have important implications for understanding the process of evolution, specifically, that of light-dependent systems controlled via neurotransmitters," says Professor Yaguchi.The data indicate that an early function of brain neurons may have been the regulation of the digestive tract in our evolutionary ancestors. Because food consumption and nutrient absorption are critical to survival, the development of a sophisticated brain-gut regulatory system may have been a major step in animal evolution.
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Biology
| 2,021 |
April 6, 2021
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https://www.sciencedaily.com/releases/2021/04/210406084037.htm
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New deadly snake from Asia named after character from Chinese myth 'Legend of White Snake'
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In 2001, the famous herpetologist Joseph B. Slowinski died from snakebite by an immature black-and-white banded krait, while leading an expedition team in northern Myanmar. The very krait that caused his death is now confirmed to belong to the same species identified as a new to science venomous snake, following an examination of samples collected between 2016 and 2019 from Yingjiang County, Yunnan Province, China.
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The new krait species, found in Southwestern China and Northern Myanmar, is described by Dr Zening Chen of Guangxi Normal University, PhD candidate Shengchao Shi, Dr Li Ding from the Chengdu Institute of Biology at the Chinese Academy of Sciences, Dr Gernot Vogel of the Society for Southeast Asian Herpetology in Germany and Dr Jingsong Shi of the Institute of Vertebrate Paleontology and Paleoanthropology at Chinese Academy of Sciences. Their study is published in the open-access, peer-reviewed journal The researchers decided to name the new species Bungarus suzhenae -- Suzhen's krait, after the mythical figure of Bai Su Zhen -- a powerful snake goddess from the traditional Chinese myth 'Legend of White Snake'.The legend says that, after thousands of years of practicing magic power, the white snake Bai Su Zhen transformed herself into a young woman and fell in love with the human man Xu Xian. Together, they ran a hospital, saving lots of human lives with medicine and magic. However, this love between goddess and human was forbidden by the world of the gods and, eventually, Bai Su Zhen was imprisoned in a tower for eternity. Since then, the Chinese regard her as a symbol of true love and good-heartedness."The black-and-white banded krait is one of the snakes most similar to the white snake in nature, so we decided to name it after Bai Su Zhen," say the authors.In fact, the discovery of Suzhen's krait was inspired by another accident from 2015, when the Chinese herpetologist Mian Hou was bitten by a black-and-white banded krait in Yingjiang. "It hurt around the wound, and the skin around it turned dark," said the unfortunate man, who luckily survived.The authors of the present study realized that the bite was different from those of the many-banded krait B. multicinctus, which go without clear symptoms or pain around the wound. This clue eventually led to the discovery of Suzhen's krait.Because kraits are highly lethal, understanding their species diversity and geographic distribution is vital for saving human lives. Thanks to adequate description and classification of deadly snakes, research on venom, antivenom development and proper snakebite treatment can advance more rapidly.The new study makes it easier to distinguish between krait species from China and adjacent southeastern Asia. "Three species of the black-and-white banded kraits from China were previously put under the same name -- many-banded krait, which would hinder appropriate medical treatment," the authors point out. Additionally, they suggest that antivenom for the many-banded krait be reevaluated accordingly.
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Biology
| 2,021 |
April 6, 2021
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https://www.sciencedaily.com/releases/2021/04/210406084026.htm
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What can we learn from vanishing wildlife species: The case of the Pyrenean Ibex
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Likely the first extinction event of the 2000s in Europe, the sad history of the Pyrenean Ibex (Capra pyrenaica pyrenaica) is a powerful example of the ever-increasing species loss worldwide due to causes related to human activity. It can, however, give us valuable information on what should be done (or avoided) to halt this extinction vortex.
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The distribution of this subspecies of Iberian Ibex was limited to the French and Spanish Pyrenees. Its first mention in an official written document, dating back to 1767, already refers to it as extremely rare. Like many other mountain goats, it was almost hunted to extinction before its killing became prohibited in 1913. Neither the institution of a national park (Ordesa & Monte Perdido), nor a conservation project with European LIFE program funding could stop the extinction of the Pyrenean Ibex eventually officialised on January 6, 2000. But the story of this charismatic animal did not end there -- a controversial cloning program was started instantly with no scientific agreement, nor support from regional environmental NGOs, claiming that de-extinction was possible even in the absence of further DNA studies.To find out more about the drivers of its extinction, an international team composed of 7 nationalities built a database of all known museum specimens and reconstructed the demographic history of the Pyrenean Ibex based on DNA evidence. Their research is published in the open-access, peer-reviewed journal The research found that after a population expansion between 14,000 and 29,000 years ago (which is quite recent from a genetic point of view), a significant loss of genetic diversity followed between approximately 15,000 and 7,500 years BP, and continued until present. By that time, the Pyrenean Ibex also lived outside the Pyrenean mountain chain, but, gradually, its distribution was reduced to only one valley in the Ordesa National Park in the Spanish Pyrenees.Written sources confirm hunting of the Pyrenean Ibex from as early as the 14th century, and during the 19th and 20th century it became a common target for trophy hunters. Undoubtedly, hunting played an important role in reducing its population numbers and distribution area, but it is not possible -- with the information currently available -- to pinpoint it as the straw that broke the camel's back. Infectious diseases that originate from livestock (for instance, those caused by the bluetongue virus, BTV, and sarcopses) are capable of decimating other subspecies of Iberian Ibex in extremely short periods of time.While the relative contribution of various factors remains largely unknown, it seems that hunting and diseases transmitted from other animals have been effective in drastically reducing the number of Pyrenean ibexes over the last two centuries, because they were acting on an already genetically weakened population. This low genetic diversity, combined with inbreeding depression and reduced fertility, brought the population beyond the minimum viable size -- from that point onwards, extinction was inevitable.This case study shows the importance of historical biological collections for genetic analyses of extinct species. A privately owned 140-year-old trophy preserved in Pau, France, was genotyped as part of this research, showing that private individuals may possess material of high value. As there is little knowledge of such resources, the authors call for the creation of an online public database of private collections hosting biological material for the benefit of biodiversity studies.
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Biology
| 2,021 |
April 5, 2021
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https://www.sciencedaily.com/releases/2021/04/210405140133.htm
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New method expands the world of small RNAs
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A team led by a biomedical scientist at the University of California, Riverside, has developed a new RNA-sequencing method -- "Panoramic RNA Display by Overcoming RNA Modification Aborted Sequencing," or PANDORA-seq -- that can help discover numerous modified small RNAs that were previously undetectable.
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RNA plays a central role in decoding the genetic information in DNA to sustain an organism's life. It is generally known as the intermediate molecule used to synthesize proteins from DNA. Cells are full of RNA molecules in complex and diverse forms, two main types being ribosomal RNA, or rRNA; and transfer RNA, or tRNA; which are involved in the synthesis of proteins.Small RNAs play essential roles in health and diseases, including cancer, diabetes, neurological diseases, and infertility. Examples of small RNAs are microRNA; piwi-interacting RNA, or piRNA; and tRNA-derived small RNA, or tsRNA. Small RNAs can get modified by chemical groups and thus acquire new functions.The development of high-throughput RNA sequencing technologies -- useful for examining the quantity and sequences of RNA in a biological sample -- has uncovered an expanding repertoire of small RNA populations that fine-tune gene expression and protect genomes."PANDORA-seq can be widely used to profile small RNA landscapes in various physiological and disease conditions to facilitate the discovery of key regulatory small RNAs involved in these conditions," said Qi Chen, an assistant professor of biomedical sciences in the UCR School of Medicine, who led the study published today in PANDORA-seq employs a stepwise enzymatic treatment to remove key RNA modifications, which then takes off the invisibility cloak used by the modified small RNAs."PANDORA-seq has opened Pandora's box of small RNAs," said Tong Zhou, a bioinformatician at the University of Nevada, Reno School of Medicine and a co-corresponding author of the study. "We can now dance with these once invisible partners in the RNA ballroom."According to Chen, PANDORA-seq uncovers a surprising small-RNA landscape that is dominated by tsRNAs and rRNA-derived small RNAs, or rsRNAs, rather than microRNAs, which were previously believed to dominate many mammalian tissues and cells."With PANDORA-seq, we found unprecedented microRNA/tsRNA/rsRNA dynamics when somatic cells are reprogrammed to induced pluripotent stem cells, which are generated by adult cells and have properties similar to those of embryonic stem cells, making them capable of differentiating into all cell types of the body," said Sihem Cheloufi, an assistant professor of biochemistry at UCR and a co-corresponding author of the paper. "Some tsRNAs and rsRNAs can impact protein synthesis and even affect embryonic stem cell lineage differentiation in embryonic stem cells."Chen explained the current best-studied classes of small RNAs in mammals are microRNAs, which are abundant in mammalian somatic cells and control the kind and amount of proteins the cells make; and piRNAs, which are mainly expressed in the testis and modulate germ cell development."Currently, these small RNAs can be comprehensively profiled by high-throughput methods such as RNA sequencing," he said. "However, the widely used small RNA sequencing protocols have intrinsic limitations, which prevent certain modified small noncoding RNAs from being detected during RNA sequencing. PANDORA-seq overcomes these limitations."Junchao Shi, a doctoral student working in Chen's lab and the research paper's first author is enthusiastic about the use of PANDORA-seq."The new method could revolutionize the view of small RNA landscapes," he said. "Frankly, all previous studies using traditional RNA-sequencing may now need to be revisited."Cheloufi said the team now wants to understand how tsRNA/rsRNA are generated, how they function in stem cells, and how they orchestrate cell fate decisions during development."Answers to these questions are timely to develop diagnostic tools, identify therapeutic targets, and advance regenerative medicine," she said.While developing PANDORA-seq, Chen was reminded of the parable of the blind men and the elephant, which teaches truth is only revealed when various parts come together."We sometimes forget the big picture, being focused on just a small part of it," he said. "Perhaps the only way to arrive at total truth -- the big picture -- is to push against our boundary of knowledge and confirm the revealed truth with newly devised technology.""It is fascinating to observe down the lenses of a microscope in the lab the profound cell fate change during cellular reprogramming and differentiation," said Reuben Franklin, a doctoral student in Cheloufi's lab and a coauthor on the study. "But PANDORA-seq allows us to eavesdrop on the molecular players during these processes."
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Biology
| 2,021 |
April 5, 2021
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https://www.sciencedaily.com/releases/2021/04/210405131039.htm
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An artful study of cellular development in leaves
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How do we become a complex, integrated multicellular organism from a single cell?
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While developmental biologists have long researched this fundamental question, Stanford University biologist and HHMI investigator Dominique Bergmann's recent work on the plant Arabidopsis thaliana has uncovered surprising answers.In a new study, published April 5 in "All the cells are coordinated, and yet they're all individuals with their own genetic programs," said Bergmann, who is the Shirley R. and Leonard W. Ely, Jr. Professor in the School of Humanities and Sciences and senior author of the study. "And so we're really working to appreciate that balance between seeing what's new and special and unique about each one while also recognizing how they are working together."While many scientists in this field focus on fruit flies and roundworms, some aspects of biological development will only be understood by studying other organisms -- such as the plant Arabidopsis thaliana, which is the Bergmann lab's specialty."As we think about flexibility and resilience in the face of a changing world, we want to learn more about how organisms can manage to build functional bodies when they are under stress or exposed to extreme environments," said Lopez-Anido, who is lead author of the study. "This requires research with organisms that have flexible and tunable lifestyles, such as the plants we study."As part of a family of artists, Lopez-Anido also embraced a uniquely artistic perspective to interpret and share this research. Within the paper itself, she used a pointillism-inspired analysis software to elegantly organize and visualize her massive dataset. Additionally, her sister, artist Virginia Lopez-Anido, created artwork inspired by Camila's research, which will be featured on the cover of While previous experiments on Arabidopsis had worked out some of the important genes and steps in making specialized cells, this new cell-by-cell data fills in additional details of development. The researchers found, for example, that cells might double-back on the developmental path they seemed to be following, and that it was also possible to jump ahead. They also noticed that there may be differences in the way new stem cells regulated transitions between cell types relative to old stem cells; and whereas they had previously known of core steps in cell differentiation, they saw there were actually many small, seemingly continuous steps along the way.One especially intriguing finding concerns a crucial gene, called SPEECHLESS, that plays a role in the formation of pores, called stomata, through which the plant exchanges gases and regulates water content. The Bergmann lab has studied SPEECHLESS extensively, but the new data hinted that it was expressed for a longer stretch of the developmental process than they expected. In a follow-up experiment, the researchers were able to selectively remove the gene after it completed its known role but sooner than the new data said it was done being expressed. Sure enough, the developmental programs went off track -- and the researchers are now working to figure out why."It was a contradiction of what we thought we knew and it was really exciting," Bergmann said. "It makes us want to dig in to other unexpected details -- what might look like insignificant blips in the data -- and see what we've missed."Bergmann credits Lopez-Anido and this work with inspiring several avenues of research, including reconsidering what it means to be a stem cell, reframing events that define final differentiation stages and reevaluating what it means to be born as a cell on the top versus bottom of a leaf.Analyzing cell identities from nearly 20,000 cells -- and 30,000 genes -- required machine learning algorithms. So, Lopez-Anido created an organizational framework built around one of the most widely used analysis tools, which is called Seurat after pointillist painter Georges Seurat. As in pointillism, individual dots, which represented individual cells and their specific gene expression signatures, blended together in visualizations that enabled the researchers to see large-scale trends.Virginia Lopez-Anido visualized Camila's work in another way. She developed a drawing series on the nature of scientific inquiry, as well as a clay model series of tissue landscapes inspired by scanning electron microscope images of stomata, which is the art that will grace the cover of "I like to engage with artists and scholars across disciplines because it can bring new layers of meaning to science -- and make science more accessible, which is very important to me," said Camila Lopez-Anido, who has taught scientific literacy at Bard College through their Citizen Science program and will soon begin work as an assistant professor of biology at Reed College. "I'm looking forward to fostering more of these meaningful research experiences and collaborations for my mentees."This research was funded by the National Institutes of Health, EMBO and The German Research Foundation. Bergmann is an investigator of the Howard Hughes Medical Institute, which also provided funding for this research.
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Biology
| 2,021 |
April 5, 2021
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https://www.sciencedaily.com/releases/2021/04/210405113636.htm
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Mysterious 'nuclear speckle' structures inside cells enhance gene activity, may help block cancers
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A team led by scientists at the Perelman School of Medicine at the University of Pennsylvania has illuminated the functions of mysterious structures in cells called "nuclear speckles," showing that they can work in partnership with a key protein to enhance the activities of specific sets of genes.
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The discovery, which will be published on April 5 in "This study shows that nuclear speckles work as major regulators of gene expression, and suggests that they have a role in some cancers," said study senior author Shelley Berger, PhD, the Daniel S. Och University Professor in the Department of Cell and Developmental Biology.Nuclear speckles, tiny structures within the nucleus of every mammalian cell, were first observed with a microscope in 1910, but in the ensuing 111 years, scientists have discovered little about their functions.One early theory was that the speckles are essentially storage depots, since they do contain important molecules needed to copy out the DNA in genes into RNA transcripts and then to process those transcripts into the finished "messenger RNAs" that can be translated into proteins. In recent years, scientists have begun to find evidence that speckles play a more direct role in gene transcription.Nevertheless, identifying their precise functions and how those are regulated has been difficult, due to the basic challenges of studying speckles.In the study, Berger and colleagues, including first author Katherine Alexander, PhD, a postdoctoral researcher in the Berger Laboratory who did most of the experiments, overcame some of these challenges to reveal that speckles work with p53 to directly enhance the activity of certain genes.While p53 has long been known as a "transcription factor" or master switch that controls the activity of a broad set of genes, the researchers showed that it exerts this effect on a subset of its target genes via nuclear speckles. The protein acts as a matchmaker, bringing together speckles and DNA containing these target genes. When the speckles and genes get close, the level of transcription of the genes jumps significantly.The researchers went even further to show that the p53 target genes whose activity is boosted via speckles have a set of functions that are broadly distinct from those of other p53 target genes."Speckle-associated p53 target genes, compared to other p53 target genes, are more likely to be involved in tumor-suppressing functions such as stopping cell growth and triggering cell suicide," Alexander said.These findings not only confirm nuclear speckles as enhancers of gene activity, but also implicate them in the functions of a key tumor-suppressor protein, which is known to be disrupted in about half of all cancers. In some cancers, p53 is mutated in a way that causes it not only to lose its tumor-suppressor function but also to actively drive cancerous growth. The researchers are now working to determine if nuclear speckles are involved in mediating this cancer-driving effect of mutant p53."If that proves to be the case," Berger said, "then in principle we could develop treatments to interfere with this association between p53 and speckles -- an association that might turn out to be a real Achilles heel for cancer."
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Biology
| 2,021 |
April 5, 2021
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https://www.sciencedaily.com/releases/2021/04/210405113600.htm
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Deep dive into key COVID-19 protein is a step toward new drugs, vaccines
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Researchers in the Oregon State University College of Science have taken a key step toward new drugs and vaccines for combating COVID-19 with a deep dive into one protein's interactions with SARS-CoV-2 genetic material.
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The virus' nucleocapsid protein, or N protein, is a prime target for disease-fighting interventions because of the critical jobs it performs for the novel coronavirus' infection cycle and because it mutates at a comparatively slow pace. Drugs and vaccines built around the work of the N protein carry the potential to be highly effective and for longer periods of time -- i.e., less susceptible to resistance.Among the SARS-CoV-2 proteins, the N protein is the viral RNA's biggest partner. The RNA holds the genetic instructions the virus uses to get living cells, such as human cells, to make more of itself, and the N protein binds to the RNA and protects it.Published in Biophysical Journal, the findings are an important jump-off point for additional studies of the N protein and its interactions with RNA as part of a thorough look at the mechanisms of SARS-CoV-2 infection, transmission and control.Elisar Barbar, professor of biochemistry and biophysics at Oregon State, and Ph.D. candidate Heather Masson-Forsythe led the study with help from undergraduate students Joaquin Rodriguez and Seth Pinckney. The researchers used a range of biophysical techniques that measure changes in the size and shape of the N protein when bound to a fragment of genomic RNA -- 1,000 nucleotides of the 30,000-nucleotide genome."The genome is rather large for a virus and requires many copies of the N protein to stick to the RNA to give the virus the spherical shape that is necessary for the virus to make more copies of itself," Barbar said. "Our study helps us quantify how many copies of N are needed and how close they are to each other when they stick to the RNA. "Biophysical studies of N with large segments of RNA by nuclear magnetic resonance are rare, Barbar said, because of the difficulty of preparing the partially disordered N protein and long RNA segments, both prone to aggregation and degradation, but these kinds of studies are a specialty of the Barbar lab. Other researchers' studies generally have been limited to much smaller pieces of RNA and smaller pieces of the N protein.Rather than just looking at the RNA-binding regions of the N protein on their own, the 1,000-nucleotide view allowed scientists to learn that the protein binds much more strongly when it's a full-length dimer -- two copies attached to one another -- and to identify regions of the protein that are essential for RNA binding."The full protein has structured parts but is actually really flexible, so we know that this flexibility is important for RNA binding," Masson-Forsythe said. "We also know that as N proteins start to bind to the longer RNA, the result is a diverse collection of bound protein/RNA complexes as opposed to one way of binding."Drugs that thwart the N protein's flexibility would thus be one potential avenue for pharmaceutical researchers, she said. Another possibility would be drugs that disrupt any of those protein/RNA complexes that prove to be of special significance.A National Science Foundation Early-concept Grant for Exploratory Research (EAGER) supported this research through the NSF's Division of Molecular and Cellular Biosciences. The Oregon State nuclear magnetic resonance facility used in the study is funded in part by the National Institutes of Health and the M.J. Murdock Charitable Trust, and the NIH also supported the native mass spectrometry data acquisition portion of the research.Zhen Yu, Richard Cooley, Phillip Zhu and Patrick Reardon of Oregon State and James Prell and Amber Rolland of the University of Oregon were the other researchers on the project.
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Biology
| 2,021 |
April 5, 2021
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https://www.sciencedaily.com/releases/2021/04/210405113550.htm
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Piping plovers breed less and move more in the northern great plains
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Piping plover breeding groups in the Northern Great Plains are notably connected through movements between habitats and show lower reproductive rates than previously thought, according to a new U.S. Geological Survey study. These new findings point to a need for further studies and suggest the species may show a higher extinction risk than currently presumed.
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Piping plovers are small-bodied, short-distance migratory shorebirds. The Northern Great Plains population has been listed as a threatened species under the U.S. Endangered Species Act since 1985. Previously, wildlife managers had assumed four separate breeding groups within the Northern Great Plains and that individuals from these groups moved infrequently between habitats. Earlier studies based on this assumption resulted in a low extinction risk for the species.Scientists analyzed movement, survival and renesting rates in two of the assumed breeding groups of piping plovers over four distinct management units along the Missouri River and alkaline wetlands distributed throughout the prairie pothole region from 2014 -- 2019. Piping plover reproductive rates were studied between 2014 -- 2016. The study areas are within North Dakota, South Dakota and Montana and include the U.S. alkali wetlands, Lake Sakakawea, the Garrison Reach of the Missouri River, and Lake Oahe.Results show river and alkali wetland habitats appear to be of higher quality than reservoir habitats, which had lower annual survival, increased movement away from the habitat, lower renesting success, and lower reproductive output.Habitat availability affected nearly every parameter examined in this study. In general, when more habitat was available, piping plover vital rates improved. These findings support the current focus of managing the Missouri River for abundant breeding habitat for piping plovers.Study findings show managing for successful first nests for Northern Great Plains piping plovers is key to improving reproductive output. Piping plovers are intensively managed throughout their range, and in the Northern Great Plains, management of habitat, water and predation, including vegetation removal and protective fences around nests, are common conservation strategies. Therefore, intensive management focused on the protection of early nests or first nest attempts would likely be more effective than strategies that assume equivalent productivity from renests.The study also shows that piping plovers move between the northern Missouri River habitat and the U.S. alkali wetlands at a rate that is substantially higher than previously assumed. Further, movement rates were unbalanced and varied between hatch-year and adult plovers. Adults were more likely to forego breeding altogether than to relocate to alternate management units and breed. This implies that either the rates of movement or the way local bird populations are managed may need to be reevaluated.
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Biology
| 2,021 |
April 5, 2021
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https://www.sciencedaily.com/releases/2021/04/210405075859.htm
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Paleopharmaceuticals from Baltic amber might fight drug-resistant infections
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For centuries, people in Baltic nations have used ancient amber for medicinal purposes. Even today, infants are given amber necklaces that they chew to relieve teething pain, and people put pulverized amber in elixirs and ointments for its purported anti-inflammatory and anti-infective properties. Now, scientists have pinpointed compounds that help explain Baltic amber's therapeutic effects and that could lead to new medicines to combat antibiotic-resistant infections.
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The researchers will present their results today at the spring meeting of the American Chemical Society (ACS). Each year in the U.S., at least 2.8 million people get antibiotic-resistant infections, leading to 35,000 deaths, according to the U.S. Centers for Disease Control and Prevention. "We knew from previous research that there were substances in Baltic amber that might lead to new antibiotics, but they had not been systematically explored," says Elizabeth Ambrose, Ph.D., who is the principal investigator of the project. "We have now extracted and identified several compounds in Baltic amber that show activity against gram-positive, antibiotic-resistant bacteria."Ambrose's interest originally stemmed from her Baltic heritage. While visiting family in Lithuania, she collected amber samples and heard stories about their medicinal uses. The Baltic Sea region contains the world's largest deposit of the material, which is fossilized resin formed about 44 million years ago. The resin oozed from now-extinct pines in the Ambrose and graduate student Connor McDermott, who are at the University of Minnesota, analyzed commercially available Baltic amber samples, in addition to some that Ambrose had collected. "One major challenge was preparing a homogeneous fine powder from the amber pebbles that could be extracted with solvents," McDermott explains. He used a tabletop jar rolling mill, in which the jar is filled with ceramic beads and amber pebbles and rotated on its side. Through trial and error, he determined the correct ratio of beads to pebbles to yield a semi-fine powder. Then, using various combinations of solvents and techniques, he filtered, concentrated and analyzed the amber powder extracts by gas chromatography-mass spectrometry (GC-MS).Dozens of compounds were identified from the GC-MS spectra. The most interesting were abietic acid, dehydroabietic acid and palustric acid -- 20-carbon, three-ringed organic compounds with known biological activity. Because these compounds are difficult to purify, the researchers bought pure samples and sent them to a company that tested their activity against nine bacterial species, some of which are known to be antibiotic resistant."The most important finding is that these compounds are active against gram-positive bacteria, such as certain "We are excited to move forward with these results," Ambrose says. "Abietic acids and their derivatives are potentially an untapped source of new medicines, especially for treating infections caused by gram-positive bacteria, which are increasingly becoming resistant to known antibiotics."
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Biology
| 2,021 |
April 5, 2021
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https://www.sciencedaily.com/releases/2021/04/210405113645.htm
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Hidden diversity of coral more important for conservation than previously thought
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In recent years, advancements in DNA sequencing have exposed a large amount of hidden diversity in reef-building corals: species that appear identical to one another but are genetically distinct. Typically ignored as they are invisible to the naked eye, a team of researchers at the California Academy of Sciences and The University of Queensland, along with over a dozen international collaborators, is taking a more holistic approach to understand these hidden species by investigating overlooked ecological differences that have wide-ranging implications for the vulnerability and resilience of reef-building corals. The team hopes that their findings, published today in
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"We know we are greatly underestimating the true number of coral species because of this hidden diversity," says lead author and Academy Curator Pim Bongaerts. "In our study, we provide one of the first clear examples of how coral species that look identical can be very different in terms of their ecology and physiology, from when they reproduce to what depths they prefer. This means that our current framework for classifying reef-building corals based primarily on morphology is limiting our ability to understand and protect them."By conducting one of the most extensive genomic studies of a coral species to date, which involved obtaining DNA samples from more than 1,400 individuals, the researchers began their study by discovering that the "serpent coral" (Using remotely-operated vehicles and specialized deep diving gear, the researchers investigated corals from shallow depths down to 80 meters beneath the surface -- into the vastly understudied mesophotic zone of coral reefs. They discovered that although individuals from each species could be found over the entire range of depths, they had distinct depths where they were most abundant, with corresponding differences in physiological traits such as protein content that affect their ability to survive and thrive at their preferred depths."Knowing what corals thrive where and at which depths is crucial for reef conservation," says study co-author at The University of Queensland Professor Ove Hoegh-Guldberg. "Most marine protected areas only protect shallow reefs, which means that hidden species at mesophotic depths are being overlooked by current conservation strategies. We need to give this gap in protection some further thought."Besides the physiological and depth differences, the research team also developed a rapid DNA test to be able to identify these species in the field and monitor their reproduction. They discovered that there were differences between the species in the timing of broadcast spawning -- the mechanism whereby environmental cues trigger an entire population of corals to synchronously release their gametes. This staggered spawning may provide an explanation for the lack of interbreeding between the species (a common occurrence for many corals) despite living side-by-side on the reef."For years we have asked ourselves about the relevance of this hidden diversity, wondering if we are missing something important," says Academy researcher and study co-author Alejandra Hernández-Agreda. "By using all of the tools at our disposal to analyze not just the morphology, but all these other aspects of these species as well, we now show how this hidden diversity can mask major differences in these species that could translate to their ability to cope with the rapidly changing conditions of our world's oceans."Ultimately, the researchers hope that their findings reveal the importance of taking a holistic approach to understanding these hidden species that appear identical, but may be harboring key differences that impact global conservation efforts."At a moment when reefs around the world are experiencing rapid degradation," Bongaerts says, "it is critical to start capturing this hidden diversity -- not only of species, but of how they live and function -- to improve our understanding and ability to protect these fragile ecosystems."
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Biology
| 2,021 |
April 2, 2021
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https://www.sciencedaily.com/releases/2021/04/210402141745.htm
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Unravelling the secret of a critical immune cell for cancer immunity
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WEHI researchers have discovered a key differentiation process that provides an essential immune function in helping to control cancer and infectious diseases.
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The research, published in Led by WEHI Professor Stephen Nutt, Dr Michael Chopin and Mr Shengbo Zhang, it defines the role for a new regulatory protein -- DC-SCRIPT -- in producing dendritic cells.Dendritic cells are immune cells that activate 'killer' T cells, which are vital for clearing viral infections and for triggering a response to cancer tumours.Through gaining a better understanding of how this process works, researchers hope to be able to determine a way of directing the body to produce large numbers of dendritic cells, to enable it to better fight off cancer and infections.Professor Nutt said the research paper highlighted the importance of DC-SCRIPT in the production of effective dendritic cells."What we found, is that without this new factor, the cells develop poorly, and their capacity to fight infection and cancer, or to clear a parasite, is diminished," he said."The next stage of our research is to try and work out how we can get the body to produce these particular dendritic cells, cDC1s, in large volumes in order to boost the body's natural tumour response."Dr Chopin said he was confident cDC1s held the clues to improving immunity to viruses and tumours."This paper clearly shows DC-SCRIPT is one of the regulators of dendritic cell production. As a result of this study, we're now focussed on ways we could harness this to increase dendritic cell production," he said."We now have a biomarker to follow when we expand this elusive cell type, which we will continue to test in pre-clinical models."This research lays the foundation for future studies into dendritic cell production and their clinical applications in response to tumours."We have generated new tools, allowing us to trace these cells within the tumour and observe how they behave in the tumour environment," Dr Chopin said. This work was made possible with funding from the National Health and Medical Research Council and the Victorian Government.
