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March 18, 2021
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https://www.sciencedaily.com/releases/2021/03/210318122509.htm
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Biofluorescent fish discovered in the Arctic
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For the first time, scientists have documented biofluorescence in an Arctic fish species. The study, led by researchers at the American Museum of Natural History who spent hours in the icy waters off of Greenland where the red-and-green-glowing snailfish was found, is published today in the American Museum Novitates.
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"Overall, we found marine fluorescence to be quite rare in the Arctic, in both invertebrate and vertebrate lineages," said John Sparks, a curator in the American Museum of Natural History's Department of Ichthyology and one of the authors of the study. "So we were surprised to find these juvenile snailfish brightly fluorescing in not just one, but two different colors, which is very unusual in a single species."In 2014, Sparks and colleague David Gruber, a research associate at the Museum and a biology professor at Baruch College, identified more than 180 new species of fishes that biofluoresce, the ability to convert blue wavelengths into green, red, or yellow light. This ability, which could be used for behaviors including communication and mating in some species, is now well documented in tropical fishes that live in regions where there is an even amount of daylight year-round. But in the Arctic, where days can be incredibly long or incredibly short, researchers were interested in seeing firsthand how prolonged periods of darkness affected fishes' ability to biofluoresce."The light regime at the poles provides for winter months of near total darkness, where biofluorescence would not be functional," Gruber said. "But given the summer months with the midnight Sun, we hypothesized that it could be present."In 2019, as part of a Constantine. S. Niarchos Expedition, Sparks and Gruber headed to the iceberg habitats off the coast of Eastern Greenland to test their theory. In addition to finding very little marine fluorescence, they observed that groups of fishes that glow brightly in tropical and temperate regions -- for example, scorpionfishes and flatfishes -- did not fluoresce in the cold waters. But there was an exception: two juvenile specimens of variegated snailfish (Liparis gibbus), the first species shown to biofluoresce in the Arctic. The species glows in both green and red, a rare example of multiple fluorescent colors emitted from a single organism. In addition, the authors report red biofluorescence from an adult kelp snailfish (L. tunicatus) collected in the Bering Strait off of Little Diomede Island, Alaska, which was collected and scanned by colleagues at NOAA Fisheries Service.In the seven years since Sparks and Gruber first reported widespread biofluorescence in fishes, it has been found in a number of new lineages, including mammals like platypuses, opossums, flying squirrels, springhares, and even marine turtles. But its exact function remains a mystery."We are now focusing our efforts on determining the function of fluorescence in various fish groups, including catsharks, where we have shown that bright green fluorescence enhances contrast in their pigmentation pattern, making it easier for individuals to see each other at depth," Sparks said.
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Biology
| 2,021 |
March 18, 2021
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https://www.sciencedaily.com/releases/2021/03/210318111430.htm
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The hidden machinery of a photosynthetic giant revealed
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Photosynthesis represents the only biological process, which converts the energy of sunlight into chemically stored energy. On molecular level, the photosynthetic key enzymes called photosystems are responsible for this conversion process. Photosystem I (PSI), one of the two photosystems, is a large membrane protein complex that can be present in different forms -- as monomers, dimers, trimers or even tetramers. New isolation technique helps revealing the structure of monomeric PSI
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Although the structure of trimeric PSI from the thermophilic cyanobacterium Thermosynechococcus elongatus was solved 20 years ago, it was not yet possible to obtain the corresponding structure of monomeric PSI. Major bottleneck was the low natural abundance of this specific PSI form. Therefore, a new extraction method was developed by the researchers at RUB, which enabled selective isolation of PSI monomers with high yield. The isolated protein complex was characterized in detail at RUB by mass-spectrometry, spectroscopy and biochemical methods, whereas the research team at Osaka University was able to solve its structure by cryo-electron microscopy. Teamwork between chlorophylls and lipids might enable uphill energy transferThe atomic structure of monomeric PSI provides novel insights into the energy transfer inside the protein complex as well as on the localization of so-called red chlorophylls -- specially arranged chlorophylls, closely interacting with each other and thus enabling the absorption of low-energy far red light, which normally cannot be used for photosynthesis. Interestingly, the structure revealed that the red chlorophylls seem to interact with lipids of the surrounding membrane. This structural arrangement might indicate that additional thermal energy is used to make far red light accessible for photosynthesis. Long-run cooperation bears further fruits
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Biology
| 2,021 |
March 18, 2021
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https://www.sciencedaily.com/releases/2021/03/210318085627.htm
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Animal model opens way to test Alzheimer's disease therapies
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Our knowledge of Alzheimer's disease has grown rapidly in the past few decades but it has proven difficult to translate fundamental discoveries about the disease into new treatments. Now researchers at the California National Primate Research Center at the University of California, Davis, have developed a model of the early stages of Alzheimer's disease in rhesus macaques. The macaque model, published March 18 in the journal
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The model was developed by Professor John Morrison's laboratory at the CNPRC, in collaboration with Professor Jeffrey Kordower of Rush University Medical Center and Paramita Chakrabarty, assistant professor at the University of Florida.Alzheimer's disease is thought to be caused by misfolding of the tau and amyloid proteins. Misfolded proteins spread through the brain, leading to inflammation and cell death. Tau protein is commonly found in neurons of the brain and central nervous system, but not elsewhere.Researchers think that decades may elapse between the silent beginnings of the disease and the first signs of cognitive decline. Understanding what happens over these years could be key to preventing or reversing symptoms of Alzheimer's disease. But it is difficult to study therapeutic strategies without a powerful animal model that resembles the human condition as closely as possible, Morrison said. Much research has focused on transgenic mice that express a human version of amyloid or tau proteins, but these studies have proven difficult to translate into new treatments.Humans and monkeys have two forms of the tau protein in their brains, but rodents only have one, said Danielle Beckman, postdoctoral researcher at the CNPRC and first author on the paper."We think the macaque is a better model, because it expresses the same versions of tau in the brain as humans do," she said.Mice also lack certain areas of neocortex such as prefrontal cortex, a region of the human brain that is highly vulnerable to Alzheimer's disease. Prefrontal cortex is present in rhesus macaques and critically important for cognitive functions in both humans and monkeys. There is a critical need for new and better animal models for Alzheimer's disease that can stand between mouse models and human clinical trials, Beckman said.Chakrabarty and colleagues created versions of the human tau gene with mutations that would cause misfolding, wrapped in a virus particle. These vectors were injected into rhesus macaques, in a brain region called the entorhinal cortex, which is highly vulnerable in Alzheimer's disease.Within three months, they could see that misfolded tau proteins had spread to other parts of the animal's brains. They found misfolding both of the introduced human mutant tau protein and of the monkey's own tau proteins."The pattern of spreading demonstrated unequivocally that tau-based pathology followed the precise connections of the entorhinal cortex and that the seeding of pathological tau could pass from one region to the next through synaptic connections," Morrison said. "This capacity to spread through brain circuits results in the damage to cortical areas responsible for higher level cognition quite distant from the entorhinal cortex," he said.The same team has previously established spreading of misfolded amyloid proteins in macaques, representing the very early stages of Alzheimer's disease, by injecting short pieces of faulty amyloid. The new tau protein model likely represents a middle stage of the disease, Beckman said."We think that this represents a more degenerative phase, but before widespread cell death occurs," she said.The researchers next plan to test if behavioral changes comparable to human Alzheimer's disease develop in the rhesus macaque model. If so, it could be used to test therapies that prevent misfolding or inflammation."We have been working to develop these models for the last four years," Morrison said. "I don't think you could do this without a large collaborative team and the extensive resources of a National Primate Research Center."Additional co-authors on the paper are: at the California National Primate Research Center, Sean Ott, Amanda Dao, Eric Zhou and Kristine Donis-Cox; William Janssen, Icahn School of Medicine, New York; Scott Muller, Rush University School of Medicine, Chicago. Morrison also has an appointment at the Department of Neurology, UC Davis School of Medicine.The work was supported by the NIH through a collaboration between the Office of Research Infrastructure Programs and National Institute of Aging, and by the Alzheimer's Association.
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Biology
| 2,021 |
March 18, 2021
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https://www.sciencedaily.com/releases/2021/03/210318084759.htm
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Advanced mouse embryos grown outside the uterus
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To observe how a tiny ball of identical cells on its way to becoming a mammalian embryo first attaches to an awaiting uterine wall and then develops into nervous system, heart, stomach and limbs: This has been a highly-sought grail in the field of embryonic development for nearly 100 years. Prof. Jacob Hanna of the Weizmann Institute of Science and his group have now accomplished this feat. The method they created for growing mouse embryos outside the womb during the initial stages after embryo implantation will give researchers an unprecedented tool for understanding the development program encoded in the genes, and it may provide detailed insight into birth and developmental defects as well as those involved in embryo implantation. The results of this research were published in
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Hanna, who is in the Institute's Molecular Genetics Department, explains that much of what is known about mammalian embryonic development today comes either from observing the process in non-mammals like frogs or fish that lay transparent eggs, or by obtaining static images from dissected mouse embryos and adding them together. The idea of growing early embryos outside the uterus has been around since before the 1930s, he adds, but experiments based on these proposals had limited success and the embryos tended to be abnormal.Hanna's team decided to renew that effort in order to advance the research in his lab, which focuses on the way the development program is enacted in embryonic stem cells. Over seven years, through trial and error, fine-tuning and double-checking, his team came up with a two-step process in which they were able to grow normally developing mouse embryos outside the uterus for six days -- around a third of their 20-day gestation -- by which time the embryos already had a well-defined body plan and visible organs. "To us, that is the most mysterious and the most interesting part of embryonic development, and we can now observe it and experiment with it in amazing detail," say Hanna.The research was led by Alejandro Aguilera-Castrejon, Dr. Bernardo Oldak, the late Dr. Rada Massarwa and Dr. Noa Novershtern in Hanna's lab and Dr. Itay Maza, a former student of Hanna's now in the Rambam Health Care Campus of the Technion -- Israel Institute of Technology.For the first step, which lasted around two days, the researchers started with several-day old mouse embryos -- right after they would have implanted in the uterus. At this stage the embryos were balls consisting of 250 identical stem cells. These were placed on a special growth medium in a laboratory dish and the team got the balls to attach to this medium as they would to the uterine wall. With this step, they succeeded in duplicating the first stage of embryonic development, in which the embryo doubles and triples in size, as it differentiates into three layers: inner, middle and outer.Beyond two days, as the embryos entered the next developmental stage -- the formation of organs from each of the layers -- they needed additional conditions. For this second step, the scientists placed the embryos in a nutrient solution in tiny beakers, setting the beakers on rollers that kept the solutions in motion and continually mixed. That mixing seems to have helped keep the embryos, which were growing without maternal blood flow to the placenta, bathed in the nutrients. In addition to carefully regulating the nutrients in the beakers, the team learned in further experiments to closely control the gases, oxygen and carbon dioxide -- not just the amounts, but the gas pressure as well.To check whether the developmental processes they were observing throughout the two steps were normal, the team conducted careful comparisons with embryos removed from pregnant mice in the relevant time period, showing that both the separation into layers and the organ formation were all but identical in the two groups. In subsequent experiments, they inserted into the embryos genes that labeled the growing organs in fluorescent colors. The success of this attempt suggested that further experiments with this system involving various genetic and other manipulations should produce reliable results. "We think you can inject genes or other elements into the cells, alter the conditions or infect the embryo with a virus, and the system we demonstrated will give you results consistent with development inside a mouse uterus," says Hanna."If you give an embryo the right conditions, its genetic code will function like a pre-set line of dominos, arranged to fall one after the other," he adds. "Our aim was to recreate those conditions, and now we can watch, in real time, as each domino hits the next one in line." Among other things, explains Hanna, the method will lower the cost and speed up the process of research in the field of developmental biology, as well as reducing the need for lab animals.In fact, the next step in Hanna's lab will be to see if they can skip the step of removing embryos from pregnant mice. He and his team intend to try to create artificial embryos made from stem cells for use in this research. Among other things, they hope to put their new method to work to answer such questions as why so many pregnancies fail to implant, why the window for implantation is so short, how stem cells gradually lose their "stemness" as differentiation progresses and what conditions in gestation may later lead to developmental disorders.Video:
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Biology
| 2,021 |
March 17, 2021
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https://www.sciencedaily.com/releases/2021/03/210317181645.htm
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Lab-created heart valves can grow with the recipient
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A groundbreaking new study led by University of Minnesota Twin Cities researchers from both the College of Science and Engineering and the Medical School shows for the first time that lab-created heart valves implanted in young lambs for a year were capable of growth within the recipient. The valves also showed reduced calcification and improved blood flow function compared to animal-derived valves currently used when tested in the same growing lamb model.
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If confirmed in humans, these new heart valves could prevent the need for repeated valve replacement surgeries in thousands of children born each year with congenital heart defects. The valves can also be stored for at least six months, which means they could provide surgeons with an "off the shelf" option for treatment.The study was published today in "This is a huge step forward in pediatric heart research," said Robert Tranquillo, the senior researcher on the study and a University of Minnesota professor in the Departments of Biomedical Engineering and the Department of Chemical Engineering and Materials Science. "This is the first demonstration that a valve implanted into a large animal model, in our case a lamb, can grow with the animal into adulthood. We have a way to go yet, but this puts us much farther down the path to future clinical trials in children. We are excited and optimistic about the possibility of this actually becoming a reality in years to come."Currently, researchers have not been able to develop a heart valve that can grow and maintain function for pediatric patients. The only accepted options for these children with heart defects are valves made from chemically treated animal tissues that often become dysfunctional due to calcification and require replacement because they don't grow with the child. These children will often need to endure up to five (or more) open heart surgeries until a mechanical valve is implanted in adulthood. This requires them to take blood thinners the rest of their lives.In this study, Tranquillo and his colleagues used a hybrid of tissue engineering and regenerative medicine to create the growing heart valves. Over an eight-week period, they used a specialized tissue engineering technique they previously developed to generate vessel-like tubes in the lab from a post-natal donor's skin cells. To develop the tubes, researchers combined the donor sheep skin cells in a gelatin-like material, called fibrin, in the form of a tube and then provided nutrients necessary for cell growth using a bioreactor.The researchers then used special detergents to wash away all the sheep cells from the tissue-like tubes, leaving behind a cell-free collagenous matrix that does not cause immune reaction when implanted. This means the tubes can be stored and implanted without requiring customized growth using the recipient's cells.The next step was to precisely sew three of these tubes (about 16 mm in diameter) together into a closed ring. The researchers then trimmed them slightly to create leaflets to replicate a structure similar to a heart valve about 19 mm in diameter.Video: "After these initial steps, it looked like a heart valve, but the question then became if it could work like a heart valve and if it could grow," Tranquillo said. "Our findings confirmed both."This second generation of tri-tube valves were implanted into the pulmonary artery of three lambs. After 52 weeks, the valve regenerated as its matrix became populated by cells from the recipient lamb, and the diameter increased from 19 mm to a physiologically normal valve about 25 mm. The researchers also saw a 17 to 34 percent increase in the length of the valve leaflets as measured from ultrasound images. In addition, researchers showed that the tri-tube valves worked better than current animal-derived valves with almost none of the calcification or blood clotting that the other valves showed after being implanted in lambs of the same age."We knew from previous studies that the engineered tubes have the capacity to regenerate and grow in a growing lamb model, but the biggest challenge was how to maintain leaflet function in a growing valved conduit that goes through 40 million cycles in a year," said Zeeshan Syedain, the lead researcher on the study and a University of Minnesota senior research associate in Tranquillo's lab. "When we saw how well the valves functioned for an entire year from young lamb to adult sheep, it was very exciting."Tranquillo said the next steps are to implant the tri-tube valve directly into the right ventricle of the heart to emulate the most common surgical repair and then start the process of requesting approval from the U.S. Food and Drug Administration (FDA) for human clinical trials over the next few years."If we can get these valves approved someday for children, it would have such a big impact on the children who suffer from heart defects and their families who have to deal with the immense stress of multiple surgeries," Tranquillo said. "We could potentially reduce the number of surgeries these children would have to endure from five to one. That's the dream."In addition to Tranquillo and Syedain, the research team included Bee Haynie (independent contractor); University of Minnesota researchers Sandra L. Johnson and Greeshma Thrivikraman (biomedical engineering), James Berry, Richard Bianco, John P. Carney, and Matthew Lahti (experimental surgical services); Jirong Li (mechanical engineering); and Ryan C. Hill and Kirk C. Hansen (University of Colorado Anschutz Medical Campus).The research was funded by the National Institutes of Health (R01 HL107572).To read the full research paper entitled "Pediatric tri-tube valved conduits made from fibroblast-produced extracellular matrix evaluated over 52 weeks in growing lambs," visit the
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Biology
| 2,021 |
March 17, 2021
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https://www.sciencedaily.com/releases/2021/03/210317141710.htm
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Modelling speed-ups in nutrient-seeking bacteria
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Many bacteria swim towards nutrients by rotating the helix-shaped flagella attached to their bodies. As they move, the cells can either 'run' in a straight line, or 'tumble' by varying the rotational directions of their flagella, causing their paths to randomly change course. Through a process named 'chemotaxis,' bacteria can decrease their rate of tumbling at higher concentrations of nutrients, while maintaining their swimming speeds. In more hospitable environments like the gut, this helps them to seek out nutrients more easily. However, in more nutrient-sparse environments, some species of bacteria will also perform 'chemokinesis': increasing their swim speeds as nutrient concentrations increase, without changing their tumbling rates. Through new research published in
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The team's findings deliver new insights into how self-swimming microbes survive, particularly in harsher environments like soils and oceans. Previously, studies have shown how chemokinesis allows bacteria to band around nutrient sources, respond quickly to short bursts of nutrients, and even form mutually beneficial relationships with algae. So far, however, none of them have directly measured how bacterial swim speeds can vary with nutrient concentration.Starting from mathematical equations describing run-and-tumble dynamics, Croze's team extended a widely used model for chemotaxis to incorporate chemokinesis. They then applied the new model to predict the dynamics of bacterial populations within the chemical gradients generated by nutrient distributions used in previous experiments. Through their approach, the researchers showed numerically how a combination of both motions can enhance the responses of populations compared with chemotaxis alone. They also presented more accurate predictions of how bacteria respond to nutrient distributions -- including sources which emit nutrients sporadically. This allowed them to better assess the biological benefits of motility.
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Biology
| 2,021 |
March 17, 2021
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https://www.sciencedaily.com/releases/2021/03/210317141654.htm
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Arctic was once lush and green, could be again
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Imagine not a white, but a green Arctic, with woody shrubs as far north as the Canadian coast of the Arctic Ocean. This is what the northernmost region of North America looked like about 125,000 years ago, during the last interglacial period, finds new research from the University of Colorado Boulder.
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Researchers analyzed plant DNA more than 100,000 years old retrieved from lake sediment in the Arctic (the oldest DNA in lake sediment analyzed in a publication to date) and found evidence of a shrub native to northern Canadian ecosystems 250 miles (400 km) farther north than its current range.As the Arctic warms much faster than everywhere else on the planet in response to climate change, the findings, published this week in the "We have this really rare view into a particular warm period in the past that was arguably the most recent time that it was warmer than present in the Arctic. That makes it a really useful analogue for what we might expect in the future," said Sarah Crump, who conducted the work as a PhD student in geological sciences and then a postdoctoral researcher with the Institute of Arctic and Alpine Research (INSTAAR).To gain this glimpse back in time, the researchers not only analyzed DNA samples, they first had to journey to a remote region of the Arctic by ATV and snowmobile to gather them and bring them back.Dwarf birch is a key species of the low Arctic tundra, where slightly taller shrubs (reaching a person's knees) can grow in an otherwise cold and inhospitable environment. But dwarf birch doesn't currently survive past the southern part of Baffin Island in the Canadian Arctic. Yet researchers found DNA of this plant in the ancient lake sediment showing it used to grow much farther north."It's a pretty significant difference from the distribution of tundra plants today," said Crump, currently a postdoctoral fellow in the Paleogenomics Lab at the University of California Santa Cruz.While there are many potential ecological effects of the dwarf birch creeping farther north, Crump and her colleagues examined the climate feedbacks related to these shrubs covering more of the Arctic. Many climate models don't include these kinds of changes in vegetation, yet these taller shrubs can stick out above snow in the spring and fall, making the Earth's surface dark green instead of white -- causing it to absorb more heat from the sun."It's a temperature feedback similar to sea ice loss," said Crump.During the last interglacial period, between 116,000 and 125,000 years ago, these plants had thousands of years to adjust and move in response to warmer temperatures. With today's rapid rate of warming, the vegetation is likely not keeping pace, but that doesn't mean it won't play an important role in impacting everything from thawing permafrost to melting glaciers and sea level rise."As we think about how landscapes will equilibrate to current warming, it's really important that we account for how these plant ranges are going to change," said Crump.As the Arctic could easily see an increase of 9 degrees Fahrenheit (5 degrees Celsius) above pre-industrial levels by 2100, the same temperature it was in the last interglacial period, these findings can help us better understand how our landscapes might change as the Arctic is on track to again reach these ancient temperatures by the end of the century.To get the ancient DNA they wanted, the researchers couldn't look to the ocean or to the land -- they had to look in a lake.Baffin Island is located on the northeastern side of Arctic Canada, kitty-corner to Greenland, in the territory of Nunavut and the lands of the Qikiqtaani Inuit. It's the largest island in Canada and the fifth-largest island in the world, with a mountain range that runs along its northeastern edge. But these scientists were interested in a small lake, past the mountains and near the coast.Above the Arctic Circle, the area around this lake is typical of a high Arctic tundra, with average annual temperatures below 15 °F (?9.5 °C). In this inhospitable climate, soil is thin and not much of anything grows.But DNA stored in the lake beds below tells a much different story.To reach this valuable resource, Crump and her fellow researchers carefully balanced on cheap inflatable boats in the summer -- the only vessels light enough to carry with them -- and watched out for polar bears from the lake ice in winter. They pierced the thick mud up to 30 feet (10 meters) below its surface with long, cylindrical pipes, hammering them deep into the sediment.The goal of this precarious feat? To carefully withdraw a vertical history of ancient plant material to then travel back out with and take back to the lab.While some of the mud was analyzed at a state-of-the-art organic geochemistry lab in the Sustainability, Energy and Environment Community (SEEC) at CU Boulder, it also needed to reach a special lab dedicated to decoding ancient DNA, at Curtin University in Perth.To share their secrets, these mud cores had to travel halfway across the world from the Arctic to Australia.Once in the lab, the scientists had to suit up like astronauts and examine the mud in an ultra-clean space to ensure that their own DNA didn't contaminate that of any of their hard-earned samples.It was a race against the clock."Your best shot is getting fresh mud," said Crump. "Once it's out of the lake, the DNA is going to start to degrade."This is why older lake bed samples in cold storage don't quite do the trick.While other researchers have also collected and analyzed much older DNA samples from permafrost in the Arctic (which acts like a natural freezer underground), lake sediments are kept cool, but not frozen. With fresher mud and more intact DNA, scientists can get a clearer and more detailed picture of the vegetation which once grew in that immediate area.Reconstructing historic vegetation has most commonly been done using fossil pollen records, which preserve well in sediment. But pollen is prone to only showing the big picture, as it is easily blown about by the wind and doesn't stay in one place.The new technique used by Crump and her colleagues allowed them to extract plant DNA directly from the sediment, sequence the DNA and infer what plant species were living there at the time. Instead of a regional picture, sedimentary DNA analysis gives researchers a local snapshot of the plant species living there at the time.Now that they have shown it's possible to extract DNA that's over 100,000 years old, future possibilities abound."This tool is going to be really useful on these longer timescales," said Crump.This research has also planted the seed to study more than just plants. In the DNA samples from their lake sediment, there are signals from a whole range of organisms that lived in and around the lake."We're just starting to scratch the surface of what we're able to see in these past ecosystems," said Crump. "We can see the past presence of everything from microbes to mammals, and we can start to get much broader pictures of how past ecosystems looked and how they functioned."
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Biology
| 2,021 |
March 17, 2021
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https://www.sciencedaily.com/releases/2021/03/210317141610.htm
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Cellular benefits of gene therapy seen decades after treatment
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An international collaboration between Great Ormond Street Hospital, the UCL GOS Institute for Child Health and Harvard Medical School has shown that the beneficial effects of gene therapy can be seen decades after the transplanted blood stem cells has been cleared by the body.
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The research team monitored five patients who were successfully cured of SCID-X1 using gene therapy at GOSH. For 3-18 years patients' blood was regularly analysed to detect which cell types and biomarker chemicals were present in their blood. The results showed that even though the stem cells transplanted as part of gene therapy had been cleared by the patients, the all-important corrected immune cells, called T-cells, were still forming.Gene therapy works by first removing some of the patients' blood-forming stem cells, which create all types of blood and immune cells. Next, a viral vector is used to deliver a new copy of the faulty gene into the DNA of the patients' cells in a laboratory. These corrected stem cells are then returned to patients in a so-called 'autologous transplant', where they go on to produce a continual supply of healthy immune cells capable of fighting infection.In the gene therapy for SCID-X1 the corrected stem cells have been eventually cleared by the body but the patients remained cured of their condition. This team of researchers suggested that the 'cure' was down to the fact that the body was still able to continually produce newly-engineered T cells -- an important part of the body's immune system.They used state-of-the-art gene tracking technology and numerous tests to give unprecedented details of the T cells in SCID-X1 patients decades after gene therapy.The team believe that this gene therapy has created the ideal conditions for the human thymus (the part of the body where T cells develop) to host a long-term store of the correct type of progenitor cells that can form new T cells. Further investigation of how this happens and how it can be exploited could be crucial for the development of next generation gene therapy and cancer immunotherapy approaches.
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Biology
| 2,021 |
March 17, 2021
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https://www.sciencedaily.com/releases/2021/03/210317141453.htm
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Death enables complexity in chemical evolution
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Simple systems can reproduce faster than complex ones. So, how can the complexity of life have arisen from simple chemical beginnings? Starting with a simple system of self-replicating fibres, chemists at the University of Groningen have discovered that upon introducing a molecule that attacks the replicators, the more complex structures have an advantage. This system shows the way forward in elucidating how life can originate from lifeless matter. The results were published on 10 March in the journal
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The road to answering the question of how life originated is guarded by Spiegelman's monster, named after the American molecular biologist Sol Spiegelman, who some 55 years ago described the tendency of replicators to become smaller when they were allowed to evolve. 'Complexity is a disadvantage during replication, so how did the complexity of life evolve?' asked Sijbren Otto, Professor of Systems Chemistry at the University of Groningen. He previously developed a self-replicating system in which self-replication produces fibres from simple building blocks and, now, he has found a way to beat the monster.'To achieve this, we introduced death into our system,' Otto explains. His fibres are made up of stacked rings that are self-assembled from single building blocks. The number of building blocks in a ring can vary, but stacks always contain rings of the same size. Otto and his team tweaked the system in such a way that rings of two different sizes were created, containing either three or six building blocks.Under normal circumstances, fibres that are made up of small rings will outgrow the fibres with larger rings. 'However, when we added a compound that breaks up rings inside the fibres, we found that the bigger rings were more resistant. This means that the more complex fibres will dominate, despite the smaller rings replicating faster. Fibres that are made from small rings are more easily "killed." 'Otto acknowledges that the difference in complexity between the two types of fibres is small. 'We did find that the fibres from the larger rings were better catalysts for the benchmark retro-aldol reaction than the simpler fibres that are made from rings with three building blocks. But then again, this reaction doesn't benefit the fibres.' However, the added complexity protects the fibres from destruction, probably by shielding the sulphur-sulphur bonds that link the building blocks into rings.'All in all, we have now shown that it is possible to beat Spiegelman's monster,' says Otto. 'We did this in a particular way, by introducing chemical destruction, but there may be other routes. For us, the next step is to find out how much complexity we can create in this manner.' His team is now working on a way to automate the reaction, which depends on a delicate balance between the processes of replication and destruction. 'At the moment, it needs constant supervision and this limits the time that we can run it.'The new system is the first of its kind and opens a route to more complex chemical evolution. 'In order to achieve real Darwinian evolution that leads to new things, we will need more complex systems with more than one building block,' says Otto. The trick will be to design a system that allows for the right amount of variation. 'When you have unlimited variation, the system won't go anywhere, it will just produce small amounts of all kinds of variants.' In contrast, if there is very little variation, nothing really new will appear.The results that were presented in the latest paper show that, starting from simple precursors, complexity can increase in the course of evolution. 'This means that we can now see a way forward. But the journey to producing artificial life through chemical evolution is still a long one,' says Otto. However, he has beaten the monster guarding the road to his destination.
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Biology
| 2,021 |
March 17, 2021
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https://www.sciencedaily.com/releases/2021/03/210317111823.htm
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Abundant and stable rocks are critical egg-laying habitat for insects in restored streams
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The abundance and other characteristics of rocks partially extending above the water surface could be important for improving the recovery of aquatic insect populations in restored streams.
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Nearly three quarters of stream insects reproduce on large rocks that sit above the water surface by crawling underneath to attach their eggs. Increasing the number of large and stable emergent rocks in streams could provide more egg-laying habitat and allow insects to quickly repopulate restored streams."We found that restored streams had fewer emergent rocks for egg-laying and fewer total eggs than naturally intact streams," says Samantha Jordt, first author of the paper and an M.Sc. student at NC State's Department of Applied Ecology.The study also found that some of the large rocks in restored streams were unstable and rolled or were buried by sediment between Samantha's visits. According to the study, these variables combined-fewer large rocks available for egg laying and that some of those rocks were unstable-may delay insect recovery."When a rock rolls, any eggs on that rock will likely be destroyed either by being crushed or scraped off as the rock rolls, being buried by sediment, or by drying out if the rock settles into a new position that exposes the eggs to the air," says Jordt. "You end up with lots of insects laying eggs on the one good rock in the stream, truly putting all of their eggs in one, rolling, basket."Less suitable egg-laying habitat means fewer larvae or adult insects -- both important for the long term health and recovery of restored streams. Aquatic insects provide several ecosystem services, including breaking down leaf litter, consuming algae, cycling nutrients, and being food for fish, salamanders, and birds."Many people rely on streams for drinking water, which means they rely on all of the ecological processes that happen upstream before the water reaches them," says Jordt. "Aquatic insects maintain water quality for free. So we develop techniques so that restored streams have habitats that they can rebound and thrive in."Most stream restoration projects focus on the recovery of physical and chemical aspects. This study highlights how incorporating the natural history of aquatic insects will be another critical tool for both the initial design and the long-term success of restoring streams."Unavailable or unstable egg-laying habitat may be a primary reason why biological recovery in restored streams lags decades behind geomorphological and hydrological recovery," says Brad Taylor, co-author of the paper and assistant professor of applied ecology at NC State. "Ensuring stable and suitable rocks for insect egg-laying could be a small design change to increase the return on our multi-million-dollar investment in stream restoration."
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Biology
| 2,021 |
March 17, 2021
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https://www.sciencedaily.com/releases/2021/03/210317111809.htm
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Hepatitis B: What people can learn from donkeys
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Hepatitis B virus (HBV) infections are among the major global health problems. Particularly problematic is the high number of chronic courses of the disease, causing the deaths of more than 800,000 people globally every year. So far, there is no therapy to cure the condition. "With the discovery of a new hepatitis B virus in donkeys and zebras capable of causing prolonged infections, we now have the opportunity for a better understanding of the chronic course of the disease and thus also for mitigation or prevention of severe clinical consequences," explains Prof. Dr. Jan Felix Drexler, DZIF researcher at the Charité -- University Medicine Berlin. In the German Center for Infection Research (DZIF), he identifies and characterizes emerging viruses that could be dangerous for humans.
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"Five years ago we were able to show for the first time that donkeys harbor viruses that are genetically related to the human hepatitis C virus," explains Andrea Rasche, lead author of the study and DZIF scientist at the Charité -- University Medicine Berlin. Since HBV and the hepatitis C virus (HCV) often occur together in humans, the researchers have also searched for HBV worldwide in donkeys. In addition to field work, extensive molecular, serological, histopathological and evolutionary biology methods were used. "We have studied nearly 3000 samples from equids, i.e. from donkeys, zebras and horses in five continents, and we found that donkeys are global carriers of the new hepatitis B virus," explains Drexler.The origins of the new HBV could be linked to the domestication of donkeys in Africa a few thousand years ago. Donkeys are naturally infected with HBV as well as with HCV. Zebras are also infected with HBV; horses are also likely to be receptive, but in initial studies, the scientists could not confirm any naturally infected horses. In naturally infected donkeys, the course of the infection is similar to chronic hepatitis B in humans."The new hepatitis B virus appears to use an unknown receptor for entry into the host cell," explains Felix Lehmann, second lead author of the study and DZIF scientist at Giessen University (JLU) where he studied the molecular biology of virus binding and entry in cell culture. The emergence of human HBV and the development of its receptor use remain unclear and are jointly investigated by the researchers from Berlin and Giessen."Since the virus is unable to infect human liver cells, human infection with this virus can be ruled out with a high degree of probability," emphasises Prof. Dr. Dieter Glebe, Head of the National Reference Centre for Hepatitis B and D viruses at JLU and DZIF scientist in the "hepatitis" research unit. The scientists are convinced that with the virus in donkeys and zebras, they can develop a better understanding of the pathogenesis of chronic hepatitis B and of HBV/HCV co-infection to lay a foundation for new therapies.