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Biology
| 2,021 |
April 2, 2021
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https://www.sciencedaily.com/releases/2021/04/210402133814.htm
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Experimental therapy for parasitic heart disease may also help stop COVID-19
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James McKerrow, MD, PhD, dean of the Skaggs School of Pharmacy and Pharmaceutical Sciences at University of California San Diego, has long studied neglected tropical diseases -- chronic and disabling parasitic infections that primarily affect poor and underserved communities in developing nations. They're called "neglected" because there is little financial incentive for pharmaceutical companies to develop therapies for them.
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One of these neglected diseases is Chagas disease, the leading cause of heart failure in Latin America, which is spread by "kissing bugs" carrying the parasite Then, in the spring of 2020, the COVID-19 pandemic began to sweep through the United States. Researchers quickly reported that SARS-CoV-2, the coronavirus that causes COVID-19, can't dock on and infect human cells unless a human enzyme called cathepsin L cleaves the virus' spike protein.And it just so happens that cathepsin L looks and acts a lot like cruzain.In a study published March 31, 2021 by "Since K777 inhibits a human enzyme, not the virus itself, it's our hope that it's less likely the virus will evolve resistance against it," said McKerrow, co-senior author of the study with Thomas Meek, PhD, of Texas A&M University.K777 wasn't equally effective in all cell lines. That's likely because not all cell lines produced the same amount of cathepsin L or the same amount of ACE2, the host cell receptor that the virus' spike protein uses to latch onto cells after it's cleaved by cathepsin L. The inhibitor was best at preventing SARS-CoV-2 infection in the cells that produced the most cathepsin L and ACE2.The cell lines tested were derived from African green monkey kidney epithelium, human cervical epithelium and two types of human lung epithelium. While an important research tool, cell lines such as these are not necessarily representative of patients. They are easy to grow and manipulate in research laboratories because they are cancer cells, but that also means their molecular features likely differ from the average person's healthy lung or cervical cells."We were surprised at just how effective K777 is in blocking viral infection in the lab," McKerrow said. "Yet under usual circumstances it would be impractical and unlikely that we ourselves would be able to move the compound so quickly into clinical trials. We're fortunate that an 'entrepreneur-in-residence' program here at UC San Diego has helped bridge that gap."Selva Therapeutics, a privately held biotechnology company, has licensed K777 from UC San Diego. In parallel with this study, the company has also found that the experimental therapeutic prevented lung damage in COVID-19 animal models and was well-tolerated by people who participated in a Phase I clinical trial to assess safety. Selva is planning a Phase IIa clinical trial in non-hospitalized COVID-19 patients for late 2021.Many people with COVID-19 experience mild disease and can recover at home with supportive care to help relieve their symptoms. Currently, severe cases of COVID-19 may be treated with the antiviral drug remdesivir, approved by the U.S. Food and Drug Administration (FDA) for use in hospitalized patients, or a medication that has received emergency use authorization from the FDA, such as monoclonal antibodies. Worldwide, more than 124 million people have been diagnosed with COVID-19 and 2.72 million have died from the infection.Co-authors of the study include: Drake M. Mellott, Bala C. Chenna, Demetrios H. Kostomiris, Jiyun Zhu, Zane W. Taylor, Klaudia I. Kocurek, Ardala Katzfuss, Linfeng Li, Frank M. Raushel, Texas A&M University; Chien-Te Tseng, Aleksandra Drelich, Jason Hsu, Vivian Tat, University of Texas; Pavla Fajtová, UC San Diego and Academy of Sciences of the Czech Republic; Miriam A. Giardini, Danielle Skinner, Ken Hirata, Michael C. Yoon, Sungjun Beck, Aaron F. Carlin, Alex E. Clark, Laura Beretta, Vivian Hook, Anthony J. O'Donoghue, Jair Lage de Siqueira-Neto, UC San Diego; Daniel Maneval, Felix Frueh, Selva Therapeutics; Brett L. Hurst, and Hong Wang, Utah State University.
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Biology
| 2,021 |
April 2, 2021
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https://www.sciencedaily.com/releases/2021/04/210402114100.htm
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How pathogenic bacteria weather the slings and arrows of infection
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Infectious diseases are a leading cause of global mortality. During an infection, bacteria experience many different stresses -- some from the host itself, some from co-colonizing microbes and others from therapies employed to treat the infection. In this arms race to outwit their competition, bacteria have evolved mechanisms to stay alive in the face of adversities. One such mechanism is the stringent response pathway. Understanding how the activation of the stringent response pathway is controlled can provide clues to treat infection.
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In new research published this week online in the journal "This has been one of the most fun and exciting projects in my career," said Hiller.The joint project established that transfer RNAs (tRNAs) serve as a crucial component in the control of the activation of the stringent response pathway. tRNAs play a critical role in translation: they help to decode the genetic information into amino acids, the building blocks of proteins.However, sometimes they can make a mistake, where the tRNA carrier and the amino acid building block are mismatched, rendering the combination toxic. In stressful conditions, tRNAs make more errors and accumulation of these errors is a trigger for the stringent response. This biological process is akin to the malfunction of a machine in an assembly line that results in flaws in the final manufactured product.Many bacteria display a thick cell wall on their surface. Amino acids are a key component of this structure, and this research revealed that a protein involved in the addition of amino acids to this cell wall, the MurM enzyme, displays a strong preference for the tRNA loaded with mismatched building blocks. By diverting these toxic blocks towards cell wall synthesis and away from translation, MurM serves as a quality control manager who ensures that the flow line remains error-free and the manufacturing process can continue unabated.In the absence of MurM, cells under stress activate the stringent response more easily than the parental strain. These findings suggested that MurM serves as a gatekeeper of this stress response pathway."It is highly rewarding when suddenly intriguing observations are explained by a simple and clear model," Filipe said. "The proposal that the cell wall can be used to divert the accumulation of toxic compounds is quite exciting. I wonder what other surprises will come from the study of the bacterial cell surface.""To explore this further, we drew parallels between the bacteria we study and other species that do not encode MurM," said Aggarwal, who is now a postdoctoral fellow at NYU Langone Medical Center. In most domains of life, including human cells, the pathological consequences of these toxic tRNAs are mitigated by AlaXp, an enzyme that also corrects the defect by decoupling the tRNA from the incorrectly coupled building block.However, Streptococcus pneumoniae, the bacteria in this study, as well as multiple other bacteria with thick cell walls, do not encode AlaXp. Aggarwal adds, "We wanted to test whether artificially introducing an additional gatekeeper in the form of AlaXp to pneumococcal cellular machinery would allow the flow line to remain functional even in the absence of MurM. This line of investigation set us on a road to test whether the stress-dependent growth defects we observed were attributable to the protein's role in preventing accumulation of toxic tRNAs."The validation was a joint effort. The research at CMU employed genetic tools to decouple the role of the MurM in the architecture of the cell wall from its role in correcting toxic carrier-building block pairs. The work at Warwick made use of biochemical tools to reveal the underlying processes that render MurM optimal to correct the toxic molecules, while studies in Lisbon captured how the correction activity of the MurM enzyme impacts cell wall architecture. To quote Lloyd: "This international consortium was able to focus disparate yet connected areas of expertise to determine how previously considered disparate areas of microbial biochemistry collaborate to enable a crucial pathogen to navigate the stresses it endures during infection. This work provides a step change in our understanding of the resilience of bacteria as they cause infection."The study suggests that MurM is an alternative evolutionary solution to the challenge of these toxic tRNAs. These findings implicate cell wall synthesis in the survival of bacteria as they encounter unpredictable and hostile conditions in the host. The association between cell wall synthesis and translational fidelity is likely to be active in many other pathogens, implicating these findings in the biology of many other pathogens.This collaborative work sets the framework for future work exploring the molecular connection between two fundamental cell processes, translation and cell wall synthesis, and stress responses. Moreover, the pivotal position of the stringent response in survival to stresses and to antibiotics, suggests these findings will also shed light on pathways associated with bacterial drug resistance, a major challenge for this century.
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Biology
| 2,021 |
April 1, 2021
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https://www.sciencedaily.com/releases/2021/04/210401151308.htm
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First-of-its-kind mechanical model simulates bending of mammalian whiskers
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Researchers have developed a new mechanical model that simulates how whiskers bend within a follicle in response to an external force, paving the way toward better understanding of how whiskers contribute to mammals' sense of touch. Yifu Luo and Mitra Hartmann of Northwestern University and colleagues present these findings in the open-access journal
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With the exception of some primates, most mammals use whiskers to explore their environment through the sense of touch. Whiskers have no sensors along their length, but when an external force bends a whisker, that deformation extends into the follicle at the base of the whisker, where the whisker pushes or pulls on sensor cells, triggering touch signals in the nervous system.Few previous studies have examined how whiskers deform within follicles in order to impinge on the sensor cells -- mechanoreceptors -- inside. To better understand this process, Luo and colleagues drew on data from experimental studies of whisker follicles to create the first mechanical model capable of simulating whisker deformation within follicles.The simulations suggest that whisker deformation within follicles most likely occurs in an "S" shape, although future experimental data may show that the deformation is "C" shaped. The researchers demonstrate that these shape estimates can be used to predict how whiskers push and pull on different kinds of mechanoreceptors located in different parts of the follicle, influencing touch signals sent to the brain.The new model applies to both passive touch and active "whisking," when an animal uses muscles to move its whiskers. The simulations suggest that, during active whisking, the tactile sensitivity of the whisker system is enhanced by increased blood pressure in the follicle and by increased stiffness of follicular muscle and tissue structures."It is exciting to use simulations, constrained by anatomical observations, to gain insights into biological processes that cannot be directly measured experimentally," Hartmann says. "The work also underscores just how important mechanics are to understanding the sensory signals that the brain has evolved to process."Future research will be needed to refine the model, both computationally and by incorporating new experimental data.
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Biology
| 2,021 |
April 1, 2021
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https://www.sciencedaily.com/releases/2021/04/210401151253.htm
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Mice with hallucination-like behaviors reveal insight into psychotic illness
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The humble lab mouse has provided invaluable clues to understanding diseases ranging from cancer to diabetes to COVID-19. But when it comes to psychiatric conditions, the lab mouse has been sidelined, its rodent mind considered too different from that of humans to provide much insight into mental illness.
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A new study, however, shows there are important links between human and mouse minds in how they function -- and malfunction. Researchers at Washington University School of Medicine in St. Louis devised a rigorous approach to study how hallucinations are produced in the brain, providing a promising entry point to the development of much-needed new therapies for schizophrenia.The study, published April 2 in the journal "It's so easy to accept the argument that psychosis is a fundamentally human thing and say, 'Forget about mice'," said senior author Adam Kepecs, PhD, a professor of neuroscience and of psychiatry, and a BJC Investigator at the School of Medicine. "But right now, we're failing people with serious psychiatric conditions. The prognosis for psychotic patients has not substantially improved over the past decades, and that's because we don't really understand the neurobiology of the disease. Animal models have driven advances in every other field of biomedicine. We're not going to make progress in treating psychiatric illnesses until we have a good way to model them in animals."Psychosis occurs when a person loses touch with reality. During a psychotic episode, people may acquire false beliefs (delusions) or confidently believe that they are seeing or hearing things that are not occurring (hallucinations). A psychotic episode can be a sign of a serious mental illness such as schizophrenia or bipolar disorder, but people without mental illness also can experience symptoms such as hallucinations.To study how hallucinations occur, Kepecs -- with first author Katharina Schmack, MD, PhD, of Cold Spring Harbor Laboratory, and colleagues -- set up a computer game that could be completed by both people and mice. The researchers played a particular sound, and subjects indicated that they'd heard it by clicking a button (people) or poking their noses into a port (mice). The task was made challenging by obscuring the sound with background noise. People in the study rated how confident they felt that they'd accurately identified a real sound by moving a slider on a scale; mice indicated their confidence by how long they waited for a reward. When a subject confidently reported that he or she had heard a sound that was not actually played, the researchers labeled that a hallucination-like event.While simple in design, the task appeared to tap into the brain circuits underlying hallucinations. People with more hallucination-like events during the experiment also were more likely to experience spontaneous hallucinations -- as measured by questionnaires designed to evaluate psychiatric symptoms in the general population -- even though no participants were diagnosed with a psychiatric condition.People's beliefs and expectations can prime them to experience hallucinations. Expecting to hear a certain word makes it more likely that people actually report that they have heard it, even when it wasn't spoken. In fact, previous studies have shown that people who are prone to hallucinations are particularly susceptible to this kind of priming."Human speech is very difficult to comprehend in a noisy environment," Kepecs said. "We are always balancing our prior knowledge of human speech against what we're hearing in the moment to understand spoken language. You can easily imagine that this system can get imbalanced, and all of a sudden you're hearing things."To test whether mice also can be primed the same way, Kepecs and colleagues manipulated the mice's expectations by adjusting how frequently the sound was played. When the sound was played frequently, the mice were even more likely to confidently but wrongly report that they'd heard it -- similar to people.To better connect mouse and human experience, the researchers also used a drug that induces hallucinations. Ketamine can induce distortions in perceptions of sight and sound and can trigger psychotic episodes in healthy people. Mice that were given ketamine before performing the task also reported more hallucination-like events.Having established these crucial similarities between mice and people, the researchers then investigated the biological roots of hallucinations. By studying mice, they could make use of an arsenal of technologies for monitoring and controlling brain circuits to figure out what happens during hallucination-like events.The brain chemical dopamine has long been known to play a role in hallucinations. People experiencing hallucinations can be treated with antipsychotic medications that block dopamine. But how dopamine changes brain circuits to produce hallucinations has remained unknown.When studying mice, the researchers observed that elevations in dopamine levels preceded hallucination-like events and that artificially boosting dopamine levels induced more hallucination-like events. These behavioral effects could be blocked by administering the antipsychotic drug haloperidol, which blocks dopamine."There seems to be a neural circuit in the brain that balances prior beliefs and evidence, and the higher the baseline level of dopamine, the more you rely on your prior beliefs," Kepecs said. "We think that hallucinations occur when this neural circuit gets unbalanced, and antipsychotics rebalance it. Our computer game probably engages this same circuit, so hallucination-like events reflect this circuit imbalance. We are very excited about this computational approach to study hallucinations across species that enables us to finally probe the neurobiological roots of this mysterious experience."
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Biology
| 2,021 |
April 1, 2021
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https://www.sciencedaily.com/releases/2021/04/210401123902.htm
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Why some cancer drugs may be ineffective
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A possible explanation for why many cancer drugs that kill tumor cells in mouse models won't work in human trials has been found by researchers with The University of Texas Health Science Center at Houston (UTHealth) School of Biomedical Informatics and McGovern Medical School.
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The research was published today in In the study, investigators reported the extensive presence of mouse viruses in patient-derived xenografts (PDX). PDX models are developed by implanting human tumor tissues in immune-deficient mice, and are commonly used to help test and develop cancer drugs."What we found is that when you put a human tumor in a mouse, that tumor is not the same as the tumor that was in the cancer patient," said W. Jim Zheng, PhD, professor at the School of Biomedical Informatics and senior author on the study. "The majority of tumors we tested were compromised by mouse viruses."Using a data-driven approach, researchers analyzed 184 data sets generated from sequencing PDX samples. Of the 184 samples, 170 showed the presence of mouse viruses.The infection is associated with significant changes in tumors, and Zheng says that could affect PDX as a drug testing model for humans."When scientists are looking for a way to kill a tumor using the PDX model, they assume the tumor in the mouse is the same as cancer patients, but they are not. It makes the results of a cancer drug look promising when you think the medication kills the tumor -- but in reality, it will not work in human trial, as the medication kills the virus-compromised tumor in mouse," Zheng said.He hopes his findings will change researchers' approach to find a way to kill tumor cells."We all share the common goal of hoping to find a cure for cancer. There are 210 ongoing NIH-funded projects relevant to PDX models, with a combined annual fiscal year budget of over $116 million. We need to tighten up quality control and use models that are not compromised so that the treatments we give to future patients are effective," Zheng said.This work is a collaboration between the Texas Therapeutics Institute, Institute of Molecular Medicine (IMM) at McGovern Medical School, and the Data Science and Informatics Core for Cancer Research at the School of Biomedical Informatics."As a team, we synergized the strengths of McGovern Medical School's virology research and School of Biomedical Informatics' data analysis expertise, and it has led to the success of this project," said Zhiqiang An, PhD, co-senior author of the study, professor and Robert A. Welch Distinguished University Chair in Chemistry at McGovern Medical School.The study is partly supported by the Cancer Prevention and Research Institute of Texas through grant RP170668, RP150551, and RP190561; the National Institutes of Health through grants 1UL1TR003167 and R01AG066749; and the Welch Foundation AU-0042-20030616.Other UTHealth authors on the study include Hua Xu, PhD, professor and director of the Center for Computational Biomedicine at the School of Biomedical Informatics; Xuejun Fan, MD, PhD, research scientist with Texas Therapeutics Institute and the IMM at McGovern Medical School; Jay-Jiguang Zhu, MD, PhD, professor and director of neuro-oncology at McGovern Medical School and with UTHealth Neurosciences; Tong-Ming Fu, PhD, with the Texas Therapeutic Institute and and IMM at McGovern Medical School; Jiaqian Wu, PhD, associate professor of neurosurgery at McGovern Medical School; and Ningyan Zhang, PhD, professor with the Texas Therapeutic Institute and the IMM at McGovern Medical School.
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Biology
| 2,021 |
April 1, 2021
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https://www.sciencedaily.com/releases/2021/04/210401112857.htm
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Skin deep: Aquatic skin adaptations of whales and hippos evolved independently
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A new study shows that the similarly smooth, nearly hairless skin of whales and hippopotamuses evolved independently. The work suggests that their last common ancestor was likely a land-dwelling mammal, uprooting current thinking that the skin came fine-tuned for life in the water from a shared amphibious ancestor. The study is published today in the journal
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"How mammals left terra firma and became fully aquatic is one of the most fascinating evolutionary stories, perhaps rivaled only by how animals traded water for land in the first place or by the evolution of flight," said John Gatesy, a senior research scientist in the American Museum of Natural History's Division of Vertebrate Zoology and a corresponding author on the study. "Our latest findings contradict the current dogma in the field -- that relatives of the amphibious hippo might have been part of the transition as mammals re-entered life in the water."Despite their contrasting appearances, fully aquatic cetaceans -- the group that includes whales, dolphins, and porpoises -- and semi-aquatic hippopotamuses are each other's closest living relatives and share a common ancestor that lived about 55 million years ago. They also share a number of characteristics that are odd for most mammals: they give birth and nurse underwater, and lack scrotal testes and sebaceous glands (that secrete oily sebum) as well as most of their hair. Since these traits are rarely found in other mammals, one would assume that they were already present in the common ancestor of hippos and cetaceans. But how and when cetacean ancestors became fully aquatic remains a subject of intense debate.Paleontological studies on transitional extinct cetaceans suggest that entry into water was a gradual process that included amphibious phases. So did hippos and cetaceans develop adaptations for an aquatic lifestyle independently? Or was their common ancestor already amphibious, and from there, cetaceans diverged to become fully aquatic?"The simplest hypothesis is that the ancestor of whales and hippos was already amphibious, but evolution isn't always the shortest distance between two points," said the study's lead author Mark Springer, a biology professor at the University of California, Riverside.To help resolve this question, the researchers looked to the animals' skin, which shows profound evolutionary changes in response to aquatic life."When a group of animals becomes aquatic, skin becomes much more streamlined and uniform throughout," said Maksim Plikus, a co-corresponding author and a skin biologist from the University of California, Irvine. "Complex derivatives like hairs, nails, or sweat glands are no longer needed, and in fact, can become a hinderance to life under water, so those go away. And it loses the barrier function performed by the outer layer of skin, which in terrestrial mammals, is vital to keeping water from evaporating out of the body and preventing pathogens from getting in."The researchers compared the anatomy of hippo and cetacean skin based on histology and used genomic screens to compile a comprehensive list of "skin genes" that have been inactivated in both hippos and cetaceans. This was aided by examining -- for the first time -- the genome of the pygmy hippo, Choeropsis liberiensis, one of only two living hippo species."When you look at the molecular signatures, there is a striking and clear answer," said study co-corresponding author and evolutionary genomicist Michael Hiller, from the Max Planck Institute of Molecular Cell Biology and Genetics and the LOEWE-Centre for Translational Biodiversity Genomics in Germany. "Our results strongly support the idea that 'aquatic' skin traits found in both hippos and cetaceans evolved independently. And not only that, we can see that the gene losses in the hippo lineage happened much later than in the cetacean lineage."These gene results are in line with examinations of the skin itself: Unlike whales, hippos actually do have a very specialized kind of sweat gland that produces "blood sweat," an orange-colored substance that is speculated to have natural anti-microbial and sunscreen properties. And while cetaceans only have a few whiskers, hippos are fully whiskered but also have sparse body hairs, most prominent on their ears and the tip of their tail. The latter are used when hippos defecate, during which they quickly spin their tail and the brush-like hairs help to pulverize the feces all around as a way to mark territory. In addition, cetacean skin is much thicker than hippo skin, and hippos are alone in having hooves."These differences are fully consistent with the record of evolutionary history that is written in their genomes, which shows the independent knockout of skin genes on the cetacean lineage and on the hippo evolutionary line," Springer said. "None of the inactivating mutations that would have suggested a common aquatic ancestry are shared between these two lineages."
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Biology
| 2,021 |
April 1, 2021
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https://www.sciencedaily.com/releases/2021/04/210401112603.htm
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Successful Zika vaccine in preclinical studies
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UConn researcher Paulo Verardi, associate professor of pathobiology and veterinary science in the College of Agriculture, Health and Natural Resources, has demonstrated the success of a vaccine against Zika virus and recently published his findings in
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Verardi, a Brazilian native, was in Brazil visiting family in the summer of 2015 when the Zika outbreak first began to make waves and soon reached epidemic status.Back in the United States, Verardi kept tabs on the Zika epidemic and its emerging connection to microcephaly, a serious birth defect that causes babies to be born with small heads and underdeveloped brains.In October of that year, Verardi called then-Ph.D.-student Brittany Jasperse (CAHNR '19) into his office and told her he wanted to apply their newly developed vaccine platform and start developing a vaccine for Zika virus.Verardi and Jasperse were among the first researchers in the US to receive NIH funding to generate a vaccine against Zika virus, thanks to Verardi recognizing the significance of Zika virus early.Modern advancements in genomic technology have expediated the vaccine development process. In the past, researchers needed to have access to the actual virus. Now just obtaining the genetic sequence of the virus can be sufficient to develop a vaccine, as was the case for the Zika vaccine Verardi and Jasperse developed, and the COVID-19 vaccines currently approved for emergency use in the United States and abroad.Using the genetic sequence of Zika virus, Verardi and Jasperse developed and tested multiple vaccine candidates that would create virus-like particles (VLPs). VLPs are an appealing vaccine approach because they resemble native virus particles to the immune system and therefore trigger the immune system to mount a defense comparable to a natural infection. Critically, VLPs lack genetic material and are unable to replicate.The vaccine Verardi and Jasperse developed is based on a viral vector, vaccinia virus, which they modified to express a portion of Zika virus' genetic sequence to produce Zika VLPs. Their vaccine has an added safety feature that it is replication-defective when given as a vaccine but replicates normally in cell culture in the lab."Essentially, we have included an on/off switch," Jasperse says. "We can turn the viral vector on in the lab when we're producing it by simply adding a chemical inducer, and we can turn it off when it's being delivered as a vaccine to enhance safety."The team developed five vaccine candidates in the lab with different mutations in a genetic sequence that acts as a signal to secrete proteins. They evaluated how these mutations affected the expression and formation of Zika VLPs and then selected the vaccine candidate that had the highest expression of VLPs to test in a mouse model of Zika virus pathogenesis. This model was developed by Helen Lazear of University of North Carolina at Chapel Hill, whose lab Jasperse now works in as a postdoctoral research associate.Verardi and Jasperse found that mice who received just a single dose of the vaccine mounted a strong immune response and were completely protected from Zika virus infection. They did not find any evidence of Zika virus in the blood of challenged mice who were exposed to the virus after vaccination.Zika virus is part of a group of viruses known as flaviviruses which include dengue virus, yellow fever virus, and West Nile virus. Verardi and Jasperse's findings, particularly the mutations they identified that enhanced expression of Zika VLPs, could be useful for improving production of vaccines against diseases caused by other related flaviviruses.Ongoing work in the Verardi lab incorporates these novel mutations into vaccine candidates against other viruses, including Powassan virus, a tick-borne flavivirus that can cause fatal encephalitis.Verardi emphasizes that developing vaccines for viruses, in this case Zika, help the world be better prepared for outbreaks of novel and emerging viruses by having vaccine development frameworks in place."Emerging viruses are not going to stop popping up any time soon, so we need to be prepared," Verardi says. "Part of being prepared is to continue the development of these platforms."
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Biology
| 2,021 |
March 31, 2021
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https://www.sciencedaily.com/releases/2021/03/210331143031.htm
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Insight into the evolution of bones
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A joint team of palaeontologists has now for the first time analyzed bone structures in 400 million-year-old fossils of marine life at unprecedentedly high resolution and in 3D. To be able to view these structures, tomography experts examined the samples under the focused ion beam of a scanning electron microscope to calculate 3D images from the data, achieving resolutions in the nanometer range using technology that was initially developed to study battery corrosion.
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Whether fish, fowl, or mammal, all vertebrates have an internal skeleton of bones. In almost all vertebrates (with the exception of certain bony fish), the bone consists of a complex composite of minerals, proteins, and living bone cells (osteocytes) entrapped in the bone matrix. The bone cells are interconnected by tiny channels so that they can exchange substances and electrochemical signals, allowing the bone to grow and regenerate. Still, this complex architecture of live and inorganic material must have emerged at some point in the course of evolution. A team at the Museum für Naturkunde Berlin headed by Dr Florian Witzmann is investigating how and when this happened. Now they have discovered a possible milestone in this development.They have examined fossilised samples of bony armour from two early fish species that lived around 400 million years ago. One sample came from Tremataspis mammillata, a jawless fish that lived in the late Silurian period about 423 million years ago and belongs to the extinct group called Osteostraci. The second, much younger sample was a piece of bone from the fish Bothriolepis trautscholdi that lived in the late Devonian period about 380 million years ago and belongs to the extinct Placodermi, the earliest group of jawed fishes. "It was already known that these early vertebrates had bone cells, but we knew little about how the cells were connected to each other, as well as anything about the detailed structure of the lacuna, or cavities, in which the bone cells were located in the living animal. In order to be able to make more precise statements about bone metabolism, we had to have far more detailed images of these structures than were previously available," says Witzmann.To achieve this, HZB expert Dr. Ingo Manke suggested a method that is available at the HZB campus in Wannsee in the Electron Microscopy Laboratory: focussed ion-beam scanning electron microscopy (FIB-SEM) tomography on the ZEISS Crossbeam 340. In this device, a focussed gallium-ion beam continuously ablates material from the sample surface, gradually digging its way deeper into the sample. At the same time, an electron beam scans the freshly revealed part of the sample and provides data for creating 3D images at a resolution that is more than a hundred times finer than computer tomography.Manke's team had already used this method to study electrode materials for batteries, which have a network of fine paths for transporting ions. HZB physicist Markus Osenberg had previously employed a sophisticated evaluation procedure developed at HZB's 3D Analytics Lab to calculate the image from the measurement data. This is a specially trained neural network, a method borrowed from machine learning, because images of these kinds of samples cannot be calculated using standard methods. "Due to the countless paths through the bone, the sample surface is as full of holes as Swiss cheese," explains Osenberg, who is doing his doctorate in Manke's team. However, after some practice, the well-trained neural network recognises where the plane of the ablation runs and where the holes are, and reconstructs an accurate image of the ablated surface. "In fact, the structures in the bone samples are relatively similar to the structures in the electrode materials of batteries. But the fact that the neural network, which learned on battery materials, can now also image the fossil bone samples so well surprised us," says Osenberg.Even in the older sample of the jawless armoured fish, the 3D images display a complex network with cavities (lacunae) for the bone cells and tiny channels through the bone interconnecting these cavities. "The channels are a thousand times narrower than a human hair and yet, amazingly, they have been almost completely preserved over these 400 million years," says Manke.Elaborate analysis of the high-resolution 3D images shows in detail how the network was constructed of cavities (lacuna) and the channels between them. "This proves that our early, still-jawless ancestors already possessed bones characterised by internal structure similar to ours and probably by many similar physiological capabilities as well," Witzmann explains. "The most important palaeobiological finding is that we can also detect actual traces of metabolism in these earliest bone samples," says Yara Haridy, who is doing her PhD at the Museum für Naturkunde Berlin. Through local osteolysis, i.e. dissolution of the bone matrix that surrounded the bone cells, the organism was probably able to cover its need for phosphorus in times of scarcity. This gave it an advantage over its more primitive contemporaries, who had cell-free bone, i.e. whose bones contained no osteocytes. "This advantage apparently led to the widespread establishment of bones with bone cells in vertebrates, as we know it in humans as well. It is an important step towards understanding how our own bone metabolism came about," Haridy explains. As a summary, she emphasizes: "Even in early fossil bone, bone cells could dissolve and restore bone minerals, this means that bones themselves act as batteries by storing minerals and releasing them later! This ability provided an undoubtable advantage to jawless fish with bone cells over vertebrates without. This advantage was possibly so profound as to alter vertebrate evolution, as later jawed vertebrates retained bone cells."
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Biology
| 2,021 |
March 31, 2021
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https://www.sciencedaily.com/releases/2021/03/210331114819.htm
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In search of the first bacterium
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Roughly five years ago, Institute Head Prof. Dr. William (Bill) Martin and his team introduced the last universal common ancestor of all living organisms and named it "LUCA." It lived approximately 3.8 billion years ago in hot deep sea hydrothermal vents.
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Now the evolutionary biologists in Duesseldorf have described a further ancient cell named "LBCA" ("Last Bacterial Common Ancestor"). It is the ancestor of today's largest domain of all living organisms: Bacteria. In Bacteria are almost as old as life itself. LBCA lived around 3.5 billion years ago in a similar environment to LUCA. In order to unlock LBCA's genetic code, its properties and its story, the research team examined the genomes of 1,089 bacterial anaerobes or bacteria that survive without oxygen. "Abandoning aerobes made sense for our work," explains first author Dr. Joana C. Xavier. "If bacteria originated at a time when the Earth was anoxic, it does not make sense to investigate their origin considering species full of adaptations caused by oxygen."Higher life forms pass on their genetic code from parent to offspring via vertical gene transfer. As a result, the genome provides information on phylogenetic history. But bacteria are masters in another form of gene transfer, namely lateral gene transfer (LGT). This allows bacteria to exchange genetic information across different strains. This posed a major challenge in reconstructing the LBCA genome, as it renders the traditional phylogenetic methods incapable of inferring the root in the bacterial evolutionary tree.For this reason, the researchers in Duesseldorf used biochemical networks together with thousands of individual trees. They investigated 1,089 anaerobic genomes and identified 146 protein families conserved in all bacteria. These proteins make up a nearly complete core metabolic network.To complete LBCA's biochemistry, just nine further genes had to be added for the reconstructed metabolic network to include all essential and universal metabolites. To be fully independent and self-generated, LBCA's network would still require further genes inherited from the last universal common ancestor, LUCA, and nutrients from the environment.With LBCA's metabolic network in hand, the authors then used statistical methods to determine which of the modern bacterial groups are most similar to LBCA. They did this using a method called Minimal Ancestor Deviation, MAD, previously developed by one of the co-authors, Fernando D. K. Tria: "The analyses revealed that the earliest branch of Bacteria to diverge was most similar to modern Clostridia, followed closely by Deltaproteobacteria, Actinobacteria and some members of Aquifex. In common, these groups have the acetyl-CoA pathway for carbon fixation and/or energy metabolism."Prof. William Martin, senior author of the study, explains: "This is the only carbon fixation pathway present in both archaea and bacteria and that traces to LUCA. This result, obtained independently, is also in line with our most recent findings on the origin and early evolution of life in hydrothermal vents.""We can infer with confidence that LBCA was most likely rod-shaped," says Xavier. "If it was similar to Clostridia, it is possible that LBCA was able to sporulate." This hypothesis was recently laid out by other researchers "and is highly compatible with our results," says Xavier. Forming spores would allow early cells to survive the inhospitable environment of the early Earth.
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Biology
| 2,021 |
March 31, 2021
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https://www.sciencedaily.com/releases/2021/03/210331103641.htm
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Tadpole nerve regeneration capacity provides clue to treating spinal cord injury
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Nagoya University researchers have identified a gene that plays a crucial role in regenerating neurons of African clawed frog tadpoles, which has an unusually high capacity for nerve regeneration. Their study, recently published in the journal
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Repairing spinal cord injuries in humans and other mammals is difficult, partly because of their limited ability to repair and regenerate neural tissues in the spinal cord. In contrast, there are animals with a high capacity for nerve regeneration, such as the African clawed frog. "As a tadpole, it is fully capable of functional recovery after a spinal cord injury," said Drs. Dasfne Lee-Liu and Juan Larrain from the P. Universidad Catolica de Chile in their study, "Genome-wide expression profile of the response to spinal cord injury in In this context, the Nagoya University research team conducted a collaborative study with Drs. Lee-Liu and Larrain to identify transcription factors that regulate nerve regeneration in the African clawed frog tadpole, with the aim of inducing regenerative effects in mammals. The team comprehensively analyzed the gene expression profiles of tadpoles in response to SCI, and found that a gene called In this study, the team also focused on the fact that in mammals, neural stem cells (known as self-renewing cells) derived from the ependymal cells lining the central canal of the spinal cord are activated and proliferate in the early stage of SCI, although these types of neural stem cells eventually transform into astrocytes -- a type of cell that forms rigid glial scars."Taking these things together, we thought that introducing To that end, the team conducted experiments in which the "Our method is to introduce a neuro regenerative gene directly into neural stem cells that are already present in the spinal cord. This could lessen the problems of rejection and tumor formation, which often occur in conventional stem cell transplantation methods. We believe this study will contribute to the development of new therapeutic approaches to spinal cord injury," he added.
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Biology
| 2,021 |
March 31, 2021
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https://www.sciencedaily.com/releases/2021/03/210331143115.htm
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How Streptococcus pyogenes can survive on skin and cause skin infections
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<em> Streptococcus pyogenes</em>
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Now, an international team led by Osaka University, Japan, in collaboration with Keio University, Japan, and University of California San Diego, USA, has discovered a way this disease organism obtains nutrition from the skin surface. This knowledge could lead to new therapeutic approaches to tackle infections. The team recently published the work in It was already known that some bacteria break down arginine (an amino acid -- one of the building blocks of proteins) via a biochemical pathway named the arginine deaminase (ADI) pathway. The team confirmed that When arginine is supplied, the ADI pathway of Using mouse skin as a model system for human skin, the team showed for the first time that "We showed that arginine from stratum corneum-derived filaggrin was a key substrate for the ADI pathway of "This represents a significant step forward in understanding how
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Biology
| 2,021 |
March 31, 2021
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https://www.sciencedaily.com/releases/2021/03/210331085847.htm
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Engineers use tiny device to change songbird pitch, improve understanding of human speech
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The human brain regions responsible for speech and communication keep our world running by allowing us to do things like talk with friends, shout for help in an emergency and present information in meetings.
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However, scientific understanding of just how these parts of the brain work is limited. Consequently, knowledge of how to improve challenges such as speech impediments or language acquisition is limited as well.Using an ultra-lightweight, wireless implant, a University of Arizona team is researching songbirds -- one of the few species that share humans' ability to learn new vocalizations -- to improve scientific understanding of human speech. A paper about their work was published today in the journal "Using new methods of antenna design and optimized electronics, we were able to shrink the devices dramatically compared to existing versions, to about a third of the size of a dime and as thin as a sheet of paper," said lead author Jokubas Ausra, a biomedical engineering doctoral student in the Gutruf Lab, where the devices were created.There are several ways the device can be used to study the link between brain behavior and vocalization. It can monitor the bird for slight temperature changes that indicate when a bird is most likely to sing. Using a technique called optogenetics, researchers can modulate neuron groups in the brain regions used for birdsong. In this study, the team found that remotely controlling specific neurons during birdsong using their unique device caused the song to change pitch."We are excited to expand the toolbox of neuroscientists and hope to enable many exciting studies that decipher the working principles of the brain," said senior author Philipp Gutruf, assistant professor of biomedical engineering and Craig M. Berge Fellow in the UArizona College of Engineering.The Gutruf Lab has developed other wireless lightweight devices used to monitor brain activity in rodents, but birds' ability to move in 3D space represents an added challenge. This tiny device allows the birds to move without restriction -- a breakthrough enabled by careful management of the energy sent wirelessly to the implant."Because of the small size and light weight, the birds can move freely and live permanently with the implant without affecting their behavior or health, which opens up many possibilities to study the basis for vocal communication," said co-senior author Julie Miller, an assistant professor of neuroscience and speech, language and hearing sciences at UArizona.The team's next goal is to expand device capabilities to also record neuron activity. This could allow researchers to visualize brain activity during song learning and performance to gain a deeper understanding of the underlying brain mechanisms.
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Biology
| 2,021 |
March 31, 2021
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https://www.sciencedaily.com/releases/2021/03/210331085745.htm
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Study finds microbial-plant interactions affect the microbial response to climate change
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University of California, Irvine, biologists have discovered that plants influence how their bacterial and fungal neighbors react to climate change. This finding contributes crucial new information to a hot topic in environmental science: in what manner will climate change alter the diversity of both plants and microbiomes on the landscape? The paper appears in
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The research took place at the Loma Ridge Global Change Experiment, a decade-long study in which scientists simulate the impacts of climate change on neighboring grasslands and coastal scrublands in Southern California. Experimental treatments there include nitrogen addition, a common result of local fossil fuel burning, and simulated drought imposed by covering patches of land with waterproof roofs during rainstorms.In the project's early years, researchers focused on answering climate questions involving plants only. A research team led by Jennifer Martiny, professor of ecology & evolutionary biology and co-director of the UCI Microbiome Initiative, decided to examine whether the vegetation itself influences how climate change affects the bacteria and fungi in the ground. Soil microbes decompose dead plants, regulating the amount of carbon dioxide exchanged with the atmosphere.The scientists sequenced microbial DNA in the grassland and scrubland, finding that the types and number of bacteria and fungi differed between them. Next, the team compared how the microbes reacted to nitrogen fertilizer and drought by monitoring the microbial DNA in plant litter, primarily dropped leaves and stems, over a three-year period."We thought diminished water might cause the scrubland microbial community to become more similar to that of the grasslands because there is evidence that scrublands start to grow increased grasses under drought conditions," said Sarai Finks, the paper's first author and UCI graduate student. "However, it didn't happen. The two microbial communities remained distinct."The team also discovered that while simulated drought affected both bacteria and fungi in grassland and scrubland, there were some unexpected differences. Nitrogen addition only affected the bacteria and its impact was far less than that of drought."Researchers have looked at this kind of interaction previously, but not on the scale we have done here. We were able to investigate two different kinds of plant communities right next to each other," Finks said, adding that the team hopes their findings will be helpful to other scientists investigating microbial communities. "Microbes are crucial to the carbon cycle and we need to learn what changes in microbial diversity mean for the environment."The researchers' paper was the latest to be published from scientific data collected before the Silverado wildfire struck the Loma Ridge Global Change Experiment in October 2020. "Scientists are now looking into researching post-fire interactions between plants and the microbial communities at the site," Finks said.
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Biology
| 2,021 |
March 30, 2021
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https://www.sciencedaily.com/releases/2021/03/210330210940.htm
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Scientists show technology can save people from shark bites
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With shark bites increasing in countries like Australia -- scientists say the use of personal electronic deterrents is an effective way to prevent future deaths and injuries which could save the lives of up to 1063 Australians along the coastline over the next 50 years.
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The research, published in scientific journal The researchers analysed per-capita shark bites around Australia from 1900 to 2020 and developed models to estimate the preventative impact of electronic deterrents if they were worn by water users, to predict how many shark bites could be avoided.With the incidence of bites increasing worldwide, researchers used the Australian Shark Attack File curated by Taronga Conservation Society Australia to develop the models of incidents, and then projected these shark bites to 2066 when the population is expected to rise to 49 million.There were 985 incidents reported in the Australian Shark Attack File from 1900 to 2020 from 20 different species.Lead author Professor Corey Bradshaw of Flinders University says efforts to reduce the risk of shark bites, even if they are extremely rare, are valuable with electronic deterrents capable of reducing the likelihood of a bite by about 60%, potentially saving hundreds of lives over the next 50 years."Avoiding death, injury, and trauma from shark bites over the next half-century would be a realistic outcome if people use these personal electronic deterrents whenever they're in the water, and as long as the technology is operating at capacity.""Given that governments are applying multiple approaches to mitigate shark bites such as drones, SMART drumlines, and acoustic monitoring, our simulations suggest electronic deterrents could make a valuable contribution to overall mitigation, and so help allay community fears.""This is especially so when you consider the additional costs associated with the loss of recreational, commercial, and tourism revenue in the tens to hundreds of millions of dollars following clusters of shark-bite events. ""For example, the New South Wales Government recently invested AU$16 million to mitigate shark bites in part due to lost revenue from businesses benefitting from water users and tourism."Despite the low probability of being bitten by a shark, the rising number of people spending time in waters frequented by sharks increase shark-bite risk to an extent.The researchers point out this approach relies on many assumptions, the biggest factors being stability in the abundance of sharks, shark behaviour, shark distribution (potentially influenced by climate), and human use of the ocean.Shark scientist and co-author Associate Professor Charlie Huveneers, who leads the Southern Shark Ecology Group at Flinders University, says the electronic deterrent devices can be beneficial, as long as people understand their effectiveness and how much they actually reduce the risk of attacks."Although several studies have demonstrated that electronic deterrents can reduce the probability of shark bites, device efficacy varies among manufacturers and even between products of the same manufacturer.""When testing these products scientifically, we need a large number of interactions to (i.e., using robust statistics) assess efficacy confidently. As a result, we often need to use bait or berley to attract sharks, which likely motivate sharks to bite more than in situations when sharks encounter a swimmer or surfer.""Therefore, the ability of electric deterrents to reduce shark bite risk might be greater than the 60% decrease we observed in our studies, further increasing the number of lives saved."
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Biology
| 2,021 |
March 30, 2021
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https://www.sciencedaily.com/releases/2021/03/210330171034.htm
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Endangered songbird challenging assumptions about evolution
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Not all species may travel the same path to existence, at least according to new findings from the University of Colorado Boulder and collaborators.
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This new research, out now in By comparing this bird to a closely related neighbor (the Tawny-Bellied Seedeater) in the same group (the southern capuchino seedeaters), the researchers determined that genetic shuffling of existing variations, rather than new random mutations, brought this species into existence -- and their own behaviors are keeping them apart.This species is one of only two known examples across the globe to have traveled this path, challenging the typical assumptions of how new species form."One of the aspects of this paper that makes it so cool is that we were able to address this question of how the Iberá Seedeaters formed from multiple different perspectives," said Sheela Turbek, a graduate student in ecology and evolutionary biology (EBIO) at University of Colorado Boulder and the study's lead author."Not only did we collect on-the-ground data on who mated with one another and the identity of their offspring, but we also generated genomic data to examine how similar these two species are on a genetic level. We then zoomed out further to look at where the Iberá Seedeater fits in the context of the broader capuchino group.""Many studies will address one of these aspects or questions but not combine all of these different pieces of information into a single study."The southern capuchino seedeaters are a group of recently evolved songbirds found throughout South America that is branching rapidly, with many of its species in the early stages of evolution. This family is best known for the dramatic variation with the males in terms of songs and plumage color, while the females are largely indistinguishable even to the most familiar researchers.The Iberá Seedeater, the most recent member of this family, was first discovered in the remote, swampy grasslands of Iberá National Park in northern Argentina by study co-authors Adrián S. Di Giacomo and Cecilia Kopuchian from Centro de Ecología Aplicada del Litoral, Argentina, in 2001, and then described in scientific literature in 2016.In that national park, though, are six other closely related species of capuchinos, including the Tawny-Bellied Seedeater, that breed closely beside each other. These species, despite occupying the same environment and eating the same food, rarely interbreed.And so, researchers wondered why -- and how -- the Iberá Seedeater even came to be.They explored these questions in two ways: First, they looked at how this new species may have formed by examining the ways in which its DNA differs from the Tawny-Bellied Seedeater, and second, looking at what mechanisms might be preventing it from interbreeding with the other species that occur in the park.To do that, Turbek went down to Argentina for the breeding season for three years, staying two and a half to three months at a time, searching for and monitoring nests, collecting blood samples from adults and nestlings, and then, in the final year, performed a behavioral experiment to see whether plumage or song played a roll in terms of species recognition."The field work involved in collecting the assortative mating and behavioral data is extraordinarily hard, which is why these kinds of datasets rarely exist. This study and publication are a testament to Sheela's skill and hard work in the field," said Scott Taylor, an assistant professor in EBIO at University of Colorado Boulder, an author on the paper and Turbek's advisor.What they found is that the two birds are closely related genetically, only distinguishable by the genes involved in plumage coloration. As well, they found that the males responded most aggressively to songs and plumage variations aligning with their own species.This all means that the species could very well reproduce and hybridize -- they just choose not to, therefore reinforcing their own reproductive barriers.On a broader level, though, when comparing the Iberá Seedeater to other capuchino species, the researchers found that the Iberá Seedeater shares genomic variants with other capuchinos in these regions, but the variants have been shuffled to form a unique combination, which, the researchers argue, could be an evolutionary shortcut that most likely underlies much of the diversity among the different subspecies of this family."This is a really beautiful story about a process that we have never seen in quite this way before," says co-author Irby Lovette, director of the Fuller Evolutionary Biology Program at the Cornell Lab of Ornithology."The classic and most common evolutionary model for new species is the accumulation of genetic mutations when those species are separated by a geographic barrier over perhaps millions of years. But here we found that genetic shuffling can happen quickly and without geographical isolation. It's almost like 'instant speciation.'"Leonardo Campagna, a research associate at the Cornell Lab of Ornithology and the senior author on the paper, agrees:"This is the clearest example in birds of how reshuffling of genetic variation can generate a brand-new species."The only other organism where this type of evolution has been seen, according to Turbek, is a group of fish found in Africa called the Lake Victoria cichlids."It's interesting to see this mechanism operating in something as different as birds," Turbek commented.While this study focused in part on the role of male behaviors, the researchers are very interested in taking it one step further, examining the role that female choice may also play in reproduction."There are many more questions that we have to address," Turbek said.
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Biology
| 2,021 |
March 30, 2021
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https://www.sciencedaily.com/releases/2021/03/210330121219.htm
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The egg in the X-ray beam
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A team of scientists has been using DESY's X-ray source PETRA III to analyse the structural changes that take place in an egg when you cook it. The work reveals how the proteins in the white of a chicken egg unfold and cross-link with each other to form a solid structure when heated. Their innovative method can be of interest to the food industry as well as to the broad field of research surrounding protein analysis. The cooperation of two groups, headed by Frank Schreiber from the University of Tübingen and Christian Gutt from the University of Siegen, with scientists at DESY and European XFEL reports the research in two articles in the journal
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Eggs are among the most versatile food ingredients. They can take the form of a gel or a foam, they can be comparatively solid and also serve as the basis for emulsions. At about 80 degrees Celsius, egg white becomes solid and opaque. This is because the proteins in the egg white form a network structure. Studying the exact molecular structure of egg white calls for energetic radiation, such as X-rays, which is able to penetrate the opaque egg white and has a wavelength that is no longer than the structures being examined."To understand the structural evolution in detail, you have to study the phenomenon on the micrometre scale," explains Nafisa Begam, the lead author of the first study, who is an Alexander von Humboldt fellow in Schreiber's group. The scientists used so-called X-ray photon correlation spectroscopy (XPCS) with a specific geometry allowing them to determine the structure and the dynamics of the proteins in the egg white.For their experiments on the P10 beamline at PETRA III the scientists used a chicken egg from a supermarket and filled the egg white into a quartz tube with a diameter of 1.5 millimetres. "Inside, the egg white was heated in a controlled manner while we analysed it with the help of the X-rays," explains DESY co-author Fabian Westermeier. "The X-ray beam was expanded to 0.1 by 0.1 millimetres, to keep the radiation dose below the damage threshold of the protein structures."The measurements reveal the protein dynamics in the egg white over a period of about a quarter of an hour. During the first three minutes, the protein network grew exponentially, reaching a plateau after about five minutes, at which virtually no more protein links were formed. At this time, the average mesh size of the protein network was about 0.4 micrometres (thousandths of a millimetre).In the second study, the team used the XPCS technique to investigate the self-organisation of protein solutions into domains with, respectively, high and low protein concentration, as an example of structure formation in cell biology. In the process, they were able to follow the temperature-dependent dynamics over time. "At high protein densities, mobility decreases, which slows down the phase separation. This is important for the special dynamics of the system," reports lead author Anita Girelli from Schreiber's group.The studies, which were funded by the German Federal Ministry of Education and Research (BMBF), not only reveal new details about the structural changes occurring in egg whites, but also prove the experimental concept, which can be used for other samples too, as demonstrated by the second study. "Successfully applying X-ray photon correlation spectroscopy opens up a new way to study the dynamics of biomolecules, which is essential if we are to understand them properly," Schreiber comments.DESY is one of the world's leading particle accelerator centres and investigates the structure and function of matter - from the interaction of tiny elementary particles and the behaviour of novel nanomaterials and vital biomolecules to the great mysteries of the universe. The particle accelerators and detectors that DESY develops and builds at its locations in Hamburg and Zeuthen are unique research tools. They generate the most intense X-ray radiation in the world, accelerate particles to record energies and open up new windows onto the universe. DESY is a member of the Helmholtz Association, Germany's largest scientific association, and receives its funding from the German Federal Ministry of Education and Research (BMBF) (90 per cent) and the German federal states of Hamburg and Brandenburg (10 per cent).
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Biology
| 2,021 |
March 30, 2021
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https://www.sciencedaily.com/releases/2021/03/210330121159.htm
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Stopping the sickness: Protein may be key to blocking a nauseating bacterium
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Washington State University researchers have discovered a protein that could be key to blocking the most common bacterial cause of human food poisoning in the United States.
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Chances are, if you've eaten undercooked poultry or cross contaminated food by washing raw chicken, you may be familiar with the food-borne pathogen."Many people that get sick think, 'oh, that's probably Salmonella,' but it is even more likely it's Campylobacter," said Nick Negretti ('20 Ph.D.), a lead member of the research team in Michael Konkel's Laboratory in WSU's School of Molecular Biosciences.According to a study on the research recently published in By gaining insight into the infection process and the specific actions of the Campylobacter secreted proteins, the work gives the WSU team and the rest of the field a foundation to understanding why infections occur and persist.Until the Konkel Lab's latest finding, the functions of the bacterium's proteins and how they infect the cell were largely unknown."We knew these things were happening, but we didn't know how," said Negretti. "Now, if we can stop this process, disease won't happen."The work was funded by a 5-year, $1.9 million grant from the National Institutes of Health and builds on two decades of research in the Konkel Lab.Most often known for the nausea, vomiting and bloody diarrhea that comes with it, once ingested, The bacteria account for 400 to 500 million cases of diarrhea annually, and the World Health Organization recognizes it as a serious threat due to its antibiotic resistance.The infection is also correlated with stunted linear growth in impoverished children, and in developed countries, a higher incidence of Guillain-Barré syndrome, when the body's immune system attacks the nerves.The research was a seven-year collaborative effort, using the latest molecular biology and biochemistry methods.The work was done in partnership with researchers Geremy Clair and Joshua Adkins with the Pacific Northwest National Laboratory. Using mass spectroscopy, Adkins and Clair were able to study protein-to-protein interaction that helped the WSU researchers narrow their focus and uncover the target of CiaD.Konkel said the research would not have been completed without post-doctoral fellow Prabhat Talukdar and graduate students Courtney Klappenbach and Cody Lauritsen leading the work through its final stretch amid the pandemic.Now, the researchers are hopeful the work will lead to real-world solutions, in particular finding ways to prevent the pathogen from stunting growth in children."With this finding, we can speculate that processes like this that affect the cell could impact the intestinal cell's ability to form the correct structures to absorb nutrients," Negretti said. "While this is a mechanistic level of understanding, the answers to how the bacteria is specifically affecting cells in the body could have broader ranging impacts into understanding the public health importance of this pathogen."The team also looks forward to learning the functions of other secreted proteins.A major breakthrough into understanding "We then identified CiaD was delivered to the host cells in 2013," Konkel said. "A major question for the past 20-years has been: what are these secreted proteins and what do they do? This is just the first protein to have an identified cell target."
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Biology
| 2,021 |
March 30, 2021
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https://www.sciencedaily.com/releases/2021/03/210330081315.htm
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Scientists identify molecular pathway that helps moving cells avoid aimless wandering
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Working with fruit flies, scientists at Johns Hopkins Medicine say they have identified a new molecular pathway that helps steer moving cells in specific directions. The set of interconnected proteins and enzymes in the pathway act as steering and rudder components that drive cells toward an "intended" rather than random destination, they say.
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In a report on the work, published March 2 in The team of scientists was led by Deborah Andrew, Ph.D., professor of cell biology and associate director for faculty development for the Institute for Basic Biomedical Sciences at the Johns Hopkins University School of Medicine.Andrew and her colleagues began this research while studying a gene called Tre1 and its role in the development of salivary glands in fruit flies. The tools to study the effects of turning the gene on and off weren't ideal, she says. So, two of the team members, Caitlin Hanlon, Ph.D., of Quinnipiac University and JiHoon Kim, Ph.D., of Johns Hopkins, generated fruit flies that lack the protein-coding portion of the Tre1 gene. The pair also put a fluorescent tag on the Tre1 protein to learn where it localized during key steps in development.In experiments with fruit fly embryos carrying an intact Tre1 gene, cells that produce future generations of the organism, called germ cells, migrate correctly to the sex organ, known as the gonad."Without the Tre1 gene, however, most of the germ cells failed to meet up with other nongerm cells, or somatic cells, of the gonad," says Andrew. "Correct navigation of germ cells is important to ensure that future generations of the organism will happen."This is not the first time that scientists noted Tre1's importance in germ cell navigation. Two research teams from Indiana University and the Massachusetts Institute of Technology had previously made the link. However, says Andrew, questions remained about what happens inside germ cells to get cells to the right place once Tre1 activates.It was already known that the Tre1 gene encodes a protein that spans the cell membrane multiple times and pokes out onto the cell's surface. It's a member of a large family of proteins called G protein-coupled receptors, which enable cells to communicate and respond to signals from other cells and light and odor cues. Nearly 35% of FDA approved medicines target G protein-coupled receptors, says Andrew.To more precisely track the molecular events downstream of Tre1, Kim, a research associate and postdoctoral fellow at the Johns Hopkins University School of Medicine, used tissue cultures of fruit fly cells to find the location of fluorescently tagged molecules that are potentially triggered by the activated Tre1 protein. In the tissue cultures and germ cells of living flies, Kim uncovered the downstream genetic pathway.He found that Tre1 functions as the cell's helmsman, controlling steering of the cell. Tre1 activates the cell's steering and rudder components by spurring on a cascade of proteins and enzymes, including a phospho-inositol kinase, PI(4,5)P2, dPIP5K, dWIP and WASp.At the end of the molecular cascade, a chain of actin proteins forms in a protrusion at the cell's leading edge to exert mechanical forces for movement.The scientists also searched for the upstream signal that activates Tre1. They used a genetically engineered protein made by researchers at the University of California, San Francisco to track the location of a signaling protein called Hedgehog, which has previously been linked to germ cell migration, although its role in this process has been disputed.In germ cells, Hedgehog signaling increases the membrane levels of a protein called Smoothened, which is found in the cells' leading edge protrusion where Tre1 is also found.The scientists plan to continue studying the pathways surrounding Tre1 and connections between the proteins and enzymes involved in the pathway."A deeper understanding of how moving cells navigate and spread has the potential to provide more targets for interrupting the spread of cancer cells," says Andrew.
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Biology
| 2,021 |
March 30, 2021
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https://www.sciencedaily.com/releases/2021/03/210330081245.htm
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Prime editing enables precise gene editing without collateral damage
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The latest gene editing technology, prime editing, expands the "genetic toolbox" for more precisely creating disease models and correcting genetic problems, scientists say.