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Biology
| 2,021 |
March 17, 2021
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https://www.sciencedaily.com/releases/2021/03/210317111801.htm
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Evolved to stop bacteria, designed for stability
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Connections are crucial. Bacteria may be most dangerous when they connect -- banding together to build fortress-like structures known as biofilms that afford them resistance to antibiotics. But a biomolecular scientist in Israel and a microbiologist in California have forged their own connections that could lead to new protocols for laying siege to biofilm-protected colonies. Their research was published in the
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This interdisciplinary collaboration began with a lecture given at the Weizmann Institute of Science in the Life Sciences Colloquium. Prof. Dianne Newman of the California Institute of Technology was the speaker, and the Institute's Prof. Sarel Fleishman, of the Biomolecular Sciences Department, decided to attend, even though the lecture had no immediately apparent bearing on his own research. Newman described an enzyme she had discovered that could interrupt the metabolism of the biofilm-building bacteria, Pseudomonas aeruginosa. The enzyme interferes with the functioning of a molecule (pyocyanin) that is generated by the bacteria as they reach a high cell density and start to run out of oxygen, and it is thus responsible for helping bacteria deep within the biofilm remain viable as well as better tolerate conventional antibiotics. This molecule, however, is a double-edged sword: It can also be toxic to P. aeruginosa in the outer layers of the biofilm, where oxygen is present. Since pyocyanin impacts both biofilm development and antibiotic tolerance, Newman's lab focused on identifying ways to disrupt its activities. Newman's only problem, she said, was that the newly discovered pyocyanin-blocking enzyme was unstable and produced in minute amounts, and thus far, standard lab methods for growing such proteins had not been successful.Pseudomonas aeruginosa is an opportunistic bacterium that causes disease mainly in those with underlying conditions: in the lungs of cystic fibrosis patients, the peripheral wounds in diabetics and on various implanted medical devices of hospital patients. Hard-to-eradicate biofilms may help infections return even after treatment, contributing to the bacteria's growing antibiotic resistance, particularly in hospital-acquired strains.After the lecture, Fleishman suggested to Newman that they try a new approach to producing larger quantities of the enzyme. His lab specializes in computational protein design, and some of their recent work had involved redesigning vaccine proteins to make them more stable.Rosalie Lipsh-Sokolik, a research student in his lab, together with Dr. Olga Khersonsky, a research associate, took up the challenge of designing an improved, more stable biofilm-busting enzyme. But the enzyme was unlike any Fleishman's lab had worked with before, and it would require them to develop a new methodology: It was a trimer -- three identical copies of a protein bundled "like barrels strapped together," says Fleishman, and that meant that, in addition to the structure of the individual protein, they would need to understand how the entire package fit together.The group's first step was to map the enzyme down to its atomic structure. This gave them a detailed picture of the forces that hold the protein together. When they added the resulting models of the three copies together to understand the trimer formation, they noticed that the areas of contact between copies were poorly packed, atomically speaking, and they thought these particular weak points would be a good place to start in designing a more stable structure.But even after narrowing down the potential sites for adjustment, the number of design possibilities for such a protein complex was huge. Lipsh-Sokolik ended up adopting a combined, two-pronged approach. The first was to look for proteins made by other bacteria that are similar but slightly different, to see what could be borrowed. The second was a sort of "subtle" atomistic design approach, identifying just a dozen or so points on the enzyme that might be tweaked and trying out different modeled combinations of amino acids at just those points.The beauty of the computer design methods developed in Fleishman's lab is not only the fact that they can produce, in a very short time, hundreds of thousands of different possible protein designs, but they also rank them from most-likely to work to not likely to work at all. Still, the only way to know if your hypothesis is correct -- about the areas that need reinforcement or the ability of an enzyme to still function despite changes to its protein sequence -- is to make those proteins and test them in real biological systems. Enter Dr. Chelsey M. VanDrisse, a postdoctoral fellow in the Newman lab, who led all the experimental tests of the Fleishman lab designs.Fleishman admits his team was nervous when VanDrisse and Newman told them that they could conduct experiments on only ten of the designed trimer enzymes due to the highly challenging nature of the experiments. Their challenges were not limited to creating these new proteins, but included figuring out how to purify them in sufficient quantities in the lab and then testing them on real biofilm-building Pseudomonas aeruginosa in combination with standard antibiotic treatment. The question was, could the team not only produce a more active protein, but determine whether its application could facilitate biofilm control and begin to understand the mechanisms underpinning the enzyme`s effects?"Both teams were over the moon when the results came in," says Fleishman: Eight of the ten designed enzymes were produced in larger-than-normal quantities in Newman's lab, without, it seemed, compromising their biofilm-fighting abilities. VanDrisse jokingly raved that she could now produce so much protein she "could have put it in my cereal every morning!" "This showed that our hypothesis about the contact areas was correct," says Fleishman. One enzyme seemed especially robust and was produced in substantial amounts, so VanDrisse and Newman went all the way: They set out to check if this version of the enzyme could, at least in the lab, work together with a commonly used clinical antibiotic to eradicate the biofilm.In fact, they found the enzyme, in combination with this antibiotic, worked much better than they had expected. Further analysis suggested the enzyme first helps the antibiotic kill the bacteria in the oxygenated outer regions of the biofilm in a way that had not before been seen, leading, in short time, to a significant reduction in the total number of viable biofilm cells.Fleishman adds that, as the collaboration between two groups of scientists who normally read different journals, attend different conferences and experiment with very different methods on different scales deepened -- VanDrisse even making it to the Weizmann lab just before the first COVID-19 lockdowns -- he realized that what had started for him as a test of his lab's computational protein design methods now had a very real chance of leading to a cure for some of the most aggressive bacterial infections. It all came down to making the right connections.Prof. Sarel-Jacob Fleishman's research is supported by the Dr. Barry Sherman Institute for Medicinal Chemistry; the Yeda-Sela Center for Basic Research; the Schwartz/Reisman Collaborative Science Program; the Sam Ousher Switzer Charitable Foundation; the Dianne and Irving Kipnes Foundation, Carolyn Hewitt and Anne Christopoulos, in Memory of Sam Switzer; the Milner Foundation; and the Ben B. and Joyce E. Eisenberg Foundation.
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Biology
| 2,021 |
March 17, 2021
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https://www.sciencedaily.com/releases/2021/03/210317111743.htm
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Solving ancient problem of nucleic acid synthesis helps to design new antiviral drugs
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An international team of scientists from the University of Turku, Finland and PennState University, USA have solved a long-standing mystery of how living organisms distinguish RNA and DNA building blocks during gene expression paving the way for the design of new antiviral drugs. The new insights were published in the journal
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All cellular organisms use two types of nucleic acids, RNA and DNA to store, propagate and utilize their genetic information. The synthesis of DNA is carried out by enzymes called DNA polymerases and is needed to accurately transfer the genetic information from generation to generation. Synthesis of RNA is carried out by enzymes called RNA polymerases and is needed to utilize the genetic information to ultimately produce proteins that in turn fulfil most structural and catalytic functions in all modern-day living organisms.The ancient problem faced by RNA and DNA polymerases is that the DNA and RNA building blocks are very hard to distinguish. Those building blocks are identical except for a small part of the molecule, called the 2'OH group that is present in the RNA building blocks but is absent from the DNA building blocks.DNA polymerases avoid using the RNA building blocks by featuring a cavity called the active site that is just big enough to bind the DNA building blocks but is too small to accommodate the slightly bigger RNA building blocks. As a result, only DNA building blocks bind to the active site cavity and get attached to the growing DNA polymer."RNA polymerases cannot use the same strategy because the smaller DNA building blocks will always fit into the same active site cavity as the RNA building blocks," explains Senior Researcher Georgi Belogurov.To understand how RNA polymerases avoid using DNA building blocks, a research team from the University of Turku headed by Belogurov performed complex biochemical measurements using RNA polymerases that were altered by carefully engineered mutations. At the same time, the research team at Penn State University, USA, led by Professor Katsuhiko Murakami obtained a detailed three-dimensional structure of RNA polymerase with the DNA building block.By the combined analysis of the biochemical and structural data Doctoral Candidate Janne Mäkinen, the first author of the study, and his colleagues discovered that RNA polymerase evolved the active site cavity that deforms the DNA building blocks so that they are no longer suitable for incorporation into the RNA chain."The deformed DNA building blocks then dissociate from the RNA polymerase instead of being attached to the growing RNA polymer," says Mäkinen.The study was financially supported by the Academy of Finland, Sigrid Juselius Foundation (Finland), and the National Institute of Health (USA) and has long-reaching implications for translational research."RNA viruses such as SARS-Cov-2 that is the causative agent of COVID-19 disease also synthesise RNA as a part of their infectious cycle. Viruses use their own RNA polymerases that are very different from RNA polymerases of the human cell but also need to select the RNA building blocks and reject the DNA building blocks," says Georgi Belogurov.By careful comparison of the newly discovered selectivity mechanism with the findings of other research teams, Mäkinen and colleagues concluded that viral and human RNA polymerases use different mechanisms to reject the DNA building blocks. They suggest it may be possible to design a synthetic molecule similar to a DNA building block that would selectively bind and inhibit viral RNA polymerase but will be rejected by the human RNA polymerases and therefore will not interfere with the synthesis of RNAs needed by the human cell."This paves the way for the designing of potent and selective antiviral drugs targeting viral RNA polymerases," says Belogurov.
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Biology
| 2,021 |
March 18, 2021
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https://www.sciencedaily.com/releases/2021/03/210318170325.htm
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Combination therapy may provide significant protection against lethal influenza
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A significant proportion of hospitalized patients with influenza develop complications of acute respiratory distress syndrome, driven by virus-induced cytopathic effects as well as exaggerated host immune response. Reporting in
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Previously, the investigators found that an excessive influx of neutrophils, infection fighting immune cells, and the networks they create to kill pathogens, known as neutrophil extracellular traps (NETs), contribute to acute lung injury in influenza infection. Formation of NETs by activated neutrophils occurs via a cell death mechanism called NETosis and the released NETs contain chromatin fibers that harbor toxic components.A mouse model, commonly used in exploring influenza pathophysiology and drug therapies, was used in the current study. Because mice are not natural hosts for influenza, further validation in larger animals is necessary before testing in humans. Therefore, researchers also tested piglets infected with swine influenza virus. The animals were treated with a combination of a CXCR2 antagonist, SCH527123, together with an antiviral agent, oseltamivir.The combination of SCH527123 and oseltamivir significantly improved survival in mice compared to either of the drugs administered alone. The combination therapy also reduced pulmonary pathology in piglets."Combination therapy reduces lung inflammation, alveolitis, and vascular pathology, indicating that aberrant neutrophil activation and release in NETs exacerbate pulmonary pathology in severe influenza," explains lead investigator Narasaraju Teluguakula, PhD, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, USA. "These findings support the evidence that antagonizing CXCR2 may alleviate lung pathology and may have significant synergistic effects with antiviral treatment to reduce influenza-associated morbidity and mortality."It can be challenging to balance the suppression of excessive neutrophil influx without compromising the beneficial host immunity conferred by neutrophils. Therefore, the researchers examined the temporal dynamics of NETs release in correlation with pathological changes during the course of infection in mice. During the early inflammatory phase, three to five days post infection, significant neutrophil activation and NETs release with relatively few hemorrhagic lesions was observed. In the late hemorrhagic exudative phase, significant vascular injury with declining neutrophil activity was seen.Dr. Teluguakula also emphasizes that these findings provide the first evidence to support the strategy of testing combination therapy in a large animal influenza model. "In view of the close similarities in pulmonary pathology and immune responses between swine and humans, pig-influenza pneumonia models can serve as a common platform in understanding pathophysiology and host-directed drug therapies in human influenza infections and may be useful in advancing the translational impact of drug treatment studies in human influenza infections."
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Biology
| 2,021 |
March 16, 2021
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https://www.sciencedaily.com/releases/2021/03/210316214645.htm
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How life on land recovered after 'The Great Dying'
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Over the course of Earth's history, several mass extinction events have destroyed ecosystems, including one that famously wiped out the dinosaurs. But none were as devastating as "The Great Dying," which took place 252 million years ago during the end of the Permian period. A new study, published today in
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To better characterize "The Great Dying," the team sought to understand why communities didn't recover as quickly as other mass extinctions. The main reason was that the end-Permian crisis was much more severe than any other mass extinction, wiping out 19 out of every 20 species. With survival of only 5% of species, ecosystems had been destroyed, and this meant that ecological communities had to reassemble from scratch.To investigate, lead author and Academy researcher Yuangeng Huang, now at the China University of Geosciences, Wuhan, reconstructed food webs for a series of 14 life assemblages spanning the Permian and Triassic periods. These assemblages, sampled from north China, offered a snapshot of how a single region on Earth responded to the crises. "By studying the fossils and evidence from their teeth, stomach contents, and excrement, I was able to identify who ate whom," says Huang. "It's important to build an accurate food web if we want to understand these ancient ecosystems."The food webs are made up of plants, molluscs, and insects living in ponds and rivers, as well as the fishes, amphibians, and reptiles that eat them. The reptiles range in size from that of modern lizards to half-ton herbivores with tiny heads, massive barrel-like bodies, and a protective covering of thick bony scales. Sabre-toothed gorgonopsians also roamed, some as large and powerful as lions and with long canine teeth for piercing thick skins. When these animals died out during the end-Permian mass extinction, nothing took their place, leaving unbalanced ecosystems for ten million years. Then, the first dinosaurs and mammals began to evolve in the Triassic. The first dinosaurs were small -- bipedal insect-eaters about one meter long -- but they soon became larger and diversified as flesh- and plant-eaters."Yuangeng Huang spent a year in my lab," says Peter Roopnarine, Academy Curator of Geology. "He applied ecological modelling methods that allow us to look at ancient food webs and determine how stable or unstable they are. Essentially, the model disrupts the food web, knocking out species and testing for overall stability.""We found that the end-Permian event was exceptional in two ways," says Professor Mike Benton from the University of Bristol. "First, the collapse in diversity was much more severe, whereas in the other two mass extinctions there had been low-stability ecosystems before the final collapse. And second, it took a very long time for ecosystems to recover, maybe 10 million years or more, whereas recovery was rapid after the other two crises."Ultimately, characterizing communities -- especially those that recovered successfully -- provides valuable insights into how modern species might fare as humans push the planet to the brink."This is an amazing new result," says Professor Zhong-Qiang Chen of the China University of Geosciences, Wuhan. "Until now, we could describe the food webs, but we couldn't test their stability. The combination of great new data from long rock sections in North China with cutting-edge computational methods allows us to get inside these ancient examples in the same way we can study food webs in the modern world."
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Biology
| 2,021 |
March 16, 2021
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https://www.sciencedaily.com/releases/2021/03/210316183645.htm
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Researchers discover how 'cryptic species' respond differently to coral bleaching
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Certain brightly colored coral species dotting the seafloor may appear indistinguishable to many divers and snorkelers, but Florida State University researchers have found that these genetically diverse marine invertebrates vary in their response to ocean warming, a finding that has implications for the long-term health of coral reefs.
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The researchers used molecular genetics to differentiate among corals that look nearly identical and to understand which species best coped with thermal stress. Their research was published in the journal "Being able to recognize the differences among these coral species that cannot be identified in the field -- which are known as 'cryptic species' -- will help us understand new ways for how coral reefs maintain resilience in the face of disturbance," said Associate Professor of Biological Science Scott Burgess, the paper's lead author.The researchers were studying the coral ecosystem at the island of Moorea in French Polynesia when a coral bleaching event struck in 2019.Corals get their color from algae that live in their tissues and with which they have a symbiotic relationship. But when corals are stressed -- by high water temperature, for example -- algae leave the coral, which turns white, hence the term "bleaching." Bleached corals are not dead, but they are more vulnerable and more likely to die.Most of the coral at Moorea belong to the genus Pocillopora. During the event, the researchers saw that about 72 percent of the coral colonies from this genus bleached, and up to 42 percent died afterward.At first, it seemed that the largest colonies were more likely to bleach, but when the scientists examined tissue samples from the coral, they found that colonies belonging to a certain genetic lineage, not coral size, was most important in determining the fate of the corals."Because Pocillopora species look so similar, they cannot be reliably identified in the field, which, in the past, has forced researchers to study them as a single group," said Erika Johnston, a postdoctoral researcher in the Department of Biological Science and a co-author of the paper. "Molecular genetics allows us to reconstruct their evolutionary ancestry and are an essential step to species identification in this case."About 86 percent of the Pocillopora corals that died belonged to a group that shares a set of DNA variations, which is known as a haplotype and reflects their common evolutionary ancestry."The good news is that not all of the corals died from bleaching, and many species survived," Burgess said. "The bad news is that the species that died is, as far as we are aware at the moment, endemic to that specific region. So on the one hand, we're worried about losing an endemic species, but on the other hand, our results show how co-occurring cryptic species can contribute to coral resilience."It's an ecological analogy to having a diverse financial portfolio, where a variety of investments decreases the likelihood of a complete loss."Having multiple species that perform a similar function for the reef ecosystem but differ in how they respond to disturbances should increase the chance that Pocillopora corals continue to perform their role in the system, even though the exact species may be shuffled around," Burgess said.Maintaining healthy ecological portfolios may be a better management option than attempting to restore a specific species."If we maintain the right type of diversity, nature in a way can pick the winners and losers," Burgess said. "However, the worry for us scientists is that unless the leaders of governments and corporations take action to reduce CO2 emissions, ecological portfolios that can maintain coral reef resilience will be increasingly eroded under current and ongoing climate change. This is concerning because coral reef ecosystems provide economic, health, cultural and ecological goods and services that humans rely on."Future research will look into the composition of the algae that live inside the coral, the depth distributions of each cryptic coral species and the evolutionary relationships among the cryptic species.Researchers from the Hong Kong University of Science and Technology, the Scripps Institution of Oceanography and California State University, Northridge contributed to this study.This work was conducted as part of a National Science Foundation grant awarded to Burgess.
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Biology
| 2,021 |
March 16, 2021
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https://www.sciencedaily.com/releases/2021/03/210316141820.htm
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Ancient bone artefact found
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The discovery of a rare bone artefact near the Lower Murray River casts more light on the rich archaeological record on Ngarrindjeri country in southern Australia.
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Details of the Murrawong bone point, dated between c. 5,300-3,800 years old, has have been described by Flinders University, Griffith University and other experts in a new paper in Probably made from a macropod (kangaroo or wallaby) bone, the point was likely used for piercing soft materials -- for example, used as a pin on a cloak made of possum furs -- or possibly as a projectile point, say the research leaders Dr Christopher Wilson and Professor Amy Roberts from Flinders University Archaeology.While stone artefacts and shell middens are commonly found on the surface, bone objects are mostly uncovered during excavations. The last similar one was uncovered in the Lower Murray River Gorge was in the 1970s.Dr Wilson, a Ngarrindjeri man, says that "even one find of this kind provides us with opportunities to understand the use of bone technologies in the region and how such artefacts were adapted to a riverine environment.""Bone artefacts have lacked the same amount of study in comparison to artefacts made of stone, so every discovery reminds us of the diverse material culture used by Aboriginal peoples in this country," adds Professor Roberts.The artefact was found during recent excavation work. The project was undertaken in collaboration with the Ngarrindjeri community.This research forms part of a larger project that Dr Wilson is leading to investigate the rich archaeological record on Ngarrindjeri country.
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Biology
| 2,021 |
March 16, 2021
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https://www.sciencedaily.com/releases/2021/03/210316132129.htm
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Non-DNA mechanism is involved in transmitting paternal experience to offspring
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It has long been understood that a parent's DNA is the principal determinant of health and disease in offspring. Yet inheritance via DNA is only part of the story; a father's lifestyle such as diet, being overweight and stress levels have been linked to health consequences for his offspring. This occurs through the epigenome -- heritable biochemical marks associated with the DNA and proteins that bind it. But how the information is transmitted at fertilization along with the exact mechanisms and molecules in sperm that are involved in this process has been unclear until now.
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A new study from McGill, published recently in "The big breakthrough with this study is that it has identified a non-DNA based means by which sperm remember a father's environment (diet) and transmit that information to the embryo," says Sarah Kimmins, PhD, the senior author on the study and the Canada Research Chair in Epigenetics, Reproduction and Development. The paper builds on 15 years of research from her group. "It is remarkable, as it presents a major shift from what is known about heritability and disease from being solely DNA-based, to one that now includes sperm proteins. This study opens the door to the possibility that the key to understanding and preventing certain diseases could involve proteins in sperm.""When we first started seeing the results, it was exciting, because no one has been able to track how those heritable environmental signatures are transmitted from the sperm to the embryo before," adds PhD candidate Ariane Lismer, the first author on the paper. "It was especially rewarding because it was very challenging to work at the molecular level of the embryo, just because you have so few cells available for epigenomic analysis. It is only thanks to new technology and epigenetic tools that we were able to arrive at these results."To determine how information that affects development gets passed on to embryos, the researchers manipulated the sperm epigenome by feeding male mice a folate deficient diet and then tracing the effects on particular groups of molecules in proteins associated with DNA.They found that diet-induced changes to a certain group of molecules (methyl groups), associated with histone proteins, (which are critical in packing DNA into cells), led to alterations in gene expression in embryos and birth defects of the spine and skull. What was remarkable was that the changes to the methyl groups on the histones in sperm were transmitted at fertilization and remained in the developing embryo."Our next steps will be to determine if these harmful changes induced in the sperm proteins (histones) can be repaired. We have exciting new work that suggest that this is indeed the case," adds Kimmins. "The hope offered by this work is that by expanding our understanding of what is inherited beyond just the DNA, there are now potentially new avenues for disease prevention which will lead to healthier children and adults."
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Biology
| 2,021 |
March 16, 2021
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https://www.sciencedaily.com/releases/2021/03/210316132111.htm
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How bacterial traffic jams lead to antibiotic-resistant, multilayer biofilms
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The bacterial equivalent of a traffic jam causes multilayered biofilms to form in the presence of antibiotics, shows a study published today in
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The study reveals how the collective behaviour of bacterial colonies may contribute to the emergence of antibiotic resistance. These insights could pave the way to new approaches for treating bacterial infections that help thwart the emergence of resistance.Bacteria can acquire resistance to antibiotics through genetic mutations. But they can also defend themselves via collective behaviours such as joining together in a biofilm -- a thin, slimy film made up of many bacteria that is less susceptible to antibiotics. Swarms of bacteria can also undergo a phenomenon similar to human traffic jams called 'motility-induced phase separation', in which they slow down when there are large numbers of bacteria crammed together."In our study, we wanted to see whether swarming bacteria can use physical interactions such as motility-induced phase separation to overcome certain stresses including exposure to antibiotics," says first author Iago Grobas, a PhD student at Warwick Medical School, University of Warwick, UK.In their study, Grobas and colleagues exposed a colony of a common environmental bacteria called Bacillus subtilis to an antibiotic called kanamycin in a dish in the laboratory. They recorded a time-lapse video of the bacteria's behaviour and found that they formed biofilms in the presence of the drug.Specifically, the team showed that the biofilm forms because bacteria begin to group together a distance away from the antibiotic, giving way to multiple layers of swarming bacteria."The layers build up through a physical mechanism whereby groups of cells moving together collide with each other," Grobas explains. "The collision generates enough stress to pile up the cells, which then move slower, attracting more cells through a mechanism similar to motility-induced phase separation. These multiple layers then lead to biofilm formation."Next, the team tested a strategy to stop this formation and thereby prevent antibiotic resistance from occurring in this way. They found that splitting a single dose in two steps without changing the total amount of antibiotics strongly reduced the emergence of a biofilm.The authors say further research is now needed to determine if bacteria that are harmful to humans use similar behaviours to survive antibiotic exposure. If they do, then future treatments should take these behaviours into account in order to reduce antibiotic resistance."Our discoveries question the way we use antibiotics and show that increasing the dosage is not always the best way to stop biofilm development," says co-senior author Munehiro Asally, Associate Professor at the School of Life Sciences, University of Warwick. "The timing of the bacteria's exposure to drugs is also important.""These insights could lead us to rethink the way antibiotics are administered to patients during some infections," concludes co-senior author Marco Polin, Associate Professor at the Department of Physics, University of Warwick, and a researcher at the Mediterranean Institute for Advanced Studies (IMEDEA), Mallorca.
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Biology
| 2,021 |
March 16, 2021
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https://www.sciencedaily.com/releases/2021/03/210316083801.htm
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Can I squeeze through here? How some fungi can grow through tiny gaps
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Fungi are a vital part of nature's recycling system of decay and decomposition. Filamentous fungi spread over and penetrate surfaces by extending fine threads known as hyphae.
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Fungi that cause disease within living organisms can penetrate the spaces between tightly connected plant or animal cells, but how their hyphae do this, and why the hyphae of other fungal species do not, has been unclear.Now, a team led by Professor Norio Takeshita at University of Tsukuba, with collaborators at Nagoya University and in Mexico, has discovered a key feature that helps explain the differences among species. They compared seven fungi from different taxonomic groups, including some that cause disease in plants.The team tested how the fungi responded when presented with an obstruction that meant they had to pass through very narrow channels. At only 1 micron wide, the channels were narrower than the diameter of fungal hyphae, typically 2-5 microns in different species.Some species grew readily through the narrow channels, maintaining similar growth rates before meeting the channel, while extending through it, and after emerging. In contrast, other species were seriously impeded. The hyphae either stopped growing or grew very slowly through the channel. After emerging, the hyphae sometimes developed a swollen tip and became depolarized so that they did not maintain their previous direction of growth.The tendency to show disrupted growth did not depend on the diameter of the hyphae, or how closely related the fungi were. However, species with faster growth rates and higher pressure within the cell were more prone to disruption.By observing fluorescent dyes in the living fungi, the team found that processes inside the cell became defective in the fungi with disrupted growth. Small packages (vesicles) that supply lipids and proteins (needed for assembling new membranes and cell walls as hypha extend) were no longer properly organized during growth through the channel."For the first time, we have shown that there appears to be a trade-off between cell plasticity and growth rate," says Professor Takeshita. "When a fast-growing hypha passes through a narrow channel, a massive number of vesicles congregate at the point of constriction, rather than passing along to the growing tip. This results in depolarized growth: the tip swells when it exits the channel, and no longer extends. In contrast, a slower growth rate allows hyphae to maintain correct positioning of the cell polarity machinery, permitting growth to continue through the confined space."As well as helping explain why certain fungi can penetrate surfaces or living tissues, this discovery will also be important for future research into fungal biotechnology and ecology.
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Biology
| 2,021 |
March 16, 2021
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https://www.sciencedaily.com/releases/2021/03/210312095810.htm
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Shutting the nano-gate
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Scientists from the Institute of Scientific and Industrial Research at Osaka University fabricated nanopores in silicon dioxide, that were only 300 nm, in diameter surrounded by electrodes. These nanopores could prevent particles from entering just by applying a voltage, which may permit the development of sensors that can detect very small concentrations of target molecules, as well as next-generation DNA sequencing technology.
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Nanopores are tiny holes that are wide enough for just a single molecule or particle to pass through. The motion of nanoparticles through these holes can usually be detected as an electrical signal, which makes them a promising platform for novel single-particle sensors. However, control of the motion of the particles has been a challenge so far.Scientists at Osaka University used integrated nanoelectromechanical systems technology to produce solid-state nanopores, only 300 nm wide, with circular platinum gate electrodes surrounding the openings that can prevent nanoparticles from passing through. This is accomplished by selecting the correct voltage that pulls ions in the solution to create a countervailing flow that blocks the entry of the nanoparticle."Single-nanoparticle motions could be controlled via the voltage applied to the surrounding gate electrode, when we fine-tuned the electroosmotic flow via the surface electric potential," first author Makusu Tsutsui says. After the particle has been trapped at the nanopore opening, a subtle force imbalance between the electrophoretic attraction and the hydrodynamic drag can then be created. At that time, the particles can be pulled in extremely slowly, which may allow long polymers, like DNA, to be threaded through at the correct speed for sequencing."The present method can not only enable better sensing accuracy of sub-micrometer objects, such as viruses, but also provides a method for protein structural analysis," senior author Tomoji Kawai says. While nanopores have already been used to determine the identity of various target molecules based on the current generated, the technology demonstrated in this project may allow for wider range of analytes to be tested this way. For example, small molecules, such as proteins and micro-RNA segments that need to be pulled in at a very controlled speed, may also be detected.
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Biology
| 2,021 |
March 16, 2021
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https://www.sciencedaily.com/releases/2021/03/210310122613.htm
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Sharing shears: Conserved protein segment activates molecular DNA scissors for DNA repair
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Scientists at Tokyo Institute of Technology (Tokyo Tech) have uncovered mechanisms underlying the activation of the MRN complex -- the cell's DNA scissors. Using purified yeast proteins, they demonstrated that phosphorylation of Ctp1, a homolog of a tumor-suppressor protein, plays a key role in activating MRN complex's DNA clipping activity. Intriguingly, a short segment of yeast Ctp1 or its human counterpart could stimulate endonuclease activity of their respective MRN complexes, suggesting its conserved function across species.
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DNA functions as a roadmap that guides the identity and functions of cells. A glitch in the DNA can have serious deleterious effects resulting in the malfunction or loss of crucial proteins, thus affecting normal cellular function and viability. These glitches often manifest as double stranded breaks in the DNA that may occur spontaneously or from exposure to certain chemicals. To deal with these kinks, cells have evolved a DNA repair machinery that scans, identifies, and fixes breaks in the DNA by ligating the gaps. However, DNA breaks often have ''dirty ends'' that cannot be directly ligated or sealed as they are unexposed or blocked by certain proteins or irregular chemical structures. Such DNA ends thus need to first be clipped and freed so that it can be processed further. Moreover, such end-resection of DNA break ends are prerequisite for them to be accurately repaired by homologous recombination. Among such molecular scissors, or nuclease enzymes, Mre11 is a key player.Mre11 teams up with proteins Rad50 and Nbs1 to collectively form the 'MRN' complex. The interaction of this complex with the tumor-suppressor protein CtIP in humans, has been shown to trigger the DNA clipping function of the complex. However, the mechanisms underlying this interaction have hitherto remained unexplored.Now, Assistant Professor Hideo Tsubouchi and Professor Hiroshi Iwasaki from Tokyo Institute of Technology and their team have decoded the stepwise interaction and activation of the MRN complex using Ctp1 proteins in yeast, which are homologous to the human CtIP. Discussing their findings that have recently been published in The scientists found that phosphorylation or the addition of phosphate groups to Ctp1 was the key first step in activating the MRN complex. More specifically, phosphorylation enabled the physical interaction of Ctp1 with the Nbs1 protein of the complex, which was vital for subsequent endonuclease stimulation. The DNA clipping activity was extremely poor when the MRN complex was mixed with unphosphorylated Ctp1.Furthermore, the scientists identified a short stretch of merely 15 amino acids at the C-terminal region of Ctp1 that was indispensable for the endonuclease activity of the Ctp1-stimulated MRN. Moreover, a synthetic peptide mimicking this region of Ctp1 or CtIP was able to activate the yeast or human MRN complex, respectively, suggesting that the function of the C-terminal Ctp1 is likely conserved across species and is the ultimate determinant in MRN activation.Excited about the prospective application of their findings, Tsubouchi remarks, "Modification of the CT15 peptide can yield a strong activator or potential inhibitor of the MRN complex. Targeting this endonuclease activity can have potentially useful applications in homologous recombination-based gene editing."With rapid advancements in recombinant DNA and molecular medicine, these findings could empower geneticists to unravel the mysteries of the genome and identify the hidden intricacies of genetic disorders with greater ease and effectiveness in the days to come.
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Biology
| 2,021 |
March 16, 2021
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https://www.sciencedaily.com/releases/2021/03/210316093436.htm
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Mitochondria found to be protected by ketogenesis
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Ketone bodies are generally an alternative energy source during starvation, but in newborns, ketogenesis is active regardless of nutritional status. In a recent study from Kumamoto University (Japan), researchers analyzed the effects of ketogenesis in mice and found that it has a protective effect on cells by maintaining the function of mitochondria. They expect that this effect can be used in future therapies for protecting mitochondria and organs.
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Ketones, along with glucose and fatty acids, are metabolites used as energy sources. In particular, ketones are known to be an alternative energy source during periods of fasting or starvation. However, ketogenesis is known to be active in the neonatal period regardless of the number of calories consumed during nursing, and role it plays in newborns is not well understood.To search for answers, researchers generated ketogenesis-deficient mice that lacked the gene for HMG-CoA Synthase 2 (HMGCS2), an important enzyme ketogenesis. Their analysis showed that, in the absence of ketone bodies, the mice developed a severely fatty liver during the neonatal period.Focusing on the mitochondria, they showed that enzymatic reactions in the mitochondria, mainly the Krebs cycle, were impaired. Nutrients are converted to acetyl CoA during the Krebs cycle, which is then converted to citric acid and seven other acids to produce energy. In the search for the cause of the dysfunction, researchers confirmed that the accumulation of the substrate acetyl CoA (due to insufficient ketogenesis) impairs the functions of proteins in the mitochondria by adding excessive acetylation."During a rapid increase in fatty acid intake with postnatal nursing, active ketogenesis under normal conditions has a protective effect by preventing excessive acetylation of mitochondrial proteins and maintaining mitochondrial function," said study leader Dr. Yuichiro Arima. "We believe that this result will be used in therapeutic applications for mitochondrial and organ protection in the future."
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Biology
| 2,021 |
March 15, 2021
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https://www.sciencedaily.com/releases/2021/03/210315160719.htm
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When 'eradicated' species bounce back with a vengeance
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Some invasive species targeted for total eradication bounce back with a vengeance, especially in aquatic systems, finds a study led by the University of California, Davis.
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The study, published today in the journal "A failure in science often leads to unexpected directions," said lead author Edwin (Ted) Grosholz, a professor and ecologist with the UC Davis Department of Environmental Science and Policy. "We slapped our foreheads at the time, but with thought and understanding, it's told us a lot about what we shouldn't be doing and provided a way forward for us. The world should get less focused on total eradication and work toward functional eradication.""Functional eradication" is described in a study led by the University of Alberta, co-authored by Grosholz, and published in the March issue of For the But one year later, in 2014, the population exploded to about 300,000 green crab in the lagoon -- a 30-fold increase over 2013 levels and nearly triple the pre-eradication population size.The scientists did not observe such population explosions of green crab at any of the four other nearby bays they were monitoring, suggesting the increase was the result of eradication efforts and not atmospheric or oceanographic changes.The study found the population explosion was due in part to the fact that adult decapod crustacea -- such as shrimp, lobster and crab -- typically cannibalize younger individuals. When most adults were removed, juveniles grew unchecked and overcompensated for the loss of adults.The study notes that this short-term overcompensation drove a process called the "hydra effect," named after a mythical serpent that grew two new heads for each one that was removed. Grosholz likens it to the Sorcerer's Apprentice in the Disney film Fantasia, in which several spellbound brooms emerge from just one chopped by apprentice Mickey.The study is also a precautionary tale for natural resource managers: "Don't try to get them all, or it could come back to bite you," Grosholz said."Instead of a one-size-fits-all approach, this study highlights the need to evaluate possible unintended consequences in selecting management strategies and tailoring these to the particular context and expected outcome," said Greg Ruiz, a co-author and marine biologist with the Smithsonian Environmental Research Center.As described in the That strategy was eventually employed at Seadrift Lagoon, aided in large part by local volunteers and residents. Such community science efforts may be key for helping other ecosystems struggling with invasive species, such as in national and state parks, where citizen engagement can be high.Co-authoring institutions on this study include Smithsonian Environmental Research Center, Portland State University and Woods Hole Oceanographic Institution.The study was funded by the National Science Foundation, Pacific States Marine Fisheries Commission, Greater Farallones Association, and Smithsonian Institution Hunterdon Fund.
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Biology
| 2,021 |
March 15, 2021
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https://www.sciencedaily.com/releases/2021/03/210315160714.htm
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Of mice and men and their different tolerance to pathogens
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Trillions of commensal microbes live on the mucosal and epidermal surfaces of the body and it is firmly established that this microbiome affects its host's tolerance and sensitivity of the host to a variety of pathogens. However, host tolerance to infection with pathogens is not equally developed in all organisms. For example, it is known that the gut microbiome of mice protects more effectively against infection with certain pathogens, such as the bacterium Salmonella typhimurium, than the human gut microbiome.
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This raises the interesting possibility that analyzing differences between host-microbiome interactions in humans and other species, such as mice, and pinpointing individual types of bacterial that either protect or sensitize against certain pathogens, could lead to entirely new types of therapeutic approaches. However, while the intestinal microbiome composition and its effect on host immune responses have been well investigated in mice, it is not possible to study how the microbiome interacts directly with the epithelial cells lining the intestine under highly defined conditions, and thereby uncover specific bacterial strains that can induce host-tolerance to infectious pathogens.Now, a collaborative team led by Wyss Founding Director Donald Ingber, M.D., Ph.D. at Harvard's Wyss Institute for Biologically Inspired Engineering and Dennis Kasper, M.D. at Harvard Medical School (HMS) has harnessed the Wyss's microfluidic Organs-on-Chip (Organ Chip) technology to model the different anatomical sections of the mouse intestine and their symbiosis with a complex living microbiome in vitro. The researchers recapitulated the destructive effects of S. typhimurium on the intestinal epithelial surface in an engineered mouse Colon Chip, and in a comparative analysis of mouse and human microbiomes were able to confirm the commensal bacterium Enterococcus faecium contributes to host tolerance to S. typhimurium infection. The study is published in The project was started under a DARPA-supported "Technologies for Host Resilience" (THoR) Project at the Wyss Institute, whose goal it was to uncover key contributions to tolerance to infection by studying differences observed in certain animal species and humans. Using a human Colon Chip, Ingber's group had shown in a previous study how metabolites produced by microbes derived from mouse and human feces have different potential to impact susceptibility to infection with an enterohemorrhagic E. coli pathogen."Biomedical research strongly depends on animal models such as mice, which undoubtedly have tremendous benefits, but do not provide an opportunity to study normal and pathological processes within a particular organ, such as the intestine, close-up and in real-time. This important proof-of-concept study with Dennis Kasper's group highlights that our engineered mouse Intestine Chip platform offers exactly this capability and provides the possibility to study host-microbiome interactions with microbiomes from different species under highly controllable conditions in vitro," said Ingber. "Given the deep level of characterization of mouse immunology, this capability could greatly help advance the work of researchers who currently use these animals to do research on microbiome and host responses. It enables them to compare their results they obtain directly with human Intestine Chips in the future so that the focus can be on identifying features of host response that are most relevant for humans." Ingber also is the Judah Folkman Professor of Vascular Biology at HMS and Boston Children's Hospital, and Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.In their new study, the team focused on the mouse intestinal tract. "It has traditionally been extremely difficult to model host-microbiome interactions outside any organism as many bacteria are strictly anaerobic and die in normal atmospheric oxygen conditions. Organ Chip technology can recreate these conditions, and it is much easier to obtain primary intestinal and immune cells from mice than having to rely on human biopsies," said first-author Francesca Gazzaniga, Ph.D., a Postdoctoral Fellow who works between Ingber's and Kasper's groups and spear-headed the project.Gazzaniga and her colleagues isolated intestinal crypts from different regions of the mouse intestinal tract, including the duodenum, jejunum, ileum, and colon, took their cells through an intermediate "organoid" step in culture in which small tissue fragments form and grow, which they then seeded into one of two parallel microfluidically perfused channels of the Wyss' Organ Chips to create region-specific Intestine Chips. The second independently perfused channel mimics the blood vasculature, and is separated from the first by a porous membrane that allows the exchange of nutrients, metabolites, and secreted molecules that intestinal epithelial cells use to communicate with vascular and immune cells.The team then honed in on S. typhimurium as a pathogen. First, they introduced the pathogen into the epithelial lumen of the engineered mouse Colon Chip and recapitulated the key features associated with the break-down of intestinal tissue integrity known from mouse studies, including the disruption of normally tight adhesions between neighboring epithelial cells, decreased production of mucus, a spike in secretion of a key inflammatory chemokine (the mouse homolog of human IL-8), and changes in epithelial gene expression. In parallel, they showed that the mouse Colon Chip supported the growth and viability of complex bacterial consortia normally present in mouse and human gut microbiomes.Putting these capabilities together, the researchers compared the effects of specific mouse and human microbial consortia that had previously been maintained stably in the intestines of 'gnotobiotic' mice that were housed in germ-free conditions by the Kasper team. By collecting complex microbiomes from the stool of those mice, and then inoculating them into the Colon Chips, the researchers observed chip-to-chip variability in consortium composition, which enabled them to relate microbe composition to functional effects on the host epithelium. "Using 16s sequencing gave us a good sense of the microbial compositions of the two consortia, and high numbers of one individual species, Enterococcus faecium, generated by only one of them in the Colon Chip, allowed the intestinal tissue to better tolerate the infection," said Gazzaniga. "This nicely confirmed past findings and validated our approach as a new discovery platform that we can now use to investigate the mechanisms that underlie these effects as well as the contribution of vital immune cell contributions to host-tolerance, as well as infectious processes involving other pathogens.""The mouse intestine on a chip technology provides a unique approach to understand the relationship between the gut microbiota, host immunity, and a microbial pathogen. This important interrelationship is challenging to study in the living animal because there are so many uncontrollable factors. The beauty of this system is that essentially all parameters you wish to study are controllable and can easily be monitored. This system is a very useful step forward," said Kasper, who is the William Ellery Channing Professor of Medicine and Professor of Immunology at HMS.The researchers believe that their comparative in vitro approach could uncover specific cross-talk between pathogens and commensal bacteria with intestinal epithelial and immune cells, and that identified tolerance-enhancing bacteria could be used in future therapies, which may circumvent the problem increasing antimicrobial resistance of pathogenic bacterial strains.
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Biology
| 2,021 |
March 15, 2021
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https://www.sciencedaily.com/releases/2021/03/210315132128.htm
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New clues about the architecture of X chromosomes
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Researchers at Massachusetts General Hospital (MGH) have uncovered new clues that add to the growing understanding of how female mammals, including humans, "silence" one X chromosome. Their new study, published in
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Female mammals have two copies of the X chromosome in all of their cells. Each X chromosome contains many genes, but only one of the pair can be active; if both X chromosomes expressed genes, the cell couldn't survive. To prevent both X chromosomes from being active, female mammals have a mechanism that inactivates one of them during development. X chromosome inactivation is orchestrated by a noncoding form of RNA called Xist, which silences genes by spreading across the chromosome, recruiting other proteins (such as Polycomb repressive complexes) to complete the task.Jeannie Lee, MD, PhD, an investigator in the Department of Molecular Biology at MGH and the paper's senior author, has led pioneering research on X chromosome inactivation. She believes that understanding the phenomenon could lead to cures for congenital diseases known as X-linked disorders, which are caused by mutations in genes on the active X chromosome. "Our goal is to reactivate the inactive X chromosome, which carries a good copy of the gene," says Lee. Doing so could have profound benefits for people with conditions such as Rett syndrome, a disorder brought on by a mutation in a gene called MECP2 that almost always occurs in girls and causes severe problems with language, learning, coordination and other brain functions. In theory, reactivating the X chromosome could cure Rett syndrome and other X-linked disorders.In this study, Lee and Andrea Kriz, a PhD student and first author of the paper, were interested in understanding the role of clusters of proteins called cohesins in X inactivation. Cohesins are known to play a critical role in gene expression. Imagine a chromosome as a long piece of string with genes and their regulatory sequences being far apart, says Lee. For the gene to be turned "on" and do its job, such as producing a specific protein, it has to come in contact with its distant regulator. Chromosomes allow this to happen by forming a small loop that brings together the gene and regulator. Ring-shaped cohesins help these loops form and stabilize. When the gene's work is done and it's time to turn off, a scissor-like protein called WAPL snips it, causing the gene to disconnect from its regulator. An active chromosome has many of these loops, which are continually forming and dissociating (or separating).These small loops, which are essential for gene expression, are relatively suppressed on an inactivated X chromosome. One reason, as Lee and her colleagues have already shown, is that Xist "evicts" most cohesins from the inactive X chromosome and that this cohesin depletion may be necessary to reorganize the shape and structure of the chromosome for silencing.In the current study, Lee and Kriz used embryonic stem cells from female mice to find out what happens when cohesin or WAPL levels are manipulated during X chromosome inactivation by using protein-degradation technology. "We found that if cohesin levels build up too high, the X chromosome cannot inactivate properly," says Lee. Normally, retaining cohesins (which are normally supposed to be evicted) prevented the X chromosome from folding into an inactive shape and gene silencing was affected. "You need a fine balance between eviction and retention of cohesins during X chromosome inactivation," says Lee.Next, the authors asked what happens when cohesin is manipulated in an active X chromosome. The short answer: It takes on some peculiar qualities of an inactivated X chromosome. First, when there is insufficient cohesin, the active X develops structures called "superloops" that are usually only seen on the inactive X. Second, when there is too much cohesin, the active X develops "megadomains," which Lee calls two "big blobs," and are also ordinarily unique to the inactive X. "The fact that we can confer some features of the inactive X chromosome onto the active X chromosome just by toggling cohesin levels is intriguing," says Lee. She and her colleagues are trying to understand how and why that happens.These findings suggests that shape and structure of the X chromosome play a vital role in allowing Xist to spread from one side to the other and achieve inactivation. "The more we learn about what's important for silencing the X chromosome," says Lee, "the more likely we'll be to find ways to reactivate it and to treat conditions like Rett syndrome."
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Biology
| 2,021 |
March 15, 2021
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https://www.sciencedaily.com/releases/2021/03/210315115047.htm
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Hidden link between cellular defense systems
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Researchers at the University of Illinois Chicago have discovered that heparanase, HPSE, a poorly understood protein, is a key regulator of cells' innate defense mechanisms.
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Innate defense responses are programmed cellular mechanisms that are triggered by various danger signals, which have been conserved in many species throughout evolution. These systems can be set into action by pathogens, such as viruses, bacteria and parasites, as well as by environmental toxins and dysfunctional cells that can accumulate in the body over time. A more thorough understanding of the commonalities and connections between these processes has the potential to generate multi-target therapy against a variety of human diseases.In a multi-institution team led by Alex Agelidis, a UIC MD/Ph.D. dual degree medical student, and Dr. Deepak Shukla, the UIC Marion Schenk Professor of Ophthalmology and UIC professor of microbiology and immunology at the College of Medicine, researchers used a systems approach to track shifts in important cellular building blocks in cells and mice genetically engineered to lack HPSE.In this collaborative multidisciplinary study, Agelidis and coauthors show for the first time that HPSE acts as a cellular crossroads between antiviral immunity, proliferative signals and cell death."HPSE has been long known to drive late-stage inflammatory diseases yet it was once thought that this was primarily due to enzymatic activity of the protein breaking down heparan sulfate, a sugar molecule present in chains on the surface of virtually all cells," Agelidis said.While a major focus of the study was on identifying mechanisms of pathogenesis of herpes simplex virus (HSV-1), their work has broad implications for the treatment of diseases involving dysregulation of HPSE, including cancer, atherosclerosis and autoimmune disorders.
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Biology
| 2,021 |
March 12, 2021
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https://www.sciencedaily.com/releases/2021/03/210312155448.htm
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SARS-CoV-2 jumped from bats to humans without much change, study finds
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How much did SARS-CoV-2 need to change in order to adapt to its new human host? In a research article published in the open access journal
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The study is a collaboration between researchers in the UK, US and Belgium. The lead authors Prof David L Robertson (at the MRC-University of Glasgow Centre for Virus Research, Scotland) and Prof Sergei Pond (at the Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia) were able to turn their experience of analysing data from HIV and other viruses to SARS-CoV-2. Pond's state-of-the-art analytical framework, HyPhy, was instrumental in teasing out the signatures of evolution embedded in the virus genomes and rests on decades of theoretical knowledge on molecular evolutionary processes.First author Dr Oscar MacLean explains, "This does not mean no changes have occurred, mutations of no evolutionary significance accumulate and 'surf' along the millions of transmission events, like they do in all viruses." Some changes can have an effect; for example, the Spike replacement D614G which has been found to enhance transmissibility and certain other tweaks of virus biology scattered over its genome. On the whole, though, 'neutral' evolutionary processes have dominated. MacLean adds, "This stasis can be attributed to the highly susceptible nature of the human population to this new pathogen, with limited pressure from population immunity, and lack of containment, leading to exponential growth making almost every virus a winner."Pond comments, "what's been so surprising is just how transmissible SARS-CoV-2 has been from the outset. Usually viruses that jump to a new host species take some time to acquire adaptations to be as capable as SARS-CoV-2 at spreading, and most never make it past that stage, resulting in dead-end spillovers or localised outbreaks."Studying the mutational processes of SARS-CoV-2 and related sarbecoviruses (the group of viruses SARS-CoV-2 belongs to from bats and pangolins), the authors find evidence of fairly significant change, but all before the emergence of SARS-CoV-2 in humans. This means that the 'generalist' nature of many coronaviruses and their apparent facility to jump between hosts, imbued SARS-CoV-2 with ready-made ability to infect humans and other mammals, but those properties most have probably evolved in bats prior to spillover to humans.Joint first author and PhD student Spyros Lytras adds, "Interestingly, one of the closer bat viruses, RmYN02, has an intriguing genome structure made up of both SARS-CoV-2-like and bat-virus-like segments. Its genetic material carries both distinct composition signatures (associated with the action of host anti-viral immunity), supporting this change of evolutionary pace occurred in bats without the need for an intermediate animal species."Robertson comments, "the reason for the 'shifting of gears' of SARS-CoV-2 in terms of its increased rate of evolution at the end of 2020, associated with more heavily mutated lineages, is because the immunological profile of the human population has changed." The virus towards the end of 2020 was increasingly coming into contact with existing host immunity as numbers of previously infected people are now high. This will select for variants that can dodge some of the host response. Coupled with the evasion of immunity in longer-term infections in chronic cases (e.g., in immunocompromised patients), these new selective pressures are increasing the number of important virus mutants.It's important to appreciate SARS-CoV-2 still remains an acute virus, cleared by the immune response in the vast majority of infections. However, it's now moving away faster from the January 2020 variant used in all of the current vaccines to raise protective immunity. The current vaccines will continue to work against most of the circulating variants but the more time that passes, and the bigger the differential between vaccinated and not-vaccinated numbers of people, the more opportunity there will be for vaccine escape. Robertson adds, "The first race was to develop a vaccine. The race now is to get the global population vaccinated as quickly as possible."
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Biology
| 2,021 |
March 12, 2021
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https://www.sciencedaily.com/releases/2021/03/210312132631.htm
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A computational guide to lead cells down desired differentiation paths
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There is a great need to generate various types of cells for use in new therapies to replace tissues that are lost due to disease or injuries, or for studies outside the human body to improve our understanding of how organs and tissues function in health and disease. Many of these efforts start with human induced pluripotent stem cells (iPSCs) that, in theory, have the capacity to differentiate into virtually any cell type in the right culture conditions. The 2012 Nobel Prize awarded to Shinya Yamanaka recognized his discovery of a strategy that can reprogram adult cells to become iPSCs by providing them with a defined set of gene-regulatory transcription factors (TFs). However, progressing from there to efficiently generating a wide range of cell types with tissue-specific differentiated functions for biomedical applications has remained a challenge.
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While the expression of cell type-specific TFs in iPSCs is the most often used cellular conversion technology, the efficiencies of guiding iPSC through different "lineage stages" to the fully functional differentiated state of, for example, a specific heart, brain, or immune cell currently are low, mainly because the most effective TF combinations cannot be easily pinpointed. TFs that instruct cells to pass through a specific cell differentiation process bind to regulatory regions of genes to control their expression in the genome. However, multiple TFs must function in the context of larger gene regulatory networks (GRNs) to drive the progression of cells through their lineages until the final differentiated state is reached.Now, a collaborative effort led by George Church, Ph.D. at Harvard's Wyss Institute for Biologically Inspired Engineering and Harvard Medical School (HMS), and Antonio del Sol, Ph.D., who leads Computational Biology groups at CIC bioGUNE, a member of the Basque Research and Technology Alliance, in Spain, and at the Luxembourg Centre for Systems Biomedicine (LCSB, University of Luxembourg), has developed a computer-guided design tool called IRENE, which significantly helps increase the efficiency of cell conversions by predicting highly effective combinations of cell type-specific TFs. By combining IRENE with a genomic integration system that allows robust expression of selected TFs in iPSCs, the team demonstrated their approach to generate higher numbers of natural killer cells used in immune therapies, and melanocytes used in skin grafts, than other methods. In a scientific first, generated breast mammary epithelial cells, whose availability would be highly desirable for the repopulation of surgically removed mammary tissue. The study is published in Nature Communications."In our group, the study naturally built on the 'TFome' project, which assembled a comprehensive library containing 1,564 human TFs as a powerful resource for the identification of TF combinations with enhanced abilities to reprogram human iPSCs to different target cell types," said Wyss Core Faculty member Church. "The efficacy of this computational algorithm will boost a number of our tissue engineering efforts at the Wyss Institute and HMS, and as an open resource can do the same for many researchers in this burgeoning field." Church is the lead of the Wyss Institute's Synthetic Biology platform, and Professor of Genetics at HMS and of Health Sciences and Technology at Harvard and MIT.Several computational tools have been developed to predict combinations of TFs for specific cell conversions, but almost exclusively these are based on the analysis of gene expression patterns in many cell types. Missing in these approaches was a view of the epigenetic landscape, the organization of the genome itself around genes and on the scale of entire chromosome sections which goes far beyond the sequence of the naked genomic DNA."The changing epigenetic landscape in differentiating cells predicts areas in the genome undergoing physical changes that are critical for key TFs to gain access to their target genes. Analyzing these changes can inform more accurately about GRNs and their participating TFs that drive specific cell conversions," said co-first author Evan Appleton, Ph.D. Appleton is a Postdoctoral Fellow in Church's group who joined forces with Sascha Jung, Ph.D., from del Sol's group in the new study. "Our collaborators in Spain had developed a computational approach that integrated those epigenetic changes with changes in gene expression to produce critical TF combinations as an output, which we were in an ideal position to test."The team used their computational "Integrative gene Regulatory Network model" (IRENE) approach to reconstruct the GRN controlling iPSCs, and then focused on three target cell types with clinical relevance to experimentally validate TF combinations prioritized by IRENE. To deliver TF combinations into iPSCs, they deployed a transposon-based genomic integration system that can integrate multiple copies of a gene encoding a TF into the genome, which allows all factors of a combination to be stably expressed. Transposons are DNA elements that can jump from one position of the genome to another, or in this case from an exogenously provided piece of DNA into the genome."Our research team composed of scientists from the LCSB and CIC bioGUNE has a long-standing expertise in developing computational methods to facilitate cell conversion. IRENE is an additional resource in our toolbox and one for which experimental validation has demonstrated it substantially increased efficiency in most tested cases," corresponding author Del Sol, who is Professor at LCSB and CIC bioGUNE. "Our fundamental research should ultimately benefit patients, and we are thrilled that IRENE could enhance the production of cell sources readily usable in therapeutic applications, such as cell transplantation and gene therapies."The researchers chose human mammary epithelial cells (HMECs) as a first cell type. Thus far HMECs are obtained from one tissue environment, dissociated, and transplanted to one where breast tissue has been resected. HMECs generated from patients' cells, via an intermediate iPSC stage, could provide a means for less invasive and more effective breast tissue regeneration. One of the combinations that was generated by IRENE enabled the team to convert 14% of iPSCs into differentiated HMECs in iPSC-specific culture media, showing that the provided TFs were sufficient to drive the conversion without help from additional factors.The team then turned their attention to melanocytes, which can provide a source of cells in cellular grafts to replace damaged skin. This time they performed the cell conversion in melanocyte destination medium to show that the selected TFs work under culture conditions optimized for the desired cell type. Two out of four combinations were able to increase the efficiency of melanocyte conversion by 900% compared to iPSCs grown in destination medium without the TFs. Finally, the researchers compared combinations of TFs prioritized by IRENE to generate natural killer (NK) cells with a state-of-the-art differentiation method based on cell culture conditions alone. Immune NK cells have been found to improve the treatment of leukemia. The researchers' approach outperformed the standard with five out of eight combinations increasing the differentiation of NK cells with critical markers by up to 250%."This novel computational approach could greatly facilitate a range of cell and tissue engineering efforts at the Wyss Institute and many other sites around the world. This advance should greatly expand our toolbox as we strive to develop new approaches in regenerative medicine to improve patients' lives," said Wyss Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at HMS and Boston Children's Hospital, and Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.
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Biology
| 2,021 |
March 12, 2021
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https://www.sciencedaily.com/releases/2021/03/210312121311.htm
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How protein essential for male fertility emerged
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Researchers have analysed, at unprecedented breadth and depth, the evolutionary history of how a protein -- which is essential for the fertility of male fruit flies and emerged from previously non-coding DNA became functional and took on a relatively stable structure.
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Proteins are the key component in all modern forms of life. Haemoglobin, for example, transports the oxygen in our blood; photosynthesis proteins in the leaves of plants convert sunlight into energy; and fungal enzymes help us to brew beer and bake bread. Researchers have long been examining the question of how proteins mutate or come into existence in the course of millennia. That completely new proteins -- and, with them, new properties -- can emerge practically out of nothing, was inconceivable for decades, in line with what the Greek philosopher Parmenides said: "Nothing can emerge from nothing" (ex nihilo nihil fit). Working with colleagues from the USA and Australia, researchers from the University of Münster (Germany) have now reconstructed how evolution forms the structure and function of a newly emerged protein in flies. This protein is essential for male fertility. The results have been published in the journal It had been assumed up to now that new proteins emerge from already existing proteins -- by a duplication of the underlying genes and by a series of small mutations in one or both gene copies. In the past ten years, however, a new understanding of protein evolution has come about: proteins can also develop from so-called non-coding DNA (deoxyribonucleic acid) -- in other words, from that part of the genetic material which does not normally produce proteins -- and can subsequently develop into functional cell components. This is surprising for several reasons: for many years, it had been assumed that, in order to be functional, proteins had to take on a highly developed geometrical form (a "3D structure"). It had further been assumed that such a form could not develop from a gene emerging at random, but would require a complex combination of amino-acids enabling this protein to exist in its functional form.Despite decades of trying, researchers worldwide have not yet succeeded in constructing proteins with the desired 3D structures and functions, which means that the "code" for the formation of a functioning protein is essentially unknown. While this task remains a puzzle for scientists, nature has proven to be more adept at the formation of new proteins. A team of researchers headed by Prof. Erich Bornberg-Bauer, from the Institute of Evolution and Biodiversity at the University of Münster, discovered, by comparing the newly analysed genomes in numerous organisms, that species not only differ through duplicated protein-coding genes adapted in the course of evolution. In addition, proteins are constantly being formed de novo ("anew") -- i.e. without any related precursor protein going through a selection process.The vast majority of these de novo proteins are useless, or even slightly deleterious, as they can interfere with existing proteins in the cell. Such new proteins are quickly lost again after several generations, as organisms carrying the new gene encoding the protein have impaired survival or reproduction. However, a select few de novo proteins prove to have beneficial functions. These proteins integrate into the molecular components of cells and eventually, after millions of years of minor modifications, become indispensable. There are some important questions which many reearchers wonder about in this context: How do such novel proteins look like upon birth? How do they change, and which functions do they assume as the "new kids on the block"? Spearheaded by Prof. Bornberg-Bauer's group in Münster, an international team of researchers has answered this question in much detail for "Goddard," a fruit fly protein that is essential for male fertility.The research proceeded on three related fronts across three continents. At the College of the Holy Cross in Massachusetts, USA, Dr. Prajal Patel and Prof. Geoff Findlay used CRISPR/Cas9 genome editing to show that male flies that do not produce Goddard are sterile, but otherwise healthy. Meanwhile, Dr. Andreas Lange and PhD student Brennen Heames of Prof. Bornberg-Bauer's group used biochemical techniques to predict the shape of the novel protein in present-day flies. They then used evolutionary methods to reconstruct the likely structure of Goddard ~50 million years ago when the protein first arose. What they found was quite a surprise: "The ancestral Goddard protein looked already very much like the ones which exist in fly species today" Erich Bornberg-Bauer explains. "Right from the beginning, Goddard contained some structural elements, so called alpha-helices, which are believed to be essential for most proteins." To confirm these findings, the scene shifted to the Australian National University in Canberra, where Dr. Adam Damry and Prof. Colin Jackson used intensive, computational simulations to verify the predicted shape of the Goddard protein. They validated the structural analysis of Dr. Lange and showed that Goddard, in spite of its young age, is already quite stable -- though not quite as stable as most fly proteins that are believed to have existed for longer, perhaps hundreds of millions of years.The results match up with several other current studies, which have shown that the genomic elements from which protein-coding genes emerge are activated frequently -- tens of thousands of times in each individual. These fragments are then "sorted" through the process of evolutionary selection. The ones which are useless or harmful -- the vast majority -- are quickly discarded. But those which are neutral, or are slightly beneficial, can be optimized over millions of years and changed into something useful.
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Biology
| 2,021 |
March 11, 2021
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https://www.sciencedaily.com/releases/2021/03/210311152817.htm
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Researchers reveal 3D structure responsible for gene expression
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For the first time ever, a Northwestern University-led research team has peered inside a human cell to view a multi-subunit machine responsible for regulating gene expression.
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Called the Mediator-bound pre-initiation complex (Med-PIC), the structure is a key player in determining which genes are activated and which are suppressed. Mediator helps position the rest of the complex -- RNA polymerase II and the general transcription factors -- at the beginning of genes that the cell wants to transcribe.The researchers visualized the complex in high resolution using cryogenic electron microscopy (cryo-EM), enabling them to better understand how it works. Because this complex plays a role in many diseases, including cancer, neurodegenerative diseases, HIV and metabolic disorders, researchers' new understanding of its structure could potentially be leveraged to treat disease."This machine is so basic to every branch of modern molecular biology in the context of gene expression," said Northwestern's Yuan He, senior author of the study. "Visualizing the structure in 3D will help us answer basic biological questions, such as how DNA is copied to RNA.""Seeing this structure allows us to understand how it works," added Ryan Abdella, the paper's co-first author. "It's like taking apart a common household appliance to see how everything fits together. Now we can understand how the proteins in the complex come together to perform their function."The study will be published March 11 in the journal He is an assistant professor of molecular biosciences in Northwestern's Weinberg College of Arts and Sciences. Abdella and Anna Talyzina, both graduate students in the He lab, are co-first authors of the paper.Famed biochemist Roger Kornberg discovered the Mediator complex in yeast in 1990, a project for which he won the 2006 Nobel Prize in Chemistry. But Mediator comprises a daunting 26 subunits -- 56 total when combined with the pre-initiation complex -- it's taken researchers until now to obtain high-resolution images of the human version."It's a technically quite challenging project," He said. "These complexes are scarce. It takes hundreds of liters of human cells, which are very hard to grow, to obtain small amounts of the protein complexes."A breakthrough came when He's team put the sample on a single layer of graphene oxide. By providing this support, the graphene sheet minimized the amount of sample needed for imaging. And compared to the typical support used -- amorphous carbon -- graphene improved the signal-to-noise ratio for higher-resolution imaging.After preparing the sample, the team used cryo-EM, a relatively new technique that won the 2017 Nobel Prize in Chemistry, to determine the 3D shape of proteins, which are often thousands of times smaller than the width of a human hair. The technique works by blasting a stream of electrons at a flash-frozen sample to take many 2D images.For this study, He's team captured hundreds of thousands of images of the Med-PIC complex. They then used computational methods to reconstruct a 3D image."Solving this complex was like assembling a puzzle," Talyzina said. "Some of those subunits were already known from other experiments, but we had no idea how the pieces assembled together or interacted with each other. With our final structure, we were finally able to see this whole complex and understand its organization."The resulting image shows the Med-PIC complex as a flat, elongated structure, measuring 45 nanometers in length. The researchers also were surprised to discover that the Mediator moves relative to the rest of the complex, binding to RNA polymerase II at a hinge point."Mediator moves like a pendulum," Abdella said. "Next, we want to understand what this flexibility means. We think it might have an impact on the activity of a key enzyme within the complex."The paper was supported by Northwestern's Chemistry of Life Sciences Institute, the Chicago Biomedical Consortium with support from the Searle Funds at The Chicago Community Trust, the American Cancer Society (award number IRG-15-173-21), the H Foundation (award number U54-CA193419) and the National Institutes of Health (award numbers R01-GM135651 and P01-CA092584).
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Biology
| 2,021 |
March 11, 2021
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https://www.sciencedaily.com/releases/2021/03/210311152804.htm
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Researchers test using environmental DNA to monitor grass pollen levels
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Grass pollen is a major outdoor allergen, responsible for widespread and costly respiratory conditions including allergic asthma and hay fever (rhinitis). Now, researchers re-porting in the journal
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"These findings represent a first step towards changing and improving our understanding of the complex relationships between pollen and population health," said Benedict Wheeler of the University of Exeter, UK. "If confirmed and refined, this research could help to improve pollen forecasts and warnings in the future, supporting individual and community-level prevention strategies and management of healthcare system responses."Wheeler and colleagues including Francis Rowney, University of Exeter, Georgina Brennan and Simon Creer, Bangor University, and Nicholas Osborne, The University of Queensland, Australia, note that over 400 million people around the world suffer from allergic rhinitis, commonly known as hay fever. Another 300 million have asthma. While grass pollen is known to be a common allergen, it hasn't been clear which of more than 11,000 grass species cause the most trouble for human health."Previous investigations of airborne grass pollen have been constrained by the way in which concentrations of grass pollen in the atmosphere are typically monitored: using optical microscopy to identify and count pollen grains collected from aerial samplers," Rowney said. "Since grass pollen grains from different taxa are generally not distinguishable using optical microscopy, most epidemiology has focused on population exposure to total grass pollen concentrations and how they associate with allergy-related health outcomes."In the new study, the researchers took a different approach, using environmental DNA (eDNA) sampling and quantitative PCR (qPCR) to measure the relative abundance of airborne pollen from common grass species over two seasons. Next, they looked for pat-terns between the prevalence of particular types of grass pollen and the incidence of severe asthma exacerbations as well as prescribing rates for allergy medicines.The data showed substantial variability in the relative abundances of airborne pollen from different grass species, both across the UK and over the course of the grass pollen season. The analyses also show that pollen from certain grasses may have a disproportionate influence on relevant health outcomes at the population level, as indicated by the number of prescriptions written for allergy medications as well as hospital admissions for asthma."We've known for a long time that grass pollen has important implications for health at population scales," Brennan said, "but, we didn't really know very much about different types of grass pollen. This research suggests that there may be important differences in the public health impacts of pollen from different grasses. It suggests we should work to find out more and to consider whether the way we manage pollen health risks -- such as warnings in the weather forecast -- can be improved."The researchers say they'd like to have broader spatial coverage and monitoring over a greater number of pollen seasons to get even more information about the relative impacts of individual grass species. Ultimately, they write, "they envisage the development of a global network of autonomous aerial samplers, able to discriminate and quan-tify airborne pollen, allowing sensitive biomonitoring of important aeroallergens at high spatial and temporal resolutions."
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Biology
| 2,021 |
March 11, 2021
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https://www.sciencedaily.com/releases/2021/03/210311152746.htm
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AI analysis of how bacteria attack could help predict infection outcomes
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Insights into how bacterial proteins work as a network to take control of our cells could help predict infection outcomes and develop new treatments.
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Much like a hacker seizes control of a company's software to cause chaos, disease-causing bacteria, such as E. coli and Salmonella, use miniature molecular syringes to inject their own chaos-inducing agents (called effectors) into the cells that keep our guts healthy.These effectors take control of our cells, overwhelming their defences and blocking key immune responses, allowing the infection to take hold.Previously, studies have investigated single effectors. Now a team led by scientists at Imperial College London and The Institute of Cancer Research, London, and including researchers from the UK, Spain and Israel, has studied whole sets of effectors in different combinations.The study, published today in The results show how effectors work together as a network, allowing them to colonise their hosts even if some effectors are removed. The investigation also revealed how the host's immune system can bypass the obstacles the effectors create, triggering complementary immune responses.The researchers suggest that knowing how the makeup of effector networks influences the ability of infections to take hold could help design interventions that disrupt their effects.Study lead Professor Gad Frankel, from the Department of Life Sciences at Imperial, said: "The data represent a breakthrough in our understanding of the mechanisms of bacterial infections and host responses. Our results show that the injected effectors are not working individually, but instead as a pack."We found there is an inherent strength and flexibility to the network, which ensures that if one or several components don't work, the infection can go on. Importantly, this work has also revealed that our cells have a built-in firewall, which means that we can deal with the hacker's corruptive networks and mount effective immune responses that can clear the infection."Study co-lead Professor Jyoti Choudhary, from the Functional Proteomics Lab at The Institute of Cancer Research, London, said: "Our study shows that we can predict how a cell will respond when attacked by different combinations of bacterial effector proteins. The research will help us to better understand how cells, the immune system and bacteria interact, and we can apply this knowledge to diseases like cancer and inflammatory bowel disease where bacteria in the gut play an important role."We hope, through further study, to build on this knowledge and work out exactly how these effector proteins function, and how they work together to disrupt host cells. In future, this enhanced understanding could lead to the development of new treatments."During their experiments, the team were able to remove different effectors when infecting mice with the pathogen, tracking how successful each infection was. This showed that the effector network produced by the pathogen could be reduced by up to 60 percent and still produce a successful infection.The team collected data on more than 100 different synthetic combinations of the 31 effectors, which Professor Alfonso Rodríguez-Patón and Elena Núñez-Berrueco at the Universidad Politécnica de Madrid used to build an artificial intelligence (AI) algorithm.The AI model was able to predict the outcomes of infection with Citrobacter rodentium expressing different effector networks, which were tested with experiments in mice. As it is impossible to test in the lab all the possible networks that 31 effectors can form, employing an AI model is the only practical approach to studying biological systems of this complexity.Co-first author Dr David Ruano-Gallego from the Department of Life Sciences at Imperial, said: "The AI allows us to focus on creating the most relevant combinations of effectors and learn from them how bacteria are counteracted by our immune system. These combinations would not be obvious from our experimental results alone, opening up the possibility of using AI to predict infection outcomes."Co-first author Dr Julia Sánchez-Garrido, from the Department of Life Sciences at Imperial, added: "Our results also mean that in the future, using AI and synthetic biology, we should be able to work out which cell functions are essential during infection, enabling us to find ways to fight the infection not by killing the pathogen with antibiotics, but instead by changing and improving our natural defence responses to infection."This project was supported by The Wellcome Trust.
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Biology
| 2,021 |
March 11, 2021
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https://www.sciencedaily.com/releases/2021/03/210311123452.htm
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Female snowy plovers are no bad mothers
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In snowy plovers, females have overcome traditional family stereotypes. They often abandon the family to begin a clutch with a new partner whereas the males continue to care for their young until they are independent. An international team led by scientists from the Max Planck Institute for Ornithology in Seewiesen, Germany, has now investigated the decision-making process that determines the duration of parental care by females. They found that offspring desertion often occurs either under poor environmental conditions, when chicks die despite being cared for by both parents, or when chicks have a good chance of survival even without the female.
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It seems cruel and somewhat senseless when bird parents desert their vulnerable young to mate again. However, theoretical and experimental studies show that this is often beneficial for the parents, even if they have already invested energy and time in the brood. After all, re-mating after deserting an unsuccessful brood can improve their overall reproductive success.A team of scientists led by researchers of the Max Planck Institute for Ornithology in Seewiesen, Germany, has now investigated in more detail which factors cause female parents to desert their broods. They studied snowy plovers (Charadrius nivosus) that often breed on salt flats or at brackish inland lakes. This barren environment puts great pressure on parents, as temporary salt ponds often dry up and many chicks die of thirst or starvation. "Males have survival advantages at all life stages," says Clemens Küpper, research group leader at Seewiesen. "Although equal numbers of females and males hatch from eggs, adult population therefore show a surplus of males."As females are less abundant in the population, they have an advantage in finding mates. Therefore, the parental roles are reversed in this species: males care for the young until they are fledged, while females often leave the family and pair up with another partner for a new breeding attempt.The research team analyzed the parental behaviour and survival of more than 260 broods over a seven-year period. Of these, more than 70 percent were deserted by the females. Although one parent is often sufficient for parental care, as the chicks are precocial and find the food on their own. However, the study shows that chicks from an abandoned brood actually survive less often than in other broods where females stay longer.So, are snowy plover mothers making the wrong decisions here? The scientists found that broods were more likely to be deserted at the beginning of the breeding season. This makes sense because there are more opportunities for the female to mate again. The current number of chicks is also important: females are especially likely to abandon broods on days when a chick dies. "This suggests that females who initially decided to care, suddenly abandon their broods when their chicks start to die," says Krisztina Kupán, first author of the study. These females try then to rescue their reproductive success by starting over with a new male.The researchers concluded that there are two main reasons for females to desert their brood and remate. First, the chicks have a good chance of survival with their fathers alone, so the female can leave and continue to reproduce. Second, the chicks begin to die despite both parents are caring for the brood. This means that conditions for chick rearing are so poor that additional parental care does little for the chick survival. Instead, the female tries to increase her reproductive success frequently starting to breed elsewhere. "Females are flexible and make sensible decisions," says Krisztina Kupán. "They are sensitive to environmental conditions and stay with the chicks if they can contribute substantially to their survival."