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In only the second published study of prime editing's use in a mouse model, Medical College of Georgia scientists report prime editing and traditional CRISPR both successfully shut down a gene involved in the differentiation of smooth muscle cells, which help give strength and movement to organs and blood vessels.However, prime editing snips only a single strand of the double-stranded DNA. CRISPR makes double-strand cuts, which can be lethal to cells, and produces unintended edits at both the work site as well as randomly across the genome, says Dr. Joseph Miano, genome editor, molecular biologist and J. Harold Harrison, MD, Distinguished University Chair in Vascular Biology at the MCG Vascular Biology Center."It's actually less complicated and more precise than traditional CRISPR," Miano says of prime editing, which literally has fewer components than the game-changing gene-editing tool CRISPR.Miano was among the first wave of scientists to use CRISPR to alter the mouse genome in 2013. Two scientists were awarded the 2020 Nobel Prize in Chemistry for the now 9-year-old CRISPR, which enabled rapid development of animal models, as well as the potential to cure genetic diseases like sickle cell, and potentially reduce the destruction caused by diseases like cancer, in which environmental and genetic factors are both at play.Prime editing is the latest gene-editing technology, and the MCG scientists report in the journal Genome Biology that they were able to use it to remove expression of a gene in smooth muscle tissue, illustrating prime editing's ability to create cell-specific knockout mice without extensive breeding efforts that may not result in an exact model, says Dr. Xiaochun Long, molecular biologist in the Vascular Biology Center. Miano and Long are corresponding authors of the new study.Long, Miano and their colleagues did a comparative study using traditional CRISPR and prime editing in the gene Tspan2, or tetraspan-2, a protein found on the surface of cells. Long had earlier found Tspan2 was the most prominent protein in smooth muscle cell differentiation and was likely mutated in cardiovascular disease. She also had identified the regulatory region of this gene in cultured cells. However, it was unclear whether this regulatory region was important in mice.They used CRISPR to create a subtle change in a snippet of DNA within the promoter region of Tspan2, in this case a three-base change, their standard approach to inactivating control regions of genes. DNA has four base pairs -- adenine, cytosine, guanine and thymine -- which pair up in endless different combinations to make us, and which gene-editing tools alter.CRISPR created a double-strand break in the DNA and following the three-base change, the Tspan2 gene was no longer turned on in the aorta and bladder of mice.They then used prime editing to make a single-strand break, or nick, and a single-base change -- like most of the gene mutations that occur in our body -- and found this subtle change also turned the Tspan2 gene off in the aorta and bladder, but without the collateral damage of CRISPR."We were trying to model what could happen with a single nucleotide change," says Miano. "We asked the question if we incorporate a single-base substitution, if we just make one base change, what happens to Tspan2 expression? The answer is it did the same thing as the traditional CRISPR editing: It killed the gene's expression."But there were also important differences. Using CRISPR, they found evidence of significant "indels," short for insertions or deletions of bases in genes, which were unintended, both near the site where the intended edit was made and elsewhere.The published paper includes a chart with numerous black bars illustrating where multiple nucleotides, the building blocks of DNA and RNA, are gone after using CRISPR. Indels are those unintended changes that genome editors strive to avoid because they can create deficits in gene expression and possible disease. With off-targeting, you could end up substituting one disease for another, Miano says.But with prime editing, they saw essentially no indels either at the Tspan2 promoter region or elsewhere.A Manhattan plot illustrated the off-targeting across all chromosomes using both techniques, with the CRISPR skyline stacking up like a real city while the prime editing skyline is comparatively flat."Prime editing is a less intrusive cut of the DNA. It's very clean," Miano says. "This is what we want: No detectable indels, no collateral damage. The bottom line is that unintended consequences are much less and it's actually less complicated to use."Traditional CRISPR has three components, the molecular scissors, Cas9, the guide RNA that takes those scissors to the precise location on DNA and a repair template to fix the problem. Traditional CRISPR cuts both strands of the DNA, which also can happen in nature, can be catastrophic to the cell and must be quickly mended.Prime editing has two arms, with a modified Cas9, called a Cas9 nickase, that will only make a single-strand cut. The scissors form a complex called the "prime editor" with a reverse transcriptase, an enzyme that can use an RNA template to produce a piece of DNA to replace the problematic piece in the case of a disease-causing mutation. PegRNA, or prime editing guide RNA, provides that RNA template, gets the prime editor where it needs to work and helps stabilize the DNA strands, which are used to being part of a couple.During the repair of the nicked strand of targeted DNA, the prime editor "copies" a portion of the pegRNA containing the programmed edit, in this case a single-base substitution, so that the repaired strand will now carry the single base edit. In the case of creating a disease model, that enables scientists to "bias" the repair so the desired mutation is created, Miano says.Dr. David Liu, chemical biologist, Richard Merkin Professor and director of the Merkin Institute of Transformative Technologies in Healthcare at Harvard University and the Massachusetts Institute of Technology, and his colleagues developed the first major gene editing technology to follow CRISPR. They reported on base editing technology in 2016, which uses "base editors" Liu described as "pencils, capable of directly rewriting one DNA letter into another by actually rearranging the atoms of one DNA base to instead become a different base." Liu and his postdoctoral fellow Dr. Andrew Anzalone, first reported on prime editing in the journal Liu's original work on prime editing was done in culture, and others have shown its efficacy in plants. This is more proof of principle, Miano says.The MCG scientists hope more of their colleagues will start using prime editing in their favorite genes to build experience and hasten movement toward its use in humans.Their long-term goals including using safe, specific gene editing to correct genetic abnormalities during human development that are known to result in devastating malformations and disease like heart defects that require multiple major surgeries to correct.Allison Yang, senior research assistant in the Miano lab, is preparing to use prime editing to do an in utero correction of the rare and lethal megacystis-microcolon-intestinal hypoperistalsis syndrome, which affects muscles of the bladder and intestines so you have difficulty moving food through the GI tract and emptying the bladder. In early work with CRISPR on vascular smooth muscle cells, Miano and colleagues inadvertently created a near-perfect mouse model of this human disease that can kill babies.
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Biology
| 2,021 |
March 30, 2021
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https://www.sciencedaily.com/releases/2021/03/210330100330.htm
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Mystery of photosynthetic algae evolution finally solved
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An evolutionary mystery that had eluded molecular biologists for decades may never have been solved if it weren't for the COVID-19 pandemic.
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"Being stuck at home was a blessing in disguise, as there were no experiments that could be done. We just had our computers and lots of time," says Professor Paul Curmi, a structural biologist and molecular biophysicist with UNSW Sydney.Prof. Curmi is referring to research published this month in Up until now, how cryptophytes acquired the proteins used to capture and funnel sunlight to be used by the cell had molecular biologists scratching their heads. They already knew that the protein was part of a sort of antenna that the organism used to convert sunlight into energy. They also knew that the cryptophyte had inherited some antenna components from its photosynthetic ancestors -- red algae, and before that cyanobacteria, one of the earliest lifeforms on earth that are responsible for stromatolites.But how the protein structures fit together in the cryptophyte's own, novel antenna structure remained a mystery -- until Prof. Curmi, PhD student Harry Rathbone and colleagues from University of Queensland and University of British Columbia pored over the electron microscope images of the antenna protein from a progenitor red algal organism made public by Chinese researchers in March 2020.Unravelling the mystery meant the team could finally tell the story of how this protein had enabled these ancient single-celled organisms to thrive in the most inhospitable conditions -- metres under water with very little direct sunlight to convert into energy.Prof. Curmi says the major implications of the work are for evolutionary biology."We provide a direct link between two very different antenna systems and open the door for discovering exactly how one system evolved into a different system -- where both appear to be very efficient in capturing light," he says."Photosynthetic algae have many different antenna systems which have the property of being able to capture every available light photon and transferring it to a photosystem protein that converts the light energy to chemical energy."By working to understand the algal systems, the scientists hope to uncover the fundamental physical principles that underlie the exquisite photon efficiency of these photosynthetic systems. Prof. Curmi says these may one day have application in optical devices including solar energy systems.To better appreciate the significance of the protein discovery, it helps to understand the very strange world of single-celled organisms which take the adage "you are what you eat" to a new level.As study lead author, PhD student Harry Rathbone explains, when a single-celled organism swallows another, it can enter a relationship of endosymbiosis, where one organism lives inside the other and the two become inseparable."Often with algae, they'll go and find some lunch -- another alga -- and they'll decide not to digest it. They'll keep it to do its bidding, essentially," Mr Rathbone says. "And those new organisms can be swallowed by other organisms in the same way, sort of like a matryoshka doll."In fact, this is likely what happened when about one and a half billion years ago, a cyanobacterium was swallowed by another single-celled organism. The cyanobacteria already had a sophisticated antenna of proteins that trapped every photon of light. But instead of digesting the cyanobacterium, the host organism effectively stripped it for parts -- retaining the antenna protein structure that the new organism -- the red algae -- used for energy.And when another organism swallowed a red alga to become the first cryptophyte, it was a similar story. Except this time the antenna was brought to the other side of the membrane of the host organism and completely remoulded into new protein shapes that were equally as efficient at trapping sunlight photons.As Prof. Curmi explains, these were the first tiny steps towards the evolution of modern plants and other photosynthetic organisms such as seaweeds."In going from cyanobacteria that are photosynthetic, to everything else on the planet that is photosynthetic, some ancient ancestor gobbled up a cyanobacteria which then became the cell's chloroplast that converts sunlight into chemical energy."And the deal between the organisms is sort of like, I'll keep you safe as long as you do photosynthesis and give me energy."One of the collaborators on this project, Dr Beverley Green, Professor Emerita with the University of British Columbia's Department of Botany says Prof. Curmi was able to make the discovery by approaching the problem from a different angle."Paul's novel approach was to search for ancestral proteins on the basis of shape rather than similarity in amino acid sequence," she says."By searching the 3D structures of two red algal multi-protein complexes for segments of protein that folded in the same way as the cryptophyte protein, he was able to find the missing puzzle piece."
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Biology
| 2,021 |
March 29, 2021
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https://www.sciencedaily.com/releases/2021/03/210329153341.htm
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Researchers notice pattern on surface of leaves, uncover new clue about plant evolution
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A doctoral student has identified a long-overlooked pattern in how plants evolved their equivalent of lungs -- tiny pores on the surfaces of leaves called stomata. Using specialized imaging techniques and a plant species not often found in laboratories, researchers say this discovery reveals a key difference in the evolution of plants that live on land versus those that can grow in water.
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"I felt this is really interesting, this was a big surprise to me. I remember well that after observation in the microscope room on the basement floor, I rushed up the stairs to tell Dr. Koga about my discovery," recalled first-year doctoral student Yuki Doll, studying in the University of Tokyo Graduate School of Science under the supervision of Assistant Professor Hiroyuki Koga."Of course, I and any scientist can see that the stomata are different, but it is easy for us to just ignore it, not sense any pattern. When I heard about Doll-kun's discovery, I was also very excited and discussed with him that we should delve into this subject," remarked Koga. (Kun is the Japanese honorific suffix attached to junior men's names.)When stomata are open, carbon dioxide, oxygen and water vapor can move in and out of the leaf for photosynthesis and respiration. Artificially manipulating the number of stomata is one potential way to keep crops healthy in a changing climate.The UTokyo team was studying multiple types of plants in the genus Callitriche, which includes both terrestrial and aquatic species."Callitriche is an interesting but minor group of plants and we are the only ones in the world using them for developmental biological research," said Koga.Recalling his first experiences examining the plants, Doll said, "When I started to analyze stomata distribution patterns in aquatic Callitriche, I felt that the arrangement of the stomata are different than what I had been taught as an undergrad in the common lab species Arabidopsis. I had the impression that this strange pattern must be the case for all Callitriche, but I thought, that's OK, Arabidopsis and Callitriche are from very different evolutionary lineages, so it's natural for them to be different. Then I analyzed a terrestrial species of Callitriche and I saw it looked much more like Arabidopsis."Specifically, Doll noticed that stomata and the cells surrounding them on the surface of aquatic plants' leaves were much more uniform than the variable cell sizes on the terrestrial plants' leaves.This pattern that two evolutionarily closely related plant species had such different patterns of stomata development hinted at the possibility that their living conditions -- on land or in water -- might regulate stomatal development.Koga and other lab members had previously perfected a method to visualize gene activity in every individual cell of intact, whole plant leaves. The technique of whole-mount fluorescence in situ hybridization is not new, but it is difficult and unusual to use those molecular biology tools without cutting a plant into ultrathin slices.The images from terrestrial and aquatic Callitriche leaves confirmed that the plants used the same two genes to develop their stomata, but the genes were active at different times.In almost all plants, the gene SPEECHLESS promotes growth and division of a group of cells on the surfaces of newly forming leaves. Eventually, the gene MUTE becomes active in these cells and blocks SPEECHLESS, causing these cells to stop dividing and then differentiate to stomata. By binding artificial fluorescent tags to the two genes, researchers could see in single-cell resolution when SPEECHLESS is suppressed and MUTE becomes active.In terrestrial Callitriche, researchers saw MUTE expressed in cells of all different ages. MUTE was much more uniformly expressed only in older cells of aquatic species, which seemed to skip the division stage and have a coordinated delay to wait until late in leaf development to activate MUTE.Researchers suspect that aquatic species evolved to delay stomatal formation to wait and sense if this new leaf will be fully submerged or if it will be above the water line. Gas exchange is less efficient under water, so submerged leaves generally have fewer stomata than leaves in air.The discovery is exciting for evolutionary biologists interested in the relationship between environmental pressures and evolutionary genetics, but is also relevant for the future of growing crops in changing or unpredictable environments."The usual assumption is that closely related species have similar stomata development patterns, but our key finding is that this is not the case," said Koga.Instead, the researchers say their new results show that a species' living environment is the important evolutionary force selecting its stomata development pattern, not just the species' genetic ancestry.By understanding the full genetic pathway that leads to flexible control of SPEECHLESS and MUTE expression between species, scientists may be able to predict which evolutionary lineages of crops are more likely to optimize their stomata to grow in a changing climate.
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Biology
| 2,021 |
March 29, 2021
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https://www.sciencedaily.com/releases/2021/03/210329122806.htm
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Differences in herpes virus symptoms may relate to variations in strain gene expression
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Why do some people with cold sores around their lips experience painful lesions, while others have no symptoms at all, yet still spread the virus? A new study conducted at Penn State finds that these differences could be due to variations in the way certain strains of herpes simplex (HSV-1) -- the virus that causes cold sores, as well as genital herpes -- activate gene expression in neurons.
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"HSV-1 occurs in more than half the global population," said Moriah Szpara, associate professor of biology and biochemistry and molecular biology. "Not only does it cause recurrent problems, such as cold sores and genital herpes, but recent research has implicated chronic HSV-1 infection with the development of disease later in life, including neurodegenerative diseases like Alzheimer's."Szpara explained that the HSV-1 lifecycle begins upon contact with mucosal surfaces, where it invades skin cells, replicates, and can induce local lesion formation. The virus also enters local nerve endings in the skin, and transits into neurons in the nervous system. There the virus can lie dormant until it reactivates on future occasions. Neuronal damage and host immune responses triggered by viral reactivations are thought to contribute to long-term neurodegeneration."Since every person carries a subtly different version of HSV-1, this might explain some of the variation in human responses to infection; for example, why people have different triggers for their outbreaks or why some people experience more painful sores. Differences in the frequency of viral outbreaks, or in virus-induced gene expression patterns, might also affect the different rates at which people with chronic infections go on to develop neurodegenerative diseases."To investigate the causes of this variation in responses, Szpara and her colleagues infected human neuronal cells with one of three HSV-1 strains that are known to differ in their ability to cause disease in the nervous system. Next, they used deep sequencing to identify and quantify the transcriptomes -- the entire set of messenger RNAs (mRNAs) made in a cell at any given time -- of the neurons during infection by HSV-1.According to Szpara, when a neuronal cell is infected with HSV-1, the resulting transcriptome includes the whole collection of mRNAs produced by both the human neuron and the HSV-1 virus. By looking at the timing and amount of mRNAs expressed during infection, scientists can gain insights on the proteins that will soon be produced from those mRNAs. It is the viral proteins and new viral progeny produced during infection that ultimately lead to health problems."By simultaneously examining both the viral and neuronal transcriptomes in the infected cells we were able to observe the interplay between the timing of viral mRNA production and protein production, and the ensuing host responses," said Szpara.The scientists used two additional techniques -- immunofluorescence staining of neurons and Western blotting for viral protein levels -- to observe the outcomes of viral and host gene expression. They also used scanning electron microscopy to directly observe changes in neuronal morphology during infection.Their findings appeared online in The researchers found that different genetic variants of HSV-1 induce different patterns of gene expression in human neuronal cells. Specifically, they found that the viral variants expressed their genes at different rates and quantities, which likely contributes to the different timing and severity of symptoms within hosts. For example, they discovered that one of the variants, which exhibits lower virulence in animal models, displays a different and seemingly delayed pace of viral and host gene expression in neurons. In another example, they found that one variant caused greater changes in expression of genes involved in cell adhesion (or ability of cells to attach to each other), which could impact cell-to-cell spread of HSV-1.The team also found that these different patterns of gene expression were dependent on the whether the infected cell was a neuron or a skin cell type."Together, these data demonstrate the importance of studying virus strain- and cell-type-specific factors that may contribute to neurovirulence in vivo. It also highlights the specificity of HSV-1-host interactions," said Szpara. "Our study suggests that differences observed between viral variants in cell-based models like neurons can be used to help understand the more-complex interactions of viruses with hosts."Other authors on the paper include Colleen Mangold, postdoctoral scholar in entomology; Molly Rathbun, graduate student in biochemistry and molecular biology; Daniel Renner, computational scientist in the Huck Institutes of the Life Sciences; and Chad Kuny, assistant research professor of biology.This research was supported by Penn State, the Pennsylvania Department of Health, the American Heart Association and the National Institutes of Health.
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Biology
| 2,021 |
March 29, 2021
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https://www.sciencedaily.com/releases/2021/03/210329085946.htm
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Cells rely on their crampons to avoid slipping
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Each human being is made of billions of cells. In order to ensure his survival, cells must coordinate with each other and attach in the right place to perform their tasks. Scientists from the University of Geneva (UNIGE), Switzerland, in collaboration with the University of Tampere in Finland, have highlighted the key role of a protein called paxillin, which enables cells to perceive their environment and anchor at the right place with the help of cellular "crampons." Indeed, without functional paxillin, the cell is unable to attach properly and slips continuously. These results, to be read in the journal
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To ensure our survival, each cell performs specific functions in coordination with their neighbours. In such a dynamic system, the migration of cells and their anchoring at the right place are essential. But how do cells manage to coordinate with each other? Scientists have long believed that cells communicate mainly through chemical signals, such as hormones. However, recent discoveries suggest that mechanical signals play a major role in cell coordination. "This is why we started to study the ability of cells to decipher and respond to their physical environment," explains Bernhard Wehrle-Haller, Professor at the Department of cell physiology and metabolism at UNIGE Faculty of Medicine. "Especially as it could help us to understand how cancer cells use these mechanisms to invade other organs and form metastases."When a cell has to move, it "senses" its environment with the help of proteins on its surface, the integrins. When the cell detects a suitable location, a complex network of proteins, called focal adhesion, is then set up to form cellular crampons that anchor the cell to its environment. "But how is this anchoring mechanism regulated? This is what we wanted to find out," explains Marta Ripamonti, researcher in the laboratory of Prof. Bernhard Wehrle-Haller and first author of the study.By studying paxillin, one of the many proteins that make up these crampons, researchers were able to unravel the mystery. "We knew that this protein played a role in the assembly of focal adhesions, but we didn't expect it to be the key regulator," says Prof. Bernhard Wehrle-Haller with enthusiasm. Without functional paxillin, cells are unable to anchor, regardless of the suitability of their environment. In addition, paxillin has also the function of informing the cell that anchoring has taken place correctly, thus transforming a mechanical response into a biological signal that the cell can understand.These in vitro experiments highlight the major role of paxillin in the migration and adhesion of healthy cells, but they could also be a starting point for a better understanding of cancer development. "It is indeed likely that cancer cells use paxillin to find a place that enhance their survival. Would it be possible to block this mechanism in tumor cells and prevent the formation of metastases? Yes, we think so! " concludes Prof. Bernhard Wehrle-Haller.
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Biology
| 2,021 |
March 26, 2021
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https://www.sciencedaily.com/releases/2021/03/210326104654.htm
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DNA: Metal double helix
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Nanowires are vital components for future nanoelectronics, sensors, and nanomedicine. To achieve the required complexity, it is necessary to control the position and growth of the metal chains on an atomic level. In the journal
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A team from Europe and the USA led by Miguel A. Galindo has now developed an elegant method for producing individual, continuous chains of palladium ions. The process is based on self-organized assembly of a special palladium complex and single-stranded DNA molecules.In recent years, DNA has become an important tool for nanoscience and nanotechnology, particularly because of the possibility of "programming" the resulting structures through the base sequence of the DNA used. The incorporation of metals in DNA structures can give them properties such as conductivity, catalytic activity, magnetism, and photoactivity.However, organizing metal ions in DNA molecules is not trivial because metal ions can bind to many different sites. Galindo's team developed a smart method for controlling the binding of palladium ions to specific sites. They use a specially constructed palladium complex that can form base pairs with natural adenine bases in a strand of DNA. The ligand in this complex is a flat, aromatic ring system that grasps three of the four binding positions available on the palladium ion. The fourth position of the palladium is then available to bind to a very specific nitrogen atom in adenine. The ligand also possesses oxygen atoms capable of forming a hydrogen bond with the neighboring NH(2) group of the adenine. This binding pattern corresponds exactly to a Watson-Crick base pairing, but now mediated by a palladium ion, which makes it considerably stronger than natural Watson-Crick pairing.If a DNA strand made exclusively of adenine bases is used, one palladium complex binds to each adenine. The flat ligands assemble themselves into coplanar stacks, just like natural bases. This results in a double strand made of DNA and palladium complexes that corresponds to a natural DNA double helix in which one strand has been replaced by a supramolecular stack of continuous palladium complexes.Although the team has yet to demonstrate the conductive properties of these systems, it can be anticipated that the correct reduction of these metal ions could lead to the formation of a conductive nanowire with a highly controlled structure. The research group is currently working in this line as well as in the modification of the ligand, which can also provide new properties to the system.
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Biology
| 2,021 |
March 26, 2021
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https://www.sciencedaily.com/releases/2021/03/210326085234.htm
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Eat me: The cell signal of death
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Scientists at the Institute for Integrated Cell-Material Sciences (iCeMS) and colleagues in Japan have revealed molecular mechanisms involved in eliminating unwanted cells in the body. A nuclear protein fragment released into the cytoplasm activates a plasma membrane protein to display a lipid on the cell surface, signalling other cells to get rid of it. The findings were published in the journal
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"Every day, ten billion cells die and are engulfed by blood cells called phagocytes. If this didn't happen, dead cells would burst, triggering an auto-immune reaction," explains iCeMS biochemist Jun Suzuki, who led the study. "It is important to understand how dead cells are eliminated as part of our body's maintenance."Scientists already know that dead cells display an 'eat me' signal on their surface that is recognized by phagocytes. During this process, lipids are flipped between the inner and outer parts of the cell membrane via a variety of proteins called scramblases. Suzuki and his team have already identified several of these lipid-scrambling proteins, but some of their activation mechanisms have been unclear.To solve this, the team used an array of screening approaches to study the scrambling protein called Xkr4. The broad aim was to single out the genes that are active during cell death and to specifically zoom in on Xkr4 and its associated proteins to understand how they interact."We found that a nuclear protein fragment activates Xkr4 to display the 'eat me' signal to phagocytes," says iCeMS cell biologist Masahiro Maruoka, the first author of the study.Specifically, the scientists found that cell death signals lead to a nuclear protein, called XRCC4, getting cut by an enzyme. A fragment of XRCC4 leaves the nucleus, activating Xkr4, which forms a dimer: the linking of identical pieces into configurations. Both XRCC4 binding and dimer formation are necessary for Xkr4 to ultimately transfer lipids on the cell surface to alert phagocytes.Xkr4 is only one of the scrambling proteins. Others are activated much faster during cell death. The team now wants to understand when and why the Xkr4 pathway is specifically activated. Since it is strongly expressed in the brain, it is likely important for brain function. "We are now studying the elimination of unwanted cells or compartments in the brain to understand this process further," says Maruoka.
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Biology
| 2,021 |
March 26, 2021
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https://www.sciencedaily.com/releases/2021/03/210317141642.htm
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Global warming helps invasive species flourish
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Increased global temperatures help invasive species establish themselves in ecosystems, new research led by a Swansea University bioscientist has shown.
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The study, published by the Royal Society, gives an insight into the probable combined effects of species invasions, which are becoming more common, and global warming.Climate warming and biological invasions result in the loss of species. They also alter the structure of ecosystems and the ways in which species interact.While there is already extensive research on how climate change and invasions affect species and ecosystems, we know surprisingly little about their combined effect, acting together in synergy.This is where the new study marks an important step forward. The work, funded by the EU Horizon programme, involved Dr Miguel Lurgi from the College of Science working with colleagues from the Institut National de la Recherche Agronomique (INRAE) and the Centre National pour la Recherche Scientifique (CNRS) in France.The team used mathematical simulations to investigate how temperature influences invasions in complex food webs comprising 30 species. They paid particular attention to the combined -- synergistic -- effects.The aim was to provide a theoretical model for how ecological communities are likely to respond to the joint effects of warming and invasions.The model accounted for factors such as reproduction and death rates, average species body size, and interactions between species -- such as predators attacking prey.The team simulated what happens when an alien species is introduced into an ecosystem. They then ran the simulation forward in time using 40 different temperature values from 0 to 40 degrees Celsius.This allowed them to model the combined effects on the ecosystem of temperature rises and of the new species being introduced.They analysed the simulation results to assess the effects of temperature on food web properties before invasion, invasion success, and the effects of invasions on community structure and stability.They found:Dr Miguel Lurgi of Swansea University, lead researcher, said:"Warming and invasions are driving major changes to our ecosystems, and it's essential that we understand their combined effects.Our study provides a first step in that direction, analysing the synergistic effects of temperature and invasions on communities.Overall, we found that temperature and invasion act synergistically to increase the rate of species loss, creating smaller and more connected networks.We have seen with COVID19 how mathematical modelling has been crucial in understanding the likely spread and impact of the virus.Similarly, our work provides theoretical expectations for the likely response of ecological communities to the joint effects of warming and invasions."The research was published in
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Biology
| 2,021 |
March 25, 2021
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https://www.sciencedaily.com/releases/2021/03/210325150105.htm
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HIV vaccine candidate's mysteries unlocked 20 years later
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About two decades after first devising a new kind of vaccine, Oregon Health & Science University researchers are unlocking why it stops and ultimately clears the monkey form of HIV, called SIV, in about half of nonhuman primates -- and why it's a promising candidate to stop HIV in people.
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In scientific papers that were simultaneously published today in the journals The findings also helped fine-tune VIR-1111, the CMV-based experimental vaccine against HIV that was developed at OHSU and is now being evaluated in a Phase 1 clinical trial. The trial is being conducted by Vir Biotechnology, which licensed the CMV vaccine platform technology from OHSU."Knowing the mechanism that the CMV-based SIV vaccine uses to work in rhesus macaques gives us a way to judge the potential of a human vaccine very quickly," said Louis Picker, M.D., the associate director of the OHSU Vaccine and Gene Therapy Institute and a professor of pathology/molecular microbiology and immunology in the OHSU School of Medicine. "If you have the wrong genes in the CMV vaccine, the critical immune response needed for efficacy won't develop. You have to thread the CMV vaccine's needle exactly if you want a high degree of protection, and you have to know what you're looking for."Two of the papers describe that the cytomegalovirus vaccine needs to generate an unusual type of CD8-positive T cell response called MHC-E-restricted T cells to effectively fight off SIV in monkeys."We knew for a while that we have unusual T cell responses in monkeys that receive our CMV vaccine against SIV," said Klaus Frueh, Ph.D., a professor of molecular microbiology and immunology in the OHSU School of Medicine and OHSU Vaccine and Gene Therapy Institute. "But we didn't know if they were important for protection against SIV. This research shows clearly that, without this special MHC-E-restricted T cell response, we don't have protection."The study published in And, in a separate This new research is being published as the OHSU Vaccine and Gene Therapy Institute celebrates the 20th anniversary of its first building opening for research in April 2001. Picker and Frueh moved to Oregon to help start the institute: Picker has led its vaccine program since its founding, and Frueh joined forces with Picker in 2006. Picker first received a $3.5 million grant from the National Institutes of Health in 2004 to develop a CMV-based HIV vaccine. Picker says the following in a May 25, 2004, OHSU announcement about the grant: "We believe a persistent viral vector could produce a superior and more durable anti-HIV immune response that would, in effect, hold the line against HIV."The following funding was awarded to OHSU in support of the research described in these three studies: the National Institute of Allergy and Infectious Diseases (grants P01 AI094417, U19 AI128741, UM1 AI124377, R37 AI054292, R01AI140888, R01 AI059457), National Institutes of Health Office of the Director (grant P51 OD011092); National Cancer Institute (contract HHSN261200800001E), and the Bill & Melinda Gates Foundation-supported Collaboration for AIDS Vaccine Discovery (OPP1033121).In the interest of ensuring the integrity of our research and as part of our commitment to public transparency, OHSU actively regulates, tracks and manages relationships that our researchers may hold with entities outside of OHSU. In regards to this research, OHSU and several individuals have a significant financial interest in Vir Biotechnology Inc., a company that may have a commercial interest in the results of this research and technology. These individuals include Picker, Frueh, Sacha, Malouli, Hansen and Hancock.
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Biology
| 2,021 |
March 25, 2021
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https://www.sciencedaily.com/releases/2021/03/210325150042.htm
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DNA damage 'hot spots' discovered within neurons
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Researchers at the National Institutes of Health (NIH) have discovered specific regions within the DNA of neurons that accumulate a certain type of damage (called single-strand breaks or SSBs). This accumulation of SSBs appears to be unique to neurons, and it challenges what is generally understood about the cause of DNA damage and its potential implications in neurodegenerative diseases.