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Biology
| 2,021 |
March 11, 2021
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https://www.sciencedaily.com/releases/2021/03/210311085327.htm
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'One step closer to unlocking mysteries of the bio/nano interface'
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An interdisciplinary research team at Lehigh University has unraveled how functional biomaterials rely upon an interfacial protein layer to transmit signals to living cells concerning their adhesion, proliferation and overall development.
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According to an article published today in In the article, "Nanostructure of bioactive glass affects bone cell attachment via protein restructuring upon adsorption," the Lehigh team demonstrates that living cells respond to interfacial layer characteristics that arise as a consequence of micro- and nano-scale structures engineered into a substrate material. These infinitesimally-tiny structures have an enormous impact upon the nature of the proteins and how they restructure themselves and electrostatically interact with the material, which in turn influences the manner in which cells attach to the substrate and develop over time."There are others who have studied the interfacial protein layer," says Himanshu Jain, the T.L. Diamond Distinguished Chair in Engineering and Applied Science and Professor of Materials Science and Engineering at Lehigh, who also serves as director of Lehigh's Institute for Functional Materials and Devices (I-FMD). "But this work showed directly and unambiguously for the first time how some specific nanoscale features of the substrate can impact the secondary molecular structure of the proteinated interface that in turn affects the response of the cells that are thousands of times larger."Joining Professor Jain in guiding this research is Matthias Falk, a Professor of Cell Biology with Lehigh's College of Arts and Sciences. The team is rounded out by two doctoral students jointly supervised by Falk and Jain -- Dr. Tia Kowal, who received PhD in Biological Sciences and is now a postdoctoral researcher at Stanford Medicine, and lead author Dr. Ukrit Thamma, who completed his doctorate in Materials Science and Engineering and is now a lecturer at King Mongkut's University of Technology in Bangkok, Thailand."Lehigh is increasingly recognized as a place where interdisciplinary team science is taking root and flourishing," says Jain. "The creation and mission of Lehigh's Interdisciplinary Research Institutes is a strategic expression of this notion -- and this project is an expression of that notion in action. And the crucial role that our students play, with support from a broad faculty team, speaks for itself."
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Biology
| 2,021 |
March 10, 2021
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https://www.sciencedaily.com/releases/2021/03/210310122535.htm
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Microbes may hold the key for treating neurological disorders
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When we think about the causes of neurological disorders and how to treat them, we think about targeting the brain. But is this the best or only way? Maybe not. New research by scientists at Baylor College of Medicine suggests that microbes in the gut may contribute to certain symptoms associated with complex neurological disorders. The findings, published in the journal
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Dr. Mauro Costa-Mattioli, professor and Cullen Foundation Endowed Chair in neuroscience and director of the Memory and Brain Research Center at Baylor, discovered with his team that different abnormal behaviors are interdependently regulated by the host's genes and microbiome. Specifically, the team found that in mouse models for neurodevelopmental disorders, hyperactivity is controlled by the host's genetics, whereas social behavior deficits are mediated by the gut microbiome.More importantly from a therapeutic perspective, they found that treatment with a specific microbe that promotes the production of compounds in the biopterin family in the gut or treatment with a metabolically active biopterin molecule improved the social behavior but not motor activity."We are the bearers of both host and microbial genes. While most of the focus has traditionally been in host genes, the gut microbiome, the community of microorganisms that live within us, is another important source of genetic information," Costa-Mattioli said.The work by Costa-Mattioli's group offers a different way of thinking about neurological disorders in which both human and microbial genes interact with each other and contribute to the condition. Their findings also suggest that effective treatments would likely need to be directed at both the brain and the gut to fully address all symptoms. Additionally, they open the possibility that other complex conditions, such as cancer, diabetes, viral infection or other neurological disorders may have a microbiome component."It's very difficult to study these complex interactions in humans, so in this study, we worked with a mouse model for neurodevelopmental disorders in which the animals lacked both copies of the Cntnap2 gene (Cntnap2-/- mice)," said co-first author Sean Dooling, a Ph.D. candidate in molecular and human genetics in the Costa-Mattioli lab. "These mice presented with social deficits and hyperactivity, similar to those observed in autism spectrum disorders (ASD). In addition, these mice, like many people with ASD, also had changes in the bacteria that make up their microbiome compared to the mice without the genetic change."Further experiments showed that modulating the gut microbiome improved the social behavior in the mutant mice, but did not alter their hyperactivity, indicating that the changes in the microbiome selectively contribute to the animals' social behavior."We were able to separate the contribution of the microbiome and that of the animal's genetic mutation on the behavioral changes," Dooling said. "This shows that the gut microbiome shouldn't be ignored as an important variable in studying health and disease."Equipped with this knowledge, the researchers dug deeper into the mechanism underlying the microbiome's effect on the animal's social deficits. Based on their previous work, the investigators treated the mice with the probiotic microbe, "We found that However, the bigger surprise came when the investigators administered to the asocial mice a metabolite or compound they found was increased in the host's gut by "This provides us with at least two possible ways to modulate the brain from the gut, with the bacteria or the bacteria-induced metabolite," said Buffington.Could this work inspire new breakthroughs in treating neurological disorders? While it is still too early to say for sure, the investigators are particularly excited about the translational implications of their findings. "Our work strengthens an emerging concept of a new frontier for the development of safe and effective therapeutics that target the gut microbiome with selective probiotic strains of bacteria or bacteria-inspired pharmaceuticals," Buffington said."As we learn more about how these bacteria work, we will be able to more precisely and effectively leverage their power to help treat the brain and perhaps more," Dooling added.This research represents important step forward in the field as many disorders, especially those affecting the brain, remain very difficult to treat."Despite all the scientific advances and the promise of gene manipulation, it is still difficult to modulate human genes to treat diseases, but modulating our microbiome may be an interesting, noninvasive alternative," said Costa-Mattioli. Indeed, "In my wildest dreams, I could have never imagined that microbes in the gut could modulate behavior and brain function. To think now that microbial-based strategies may be a viable way to treat neurological dysfunction, is still wild, but very exciting."
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Biology
| 2,021 |
March 10, 2021
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https://www.sciencedaily.com/releases/2021/03/210310122521.htm
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Placenta is a dumping ground for genetic defects
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In the first study of the genomic architecture of the human placenta, scientists at the Wellcome Sanger Institute, the University of Cambridge and their collaborators have confirmed that the normal structure of the placenta is different to any other human organ and resembles that of a tumour, harbouring many of the same genetic mutations found in childhood cancers.
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The study, published today (10 March 2021) in In the earliest days of pregnancy, the fertilized egg implants into the wall of the uterus and begins dividing from one cell into many. Cells differentiate into various types of cell and some of them will form the placenta. Around week ten of pregnancy, the placenta begins to access the mother's circulation, obtaining oxygen and nutrients for the fetus, removing waste products and regulating crucial hormones.It has long been known that the placenta is different from other human organs. In one to two per cent of pregnancies, some placental cells have a different number of chromosomes to cells in the fetus -- a genetic flaw that could be fatal to the fetus, but with which the placenta often functions reasonably normally.Despite this genetic robustness, problems with the placenta are a major cause of harm to the mother and unborn child, such as growth restriction or even stillbirths.This new study is the first high-resolution survey of the genomic architecture of the human placenta. Scientists at the Wellcome Sanger Institute and the University of Cambridge conducted whole genome sequencing of 86 biopsies and 106 microdissections from 42 placentas, with samples taken from different areas of each organ.The team discovered that each one of these biopsies was a genetically distinct 'clonal expansion' -- a cell population descended from a single common ancestor -- indicating a clear parallel between the formation of the human placenta and the development of a cancer.Analysis also identified specific patterns of mutation that are commonly found in childhood cancers, such as neuroblastoma and rhabdomyosarcoma, with an even higher number of these mutations in the placenta than in the cancers themselves.Professor Steve Charnock-Jones, a senior author of the study from the University of Cambridge, said: "Our study confirms for the first time that the placenta is organised differently to every other human organ, and in fact resembles a patchwork of tumours. The rates and patterns of genetic mutations were also incredibly high compared to other healthy human tissues."The team used phylogenetic analysis to retrace the evolution of cell lineages from the first cell divisions of the fertilised egg and found evidence to support the theory that the placenta tolerates major genetic flaws.In one biopsy, the researchers observed three copies of chromosome 10 in each cell, two from the mother and one from the father, instead of the usual one copy from each parent. But other biopsies from the same placenta and from the fetus carried two copies of chromosome 10, both from the mother. A chromosomal copy number error such as this in any other tissue would be a major genetic flaw.Professor Gordon Smith, a senior author of the study from the University of Cambridge, said: "It was fascinating to observe how such a serious genetic flaw as a chromosomal copy number error was ironed out by the baby but not by the placenta. This error would have been present in the fertilized egg. Yet derivative cell populations, and most importantly those that went on to form the child, had the correct number of copies of chromosome 10, whereas parts of the placenta failed to make this correction. The placenta also provided a clue that the baby had inherited both copies of the chromosome from one parent, which can itself be associated with problems."Now that the link between genetic aberrations in the placenta and birth outcomes has been established, further studies using larger sample sizes could help to uncover the causes of complications and diseases that arise during pregnancy.Dr Sam Behjati, a senior author of the study from the Wellcome Sanger Institute, said: "The placenta is akin to the 'wild west' of the human genome, completely different in its structure from any other healthy human tissue. It helps to protect us from flaws in our genetic code, but equally there remains a high burden of disease associated with the placenta. Our findings provide a rationale for studying the association between genetic aberrations in the placenta and birth outcomes at the high resolution we deployed and at massive scale."
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Biology
| 2,021 |
March 10, 2021
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https://www.sciencedaily.com/releases/2021/03/210310122516.htm
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The 3Rs of the genome: Reading, writing, and regulating
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A massive effort to map the precise binding locations of over 400 different kinds of proteins on the yeast genome has produced the most thorough and high-resolution map of chromosome architecture and gene regulation to date. The study reveals two distinct gene regulatory architectures, expanding the traditional model of gene regulation. So-called constitutive genes, those that perform basic 'housekeeping' functions and are nearly always active at low levels require only a basic set of regulatory controls; whereas those that that are activated by environmental signals, known as inducible genes, have a more specialized architecture. This finding in yeast could open the door to a better understanding of the regulatory architecture of the human genome.
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A paper describing the research by Penn State and Cornell University scientists appears March 10, 2021 in the journal "When I first learned about DNA, I was taught to think of the genome as a library containing every book ever written," said Matthew J. Rossi, research assistant professor at Penn State and the first author of the paper. "The genome is stored as part of a complex of DNA, RNA and proteins, called 'chromatin.' The interactions of the proteins and DNA regulate when and where genes are expressed to produce RNA (i.e. reading a book to learn or make something specific). But what I always wondered was with all that complexity, how do you find the right book when you need it? That is the question we are trying to answer in this study."How a cell chooses the right book depends on regulatory proteins and their interaction with DNA in chromatin, what can be referred to as the regulatory architecture of the genome. Yeast cells can respond to changes in their environment by altering this regulatory architecture to turn different genes on or off. In multicellular organisms, like humans, the difference between muscle cells, neurons, and every other cell type is determined by regulating the set of genes those cells are expressing. Deciphering the mechanisms that control this differential gene expression is therefore vital for understanding responses to the environment, organismal development, and evolution."Proteins need to be recruited and assembled at genes for them to be switched 'on,'" said B. Franklin Pugh, professor of molecular biology and genetics at Cornell University and a leader of the research project that was started when he was a professor at Penn State. "We've put together the most complete and high-resolution map of these proteins showing the locations that they bind to the yeast genome and revealing aspects of how they interact with each other to regulate gene expression."The team used a technique called ChIP-exo, a high-resolution version of ChIP-seq, to precisely and reproducibly map the binding locations of about 400 different proteins that interact with the yeast genome, some at a few locations and others at thousands of locations. In ChIP-exo, proteins are chemically cross-linked to the DNA inside living cells, thereby locking them into position. The chromosomes are then removed from cells and sheared into smaller pieces. Antibodies are used to capture specific proteins and the piece of DNA to which they are bound. The location of the protein-DNA interaction can then be found by sequencing the DNA attached to the protein and mapping the sequence back to the genome."In traditional ChIP-seq, the pieces of DNA attached to the proteins are still rather large and variable in length -- ranging anywhere from 100 to 500 base pairs beyond the actual protein binding site," said William K.M. Lai, assistant research professor at Cornell University and an author of the paper. "In ChIP-exo, we add an additional step of trimming the DNA with an enzyme called an exonuclease. This removes any excess DNA that is not protected by the cross-linked protein, allowing us to get a much more precise location for the binding event and to better visualize interactions among the proteins."The team performed over 1,200 individual ChIP-exo experiments producing billions of individual points of data. Analysis of the massive data leveraged Penn State's supercomputing clusters and required the development of several novel bioinformatic tools including a multifaceted computational workflow designed to identify patterns and reveal the organization of regulatory proteins in the yeast genome.The analysis, which is akin to picking out repeated types of features on the ground from hundreds of satellite images, revealed a surprisingly small number of unique protein assemblages that are used repeatedly across the yeast genome."The resolution and completeness of the data allowed us to identify 21 protein assemblages and also to identify the absence of specific regulatory control signals at housekeeping genes," said Shaun Mahony, assistant professor of biochemistry and molecular biology at Penn State and an author of the paper. "The computational methods that we've developed to analyze this data could serve as a jumping off point for further development for gene regulatory studies in more complex organisms."The traditional model of gene regulation involves proteins called 'transcription factors' that bind to specific DNA sequences to control the expression of a nearby gene. However, the researchers found that the majority of genes in yeast do not adhere to this model."We were surprised to find that housekeeping genes lacked a protein-DNA architecture that would allow specific transcription factors to bind, which is the hallmark of inducible genes," said Pugh. "These genes just seem to need a general set of proteins that allow access to the DNA and its transcription without much need for regulation. Whether or not this pattern holds up in multicellular organisms like humans is yet to be seen. It's a vastly more complex proposition, but like the sequencing of the yeast genome preceded the sequencing of the human genome, I'm sure we will eventually be able to see the regulatory architecture of the human genome at high resolution."This work was supported by the U.S. National Institutes of Health, the U.S. National Science Foundation, the Penn State Institute for Computational and Data Sciences, and Advanced CyberInfrastructure (ROAR) at Penn State.
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Biology
| 2,021 |
March 10, 2021
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https://www.sciencedaily.com/releases/2021/03/210310122502.htm
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Learning to help the adaptive immune system
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Scientists from the Institute of Industrial Science at The University of Tokyo demonstrated how the adaptive immune system uses a method similar to reinforcement learning to control the immune reaction to repeat infections. This work may lead to significant improvements in vaccine development and interventions to boost the immune system.
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In the human body, the adaptive immune system fights germs by remembering previous infections so it can respond quickly if the same pathogens return. This complex process depends on the cooperation of many cell types. Among these are T helpers, which assist by coordinating the response of other parts of the immune system -- called effector cells -- such as T killer and B cells. When an invading pathogen is detected, antigen presenting cells bring an identifying piece of the germ to a T cell. Certain T cells become activated and multiply many times in a process known as clonal selection. These clones then marshal a particular set of effector cells to battle the germs. Although the immune system has been extensively studied for decades, the "algorithm" used by T cells to optimize the response to threats is largely unknown.Now, scientists at The University of Tokyo have used an artificial intelligence framework to show that the number of T helpers act like the "hidden layer" between inputs and outputs in an artificial neural network commonly used in adaptive learning. In this case, the antigens presented are the inputs, and the responding effector immune cells are the output."Just as a neural network can be trained in machine learning, we believe the immune network can reflect associations between antigen patterns and the effective responses to pathogens," first author Takuya Kato says.The main difference between the adaptive immune system compared with computer machine learning is that only the number of T helper cells of each type can be varied, as opposed to the connection weights between nodes in each layer. The team used computer simulations to predict the distribution of T cell abundances after undergoing adaptive learning. These values were found to agree with experimental data based on the genetic sequencing of actual T helper cells."Our theoretical framework may completely change our understanding of adaptive immunity as a real learning system," says co-author Tetsuya Kobayashi. "This research can shed light on other complex adaptive systems, as well as ways to optimize vaccines to evoke a stronger immune response."
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Biology
| 2,021 |
March 9, 2021
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https://www.sciencedaily.com/releases/2021/03/210309185656.htm
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Researchers use silkworm silk to model muscle tissue
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Researchers at Utah State University are using silkworm silk to grow skeletal muscle cells, improving on traditional methods of cell culture and hopefully leading to better treatments for muscle atrophy.
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When scientists are trying to understand disease and test treatments, they generally grow model cells on a flat plastic surface (think petri dish). But growing cells on a two-dimensional surface has its limitations, primarily because muscle tissue is three-dimensional. Thus, USU researchers developed a three-dimensional cell culture surface by growing cells on silk fibers that are wrapped around an acrylic chassis. The team used both native and transgenic silkworm silk, the latter produced by silkworms modified with spider silk genes.Native silkworm silks have been used previously as three-dimensional cell culture models, but this is the first time that transgenic silkworm silk has been used for skeletal muscle modeling. Elizabeth Vargis, Matthew Clegg, and Jacob Barney of the Biological Engineering Department, and Justin Jones, Thomas Harris, and Xiaoli Zhang of the Biology Department published their findings in Cells grown on silkworm silk proved to more closely mimic human skeletal muscle than those grown on the usual plastic surface. These cells showed increased mechanical flexibility and increased expression of genes required for muscle contraction. Silkworm silk also encouraged proper muscle fiber alignment, a necessary element for robust muscle modeling.Skeletal muscle is responsible for moving the skeleton, stabilizing joints, and protecting internal organs. The deterioration of these muscles can happen for myriad reasons, and it can happen swiftly. For example, after only two weeks of immobilization, a person can lose almost a quarter of their quadricep muscle strength. Understanding how muscles can atrophy so quickly must begin at a cellular level, with cells grown to better represent reality."The overarching goal of my research is to build better in vitro models," said Elizabeth Vargis, associate professor of biological engineering at USU. "Researchers grow cells on these 2D platforms, which aren't super realistic, but give us a lot of information. Based on those results, they usually transition into an animal model, then they move onto clinical trials, where a vast majority of them fail. I'm trying to add to that first step by developing more realistic in vitro models of normal and diseased tissue."
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Biology
| 2,021 |
March 9, 2021
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https://www.sciencedaily.com/releases/2021/03/210309153848.htm
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Chemical signal in plants reduces growth processes in favor of defense
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Arabidopsis thaliana plants produce beta-cyclocitral when attacked by herbivores. This volatile signal inhibits the MEP pathway which is instrumental in plant growth processes, such as the production of pigments for photosynthesis. Since the MEP pathway is only found in plants and microorganisms, but not animals, knowledge of a signal molecule like beta-cyclocitral opens up new possibilities for the development of herbicides or antimicrobial agents that block this pathway.
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In a new study in PNAS, an international team of researchers including scientists from the Max Planck Institute for Chemical Ecology has shown that Arabidopsis thaliana plants produce beta-cyclocitral when attacked by herbivores and that this volatile signal inhibits the methylerythritol 4-phosphate (MEP) pathway. The MEP pathway is instrumental in plant growth processes, such as the production of pigments for photosynthesis. In addition to down-regulating the MEP pathway, beta-cyclocitral also increases plant defenses against herbivores. Since the MEP pathway is only found in plants and microorganisms, but not animals, knowledge of a signal molecule like beta-cyclocitral opens up new possibilities for the development of herbicides or antimicrobial agents that block this pathway.Researchers have long known that plants have limited resources that they can invest in defense against enemies or in growth and reproduction, depending on their environmental conditions. Many studies have already shown that plants increase their defenses when attacked by insects producing, for example, toxins or inhibitors of digestive enzymes that harm their attackers. However, much less is known about how herbivore attack affects growth processes in the plant. "We wanted to investigate how herbivory might affect photosynthesis and the methylerythritol 4-phosphate (MEP) pathway, a pathway making metabolites for growth that is directly supplied from photosynthesis," says first author Sirsha Mitra, who had started working on this project at the Max Planck Institute and is now an assistant professor at Savitribai Phule Pune University in Pune, India.The MEP pathway has been a research topic at the Max Planck Institute for Chemical Ecology in Jena for several years "The MEP pathway makes the building blocks for plant isoprenoids or terpenoids, a very large family of plant metabolites involved in growth, defense and signaling," says Jonathan Gershenzon, the head of the Department of Biochemistry and one of the authors.The international research team, which also included partners from the Universitat Ramon Llull in Barcelona, Spain, the Technical University in Lyngby, Denmark, and the University of Toronto, Canada, demonstrated that plants of the thale cress Arabidopsis thaliana which were fed to caterpillars of the African cotton leafworm, a generalist feeder that attacks many different plant species, increased defenses while simultaneously reducing growth processes. Using a variety of techniques from molecular biology and analytical chemistry, as well as caterpillar bioassays, the scientists were able to show that a specific volatile compound, beta-cyclocitral, formed by cleavage of beta-carotene due to a reactive form of oxygen, was responsible for this shift of resources. While beta-cyclocitral acts as a chemical signal to increase defenses, it simultaneously decreases the formation of compounds in the MEP pathway by directly inhibiting the rate-controlling enzyme of this pathway. "Of particular importance to our study was the exposure of plants to isotopically labeled carbon dioxide (13CO2) instead of the dominant atmospheric carbon dioxide (12CO2). Carbon dioxide is easily introduced into the MEP pathway via photosynthesis. This allowed us to track how the metabolic flux in the MEP pathway changed when plants switched to a defensive mode after herbivore attack and beta-cyclocitral slowed down the MEP pathway," says Louwrance Wright, one of the lead authors who is now working in South Africa. Caterpillars feeding on plants treated with beta-cyclocitral exhibited decreased growth in comparison to caterpillars feeding on untreated plants. This is further evidence of the importance of this volatile signal for plant defense.When plants are attacked, they may have to stop growth processes in order to release sufficient resources for their defense. Beta-cyclocitral signaling is a mechanism that precisely controls this shift in resources. Beta-cyclocitral, or a more stable derivative, could therefore be applied to crops to stimulate defenses during a pest outbreak. "Since the MEP pathway is found in all plants and many microorganisms, but not in animals, it is of particular interest for the development of herbicides, as well as drugs with antimicrobial activity," says Jonathan Gershenzon, explaining the potential applications of this research. Further studies in India will now investigate whether beta-cyclocitral can increase insect resistance in crops, such as tomatoes, and whether it interacts with other already known defense signals.
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Biology
| 2,021 |
March 9, 2021
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https://www.sciencedaily.com/releases/2021/03/210309153825.htm
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Immune cell implicated in development of lung disease following viral infection
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Scientists at Washington University School of Medicine in St. Louis have implicated a type of immune cell in the development of chronic lung disease that sometimes is triggered following a respiratory viral infection. The evidence suggests that activation of this immune cell -- a type of guardian cell called a dendritic cell -- serves as an early switch that, when activated, sets in motion a chain of events that drives progressive lung diseases, including asthma and chronic obstructive pulmonary disease (COPD).
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The new study, published in The Studying mice with a respiratory viral infection that makes the animals prone to developing chronic lung disease, the researchers showed that these dendritic cells communicate with the lining of the airway in ways that cause the airway-lining cells to ramp up their growth and inflammatory signals. The inflammation causes airway-lining cells to grow beyond their normal boundaries and turn into cells that overproduce mucus and cause inflammation, which in turn causes cough and difficulty breathing."We're trying to understand how a viral infection that seems to be cleared by the body can nevertheless trigger chronic, progressive lung disease," said senior author Michael J. Holtzman, MD, the Selma and Herman Seldin Professor of Medicine. "Not everyone experiences this progression. We believe there's some switch that gets flipped, triggering the bad response. We're identifying that switch and ways to control it. This work tells us that this type of dendritic cell is sitting right at that switch point."Holtzman's past work had implicated the lining of the airway -- where the viral infection takes hold -- as the likely trigger for this process."But this study suggests that the cascade starts even further upstream," said Holtzman, also director of the Division of Pulmonary and Critical Care Medicine. "Dendritic cells are telling the cells lining the airway what to do. There's more work to be done, but this data tells us that the dendritic cells play an important role in getting the airway-lining cells onto the wrong path."Holtzman calls this dendritic cell a type of sentinel because its job is to detect an invading virus and trigger the body's initial immune response against the infection. The problem comes when the cell doesn't shut down properly after the threat has passed."Many people never develop chronic lung disease after a viral infection," Holtzman said. "But others have a genetic susceptibility to this type of disease. People who are susceptible to virus-triggered disease include patients with asthma, COPD, and viral infections such as COVID-19. It's really critical to look for ways to fix this disease response and prevent the problems that might occur after the virus has gone."In the meantime, Holtzman said, high levels of these dendritic cells and their products in the lungs of hospitalized patients could serve as a warning to doctors that such patients are likely to develop severe disease and should be provided with respiratory interventions and other supportive therapies that are precisely tailored to their disease process."Similarly, if this process is not underway, the patient might be more likely to avoid these types of long-term problems," Holtzman said. "We're pursuing this line of research to help improve prediction of severe lung disease after infection and to provide companion therapies that could prevent this switch from being flipped or flip it back to reverse the disease."This work was supported by the National Institute of Allergy and Infectious Diseases (NIAID), grant number R01 AI130591 and the National Heart, Lung, and Blood Institute (NHLBI), grant number R35 HL145242, both of the National Institutes of Health (NIH); the Cystic Fibrosis Foundation; and the Hardy Trust and Schaeffer Funds.
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Biology
| 2,021 |
March 9, 2021
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https://www.sciencedaily.com/releases/2021/03/210309114338.htm
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Citizen scientists help expose presence of invasive Asian bamboo longhorn beetle in Europe
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A worryingly high number of Asian bamboo longhorn beetles (
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In our globalised world, which has already become victim to climate change and biodiversity loss, non-native species present a further threat to our ecosystems. Thus, the rising accounts of newly recorded alien species are of serious concern to both scientists and (inter)national institutions. However, surveying non-native species remains limited to a small fraction of species: those known to be particularly invasive and harmful.One of the multitude of non-native species that are currently lacking efficient and coordinated surveying efforts is the Asian bamboo longhorn beetle (Back to our days, during a fieldwork practice for students at the University of Hamburg, held within the city because of the COVID-19 travelling restrictions, the team stumbled across a longhorn beetle, later identified by scientists as the Asian bamboo borer. Furthermore, it became clear that there were even more recent records published across different citizen science platforms, such as iNaturalist, iRecord and Waarneming.nl. Having taken the contacts of the citizen scientists from there, the researchers approached them to ask for additional collection details and images, which were readily provided. As a result, the researchers formally confirmed the presence of the Asian bamboo borer in Belgium and the Netherlands. In total, they reported thirteen new introductions of the species in Europe, which translates to a 42% increase of the records of the species for the continent."In light of the warming climate and a growing abundance of ornamental bamboo plants in Europe, the beetle might get permanently established. Not only could it become a garden pest, but it could also incur significant costs to the bamboo-processing industry," comments Dr Matthias Seidel, lead author of the study.Having realised the potential of citizen science for bridging the gaps in invasive species monitoring, the researchers now propose for specialised platforms to be established with the aim to familiarise non-professional scientists with non-native species of interest and provide them with more sophisticated reporting tools. The aim is to speed up the identification of important alien species by collating records of specific species of interest, which are flagged and regularly exported from other citizen science databases and platforms.
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Biology
| 2,021 |
March 9, 2021
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https://www.sciencedaily.com/releases/2021/03/210309114328.htm
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Plants as protein factories: Antioxidant boosts the yield of valuable biologics
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Producing high-value pharmaceutical proteins in plants -- sometimes called "molecular pharming" -- offers advantages over some other manufacturing methods, notably the low cost and ease of scaling up production to meet demand. But expressing large quantities of "foreign" proteins in plants can also sometimes lead to problems, such as dehydration and premature cell death in the leaves.
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Now a team led by Professor Kenji Miura of the University of Tsukuba has discovered that spraying leaves with high concentrations of the antioxidant ascorbic acid (vitamin C) can increase protein production three-fold or even more. They recently published their findings in The team worked with a close relative of tobacco, While some foreign proteins cause few problems for the plant cells, others can lead to side-effects that seem to be caused by an excess of damaging reactive oxygen species. Applying ascorbic acid as an antioxidant counteracts the harmful effects and allows substantially higher rates of protein production."We tested the method with several different types of proteins," says Professor Miura. "We used green fluorescent protein (a common tool in the lab) and two human proteins, called Cul1 and an F-box protein. Spraying the leaves with ascorbic acid made a surprisingly big difference, but only when we applied high concentrations of the antioxidant. It seems that ascorbic acid prevents cell death and also reduces the breakdown of the foreign proteins, so the yield is higher."The team went on to successfully produce both the heavy chain and light chain of an antibody protein. They showed that the chains produced in leaves assembled correctly into a functional antibody (comprising two heavy and two light chains), and ascorbic acid did not interfere with its immunological properties."We are delighted by our results," says Professor Miura. "As this method of spraying the leaves is so simple, we expect it can be widely adopted and should help to improve the production of many types of valuable proteins for research and medical applications."
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Biology
| 2,021 |
March 9, 2021
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https://www.sciencedaily.com/releases/2021/03/210309114325.htm
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X marks the spot: How genes on the sex chromosomes are controlled
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Because human females have two X chromosomes and males have one X and one Y, somatic cells have special mechanisms that keep expression levels of genes on the X chromosome the same between both sexes. This process is called dosage compensation and has been extensively studied in the fruit fly Drosophila. Now, researchers at the University of Tsukuba (UT) continued work with Drosophila to show that dosage compensation does not occur in the germ cells of male flies.
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In an article published in Genetic research in somatic cells has shown that expression of X-linked genes in male fruit flies is upregulated to reach equivalent levels to that of their female counterparts. A group of proteins, called the male-specific lethal (MSL) complex, is responsible for carrying out this role. These findings made the UT group interested in if this mechanism also occurs in the male germ cells. Distinct molecular events occur in the PGCs during embryonic development between male and female fruit flies. Because results shown in earlier publications did not align, the researchers chose to address their main question differently."The MSL complex leaves a signature mark, called acetylation, on a specific amino acid of the histone H4 protein of the X chromosome," says Professor Satoru Kobayashi, senior author of the study. "The acetyl group being added tells the cell to express the X-linked genes at a higher level, which results in dosage compensation."To address their questions, the researchers used a process called transcriptome analysis to compare gene expression levels between male and female fruit fly PGCs. They also examined the histone H4 protein to determine if acetylation had occurred."We found that X-linked gene expression in male PGCs was about half that of female PGCs," describes Professor Kobayashi. "We also could not detect the acetylation signature of the MSL complex."The authors also determined that the main components of the MSL complex are only present in very low amounts in the fly PGCs. Interestingly, they then created transgenic flies that were engineered to express higher levels of the MSL complex proteins. Male PGCs in these flies showed greater activation of X-linked genes, as well as the acetylation signature.The researchers believe that the findings of this study have high biological significance, possibly suggesting that the absence of dosage compensation affects sex determination in Drosophila PGCs. This work provides novel insight that will be crucial for further investigation of embryo development and germ cell maturation.
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Biology
| 2,021 |
March 9, 2021
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https://www.sciencedaily.com/releases/2021/03/210309114323.htm
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Two species and a single name: 'Double identity' revealed in a venomous banana spider
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Spiders from the genus Phoneutria -- also known as banana spiders -- are considered aggressive and among the most venomous spiders in the world, with venom that has a neurotoxic action. These large nocturnal spiders usually inhabit environments disturbed by humans and are often found in banana plantations in the Neotropical region.
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One of these spiders, Everything started when N. Hazzi was examining specimens of banana spiders identified in the past by experts as To prove that these two "forms" were different species, the authors conducted fieldwork in the Amazon, Andes, and Central America, collecting specimens of these venomous spiders to explore if the genomic signal also suggests two species. They discovered that genetic differences separating these two forms were similar compared to the genetic differences separating other recognized species of banana spiders. Using morphological, genomic and geographic distribution data, the authors concluded that To obtain more distribution records for these species, the research team used the citizen science platform iNaturalist. Since the two species are among the few spiders that can be identified using only images, the platform turned out to be a very helpful tool. Data submitted by the iNaturalist community helped identify where the two species of Phoneutria are found. Curiously enough, for these two species, iNaturalist presented higher and more widely distributed records than the scientists' own database."To our knowledge, this is the first study that has used iNaturalist to gather occurrence records on venomous species to estimate distribution models," the researchers say.This is how the two spiders can be distinguished using only photographs: Interestingly, P. depilata has been mislabeled as The study provides detailed diagnoses with images to distinguish both species and distribution maps."This valuable information will help identify risk areas of accidental bites and assist health professionals in determining the identity of the species involved, especially for P. depilata. This is a significant discovery that will affect studies about toxicology, opening new opportunities to compare the venom composition and the effect of these two species," the authors conclude.
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Biology
| 2,021 |
March 9, 2021
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https://www.sciencedaily.com/releases/2021/03/210309114304.htm
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Scientists' discovery ends long-standing photosynthesis controversy
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Scientists have pinpointed the location of an essential enzyme in plant cells involved in photosynthesis, according to a study published today in
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The findings overturn conventional thinking about where the enzyme resides in plant cells and suggest a probable role in regulating energy processes as plants adapt from dark to light conditions.During photosynthesis, plants convert carbon into energy stores through 'electron transport', involving an enzyme called ferredoxin:NADP(H) oxidoreductase, or FNR.Plants can switch rapidly between two types of electron transport -- linear electron flow (LEF) and cyclic electron flow (CEF) in response to environmental conditions. The transfer of FNR between membrane structures in the chloroplast, where photosynthesis takes place, has been linked to this switch."Current dogma states that FNR carries out its function in the soluble compartment of the chloroplast, but evidence suggests that the activity of FNR increases when it is attached to an internal membrane," explains first author Manuela Kramer, a PhD student at the School of Biological and Chemical Sciences, Queen Mary University of London, UK. "We needed to find out precisely where FNR is located in the chloroplast, how it interacts with other proteins, and how this affects its activity in order to understand its role in switching between electron transport processes."The researchers used immuno-gold staining to pinpoint FNR in more than 300 chloroplasts from 18 individual Arabidopsis plants. The staining density of FNR was five times higher in the internal membrane system of the chloroplast (thylakoids) than in the soluble compartment (stroma), where it did not rise above background levels. This significantly higher labelling in the membrane proved that chloroplasts contain little soluble FNR, and confirmed for the first time where the enzyme is located.To understand more about FNR's location, the team generated plants where the enzyme is specifically bound to different proteins called 'tether proteins'. In Arabidopsis plants with decreased FNR content, they substituted three versions of FNR from maize, each with a different capacity for binding to the tether proteins TROL and Tic62. They found that rescue with maize FNR types that strongly bound to the Tic62 tether protein resulted in much higher density of gold FNR labelling in specific, lamellar membrane regions of the thylakoids. This suggests that the distribution of FNR throughout the chloroplast in plant cells is dependent on binding to the tether proteins.Finally, the team tested how FNR location affects electron transport, by comparing electron flow rates when plants were adapted to the dark with electron flow after their acclimatisation to light. In normal dark-adapted plants, a short exposure to light resulted in a switch to higher CEF activity. However, this was not seen in plants lacking strong interaction between FNR and the tether proteins, suggesting these plants lack the ability to switch on CEF. After light acclimatisation, both the wild-type and mutant plants had similar, decreased CEF activity, suggesting that the impact of FNR is related to light-dependent changes in the interactions between the enzyme and tether proteins."Our results show a link between the interaction of FNR with different proteins and the activity of an alternative photosynthetic electron transport pathway," concludes senior author Guy Hanke, Senior Lecturer in Plant Cell and Molecular Biology at the School of Biological and Chemical Sciences, Queen Mary University of London. "This supports a role for FNR location in regulating photosynthetic electron flow during the transition of plants from dark to light."
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Biology
| 2,021 |
March 9, 2021
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https://www.sciencedaily.com/releases/2021/03/210309113935.htm
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First the treats, then the tough stuff: A bacterial dinner plan for degrading algal blooms
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The annually occurring algal spring blooms play an important role for our climate, as they remove large amounts of carbon dioxide from the atmosphere. However, they are an ephemeral phenomenon. Most of the carbon is released into the water once the algae die. There, bacteria are already waiting to finish them off and consume the algal remains.
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Previous studies have shown that in these blooms, different algae can come out on top each year. However, within the bacteria subsequently degrading the algae, the same specialised groups prevail year after year. Apparently not the algae themselves but rather their components - above all chains of sugar molecules, the so-called polysaccharides - determine which bacteria will thrive. However, the details of the bacterial response to the algal feast are still not fully understood.Therefore, Ben Francis together with colleagues from the Max Planck Institute for Marine Microbiology, the University of Greifswald and the MARUM - Center for Marine Environmental Sciences at the University of Bremen now took a closer look at the bacterial insides. "We decided to center on a method called metaproteomics, which involves studying all proteins in a microbial community, in our case in the seawater", Francis explains. "In particular, we looked at transporter proteins, whose activity is critical in understanding the uptake of algal sugars into bacterial cells." In the metaproteomic data, the scientists saw that these transporter proteins distinctly changed over time. "We saw a pronounced shift in the abundance of transporter proteins predicted to be involved in uptake of different types of polysaccharide", Francis continues. "This indicates that the bacteria start off by mostly focusing on the 'easy to degrade' substrates, such as laminarin and starch. Then later on they move on and attack the 'harder to degrade' polymers composed of mannose and xylose."In other words, the bacteria take the easy road first, and only when the treats have been consumed, they aim for the chewy bits. When does this shift happen? Ben Francis and his colleagues see two possible triggers: It could either take place when competition for the easy food sources gets more intense, because the bacteria reproduce quickly in this lush environment and thus cell numbers increase. Or, alternatively, it depends more on the algae: Once the algal bloom breaks down and more algae have died, more of the hard substrates accumulate and they become a viable food source at that point.Even though the scientists from Bremen and Greifswald have studied the dynamics of algal and bacterial blooms in the North Sea for a long time, this temporal course was something that had so far gone undetected. "Combining state-of-the-art proteomics techniques with sample preparation methods, which specifically consider the high complexity of these very challenging samples, enabled us to establish one of the most comprehensive proteome data set with more than 20 000 protein groups. These data revealed that substrate specificities of transporter proteins change over time. These changes were not visible in the corresponding metagenomic data set used to investigate bacterial diversity", says Dörte Becher from the University of Greifswald. "It clearly shows that we need to dig very deep to understand the underlying ecological processes that govern marine carbon cycling." Quantifying transporter proteins could indeed become an important piece in solving the highly complex puzzle of marine carbon cycling."This detailed 'meta-proteogenomic' study combines the exceptional expertise of the University of Greifswald in the identification and quantification of proteins in complex environmental samples with our expertise in molecular microbial ecology", says Rudolf Amann, co-author on the study and director of the Max Planck Institute for Marine Microbiology in Bremen. "Our results indicate that the complex heterotrophic microbiome of the North Sea reacts to phytoplankton blooms not only in substrate-driven successions of recurrent bacterial species, but also in distinct changes of the expression of transporter proteins and degradative enzymes." Ultimately, it will be the combination of various methods that will advance our knowledge of the molecules, enzymatic reactions, and rates underlying the marine carbon cycle, which is a prerequisite for predicting and managing atmospheric carbon dioxide levels.
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Biology
| 2,021 |
March 9, 2021
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https://www.sciencedaily.com/releases/2021/03/210309091248.htm
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Full evolutionary journey of hospital superbug mapped
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Modern hospitals and antibiotic treatment alone did not create all the antibiotic resistant strains of bacteria we see today. Instead, selection pressures from before widespread use of antibiotics influenced some of them to develop, new research has discovered.
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By using analytical and sequencing technology that has only been developed in recent years, scientists from Wellcome Sanger Institute, University of Oslo and University of Cambridge have created an evolutionary timeline of the bacterium, Enterococcus faecalis, which is a common bacterium that can cause antibiotic resistant infections in hospitals.The results, published today (9th March 2021) in Enterococcus faecalis is a common bacterium that, in most people, is found in the intestinal tract and doesn't cause harm to the host. However, if someone is immunocompromised and this bacterium gets into the bloodstream, it can cause a serious infection.In hospitals, it is more common to find antibiotic resistant strains of E. faecalis and it was initially thought that the wide use of antibiotics and other antibacterial control measures in modern hospitals caused these strains to develop.In a new study, scientists from Wellcome Sanger Institute, University of Oslo and University of Cambridge analysed around 2000 samples of E. faecalis from 1936 to present day using blood stream isolates from patients and stool samples from animals and healthy humans.By sequencing the genome (including chromosomes and plasmids) using technology from Oxford Nanopore, the team mapped the evolutionary journey of the bacterium and created a timeline of when and where different strains developed, including those nowadays found to be resistant to antibiotics. They found that antibiotic resistant strains developed earlier than previously thought, before the widespread use of antibiotics, and therefore it was not antibiotic use alone that caused these to emerge.Researchers found that agricultural and early medical practices, such as the use of arsenic and mercury, influenced the evolution of some of the strains we see now. In addition to this, strains similar to the antibiotic resistant variants we see in hospitals now were found in wild birds. This shows how adaptable and flexible this species of bacterium is at evolving into new strains in the face of different adversity.Professor Jukka Corander, co-lead author and Associate Faculty member at the Wellcome Sanger Institute, said: "This is the first time we have been able to map out the full evolution of E. faecalis from samples up to 85 years old, which enables us to see the detailed effect of human lifestyles, agriculture and medicines on the development of different bacterial strains. Having the full timeline of evolutionary changes would not have been possible without analytical and sequencing techniques that can be found at the Sanger Institute."Dr Anna Pöntinen, co-lead author and post-doctoral fellow at University of Oslo, said: "Currently, when patients are admitted to hospital, they are swabbed for some antibiotic resistant bacteria and fungi and are isolated to ensure that infection rates are kept as low as possible. Thanks to this study, it is possible to scrutinize the diversity of E. faecalis and identify those that are more prone to spread within hospitals and thus could cause harm in immunocompromised people. We believe that it could be beneficial to also screen for E. faecalis on admission to hospitals."Professor Julian Parkhill, co-author and Professor in the Department of Veterinary Medicine at University of Cambridge, said: "This research has discovered that these hospital-associated strains of antibiotic resistant bacteria are much older than we previously thought, and has highlighted their incredible metabolic flexibility combined with numerous mechanisms enhancing their survival under harsh conditions that has allowed them to spread widely across the globe."
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Biology
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March 8, 2021
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https://www.sciencedaily.com/releases/2021/03/210308165234.htm
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A plant's place in history can predict susceptibility to pathogens
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Found around the world, powdery mildew is a fungal disease especially harmful to plants within the sunflower family. Like most invasive pathogens, powdery mildew is understudied and learning how it affects hosts can help growers make more informed decisions and protect their crops.
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Scientists at the University of Washington and the University of Central Florida inoculated 126 species of plants in the sunflower family with powdery mildew, growing 500 plants from seeds that were collected from the wild and provided from the USDA germplasm network. Through this large-scale study, they were able to measure the various plants' susceptibility to powdery mildew."We observed that the amount of disease present on a host can be dependent on where that host lies on the tree of life -- that is, the evolutionary history of a host can predict how susceptible that host is to disease," explained Michael Bradshaw, a plant pathologist involved with the study.They also measured common plant traits, such as biomass, trichome density, and chlorophyll content, and found that none of them were associated with the disease, underscoring the unimportance of commonly assessed host plant traits in powdery mildew severity and pointing further to the role that evolutionary history plays in plant susceptibility to disease."Any tools we can use to predict the severity of a disease can be valuable and improve management guidelines. Especially with fungal pathogens, where there is often a large lag time between the introduction of a pathogen and the formation of an epidemic," Bradshaw said. "I am hopeful that this research could spur future work and provide ideas and techniques for other researchers studying the evolution of disease."This research provides information on species of sunflower plants that are resistant to powdery mildew disease, which can be beneficial to breeding programs. Bradshaw also hopes that this study will inspire other studies that mine the genome of different plant species involved to potentially locate genes involved with resistance.
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Biology
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March 8, 2021
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https://www.sciencedaily.com/releases/2021/03/210308165231.htm
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Young white-tailed deer that disperse survive the same as those that stay home
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Juvenile white-tailed deer that strike out to find new home ranges -- despite facing more risks -- survive at about the same rate as those that stay home, according to a team of researchers who conducted the first mortality study of male and female dispersal where deer were exposed to threats such as hunting throughout their entire range.
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Dispersal occurs when a juvenile leaves the area where it was born and moves to a new location where the young animal establishes its adult home range, explained Duane Diefenbach, Penn State adjunct professor of wildlife ecology. The instinctual dispersal of young deer from the area where they were born to a new home range protects the species' gene pool from inbreeding with close relatives.Diefenbach's research group in the College of Agricultural Sciences has radio-collared hundreds of Pennsylvania deer over the last 20 years, monitoring their survival, movement and behavior. Earlier research done by his lab, in collaboration with the Pennsylvania Game Commission, revealed that about three of every four young, male white-tailed deer disperse, with yearling female dispersal rates much lower.Dispersal distances depend on forested cover, Diefenbach and colleagues demonstrated in previous research. But on average in Pennsylvania, males travel more than three miles, typically in direct, straight-line fashion; females that disperse often seemingly wander around before settling down an average of about nine miles from where they started."We wanted to know how risky dispersal is," said lead researcher Eric Long, now a professor of biology at Seattle Pacific University, who was a doctoral degree student at Penn State advised by Diefenbach when early stages of the research unfolded. He was surprised to find no detectable increase in death among dispersing deer."We expected to find that dispersal results in added mortality because deer are traveling across unfamiliar territory and are more likely to encounter predators or vehicles," Long said. "Going into this research, I expected to have a lot of our dispersers killed by vehicles as they were making the movement. We were surprised at how effective deer are at dispersing, especially when they have to deal with relatively modern risks like roads and hunting."For this study, researchers captured 398 juvenile male and 276 juvenile female white-tailed deer and compared survival rates of dispersers and nondispersers.Over three years, 381 males were equipped with very high frequency -- or VHF -- radio-transmitters and were located with telemetry at least weekly; 17 were equipped with global positioning system, or GPS, radio-transmitters that recorded positions at least twice daily. Over six years, 245 females were equipped with VHF transmitters and located at least weekly; 32 were equipped with GPS transmitters that recorded position at least daily.Juvenile deer were captured in the winter through early spring. At the time of capture, they were seven to 10 months old. For both male and female white-tailed deer, natal dispersal prior to 11 months of age is rare, Long noted, so capture between December and April decreased the likelihood of capturing juveniles that had already dispersed.Results of the research, recently published in So, why do dispersing juvenile deer fare as well as nondispersers despite facing more risk? Researchers are not sure, but Long suspects that deer with the predisposition to be more adventurous might have a genetic makeup that helps them to avoid threats. Also, he said, there is some evidence to suggest that yearlings in better condition, with bigger bodies, are more likely to disperse than deer in poorer condition."It may be that only those deer that are up to the challenge of dispersal even try it," he said. "Bucks, which are more likely to disperse, seem much more efficient at dispersal than females. They don't mess around and wander all over the place like does -- and that likely decreases their risk."
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Biology
| 2,021 |
March 8, 2021
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https://www.sciencedaily.com/releases/2021/03/210308165229.htm
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Research pinpoints unique drug target in antibiotic resistant bacteria
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Researchers have identified a critical mechanism that allows deadly bacteria to gain resistance to antibiotics.
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The findings offer a potential new drug target in the search for effective new antibiotics as we face the growing threat of antimicrobial resistance (AMR) and infections caused by bacterial pathogens.The study investigated quinolone antibiotics which are used to treat a range of bacterial infections, including TB (tuberculosis). Quinolones work by inhibiting bacterial enzymes, gyrase and topoisomerase IV, thereby preventing DNA replication and RNA synthesis essential to growth.They are highly-successful antimicrobial agents widely used in current medicine, however bacterial resistance to them and other treatments is a serious problem.Previous studies had identified one resistance mechanism caused by the production of pentapeptide repeat proteins (PRPs), a family of molecules that also act as DNA gyrase inhibitors.One of these, called MfpA, confers quinolone resistance to Mycobacterium tuberculosis, the causative agent of TB.In this study John Innes Centre researchers in the group of Professor Tony Maxwell set out to discover how PRPs such as MfpA, work at the molecular level.They purified MfpA from Mycobacterium smegmatis, a close relative of M. tuberculosis, and showed that it can inhibit the supercoiling reaction of DNA gyrase, the target of quinolones in TB causing mycobacteria.Further investigations showed that MfpA can prevent poisoning of gyrase by quinolones, thus protecting the bacterial host cell from the antibiotic.Using X-ray crystallography, the researchers showed that MfpA binds to the ATPase domain of gyrase, and that this explains its ability to both inhibit the supercoiling reaction and prevent quinolone poisoning."We did not expect the exact mechanism of MfpA to be the prevention of DNA binding to the gyrase ATPase domain; this is a unique mode of action," said Professor Tony Maxwell, corresponding author of the study."We believe this understanding will help drive new ideas for antibiotic development among academics and researchers in the pharma industry," he added.Further investigative work will involve molecular modelling based on the MfpA-gyrase structure to design small molecules that could mimic this interaction and offer more insights into how it works.
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Biology
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March 8, 2021
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https://www.sciencedaily.com/releases/2021/03/210308152514.htm
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Basic mechanisms that regulate HIV expression
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Despite the positive advances that anti-human immunodeficiency virus (HIV) therapy, commonly called anti-retroviral therapy (ART) or highly active antiretroviral therapy (HAART), has had on the life expectancy of HIV-positive people, finding a cure for HIV or acquired immunodeficiency syndrome (AIDS) has remained elusive.
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"One of the major challenges in curing HIV is that there is a persistent latent reservoir of virus that is not targeted by current antiretroviral treatments and is hidden from immune cells. When treatment is interrupted, this reservoir of the virus allows the HIV to rapidly rebound," explained corresponding author Andrew J. Henderson, PhD, professor of medicine and microbiology at Boston University School of Medicine.In an effort to identify cellular pathways that influence the establishment, maintenance and reversal of HIV persistence, the researchers conducted studies with yeast to screen a large library of human factors for binding to HIV deoxyribonucleic acid (DNA) sequences responsible for virus' expression. As a result, they identified several factors as potential regulators and confirmed that a subset of factors did control HIV in infected cells by increasing and decreasing levels of HIV expression."Our study identified novel transcription factors that influence HIV and provide an appreciation into cellular networks that influence activation and repression of different HIV strains," said Henderson.According to the researchers, understanding the mechanisms that control HIV expression will provide insight into HIV replication, latency and pathogenesis. "By gaining an understanding of the cellular pathways that control HIV, we might be able to target them and alter the behavior of this latent reservoir," Henderson added.These findings appear online in the journal Funding for this study was provided by the NIH, NIAID RO1 Al138960 to AJH, NIH NIGMS R35 GM128625 to JIFBand the Providence /Boston CFAR (P30A1042853) and amfAR Mathilde Krim Fellowship (109263 59 RKRL) to LMA.
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Biology
| 2,021 |
March 8, 2021
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https://www.sciencedaily.com/releases/2021/03/210308152449.htm
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Speeding treatment for urinary tract infections in children
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A study led by UT Southwestern and Children's Health researchers defines parameters for the number of white blood cells that must be present in children's urine at different concentrations to suggest a urinary tract infection (UTI). The findings, published recently in
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UTIs account for up to 7 percent of fevers in children up to 24 months old and are a common driver of hospital emergency room visits. However, says study leader Shahid Nadeem, M.D., assistant professor of pediatrics at UTSW as well as an emergency department physician and pediatric nephrologist at Children's Medical Center Dallas, these bacterial infections in infants and toddlers can be difficult to diagnose because their symptoms are similar to other fever-causing conditions.If a diagnosis is delayed, he explains, a UTI can develop into a serious infection that can cause lasting consequences. For example, UTI-related kidney scarring has been linked with hypertension and chronic kidney disease later in life.To diagnose a UTI, doctors must culture a urine sample and wait for it to grow telltale bacteria in a petri dish containing nutrients. However, says Nadeem, this process can take up to two days, delaying treatment. Consequently, he and other doctors typically rely on testing urine for a white blood cell-linked protein known as leukocyte esterase (LE), then confirm the presence of white blood cells -- a sign of immune activity -- by looking for them in urine under a microscope.In children, he adds, the number of white blood cells can be highly variable, with some of this variation potentially due to varying urine concentration. As such, it's been unknown what white blood cell number threshold should be used to begin treating a suspected UTI based on urine concentration.To determine these parameters, Nadeem and his colleagues searched medical records of children younger than 24 months old who were brought to the emergency department at Children's Medical Center between January 2012 and December 2017 with a suspected UTI and had both a urinalysis -- in which their urine concentration and the presence of LE and white blood cells were assessed -- and a urine culture. The search turned up 24,171 patients, 2,003 of whom were diagnosed with a UTI based on urine culture.Using their urine's specific gravity -- the density of urine compared with water, a measurement that serves as a surrogate for concentration -- and the number of white blood cells present in the field of a high-power microscope, the researchers came up with cutoff points for three urine concentration groups: For low urine concentrations, children needed only three white blood cells to suspect UTI; for moderate concentrations, that number was six; and for high concentrations, it was eight.For each of these concentration groups, leukocyte esterase remained constant, says Nadeem -- suggesting that it's a good trigger for analyzing urine for the presence of white blood cells.Knowing how many white blood cells tend to be present in urine samples at different concentrations in children with UTIs could help physicians start treating these infections before they receive urine culture results, he adds, giving relief to patients and their parents and preventing complications."The earlier we can start treatment, the better it is for these young patients," Nadeem says. "Our results add more information to physicians' toolboxes to make this decision."Other UTSW/Children's Health researchers who contributed to this study include Mohamed Badawy, Oluwaseun Oke, Laura M. Filkins, Jason Y. Park, and Halim M. Hennes.
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Biology
| 2,021 |
March 8, 2021
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https://www.sciencedaily.com/releases/2021/03/210308131728.htm
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Squids: Sophisticated skin
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Squids have long been a source of fascination for humans, providing the stuff of legend, superstition and myth. And it's no wonder -- their odd appearances and strange intelligence, their mastery of the open ocean can inspire awe in those who see them.
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Legends aside, squids continue to intrigue people today -- people like UC Santa Barbara professor Daniel Morse -- for much the same, albeit more scientific, reasons. Having evolved for hundreds of millions of years to hunt, communicate, evade predators and mate in the vast, often featureless expanses of open water, squids have developed some of the most sophisticated skin in the animal kingdom."For centuries, people have been amazed at the ability of squids to change the color and patterns of their skin -- which they do beautifully -- for camoflage and underwater communication, signaling to one another and to other species to keep away, or as attraction for mating and other kinds of signaling," said Morse, a Distinguished Professor Emeritus of Biochemistry and Molecular Genetics.Like their cephalopod cousins the octopus and cuttlefish, squids have specialized pigment-filled cells called chromatophores that expand to expose them to light, resulting in various shades of pigmentary color. Of particular interest to Morse, however, is the squids' ability to shimmer and flicker, reflecting different colors and breaking light over their skin. It's an effect that is thought to mimic the dappled light of the upper ocean -- the only feature in an otherwise stark seascape. By understanding how squids manage to fade themselves into even the plainest of backgrounds -- or stand out -- it may be possible to produce materials with the same, light tuning properties for a variety of applications.Morse has been working to unlock the secret of squid skin for the last decade, and with support from the Army Research Office and research published in the journal "What we've discovered is that not only is the squid able to tune the color of the light that's reflected, but also its brightness," Morse said. Research had thus far has established that certain proteins called reflectins were responsible for iridescence, but the squid's ability to tune the brightness of the reflected light was still something of a mystery, he said.Previous research by Morse had uncovered structures and mechanisms by which iridocytes -- light-reflecting cells -- in the opalescent inshore squid's (Doryteuthis opalescens) skin can take on virtually every color of the rainbow. It happens with the cell membrane, where it folds into nanoscale accordion-like structures called lamellae, forming tiny, subwavelength-wide exterior grooves."Those tiny groove structures are like the ones we see on the engraved side of a compact disc," Morse said. The color reflected depends on the width of the groove, which corresponds to certain light wavelengths (colors). In the squid's iridocytes, these lamellae have the added feature of being able to shapeshift, widening and narrowing those grooves through the actions of a remarkably finely tuned "osmotic motor" driven by reflectin proteins condensing or spreading apart inside the lamellae.While materials systems containing reflectin proteins were able to approximate the iridescent color changes squid were capable of, attempts to replicate the ability to intensify brightness of these reflections always came up short, according to the researchers, who reasoned that something had to be coupled to the reflectins in squid skin, amplifying their effect.That something turned out to be the very membrane enclosing the reflectins -- the lamellae, the same structures responsible for the grooves that split light into its constituent colors."Evolution has so exquisitely optimized not only the color tuning, but the tuning of the brightness using the same material, the same protein and the same mechanism," Morse said.It all starts with a signal, a neuronal pulse from the squid's brain."Reflectins are normally very strongly positively charged," Morse said of the iridescent proteins, which, when not activated, look like a string of beads. Their same charge means they repel each other.But that can change when a neural signal causes the reflectins to bind negatively charged phosphate groups that neutralize the positive charge. Without the repulsion keeping the proteins in their disordered state they fold and attract each other, accumulating into fewer, larger aggregations in the lamellae.These aggregations exert osmotic pressure on the lamellae, a semipermeable membrane built to withstand only so much pressure created by the clumping reflectins before releasing water outside the cell."Water gets squished out of the accordion-like structure, and that collapses the accordion so the thickness in spacing between the folds gets reduced, and that's like bringing the grooves of a compact disc closer together," Morse explained. "So the light that's reflected can shift progressively from red to green to blue."At the same time, the membrane's collapse concentrates the reflectins, causing an increase in their refractive index, amplifying brightness. Osmotic pressure, the motor that drives these tunings of optical properties, couples the lamellae tightly to the reflectins in a highly calibrated relationship that optimizes the output (color and brightness) to the input (neural signal). Wipe away the neural signal and the physics reverses, Morse said."It's a very clever, indirect way of changing color and brightness by controlling the physical behavior of what's called a colligative property -- the osmotic pressure, something that's not immediately obvious, but it reveals the intricacy of the evolutionary process, the millennia of mutation and natural selections that have honed and optimized these processes together."The presence of a membrane may be the vital link for the development of bioinspired thin films with the optical tuning capacity of the opalescent inshore squid."This discovery of the key role the membrane plays in tuning the brightness of reflectance has intriguing implications for the design of future buihybrid materials and coatings with tunable optical properties that could protect soldiers and their equipment," said Stephanie McElhinny, a program manager at the the Army Research Office, an element of the U.S. Army Combat Capabilities Development Command's Army Research Laboratory.According to the researchers, "This evolutionarily honed, efficient coupling of reflectin of its osmotic amplifier is closely analogous to the impedance matched coupling of activator-transducer-amplifier networks in well-engineered electronic, magnetic, mechanical and acoustic systems." In this case the activator would be the neuronal signal, while the reflectins acts as transducers and the osmotically controlled membranes serve as the amplifiers."Without that membrane surrounding the reflectins, there's no change in the brightness for these artificial thin-films," said Morse, who is collaborating with engineering colleagues to investigate the potential for a more squid skin-like thin-film. "If we want to capture the power of the biological, we have to include some kind of membrane-like enclosure to allow reversible tuning of the brightness."
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Biology
| 2,021 |
March 8, 2021
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https://www.sciencedaily.com/releases/2021/03/210308131703.htm
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New discovery explains antihypertensive properties of green and black tea
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A new study from the University of California, Irvine shows that compounds in both green and black tea relax blood vessels by activating ion channel proteins in the blood vessel wall. The discovery helps explain the antihypertensive properties of tea and could lead to the design of new blood pressure-lowering medications.
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Published in Results from the research revealed that two catechin-type flavonoid compounds (epicatechin gallate and epigallocatechin-3-gallate) found in tea, each activate a specific type of ion channel protein named KCNQ5, which allows potassium ions to diffuse out of cells to reduce cellular excitability. As KCNQ5 is found in the smooth muscle that lines blood vessels, its activation by tea catechins was also predicted to relax blood vessels -- a prediction confirmed by collaborators at the University of Copenhagen."We found by using computer modeling and mutagenesis studies that specific catechins bind to the foot of the voltage sensor, which is the part of KCNQ5 that allows the channel to open in response to cellular excitation. This binding allows the channel to open much more easily and earlier in the cellular excitation process," explained Abbott.Because as many as one third of the world's adult population have hypertension, and this condition is considered to be the number one modifiable risk factor for global cardiovascular disease and premature mortality, new approaches to treating hypertension have enormous potential to improve global public health. Prior studies demonstrated that consumption of green or black tea can reduce blood pressure by a small but consistent amount, and catechins were previously found to contribute to this property. Identification of KCNQ5 as a novel target for the hypertensive properties of tea catechins may facilitate medicinal chemistry optimization for improved potency or efficacy.In addition to its role in controlling vascular tone, KCNQ5 is expressed in various parts of the brain, where it regulates electrical activity and signaling between neurons. Pathogenic KCNQ5 gene variants exist that impair its channel function and in doing so cause epileptic encephalopathy, a developmental disorder that is severely debilitating and causes frequent seizures. Because catechins can cross the blood-brain barrier, discovery of their ability to activate KCNQ5 may suggest a future mechanism to fix broken KCNQ5 channels to ameliorate brain excitability disorders stemming from their dysfunction.Tea has been produced and consumed for more than 4,000 years and upwards of 2 billion cups of tea are currently drunk each day worldwide, second only to water in terms of the volume consumed by people globally. The three commonly consumed caffeinated teas (green, oolong, and black) are all produced from the leaves of the evergreen species Camellia sinensis, the differences arising from different degrees of fermentation during tea production.Black tea is commonly mixed with milk before it is consumed in countries including the United Kingdom and the United States. The researchers in the present study found that when black tea was directly applied to cells containing the KCNQ5 channel, the addition of milk prevented the beneficial KCNQ5-activating effects of tea. However, according to Abbott, "We don't believe this means one needs to avoid milk when drinking tea to take advantage of the beneficial properties of tea. We are confident that the environment in the human stomach will separate the catechins from the proteins and other molecules in milk that would otherwise block catechins' beneficial effects."This hypothesis is borne out by other studies showing antihypertensive benefits of tea regardless of milk co-consumption. The team also found, using mass spectrometry, that warming green tea to 35 degrees Celsius alters its chemical composition in a way that renders it more effective at activating KCNQ5."Regardless of whether tea is consumed iced or hot, this temperature is achieved after tea is drunk, as human body temperature is about 37 degrees Celsius," explained Abbott. "Thus, simply by drinking tea we activate its beneficial, antihypertensive properties."This study was supported in part by the National Institutes of Health, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, the Lundbeck Foundation and the Danmarks Frie Forskningsfond.
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Biology
| 2,021 |
March 8, 2021
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https://www.sciencedaily.com/releases/2021/03/210308111922.htm
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These sea slugs sever their own heads and regenerate brand-new bodies
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You've heard of animals that can lose and then regenerate a tail or limb. But scientists reporting in the journal
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"We were surprised to see the head moving just after autotomy," said Sayaka Mitoh of Nara Women's University in Japan. "We thought that it would die soon without a heart and other important organs, but we were surprised again to find that it regenerated the whole body."The discovery was a matter of pure serendipity. Mitoh is a PhD candidate in the lab of Yoichi Yusa. The Yusa lab raises sea slugs from eggs to study their life history traits. One day, Mitoh saw something unexpected: a sacoglossan individual moving around without its body. They even witnessed one individual doing this twice.The researchers report that the head, separated from the heart and body, moved on its own immediately after the separation. Within days, the wound at the back of the head closed. The heads of relatively young slugs started to feed on algae within hours. They started regeneration of the heart within a week. Within about three weeks, regeneration was complete.The heads of older individuals didn't feed and died in about 10 days. In either case, the cast-off bodies didn't regenerate a new head. But the headless bodies did move and react to being touched for several days or even months.Mitoh and Yusa aren't sure how the sea slugs manage it. But, Mitoh says, they suspect there must be stem-like cells at the cut end of the neck that are capable of regenerating the body. It's also unclear why they would do this. One possibility is it helps to remove internal parasites that inhibit their reproduction. They also don't know what immediate cue prompts them to cast off the rest of the body. These are areas for future study.The sea slugs in question already were unique in that they incorporate chloroplasts from algae they eat into their own bodies, a habit known as kleptoplasty. It gives the animals an ability to fuel their bodies by photosynthesis. They suggest this ability might help them survive after autotomy (the casting off of a part of the body) long enough to regenerate a body.These findings in sea slugs represent a new type of autotomy in which animals with complex body plans shed most of their body."As the shed body is often active for months, we may be able to study the mechanism and functions of kleptoplasty using living organs, tissues, or even cells," Mitoh said. "Such studies are almost completely lacking, as most studies on kleptoplasty in sacoglossans are done either at the genetic or individual levels."
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Biology
| 2,021 |
March 8, 2021
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https://www.sciencedaily.com/releases/2021/03/210308111844.htm
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Research shows we're surprisingly similar to Earth's first animals
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The earliest multicellular organisms may have lacked heads, legs, or arms, but pieces of them remain inside of us today, new research shows.
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According to a UC Riverside study, 555-million-year-old oceanic creatures from the Ediacaran period share genes with today's animals, including humans."None of them had heads or skeletons. Many of them probably looked like three-dimensional bathmats on the sea floor, round discs that stuck up," said Mary Droser, a geology professor at UCR. "These animals are so weird and so different, it's difficult to assign them to modern categories of living organisms just by looking at them, and it's not like we can extract their DNA -- we can't."However, well-preserved fossil records have allowed Droser and the study's first author, recent UCR doctoral graduate Scott Evans, to link the animals' appearance and likely behaviors to genetic analysis of currently living things. Their research on these links has been recently published in the journal For their analysis, the researchers considered four animals representative of the more than 40 recognized species that have been identified from the Ediacaran era. These creatures ranged in size from a few millimeters to nearly a meter in length.Kimberella were teardrop-shaped creatures with one broad, rounded end and one narrow end that likely scraped the sea floor for food with a proboscis. Further, they could move around using a "muscular foot" like snails today. The study included flat, oval-shaped Dickinsonia with a series of raised bands on their surface, and Tribrachidium, who spent their lives immobilized at the bottom of the sea.Also analyzed were Ikaria, animals recently discovered by a team including Evans and Droser. They were about the size and shape of a grain of rice, and represent the first bilaterians -- organisms with a front, back, and openings at either end connected by a gut. Evans said it's likely Ikaria had mouths, though those weren't preserved in the fossil records, and they crawled through organic matter "eating as they went."All four of the animals were multicellular, with cells of different types. Most had symmetry on their left and right sides, as well as noncentralized nervous systems and musculature.Additionally, they seem to have been able to repair damaged body parts through a process known as apoptosis. The same genes involved are key elements of human immune systems, which helps to eliminate virus-infected and pre-cancerous cells.These animals likely had the genetic parts responsible for heads and the sensory organs usually found there. However, the complexity of interaction between these genes that would give rise to such features hadn't yet been achieved."The fact that we can say these genes were operating in something that's been extinct for half a billion years is fascinating to me," Evans said.The work was supported by a NASA Exobiology grant, and a Peter Buck postdoctoral fellowship.Going forward, the team is planning to investigate muscle development and functional studies to further understand early animal evolution."Our work is a way to put these animals on the tree of life, in some respects," Droser said. "And show they're genetically linked to modern animals, and to us."
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Biology
| 2,021 |
March 8, 2021
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https://www.sciencedaily.com/releases/2021/03/210308111833.htm
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Hybrid microbes: Genome transfer between different bacteria strains explored
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Bacteria integrate genetic material from other bacterial strains more easily than previously thought, which can lead to improved fitness and accelerated evolution. This is shown in a recent study by biophysicists at the University of Cologne. The team analysed genome transfer between bacteria of different lineages. The study was published in the journal
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In the experiment, the team brought one strain of bacteria into contact with DNA fragments from another strain. The uptake of foreign genetic material is known as horizontal gene transfer -- in contrast to vertical gene transfer, by which genes are inherited from a parent cell of the same lineage. The results show that laboratory evolution through horizontal gene transfer can rapidly produce hybrid organisms of different lineages with extensive genomic and functional changes. "It is a bit like interbreeding modern humans and Neandertals'," says Dr. Fernanda Pinheiro of the Institute of Biological Physics at the University of Cologne and author of the study. The bacteria readily integrated foreign DNA at many sites in the genome. Within 200 generations, the research team observed the exchange of up to 14 percent of the bacterium's core genes.Horizontal gene transfer is an important factor in bacterial evolution that can operate across species boundaries. "Yet we know little about the rate and genomic targets of cross-strain gene transfer. Also, little is known so far about the effects on the physiology and fitness of the recipient organism," says Pinheiro. From a scientific perspective, hybrid creatures whose parents belong to different species raise fundamental evolutionary biology questions: What combinations of traits yield viable organisms? What are the limits of evolutionary processes when more than one species is involved in reproduction? "Our study makes an important contribution here," Pinheiro adds.Is the uptake of genes random or does it follow a definite pattern? As the researchers observed, some functional units of the foreign genome were repeatedly imported and the resulting hybrid bacteria had higher growth rates. "This implies that cross-lineage gene exchange drives evolution very efficiently," Pinheiro says. Integrating foreign genes through horizontal gene transfer produces new combinations of genes yet preserves essential structures that make a cell viable. Thus, the study opens new perspectives for future work: to combine transfer evolution experiments and synthetic biology methods to engineer functional innovations.
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Biology
| 2,021 |
March 8, 2021
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https://www.sciencedaily.com/releases/2021/03/210308111828.htm
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A biosensor for measuring extracellular hydrogen peroxide concentrations
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Several processes in the human body are regulated by biochemical reactions involving hydrogen peroxide (H
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The biosensor consists of a gold nanoparticle with organic molecules attached to it. The whole cluster is designed so that it anchors easily to the outside of a cell's membrane, which is exactly where the hydrogen peroxide molecules to be detected are. As attachment molecules, the scientists used a compound called 4MPBE, known to have a strong Raman scattering response: when irradiated by a laser, the molecules consume some of the laser light's energy. By measuring the frequency change of the laser light, and plotting the signal strength as a function of this change, a unique spectrum is obtained -- a signature of the 4MPBE molecules. When a 4MPBE molecule reacts with a HAfter developing a calibration procedure for their nanosensor -- relating the HPuppulin and colleagues conclude that their "novel approach may be useful for the study of actual HThe biosensor developed by Leonardo Puppulin from Kanazawa University and colleagues is based on a method called surface-enhanced Raman spectroscopy (SERS). The principle derives from Raman spectroscopy, in which differences between the incoming and the outcoming frequencies of laser light irradiated onto a sample are analyzed. The spectrum obtained by plotting the signal strength as a function of frequency difference is characteristic for the sample, which can in principle be a single molecule. Typically, however, the signal coming from one molecule is too weak to detect, but the effect can be enhanced when the molecule is absorbed on a rough metal surface. Puppulin and colleagues applied the technique to (indirectly) detect hydrogen peroxide; their Raman-responsive molecule is a compound called 4MPBE, which is modified when exposed to hydrogen peroxide.