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Because neurons require considerable amounts of oxygen to function properly, they are exposed to high levels of free radicals -- toxic compounds that can damage DNA within cells. Normally, this damage occurs randomly. However, in this study, damage within neurons was often found within specific regions of DNA called "enhancers" that control the activity of nearby genes.Fully mature cells like neurons do not need all of their genes to be active at any one time. One way that cells can control gene activity involves the presence or absence of a chemical tag called a methyl group on a specific building block of DNA. Closer inspection of the neurons revealed that a significant number of SSBs occurred when methyl groups were removed, which typically makes that gene available to be activated.An explanation proposed by the researchers is that the removal of the methyl group from DNA itself creates an SSB, and neurons have multiple repair mechanisms at the ready to repair that damage as soon as it occurs. This challenges the common wisdom that DNA damage is inherently a process to be prevented. Instead, at least in neurons, it is part of the normal process of switching genes on and off. Furthermore, it implies that defects in the repair process, not the DNA damage itself, can potentially lead to developmental or neurodegenerative diseases.This study was made possible through the collaboration between two labs at the NIH: one run by Michael E. Ward, M.D., Ph.D. at the National Institute of Neurological Disorders and Stroke (NINDS) and the other by Andre Nussenzweig, Ph.D. at the National Cancer Institute (NCI). Dr. Nussenzweig developed a method for mapping DNA errors within the genome. This highly sensitive technique requires a considerable number of cells in order to work effectively, and Dr. Ward's lab provided the expertise in generating a large population of neurons using induced pluripotent stem cells (iPSCs) derived from one human donor. Keith Caldecott, Ph.D. at the University of Sussex also provided his expertise in single strand break repair pathways.The two labs are now looking more closely at the repair mechanisms involved in reversing neuronal SSBs and the potential connection to neuronal dysfunction and degeneration.
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Biology
| 2,021 |
March 25, 2021
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https://www.sciencedaily.com/releases/2021/03/210325150024.htm
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Wisdom, loneliness and your intestinal multitude
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The evolving science of wisdom rests on the idea that wisdom's defined traits correspond to distinct regions of the brain, and that greater wisdom translates into greater happiness and life satisfaction while being less wise results in opposite, negative consequences.
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Scientists have found in multiple studies that persons deemed to be wiser are less prone to feel lonely while those who are lonelier also tend to be less wise. In a new study, published in the March 25, 2021 issue of the journal The human gut microbiota is comprised of trillions of microbes -- bacteria, viruses, fungi -- that reside within the digestive tract. Researchers have known for a while about the "gut-brain axis," which is a complex network that links intestinal function to the emotional and cognitive centers of the brain.This two-way communication system is regulated by neural activity, hormones and the immune system; alterations can result in disruptions to stress response and behaviors, said the authors, from emotional arousal to higher-order cognitive abilities, such as decision-making.Past studies have associated gut microbiota with mental health disorders including depression, bipolar disorder and schizophrenia, as well as personality and psychological traits regarded as key, biologically based components of wisdom. Recent research has connected the gut microbiome to social behavior, including findings that people with larger social networks tend to have more diverse gut microbiotas.The new "We found that lower levels of loneliness and higher levels of wisdom, compassion, social support and engagement were associated with greater phylogenetic richness and diversity of the gut microbiome," said first author Tanya T. Nguyen, PhD, assistant professor of psychiatry at UC San Diego School of Medicine.The authors said that the mechanisms that may link loneliness, compassion and wisdom with gut microbial diversity are not known, but observed that reduced microbial diversity typically represents worse physical and mental health, and is associated with a variety of diseases, including obesity, inflammatory bowel disease and major depressive disorder.A more diverse gut microbiota may be less susceptible to invasion by outside pathogens, which could contribute to and help promote better resilience and stability of the community."It is possible that loneliness may result in decreased stability of the gut microbiome and, consequently, reduced resistance and resilience to stress-related disruptions, leading to downstream physiological effects, such as systemic inflammation," the authors wrote."Bacterial communities with low alpha-diversity may not manifest overt disease, but they may be less than optimal for preventing disease. Thus, lonely people may be more susceptible to developing different diseases."The relationship between loneliness and microbial diversity was particularly strong in older adults, suggesting that older adults may be especially vulnerable to health-related consequences of loneliness, which is consistent with prior research.Conversely, the researchers said that social support, compassion and wisdom might confer protection against loneliness-related instability of the gut microbiome. Healthy, diverse gut microflora may buffer the negative effects of chronic stress or help shape social behaviors that promote either wisdom or loneliness. They noted that animal studies suggest that gut microbiota may influence social behaviors and interactions, though the hypothesis has not been tested in humans.The complexity of the topic and study limitations, such as the absence of data about individuals' social networks, diet and degree of objective social isolation versus subjective reports of loneliness, argue for larger, longer studies, wrote the authors."Loneliness may lead to changes in the gut microbiome or, reciprocally, alterations of the gut milieu may predispose an individual to become lonely," said Dilip V. Jeste, MD, Distinguished Professor of Psychiatry and Neurosciences at UC San Diego School of Medicine and senior author of the paper. "We need to investigate much more thoroughly to better understand the phenomenon of the gut-brain axis."
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Biology
| 2,021 |
March 25, 2021
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https://www.sciencedaily.com/releases/2021/03/210325145454.htm
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New study sheds light on how X and Y chromosomes interact
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Researchers at Lund University in Sweden have investigated how the X and Y chromosomes evolve and adapt to each other within a population. The results show that breaking up coevolved sets of sex chromosomes could lead to lower survival rates among the offspring -- something that could be of importance in species conservation, for example. The study is published in the journal
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The results provide new clues on how species are formed, and suggest it could be harmful to bring together individuals from different populations that have been separated for a long time. The reason is that the offspring have lower survival rates."This is something worth keeping in mind in conservation biology, where you want to see a population grow," says Jessica Abbott, researcher in evolutionary ecology at Lund University.It is previously known that hybrids between different species often do better if they are female (two X chromosomes) rather than male (X and Y chromosome).In the study, the researchers crossed fruit flies from five different populations from different continents in order to combine X and Y chromosomes with different origins. They then followed and studied the subsequent generations.The results show that males with X and Y chromosomes that don't match had higher reproductive success than males with matching X and Y chromosomes. However, the higher male fertility was paired with lower survival rates among their offspring."We were expecting the opposite, that males with different origin X and Y chromosomes would have lower reproductive success, so that was surprising," says Jessica Abbott.
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Biology
| 2,021 |
March 25, 2021
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https://www.sciencedaily.com/releases/2021/03/210325115335.htm
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A divided cell is a doubled cell
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One big challenge for the production of synthetic cells is that they must be able to divide to have offspring. In the journal
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Organisms cannot simply emerge from inanimate material ("abiogenesis"), cells always come from pre-existing cells. The prospect of synthetic cells newly built from the ground up is shifting this paradigm. However, one obstacle on this path is the question of controlled division -- a requirement for having "progeny."A team from the Max Planck Institute for Medical Research in Heidelberg, Heidelberg University, the Max Planck School Matter to Life, and Exzellenzcluster 3D Matter Made to Order, headed by Kerstin Göpfrich, has now reached a milestone by achieving complete control over the division of vesicles. To achieve this, they produced "gigantic unilamellar vesicles," which are micrometer-sized bubbles with a shell made of a lipid bilayer that resembles a natural membrane. A variety of lipids were combined to produce phase-separated vesicles -- vesicles with membrane hemispheres that have different compositions. When the concentration of dissolved substances in the surrounding solution is increased, osmosis causes water to exit the vesicle through the membrane. This shrinks the volume of the vesicle while keeping the membrane surface equal. The resulting tension at the phase interface deforms the vesicles. They constrict themselves along their "equator" -- increasingly with increasing osmotic pressure -- until the two halves separate completely to form two (now single-phase) "daughter cells" with different membrane compositions. When the separation that occurs depends only on the concentration ratio of osmotically active particles (osmolarity) and is independent of the size of the vesicle.The method by which the osmolarity is raised also plays no role. The methods used by the team included using a sucrose solution and adding an enzyme that splits glucose and fructose to slowly increase the concentration. Using light to initiate splitting of molecules in the solution gave the researchers complete spatial and temporal control over the separation. Using tightly controlled, local irradiation allowed the concentration to be increased selectively around a single vesicle, triggering it to selectively divide.The team is also able to grow the single-phase cells back into phase-separated vesicles by fusing them with tiny vesicles that have the other type of membrane. This was made possible by attaching single strands of DNA to both different types of membrane. These bind to each other and bring the membranes of the daughter cell and the mini vesicle into very close contact so that they can fuse. The resulting gigantic vesicles can subsequently undergo further division cycles."Although these synthetic division mechanisms differ significantly from those of living cells," says Göpfrich, "the question arises of whether similar mechanisms played a role in the beginnings of life on earth or are involved in the formation of intracellular vesicles."
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Biology
| 2,021 |
March 25, 2021
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https://www.sciencedaily.com/releases/2021/03/210325115259.htm
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A new way to visualize mountains of biological data
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Studying genetic material on a cellular level, such as single-cell RNA-sequencing, can provide scientists with a detailed, high-resolution view of biological processes at work. This level of detail helps scientists determine the health of tissues and organs, and better understand the development of diseases such as Alzheimer's that impacts millions of people. However, a lot of data is also generated, and leads to the need for an efficient, easy-to-use way to analyze it.
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Now, a team of engineers and scientists from the University of Missouri and the Ohio State University have created a new way to analyze data from single-cell RNA-sequencing by using a computer method called "machine learning." This method uses the power of computers to intelligently analyze large amounts of data and help scientists draw faster conclusions and move to the next stage of the research. Their methodology is detailed in a new paper published by "Single cell genetic profiling is on the cutting edge of today's technological advances because it measures how many genes are present and how they are expressed from the level of an individual biological cell," said Dong Xu, a professor in the MU College of Engineering. "At a minimum, there could be tens of thousands of cells being analyzed in this manner, so there ends up being a huge amount of data collected. Currently, determining conclusions from this type of data can be challenging because a lot of data must be filtered through in order to find what researchers are looking for. So, we applied one of the newest machine-learning methods to tackle this problem -- a graph neural network."After computers intelligently analyze the data through a machine learning process, the graph neural network then takes the results and creates a visual representation of the data to help easily identify patterns. The graph is made up of dots -- each dot representative of a cell -- and similar types of cells are color coded for easy recognition. Xu said precision medicine is a good example of how single-cell RNA-sequencing can be used."With this data, scientists can study the interactions between cells within the micro-environment of a cancerous tissue, or watch the T-cells, B-cells and immune cells all try to attack the cancerous cells," Xu said. "Therefore, in cases where a person has a strong immune system, and the cancer hasn't fully developed yet, we can learn how the cancer can possibly be killed at an early stage, and we have our results sooner because of machine learning, which leads us to a viable treatment faster."Xu believes this is a great example of how engineers and biologists can work together to study problems or issues in biology. He hopes this method can be used by biologists as a new tool to help solve complex biological questions, such as a possible treatment for Alzheimer's disease.
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Biology
| 2,021 |
March 25, 2021
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https://www.sciencedaily.com/releases/2021/03/210325115256.htm
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Does selfishness evolve? Ask a cannibal
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One of nature's most prolific cannibals could be hiding in your pantry, and biologists have used it to show how social structure affects the evolution of selfish behavior.
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Researchers revealed that less selfish behavior evolved under living conditions that forced individuals to interact more frequently with siblings. While the finding was verified with insect experiments, Rice University biologist Volker Rudolf said the evolutionary principal could be applied to study any species, including humans.In a study published online this week in Also known as weevil moths and pantry moths, Indian meal moths are common pantry pests that lay eggs in cereals, flour and other packaged foods. As larvae, they're vegetarian caterpillars with one exception: They sometimes eat one another, including their own broodmates.In laboratory tests, researchers showed they could predictably increase or decrease rates of cannibalism in Indian meal moths by decreasing how far individuals could roam from one another, and thus increasing the likelihood of "local" interactions between sibling larvae. In habitats where caterpillars were forced to interact more often with siblings, less selfish behavior evolved within 10 generations.Rudolf, a professor of biosciences at Rice, said increased local interactions stack the deck against the evolution of selfish behaviors like cannibalism.To understand why, he suggests imagining behaviors can be sorted from least to most selfish."At one end of the continuum are altruistic behaviors, where an individual may be giving up its chance to survive or reproduce to increase reproduction of others," he said. "Cannibalism is at the other extreme. An individual increases its own survival and reproduction by literally consuming its own kind."Rudolf said the study provided a rare experimental test of a key concept in evolutionary theory: As local interactions increase, so does selective pressure against selfish behaviors. That's the essence of a 2010 theoretical prediction by Rudolf and Boots, the corresponding author of the meal moth study, and Rudolf said the study's findings upheld the prediction."Families that were highly cannibalistic just didn't do as well in that system," he said. "Families that were less cannibalistic had much less mortality and produced more offspring."In the meal moth experiments, Rudolf said it was fairly easy to ensure that meal moth behavior was influenced by local interactions."They live in their food," he said. "So we varied how sticky it was."Fifteen adult females were placed in several enclosures to lay eggs. The moths lay eggs in food, and larval caterpillars eat and live inside the food until they pupate. Food was plentiful in all enclosures, but it varied in stickiness."Because they're laying eggs in clusters, they're more likely to stay in these little family groups in the stickier foods that limit how fast they can move," Rudolf said. "It forced more local interactions, which, in our system, meant more interactions with siblings. That's really what we think was driving this change in cannibalism."Rudolf said the same evolutionary principal might also be applied to the study of human behavior."In societies or cultures that live in big family groups among close relatives, for example, you might expect to see less selfish behavior, on average, than in societies or cultures where people are more isolated from their families and more likely to be surrounded by strangers because they have to move often for jobs or other reasons," he said.Rudolf has studied the ecological and evolutionary impacts of cannibalism for nearly 20 years. He finds it fascinating, partly because it was misunderstood and understudied for decades. Generations of biologists had such a strong aversion to human cannibalism that they wrote off the behavior in all species as a "freak of nature," he said.That finally began to change slowly a few decades ago, and cannibalism has now been documented in well over 1,000 species and is believed to occur in many more."It's everywhere. Most animals that eat other animals are cannibalistic to some extent, and even those that don't normally eat other animals -- like the Indian meal moth -- are often cannibalistic," Rudolf said. "There's no morality attached to it. That's just a human perspective. In nature, cannibalism is just getting another meal."But cannibalism "has important ecological consequences," Rudolf said. "It determines dynamics of populations and communities, species coexistence and even entire ecosystems. It's definitely understudied for its importance."He said the experimental follow-up to his and Boots' 2010 theory paper came about almost by chance. Rudolf saw an epidemiological study Boots published a few years later and realized the same experimental setup could be used to test their prediction.While the moth study showed that "limiting dispersal," and thus increasing local interactions, can push against the evolution of cannibalism by increasing the cost of extreme selfishness, Rudolf said the evolutionary push can probably go the other way as well. "If food conditions are poor, cannibalism provides additional benefits, which could push for more selfish behavior."He said it's also possible that a third factor, kin recognition, could also provide an evolutionary push."If you're really good at recognizing kin, that limits the cost of cannibalism," he said. "If you recognize kin and avoid eating them, you can afford to be a lot more cannibalistic in a mixed population, which can have evolutionary benefits."Rudolf said he plans to explore the three-way interaction between cannibalism, dispersal and kin recognition in future studies."It would be nice to get a better understanding of the driving forces and be able to explain more of the variation that we see," he said. "Like, why are some species extremely cannibalistic? And even within the same species, why are some populations far more cannibalistic than others. I don't think it's going to be one single answer. But are there some basic principles that we can work out and test? Is it super-specific to every system, or are there more general rules?"Additional co-authors include Dylan Childs and Jessica Crossmore of the University of Sheffield, and Hannah Tidbury of both the University of Sheffield and the Centre for Environment, Fisheries and Aquaculture Science in Weymouth, England.The research was funded by the National Science Foundation (1256860, 0841686, 2011109) the National Institutes of Health (R01GM122061) and the Natural Environment Research Council (NEJ0097841).
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Biology
| 2,021 |
March 25, 2021
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https://www.sciencedaily.com/releases/2021/03/210325115253.htm
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Should you take fish oil? Depends on your genotype
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Fish oil supplements are a billion-dollar industry built on a foundation of purported, but not proven, health benefits. Now, new research from a team led by a University of Georgia scientist indicates that taking fish oil only provides health benefits if you have the right genetic makeup.
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The study, led by Kaixiong Ye and published in "We've known for a few decades that a higher level of omega-3 fatty acids in the blood is associated with a lower risk of heart disease," said Ye, assistant professor of genetics in the Franklin College of Arts and Sciences. "What we found is that fish oil supplementation is not good for everyone; it depends on your genotype. If you have a specific genetic background, then fish oil supplementation will help lower your triglycerides. But if you do not have that right genotype, taking a fish oil supplement actually increases your triglycerides."Ye's team, including first author and graduate student Michael Francis, examined four blood lipids (fats) -- high-density lipoprotein, low-density lipoprotein, total cholesterol and triglycerides -- that are biomarkers for cardiovascular disease. The data for their sample of 70,000 individuals was taken from UK Biobank, a large-scale cohort study collecting genetic and health information from half a million participants.The team divided the sample into two groups, those taking fish oil supplements (about 11,000) and those not taking fish oil supplements. Then they performed a genome-wide scan for each group, testing for 8 million genetic variants to compare. After running over 64 million tests, their results revealed a significant genetic variant at gene GJB2. Individuals with the AG genotype who took fish oil decreased their triglycerides. Individuals with the AA genotype who took fish oil slightly increased their triglycerides. (A third possible genotype, GG, was not evident in enough study volunteers to draw conclusions.)Determining your genotype is not as far-fetched as it sounds, thanks to direct-to-consumer genetic testing companies. Companies may not report that specific genetic variant yet, but a tech-savvy consumer should be able to download the raw data and look at the specific position to discover the genotype, according to Ye. The ID for the variant is rs112803755 (A>G).The study's findings may also shed light on previous trials, most of which found that fish oil provides no benefit in preventing cardiovascular disease."One possible explanation is that those clinical trials didn't consider the genotypes of the participants," Ye said. "Some participants may benefit, and some may not, so if you mix them together and do the analysis, you do not see the impact."Now that Ye has identified a specific gene that can modify an individual's response to fish oil supplementation, his next step will be directly testing the effects of fish oil on cardiovascular disease."Personalizing and optimizing fish oil supplementation recommendations based on a person's unique genetic composition can improve our understanding of nutrition," he said, "and lead to significant improvements in human health and well-being."
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Biology
| 2,021 |
March 25, 2021
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https://www.sciencedaily.com/releases/2021/03/210325101256.htm
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More protein doesn't mean more strength in resistance-trained middle-aged adults
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A 10-week muscle-building and dietary program involving 50 middle-aged adults found no evidence that eating a high-protein diet increased strength or muscle mass more than consuming a moderate amount of protein while training. The intervention involved a standard strength-training protocol with sessions three times per week. None of the participants had previous weightlifting experience.
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Published in the The team assessed participants' strength, lean-body mass, blood pressure, glucose tolerance and several other health measures before and after the program. They randomized participants into moderate- and high-protein diet groups. To standardize protein intake, the researchers fed each person a freshly cooked, minced beef steak and carbohydrate beverage after every training session. They also sent participants home with an isolated-protein drink to be consumed every evening throughout the 10 weeks of the study."The moderate-protein group consumed about 1.2 grams of protein per kilogram of body weight per day, and the high-protein group consumed roughly 1.6 grams per kilogram per day," said Colleen McKenna, a graduate student in the division of nutritional sciences and registered dietician at the University of Illinois Urbana-Champaign who led the study with U. of I. kinesiology and community health professor Nicholas Burd. The team kept calories equivalent in the meals provided to the two groups with additions of beef tallow and dextrose.The study subjects kept food diaries and McKenna counseled them every other week about their eating habits and protein intake.In an effort led by U. of I. food science and human nutrition professor Hannah Holscher, the team also analyzed gut microbes in fecal samples collected at the beginning of the intervention, after the first week -- during which participants adjusted to the new diet but did not engage in physical training -- and at the end of the 10 weeks. Previous studies have found that diet alone or endurance exercise alone can alter the composition of microbes in the digestive tract."The public health messaging has been that Americans need more protein in their diet, and this extra protein is supposed to help our muscles grow bigger and stronger," Burd said. "Middle age is a bit unique in that as we get older, we lose muscle and, by default, we lose strength. We want to learn how to maximize strength so that as we get older, we're better protected and can ultimately remain active in family and community life."The American Food and Nutrition Board recommends that adults get 0.8 grams of protein per kilogram of body weight per day to avoid developing a protein deficiency. The team tried to limit protein consumption in the moderate-protein group to the Recommended Daily Allowance, but their food diaries revealed those participants were consuming, on average, 1.1 to 1.2 grams of protein per kilogram of body weight per day. Those in the high-protein group ate about 1.6 grams of protein per kilogram per day -- twice the recommended amount.Burd and his colleagues hypothesized that getting one's protein from a high-quality source like beef and consuming significantly more protein than the RDA would aid in muscle growth and strength in middle-aged adults engaged in resistance training. But at the end of the 10 weeks, the team saw no significant differences between the groups. Their gains in strength, their body fat, lean body mass, glucose tolerance, kidney function, bone density and other "biomarkers" of health were roughly the same.The only potentially negative change researchers recorded between the groups involved alterations to the population of microbes that inhabit the gut. After one week on the diet, those in the high-protein group saw changes in the abundance of some gut microbes that previous studies have linked to negative health outcomes. Burd and his colleagues found that their strength-training intervention reversed some of these changes, increasing beneficial microbes and reducing the abundance of potentially harmful ones."We found that high protein intake does not further increase gains in strength or affect body composition," Burd said. "It didn't increase lean mass more than eating a moderate amount of protein. We didn't see more fat loss, and body composition was the same between the groups. They got the gain in weight, but that weight gain was namely from lean-body-mass gain."Burd said the finding makes him question the push to increase protein intake beyond 0.8-1.1 grams per kilogram of body weight, at least in middle-aged weightlifters consuming high-quality animal-based protein on a regular basis.McKenna said the team's multidisciplinary approach and in-depth tracking of participants' dietary habits outside the laboratory makes it easier to understand the findings and apply them to daily life."We have recommendations for healthy eating and we have recommendations for how you should exercise, but very little research looks at how the two together impact our health," she said. The study team included exercise physiologists, registered dietitians and experts on gut microbiology."This allowed us to address every aspect of the intervention in the way it should be addressed," McKenna said. "We're honoring the complexity of human health with the complexity of our research."
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Biology
| 2,021 |
March 25, 2021
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https://www.sciencedaily.com/releases/2021/03/210325101238.htm
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3D super-resolution images in living mice
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Researchers have developed a new microscopy technique that can acquire 3D super-resolution images of subcellular structures from about 100 microns deep inside biological tissue, including the brain. By giving scientists a deeper view into the brain, the method could help reveal subtle changes that occur in neurons over time, during learning, or as result of disease.
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The new approach is an extension of stimulated emission depletion (STED) microscopy, a breakthrough technique that achieves nanoscale resolution by overcoming the traditional diffraction limit of optical microscopes. Stefan Hell won the 2014 Nobel Prize in Chemistry for developing this super-resolution imaging technique.In "Our microscope is the first instrument in the world to achieve 3D STED super-resolution deep inside a living animal," said leader of the research team Joerg Bewersdorf from Yale School of Medicine. "Such advances in deep-tissue imaging technology will allow researchers to directly visualize subcellular structures and dynamics in their native tissue environment," said Bewersdorf. "The ability to study cellular behavior in this way is critical to gaining a comprehensive understanding of biological phenomena for biomedical research as well as for pharmaceutical development."Conventional STED microscopy is most often used to image cultured cell specimens. Using the technique to image thick tissue or living animals is a lot more challenging, especially when the super-resolution benefits of STED are extended to the third dimension for 3D-STED. This limitation occurs because thick and optically dense tissue prevents light from penetrating deeply and from focusing properly, thus impairing the super-resolution capabilities of the STED microscope.To overcome this challenge, the researchers combined STED microscopy with two-photon excitation (2PE) and adaptive optics. "2PE enables imaging deeper in tissue by using near-infrared wavelengths rather than visible light," said Mary Grace M. Velasco, first author of the paper. "Infrared light is less susceptible to scattering and, therefore, is better able to penetrate deep into the tissue."The researchers also added adaptive optics to their system. "The use of adaptive optics corrects distortions to the shape of light, i.e., the optical aberrations, that arise when imaging in and through tissue," said Velasco. "During imaging, the adaptive element modifies the light wavefront in the exact opposite way that the tissue in the specimen does. The aberrations from the adaptive element, therefore, cancel out the aberrations from the tissue, creating ideal imaging conditions that allow the STED super-resolution capabilities to be recovered in all three dimensions."The researchers tested their 3D-2PE-STED technique by first imaging well-characterized structures in cultured cells on a cover slip. Compared to using 2PE alone, 3D-2PE-STED resolved volumes more than 10 times smaller. They also showed that their microscope could resolve the distribution of DNA in the nucleus of mouse skin cells much better than a conventional two-photon microscope.After these tests, the researchers used their 3D-2PE-STED microscope to image the brain of a living mouse. They zoomed-in on part of a dendrite and resolved the 3D structure of individual spines. They then imaged the same area two days later and showed that the spine structure had indeed changed during this time. The researchers did not observe any changes in the structure of the neurons in their images or in the mice's behavior that would indicate damage from the imaging. However, they do plan to study this further."Dendritic spines are so small that without super-resolution it is difficult to visualize their exact 3D shape, let alone any changes to this shape over time," said Velasco. "3D-2PE-STED now provides the means to observe these changes and to do so not only in the superficial layers of the brain, but also deeper inside, where more of the interesting connections happen."
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Biology
| 2,021 |
March 25, 2021
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https://www.sciencedaily.com/releases/2021/03/210325101221.htm
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New protein helps carnivorous plants sense and trap their prey
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The brush of an insect's wing is enough to trigger a Venus flytrap to snap shut, but the biology of how these plants sense and respond to touch is still poorly understood, especially at the molecular level. Now, a new study by Salk and Scripps Research scientists identifies what appears to be a key protein involved in touch sensitivity for flytraps and other carnivorous plants.
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The findings, published March 16, 2021, in the journal "We know that plants sense touch," says co-corresponding author Joanne Chory, director of Salk's Plant Molecular and Cellular Biology Laboratory and holder of the Howard H. and Maryam R. Newman Chair in Plant Biology. "The Venus flytrap, which has a very fast response to touch, provides an opportunity to study a sensory modality that historically has been poorly understood."Scientists have long been fascinated by Venus flytraps and carnivorous plants; Charles Darwin devoted an entire book to them. But while previous studies have looked at the structural mechanism of their bizarre leaves, not much is known about how they work at the cellular level. That's partly because flytraps are challenging to study. They're extremely slow to grow, and the flytrap genome had not been sequenced until recently, opening the door for deeper genetic research."Because they're so unusual, people have been interested in these plants for hundreds of years, so there's quite a bit known about them at the gross, macroscopic level, but the molecular details have been hard to tease out," says Carl Procko, a staff scientist in Salk's Plant Molecular and Cellular Biology Laboratory.In the new study, the authors grew cloned flytraps from cuttings to get plants that were genetically identical. Then they carefully cut thousands of microscopic, touch-sensitive trigger hairs from these plants and used sequencing technology to identify which proteins were most abundant in the hairs.Based on previous research, they knew that the proteins involved in sensing touch were likely to have the capability of moving an electrical current across the cell. Sure enough, this type of protein was the second most common type found in the hairs. The scientists named the new protein FLYCATCHER1. To test the protein, colleagues at Scripps Research put it into mammalian cells. The cells responded by producing an electrical current when touched, proving that the protein is sensitive to mechanical stimuli.The team found the same protein in the tentacles of the sundew, a carnivorous plant that's a close relative of the Venus flytrap. In the sundew, these sticky tentacles sense the movement of a struggling insect, stimulating the leaf to curl up and trap its prey."These findings are further evidence that the FLYCATCHER1 protein plays a critical role in the trigger hairs of the Venus flytrap and the mechanisms of the plant that sense and respond to touch," says Chory.As a next step, the study authors want to do a "knockout" test and grow genetically modified flytraps with the protein missing. If these flytraps are unable to sense touch, it will prove conclusively that the FLYCATCHER1 protein is responsible.Video:
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Biology
| 2,021 |
March 24, 2021
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https://www.sciencedaily.com/releases/2021/03/210324155119.htm
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Decline in black cherry regeneration may herald wider forest change
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In the heart of black cherry's native range, including a part of the Allegheny Hardwoods that bills itself as the "Black Cherry Capital of the World," the tree's regeneration, growth and survival have all been declining for more than a decade. In a new analysis, a team of USDA Forest Service and University of Missouri scientists identify likely factors behind the tree's decline and, more significantly, conclude that black cherry may be the tip of the iceberg in terms of change in eastern deciduous forests.
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Scientists used a combination of synthesis of existing research and new analyses to examine the leading hypotheses for black cherry's regeneration failure. They conclude that the two factors that are most likely contributing to declining abundance of black cherry are an increase in pathogens and less nitrogen deposition in soil."We began this project wanting to narrow down the potential drivers behind the change in black cherry; what we found is that this may be a story of change on a much bigger scale, with mixed species forests in the coming century likely to reflect the response of many individual tree species to changing environmental conditions, biotic stressors, and their interactions," said Alejandro Royo, a research ecologist with the Northern Research Station and the study's lead author.