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Biology
| 2,021 |
March 6, 2021
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https://www.sciencedaily.com/releases/2021/03/210306113147.htm
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New 'split-drive' system puts scientists in the (gene) driver seat
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Powerful new genetic engineering methods have given scientists the potential to revolutionize several sectors of global urgency.
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So-called gene drives, which leverage CRISPR technology to influence genetic inheritance, carry the promise of rapidly spreading specific genetic traits throughout populations of a given species. Gene-drive technologies applied in insects, for example, are being designed to halt the spread of devastating diseases such as malaria and dengue by preventing mosquito hosts from becoming infected. In agricultural fields, gene-drives are being developed to help control or eliminate economically damaging crop pests.But along with the capacity to alter populations, concerns have been raised regarding the long-term effects of these transformative new technologies in the wild. Researchers and ethicists have voiced questions about how gene drives, once turned loose in a regional population, could be held in check if necessary.Now, researchers at the University of California San Diego, Tata Institute for Genetics and Society (TIGS) at UC San Diego and their colleagues at UC Berkeley have developed a new method that provides more control over gene drive releases. Details of the new "split drive" are published March 5 in the journals The most common gene drives employ a two-component system that features a DNA-cutting enzyme (called Cas9) and a guide RNA (or gRNA) that targets cuts at specific sites in the genome. Following the Cas9/gRNA cut, the gene drive, along with the cargo it carries, is copied into the break site through a DNA repair process.While classic gene drives are designed to spread autonomously, the newly developed system is designed with controls that separate the genetic implementation processes. The split-drive system consists of a non-spreadable Cas9 component inserted into one location in the genome and a second genetic element that can copy itself -- along with a beneficial trait -- at a separate site. When both elements are present together in an individual, an "active gene drive" is created that spreads the element carrying the beneficial trait to most of its progeny. Yet, when uncoupled, the element carrying the beneficial trait is inherited under typical generational genetics rules, or Mendelian frequencies, rather than spreading unrestrained.As described in the "Studying drives in essential genes is not a novel idea, per se, but we observed that certain split situations were able to spread a cargo effectively upon a first introduction while leaving no trace of Cas9 after a few generations, as well as few mistakes in the DNA repair process that got rapidly diluted out," said Gerard Terradas, first author in the The The new split-drive system follows research announced in September in which UC San Diego researchers led the development of two new active genetics neutralizing strategies that are designed to halt or inactivate gene drives released in the wild."We hope that the flexible design features we have developed will be broadly applicable by enabling tailored approaches to controlling insect vectors and pests in diverse contexts," said UC San Diego Distinguished Professor Ethan Bier, senior author of the "These seminal papers reflect a tremendous effort, and fruitful cross-UC collaborations, to demonstrate novel gene drive architectures for mitigating the formation of resistant alleles while providing a safe confinable means for modification of wild populations," said UC San Diego Associate Professor Omar Akbari, senior author of the
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Biology
| 2,021 |
March 6, 2021
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https://www.sciencedaily.com/releases/2021/03/210306113142.htm
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Study reveals how egg cells get so big
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Egg cells are by far the largest cells produced by most organisms. In humans, they are several times larger than a typical body cell and about 10,000 times larger than sperm cells.
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There's a reason why egg cells, or oocytes, are so big: They need to accumulate enough nutrients to support a growing embryo after fertilization, plus mitochondria to power all of that growth. However, biologists don't yet understand the full picture of how egg cells become so large.A new study in fruit flies, by a team of MIT biologists and mathematicians, reveals that the process through which the oocyte grows significantly and rapidly before fertilization relies on physical phenomena analogous to the exchange of gases between balloons of different sizes. Specifically, the researchers showed that "nurse cells" surrounding the much larger oocyte dump their contents into the larger cell, just as air flows from a smaller balloon into a larger one when they are connected by small tubes in an experimental setup."The study shows how physics and biology come together, and how nature can use physical processes to create this robust mechanism," says Jörn Dunkel, an MIT associate professor of physical applied mathematics. "If you want to develop as an embryo, one of the goals is to make things very reproducible, and physics provides a very robust way of achieving certain transport processes."Dunkel and Adam Martin, an MIT associate professor of biology, are the senior authors of the paper, which appears this week in the In female fruit flies, eggs develop within cell clusters known as cysts. An immature oocyte undergoes four cycles of cell division to produce one egg cell and 15 nurse cells. However, the cell separation is incomplete, and each cell remains connected to the others by narrow channels that act as valves that allow material to pass between cells.Members of Martin's lab began studying this process because of their longstanding interest in myosin, a class of proteins that can act as motors and help muscle cells contract. Imran Alsous performed high-resolution, live imaging of egg formation in fruit flies and found that myosin does indeed play a role, but only in the second phase of the transport process. During the earliest phase, the researchers were puzzled to see that the cells did not appear to be increasing their contractility at all, suggesting that a mechanism other than "squeezing" was initiating the transport."The two phases are strikingly obvious," Martin says. "After we saw this, we were mystified, because there's really not a change in myosin associated with the onset of this process, which is what we were expecting to see."Martin and his lab then joined forces with Dunkel, who studies the physics of soft surfaces and flowing matter. Dunkel and Romeo wondered if the cells might be behaving the same way that balloons of different sizes behave when they are connected. While one might expect that the larger balloon would leak air to the smaller until they are the same size, what actually happens is that air flows from the smaller to the larger.This happens because the smaller balloon, which has greater curvature, experiences more surface tension, and therefore higher pressure, than the larger balloon. Air is therefore forced out of the smaller balloon and into the larger one. "It's counterintuitive, but it's a very robust process," Dunkel says.Adapting mathematical equations that had already been derived to explain this "two-balloon effect," the researchers came up with a model that describes how cell contents are transferred from the 15 small nurse cells to the large oocyte, based on their sizes and their connections to each other. The nurse cells in the layer closest to the oocyte transfer their contents first, followed by the cells in more distant layers."After I spent some time building a more complicated model to explain the 16-cell problem, we realized that the simulation of the simpler 16-balloon system looked very much like the 16-cell network. It is surprising to see that such counterintuitive but mathematically simple ideas describe the process so well," Romeo says.The first phase of nurse cell dumping appears to coincide with when the channels connecting the cells become large enough for cytoplasm to move through them. Once the nurse cells shrink to about 25 percent of their original size, leaving them only slightly larger than their nuclei, the second phase of the process is triggered and myosin contractions force the remaining contents of the nurse cells into the egg cell."In the first part of the process, there's very little squeezing going on, and the cells just shrink uniformly. Then this second process kicks in toward the end where you start to get more active squeezing, or peristalsis-like deformations of the cell, that complete the dumping process," Martin says.The findings demonstrate how cells can coordinate their behavior, using both biological and physical mechanisms, to bring about tissue-level behavior, Imran Alsous says."Here, you have several nurse cells whose job it is to nurse the future egg cell, and to do so, these cells appear to transport their contents in a coordinated and directional manner to the oocyte," she says.Oocyte and early embryonic development in fruit flies and other invertebrates bears some similarities to those of mammals, but it's unknown if the same mechanism of egg cell growth might be seen in humans or other mammals, the researchers say."There's evidence in mice that the oocyte develops as a cyst with other interconnected cells, and that there is some transport between them, but we don't know if the mechanisms that we're seeing here operate in mammals," Martin says.The researchers are now studying what triggers the second, myosin-powered phase of the dumping process to start. They are also investigating how changes to the original sizes of the nurse cells might affect egg formation.The research was funded by the National Institute of General Medical Sciences, a Complex Systems Scholar Award from the James S. McDonnell Foundation, and the Robert E. Collins Distinguished Scholarship Fund.
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Biology
| 2,021 |
March 5, 2021
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https://www.sciencedaily.com/releases/2021/03/210305123802.htm
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The gut mycobiome influences the metabolism of processed foods
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Studies of the microbiome in the human gut focus mainly on bacteria. Other microbes that are also present in the gut -- viruses, protists, archaea and fungi -- have been largely overlooked.
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New research in mice now points to a significant role for fungi in the intestine -- the communities of molds and yeasts known as the mycobiome -- that are the active interface between the host and their diet."We showed that the gut mycobiome of healthy mice was shaped by the environment, including diet, and that it significantly correlated with metabolic outcomes," said Kent Willis, M.D., an assistant professor at the University of Alabama at Birmingham and co-corresponding author of the study, published in the journal Willis and colleagues looked at fungi in the jejunum of the mouse small intestine, site of the most diverse fungal population in the mouse gut. They found that exposure to a processed diet, which is representative of a typical Western diet rich in purified carbohydrates, led to persistent differences in fungal communities that significantly associated with differential deposition of body mass in male mice, as compared to mice fed a standardized diet.The researchers found that fat deposition in the liver, transcriptional adaptation of metabolically active tissues and serum metabolic biomarker levels were all linked with alterations in fungal community diversity and composition. Variations of fungi from two genera -- Thermomyces and Saccharomyces -- were the most strongly associated with metabolic disturbance and weight gain.The study had an ingenious starting point. The researchers obtained genetically identical mice from four different research animal vendors. It is known that gut bacterial communities vary markedly by vendor. Similarly, the researchers found dramatically different variability by vendor for the jejunum mycobiomes, as measured by sequencing internal transcribed spacer rRNA. At baseline, mice from one of the vendors had five unique fungal genera, and mice from the other three vendors had three, two and one unique genera, respectively.They also looked at interkingdom community composition -- meaning bacteria as well as fungi -- and found large baseline bacterial community differences. From this initial fungal and bacterial diversity, they then measured the effects of time and differences in diet -- standardized chow versus the highly processed diet -- on fungal and bacterial community composition.The researchers also addressed a fundamental question: Are the fungal organisms detected by next-generation sequencing coming from the diet, or are they true commensal organisms that colonize and replicate in the gut? They compared sequencing of the food pellets, which contained some fungi, and the contents of the mouse jejunum to show the jejunum fungi were true commensal colonizers.Thus, this study, led by Willis -- and co-corresponding author Joseph Pierre, Ph.D., and co-first authors Tahliyah S. Mims and Qusai Al Abdallah, Ph.D., from the University of Tennessee Health Science Center, Memphis, Tennessee -- showed that variations in the relative abundance and composition of the gut mycobiome correlate with key features of host metabolism. This lays a foundation towards understanding the complex interkingdom interactions between bacteria and fungi and how they both collectively shape, and potentially contribute to, host homeostasis."Our results highlight the potential importance of the gut mycobiome in health, and they have implications for human and experimental metabolic studies," Pierre said. "The implication for human microbiome studies, which often examine only bacteria and sample only fecal communities, is that the mycobiome may have unappreciated effects on microbiome-associated outcomes."The research was mostly done at the University of Tennessee Health Science Center, where Willis was an assistant professor before joining the Division of Neonatology in the UAB Department of Pediatrics last summer.The translational research in the Willis Lung Lab at UAB seeks to understand how such commensal fungi influence newborn physiology and disease, principally via exploring the gut-lung axis in bronchopulmonary dysplasia, a lung disease of premature newborns. The study in Co-authors with Willis, Pierre, Mims and Al Abdallah in the study, "The gut mycobiome of healthy mice is shaped by the environment and correlates with metabolic outcomes in response to diet," are Justin D. Stewart, Villanova University, Radnor, Pennsylvania; and Sydney P. Watts, Catrina T. White, Thomas V. Rousselle, Ankush Gosain, Amandeep Bajwa and Joan C. Han, the University of Tennessee Health Science Center.Support came from National Institutes of Health grants CA253329, HL151907, DK117183 and DK125047.
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Biology
| 2,021 |
March 5, 2021
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https://www.sciencedaily.com/releases/2021/03/210305113510.htm
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New method facilitates development of antibody-based drugs
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In recent years, therapeutic antibodies have transformed the treatment of cancer and autoimmune diseases. Now, researchers at Lund University in Sweden have developed a new, efficient method based on the genetic scissors CRISPR-Cas9, that facilitates antibody development. The discovery is published in
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Antibody drugs are the fastest growing class of drug, and several therapeutic antibodies are used to treat cancer. They are effective, often have few side effects and benefit from the body's own immune system by identifying foreign substances in the body. By binding to a specific target molecule on a cell, the antibody can either activate the immune system, or cause the cell to self-destruct.However, most antibody drugs used today have been developed against an antibody target chosen beforehand. This approach is limited by the knowledge of cancer we have today and restricts the discovery of new medicines to currently known targets."Many antibody drugs currently target the same molecule, which is a bit limiting. Antibodies targeting new molecules could give more patients access to effective treatment," says Jenny Mattsson, doctoral student at the Department of Hematology and Transfusion Medicine at Lund University.Another route -- that pharmaceutical companies would like to go down -- would be to search for antibodies against cancer cells without being limited to a pre-specified target molecule. In this way, new, unexpected target molecules could be identified. The problem is that this method (so-called "phenotypic antibody development") requires that the target molecule be identified at a later stage, which has so far been technically difficult and time-consuming."Using the CRISPR-Cas9 gene scissors, we were able to quickly identify the target molecules for 38 of 39 test antibodies. Although we were certain that the method would be effective, we were surprised that the results would be this precise. With previous methods, it has been difficult to find the target molecule even for a single antibody," says Jenny Mattsson.The research project is a collaboration between Lund University, BioInvent International and the Foundation for Strategic Research. The researchers' method has already been put into practical use in BioInvent's ongoing research projects."We believe the method can help antibody developers and hopefully contribute to the development of new antibody-based drugs in the future," concludes Professor Björn Nilsson, who led the project.
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Biology
| 2,021 |
March 5, 2021
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https://www.sciencedaily.com/releases/2021/03/210305113501.htm
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'Fungal ghosts' protect skin, fabric from toxins, radiation
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The idea of creating selectively porous materials has captured the attention of chemists for decades. Now, new research from Northwestern University shows that fungi may have been doing exactly this for millions of years.
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When Nathan Gianneschi's lab set out to synthesize melanin that would mimic that which was formed by certain fungi known to inhabit unusual, hostile environments including spaceships, dishwashers and even Chernobyl, they did not initially expect the materials would prove highly porous -- a property that enables the material to store and capture molecules.Melanin has been found across living organisms, on our skin and the backs of our eyes, and as pigments for many animals and plants. It also plays a role in protecting species from environmental stressors. Turtle-headed sea snakes' stripes darken, for example, in the presence of polluted water; moths living in industrial areas turn black as their cells absorb toxins in soot. The researchers wondered whether this type of biomaterial could be made more sponge-like, to optimize these properties. And, in turn, whether sponge-like melanins existed already in nature."Melanin's function isn't fully known all the time and in all cases," Gianneschi, the corresponding author on the study, said. "It's certainly a radical scavenger in human skin and protects against UV damage. Now, through synthesis we've happened upon this exciting material that very well may exist in nature. Fungi might make this material to add mechanical strength to their cells, but is porous, allowing nutrients across."The study will be published Friday, March 5, in the Gianneschi is the Jacob and Rosaline Cohn Professor of Chemistry in the Weinberg College of Arts and Sciences. With appointments in the materials science and biomedical engineering departments in the McCormick School of Engineering, Gianneschi also is associate director of the International Institute for Nanotechnology.The ability to create this material in a lab is encouraging for a number of reasons. In typical non-porous materials, particles adsorb only superficially on the surface. But porous materials like allomelanin soak up and hold undesirable toxins while letting good stuff like air, water and nutrients through. This may allow manufacturers to create breathable, protective coatings for uniforms."You're always excited by discovering something that's potentially useful," Gianneschi said. "But there's also the intriguing idea that by discovering this, maybe more materials like this exist out there in biology already. There aren't many examples where chemical synthesis leads to a biological discovery. It's most often the other way around."Naneki McCallum, a graduate student researcher in the lab and first author on the paper, had noticed that under the right conditions, melanin appeared to be hollow, or could be made to contain what looked like voids by electron microscopy. When the team came across the synthetic material, they began experimenting with porosity and selectivity of the materials for adsorbing molecules in those voids.In a key demonstration, the team, working with researchers at the Naval Research Laboratory, was able to show that the new porous melanin would act as a protective coating, preventing simulants of nerve gas from getting through. Inspired by this result, they then isolated naturally occurring melanin from fungal cells. This was done by etching away biomaterial from within, leaving a shell containing melanin. They call these structures "fungal ghosts" for the elusive, hollow shape's "Casper"-like quality. The material, derived from fungi could also, in turn be used as a protective layer in fabrics. Remarkably, the material stays breathable, allowing water to pass, while trapping toxins.Another benefit to this material is its simplicity, as it's easily produced and scaled from simple molecular precursors. In the future, it could be used to make protective masks and face shields and has potential for applications in long distance space flight. Coating materials in space would allow astronauts to store toxins they're breathing out while protecting themselves from harmful radiation, making for less waste and weight.It's also a step toward selective membranes, a highly complex field of study that aims to take compounds like water and allow healthy minerals to pass through while blocking heavy metals like mercury."Fungi can thrive in places where other organisms struggle, and they have melanin to help them do it," McCallum said. "So, we ask, what are the properties that we can harness by recreating such materials in the lab?"The study was supported by a MURI through the Air Force Office of Scientific Research (AFOSR FA9550-18-1-0142) and the Defense Threat Reduction Agency (HDTRA1-19-19-1-0010).
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Biology
| 2,021 |
March 5, 2021
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https://www.sciencedaily.com/releases/2021/03/210305080132.htm
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Tracking proteins in the heart of cells
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In order to stay alive, the cell must provide its various organelles with all the energy elements they need, which are formed in the Golgi apparatus, its centre of maturation and redistribution of lipids and proteins. But how do the proteins that carry these cargoes -- the kinesins -- find their way and direction within the cell's "road network" to deliver them at the right place? Chemists and biochemists at the University of Geneva (UNIGE), Switzerland, have discovered a fluorescent chemical dye, making it possible for the first time to track the transport activity of a specific motor protein within a cell. A discovery to be read in the magazine
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"It all started from a research that didn't go as planned," laughs Nicolas Winssinger, professor at the Department of Organic Chemistry of the Faculty of Science at UNIGE. "Initially, we wanted to develop a molecule that would make it possible to visualise the stress level of the cell, i.e. when it accumulates too much active oxygen species. During the experiment, the molecule did not work, but crystallised. Why did it crystallise? What were these crystals?"Three hypotheses emerged as possible and the team reached out to Charlotte Aumeier, professor in the Department of Biochemistry of the Faculty of Sciences of the UNIGE to verify them. The first hypothesis suggested that crystallisation was due to the microtubules that polymerise. "Microtubules are small, rigid tubes that can grow or shrink and constitute the "road network" that allows molecules to move around the cell," explains Charlotte Aumeier. The second hypothesis made Golgi's apparatus responsible for this chemical reaction. The last possibility suggested that the crystals were the result of the small steps made by the kinesin proteins in the microtubules as they moved within the cell.To verify these different options, the UNIGE team joined forces with the National Institute of Health (NIH) in Bethesda (USA), which specialises in electron microscopy. "We first recreated microtubules that we purified, which takes 14 hours," explains Charlotte Aumeier. "For the kinesins, the motor proteins that move on microtubules and transport cargo, we isolated them from bacteria." The scientists then put together about 20 different mixtures containing the small molecule QPD, which is systematically present in the crystals, and observed which solution worked. "We wanted to know what was needed to form the crystals. The microtubules? The kinesin? Yet another protein?" asks Nicolas Winssinger.Following various experiments, the team discovered that the formation of these crystals was caused by one of the 45 types of kinesin present in the cell. "With each small step that this kinesin protein takes on the microtubule, it uses energy that leaves a trace identified by the QPD molecule," continues the Geneva-based researcher. It is from this recognition that the crystals are formed. In this way, the crystals are chemically left behind by the passage of the kinesin, which can be tracked by scientists like a small thumb."Until now, it has not been possible to track a particular protein. With current techniques, we couldn't separate the individual kinesins, so we couldn't see which path they took precisely," continues Charlotte Aumeier. "Thanks to the development of our new chemical fluorescent dye, we can observe in detail how a protein behaves, which route it takes, its direction or even its preferred path." For the first time, scientists can visualise the walking path of motor proteins and study the fundamental question of the transport activity and distribution of cargoes in cells.
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Biology
| 2,021 |
March 5, 2021
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https://www.sciencedaily.com/releases/2021/03/210305092406.htm
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HSC transplants in embryos: Opening the door for hematopoiesis research
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Most people have heard of stem cells, cells from which all other cells with specialized functions are generated. Hematopoietic stem cells (HSCs) are the architects of blood cell development and are responsible for blood cell formation throughout the life of an organism. HSCs are also used in the treatment of cancer and immune disturbances.
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Previous research into HSC transplantation has involved the use of adult and fetal mice. This has involved the removal of recipient HSCs using approaches including irradiation and the administration of DNA damaging drugs. In a first of its kind, researchers from the University of Tsukuba devised a novel approach for HSC deletion in mouse embryos. This report provides the first description of embryonic HSC depletion and transplantation of donor HSCs into the embryo via the placenta.In describing their approach, Assistant Professor Michito Hamada says: "We were able to exploit the genetics of HSC development in mice to generate mice that completely lack HSCs in the fetal liver, making these mice the perfect recipients for HSC transplantation." Mice lacking the Runx1 gene do not survive into adulthood and die at embryonic day 12.5, in part because they lack HSCs. The recipient mice developed by this team have Runx1 transgenes that partially restore the effects of Runx1 absence, and while these mice still lack HSCs, they can develop until embryonic day 18.5.Using these recipient mice, the research team explored the effects of transplanting HSCs from the same species (allogenic) or from a different species (xenogeneic). The placentas of recipient mice were injected with donor HSCs at embryonic day 11.5, before the development of the immune system. Excitingly, over 90% the HSCs of recipient fetuses were from the donor, irrespective of species.Analysis of the HSCs that developed in recipient mice after transportation revealed that they contributed to the development of both white and red blood cells. Furthermore, additional transplant of these cells into adult recipients revealed that the HSCs were functional and had retained normal abilities."These results are really exciting," explains Professor Satoru Takahashi. "These mice represent a new tool that can be used to advance HSC research. The ability to perform HSC transplants at an earlier developmental stage really allows us to explore fetal hematopoiesis and, in the future, this model could be 'humanized' using human HSCs. The applications appear endless."
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Biology
| 2,021 |
March 4, 2021
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https://www.sciencedaily.com/releases/2021/03/210304145430.htm
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This frog has lungs that act like noise-canceling headphones
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To succeed in mating, many male frogs sit in one place and call to their potential mates. But this raises an important question familiar to anyone trying to listen to someone talking at a busy cocktail party: how does a female hear and then find a choice male of her own species among all the irrelevant background noise, including the sound of other frog species? Now, researchers reporting March 4 in the journal
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"In essence, the lungs cancel the eardrum's response to noise, particularly some of the noise encountered in a cacophonous breeding 'chorus,' where the males of multiple other species also call simultaneously," says lead author Norman Lee of St. Olaf College in Minnesota.The researchers explain that what their lungs are doing is called "spectral contrast enhancement." That's because it makes the frequencies in the spectrum of a male's call stand out relative to noise at adjacent frequencies."This is analogous to signal-processing algorithms for spectral contrast enhancement implemented in some hearing aids and cochlear implants," says senior author Mark Bee of the University of Minnesota-Twin Cities. "In humans, these algorithms are designed to amplify or 'boost' the frequencies present in speech sounds, attenuate or 'filter out' frequencies present between those in speech sounds, or both. In frogs, the lungs appear to attenuate frequencies occurring between those present in male mating calls. We believe the physical mechanism by which this occurs is similar in principle to how noise-canceling headphones work."It's long been known to scientists that vocal signals are key to reproduction in most frogs. In fact, frogs possess a unique sound pathway that can transmit sounds from their air-filled lungs to their air-filled middle ears through the glottis, mouth cavity, and Eustachian tubes. But the precise function of this lung-to-ear sound transmission pathway had been a puzzle. Earlier studies suggested that the frog's lungs might play a role in increasing the degree to which eardrum vibrations were direction dependent, thereby improving the ability of listeners to locate a sexually advertising male. But Bee's team has found that wasn't the case.Further analysis of the data suggested a different explanation: while the state of the lungs' inflation had no effect on directional hearing, there was a substantial impact on the sensitivity of the eardrum. With inflated lungs, the eardrum vibrated less in response to sounds in a specific frequency range. It led them to a new idea: that the lungs were dampening vibrations, thereby canceling out noise.Indeed, their studies using laser vibrometry showed that the resonance of inflated lungs selectively reduces the eardrum's sensitivity to frequencies between the two spectral peaks present in the mating calls of frogs of the same species. It confirmed that a female can hear males of her own species no matter the state of her lungs' inflation. So, the lungs had no impact on the "signals" of interest to a female. But what about the "noise"?They already knew that a major source of noise for any given species of frog is the calls of other frog species breeding at the same time and calling in the same choruses. But they had no idea how many or which other species might "co-call" in a mixed species chorus with green treefrogs across its geographic range, much less how the frequency spectrum of their calls looked. To find out, they turned to publicly available data from a citizen science project called the North American Amphibian Monitoring Program. Their analysis of those data suggests that the green treefrog's inflated lungs would make it harder to hear the calls of other species while leaving their ability to hear the calls of their own species intact."Needless to say, we think this result -- a frog's lungs canceling the eardrum's response to noise created by other species of frogs -- is pretty cool!" Bee says.Finally, they created a physiological model of sound processing by the green treefrog's inner ear to examine how the lung's impact on the eardrum might be converted into more robust neural responses to the calls of their own species. They think it works like this: the inner ear is, in some ways, "tuned" to respond best to the frequencies in the species' own calls. But that tuning is not perfect. The authors suggest that a primary function of the lungs in hearing is to sharpen or improve this tuning, allowing the inner ear to generate relatively stronger neural responses to the species' own calls by reducing the neural responses driven by the calls of other species.The findings demonstrate the power of evolution to co-opt pre-existing adaptations for new functions, the researchers say. In future work, they want to find out more about the physical interaction between the three sources of sound (external, internal via the opposite ear, and internal via the lungs) that determine the eardrum's vibration response. They also want to know more about how widespread noise cancellation is in frogs.
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Biology
| 2,021 |
March 4, 2021
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https://www.sciencedaily.com/releases/2021/03/210304133505.htm
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Newly discovered millipede, Nannaria hokie, lives at Virginia Tech
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Hearing the words "new species discovered" may conjure images of deep caves, uncharted rainforests, or hidden oases in the desert.
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But the reality is that thousands of new species are discovered each year by enterprising scientists all over the world. Many of these new species do come from exotic locations, but more surprisingly, many come from just down the road, including the newest member of the Hokie Nation, the millipede Nannaria hokie.The newest Hokie -- which has about 60 more legs than the HokieBird -- was discovered living under rocks by the Duck Pond behind the Grove on Virginia Tech's Blacksburg campus. Since then, the critter has been found at the area commonly referred to as stadium woods and in town in Blacksburg as well."It's not every day that we find new species, let alone on our campus, so we wanted to name the new species for the Virginia Tech community and to highlight the importance of conserving native habitat in the region," said Paul Marek, a systematics and taxonomy associate professor in Virginia Tech's Department of Entomology in the College of Agriculture and Life Sciences.Nannaria hokie (pronounced nan-aria ho-key) is about 2 centimeters long, and a dark reddish millipede with yellow-white highlights (apologies to those who thought it would be maroon and orange). These creatures are roughly the size of a penny and usually find their home under rocks, leaves, and among other forest floor debris. The common name "Hokie twisted-claw millipede" comes from the presence of twisted claws on their feet before their reproductive organs.Millipede biodiversity is the primary focus of Marek's lab, which investigates habitats all over the world, including Vietnam, Japan, and the United States. Marek, recent entomology graduate Jackson Means, and other co-authors recently published a paper in the journal The announcement of these new species speaks to the biodiversity that has yet to be discovered, not just in far off exotic locations, but in your backyard."Millipedes are surprisingly abundant and diverse yet have thus far avoided major attention from both the scientific community and the public," Jackson said. "I guarantee that if you just go out into a forest near your home and start looking under leaves you will find several species of millipede, some of which will likely be large and colorful."Millipedes are a unique group of arthropods that are characterized by having two pairs of jointed legs on most segments of their bodies. For anyone who may have turned over a rock in the dirt, the shiny exoskeleton of these types of arthropods should be familiar. These critters boast an incredible amount of biodiversity and have many fascinating and unique traits; some have bright colors, some glow in the dark, and some can even exude cyanide in self-defense. Most millipedes are known as detritivores, or decomposers, and feed on decaying plant matter on forest floors.Including the Hokie millipede, the publication goes on to detail nine other millipedes, all native to Appalachian forests. As the scientists who discovered these arthropods, the Marek lab had the honor of naming these new species, including references to Virginia Tech alumnus and arachnologist Jason Bond (Appalachioria bondi), alumna Ellen Brown (Appalachioria brownae), and even one named after Marek's wife Charity (Rudiloria charityae). This millipede he named for his wife after he found it while taking a quick stroll with family before their wedding by the Chagrin River where he grew up in northeastern Ohio.Millipedes have existed far longer than humans have and represent some of the first land animals discovered by scientists in fossil records. Their role as detritivores is crucial to forest ecosystems, and the primary role of millipedes in this environment is to break down plant matter into smaller material, so that bacteria and other smaller organisms can continue to recycle the material into the soil and make its nutrients available for future generations of life.Despite an ancient lineage and a plentiful food source, the threat of extinction is very real for many millipede species. Millipedes typically remain confined to select, relatively small geographical regions, due to their limited mobility and their dependency on specific habitats. As such, changing climate and habitat destruction is highly threatening to the survival of these organisms."The forests of Appalachia are important carbon sinks, providing habitat to diverse species occupying many trophic levels. Deforestation and habitat loss threaten this biodiversity," Marek said. "Many Appalachian invertebrates, which make up the most diverse component of this fauna, are unknown to science, and without immediate taxonomic attention, species may be irrecoverably lost. My lab's motivation is to preserve biodiversity. Intertwined is our goal to educate and promote an understanding of organismal biology, appreciation of nature, and its immense ecological value."Discovering and preserving these new species and their habitat is the noble goal of Virginia Tech researchers and scientists who seek to understand what crucial role these often-overlooked creatures play in their environments. Investigation into the different types of millipedes out in the world could have any number of repercussions when it comes to understanding evolution, adaptation, and interdependence within an ecosystem.Research was supported by a National Science Foundation Advancing Revisionary Taxonomy and Systematics grant.
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Biology
| 2,021 |
March 4, 2021
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https://www.sciencedaily.com/releases/2021/03/210304133500.htm
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Key enzymes for synthesizing natural products
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Plants, fungi, and bacteria produce natural products that function, among other things, as defenses that are deployed against predators and competitors. In medicine, these compounds are used for antibiotics, cancer drugs, and cholesterol reducers. The team working with associate professor Dr. Robin Teufel and Dr. Britta Frensch of the Institute of Biology II of the Faculty of Biology of the University of Freiburg was able, together with researchers from the ETH Zürich in Switzerland, to shed light on the key role of three enzymes that are involved in synthesizing a class of natural products. The researchers are publishing their findings in the latest edition of
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Actinobacteria produce many natural products, such as those that are known as aromatic polyketides. The Freiburg researchers examined how actinobacteria -- aided by enzymes -- were able to synthesize such bioactive substances from simple, molecular components. Teufel and his team were able to illuminate the key roles played by three enzymes in the biosynthesis of rubromycins, which belong to the most structurally complex aromatic polyketides.The researchers discovered that the enzymes drastically restructure a chemical precursor molecule. Through this process they create the carbon backbone of the rubromycins, which is key to the diverse, pharmacological effects of these compounds. Using chemical and biochemical methods, the researchers succeeded in examining the functions of the enzymes more closely and identifying several previously unknown intermediates in the biosynthesis of the rubromycins. Teufel explains, "We've made important findings about the ways such enzymes control the formation of complex natural products in microorganisms. These findings could play a central role in applying bioengineering to make new types of bioactive rubromycin-polyketides."
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Biology
| 2,021 |
March 4, 2021
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https://www.sciencedaily.com/releases/2021/03/210304112449.htm
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Ancient DNA reveals clues about how tuberculosis shaped the human immune system
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COVID-19 is only the latest infectious disease to have had an outsized impact on human life. A new study employing ancient human DNA reveals how tuberculosis has affected European populations over the past 2,000 years, specifically the impact that disease has had on the human genome. This work, which publishes March 4 in the
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"Present-day humans are the descendants of those who have survived many things -- climate changes and big epidemics, including the Black Death, Spanish flu, and tuberculosis," says senior author Lluis Quintana-Murci of the Institut Pasteur in France. "This work uses population genetics to dissect how natural selection has acted on our genomes."This research focused on a variant of the gene TYK2, called P1104A, which first author Gaspard Kerner had previously found to be associated with an increased risk of becoming ill after infection with Mycobacterium tuberculosis when the variant is homozygous. (TYK2 has been implicated in immune function through its effect on interferon signaling pathways.) Kerner, a PhD student studying genetic diseases at the Imagine Institute of Paris University, began collaborating with Quintana-Murci, an expert in evolutionary genomics, to study the genetic determinants of human tuberculosis in the context of evolution and natural selection.Using a large dataset of more than 1,000 European ancient human genomes, the investigators found that the P1104A variant first emerged more than 30,000 years ago. Further analysis revealed that the frequency of the variant drastically decreased about 2,000 years ago, around the time that present-day forms of infectious Mycobacterium tuberculosis strains became prevalent. The variant is not associated with other infectious bacteria or viruses."If you carry two copies of this variant in your genome and you encounter Mycobacterium tuberculosis, you are very likely to become sick," Kerner says. "During the Bronze Age, this variant was much more frequent, but we saw that it started to be negatively selected at a time that correlated with the start of the tuberculosis epidemic in Europe.""The beauty of this work is that we're using a population genetics approach to reconstruct the history of an epidemic," Quintana-Murci explains. "We can use these methods to try to understand which immune gene variants have increased the most over the last 10,000 years, indicating that they are the most beneficial, and which have decreased the most, due to negative selection."He adds that this type of research can be complementary to other types of immunology studies, such as those performed in the laboratory. Moreover, both researchers say these tools can be used to study the history and implications of many different genetic variants for multiple infectious diseases.
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Biology
| 2,021 |
March 3, 2021
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https://www.sciencedaily.com/releases/2021/03/210303142516.htm
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Birds: Scientists find strongest evidence yet of 'migration gene'
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A team from the Chinese Academy of Sciences and Cardiff University say they have found the strongest evidence yet of a "migration gene" in birds.
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The team identified a single gene associated with migration in peregrine falcons by tracking them via satellite technology and combining this with genome sequencing.They say their findings add further evidence to suggest genetics has a strong role to play in the distance of migration routes.The study, published today in the journal The researchers tagged 56 Arctic peregrine falcons and tracked their journeys by satellite, following their annual flight distances and directions in detail.They found the studied peregrines used five migration routes across Eurasia, probably established between the last ice age 22,000 years ago and the middle-Holocene 6,000 years ago.The team used whole genome sequencing and found a gene -- ADCY8, which is known to be involved in long-term memory in other animals -- associated with differences in migratory distance.They found ADCY8 had a variant at high frequency in long-distance (eastern) migrant populations of peregrines, indicating this variant is being preferentially selected because it may increase powers of long-term memory thought to be essential for long-distance migration.One of the authors on the study, Professor Mike Bruford, a molecular ecologist from Cardiff University's School of Biosciences, said: "Previous studies have identified several candidate genomic regions that may regulate migration -- but our work is the strongest demonstration of a specific gene associated with migratory behaviour yet identified."The researchers also looked at simulations of likely future migration behaviour to predict the impact of global warming.If the climate warms at the same rate it has in recent decades, they predict peregrine populations in western Eurasia have the highest probability of population decline and may stop migrating altogether."In this study we were able to combine animal movement and genomic data to identify that climate change has a major role in the formation and maintenance of migration patterns of peregrines," said Professor Bruford.Professor Xiangjiang Zhan, honorary visiting professor at Cardiff University, now based at the Chinese Academy of Sciences, said: "Our work is the first to begin to understand the way ecological and evolutionary factors may interact in migratory birds -- and we hope it will serve as a cornerstone to help conserve migratory species in the world."The work was carried out by a joint laboratory for biocomplexity research established in 2015 between Cardiff University and the Institute of Zoology at the Chinese Academy of Sciences in Beijing.
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Biology
| 2,021 |
March 3, 2021
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https://www.sciencedaily.com/releases/2021/03/210303142514.htm
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Study reveals details of immune defense guidance system
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At the beginning of an immune response, a molecule known to mobilize immune cells into the bloodstream, where they home in on infection sites, rapidly shifts position, a new study shows. Researchers say this indirectly amplifies the attack on foreign microbes or the body's own tissues.
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Past studies had shown that the immune system regulates the concentration of the molecule, sphingosine 1 phosphate (S1P), in order to draw cells to the right locations. The targeted cells have proteins on their surface that are sensitive to levels of this molecule, enabling them to follow the molecule's "trail," researchers say. S1P concentration gradients, for instance, can guide immune T cells to either stay in lymph nodes, connected glands in which these cells mature, or move into blood vessels.For the first time, researchers at NYU Grossman School of Medicine showed in mice experiments that S1P levels in lymph nodes increase as the immune response mounts. Such activation of immune cells can cause inflammation, swelling, and/or death of targeted cells.While past work had shown that S1P is produced by cells attached to lymph nodes, the new study found that monocytes, circulating immune cells, also produced it when mice were infected with a virus. This in turn may influence the migration of T cells, a set of white blood cells that expands rapidly in response to infection, say the study authors.Publishing in the journal "Our research shows a larger role for sphingosine 1 phosphate in coordinating immune defenses in response to infection and inflammation," says study lead investigator Audrey Baeyens, PhD, a postdoctoral fellow at NYU Langone and its Skirball Institute of Biomolecular Medicine. "While further testing is needed, our findings raise the prospect of controlling levels of S1P to either boost or diminish the body's immune response, as needed."Moreover, the researchers found that when lymph node levels of S1P went up, it signaled T cells to remain in lymph nodes. Such "trapped" T cells, with longer time to mature and become fully armed in the node, increase in their toxicity. These mature T cells can attack cells infected by viruses, or healthy cells as part of autoimmune diseases.Indeed, medications that block S1P, preventing immune cells from leaving the lymph nodes, are used to curb unwanted and autoimmune inflammation related to inflammatory bowel disease, psoriasis, and multiple sclerosis, a disease for which fingolimod (Gilenya) is one of the few approved treatments.Researchers say their findings could also explain why multiple sclerosis patients can experience severe disease relapse immediately after ceasing fingolimod treatment, as T cells held long in lymph nodes are then freed to attack the body's nerves, a key trait of the disease."Now that we have a better understanding of sphingosine 1 phosphate inhibition, we can work on finding new uses for this class of medications, perhaps by manipulating the time T cells spend in the lymph nodes," says study senior investigator Susan Schwab, PhD. Schwab is an associate professor in the Department of Pathology at NYU Langone and Skirball.For the study, S1P levels were measured in mice bred to develop symptoms of multiple sclerosis, a disease involving severe inflammation of the brain and spine. They also measured S1P levels in mice exposed to viral genetic material to mimic the inflammation that occurs in infection.Schwab says the team next plans to study how different S1P levels affect T cell maturation, and how these different maturation times strengthen or weaken the overall immune response to infection.
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Biology
| 2,021 |
March 3, 2021
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https://www.sciencedaily.com/releases/2021/03/210303142452.htm
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Tackling tumors with two types of virus
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An international research group led by the University of Basel has developed a promising strategy for therapeutic cancer vaccines. Using two different viruses as vehicles, they administered specific tumor components in experiments on mice with cancer in order to stimulate their immune system to attack the tumor. The approach is now being tested in clinical studies.
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Making use of the immune system as an ally in the fight against cancer forms the basis of a wide range of modern cancer therapies. One of these is therapeutic cancer vaccination: following diagnosis, specialists set about determining which components of the tumor could function as an identifying feature for the immune system. The patient is then administered exactly these components by means of vaccination, with a view to triggering the strongest possible immune response against the tumor.Viruses that have been rendered harmless are used as vehicles for delivering the characteristic tumor molecules into the body. In the past, however, many attempts at creating this kind of cancer therapy failed due to an insufficient immune response. One of the hurdles is that the tumor is made up of the body's own cells, and the immune system takes safety precautions in order to avoid attacking such cells. In addition, the immune cells often end up attacking the "foreign" virus vehicle more aggressively than the body's own cargo. With almost all cancer therapies of this kind developed so far, therefore, the desired effect on the tumor has failed to materialize. Finding the appropriate vehicle is just as relevant in terms of effectiveness as the choice of tumor component as the point of attack.The research group led by Professor Daniel Pinschewer of the University of Basel had already discovered in previous studies that viruses from the arenavirus family are highly suitable as vehicles for triggering a strong immune response. The group now reports in the journal The researchers focused on two distantly related viruses called Pichinde virus and Lymphocytic choriomeningitis virus, which they adapted via molecular biological methods for use as vaccine vectors. When they took the approach of administering the selected tumor component first with the one virus and then, at a later point, with the other, the immune system shifted its attack away from the vehicle and more towards the cargo. "By using two different viruses, one after the other, we focus the triggered immune response on the actual target, the tumor molecule," explains Pinschewer.In experiments with mice, the researchers were able to measure a potent activation of killer T cells that eliminated the cancer cells. In 20% to 40% of the animals -- depending on the type of cancer -- the tumor disappeared, while in other cases the rate of tumor growth was at least temporary slowed."We can't say anything about the efficacy of our approach in humans as yet," Pinschewer points out. However, ongoing studies with a cancer therapy based on a single arenavirus have already shown promising results. The effects on tumors in animal experiments cannot be assumed to translate directly into the effect on corresponding cancer types in humans. "However, since the therapy with two different viruses works better in mice than the therapy with only one virus, our research results make me optimistic," Pinschewer adds.The biotech company Hookipa Pharma, of which Pinschewer is one of the founders, is now investigating the efficacy of this novel approach to cancer therapy in humans. "We are currently exploring what our approach by itself can actually achieve," the researcher says. "If it proves successful, a wide range of combinations with existing therapies could be envisaged, in which the respective mechanisms would join forces to eliminate tumors even better."
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Biology
| 2,021 |
March 3, 2021
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https://www.sciencedaily.com/releases/2021/03/210303142448.htm
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Fluorescent nanodiamonds successfully injected into living cells
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As odd as it sounds, many scientists have attempted to place extremely small diamonds inside living cells. Why? Because nanodiamonds are consistently bright and can give us unique knowledge about the inner life of cells over a long time. Now physics researchers at Lund University in Sweden have succeeded in injecting a large number of nanodiamonds directly to the cell interior.
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Diamonds are not only sought after for their beauty, but also for their uniquely luminescent properties, at least among scientists. Unlike other fluorescent materials, they do not bleach."We actually think of them as a dye. In addition, they are biocompatible," says Elke Hebisch, researcher at solid state physics at Lund University.Together with Professor Christelle Prinz, she has "injected" fluorescent nano-sized diamonds into living cells.As a researcher, having such a reporter from inside a cell has many advantages: gaining new knowledge about the cell, as well as monitoring what happens inside the cell over time."Especially the latter would be a great step forward, as it is currently possible to take snapshots of, for example, proteins in a cell, but difficult to follow changes over time," explains Elke Hebisch.What would researchers want to know? It could be about separating healthy cells from diseased ones, targeting disease-causing proteins and other proteins within a specific cell, or monitoring variations in temperature and pH-levels. The knowledge gained could be pure basic research but can also be used to understand diseases and develop drugs.Other researchers have previously tried to do the same thing, but the diamonds were then taken care of by the cell's "cleaners," the so-called lysosomes, that quickly encapsulated the foreign substance."In that scenario,they are not useful since they are trapped in lysosomes and unable to interact with the cell components. Others have managed to get the diamonds into the cell one cell at a time, but that is far too time-consuming to become a realistic alternative," says Christelle Prinz.The same technique could eventually be used to transport other molecules in order to alter cells or heal diseased cells.On a final note: is using nanodiamonds expensive? No, Elke Hebisch explains -- the quantities needed are extremely small. They are bought in a bottle where they are suspended around in water, and cost the same as regular antibodies.The researchers built nanostraws onto a substrate. They then added cells on the nanostraws , and when mild electrical pulses were applied across the subtrate, the "pores" of the cell membrane dilated and the nanodiamonds went through the nanostraws into the cells. The method was inspired by a similar method developed at Standford University for a different purpose.
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Biology
| 2,021 |
March 3, 2021
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https://www.sciencedaily.com/releases/2021/03/210303142439.htm
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New search engine for single cell atlases
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A new software tool allows researchers to quickly query datasets generated from single-cell sequencing. Users can identify which cell types any combination of genes are active in. Published in
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Processing times for such datasets are just a few seconds, saving time and computing costs. The tool, developed by researchers at the Wellcome Sanger Institute, can be used much like a search engine, as users can input free text as well as gene names.Techniques to sequence the genetic material from an individual cell have advanced rapidly over the last 10 years. Single-cell RNA sequencing (scRNAseq), used to assess which genes are active in individual cells, can be used on millions of cells at once and generates vast amounts of data (2.2 GB for the Human Kidney Atlas). Projects including the Human Cell Atlas and the Malaria Cell Atlas are using such techniques to uncover and characterise all of the cell types present in an organism or population. Data must be easy to access and query, by a wide range of researchers, to get the most value from them.To allow for fast and efficient access, a new software tool called scfind uses a two-step strategy to compress data ~100-fold. Efficient decompression makes it possible to quickly query the data. Developed by researchers at the Wellcome Sanger Institute, scfind can perform large scale analysis of datasets involving millions of cells on a standard computer without special hardware. Queries that used to take days to return a result, now take seconds.The new tool can also be used for analyses of multi-omics data, for example by combining single-cell ATAC-seq data, which measures epigenetic activity, with scRNAseq data.Dr Jimmy Lee, Postdoctoral Fellow at the Wellcome Sanger Institute, and lead author of the research, said: "The advances of multiomics methods have opened up an unprecedented opportunity to appreciate the landscape and dynamics of gene regulatory networks. Scfind will help us identify the genomic regions that regulate gene activity -- even if those regions are distant from their targets."Scfind can also be used to identify new genetic markers that are associated with, or define, a cell type. The researchers show that scfind is a more accurate and precise method to do this, compared with manually curated databases or other computational methods available.To make scfind more user friendly, it incorporates techniques from natural language processing to allow for arbitrary queries.Dr Martin Hemberg, former Group Leader at the Wellcome Sanger Institute, now at Harvard Medical School and Brigham and Women's Hospital, said: "Analysis of single-cell datasets usually requires basic programming skills and expertise in genetics and genomics. To ensure that large single-cell datasets can be accessed by a wide range of users, we developed a tool that can function like a search engine -- allowing users to input any query and find relevant cell types."Dr Jonah Cool, Science Program Officer at the Chan Zuckerberg Initiative, said: "New, faster analysis methods are crucial for finding promising insights in single-cell data, including in the Human Cell Atlas. User-friendly tools like scfind are accelerating the pace of science and the ability of researchers to build off of each other's work, and the Chan Zuckerberg Initiative is proud to support the team that developed this technology."
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Biology
| 2,021 |
March 3, 2021
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https://www.sciencedaily.com/releases/2021/03/210301112355.htm
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Assessing a compound's activity, not just its structure, could accelerate drug discovery
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Assessing a drug compound by its activity, not simply its structure, is a new approach that could speed the search for COVID-19 therapies and reveal more potential therapies for other diseases.
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This action-based focus -- called biological activity-based modeling (BABM) -- forms the core of a new approach developed by National Center for Advancing Translational Sciences (NCATS) researchers and others. NCATS is part of the National Institutes of Health (NIH). Researchers used BABM to look for potential anti-SARS-CoV-2 agents whose actions, not their structures, are similar to those of compounds already shown to be effective.NCATS scientists Ruili Huang, Ph.D., and Wei Zheng, Ph.D., led the research team that created the approach. Their findings were posted online Feb. 23 by the journal "With this new method, you can find completely new chemical structures based on activity profiles and then develop completely new drugs," Huang explained. Thus, using information about a compound's biological activity may expand the pool of promising treatments for a wide range of diseases and conditions.When researchers seek new compounds or look for existing drugs to repurpose against new diseases, they are increasingly using screening tools to predict which drugs might be good candidates. Virtual screening, or VS, allows scientists to use advanced computer analyses to find potentially effective candidates from among millions of compounds in collections.Traditional VS techniques look for compounds with structures similar to those known to be effective against a particular target on a pathogen or cell, for example. Those structural similarities are then assumed to deliver similar biological activities.With BABM, however, researchers don't need to know a compound's chemical structure, according to Huang. Instead, they use a profile of a compound's activity patterns -- how it behaves at multiple concentrations against a panel of targets or tests -- to predict its potential effectiveness against a new target or in a new drug assay.The now-widespread use of quantitative high-throughput screening (qHTS) allows BABM more accuracy in its predictions. qHTS assesses a compound's effectiveness at multiple concentrations in thousands of tests over time. That practice provides far more detail about how a compound behaves than does traditional high-throughput screening, which tests only a single concentration of the compound. The information generated by qHTS creates a stronger biological activity profile -- also known as a signature -- for each one of millions of compounds.To test the BABM approach, the researchers tapped the vast pool of data generated by hundreds of qHTS analyses run on NCATS' in-house collection of more than 500,000 compounds and drugs. First, they verified BABM's ability to use activity profiles to identify compounds already shown to be effective against the Zika and Ebola viruses. BABM also identified new compounds that showed promise against those viruses.The scientists then turned to SARS-CoV-2, the virus that causes COVID-19. They applied BABM, a structure-based model and a combined approach to analyze the NCATS library's compounds to find potential anti-SARS-CoV-2 agents. BABM predicted that the activity profiles of 311 compounds might indicate promise against the coronavirus.The researchers then had an outside laboratory test those 311 compounds against the live SARS-CoV-2 virus. The result: Nearly one-third of the BABM-backed compounds (99) showed antivirus activity in the test. The BABM-driven prediction hit rate topped that of the structure-based model -- and combining the activity-based and structure-based models yielded even better predictive results.A key advantage to BABM is speed. "This method is very fast -- you essentially just run a computer algorithm, and you can identify many new drug leads, even with new chemical structures," Huang noted. In fact, screening the entire NCATS library of half a million compounds for anti-SARS-CoV-2 candidates took only a few minutes.BABM also is a transferable tool -- it's not limited to use in the NCATS compound libraries. "Anyone can use this method by applying any biological activity profile data, including publicly available NCATS data," Huang emphasized.The NCATS researchers predict their activity-based model's impact could extend far beyond the search for COVID-19 treatments and small-molecule drug discovery. Given any substance with an available activity profile, scientists can predict its activity against a new target, for a new indication, or against a new disease."In addition to small molecules, this approach can be applied to biologics, antibodies, and other therapies," Huang said. "BABM is for all drug discovery projects."
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Biology
| 2,021 |
March 3, 2021
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https://www.sciencedaily.com/releases/2021/03/210303093453.htm
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Key steps discovered in production of critical immune cell
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WEHI researchers have uncovered a process cells use to fight off infection and cancer that could pave the way for precision cancer immunotherapy treatment.
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Through gaining a better understanding of how this process works, researchers hope to be able to determine a way of tailoring immunotherapy to better fight cancer.Led by Dr Dawn Lin and Dr Shalin Naik and published in This research lays the foundation for future studies into the body's response to environmental stressors, such as injury, infection or cancer, at a single cell level.Dendritic cells are immune cells that activate 'killer' T cells, which are vital for clearing viral infections, such as COVID-19, but also for triggering a response to cancers such as melanoma and bowel cancer.The Flt3L hormone can increase dendritic cell numbers, helping the immune system to fight off cancer and infection.Dr Naik and his team studied developing immune cells at a single cell level to gain a deeper understanding of how the body uses these cells to trigger immune responses."There is one type of dendritic cell that the body uses to fight some infections and cancer. The Flt3L hormone increases numbers of this particular dendritic cell," he said."We know quite well how the dendritic cell fights the cancer, but we don't know how the Flt3L hormone increases the numbers of those dendritic cells."Researchers used a single-cell 'barcoding' technique to uncover what happened when dendritic cells multiplied."By using cellular barcoding -- where we insert short synthetic DNA sequences, we call barcodes inside cells -- we were able to determine which cells produced dendritic cells in pre-clinical models," Dr Naik said."As a result of this research, we now better understand the actions of the Flt3L hormone that is currently used in cancer immunotherapy trials, and how it naturally helps the body fight cancer and infection. This is a first step to design better precision immunotherapy treatments for cancer."This research answers a 50-year-long question as to what causes a stem cell to react in response to immense stress, such as infection or inflammation."We have known that the Flt3L hormone increases the number of dendritic cells for decades but now there is a focus on applying this knowledge to cancer immunotherapy and potentially to infection immunotherapy as well," Dr Naik said."The next stage in our research is to create 'dendritic cell factories' using our new knowledge, to produce millions to billions of these infection fighting cells and then use those in immunotherapy treatments.""These findings are a vital first step to improving immunotherapy treatments for patients, to help them better fight cancer and infection."This work was made possible with funding from the National Health and Medical Research Council, the Australia Research Council, Gilead, the Victorian Cancer Agency and the Victorian Government.
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Biology
| 2,021 |
March 3, 2021
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https://www.sciencedaily.com/releases/2021/03/210303090414.htm
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Vaccine shows signs of protection against dozen-plus flu strains
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Ask Eric Weaver about pandemics, and he's quick to remind you of a fact that illustrates the fleeting nature of human memory and the proximal nature of human attention: The first pandemic of the 21st century struck not in 2019, but 2009.
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That's when the H1N1/09 swine flu emerged, eventually infecting upwards of 1.4 billion people -- nearly one of every five on the planet at the time. True to the name, swine flus jump to humans from pigs. It's a phenomenon that has been documented more than 400 times since the mid-2000s in the United States alone."They're considered the great mixing vessel," said Weaver, associate professor of biological sciences at the University of Nebraska-Lincoln. "They're susceptible to their own circulating influenzas, as well as many of the avian and human influenzas."If you put an avian, a swine and a human virus into the same cell, they can swap genome segments. When you mix those viruses in the swine, what pops out could be all swine, or a little human and swine, or a little avian and swine, or a little of all three. And you never know: You might get the perfect combination of parts that makes for a very high-fitness virus that is highly transmissible and new to humans, meaning that people don't have immunity to it."All of it helps explain why Weaver has spent years researching how to develop a vaccine that protects against as many strains of influenza as possible, including those that have yet to emerge. In a new study, Weaver, doctoral candidate Brianna Bullard and colleagues have debuted the results of an approach that demonstrates promising signs of protection against more than a dozen swine flu strains -- and more than a leading, commercially available vaccine."This is the best data I've ever seen in the (research) literature," Weaver said of the team's findings, recently published in the journal The "H" and "N" in H1N1 refer to two crucial proteins, hemagglutinin and neuraminidase, that reside on the surface of influenza viruses and allow them to enter and exit cells. But it's the H3 subtype of influenza -- H3N2, specifically -- that has accounted for more than 90% of swine-to-human infections in the United States since 2010, making it the target of Weaver's most recent research.In his efforts to combat multiple strains of swine H3N2, Weaver employed a computational program, Epigraph, that was co-developed by Bette Korber of Los Alamos National Laboratory. The "epi" is short for epitope: the bit of a viral protein, such as hemagglutinin, that draws the attention of an immune system. Any one epitope, if administered as a vaccine, will stimulate an immune response against only a limited number of closely related viral strains.So Weaver put Epigraph to work analyzing data on every known and available mutational variant of hemagglutinin, which it then used to predict which collection of epitopes would grant immunity against the broadest, most diverse range of strains. Those hemagglutinin proteins are usually composed of around 560 amino acids, whose type and sequence determine the structure and function of the epitopes. Starting at the start of an amino acid string, Epigraph analyzed the sequence of amino acids No. 1 through No. 9 before sliding down to analyze Nos. 2-10, then 3-11, and so on. After doing the same for every epitope, the program determined the most common nine-acid sequences from the entire batch -- the entire catalogue of known H3N2 strains in pigs."So what you end up with are the most common epitopes that exist in nature linked together, then the second-most common, and then the third-most common," Weaver said. "When you look at it from an evolutionary standpoint, the first resembles what most of the viruses look like. The second starts to look a bit different, and the third looks even more different."But all three of these make a contribution to the vaccine itself, and they work through slightly different mechanisms."When testing the resulting three-epitope cocktail in mice and pigs, the team found that it yielded immune response signatures and physiological protection against a much wider variety of strains than did FluSure, a commercial swine vaccine.In mice, the team tested its vaccine against 20 strains of swine-derived H3 flu. The vaccine generated clinically relevant concentrations of antibodies -- the molecules that neutralize a virus before it enters a cell -- against 14 of those 20 strains. FluSure managed the same feat against just four of the 20. A separate experiment presented the mice with four strains that represented a cross-section of H3 diversity. In all four cases, Epigraph-vaccinated mice produced notable levels of T-cells, which, among other responsibilities, instruct infected cells to die for the sake of avoiding further viral transmission. FluSure-vaccinated mice, by contrast, showed little T-cell response to any of the four strains.Those cellular-level responses appeared to scale up, too. When challenged with flu viruses, Epigraph-vaccinated mice generally lost less weight, and exhibited fewer viral particles in the lungs, than did their FluSure-vaccinated counterparts. And when mice were challenged with a lethal H3 strain derived from humans, only the Epigraph vaccine protected all of the specimens that received it.That performance carried over to pigs. Cells taken from swine injected with just one dose of the Epigraph vaccine produced substantial antibodies in response to 13 of 20 H3 strains, including 15 of 16 that originated in North America or were derived from humans. A single dose of FluSure, meanwhile, generated significant antibodies against none of the 20. Though a second dose of FluSure did elevate those antibody concentrations, they remained about four times lower, on average, than the Epigraph-induced responses. T-cell responses, too, remained higher in Epigraph-vaccinated pigs.More, and more-generalizable, experiments will be needed to verify the Epigraph vaccine's performance, Weaver said. For one, the team is looking to test whether the vaccine candidate generates actual immunity in living pigs, beyond the promising immune responses from their cells in a lab. There's also the matter of determining how long any immunity might last.But Weaver has already developed a human equivalent of the swine flu vaccine cocktail that he's likewise preparing to test. Considering the similarities between flu infections in humans and pigs -- susceptibilities to subtypes, clinical symptoms, even viral receptors in respiratory tracts -- he said the recent findings bode well for those future, human-centric efforts. Success on that front could eventually mean pivoting away from the current approach to flu vaccinations, whereby virologists are forced to predict which strains will dominate a flu season -- and, despite their best efforts, sometimes miss the mark."This study is equivalent to a bench-to-bedside study, where the positive results in the preclinical mouse study are confirmed by positive results in a clinical pig study," Weaver said. "This gives us confidence that when the concept is applied to human influenza virus, we'll see the same translation from preclinical studies to clinical studies in humans."Weaver, Bullard and Korber authored the
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Biology
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March 2, 2021
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https://www.sciencedaily.com/releases/2021/03/210302212001.htm
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Fast-learning cuttlefish pass the 'marshmallow test'
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Much like the popular TikTok challenge where kids resist eating snacks, cuttlefish can do the same! Cuttlefish can delay gratification -- wait for a better meal rather than be tempted by the one at hand -- and those that can wait longest also do better in a learning test, scientists have discovered.
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This intriguing report marks the first time a link between self-control and intelligence has been found in an animal other than humans and chimpanzees. It is published this week in The research was conducted at the Marine Biological Laboratory (MBL), Woods Hole, while lead author Alexandra Schnell of University of Cambridge, UK, was in residence there as a Grass Fellow. Among Schnell's collaborators was MBL Senior Scientist Roger Hanlon, a leading expert in cephalopod behavior and joint senior author on the paper."We used an adapted version of the Stanford marshmallow test, where children were given a choice of taking an immediate reward (1 marshmallow) or waiting to earn a delayed but better reward (2 marshmallows)," Schnell says. "Cuttlefish in the present study were all able to wait for the better reward and tolerated delays for up to 50-130 seconds, which is comparable to what we see in large-brained vertebrates such as chimpanzees, crows and parrots."Cuttlefish that could wait longer for a meal also showed better cognitive performance in a learning task. In that experiment, cuttlefish were trained to associate a visual cue with a food reward. Then, the situation was reversed, so the reward became associated with a different cue. "The cuttlefish that were quickest at learning both of those associations were better at exerting self-control," Schnell says.Why cuttlefish have evolved this capacity for self-control is a bit mysterious. Delayed gratification in humans is thought to strengthen social bonds between individuals -- such as waiting to eat so a partner can first -- which benefits the species as a whole. It may also be a function of tool-building animals, who need to wait to hunt while constructing the tool.But cuttlefish are not social species, and they don't build tools. Instead, the authors suggest, delayed gratification may be a by-product of the cuttlefish's need to camouflage to survive."Cuttlefish spend most of their time camouflaging, sitting and waiting, punctuated by brief periods of foraging," Schnell says. "They break camouflage when they forage, so they are exposed to every predator in the ocean that wants to eat them. We speculate that delayed gratification may have evolved as a byproduct of this, so the cuttlefish can optimize foraging by waiting to choose better quality food."Finding this link between self-control and learning performance in a species outside of the primate lineage is an extreme example of convergent evolution, where completely different evolutionary histories have led to the same cognitive feature.Other collaborators include joint senior author Nicola Clayton at University of Cambridge and scientists at Ripon College in Wisconsin and the Karl Landsteiner University of Health Science, Krems, Austria.
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Biology
| 2,021 |
March 2, 2021
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https://www.sciencedaily.com/releases/2021/03/210302130656.htm
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A new blindness gene uncovered in a canine study
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Inherited retinal dystrophy is a common cause of blindness, with as many as two million people suffering from the disorder globally. No effective treatment is available for retinal dystrophies. Gene therapy is expected to offer a solution, but developing such therapies is possible only when the genetic cause of the disease is known. Related mutations have been identified in more than 70 genes so far, but the genetic background of the disease remains unknown in as many as half of the patients.
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"Retinal dystrophy has been described in over 100 dog breeds, with related investigations helping to identify new genes associated and pathogenic mechanisms with blindness across different breeds. IFT122 is a good example, offering a potential explanation for unsolved human cases as well," Professor Hannes Lohi states.Data encompassing more than a thousand Lapponian Herders and Finnish Lapphunds from a canine DNA bank were utilised in the study. Previously, several retinal dystrophy genes have been described in both breeds."Among other finds, two eye disease genes have previously been identified in Lapponian Herders, but they have not accounted for all cases. In some dogs, the disease is caused by the IFT122 gene. The finding is significant since gene tests can now distinguish between retinal dystrophies associated with different genes in breeds, which makes a difference in monitoring disease progression, making prognoses, and developing novel treatments. Diagnostics are getting better and making the job of veterinarians easier," explains Maria Kaukonen, Doctor of Veterinary Medicine.The gene discovery also facilitates the understanding of retinal biology. IFT122 is part of a protein complex linked with ciliary function in the retina."The age of onset varies, and the disease progresses slowly in some dogs. IFT122 is known to contribute to the transport of opsin in photoreceptor cells. The gene variant disturbs this transport and results in progressive blinding. Since IFT122 is associated with cilia's function, which is important to the body, we studied some of the dogs even more closely with regard to other issues potentially linked with cilia-related disturbances, such as renal abnormalities or serious developmental disorders of the internal organs. We found that the damage seems to be limited to the retina alone. This information helps us understand the gene's mechanisms of action," Kaukonen adds.The findings are also significant for further plans to remove the disease from different breeds. In the Lapponian Herders and Finnish Lapphunds, the share of individuals carrying the gene variant was 28% and 12%, respectively."This is a recessively inherited disease, which means that a dog that will become blind inherits the variant from both parents, who are both carriers of the variant. Gene testing can help avoid carrier-carrier combinations, easily preventing the birth of sick dogs. A new concrete tool has been developed based on the study for the benefit of breeders," says Lohi.The new study is part of a broader research project on the genetic background of inherited diseases by Professor Lohi's research group. Kaukonen recently transferred to a research group active at the University of Oxford, focusing on developing gene therapies for retinal dystrophy. At the same time, Kaukonen and Lohi are continuing close collaboration to survey a range of eye diseases together with the Helsinki University Hospital and other operators."There are a lot more gene findings associated with eye diseases on the way in canine research. We are only just getting started. Among other things, we are currently investigating the genetic background of glaucoma as well as corneal and retinal dystrophia in roughly 30 breeds. The preliminary results are promising," says Lohi.
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Biology
| 2,021 |
March 2, 2021
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https://www.sciencedaily.com/releases/2021/03/210302130647.htm
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Bitter receptor involved in anti-inflammatory effect of resveratrol?
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Resveratrol is a plant compound found primarily in red grapes and Japanese knotweed. Its synthetic variant has been approved as a food ingredient in the EU since 2016. At least in cell-based test systems, the substance has anti-inflammatory properties. A recent collaborative study by the Leibniz Institute for Food Systems Biology at the Technical University of Munich and the Institute of Physiological Chemistry at the University of Vienna has now shown that the bitter receptor TAS2R50 is involved in this effect. The team of scientists led by Veronika Somoza published its results in the
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Bitter food ingredients not only influence the taste of a food, but often also exert other physiological effects. For example, resveratrol not only tastes bitter, but also reduces biomarkers of inflammation as shown in various clinical trials including, e.g., patients with metabolic syndrome and related disorders. No research group had yet investigated whether bitter receptors also play a role in this.To investigate this question, the team led by Veronika Somoza carried out experiments with a human cell line derived from a gum biopsy. The cells of this cell line are a suitable test system for investigating interactions between bitter substances, bitter receptors and the release of inflammatory markers. As the team shows for the first time, these cells have active bitter receptor genes and are also immunocompetent. That is, when the cells are treated with surface antigens from bacteria that trigger gingival inflammation, they release quantifiable amounts of the inflammatory marker interleukin-6.In the current study, resveratrol reduced the amount of inflammatory marker released by about 80 percent. Additional administration of the bitter-masking substance homoeriodictyol reduced this anti-inflammatory effect by about 17 percent. "This is remarkable because homoeriodictyol is a natural substance that has been shown to reduce the bitterness of food ingredients mediated via certain bitter receptors. These receptors include the bitter receptor TAS2R50, which is also expressed by the cells of our test system," explains Veronika Somoza, deputy director of the Institute of Physiological Chemistry in Vienna and director of the Leibniz Institute in Freising. Additional knock-down experiments performed by the researchers as well as computer-assisted structure-function analyses support this finding. "Therefore, it is reasonable to conclude that this receptor type is involved in mediating the anti-inflammatory resveratrol effect," Somoza says.She adds: "Of course, there is still a great deal of research to be done. Nevertheless, the study results already provided new insights to help elucidate the molecular interactions between bitter-tasting food ingredients, bitter receptors and immune responses. In the future, it will also be exciting to find out whether bitter substances and bitter receptors could play a role with regard to inflammatory gum diseases such as periodontitis."
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Biology
| 2,021 |
March 2, 2021
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https://www.sciencedaily.com/releases/2021/03/210302130639.htm
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Division of labor within regenerating liver maintains metabolism, mouse study finds
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The liver has a rare superpower among body organs -- the ability to regenerate, even if 70% of its mass is removed. It also keeps up its metabolic and toxin-removing work during the process of regeneration, thanks to a subset of cells that expand their workload while the rest focus on multiplication, a new study in mice found.
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Furthermore, the cells of the liver communicate with each other to coordinate regeneration activity, which progresses from the center to the periphery of the missing liver lobes, researchers at the University of Illinois Urbana-Champaign said."It's remarkable how we still don't understand many aspects of liver regeneration," said Illinois biochemistry professor Auinash Kalsotra, who led the study published in the journal Previous work from Kalsotra's group found that, during regeneration, mature liver cells -- normally stable and slow to divide -- revert to a more pliable neonatal state. This allows them to divide quickly but causes them to lose their metabolic function. Questions remained of how the liver maintained mature metabolic function while its cells reverted to an immature state, and how the cells know when to stop proliferating."Whether regeneration follows a surgical resection of the liver, or is due to an underlying liver disease or chronic liver injury from alcohol or toxins, the liver has to keep functioning. This study revealed a division of labor within the liver that allowed it to address the body's metabolic needs while regenerating," said Kalsotra, a member of the Carl R.. Woese Institute for Genomic Biology at Illinois.The researchers used a technique that allowed them to individually sequence the RNA of each cell in regenerating mouse livers, revealing its activity. They studied mouse livers at various points during the regeneration process to map how regeneration progressed, as well as where metabolic function was maintained.They identified a specific class of cells that do not proliferate, but instead ramp up their metabolic function, taking on a greater workload. These were localized near blood vessels, said graduate students Ullas Chembazhi and Sushant Bangru, the co-first authors of the paper.Meanwhile, the regenerating cells multiplied in a coordinated manner, starting from the middle regions and progressing outward toward the liver's periphery -- contrary to prevailing theories in the field that proliferation begins near the veins."We found it's actually the midlobular cells that are the most prolific, and that made perfect sense to us because we had just found that there are certain cells that keep and actually turn up their metabolic profiles. These metabolic cells live near the blood vessels, so it makes sense that those cells should stay put, and the interior cells are the ones that divide," Kalsotra said.The researchers found that the regeneration and metabolic activities were coordinated through extensive cell-to-cell communication. The communication dramatically increased after part of the liver was removed, but by the time regeneration slowed and stopped, the signaling had gone back down toward base levels.In studying the coordination between cells, they also found a possible explanation for how the regeneration process regulates itself so the liver stops growing when it reaches its original size. Mature liver cells had an abundance of receptors on their surfaces that were activated by molecules their neighboring cells released after surgery, triggering the cells to become neonatal-like and divide. During the proliferation process, however, the cells stopped expressing the receptors, allowing them to return to a mature state when division was complete."Normally, the cells are ready to receive these signals. But once they do and are regenerating, they don't need to keep receiving those signals because they would get into an endless run of proliferation. So they stop expressing these receptors. Once the triggers are gone and regeneration is complete, the cells start to make more of the receptors so they are ready if there's an injury again," Kalsotra said.The National Institutes of Health, the Muscular Dystrophy Association, the Cancer Center at Illinois and the Center for Advanced Study at Illinois supported this work.