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Biology
| 2,021 |
March 24, 2021
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https://www.sciencedaily.com/releases/2021/03/210324155108.htm
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Zooming in on muscle cells
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Sarcomeres are small repeating subunits of myofibrils, the long cylinders that bundle together to make the muscle fibres. Inside the sarcomeres, filaments of the proteins myosin and actin interact to generate muscle contraction and relaxation. So far, traditional experimental approaches to investigate the structure and function of muscle tissue were performed on reconstructed protein complexes or suffered from low resolution. "Electron cryo-tomography, instead, allows us to obtain detailed and artefact-free 3D images of the frozen muscle," says Raunser.
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Cryo-ET was for a long time an established yet niche methodology. But recent technical advances in electron cryo-microscopy (cryo-EM) as well as the new development of cryo focused ion beam (FIB) milling are pushing cryo-ET resolution. Similar to cryo-EM, researchers flash-freeze the biological sample at a very low temperature (- 175 °C). Through this process, the sample preserves its hydration and fine structure and remains close to its native state. FIB milling is then applied to shave away extra material and obtain an ideal thickness of around 100 nanometers for the transmission electron microscope, which acquires multiple images as the sample is tilted along an axis. Finally, computational methods reconstruct a three-dimensional picture at high resolution.Raunser's team performed cryo-ET on mouse myofibrils isolated at the King's College, and obtained a resolution of one nanometer (a millionth of a millimetre, enough to see fine structures within a protein): "We can now look at a myofibril with details thought unimaginable only four years ago. It's fascinating!," says Raunser.The calculated reconstruction of the myofibrils revealed the three-dimensional organisation of the sarcomere, including the sub regions M-, A-, and I- bands, and the Z-disc, which unexpectedly forms a more irregular mesh and adopts different conformations. The scientists used a sample with myosin strongly bound to actin, representing a stage of the contracting muscle that is called the rigor state. And indeed, they could visualise for the first time in the native cell how two heads of the same myosin bind to an actin filament. They also discovered that the double head not only interacts with the same actin filament but is also found split between two actin filaments. This has never been seen before and shows that proximity to the next actin filament is stronger than the cooperative effect between the neighbouring heads."This is just the beginning. Cryo-ET is moving from niche to widespread technology in structural biology," says Raunser. "Soon we will be able to investigate muscle diseases at molecular and even atomic level." Mouse muscles are very similar to those of humans, yet scientists plan to investigate muscle tissue from biopsies or derived from pluripotent stem cells.
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Biology
| 2,021 |
March 24, 2021
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https://www.sciencedaily.com/releases/2021/03/210324142839.htm
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Photosynthesis could be as old as life itself
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Researchers find that the earliest bacteria had the tools to perform a crucial step in photosynthesis, changing how we think life evolved on Earth.
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The finding also challenges expectations for how life might have evolved on other planets. The evolution of photosynthesis that produces oxygen is thought to be the key factor in the eventual emergence of complex life. This was thought to take several billion years to evolve, but if in fact the earliest life could do it, then other planets may have evolved complex life much earlier than previously thought.The research team, led by scientists from Imperial College London, traced the evolution of key proteins needed for photosynthesis back to possibly the origin of bacterial life on Earth. Their results are published and freely accessible in Lead researcher Dr Tanai Cardona, from the Department of Life Sciences at Imperial, said: "We had previously shown that the biological system for performing oxygen-production, known as Photosystem II, was extremely old, but until now we hadn't been able to place it on the timeline of life's history. Now, we know that Photosystem II show patterns of evolution that are usually only attributed to the oldest known enzymes, which were crucial for life itself to evolve."Photosynthesis, which converts sunlight into energy, can come in two forms: one that produces oxygen, and one that doesn't. The oxygen-producing form is usually assumed to have evolved later, particularly with the emergence of cyanobacteria, or blue-green algae, around 2.5 billion years ago.While some research has suggested pockets of oxygen-producing (oxygenic) photosynthesis may have been around before this, it was still considered to be an innovation that took at least a couple of billion years to evolve on Earth.The new research finds that enzymes capable of performing the key process in oxygenic photosynthesis -- splitting water into hydrogen and oxygen -- could actually have been present in some of the earliest bacteria. The earliest evidence for life on Earth is over 3.4 billion years old and some studies have suggested that the earliest life could well be older than 4.0 billion years old.Like the evolution of the eye, the first version of oxygenic photosynthesis may have been very simple and inefficient; as the earliest eyes sensed only light, the earliest photosynthesis may have been very inefficient and slow.On Earth, it took more than a billion years for bacteria to perfect the process leading to the evolution of cyanobacteria, and two billion years more for animals and plants to conquer the land. However, that oxygen production was present at all so early on means in other environments, such as on other planets, the transition to complex life could have taken much less time.The team made their discovery by tracing the 'molecular clock' of key photosynthesis proteins responsible for splitting water. This method estimates the rate of evolution of proteins by looking at the time between known evolutionary moments, such as the emergence of different groups of cyanobacteria or land plants, which carry a version of these proteins today. The calculated rate of evolution is then extended back in time, to see when the proteins first evolved.They compared the evolution rate of these photosynthesis proteins to that of other key proteins in the evolution of life, including those that form energy storage molecules in the body and those that translate DNA sequences into RNA, which is thought to have originated before the ancestor of all cellular life on Earth. They also compared the rate to events known to have occurred more recently, when life was already varied and cyanobacteria had appeared.The photosynthesis proteins showed nearly identical patterns of evolution to the oldest enzymes, stretching far back in time, suggesting they evolved in a similar way.First author of the study Thomas Oliver, from the Department of Life Sciences at Imperial, said: "We have used a technique called Ancestral Sequence Reconstruction to predict the protein sequences of ancestral photosynthetic proteins. These sequences give us information on how the ancestral Photosystem II would have worked and we were able to show that many of the key components required for oxygen evolution in Photosystem II can be traced to the earliest stages in the evolution of the enzyme."Knowing how these key photosynthesis proteins evolve is not only relevant for the search for life on other planets, but could also help researchers find strategies to use photosynthesis in new ways through synthetic biology.Dr Cardona, who is leading such a project as part of his UKRI Future Leaders Fellowship, said: "Now we have a good sense of how photosynthesis proteins evolve, adapting to a changing world, we can use 'directed evolution' to learn how to change them to produce new kinds of chemistry. We could develop photosystems that could carry out complex new green and sustainable chemical reactions entirely powered by light."
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Biology
| 2,021 |
March 24, 2021
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https://www.sciencedaily.com/releases/2021/03/210324132309.htm
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Green leafy vegetables essential for muscle strength
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Eating just one cup of leafy green vegetables every day could boost muscle function, according to new Edith Cowan University (ECU) research.
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The study, published today in the Poor muscle function is linked to greater risk of falls and fractures and is considered a key indicator of general health and wellbeing.Researchers examined data from 3,759 Australians taking part in Melbourne's Baker Heart and Diabetes Institute AusDiab study over a 12-year period. They found those with the highest regular nitrate consumption had 11 per cent stronger lower limb strength than those with the lowest nitrate intake. Up to 4 per cent faster walking speeds were also recorded.Lead researcher Dr Marc Sim from ECU's Institute for Nutrition Research said the findings reveal important evidence for the role diet plays in overall health."Our study has shown that diets high in nitrate-rich vegetables may bolster your muscle strength independently of any physical activity," he said."Nevertheless, to optimise muscle function we propose that a balanced diet rich in green leafy vegetables in combination with regular exercise, including weight training, is ideal."Muscle function is vital for maintaining good overall health, especially bone strength later in life."With around one in three Australians aged over 65 suffering a fall each year, it's important to find ways of preventing these events and their potentially serious consequences," said Dr Sim.While leafy greens may be some of our least favourite vegetables, they could be the most important, according to Dr Sim.The research found nitrate-rich vegetables, such as lettuce, spinach, kale and even beetroot, provided the greatest health benefits."Less than one in ten Australians eat the recommended five to six serves of vegetables per day," Dr Sim said."We should be eating a variety of vegetables every day, with at least one of those serves being leafy greens to gain a range of positive health benefits for the musculoskeletal and cardiovascular system.""It's also better to eat nitrate-rich vegetables as part of a healthy diet rather than taking supplements. Green leafy vegetables provide a whole range of essential vitamins and minerals critical for health."The study, a collaboration with Deakin University's Institute of Physical Activity and Nutrition and the Baker Heart and Diabetes Institute, builds on Dr Sim's previous research into nitrate and muscle function in older women.It also adds to growing evidence linking vegetables with cardiovascular health, including a recent ECU study into cruciferous vegetables and blood vessel health.Dr Sim said the next step of his research will be exploring strategies to increase leafy green vegetable consumption in the general population."We are currently recruiting for the MODEL Study, which examines how knowledge of disease can be used to prompt people in making long-term improvements to their diet and exercise," said Dr Sim.
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Biology
| 2,021 |
March 24, 2021
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https://www.sciencedaily.com/releases/2021/03/210324113410.htm
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Study illuminates the molecular details of lung development
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Researchers at the Perelman School of Medicine at the University of Pennsylvania have produced a detailed molecular atlas of lung development, which is expected to be a fundamental reference in future studies of mammalian biology and of new treatments for diseases, such as COVID-19, that affect the lungs.
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The researchers, who published their study in "This study provides foundational information to guide our understanding of how lung function develops, and how the early postnatal period of life is a time of rapid adjustment in the lungs to optimize gas exchange," said study senior investigator Edward Morrisey, PhD, the Robinette Foundation Professor of Medicine, a professor of Cell and Developmental Biology, and director of the Penn-CHOP Lung Biology Institute at Penn Medicine.The trove of new data is likely to be valuable in the development of future treatments for early-life lung problems, including insufficient lung development in premature babies. It may also speed the search for better therapies for pneumonia and chronic obstructive pulmonary disease (COPD), two of the leading causes of death worldwide.The study focused largely on the developmental steps leading to the maturation of alveoli. These delicate sac-like structures in the lungs contain thin, capillary-rich membranes that orchestrate the exchange of carbon dioxide in the bloodstream for oxygen in inhaled air. There are hundreds of millions of alveoli in an average human lung, and the total surface area of their gas-exchange membranes has been estimated as approximately the same as a tennis court's.Many human diseases, from birth to old age, disrupt these vital structures. Yet the details of how cells emerge and signal to each other to bring about the formation of alveoli in early life have remained largely mysterious.Morrisey's team used two relatively new techniques called single-cell RNA sequencing and single cell ATAC sequencing to record the expression and accessibility of genes in thousands of individual cells at seven different time-points during lung development in mice. They then analyzed the gene activity in each cell type, at each time point, to predict which cells were making important signaling molecules and which were expressing the receptors that receive those signals. In this way they made a map of predicted interactions among all these cells, from which they could identify key factors in alveolar development. Lastly, they confirmed the activity of two of these pathways, the Wnt and Sonic Hedgehog (Shh) pathway, using genetic mouse models to inactivate their function in specific cell types identified in the single cell experiments.A novel finding of the study was the identification of a cell type known as the alveolar type 1 epithelial cell (AT1), which was already known to help form alveolar gas exchange interface, as a crucial originator and hub of molecular signals that guide alveolar development. The researchers also determined that another cell type known as the secondary crest myofibroblast (SCMF) plays a key role in guiding the maturation of alveolar structures. Morrisey's team moreover identified several transcription factor proteins -- which regulate gene activity -- as crucial for normal alveolar development. Some of these findings were also confirmed to occur in the human pediatric lung. The vast new dataset generated by the researchers should empower many future studies, including deeper studies of human lung development.The molecular details of how alveoli develop will also inform future research aimed at treating disorders that affect these structures. Babies that are born very prematurely often suffer from respiratory distress because their alveoli are not yet fully developed. Pneumonias, which can be caused by bacteria or viruses -- including SARS-CoV-2 -- and can affect anyone from childhood to old age, usually feature a storm of alveoli-damaging immune molecules and immune cells, and the destruction of the alveolar gas-exchange interface. Similarly, COPD, which can result from long-term cigarette smoking, involves chronic inflammation and degeneration of alveolar structures."We are hopeful that our study will provide a framework for a better understanding of the molecular pathways that could be harnessed to promote lung regeneration after acute or chronic injury," Morrisey said.
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Biology
| 2,021 |
March 24, 2021
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https://www.sciencedaily.com/releases/2021/03/210324094735.htm
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Capturing the structure of large molecular complexes
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SMN or in full Survival Motor Neuron: Professor Utz Fischer has been analyzing this protein and the large molecular complex of the same name, of which SMN is one of the building blocks, for many years. He holds the Chair of the Department of Biochemistry at the Julius-Maximilian's University of Würzburg (JMU), and he first discovered the molecule during his search for the root cause of spinal muscular atrophy. As scientists found out a few years ago, this disease is caused by a lack of the SNM complex.
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The work group around Prof. Fischer has now succeeded in presenting a first three-dimensional model of the entire SNM complex. Once the structure of the complex is known, it is possible to understand the way how the complex works, and why the loss of its function leads to muscular atrophy. The scientists have published their findings in the current issue of the journal The new findings have been made possible by an integrative structural-biological approach that combines biochemical, genetic and biophysical technologies."The structural analysis of large and complex molecules in atomic detail has been made possible by the 'revolution-resolution', which was primarily brought about by the developments in cryo-electron microscopy," says Utz Fischer. The only snag about the technology, however, is the fact that it works best on structures that are more or less rigid and have few flexible sections.Unfortunately, many molecular entities are not built like this, including the SMN complex. "This complex is of central importance for our cells because it supports the formation of molecular machines required for the expression of our genes," says Prof. Fischer. However, in order to serve its function in the cell, it must be highly flexible and dynamic. As a result, a structural analysis by traditional strategies has been impossible so far.Therefore the Fischer and his team chose an alternative approach: "Our starting point was a cooperation with the group of Dr. Rémy Bordonné from Montpellier in France, that enabled us to identify the SMN complex of the yeast Schizosaccharomyces pombe," he explains. This complex was ideally suited for an integrative structural analysis because it comprises less individual components than its human counterpart and has a less dynamic behavior."In a first step, we visualized, by X-ray diffraction analysis, individual sections that are important for keeping the complex together," says Fischer about the scientists' approach. In a second step, they characterized the entire complex and parts of it by means of small-angle X-ray scattering. This method also provides information on the dynamic behavior of unfolded sections of the complex. In parallel, missing sections were reconstructed by means of a bioinformatic method called 3D homology modeling.This combination of different structural-biological methods will gain in importance in the future because it produces results that have never been achieved before -- such is the conviction of Dr. Clemens Grimm. He is the Head of the "Structural Analysis" unit of Fischer's department, and has contributed to the recently published work.The result was a model of the entire SMN complex that provides an excellent explanation of its function. Similar as in an octopus, the central "body" of the complex has a number of long and very flexible "arms," which enable the complex to catch proteins and assemble them, together with other biomolecules, into molecular machines.The model also provides insight into the processes that lead to spinal muscular atrophy. "The mutations causing this disease concentrate in the central body" explains Fischer's doctoral student Jyotishman Veepaschit, who performed experiments of this study together with his colleague Aravindan Viswanathan. They prevent the full development of the complex, so that it cannot serve its function in the cell.Spinal muscular atrophy is a congenital disease that can appear in children, adolescents and adults with symptoms of variable severity. In its most severe forms, the patients affected by it die as early as infancy from the consequences of muscular weakness and progressive paralysis. In other cases, medical care including physiotherapy and orthopedic aids can preserve their mobility and vitality for quite some time.Spinal muscular atrophy is not rare: It affects about one of 6,000 persons. Due to a genomic mutation, such persons suffer from a lack of the protein SMN. This lack manifests itself especially in the nerve cells that control muscle movements. These cells, known as motor neurons, lose their contact with the muscle and die.
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Biology
| 2,021 |
March 24, 2021
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https://www.sciencedaily.com/releases/2021/03/210324094732.htm
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Scaled, armored or naked: How does the skin of fish evolve?
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Usually scaled, the skin of fish can also be naked or made up of bony plates that form an armour, sometimes even covered with teeth. But how has this skin evolved over the ages? To answer this question, researchers at the University of Geneva (UNIGE), Switzerland, have reconstructed the evolution of the protective skin structures in fish, going back to the common ancestor of ray-finned fish, more than 420 million years ago. They found that only fish that had lost their scales were able to develop a bony armour, and that the protective state of their skin influenced their choice of open water or sea floor habitats. This study, published in the journal
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Ray-finned fish, such as catfish or goldfish, constitute the most diverse lineage of vertebrates on Earth, with no less than 25,000 species, i.e. half of the planet's vertebrates. "Far from being limited to scales, these fish species can also have completely naked skin or a bony armour, sometimes covered with teeth, as is the case with certain catfish," notes Juan Montoya, a researcher in the Department of Genetics and Evolution at the UNIGE Faculty of Science. But how did the protective structure of the skin evolve in these fish?The researchers used an evolutionary tree of fish that lists 11,600 species. "In order to reconstruct the ancestral characteristics of the species, we worked in parallel with a second tree of 304 species, which precisely establishes the links of relationship," explains Alexandre Lemopoulos, a researcher in the Department of Genetics and Evolution at the Faculty of Science of the UNIGE. They asked themselves two questions: What type of protection do the fish have on their skin? And do they live in the open water or on the seabed?Using mathematical models, they reconstructed the most likely ancestral state and, as they went up the family tree, they reconstructed the transitions between the three skin types and observed whether these had conditioned their habitat. "We were able to go back to the first ancestor of ray-finned fish, more than 420 million years ago, who had scales," enthuses Juan Montoya.By analysing the transitional stages, the Geneva researchers found several lineages of fish that lost their scales, but at different positions in the tree. "There is therefore no temporal coincidence in this evolution," emphasises Alexandre Lemopoulos. Moreover, once a lineage of fish has lost its scales, it cannot find them again. "On the other hand, some of these naked fish subsequently developed bony plates covering part or all of their body, forming a solid armour," points out Juan Montoya. "We now need to discover the underlying genetic mechanism, which probably no longer allows a return to the scale stage, but makes it possible to build a compensatory external skeleton." Thus, only naked fish were able to build up this armour. "It does not seem possible to go directly from a scaly skin to a cuirassed skin, nor to have a mixture of these two structures," he says.The researchers also observed that the change in skin condition conditioned the place of habitation. "Several species of fish that have lost their scales have left the open waters in which they lived for the seabed, certainly finding an advantage in this new environment," explains Alexandre Lemopoulos. This is a pre-adaptation: the fish lose their scales, change environment and find advantages. As this sequence was repeated independently in several groups of fish, the researchers deduce that a skin without scales offers a real advantage for living on the bottom. "It should be noted that once a lineage of fish establishes itself on the seabed, it no longer returns to the open water, even if it subsequently develops a bony armour," he continues.Two hypotheses seem to explain this 'move': respiration and immune defence. "Fish breathe through their gills, but also through their skin. Bare skin improves gas exchange in poorly oxygenated water by increasing the respiratory surface," suggests Alexandre Lemopoulos. Furthermore, recent studies have shown that the immune defence against viruses and bacteria, which are very present in the seabed, was more effective when the skin had no scales.It is therefore thanks to the evolution of the protective structures of the skin that several families of fish have migrated to the seabed and opened up new ecological niches, colonising more and more different environments, whether in fresh or salt water. "This has contributed to the establishment of this enormous diversity, which makes ray-finned fish the largest group of vertebrates on the planet," concludes Juan Montoya.
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Biology
| 2,021 |
March 24, 2021
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https://www.sciencedaily.com/releases/2021/03/210324094716.htm
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Automatic trail cameras keep wildlife research going during pandemic
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For scientists, especially graduate students, who conduct fieldwork, every day is precious. Researchers meticulously prepare their equipment, procedures and timelines to make sure they get the data they need to do good science. So you can imagine the collective anxiety that fell across academia in spring 2020 when COVID-19 struck and many universities suspended in-person activities, including fieldwork.
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But for Austin Green, a doctoral student in the School of Biological Sciences and 2019 recipient of a National Geographic Society Early Career Grant, who studies the wildlife that lives in the canyons of the Wasatch Front, that anxiety was tempered by the knowledge that pandemic or no pandemic, his network of automated motion-activated trail cameras would keep their silent watch over the canyons' mammals and birds."You can set them up at the beginning of the year and leave them up until your field season is over," Green says. "And we were not the only ones that did this. In fact, there were entire nationwide and global initiatives that were able to continue gathering data during pandemic restrictions on field research."Now Green and his colleagues are sharing what they've learned about the importance of trail cameras for wildlife conservation and management in the journal Trail cameras (also called camera traps although they don't trap or restrain anything) are motion-activated cameras that researchers can attach to a tree or pole, usually at knee-height, in remote areas. The cameras then take photos whenever something walks by. Some models transmit photos wirelessly, but many collect photos on an SD card, which researchers like Green change out periodically when they change the camera's batteries. They can also be programmed to capture video to document fascinating vignettes of animal behavior."All newer models have exceptional battery life and photo storage capacity," Green says. "So, we set them up before restrictions went into place and kept them up throughout the entire field season, allowing us to gather another full season of data."Even before the COVID-19 pandemic, biologists were already turning to trail cameras as a way to conduct biological surveys that avoided the difficult, labor-intensive process of physically trapping, tagging and releasing of animals."However, with trail cameras, researchers can monitor individual animals passively over a large number of cameras and a large area, as long as the individuals can be individually identified through photographs," Green says. "Cameras do not need to be maintained on a daily basis, and no individual animals ever need to be processed."For Green's purposes, trail cameras are perfect. He's looking to study the wildlife that inhabit the canyons of the Wasatch Front, and with the help of a team of more than 200 community volunteers, maintains 300 trail cameras stretching as far north as Logan, Utah and as far south as Point of the Mountain. The cameras have captured images of turkeys, herons, moose, coyotes, cougars and many others.When COVID-19 restrictions began, Green quickly adapted his operation, moving training materials online and setting up a contactless pick-up method for equipment. Crowdsourced data entry proceeded as it had before. Green calls the efforts of his community volunteers inspiring."No matter what changes we threw at them, whether it was going completely online for all non-fieldwork related logistics or having to individually find time to disperse equipment, these amazing people never missed a beat," Green says. "One thing I'll take from this and apply to my research moving forward is that, even in hard times, there are always those willing to do what is necessary to get the job done."And it was a good thing he and his volunteers were able to keep the cameras running, because the early weeks of the pandemic provided a unique research opportunity."The pandemic has created so much hardship and tragedy for so many people, and this can make it difficult to find any silver linings," Green says, "However, the sudden change in human traffic, deemed by scientists as the 'anthropause,' has presented an opportunity to study how wildlife react to quasi-experimental changes in human influence."Çağan Şekercioğlu, associate professor in the School of Biological Sciences, says that trail cameras can also perform an important conservation function. While the general public, conservationists, rangers and others often had to stay home due to mandatory lockdowns, trespassers, poachers and illegal loggers continued going into wild areas. "During the lockdown, to this day in many places, trail cameras are our only eyes on the ground," Şekercioğlu says.Green, Şekercioğlu and colleagues write in Biological Conservation that trail cameras are well-suited for fundamental research questions like investigating the presence, relative abundance, density, occupancy, and activity of animal species. They can be instrumental in discovering the presence of a new species or the expansion of its range. Further, they write, while more cameras are better, even a single camera can yield valuable information.Trail cameras can go further as well to address questions of human impacts on wildlife, trends in biodiversity, reproductive ecology, behavior and interactions between species, and even which predators are raiding bird nests.As a research tool, trail cameras are a complement to good research design. "My advice for other researchers will always be to first and foremost clearly articulate the particular question they hope to address and decide what tools can be used to help them address it," Green says. "Although I'm not sure research can ever be fully 'pandemic-proofed' or resistant to disruptions, I can say that being willing, flexible and creative enough to adapt to unique situations will always be critical to the advancement of science. After all, so many great scientific discoveries were unexpected beforehand."
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Biology
| 2,021 |
March 23, 2021
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https://www.sciencedaily.com/releases/2021/03/210323150723.htm
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New test traces DNA origins to monitor transplant rejection and reveal hidden cancers
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A new technique that can trace which tissues and organs the DNA in our blood comes from has been reported today in the open-access
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The method, called GETMap, could be used in prenatal screening, to monitor organ transplant rejection, or test for cancers that are concealed in the body."Analysis of circulating free DNA has been shown to be useful for screening for early asymptomatic cancers," explains first author Wanxia Gai, Postdoctoral Fellow at the Chinese University of Hong Kong, Hong Kong SAR, China. "As cancer-associated DNA changes are present in a wide range of cancer types, detection of such changes can be used as a universal test for concealed cancers. However, in patients with a positive test result, you still need to follow up with tests to find the tumour's location, for example, with a whole-body positron emission tomography, or PET, scan."To address this, the team developed a test that looks for genetic differences, as well as epigenetic changes to DNA (changes which do not affect DNA sequences) known as methylation. The DNA in our cells has a unique methylation 'fingerprint'. Comparing the methylation fingerprints of different genetic types of DNA molecules circulating in the blood, for example molecules from a fetus, transplanted organ or tumour, with that of different tissues identifies where the DNA has come from.The team first tested their approach in pregnant women, where they knew that blood DNA would include DNA from the mother, fetus, or both. As expected, GETMap found that DNA carrying fetus-specific genetic markers carried methylation signatures exclusively from the placenta. On the other hand, DNA molecules carrying mother-specific genetic markers carried methylation signatures from white blood cells. DNA molecules carrying genetic markers shared by both the mother and fetus were derived from both tissues.Next, they tested the approach in blood donated by patients following a lung transplant. Detecting unusually high concentrations of DNA from a transplanted organ in blood can be a sign of organ rejection. But immediately after a transplant, there is often an unexplained surge in donor-derived DNA in the transplant recipient's blood. This makes it challenging to detect whether the organ is being rejected if only genetic markers are used. By using a combination of genetic and epigenetic markers, the team identified the origins of this surge in donor DNA. At 72 hours after transplantation, only 17% of the circulating DNA was from the lung, compared with 78% from blood cells. This surprisingly high contribution from the blood cells was likely due to the release of DNA from blood cells in the blood vessels of the transplanted lung. With time, the amount of circulating DNA from the lung increased, and the amount from blood cells decreased. There also seemed to be more donor lung DNA in the blood of patients whose new lungs were rejected, compared to those who had a successful transplant.The team also tested whether GETMap could detect the origin of tumour-derived DNA in the blood. In two patients with liver cancer, they found that 90% and 87% of the plasma DNA carrying mutations had come from the liver. To test this, they needed to know the exact tumour mutations they were looking for, and tumour tissue is not always available if its location is unknown. The team therefore tried to use methylation fingerprints to identify cancer mutations directly from blood DNA rather than tumour tissue. Although fewer mutations were found, the liver was still correctly identified as the source of the tumour-derived molecules. This suggests GETMap could help to reveal the tissue and location of concealed cancers in people who have tumour markers in their blood.Finally, they challenged the GETMap test in a woman who developed lymphoma during pregnancy. In this instance, they were able to distinguish between the fetal-specific genes which were derived from the placenta, and the tumour-specific genes which originated solely from a family of white blood cells that were related to the cell type of the lymphoma."We have demonstrated the powerful synergy between genetic and epigenetic approaches for identifying the origin of circulating DNA in the blood, and shown its potential applications in cancer screening, prenatal testing and organ transplant monitoring," says co-senior author Dennis Lo, Director of the Li Ka Shing Institute of Health Sciences, and the Li Ka Shing Professor of Medicine at the Chinese University of Hong Kong."Our test could bring us closer to the vision of a blood test for a universal cancer marker, by allowing more targeted follow-up tests in specific organs," concludes co-senior author Allen Chan, Professor of Chemical Pathology at the Chinese University of Hong Kong. "This could make cancer diagnosis earlier and more accurate, and reduce the use of whole-body scans and the associated exposure to radiation."
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Biology
| 2,021 |
March 23, 2021
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https://www.sciencedaily.com/releases/2021/03/210323150719.htm
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Rare fossilized algae, discovered unexpectedly, fill in evolutionary gaps
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When geobiology graduate student Katie Maloney trekked into the mountains of Canada's remote Yukon territory, she was hoping to find microscopic fossils of early life. Even with detailed field plans, the odds of finding just the right rocks were low. Far from leaving empty-handed, though, she hiked back out with some of the most significant fossils for the time period.
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Eukaryotic life (cells with a DNA-containing nucleus) evolved over two billion years ago, with photosynthetic algae dominating the playing field for hundreds of millions of years as oxygen accumulated in the Earth's atmosphere. Geobiologists think that algae evolved first in freshwater environments on land, then moved to the oceans. But the timing of that evolutionary transition remains a mystery, in part because the fossil record from early Earth is sparse.Maloney's findings were published yesterday in Although the field site was carefully chosen by Maloney's field team leader, sedimentologist Galen Halverson, who has worked in the region for years, the discovery was an unexpected stroke of luck."I was thinking, 'maybe we'll find some microfossils,'" Maloney said. The possibility of finding larger fossils didn't cross her mind. "So as we started to find well-preserved specimens, we stopped everything and the whole team gathered to collect more fossils. Then we started to find these big, complex slabs with hundreds of specimens. That was really exciting!"Determining if traces like the ones Maloney found are biogenic (formed by living organisms) is a necessary step in paleobiology. While that determination is ultimately made in the lab, a few things tipped her off in the field. The traces were very curvy, which can be a good indicator of life, and there were visible structures within them. The fact that there were hundreds of them twisted together sealed the deal for her.Few people would likely have noticed the fossils that day."We were really lucky that Katie was there to find them because at first glance, they don't really look like anything," Maloney's advisor, Marc Laflamme, said. "Katie is used to looking at very weird looking fossils, so she has a bit of an eye for saying, 'This is something worth checking out.'"Maloney and her colleagues in the field wrestled the heavy slabs into their helicopter for safe transport back to the lab at the University of Toronto-Mississauga. She, Laflamme, and their collaborators used microscopy and geochemical techniques to confirm that the fossils were indeed early eukaryotes. They then mapped out the specimens' cellular features in detail, allowing them to identify multiple species in the community.While Maloney and her coauthors were writing up their results, they were confident they had found the first macroscopic specimens from this critical time period. During the peer review process, though, they received word from a collaborator that another group in China had made a similar discovery at about the same time -- macrofossils from a similar period. That did not dissuade them."What's a few hundred million years between friends?" Laflamme laughed. "I think our fossils have more detail, which makes them easier to interpret... They're beautiful. They're huge, they're well detailed, there's anatomy. Your eyes are just drawn to them."Ultimately, having two sets of macrofossils from approximately the same time can only improve the timeline of eukaryotic evolution, serving as critical calibration points for DNA-based biologic dating techniques. The new fossils also push back the time when algae were living in marine environments, indicating that evolution had already occurred in lakes on land. But for Maloney, an expert in sedimentology, they also raise questions about what gets preserved in the rock record and why."Algae became really important early on because of their role in oxygenation and biogeochemical cycles," Maloney said. "So why does it take them so long to show up reliably in the fossil record? It's definitely making us think more about animal ecosystems and whether or not we're seeing the whole picture, or if we're missing quite a bit from a lack of preservation."The whole project has been engaging for Maloney, who pivoted to algae from more recent biota. "I never expected to be fascinated by algae," she said. "But I was pleasantly surprised as I started investigating modern algae, finding what an important role they play in sustainability and climate change -- all these big issues that we're dealing with today. So it's been amazing contributing to algae's origin story."This fieldwork was carried out with permits on traditional lands of the First Nation of Na-Cho Nyak Dun with their consent.
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Biology
| 2,021 |
March 23, 2021
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https://www.sciencedaily.com/releases/2021/03/210323131314.htm
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Corals may need their predators' excrement
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Fish that dine on corals may pay it forward with feces
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It's an unexpected twist on coral reef symbiosis, said Rice University marine biologist Adrienne Correa, whose lab discovered coral predator feces are jam-packed with living symbiotic algae that corals depend on for survival. The discovery confirms that feces from coral-eating fish is an important environmental source of symbiotic dinoflagellate algae on coral reefs.Correa said coral-eating predators are typically thought of as biting and weakening reef structures, thereby generating hiding spaces for other organisms and, ultimately, beach sand. In contrast, grazing fish that crop down bushy algae get the limelight for helping reefs maintain healthy coral cover."The message is, 'Move over grazers, it's not just you helping maintain coral dominance. These coral-eating fishes are probably helping too by spreading beneficial coral symbionts,'" she said.Rice doctoral student Carsten Grupstra, lead author of the study in In exchange for a sheltered life, dinoflagellates nourish their hosts by sharing the food they photosynthesize. Millions of symbionts live in each coral, but some corals aren't born with dinoflagellates. They acquire them as babies."When many baby corals settle on the reef bottom, they have to get their symbionts from the environment," Correa said. "We've seen symbionts in the water and sediments and on big bushy algae on reefs, but we haven't really looked at how those microorganisms get to all those places."In thinking about ways symbionts might be distributed on reefs, Grupstra, Correa, graduate student Lauren Howe-Kerr and undergraduate Kristen Rabbitt were inspired by studies of pollinating insects and birds that pass beneficial bacteria between flowering plants. Like pollinating bees that visit many flowers in a single flight, coral-eating fish constantly crisscross reefs and interact with many corals each day."Most of them take small bites of adult corals and don't kill the colonies they're eating," Grupstra explained.During an expedition to the Mo'orea Coral Reef Long-term Ecological Research station in French Polynesia, Grupstra, Howe-Kerr, Rabbitt and Correa followed fish that ate different amounts of coral and algae. Using underwater clipboards, they made note of what the fish ate and where and how often they defecated. Grupstra also gathered samples of predator and grazer feces to examine in the lab."I left some samples in the window sill for a couple of weeks in Mo'orea" he said. "Later, when I started looking at them (under a microscope), I found tons of symbionts. A lot of them were swimming around and some were dividing."The sheer number of live symbionts was both unexpected and potentially important in the larger picture of reef ecology, Correa said. While symbionts had previously been reported in feces from a limited number of coral predators, it was unclear how many of them were alive and potentially useful to corals. Her group found high concentrations of live symbionts in the feces of a diverse group of coral predators. For example, the Rice team estimated that two species at the Mo'orea research station, Chaetodon ornatissimus and Chaetodon reticulatus, each spread about 100 million live symbionts per day over an area of reef approximately the size of six parking spaces."This expands how we can think about the roles of coral-eating fishes on reefs," Correa said. "They don't just break up reef frameworks. They also disperse symbionts that corals and other organisms need."The knowledge that predator feces creates "hotspots" of live symbiotic dinoflagellates on reefs raises questions about whether and how coral use them. Correa's team has planned a series of experiments on both juvenile and stressed adult corals to determine how readily they absorb beneficial symbionts from the feces.She said many questions remain about how and how frequently corals take up symbionts from the environment. For example, marine biologists widely agree that many coral babies get their symbionts from the environment, but it is unclear how often adults do this and under what conditions. Better understanding symbiont uptake could lead to new methods to help reefs recover from stress-induced "bleaching."Bleaching occurs when stressed corals expel their symbionts en masse, frequently leaving corals colorless, as the name implies. Bleaching events are increasingly common due to climate change. While some corals never recover from bleaching, others do, which raises the question of how bleached corals repopulate their symbiont communities. Grupstra and Correa are conducting research to find out whether contact with coral predator feces can improve bleaching recovery rates and long-term coral health.
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Biology
| 2,021 |
March 23, 2021
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https://www.sciencedaily.com/releases/2021/03/210323131305.htm
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How human cells coordinate the start of DNA replication
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Cold Spring Harbor Laboratory (CSHL) President and CEO Bruce Stillman has been dissecting DNA replication, a critical step in cell division, since the 1980s. His lab studies how Origin Recognition Complexes -- ORCs -- coordinate DNA duplication. They discovered how our cells assemble and disassemble ORCs during the cell division cycle. One ORC protein is sequestered into small liquid droplets, keeping it apart until the right time to recruit other proteins and initiate DNA replication.
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The ORC recognizes where to initiate replication at numerous locations along the long, linear stretches of DNA in our cells' chromosomes. Fully assembled ORCs recruit other proteins to make precise copies of the chromosomes. This mechanism is necessary to inherit DNA accurately without errors that can lead to disorders such as cancer.Scientists have studied the structure of ORCs in several species. Stillman explains:"We've previously studied this in baker's yeast, but it turns out that human cells have a different way of doing things."Unlike single-celled yeast, humans have a variety of cells that divide at different times. To choreograph this, the researchers found that one human ORC protein, ORC1, has certain regions that yeast ORC1 lacks. When ORC binds to DNA, ORC1 recruits CDC6, a protein that assembles other DNA replication proteins. Some of the human-specific regions of ORC1 and CDC6 bind other proteins that regulate DNA replication. Manzar Hossain, a research investigator in Stillman's lab, says:"We found that ORC1 and CDC6 interact in a very tangential manner. We found a very short time period which allows them to interact."DNA-bound ORC1 is sequestered into liquid droplets that briefly change shape, then brings in CDC6. Kuhulika Bhalla, a postdoc in Stillman's lab, explains:"So if you can imagine a lava lamp, like you've got liquid, but you've got other colored liquid within it. And they still managed to stay separated."Throughout most of the cell division cycle, ORC1 and CDC6 amounts oscillate in the cell. Stillman explains that "both high and low amounts of ORC1 lead to severe consequences for cell viability. So, you have to have just the right amount" of each protein throughout the cell cycle. Stillman and his colleagues have shown that CDC6 recruits other regulatory proteins that control the activity and levels of ORC1 in both space and time. They published their findings in
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Biology
| 2,021 |
March 23, 2021
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https://www.sciencedaily.com/releases/2021/03/210323131233.htm
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Cephalopods: Older than was thought?
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The possibly oldest cephalopods in the earth's history stem from the Avalon Peninsula in Newfoundland (Canada). They were discovered by earth scientists from Heidelberg University. The 522 million-year-old fossils could turn out to be the first known form of these highly evolved invertebrate organisms, whose living descendants today include species such as the cuttlefish, octopus and nautilus. In that case, the find would indicate that the cephalopods evolved about 30 million years earlier than has been assumed.
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"If they should actually be cephalopods, we would have to backdate the origin of cephalopods into the early Cambrian period," says Dr Anne Hildenbrand from the Institute of Earth Sciences. Together with Dr Gregor Austermann, she headed the research projects carried out in cooperation with the Bavarian Natural History Collections. "That would mean that cephalopods emerged at the very beginning of the evolution of multicellular organisms during the Cambrian explosion."The chalky shells of the fossils found on the eastern Avalon Peninsula are shaped like a longish cone and subdivided into individual chambers. These are connected by a tube called the siphuncle. The cephalopods were thus the first organisms able to move actively up and down in the water and thus settle in the open ocean as their habitat. The fossils are distant relatives of the spiral-shaped nautilus, but clearly differ in shape from early finds and the still existing representatives of that class."This find is extraordinary," says Dr Austermann. "In scientific circles it was long suspected that the evolution of these highly developed organisms had begun much earlier than hitherto assumed. But there was a lack of fossil evidence to back up this theory." According to the Heidelberg scientists, the fossils from the Avalon Peninsula might supply this evidence, as on the one hand, they resemble other known early cephalopods but, on the other, differ so much from them that they might conceivably form a link leading to the early Cambrian.The former and little explored micro-continent of Avalonia, which -- besides the east coast of Newfoundland -- comprises parts of Europe, is particularly suited to paleontological research, since many different creatures from the Cambrian period are still preserved in its rocks. The researchers hope that other, better preserved finds will confirm the classification of their discoveries as early cephalopods.The research results about the 522 million-year-old fossils were published in the Nature journal
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Biology
| 2,021 |
March 23, 2021
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https://www.sciencedaily.com/releases/2021/03/210323131227.htm
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Researchers show where and how plants detect the nutrient potassium
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Potassium is an essential nutrient for all living things. Plants need it in large quantities, especially for growth and in order to withstand stress better. For this reason, they absorb large quantities of potassium from the soil. In agriculture, this leads to a lack of available potassium in the soil -- which is why the mineral is an important component in fertilizers. A team of German and Chinese researchers has now shown, for the first time, where and how plants detect potassium deficiency in their roots, and which signalling pathways coordinate the adaptation of root growth and potassium absorption to to uphold the plants potassium supply.
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The background: The absorption and transportation of potassium at the level of individual cells have been relatively well characterized, and many of the molecular structures and mechanisms which play a role in these processes are known. Also, researchers demonstrated decades ago that plants adapt very specifically to potassium deficiency. One puzzle that still remains, however, is how plants detect the availability of potassium in the soil and which mechanisms are behind the adaptational reactions in the plant's organism. The new study sheds light on these questions. The results have been published in the journal The researchers examined thale cress plants (Arabidopsis thaliana) which were transformed with the newly developed potassium reporter protein GEPII. This reporter protein enables the microscopic detection of the concentration and distribution of potassium ions in cells and tissues. Even when there was no potassium deficiency, the research team made a very surprising discovery: the concentration of this nutrient in the cytoplasm of the cells increased with each cell layer within the root, from the outside to the inside."These observations were really surprising," says Prof. Jörg Kudla from the Institute of Plant Biology and Biotechnology at the University of Münster (Germany). "They contradict the textbooks, which say that the nutrients are passed on evenly, from the outside to the inside, towards the root's vascular tissue -- not only from cell to cell but also through the intercellular spaces."The team of researchers subsequently examined how roots react to potassium deficiency. In doing so, they demonstrated for the first time that if plants are subjected to potassium deficiency, the concentration of potassium is reduced only within certain cells in the root tip. These "postmeristematic cells" directly above the viable stem cells in the root tip react extremely rapidly to potassium deficiency; the concentration of potassium inside the cell (in the cytoplasm) decreases within seconds. It had not previously been known that a certain group of cells located centrally inside the root tip reacts to a potassium deficiency in its surroundings. The researchers named this group of cells "potassium-sensitive niche.""These observations, too, were very surprising," says Kudla. "If plants are deprived of potassium, only the cells in the potassium-sensitive niche show a reaction; the concentration of potassium in the other root cells remains unchanged. Previously it was assumed that naturally the cells in the outermost cell layer, the epidermis, would react first to a reduction in the concentration of potassium in the soil."Simultaneously with the decrease in the potassium concentration in the potassium-sensitive niche, calcium signals occur in these cells and spread out in the root. As a messenger substance, calcium controls many processes in living organisms -- just as it does here: the calcium signals start off a complex molecular signalling cascade. This chain of signals, which the researchers were the first to define in detail, ultimately causes not only an increased formation of potassium transport proteins, but also brings about changes in tissue differentiation in the root. This facilitates a more efficient absorption of potassium ions and maintains its distribution in the plant. "For the first time," says Kudla, "using imaging methods, we have visualized the path of potassium in a living organism."The results provide fundamental insights into where plants detect the availability of the essential nutrient potassium and how they adapt to it. Understanding these processes could in future help to breed better plants for agricultural purposes and deploy fertilizers in a more tailor-made way.To visualize the distribution of potassium in the plant's roots, the researchers used special microscopic methods (for example, Förster resonance energy transfer, FRET), in combination with sensor proteins for potassium, calcium and hydrogen peroxide. In order to examine the molecular mechanisms, the researchers produced and compared transgenic Arabidopsis plants which, due to different genetic mutations, showed symptoms of potassium deficiency. They used a variety of genetic, molecular-biological and biochemical methods to identify and characterize the proteins and mechanisms involved in the transmission of the potassium and calcium signals.
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Biology
| 2,021 |
March 23, 2021
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https://www.sciencedaily.com/releases/2021/03/210323130808.htm
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Highlands of diversity: Another new chameleon from the Bale region, Ethiopia
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The Bale Mountains in south-central Ethiopia are considered to be one of the most unique centers of endemism, with an extraordinary number of plants and animals that can only be found there. Numerous species are already known from this Afromontane high-elevation plateau, making it a biodiversity hotspot, but ongoing research continues to reveal the presence of so far unknown and undescribed organisms.
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Zoologists Thore Koppetsch and Benjamin Wipfler of the Research Museum Alexander Koenig in Bonn, Germany, and Petr Ne?as from the Czech Republic, describe one such species: a new small-sized chameleon living on the edge of the forest. Their findings were published in the open-access, peer-reviewed life science journal There were already two species of the chameleon genus Trioceros known to be restricted to the Bale region when Thore Koppetsch and his colleagues discovered another unique representative of this group from the northern slopes of the Bale Mountains. Interestingly, this new chameleon is considered to be part of a species complex of the wide-spread Ethiopian Chameleon Trioceros affinis. Previous studies have indicated divergence between its different populations across the Ethiopian Highlands -- with some of them separated by the northern extension of the Great Rift Valley, which also shaped the evolution of early humans.The new chameleon, Trioceros wolfgangboehmei, has a special name. It honours the scientific work of Wolfgang Böhme, senior herpetologist at the Zoological Research Museum Alexander Koenig in Bonn, and his passion for chameleons and other reptiles.Apart from its biogeographical patterns, the new species also has a characteristic appearance, displaying enlarged spiny scales on its back and tail that form a prominent crest. It usually lives on small trees and bushes at an altitude of above 2,500 m above sea level."Given the variation in colour patterns and morphology between different populations of these chameleons in Ethiopia, it is likely that these groups still bear a higher hidden diversity than expected, which might be revealed by further ongoing investigations" Thore Koppetsch notes. Furthermore, the research team urges for sustainable preservation and conservation of its habitat to mitigate the impact of human activity.
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Biology
| 2,021 |
March 23, 2021
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https://www.sciencedaily.com/releases/2021/03/210323103823.htm
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Short-lived plant species are more climate-sensitive
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Plant species with short generation times are more sensitive to climate change than those with long generation times. This is one of the findings of a synthesis study by researchers from the German Centre for Integrative Biodiversity Research (iDiv), the Martin Luther University Halle-Wittenberg (MLU) and the Helmholtz-Centre for Environmental Research (UFZ). The international team comprehensively compiled worldwide available data, mostly from Europe and North America, to address the question of how plant populations react to climate change. The study, published in
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Climate change is considered to be one of the greatest threats to plant species diversity. To set the right priorities in nature conservation policy, it is crucial to know which regions of the world and which types of species are particularly threatened by climate change.As part of the iDiv synthesis centre sDiv, which brings together international experts in workshops, a working group compiled all long-term studies on plants that quantify population growth rate. They assessed how the climate factors during those years of study, in particular precipitation and temperature, influenced population growth rate. Afterwards, they tested how features of the plant species, such as the length of a generation, influence how responsive the plant population growth rates were to climate variation in the past."We were able to show that generation duration is a useful indicator value for a species' susceptibility to climate change," said first author Dr Aldo Compagnoni, a postdoctoral researcher at iDiv and MLU. For example, the scientists found that especially plants with short lifespans, such as those that only live a few years on average, suffered from climate extremes much worse than long-lived species. The analyses also showed that the main limiting factor of climate change is not the temperature increase itself. On average, precipitation had a three times greater impact on plant populations than temperature."This work helps us identify which species might be climate-vulnerable, even if we have limited information about those species," says last author Prof Tiffany Knight from iDiv, MLU and UFZ. "For example, while we have long-term population data for a small subset of plant species on Earth, we can estimate the approximate generation duration for most plant species. This is an important first step towards determining species' vulnerability to climate change at a global scale."However, there are important data gaps that limit the ability to make general predictions on a global scale. The researchers found appropriate long-term datasets only for 62 of the 350,000 plant species on Earth, and the vast majority of these were species occurring in temperate zones of the USA and Western Europe. Apart from a few tree and shrub species, the data set included only grasses and herbs. To be able to make reliable predictions about the consequences of climate change for all regions of the world and all known species, new population ecology research is needed on woody plant species and on plants in the tropics, the researchers conclude.
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Biology
| 2,021 |
March 23, 2021
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https://www.sciencedaily.com/releases/2021/03/210322112929.htm
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How cellular 'fingertips' may help cells 'speak' to each other
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What if you found out that you could heal using only a finger? It sounds like science fiction, reminiscent of the 1982 movie E.T. Well, it turns out that your body's own cells can do something similarly unexpected. Researchers at Nara Institute of Science and Technology (NAIST) report in a new study seen in
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NAIST project leader Shiro Suetsugu has devoted his career to studying how cells shape themselves, initiate and accept communication among one other. An under-appreciated means of doing so is through filopodia, small finger-like cellular projections that are more commonly known to help certain cells crawl in the body."Filopodia are well-recognized as cellular locomotion machinery. Less understood is how filopodia help cells communicate, and the molecular details of how this is done," says Suetsugu.A focus of this line of research should be the proteins known by the acronym I-BAR. I-BAR proteins are well-known to help bend the plasma membrane, the "skin" of many cells, for filopodia formation and thus facilitate movement."We identified an I-BAR protein that severs filopodia," says Suetsugu. An important element of this scission may be mechanical force, a stimulus that your body commonly applies to cells."Laser experiments showed that the force required for scission is approximately 8-20 kilopascals. These forces are similar to the 4-13 kilopascals, experienced by cells in blood capillaries," Suetsugu says.Severed filopodia go on to form structures called extracellular vesicles, a popular research topic in biology. Extracellular vesicles were used to basically be considered the trash bags of cells, used for disposing cellular waste. However, the vesicles are now considered to be communication packets rather than waste bags. "The pertinence of these vesicles to cancer metastasis has piqued researchers' and clinicians' interest," notes Suetsugu.What does this have to do with cell-cell communication? A simulated cell-scale wound healed faster when it was treated with filopodia-derived extracellular vesicles than if untreated. In other words, an I-BAR protein first induced filopodia scission and vesicle production. These vesicles then sent cellular signals that promoted cell migration toward one another, in a way that may promote wound closure.By understanding how cells fully use their molecular machinery to send instructions to other cells, Suetsugu is optimistic that medical practitioners will develop new means to safely treat cancer and other diseases."Certain BAR proteins are pertinent to cancer cell biology. BAR proteins are also pertinent to cell locomotion. By learning more about how these proteins aid cell-cell communication, we may find better ways to stop cancer cells from spreading," he says.
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Biology
| 2,021 |
March 23, 2021
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https://www.sciencedaily.com/releases/2021/03/210323103854.htm
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Penguin hemoglobin evolved to meet oxygen demands of diving
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Call it the evolutionary march of the penguins.
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More than 50 million years ago, the lovable tuxedoed birds began leaving their avian relatives at the shoreline by waddling to the water's edge and taking a dive in the pursuit of seafood.Webbed feet, flipper-like wings and unique feathers all helped penguins adapt to their underwater excursions. But new research from the University of Nebraska-Lincoln has shown that the evolution of diving is also in their blood, which optimized its capture and release of oxygen to ensure that penguins wouldn't waste their breath while holding it.Relative to land-dwelling birds, penguin blood is known to contain more hemoglobin: the protein that picks up oxygen from the lungs and transports it through the bloodstream before dropping it off at various tissues. That abundance could partly explain the underwater proficiency of, say, the emperor penguin, which dives deeper than any bird and has been documented holding its breath for more than 30 minutes while preying on krill, fish and squid.Still, the particulars of their hemoglobin -- and how much it actually evolved to help penguins become fish-gobbling torpedoes that spend up to half of their lives underwater -- remained open questions. So Nebraska biologists Jay Storz and Anthony Signore, who often study the hemoglobin of birds that survive miles above sea level, decided to investigate the birds most adept at diving beneath it."There just wasn't a lot of comparative work on blood-oxygen transport as it relates to diving physiology in penguins and their non-diving relatives," said Signore, a postdoctoral researcher in Storz's lab.Answering those questions meant sketching in the genetic blueprints of two ancient hemoglobins. One belonged to the common ancestor of all penguin species, which began branching from that ancestor about 20 million years ago. The other, dating back roughly 60 million years, resided in the common ancestor of penguins and their closest non-diving relatives -- albatrosses, shearwaters and other flying seabirds. The thinking was simple: Because one hemoglobin originated before the emergence of diving in the lineage, and the other after, any major differences between the two would implicate them as important to the evolution of diving in penguins.Actually comparing the two was less simple. To start, the researchers literally resurrected both proteins by relying on models that factored in the gene sequences of modern hemoglobins to estimate the sequences of their two ancient counterparts. Signore spliced those resulting sequences into E. coli bacteria, which churned out the two ancient proteins. The researchers then ran experiments to evaluate the performance of each.They found that the hemoglobin from the common ancestor of penguins captured oxygen more readily than did the version present in the blood of the older, non-diving ancestor. That stronger affinity for oxygen would mean less chance of leaving behind traces in the lungs, an especially vital issue among semi-aquatic birds needing to make the most of a single breath while hunting or traveling underwater.Unfortunately, the very strength of that affinity can present difficulties when hemoglobin arrives at tissues starved for the oxygen it's carrying."Having a greater hemoglobin-oxygen affinity sort of acts like a stronger magnet to pull more oxygen from the lungs," Signore said. "It's great in that context. But then you're at a loss when it's time to let go."Any breath-holding benefits gained by picking up extra oxygen, in other words, can be undone if the hemoglobin struggles to relax its iron-clad grip and release its prized cargo. The probability that it will is dictated in part by acidity and carbon dioxide in the blood. Higher levels of either make hemoglobins more likely to loosen up.As Storz and Signore expected, the hemoglobin of the recent penguin ancestor was more sensitive to its surrounding pH, with its biochemical grip on oxygen loosening more in response to elevated acidity. And that, Signore said, made the hemoglobin more biochemically attuned to the exertion and oxygen needs of the tissues it served."It really is a beautiful system, because tissues that are working hard are becoming acidic," he said. "They need more oxygen, and hemoglobin's oxygen affinity is able to shift in response to that acidity to provide more oxygen."If pH drops by, say, 0.2 units, the oxygen affinity of penguin hemoglobin is going to decrease by more than would the hemoglobin of their non-diving relatives."Together, the findings indicate that as penguins took to the seas, their hemoglobin evolved to maximize both the pick-up and drop-off of available oxygen -- especially when it was last inhaled five, or 10, or even 20 minutes earlier. They also illustrate the value of resurrecting proteins that last existed 20, or 40, or even 60 million years ago."These results demonstrate how the experimental analysis of ancestral proteins can reveal the mechanisms of biochemical adaptation," Storz said, "and also shed light on how organismal physiology evolved in response to new environmental challenges."The researchers received support from the National Institutes of Health and the National Science Foundation.
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Biology
| 2,021 |
March 23, 2021
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https://www.sciencedaily.com/releases/2021/03/210323084732.htm
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New evidence in search for the mysterious Denisovans
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An international group of researchers led by the University of Adelaide has conducted a comprehensive genetic analysis and found no evidence of interbreeding between modern humans and the ancient humans known from fossil records in Island Southeast Asia. They did find further DNA evidence of our mysterious ancient cousins, the Denisovans, which could mean there are major discoveries to come in the region.
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In the study published in In particular, they focused on detecting signatures that suggest interbreeding from deeply divergent species known from the fossil record of the area.The region contains one of the richest fossil records (from at least 1.6 million years) documenting human evolution in the world. Currently there are three distinct ancient humans recognised from the fossil record in the area: Homo erectus, Homo floresiensis (known as Flores Island hobbits) and Homo luzonensis.These species are known to have survived until approximately 50,000-60,000 years ago in the cases of Homo floresiensis and Homo luzonensis, and approximately 108,000 years for Homo erectus, which means they may have overlapped with the arrival of modern human populations.The results of the study showed no evidence of interbreeding. Nevertheless, the team were able to confirm previous results showing high levels of Denisovan ancestry in the region.Lead author and ARC Research Associate from the University of Adelaide Dr João Teixeira, said: "In contrast to our other cousins the Neanderthals, which have an extensive fossil record in Europe, the Denisovans are known almost solely from the DNA record. The only physical evidence of Denisovan existence has been a finger bone and some other fragments found in a cave in Siberia and, more recently, a piece of jaw found in the Tibetan Plateau.""We know from our own genetic records that the Denisovans mixed with modern humans who came out of Africa 50,000-60,000 years ago both in Asia, and as the modern humans moved through Island Southeast Asia on their way to Australia."The levels of Denisovan DNA in contemporary populations indicates that significant interbreeding happened in Island Southeast Asia."The mystery then remains, why haven't we found their fossils alongside the other ancient humans in the region? Do we need to re-examine the existing fossil record to consider other possibilities?"Co-author Chris Stringer of the Natural History Museum in London added:"While the known fossils of Homo erectus, Homo floresiensis and Homo luzonensis might seem to be in the right place and time to represent the mysterious 'southern Denisovans', their ancestors were likely to have been in Island Southeast Asia at least 700,000 years ago. Meaning their lineages are too ancient to represent the Denisovans who, from their DNA, were more closely related to the Neanderthals and modern humans."Co-author Prof Kris Helgen, Chief Scientist and Director of the Australian Museum Research Institute, said: "These analyses provide an important window into human evolution in a fascinating region, and demonstrate the need for more archaeological research in the region between mainland Asia and Australia."Helgen added: "This research also illuminates a pattern of 'megafaunal' survival which coincides with known areas of pre-modern human occupation in this part of the world. Large animals that survive today in the region include the Komodo Dragon, the Babirusa (a pig with remarkable upturned tusks), and the Tamaraw and Anoas (small wild buffalos)."This hints that long-term exposure to hunting pressure by ancient humans might have facilitated the survival of the megafaunal species in subsequent contacts with modern humans. Areas without documented pre-modern human occurrence, like Australia and New Guinea, saw complete extinction of land animals larger than humans over the past 50,000 years."Dr Teixeira said: "The research corroborates previous studies that the Denisovans were in Island Southeast Asia, and that modern humans did not interbreed with more divergent human groups in the region. This opens two equally exciting possibilities: either a major discovery is on the way, or we need to re-evaluate the current fossil record of Island Southeast Asia.""Whichever way you choose to look at it, exciting times lie ahead in palaeoanthropology."
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Biology
| 2,021 |
March 22, 2021
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https://www.sciencedaily.com/releases/2021/03/210322175039.htm
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Fruit fly egg takes an active hand in its own growth, highlighting parallels to mammals
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A cast of so-called 'nurse cells' surrounds and supports the growing fruit fly egg during development, supplying the egg -- or 'oocyte' -- with all the nutrients and molecules it needs to thrive. Long viewed as passive in this process, the
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"Here we show an example of bidirectional communication -- a dialogue -- between different cells. The egg is taking an active hand in controlling its own feeding by these supporting cells," says Stanislav Shvartsman, head of the developmental dynamics group within the Flatiron Institute's Center for Computational Biology and professor of molecular biology at Princeton. The discovery of bidirectional communication in fruit flies has implications for understanding development in mammals, in which the egg is also nursed by surrounding cells.The research was led by Shvartsman and Elizabeth Gavis, also professor of molecular biology; Caroline Doherty was lead author, and Rocky Diegmiller and Manisha Kapasiawala contributed to the study.In early development, four cell divisions give rise to the 16 connected cells that make up the Researchers honed in on a protein called Dap (short for 'Da capo', meaning 'from the top'), which is known to influence cell cycle progression. Nurse cells supply the oocyte with RNA molecules needed to make the Dap protein. Doherty noticed that oocyte-manufactured Dap protein appeared in the nurse cells, at a rate suggesting that it diffused from the oocyte. After fusing a tiny Dap-recognizing antibody (called a nanobody) to a protein that could trap Dap within the egg, Doherty saw a decrease of the Dap level in the nurse cells. Together, these experiments showed that once the egg makes Dap, it diffuses to the very nurse cells that donated Dap RNA, providing the first evidence for two-way oocyte-nurse cell communication in fruit flies. "It was so exciting to see the oocyte is communicating with the nurse cells -- this is something scientists hadn't considered," says Gavis. Further, the egg communicates via Dap, which controls the nurse cell cycles, which in turn influence the egg's growth. So, in a feedback loop, "the egg is controlling the growth of the cells that load it with nutrients and information" says Doherty.To better understand the logic of this bidirectional communication, researchers modeled the system as a network of coupled oscillators: models based on the biochemical clocks that drive cell cycles. The model underscored the role of a diffusible cell cycle inhibitor (like Dap) in creating a hierarchy of cell sizes similar to what is observed in As a next step, Doherty plans to investigate signaling between the oocyte-nurse cells cyst and the sheet of follicle cells that surrounds it. "These two tissue types need to grow together, and later, the follicle cells that stay over the nurse cells stretch out. Is this positioning necessary to properly stretch the follicle cells?" Doherty asks. "We might move from a dialogue to a conversation between these three cell types," adds Shvartsman.The discovery of bidirectional communication in fruit fly development points to the notion of universal mechanisms at play in biology, as back-and-forth communication between the oocyte and supporting cells is also seen in mammals. "This study opens up the possibility to discover many more instances of this kind of cellular crosstalk in development," says Yukiko Yamashita, professor of biology at the Massachusetts Institute of Technology. Although previous work on mammals focused on the egg's control of the metabolism of surrounding cells, this study may spur researchers to investigate the egg's impact on cell cycle regulation in mammals, says Francesca Duncan, co-director of the Center for Reproductive Science at the Feinberg School of Medicine at Northwestern University. "This work solidifies the parallels between fruit flies and mammals," adds Gavis.
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Biology
| 2,021 |
March 22, 2021
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https://www.sciencedaily.com/releases/2021/03/210322120108.htm
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Heritable traits that appear in teen years raise risk for adult cannabis use
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While some youth experiment with marijuana but don't go on to long-term use, others develop a problematic pot habit that continues into adulthood. A major new analysis shows that at least a small portion of the risk for developing into an adult marijuana user may be related to inherited behaviors and traits that appear during adolescence.
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The journal "Our analysis suggests that some early adolescent behaviors and traits -- like depression, neuroticism and acting out -- can be indicative for cannabis use later in life," says Rohan Palmer, senior author of the paper and assistant professor in Emory's Department of Psychology, where he heads the Behavioral Genetics of Addiction Laboratory."Decades of research has shown that behaviors can have a genetic component," adds Leslie Brick, lead author and assistant professor in the Department of Psychiatry and Human Behavior in Brown's Alpert Medical School. "And while there is not one genetically-influenced trait that determines whether you're going to be a long-term cannabis user, our paper indicates that there are polygenic effects across multiple inherited behaviors and traits that show a propensity for increased risk."Brick, a long-time collaborator with Rohan, also holds an adjunct faculty appointment in Emory's Department of Psychology.The Transmissible Liability Index is a well-known measure for a constellation of heritable traits that may appear during the developmental years that are associated with the risk of a substance use disorder. For the current paper, the researchers wanted to tease out which of these heritable characteristics might be associated with repeated marijuana use later in life."Cannabis use has been less studied than tobacco and alcohol," Palmer says. "For one thing, it's harder to get people to answer detailed questionnaires honestly about cannabis, since it's an illegal substance. And it's also much more difficult to standardize the amount of cannabis consumed, as compared to cigarettes and liquor."Cannabis use, however, is widespread among adolescents and young adults. In 2018, more than 35 percent of high school seniors surveyed reported having used marijuana during the past year and more than 20 percent reported doing so during the past month, according to the National Institute on Drug Abuse (NIDA).As cultural norms have shifted, including the legalization of marijuana for adult recreational use in many states, teens' perceptions of the risks of marijuana use have declined.Those risks, however, are real."Adolescence is a major period of brain development," Brick says. "In fact, our brains don't stop developing until we are around 25 years old. Research indicates that cannabis has some major impacts on our biology, although its full effects are still not well understood."The researchers drew data from the National Longitudinal Study of Adolescent Health, or Add Health, which includes a nationally representative sample of 20,000 adolescents in grades 7 to 12 in the United States who have been followed into adulthood. Comprehensive data from early adolescence to adulthood was collected on health and health-related behavior, including substance use, personality and genetics.For the current paper, the researchers identified a large homogenous subgroup of individuals from the Add Health study, about 5,000 individuals of European ancestry, for their final analytic sample. They then leveraged existing genome-wide association studies to examine whether certain heritable behavioral traits noted during adolescence were associated with the Transmissible Liability Index, and whether any of these traits were also associated with risk for later cannabis use.The results showed that a small portion of the risk for repeated cannabis use into adulthood can be attributed to the genetic effects of neuroticism, risk tolerance and depression that can appear during adolescence."While this work marks an important step in identifying genetic factors that can increase the risk for cannabis use, a substantial portion of factors that raise the risk remain unexplained," Palmer says. "We've shown how you can use existing data to assess the utility of a polygenic risk score. More studies are needed to continue to identify unique genetic and other environmental sources for the risk of long-term, problematic use of cannabis.""Better understanding of what behaviors and traits may give someone a pre-disposition for long-term cannabis use gives us a better shot of identifying those most at risk so we can home in on effective interventions," Brick says.A major limitation of the current study, the researchers add, is that it focused on individuals of European ancestry, because no sample size large enough for the genome-wide analysis was available for other ancestral groups.The work was supported by an Avenir grant from the National Institute on Drug Abuse.
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Biology
| 2,021 |
March 22, 2021
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https://www.sciencedaily.com/releases/2021/03/210322112621.htm
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Upgrade for CRISPR/Cas: Researchers knock out multiple genes in plants at once
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Using an improved version of the gene editing tool CRISPR/Cas9, researchers knocked out up to twelve genes in plants in a single blow. Until now, this had only been possible for single or small groups of genes. The approach was developed by researchers at Martin Luther University Halle-Wittenberg (MLU) and the Leibniz Institute of Plant Biochemistry (IPB). The method makes it easier to investigate the interaction of various genes. The study appeared in
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The inheritance of traits in plants is rarely as simple and straightforward as Gregor Mendel described. The monk, whose experiments in the 19th century on trait inheritance in peas laid the foundation of genetics, in fact got lucky. "In the traits that Mendel studied, the rule that only one gene determines a specific trait, for example the colour of the peas, happened to apply," says plant geneticist Dr Johannes Stuttmann from the Institute of Biology at MLU. According to the researcher, things are often much more complicated. Frequently there are different genes that, through their interaction with one another, result in certain traits or they are partly redundant, in other words they result in the same trait. In this case, when only one of these genes is switched off, the effects are not visible in the plants.The scientists at MLU and IPB have now developed a way to study this complex phenomenon in a more targeted way by improving CRISPR/Cas9. These gene editing tools can be used to cut the DNA of organisms at specific sites. The team built on the work of biologist Dr Sylvestre Marillonnet who developed an optimised building block for the CRISPR/Cas9 system at the IPB. "This building block helps to produce significantly more Cas9 enzyme in the plants, which acts as a scissor for the genetic material," explains Stuttmann. The researchers added up to 24 different guide RNAs which guide the scissor enzyme to the desired locations in the genetic material. Experiments on thale cress (Arabidopsis thaliana) and the wild tobacco plant Nicotiana benthamiana proved that the approach works. Up to eight genes could be switched off simultaneously in the tobacco plants while, in the thale cress, up to twelve genes could be switched off in some cases. According to Stuttmann, this is a major progress: "As far as I know, our group has been the first to successfully address so many target genes at once. This may make it possible to overcome the redundancy of genes," says the biologist.Until now, creating multiple mutations was a much more complex process. The plants had to be bred in stages with a single mutation each and then crossed with one another. "This is not only time-consuming, it's also not possible in every case," says Stuttmann. The new approach developed at the MLU and the IPB overcomes these disadvantages and could prove to be a more efficient method of research. In future, it will also be possible to test random combinations of several genes in order to identify redundancies. Only in the case of conspicuous changes in the plant's traits would it then be necessary to specifically analyse the genetic material of the new plants.The study was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation).
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Biology
| 2,021 |
March 22, 2021
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https://www.sciencedaily.com/releases/2021/03/210322085517.htm
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Bacteria may aid anti-cancer immune response
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Cancer immunotherapy may get a boost from an unexpected direction: bacteria residing within tumor cells. In a new study published in
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Immunotherapy treatments of the past decade or so have dramatically improved recovery rates from certain cancers, particularly malignant melanoma; but in melanoma, they still work in only about 40% of the cases. Prof. Yardena Samuels of Weizmann's Molecular Cell Biology Department studies molecular "signposts" -- protein fragments, or peptides, on the cell surface -- that mark cancer cells as foreign and may therefore serve as potential added targets for immunotherapy. In the new study, she and colleagues extended their search for new cancer signposts to those bacteria known to colonize tumors.Using methods developed by departmental colleague Dr. Ravid Straussman, who was one of the first to reveal the nature of the bacterial "guests" in cancer cells, Samuels and her team, led by Dr. Shelly Kalaora and Adi Nagler (joint co-first authors), analyzed tissue samples from 17 metastatic melanoma tumors derived from nine patients. They obtained bacterial genomic profiles of these tumors and then applied an approach known as HLA-peptidomics to identify tumor peptides that can be recognized by the immune system.The research was conducted in collaboration with Dr. Jennifer A. Wargo of the University of Texas MD Anderson Cancer Center, Houston, Texas; Prof Scott N. Peterson of Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California; Prof Eytan Ruppin of the National Cancer Institute, USA; Prof Arie Admon of the Technion -- Israel Institute of Technology and other scientists.The HLA peptidomics analysis revealed nearly 300 peptides from 41 different bacteria on the surface of the melanoma cells. The crucial new finding was that the peptides were displayed on the cancer cell surfaces by HLA protein complexes -- complexes that are present on the membranes of all cells in our body and play a role in regulating the immune response. One of the HLA's jobs is to sound an alarm about anything that's foreign by "presenting" foreign peptides to the immune system so that immune T cells can "see" them. "Using HLA peptidomics, we were able to reveal the HLA-presented peptides of the tumor in an unbiased manner," Kalaora says. "This method has already enabled us in the past to identify tumor antigens that have shown promising results in clinical trials."It's unclear why cancer cells should perform a seemingly suicidal act of this sort: presenting bacterial peptides to the immune system, which can respond by destroying these cells. But whatever the reason, the fact that malignant cells do display these peptides in such a manner reveals an entirely new type of interaction between the immune system and the tumor.This revelation supplies a potential explanation for how the gut microbiome affects immunotherapy. Some of the bacteria the team identified were known gut microbes. The presentation of the bacterial peptides on the surface of tumor cells is likely to play a role in the immune response, and future studies may establish which bacterial peptides enhance that immune response, enabling physicians to predict the success of immunotherapy and to tailor a personalized treatment accordingly.Moreover, the fact that bacterial peptides on tumor cells are visible to the immune system can be exploited for enhancing immunotherapy. "Many of these peptides were shared by different metastases from the same patient or by tumors from different patients, which suggests that they have a therapeutic potential and a potent ability to produce immune activation," Nagler says.In a series of continuing experiments, Samuels and colleagues incubated T cells from melanoma patients in a laboratory dish together with bacterial peptides derived from tumor cells of the same patient. The result: T cells were activated specifically toward the bacterial peptides."Our findings suggest that bacterial peptides presented on tumor cells can serve as potential targets for immunotherapy," Samuels said. "They may be exploited to help immune T cells recognize the tumor with greater precision, so that these cells can mount a better attack against the cancer. This approach can in the future be used in combination with existing immunotherapy drugs."
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Biology
| 2,021 |
March 22, 2021
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https://www.sciencedaily.com/releases/2021/03/210322085520.htm
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Cells burn more calories after just one bout of moderate aerobic exercise, OSU study finds
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In a recent study testing the effects of exercise on overall metabolism, researchers at Oregon State University found that even a single session of moderate aerobic exercise makes a difference in the cells of otherwise sedentary people.
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Mitochondria are the part of the cell responsible for the biological process of respiration, which turns fuels such as sugars and fats into energy, so the researchers focused only on mitochondria function."What we found is that, regardless of what fuel the mitochondria were using, there were mild increases in the ability to burn off the fuels," said Matt Robinson, lead author on the study and an assistant professor in the College of Public Health and Human Sciences.OSU researchers recruited participants who do not follow a regular exercise routine and had them ride a stationary bike for an hour at a moderate intensity. They biopsied their muscles 15 minutes later to test how efficient the mitochondria were after the exercise was completed and compared those results with a resting day.Post-exercise, study participants' mitochondria burned 12-13% more fat-based fuel and 14-17% more sugar-based fuel. While the effects were not drastic, they were consistent, Robinson said."It's pretty remarkable that even after just one hour of exercise, these people were able to burn off a little more fuel," he said.Previous research in the field has long established that regular exercise creates lasting change in people's metabolism, making their bodies burn more energy even when they're not working out.Prior studies have looked at highly trained or athletic people, but Robinson's team wanted to look specifically at singular bouts of exercise in people who were generally active and disease-free but who did not have structured exercise regimes. These people were on the lower end of fitness, which is associated with low mitochondrial abundance and energy production. Participants were monitored while working out at approximately 65% of their maximal effort, where they could keep up the cycling pace for an hour or more and still comfortably carry on a conversation.Robinson said they're hoping these results help break down the mental barrier of people thinking they need to be elite athletes for exercise to make an impact on their health."From a big picture health perspective, it's very encouraging for people to realize that you can get health benefits from a single session of exercise," Robinson said. "We're trying to encourage people, 'You did one, why don't you try to do two? Let's do three.'"We know that exercise is good for you, in general. But those benefits of that single bout of exercise seem to fade away after a day or two. You get the long-term benefits when you do that exercise again and again and you make it a regular habit."In this study, Robinson's research team focused narrowly on mitochondria to find out how big a role mitochondria play in the overall function of muscle metabolism. Other studies are looking at changes in blood flow to the muscle and how the muscle metabolizes fats versus sugars.From a disease perspective, Robinson said it's clear that obesity and diabetes involve impairments in metabolism. Physiologically, when the body undergoes exercise, sugars tend to be burned off first while fats are stored, but in cases of diabetes and obesity, there is some dysregulation in metabolism that causes the body to not be able to switch between the two types of fuel.Exercise can help reset that system, he said."Since those get burned off in the mitochondria, our hope is that with exercise, we could increase the mitochondria and then improve how the body burns off fats and sugars," he said.
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Biology
| 2,021 |
March 19, 2021
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https://www.sciencedaily.com/releases/2021/03/210319125513.htm
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New antibiotic clears multi-drug resistant gonorrhea in mice in single dose
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A new antibiotic compound clears infection of multi-drug resistant gonorrhea in mice in a single oral dose, according to a new study led by researchers at Penn State and Emory University. The compound targets a molecular pathway found in bacteria but not humans and could lead to new treatments for gonorrhea and infections from other bacteria, such as tuberculosis and MRSA.
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The research team, which also includes scientists from the biopharmaceutical company Microbiotix, the Uniformed Services University, and Florida State, published their results in a paper appearing March 19 in the journal Gonorrhea infects more than 500 thousand people in the United States each year, and several strains of the bacteria that causes the disease, Neisseria gonorrhoeae, are resistant to multiple antibiotics in use today. For this reason, the Centers for Disease Control and Prevention (CDC) lists multi-drug resistant gonorrhea as one of the five most dangerous urgent threats today."Many current antibiotics target the process of translation -- when proteins are made based on information in genetic material -- within the bacteria," said Ken Keiler, professor of biochemistry and molecular biology at Penn State and an author of the paper. "Over the last decade, we have been investigating a family of compounds that instead inhibit the trans-translation pathway in bacteria, which bacteria use to fix certain kinds of errors during protein synthesis. In this paper, we provide a proof-of-concept that inhibiting the trans-translation pathway can effectively clear multi-drug resistant gonorrhea in animals."The researchers previously identified a promising trans-translation inhibitor that clears gonorrhea infection in lab cultures but is ineffective in animals because the compound breaks down. In this study, members of the research team at Microbiotix strategically altered the compound to identify which portions of its structure were necessary to inhibit the pathway and which could be changed to improve its stability."Our iterative optimization campaign evaluated over 500 versions of the compound to assess their potency, toxicity, and other pharmacological properties," said Zachary Aron, director of chemistry at Microbiotix and an author of the paper. "We determined that the central region of the compound plays a critical role in blocking the trans-translation pathway, however modifications at the periphery could be altered to modulate its pharmacological properties. By altering a functional group to sidestep the primary mechanism of metabolism, we can create versions of the compound that are much more stable in animals."Members of the research team at the Uniformed Services University then tested one of these modified compounds, MBX-4132, in mice. Their experiments utilized the gonorrhea strain WHO-X, an extremely virulent pathogen that is resistant to almost all approved antibiotics. A single oral dose of the compound completely cleared the infection in 80% of mice within six days, and the bacterial load in the remaining 20% was dramatically reduced."Developing a single dose therapy for gonorrhea is incredibly important," said Keiler. "In some cases, bacteria can develop resistance to a drug when additional doses are skipped, for example when a patient starts to feel better and stops taking antibiotics. With a single dose therapy, a patient could complete the treatment during a visit to their health provider."To better determine how the compound inhibits the trans-translation pathway, members of the research team at Emory University and Florida State University used cryo-electron microscopy (cryo-EM) to produce high-resolution images of the compound as it binds to the bacterial ribosome -- the macromolecule where proteins are synthesized."A derivative of MBX-4132 binds to a location on the ribosome that is different from all known antibiotic binding sites," said Christine Dunham, associate professor of biochemistry at Emory University and an author of the paper. "The new drug also displaces a region of a ribosomal protein that we think could be important during the normal process of trans-translation. Because trans-translation only occurs in bacteria and not in humans, we hope that the likelihood of the compound affecting protein synthesis in humans is greatly reduced, a hypothesis strongly supported by the safety and selectivity studies performed by Microbiotix."The research team plans to further optimize the compound before pursuing preclinical trials."This type of compound is actually a broad-spectrum inhibitor," said Keiler. "It is effective against most Gram-positive bacteria -- including tuberculosis and difficult-to-treat staph infections (MRSA) -- and some Gram-negative bacteria and could be a promising candidate for future treatments. In this study, we lay the groundwork for using this type of compound and demonstrate that inhibiting the trans-translation pathway in bacteria is a viable antibiotic strategy."This research was supported by the National Institutes of Health.
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Biology
| 2,021 |
March 19, 2021
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https://www.sciencedaily.com/releases/2021/03/210319125519.htm
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Medical cannabis can reduce essential tremor: Turns on overlooked cells in central nervous system
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Medical cannabis is a subject of much debate. There is still a lot we do not know about cannabis, but researchers from the Department of Neuroscience at the Faculty of Health and Medical Sciences have made a new discovery that may prove vital to future research into and treatment with medical cannabis.
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Cannabinoids are compounds found in cannabis and in the central nervous system. Using a mouse model, the researchers have demonstrated that a specific synthetic cannabinoid (cannabinoid WIN55,212-2) reduces essential tremor by activating the support cells of the spinal cord and brain, known as astrocytes. Previous research into medical cannabis has focussed on the nerve cells, the so-called neurons.'We have focussed on the disease essential tremor. It causes involuntary shaking, which can be extremely inhibitory and seriously reduce the patient's quality of life. However, the cannabinoid might also have a beneficial effect on sclerosis and spinal cord injuries, for example, which also cause involuntary shaking', says Associate Professor Jean-François Perrier from the Department of Neuroscience, who has headed the research project.'We discovered that an injection with the cannabinoid WIN55,212-2 into the spinal cord turns on the astrocytes in the spinal cord and prompts them to release the substance adenosine, which subsequently reduces nerve activity and thus the undesired shaking'.That astrocytes are part of the explanation for the effect of cannabis is a completely new approach to understanding the medical effect of cannabis, and it may help improve the treatment of patients suffering from involuntary shaking.The spinal cord is responsible for most our movements. Both voluntary and spontaneous movements are triggered when the spinal cord's motor neurons are activated. The motor neurons connect the spinal cord with the muscles, and each time a motor neuron sends impulses to the muscles, it leads to contraction and thus movement. Involuntary shaking occurs when the motor neurons send out conflicting signals at the same time. And that is why the researchers have focussed on the spinal cord.'One might imagine a new approach to medical cannabis for shaking, where you -- during the development of cannabis-based medicinal products -- target the treatment either at the spinal cord or the astrocytes -- or, at best, the astrocytes of the spinal cord', says Postdoc Eva Carlsen, who did most of the tests during her PhD and postdoc projects.'Using this approach will avoid affecting the neurons in the brain responsible for our memory and cognitive abilities, and we would be able to offer patients suffering from involuntary shaking effective treatment without exposing them to any of the most problematic side effects of medical cannabis'.The next step is to do clinical tests on patients suffering from essential tremor to determine whether the new approach has the same effect on humans.
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Biology
| 2,021 |
March 18, 2021
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https://www.sciencedaily.com/releases/2021/03/210318185328.htm
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Novel coronavirus circulated undetected months before first COVID-19 cases in Wuhan, China
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Using molecular dating tools and epidemiological simulations, researchers at University of California San Diego School of Medicine, with colleagues at the University of Arizona and Illumina, Inc., estimate that the SARS-CoV-2 virus was likely circulating undetected for at most two months before the first human cases of COVID-19 were described in Wuhan, China in late-December 2019.
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Writing in the March 18, 2021 online issue of "Our study was designed to answer the question of how long could SARS-CoV-2 have circulated in China before it was discovered," said senior author Joel O. Wertheim, PhD, associate professor in the Division of Infectious Diseases and Global Public Health at UC San Diego School of Medicine."To answer this question, we combined three important pieces of information: a detailed understanding of how SARS-CoV-2 spread in Wuhan before the lockdown, the genetic diversity of the virus in China and reports of the earliest cases of COVID-19 in China. By combining these disparate lines of evidence, we were able to put an upper limit of mid-October 2019 for when SARS-CoV-2 started circulating in Hubei province."Cases of COVID-19 were first reported in late-December 2019 in Wuhan, located in the Hubei province of central China. The virus quickly spread beyond Hubei. Chinese authorities cordoned off the region and implemented mitigation measures nationwide. By April 2020, local transmission of the virus was under control but, by then, COVID-19 was pandemic with more than 100 countries reporting cases.SARS-CoV-2 is a zoonotic coronavirus, believed to have jumped from an unknown animal host to humans. Numerous efforts have been made to identify when the virus first began spreading among humans, based on investigations of early-diagnosed cases of COVID-19. The first cluster of cases -- and the earliest sequenced SARS-CoV-2 genomes -- were associated with the Huanan Seafood Wholesale Market, but study authors say the market cluster is unlikely to have marked the beginning of the pandemic because the earliest documented COVID-19 cases had no connection to the market.Regional newspaper reports suggest COVID-19 diagnoses in Hubei date back to at least November 17, 2019, suggesting the virus was already actively circulating when Chinese authorities enacted public health measures.In the new study, researchers used molecular clock evolutionary analyses to try to home in on when the first, or index, case of SARS-CoV-2 occurred. "Molecular clock" is a term for a technique that uses the mutation rate of genes to deduce when two or more life forms diverged -- in this case, when the common ancestor of all variants of SARS-CoV-2 existed, estimated in this study to as early as mid-November 2019.Molecular dating of the most recent common ancestor is often taken to be synonymous with the index case of an emerging disease. However, said co-author Michael Worobey, PhD, professor of ecology and evolutionary biology at University of Arizona: "The index case can conceivably predate the common ancestor -- the actual first case of this outbreak may have occurred days, weeks or even many months before the estimated common ancestor. Determining the length of that 'phylogenetic fuse' was at the heart of our investigation."Based on this work, the researchers estimate that the median number of persons infected with SARS-CoV-2 in China was less than one until November 4, 2019. Thirteen days later, it was four individuals, and just nine on December 1, 2019. The first hospitalizations in Wuhan with a condition later identified as COVID-19 occurred in mid-December.Study authors used a variety of analytical tools to model how the SARS-CoV-2 virus may have behaved during the initial outbreak and early days of the pandemic when it was largely an unknown entity and the scope of the public health threat not yet fully realized.These tools included epidemic simulations based on the virus's known biology, such as its transmissibility and other factors. In just 29.7 percent of these simulations was the virus able to create self-sustaining epidemics. In the other 70.3 percent, the virus infected relatively few persons before dying out. The average failed epidemic ended just eight days after the index case."Typically, scientists use the viral genetic diversity to get the timing of when a virus started to spread," said Wertheim. "Our study added a crucial layer on top of this approach by modeling how long the virus could have circulated before giving rise to the observed genetic diversity."Our approach yielded some surprising results. We saw that over two-thirds of the epidemics we attempted to simulate went extinct. That means that if we could go back in time and repeat 2019 one hundred times, two out of three times, COVID-19 would have fizzled out on its own without igniting a pandemic. This finding supports the notion that humans are constantly being bombarded with zoonotic pathogens."Wertheim noted that even as SARS-CoV-2 was circulating in China in the fall of 2019, the researchers' model suggests it was doing so at low levels until at least December of that year."Given that, it's hard to reconcile these low levels of virus in China with claims of infections in Europe and the U.S. at the same time," Wertheim said. "I am quite skeptical of claims of COVID-19 outside China at that time."The original strain of SARS-CoV-2 became epidemic, the authors write, because it was widely dispersed, which favors persistence, and because it thrived in urban areas where transmission was easier. In simulated epidemics involving less dense rural communities, epidemics went extinct 94.5 to 99.6 percent of the time.The virus has since mutated multiple times, with a number of variants becoming more transmissible."Pandemic surveillance wasn't prepared for a virus like SARS-CoV-2," Wertheim said. "We were looking for the next SARS or MERS, something that killed people at a high rate, but in hindsight, we see how a highly transmissible virus with a modest mortality rate can also lay the world low."Co-authors include: Jonathan Pekar and Niema Moshiri, UC San Diego; and Konrad Scheffler, Illumina, Inc.Funding for this research came, in part, from the National Institutes of Health (grants AI135992, AI136056, T15LM011271), the Google Cloud COVID-19 Research Credits Program, the David and Lucile Packard Foundation, the University of Arizona and the National Science Foundation (grant 2028040).
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Biology
| 2,021 |
March 18, 2021
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https://www.sciencedaily.com/releases/2021/03/210318142516.htm
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Scientists uncover the underlying genetics that make flies champion fliers
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Flies have developed excellent flying skills thanks to a set of complicated interactions between numerous genes influencing wing shape, muscle function, and nervous system development, as well as the regulation of gene expression during development. Adam Spierer and David Rand in collaboration with colleagues at Brown University identified these interactions, which they report March 18th in the journal
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Just like their name suggests, flies are exceptional fliers who rely on flight for vital tasks, like courtship, finding food and dispersing to new areas. But despite the importance of this ability, scientists know little about the genetics underlying flight performance. In the new study, Spierer, Rand and colleagues performed a genetic analysis, called a genome-wide association study, to identify genes associated with flight. Using 197 genetically different fruit fly lines, they tested the flies' ability to pull out of a sudden drop. Then, using multiple computational approaches, they related the flies' performance to different genes and genetics variants, as well as to networks of gene-gene and protein-protein interactions.The researchers discovered that many genes and genetic variants involved in flight performance mapped to regions of the fly genome that determine wing shape, muscle and nervous system function, and regulate whether other genes are turned on or off. They also identified a gene called pickpocket 23 (ppk23) that serves as a central hub for regulating the interactions of these genes. Pickpocket family genes are involved in proprioception -- a sense of how the body moves in space -- and in detecting pheromones and other chemical signals.This "snapshot" of the genetic variants that affect fruit fly flight performance may have implications for studying flight in other insects. Additionally, the researchers have demonstrated the benefit of using multiple approaches to unravel the complex genetic interactions underlying traits like flight, which involve a number of different genes.
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Biology
| 2,021 |
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