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Biology
| 2,021 |
March 2, 2021
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https://www.sciencedaily.com/releases/2021/03/210302104819.htm
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A mechanism by which cells build 'mini-muscles' underneath their nucleus identified
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Research groups at the University of Helsinki uncovered how motor protein myosin, which is responsible for contraction of skeletal muscles, functions also in non-muscle cells to build contractile structures at the inner face of the cell membrane. This is the first time when such 'mini-muscles', also known as stress fibers, have been seen to emerge spontaneously through myosin-driven reorganization of the pre-existing actin filament network in cells. Defects in the assembly of these 'mini-muscles' in cells lead to multiple disorders in humans, and in the most severe cases to cancer progression.
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A new study published in "Previous studies from our group at University of Helsinki and other laboratories abroad demonstrated that stress fibers can arise at the front of the cell from small actin- and myosin-containing precursor structures, and that stress fibers disassemble at the back of the cell as it moves forward. Now we reveal a completely new mechanism by which stress fibers can form in cells, and provide an explanation for why 'mysterious' myosin pulses occur at the cell cortex," Lappalainen comments."Intriguingly, we also observed that this type of stress fiber generation was most prominent under the nucleus, which stores all genetic information and is the largest organelle in our cells. It could be that cortical stress fibers protect the nucleus or aid the movement of the nucleus along with the rest of the cell body," adds Dr. Jaakko Lehtimaki who is the lead author of this study.The new findings bring forth an important new feature in the stress fiber toolbox. Cells in the three-dimensional tissue environment rarely display stress fiber precursors typically seen in cells migrating on a cell culture dish. Thus, myosin pulse-mediated assembly process enables assembly of contractile structures in cells migrating in various environments. Because myosin pulses have been witnessed in many different cell- and tissue types, this might serve as a universal mechanism for local force-production in the non-muscle tissues.The most abundant components of our muscles are myosin motor proteins, and bar-like filaments assembled from protein actin. Coordinated 'crawling' of myosin motor proteins along actin filaments is the principal mechanism that generates the force for muscle contraction. However, such myosin-based force-production is not limited to muscles, because also cells in other tissues within our bodies have similar contractile structures. These 'mini-muscles' of non-muscle cells, called stress fibers, are composed of the same central players (actin and myosin) as the contractile units of muscles.Within our bodies, skeletal muscles attach to bones via tendons, whereas special adhesion structures named focal adhesions connect stress fibers to the surroundings of the cell. This enables the stress fibers to sense and emit forces between cells and their environment. In addition to being the major force-sensitive structures in cells, stress fibers are important for proper differentiation that is, specialization of cells to different tasks in the body. They also protect the nucleus when the cell is migrating in a challenging three-dimensional tissue environment. Consequently, defects in stress fiber assembly in cells contribute to multiple disorders, such as atherosclerosis, neuropathies, and cancer progression.
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Biology
| 2,021 |
March 2, 2021
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https://www.sciencedaily.com/releases/2021/03/210302094102.htm
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Origin of life: The chicken-and-egg problem
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A Ludwig-Maximilians-Universitaet (LMU) in Munich team has shown that slight alterations in transfer-RNA molecules (tRNAs) allow them to self-assemble into a functional unit that can replicate information exponentially. tRNAs are key elements in the evolution of early life-forms.
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Life as we know it is based on a complex network of interactions, which take place at microscopic scales in biological cells, and involve thousands of distinct molecular species. In our bodies, one fundamental process is repeated countless times every day. In an operation known as replication, proteins duplicate the genetic information encoded in the DNA molecules stored in the cell nucleus -- before distributing them equally to the two daughter cells during cell division. The information is then selectively copied ('transcribed') into what are called messenger RNA molecules (mRNAs), which direct the synthesis of the many different proteins required by the cell type concerned. A second type of RNA -- transfer RNA (tRNA) -- plays a central role in the 'translation' of mRNAs into proteins. Transfer RNAs act as intermediaries between mRNAs and proteins: they ensure that the amino-acid subunits of which each particular protein consists are put together in the sequence specified by the corresponding mRNA.How could such a complex interplay between DNA replication and the translation of mRNAs into proteins have arisen when living systems first evolved on the early Earth? We have here a classical example of the chicken-and-the-egg problem: Proteins are required for transcription of the genetic information, but their synthesis itself depends on transcription.LMU physicists led by Professor Dieter Braun have now demonstrated how this conundrum could have been resolved. They have shown that minor modifications in the structures of modern tRNA molecules permit them to autonomously interact to form a kind of replication module, which is capable of exponentially replicating information. This finding implies that tRNAs -- the key intermediaries between transcription and translation in modern cells -- could also have been the crucial link between replication and translation in the earliest living systems. It could therefore provide a neat solution to the question of which came first -- genetic information or proteins?Strikingly, in terms of their sequences and overall structure, tRNAs are highly conserved in all three domains of life, i.e. the unicellular Archaea and Bacteria (which lack a cell nucleus) and the Eukaryota (organisms whose cells contain a true nucleus). This fact in itself suggests that tRNAs are among the most ancient molecules in the biosphere.Like the later steps in the evolution of life, the evolution of replication and translation -- and the complex relationship between them -- was not the result of a sudden single step. It is better understood as the culmination of an evolutionary journey. "Fundamental phenomena such as self-replication, autocatalysis, self-organization and compartmentalization are likely to have played important roles in these developments," says Dieter Braun. "And on a more general note, such physical and chemical processes are wholly dependent on the availability of environments that provide non-equilibrium conditions."In their experiments, Braun and his colleagues used a set of reciprocally complementary DNA strands modeled on the characteristic form of modern tRNAs. Each was made up of two 'hairpins' (so called because each strand could partially pair with itself and form an elongated loop structure), separated by an informational sequence in the middle. Eight such strands can interact via complementary base-pairing to form a complex. Depending on the pairing patterns dictated by the central informational regions, this complex was able to encode a 4-digit binary code.Each experiment began with a template -- an informational structure made up of two types of the central informational sequences that define a binary sequence. This sequence dictated the form of the complementary molecule with which it can interact in the pool of available strands. The researchers went on to demonstrate that the templated binary structure can be repeatedly copied, i.e. amplified, by applying a repeating sequence of temperature fluctuations between warm and cold. "It is therefore conceivable that such a replication mechanism could have taken place on a hydrothermal microsystem on the early Earth," says Braun. In particular, aqueous solutions trapped in porous rocks on the seafloor would have provided a favorable environment for such reaction cycles, since natural temperature oscillations, generated by convection currents, are known to occur in such settings.During the copying process, complementary strands (drawn from the pool of molecules) pair up with the informational segment of the template strands. In the course of time, the adjacent hairpins of these strands also pair up to form a stable backbone, and temperature oscillations continue to drive the amplification process. If the temperature is increased for a brief period, the template strands are separated from the newly formed replicate, and both can then serve as template strands in the next round of replication.The team was able to show that the system is capable of exponential replication. This is an important finding, as it shows that the replication mechanism is particularly resistant to collapse owing to the accumulation of errors. The fact that the structure of the replicator complex itself resembles that of modern tRNAs suggests that early forms of tRNA could have participated in molecular replication processes, before tRNA molecules assumed their modern role in the translation of messenger RNA sequences into proteins. "This link between replication and translation in an early evolutionary scenario could provide a solution to the chicken-and-the-egg problem," says Alexandra Kühnlein. It could also account for the characteristic form of proto-tRNAs, and elucidate the role of tRNAs before they were co-opted for use in translation.Laboratory research on the origin of life and the emergence of Darwinian evolution at the level of chemical polymers also has implications for the future of biotechnology. "Our investigations of early forms of molecular replication and our discovery of a link between replication and translation brings us a step closer to the reconstruction of the origin of life," Braun concludes.
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Biology
| 2,021 |
March 2, 2021
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https://www.sciencedaily.com/releases/2021/03/210302075412.htm
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Common bacteria modified to make designer sugar-based drug
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Envisioning an animal-free drug supply, scientists have -- for the first time -- reprogrammed a common bacterium to make a designer polysaccharide molecule used in pharmaceuticals and nutraceuticals. Published today in
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Genetically engineered E. coli is used to make a long list of medicinal proteins, but it took years to coax the bacteria into producing even the simplest in this class of linked sugar molecules -- called sulfated glycosaminoglycans -- that are often used as drugs and nutraceuticals.."It's a challenge to engineer E. coli to produce these molecules, and we had to make many changes and balance those changes so that the bacteria will grow well," said Mattheos Koffas, lead researcher and a professor of chemical and biological engineering at Rensselaer Polytechnic Institute. "But this work shows that it is possible to produce these polysaccharides using E. coli in animal-free fashion, and the procedure can be extended to produce other sulfated glycosaminoglycans."At Rensselaer, Koffas worked with Jonathan Dordick a fellow professor of chemical and biological engineering, and Robert Linhardt a professor of chemistry and chemical biology. All three are members of the Center for Biotechnology and Interdisciplinary Studies. Dordick is a pioneer in using enzymes for material synthesis and designing biomolecular tools for the development of better drugs. Linhardt is a glycans expert and one of the world's foremost authorities on the blood-thinner heparin, a sulfated glycosaminoglycans currently derived from pig intestine.Linhardt, who developed the first synthetic version of heparin, said engineering E. coli to produce the drug has many advantages over the current extractive process or even a chemoenzymatic process."If we prepare chondroitin sulfate chemoenzymatically, and we make one gram, and it takes a month to make, and someone calls us and says, 'Well, now I need 10 grams,' we're going to have to spend another month to make 10 grams," Linhardt said. "Whereas, with the fermentation, you throw the engineered organism in a flask, and you have the material, whether it's one gram, or 10 grams, or a kilogram. This is the future.""The ability to endow a simple bacterium with a biosynthetic pathway only found in animals is critical for synthesis at commercially relevant scales. Just as important is that the complex medicinal product that we produced in E. coli is structurally the same as that used as the dietary supplement." said Dordick.Koffas outlined three major steps the team had to build into the bacteria so that it would produce chondroitin sulfate: introducing a gene cluster to produce an unsulfated polysaccharide precursor molecule, engineering the bacteria to make an ample supply of an energetically expensive sulfur donor molecule, and introducing a sulfur transferase enzyme to put the sulfur donor molecule onto the unsulfated polysaccharide precursor molecule.Introducing a working sulfotransferase enzyme posed a particularly difficult challenge."The sulfotransferases are made by much more complex cells," Koffas said. "When you take them out of a complex eukaryotic cell and put them into E. coli, they're not functional at all. You basically get nothing. So we had to do quite a bit of protein engineering to make it work."The team first produced a structure of the enzyme, and then used an algorithm to help identify mutations they could make to the enzyme to produce a stable version that would work in E. coli.Although the modified E. coli produce a relatively small yield -- on the order of micrograms per liter -- they thrive under ordinary lab conditions, offering a robust proof of concept."This work is a milestone in engineering and manufacturing of biologics and it opens new avenues in several fields such as therapeutics and regenerative medicine that need a substantial supply of specific molecules whose production is lost with aging and diseases," said Deepak Vashishth, director of the CBIS. "Such advances take birth and thrive in interdisciplinary environments made possible through the unique integration of knowledge and resources available at the Rensselaer CBIS."
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Biology
| 2,021 |
March 2, 2021
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https://www.sciencedaily.com/releases/2021/03/210302075358.htm
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High fat diets may over-activate destructive heart disease protein
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Consumption of a high fat diet may be activating a response in the heart that is causing destructive growth and lead to greater risk of heart attacks, according to new research.
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In a paper published in Named first author Dr Sunbal Naureen Bhatti, from the University of Reading said:"Our research shows one way in which a high fat diet can cause damage to the muscle cells that make up our hearts. It appears that a switch happens at a cellular level when the mice were fed on a high fat regime which causes a normally harmless protein, Nox2, to become overactive. The precise nature of how the Nox2 protein goes onto cause oxidative damage and set off destructive hypertrophy is still being researched."We are really just scratching the surface of how the protein Nox2 responds to diets, but our research clearly demonstrates that high fat diets has the potential to cause significant damage to the heart."The researchers focused on a key protein Nox2 which believed to be associated with increasing oxidative stress in the heart. The study found that the mice fed a high fat diet had twice the amount of Nox2 activity, which also led to a similar amount of reactive oxygen species (ROS), a free radical that is associated with pathological damage of the body.To check whether Nox2 was involved in causing the cardiac stress, the team compared the results with mice bred specifically to 'knock out' Nox2, stopping the protein from activating at a cellular level. The 'knock out' mice were also fed a high fat diet, but showed little or none of the same raised levels of oxidative stress.In addition, the team used three experimental treatments which are known to reduce Nox2-related ROS production, and found that all three showed some promise in reducing the effect of ROS in damaging the mice hearts.The mice that were fed high fat diets received 45% of their calorie consumption from fat, 20% from protein and 35% carbohydrate.
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Biology
| 2,021 |
March 2, 2021
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https://www.sciencedaily.com/releases/2021/03/210301093537.htm
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Root cause: Plant root tips are constrained to a dome shape common to arch bridges
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Nature is full of diversity, but underneath the differences are often shared features. Researchers from Japan investigating diversity in plant features have discovered that plant root tips commonly converged to a particular shape because of physical restrictions on their growth.
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In a study published in February in In plants and animals, the outlines of organs are defined by shape and size. But despite species differences, these outlines retain a basic similarity (e.g., songbird beaks). Plant root tips are no exception, sharing a domed shape. Root tips need to be able to push through soil effectively without disintegrating, and the similarity of their shape between plant species suggests that it may be constrained by evolution.To investigate how the shape of root tips is defined, the team used morphometric (i.e., measurements of shape and form) analysis and mathematical modeling. They looked at the shape of primary and lateral root tips in "We found that the shape of the root tips in these species commonly converged to a unique curve by rescaling their size," says lead author of the study Tatsuaki Goh. "This curve can be described as a catenary curve -- like that of arch bridges, or of a chain hanging between two points."The team also revealed with simulations that, with this shape, mechanical force is evenly spread over the surface of a root tip, and propose that this may help the tip to efficiently push through the soil. Mechanically, the formation of a curve like this in a growing structure needs a distinct boundary between a growing and non-growing region at the lateral edge of the young root, as well as spatially even, one-directional (oriented) tissue growth in the growing root tip."The very young roots of Future studies could look at how localized and spatially even occurrence of one-directional tissue growth are shared constraints for the maintenance of the dome shape between different species and classes of roots and have potential applications in plant conservation and plant biotechnology.
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Biology
| 2,021 |
March 2, 2021
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https://www.sciencedaily.com/releases/2021/03/210302085244.htm
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Designing soft materials that mimic biological functions
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Northwestern Engineering researchers have developed a theoretical model to design soft materials that demonstrate autonomous oscillating properties that mimic biological functions. The work could advance the design of responsive materials used to deliver therapeutics as well as for robot-like soft materials that operate autonomously.
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The design and synthesis of materials with biological functions require a delicate balance between structural form and physiological function. During embryonic development, for instance, flat sheets of embryonic cells morph through a series of folds into intricate three-dimensional structures such as branches, tubes, and furrows. These, in turn, become dynamic, three-dimensional building blocks for organs performing vital functions like heartbeat, nutrient absorption, or information processing by the nervous system.Such shape-forming processes, however, are controlled by chemical and mechanical signaling events, which are not fully understood on the microscopic level. To bridge this gap, researchers led by Monica Olvera de la Cruz designed computational and experimental systems that mimic these biological interactions. Hydrogels, a class of hydrophilic polymer materials, have emerged as candidates capable of reproducing shape changes upon chemical and mechanical stimulation observed in nature.The researchers developed a theoretical model for a hydrogel-based shell that underwent autonomous morphological changes when induced by chemical reactions."We found that the chemicals modified the local gel microenvironment, allowing swelling and deswelling of materials via chemo-mechanical stresses in an autonomous manner," said de la Cruz, Lawyer Taylor Professor of Materials Science and Engineering at the McCormick School of Engineering. "This generated dynamic morphological change, including periodic oscillations reminiscent of heartbeats found in living systems."A paper, titled "Chemically Controlled Pattern Formation in Self-oscillating Elastic Shells," was published March 1 in the journal In the study, the researchers designed a chemical-responsive polymeric shell meant to mimic living matter. They applied the water-based mechanical properties of the hydrogel shell to a chemical species, a chemical substance that produces specific patterned behavior -- in this case, wave-like oscillations -- located within the shell. After conducting a series of reduction-oxidation reactions -- a chemical reaction that transfers of electrons between two chemical species -- the shell generated microcompartments capable of expanding or contracting, or inducing buckling-unbuckling behavior when mechanical instability was introduced."We coupled the mechanical response of the hydrogel to changes in the concentration of the chemical species within the gel as a feedback loop," Matoz-Fernandez said. "If the level of chemicals goes past a certain threshold, water gets absorbed, swelling the gel. When the gel swells, the chemical species gets diluted, triggering chemical processes that expel the gel's water, therefore contracting the gel."The researchers' model could be used as the basis to develop other soft materials demonstrating diverse, dynamic morphological changes. This could lead to new drug delivery strategies with materials that enhance the rate of diffusion of compartmentalized chemicals or release cargos at specific rates."One could, in principle, design catalytic microcompartments that expand and contract to absorb or release components at a specific frequency. This could lead to more targeted, time-based therapeutics to treat disease," Li said.The work could also inform the future development of soft materials with robot-like functionality that operate autonomously. These 'soft robotics' have emerged as candidates to support chemical production, tools for environmental technologies, or smart biomaterials for medicine. Yet the materials rely on external stimuli, such as light, to function."Our material operates autonomously, so there's no external control involved," Li said. "By 'poking' the shell with a chemical reaction, you trigger the movement."The researchers plan to build on their findings and further bridge the gap between what's possible in nature and the science lab."The long-term goal is to create autonomous hydrogels that can perform complex functions triggered by clues as simple as a local mechanical deformation," Olvera de la Cruz said.
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Biology
| 2,021 |
March 1, 2021
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https://www.sciencedaily.com/releases/2021/03/210301211628.htm
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Rarest seal breeding site discovered
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Scientists have discovered a previously unknown breeding site used by the world's rarest seal species.
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The Mediterranean monk seal is classified as "endangered," with a total population of about 700.The new study -- by the University of Exeter and the Society for the Protection of Turtles (SPOT) -- used camera-traps to confirm breeding in caves in northern Cyprus, with at least three pups born from 2016-19 at one cave.Only certain caves are suitable for monk seal breeding and resting, so -- although the numbers are small -- the researchers say urgent action is needed to protect these caves."This area of coastline in being developed rapidly, especially for construction of hotels," said Dr Robin Snape, of the Centre for Ecology and Conservation on Exeter's Penryn Campus in Cornwall."A survey of the coast in 2007 found 39 possible breeding caves, and some of these have already been destroyed."The main breeding site we identify in this study currently has no protected status, and we are working with local authorities to try to change this."Lead author Dr Damla Beton, of SPOT, added: "Another major threat to monk seals in this area is bycatch (accidental catching by fisheries)."We are working with fishers and government ministries to ensure protection areas at sea, because at present no measures are implemented to mitigate bycatch in the core areas used by these seals."The team has now established long-term monitoring of the breeding caves, aiming to determine the size of this seal population.The study, carried out in collaboration with the Middle Eastern Technical University with the support of the local authorities, received funding from the MAVA Foundation.
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Biology
| 2,021 |
March 1, 2021
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https://www.sciencedaily.com/releases/2021/03/210301171027.htm
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Predicting microbial interactions in the human gut
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The human gut consists of a complex community of microbes that consume and secrete hundreds of small molecules -- a phenomenon called cross-feeding. However, it is challenging to study these processes experimentally. A new study, published in
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The microbial community, or microbiome, of the gut is known to influence human health. Previous studies have focused on determining the types of microbes that are present. Unfortunately, this information is not enough to understand the microbiome."The gut environment is shaped by small molecules known as metabolites, which are excreted by the microbial community," said Sergei Maslov (BCXT/CABBI), a professor of bioengineering and Bliss faculty scholar. "Although it is possible to measure these metabolites experimentally, it is cumbersome and expensive."The researchers had previously published a study where they used experimental data from other studies to model the fate of metabolites as they pass through the gut microbiome. In the new study, they have used the same model to predict new microbial processes that have not been determined before."What we eat passes into our gut, and there is a cascade of microbes which release metabolites," said Akshit Goyal, a postdoctoral fellow at MIT and a collaborator of the Maslov lab. "Biologists have measured these molecules in human stools, we have shown that you can use computational models to predict the levels of some."Measuring every metabolite and trying to understand which microbe might be releasing it can be challenging. "There is a large universe of possible cross-feeding interactions. Using this model, we can aid experiments by predicting which ones are more likely to occur in the gut," Goyal said.The model was also supported by genomic annotations, which explain which microbial genes are responsible for processing the metabolites. "We are confident of our modelling predictions because we also checked whether the microbes contain the genes necessary for carrying out the associated reactions. About 65% of our predictions were supported by this information," said Veronika Dubinkina, a PhD student in bioengineering.The researchers are now working to improve the model by including more experimental data. "Different people have different strains of gut microbes. Although these different strains have many genes in common, they differ in their capabilities," Dubinkina said. "We need to collect more data from patients to understand how different microbial communities behave in different hosts.""We are also interested in determining how fast the microbes consume and secrete the metabolites," said Tong Wang, a PhD student in physics. "Currently the model assumes that all the microbes consume metabolites at the same rate. In reality, the rates are different and we need to understand them to capture the metabolite composition in the gut."
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Biology
| 2,021 |
March 1, 2021
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https://www.sciencedaily.com/releases/2021/03/210301151545.htm
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Scientists use lipid nanoparticles to precisely target gene editing to the liver
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The genome editing technology CRISPR has emerged as a powerful new tool that can change the way we treat disease. The challenge when altering the genetics of our cells, however, is how to do it safely, effectively, and specifically targeted to the gene, tissue and organ that needs treatment. Scientists at Tufts University and the Broad Institute of Harvard and MIT have developed unique nanoparticles comprised of lipids -- fat molecules -- that can package and deliver gene editing machinery specifically to the liver. In a study published today in the
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The problem of high cholesterol plagues more than 29 million Americans, according to the Centers for Disease Control and Prevention. The condition is complex and can originate from multiple genes as well as nutritional and lifestyle choices, so it is not easy to treat. The Tufts and Broad researchers, however, have modified one gene that could provide a protective effect against elevated cholesterol if it can be shut down by gene editing.The gene that the researchers focused on codes for the angiopoietin-like 3 enzyme (Angptl3). That enzyme tamps down the activity of other enzymes -- lipases -- that help break down cholesterol. If researchers can knock out the Angptl3 gene, they can let the lipases do their work and reduce levels of cholesterol in the blood. It turns out that some lucky people have a natural mutation in their Angptl3 gene, leading to consistently low levels of triglycerides and low-density lipoprotein (LDL) cholesterol, commonly called "bad" cholesterol, in their bloodstream without any known clinical downsides."If we can replicate that condition by knocking out the angptl3 gene in others, we have a good chance of having a safe and long term solution to high cholesterol," said Qiaobing Xu, associate professor of biomedical engineering at Tufts' School of Engineering and corresponding author of the study. "We just have to make sure we deliver the gene editing package specifically to the liver so as not to create unwanted side effects."Xu's team was able to do precisely that in mouse models. After a single injection of lipid nanoparticles packed with mRNA coding for CRISPR-Cas9 and a single-guide RNA targeting Angptl3, they observed a profound reduction in LDL cholesterol by as much as 57% and triglyceride levels by about 29 %, both of which remained at those lowered levels for at least 100 days. The researchers speculate that the effect may last much longer than that, perhaps limited only by the slow turnover of cells in the liver, which can occur over a period of about a year. The reduction of cholesterol and triglycerides is dose dependent, so their levels could be adjusted by injecting fewer or more LNPs in the single shot, the researchers said.By comparison, an existing, FDA-approved version of CRISPR mRNA-loaded LNPs could only reduce LDL cholesterol by at most 15.7% and triglycerides by 16.3% when it was tested in mice, according to the researchers.The trick to making a better LNP was in customizing the components -- the molecules that come together to form bubbles around the mRNA. The LNPs are made up of long chain lipids that have a charged or polar head that is attracted to water, a carbon chain tail that points toward the middle of the bubble containing the payload, and a chemical linker between them. Also present are polyethylene glycol, and yes, even some cholesterol -- which has a normal role in lipid membranes to make them less leaky -- to hold their contents better.The researchers found that the nature and relative ratio of these components appeared to have profound effects on the delivery of mRNA into the liver, so they tested LNPs with many combinations of heads, tails, linkers and ratios among all components for their ability to target liver cells. Because the in vitro potency of an LNP formulation rarely reflects its in vivo performance, they directly evaluated the delivery specificity and efficacy in mice that have a reporter gene in their cells that lights up red when genome editing occurs. Ultimately, they found a CRISPR mRNA-loaded LNP that lit up just the liver in mice, showing that it could specifically and efficiently deliver gene-editing tools into the liver to do their work.The LNPs were built upon earlier work at Tufts, where Xu and his team developed LNPs with as much as 90% efficiency in delivering mRNA into cells. A unique feature of those nanoparticles was the presence of disulfide bonds between the long lipid chains. Outside the cells, the LNPs form a stable spherical structure that locks in their contents. When they are inside a cell, the environment within breaks the disulfide bonds to disassemble the nanoparticles. The contents are then quickly and efficiently released into the cell. By preventing loss outside the cell, the LNPs can have a much higher yield in delivering their contents."CRISPR is one of the most powerful therapeutic tools for the treatment of diseases with a genetic etiology. We have recently seen the first human clinical trail for CRISPR therapy enabled by LNP delivery to be administered systemically to edit genes inside the human body. Our LNP platform developed here holds great potential for clinical translation," said Min Qiu, post-doctoral researcher in Xu's lab at Tufts. "We envision that with this LNP platform in hand, we could now make CRISPR a practical and safe approach to treat a broad spectrum of liver diseases or disorders," said Zachary Glass, graduate student in the Xu lab. Qiu and Glass are co-first authors of the study.
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Biology
| 2,021 |
March 1, 2021
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https://www.sciencedaily.com/releases/2021/03/210301151542.htm
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Velcro-like cellular proteins key to tissue strength
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Where do bodily tissues get their strength? New University of Colorado Boulder research provides important new clues to this long-standing mystery, identifying how specialized proteins called cadherins join forces to make cells stick -- and stay stuck -- together.
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The findings, published this week in the "Better understanding these proteins allows for the design of more effective engineered tissues that better mimic biological materials as well as cancer therapeutics that are more efficient and target-specific," said Connor Thompson, lead author and graduate student in the Department of Chemical & Biological Engineering.For example: If a cancer treatment could block a specific interaction of these cadherin proteins, it could potentially slow tumor growth by stopping or slowing the formation of new blood vessels in tumors, said Thompson.Cadherin proteins are important in our bodies because they facilitate the binding and adhesion of cells in neural, cardiac, placental and skin tissues, among others, helping them maintain their function and shape.These large, rod-like proteins in the cell membrane mediate information between the inside and outside of the cell. Where they stick out, they can bond with other cadherin proteins from the same cell, as well as those from other cells.These proteins were first discovered more than 40 years ago. But in their work on them since, scientists have been perplexed by the fact that the individual bonds between these proteins are weak."There are some major unanswered questions about the glue that holds these cells and tissues together," said Daniel K. Schwartz, co-author on the paper and Glenn L. Murphy Endowed Professor in Chemical & Biological Engineering. "There's been a gap in understanding between the seemingly fairly weak interactions between the proteins and this very strong sticking together that cells have in tissues."This new research helps fill the gap.Like Velcro, the study found, the more pieces stick together, the stronger the bond and the longer it lasts. This amplified strength not only between proteins which exist on the same cell, but between proteins located on different cells -- creating bonds 30 times stronger than the sum of their individual strengths. And once the bonding begins, these bonds become progressively stronger and stronger.Proteins are formed out of a very limited palette of ingredients, said Schwartz.Unlike the infamous "spike proteins" found on the virus that causes COVID-19, cadherins move around in a fluid membrane, able to rearrange themselves, and team up to bond with other proteins to form clusters and grids.In Thompson's previous publications on cadherin proteins, he studied the motion of these proteins and how they interact and bond with each other on the same cell membrane. In this new research, he's finally discovered how they bond so strongly between different cell membranes."It sounds like a small advance, but that was actually a huge leap, and it required him to develop entirely new methods," said Schwartz. "Those methods themselves may end up being some of the greatest impact that comes out of this work."Thompson conducted experiments using single molecule microscopy and Förster Resonance Energy Transfer (FRET) at the BioFrontiers Advanced Light Microscopy Core facilities, developed entirely new methods to control and study cadherin protein interactions and analyzed big data using novel machine learning algorithms as part of a collaborative, multi-university team.With this technology, Thompson could simultaneously see the molecules move and when they would bind to one another -- at which point a color change occurs. Using big data allowed the researchers to look at tens of thousands of interactions between the molecules.The nature of the world on a molecular level is that everything is constantly bumping into everything else, including the bonds that cadherin proteins have formed, according to Schwartz."But when interactions are very strong, they stay bound longer," said Thompson.Additional authors on this paper include Vinh H. Vu in the Department of Biochemistry and Deborah E. Leckband in the Department of Biochemistry and Department of Chemical and Biomolecular Engineering at the University of Illinois, Urbana-Champaign.
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Biology
| 2,021 |
March 1, 2021
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https://www.sciencedaily.com/releases/2021/03/210301151532.htm
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Goodbye UTIs: Scientists develop vaccine strategy for urinary tract infections
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Anyone who has ever developed a urinary tract infection (UTI) knows that it can be painful, pesky and persistent. UTIs have a high recurrence rate and primarily afflict women -- as many as 50% of women will experience at least one UTI during their lifetime.
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However, what if patients could take a vaccine that would prevent future UTIs? In a March 1 study in the "Although several vaccines against UTIs have been investigated in clinical trials, they have so far had limited success," said Soman Abraham, Ph.D., Grace Kerby Distinguished Professor of Pathology, Immunology and Molecular Genetics & Microbiology in the School of Medicine and senior author on the paper."There are currently no effective UTI vaccines available for use in the U.S. in spite of the high prevalence of bladder infections," Abraham said. "Our study describes the potential for a highly effective bladder vaccine that can not only eradicate residual bladder bacteria, but also prevent future infections."The strategy, which the team showed to be effective in mouse models, involves re-programming an inadequate immune response that the team identified last year. They observed that when mouse bladders get infected with E. coli bacteria, the immune system dispatches repair cells to heal the damaged tissue, while launching very few warrior cells to fight off the attacker. This causes bacteria to never fully clear, living on in the bladder to attack again.According to lead author Jianxuan Wu, Ph.D., who recently earned his doctorate from the Department of Immunology at Duke, "the new vaccine strategy attempts to 'teach' the bladder to more effectively fight off the attacking bacteria. By administering the vaccine directly into the bladder where the residual bacteria harbor, the highly effective vaccine antigen, in combination with an adjuvant known to boost the recruitment of bacterial clearing cells, performed better than traditional intramuscular vaccination."The researchers reported that bladder-immunized mice effectively fought off infecting E. coli and eliminated all residual bladder bacteria, suggesting the site of administration could be an important consideration in determining the effectiveness of a vaccine."We are encouraged by these findings, and since the individual components of the vaccine have previously been shown to be safe for human use, undertaking clinical studies to validate these findings could be done relatively quickly," Abraham said.In addition to Abraham and Wu, study authors include Chunjing Bao and R. Lee Reinhardt.The study received funding support from the National Institutes of Health (R01DK121032 and R01DK121969).
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Biology
| 2,021 |
March 1, 2021
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https://www.sciencedaily.com/releases/2021/03/210301133837.htm
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How a plant regulates its growth
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Plants grow towards the light. This phenomenon, which already fascinated Charles Darwin, has been observed by everyone who owns houseplants. Thus, the plant ensures that it can make the best use of light to photosynthesize and synthesize sugars. Similarly, the roots grow into the soil to ensure that the plant is supplied with water and nutrients.
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These growth processes are controlled by a hormone called "auxin," which plays a key role in the formation of polarity in plants. To do this, auxin is transported in the plant body polar, from the shoot through the plant body into the roots. In this process, a family of polar transport proteins distributes the auxin throughout the plant. To better understand this process, the research team investigated it in more detail with the help of a chemical.Scientists around the world are studying transporter proteins in more detail due to their central role in plant development processes. Naptalam (NPA) is an important tool to elucidate the structure of the transporters.Naptalam is the registered name of Napthylphphthalic acid. It inhibits the directional flow of auxin, thus severely inhibiting plant growth. It was used in in the European Union until 2002, and the sodium salt of naptalam is still used in the USA as a pre-emergence herbicide to control broadleaf weed in cucurbits and nursery stock."We wanted to know how naptalam exerts its effects," says PD Dr. Ulrich Hammes, the study's principal investigator. "Our studies show that the activity of the auxin transporters is really completely shut down by the inhibitor." When NPA binds to the transporter proteins, auxin can no longer get out of the cell, and thus the plant is no longer able to grow polarly. The roots no longer grow to the center of the earth, and flowers and seed formations are massively disrupted.An effect of the inhibitor NPA on the activators of the transporters, known as kinases, could be ruled out through collaboration with Claus Schwechheimer, Professor of Plant Systems Biology of at the TUM, where the work was carried out. He explains, "This makes it clear that the inhibitor NPA acts directly on the transport proteins.""We can now clearly explain the molecular mechanism by which polar plant growth can be disrupted pharmacologically," says Ulrich Hammes.The research groups in Vienna were able to show that naptalam not only binds the transporters, but also prevents the transporters from binding to each other. "This mechanism of binding to each other seems to apply universally in the family of auxin transporters, as we observed the effect in all transporters studied," says Martina Kolb, first author of the study.Overall, the study provides a significant step forward in understanding the mechanism of the molecular machinery of plant polarity. The new findings make it possible to study polar growth more precisely and to understand the molecular mechanism of auxin transport.
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Biology
| 2,021 |
March 1, 2021
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https://www.sciencedaily.com/releases/2021/03/210301112313.htm
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Searching for novel targets for new antibiotics
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Ribosome formation is viewed as a promising potential target for new antibacterial agents. Researchers from Charité -- Universitätsmedizin Berlin have gained new insights into this multifaceted process. The formation of ribosomal components involves multiple helper proteins which, much like instruments in an orchestra, interact in a coordinated way. One of these helper proteins -- protein ObgE -- acts as the conductor, guiding the entire process. The research, which produced the first-ever image-based reconstruction of this process, has been published in
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Ribosomes are an essential component of all living cells. Frequently referred to as 'molecular protein factories', they translate genetic information into chains of linked-up amino acids which are otherwise known as proteins. The process of protein biosynthesis is the same in all cells, even in bacteria (including the widely known intestinal bacterium Escherichia coli). If this process cannot take place, the cell dies; single-celled organism (such as E. coli and other bacteria) cannot survive. Researchers are hoping to exploit this circumstance for the development of novel antibiotic agents. The need for these new drugs is not only the result of an increase in antibiotic resistance and the emergence and spread of new multidrug-resistant pathogens, but also because it has been a long time since a new class of antibiotic substances emerged. A new type of antibiotic might be designed to interfere with ribosome formation in a way that inhibits their assembly."It is a coincidence that we are currently in the middle of a viral pandemic. The next pandemic could easily be of bacterial origin because both bacterial antibiotic resistance and multidrug resistance are spreading rapidly, across species barriers," explains the study's last author, Prof. Dr. Christian Spahn, Director of Charité's Institute of Medical Physics and Biophysics. He adds: "The long-term aim of our basic research is therefore to contribute to the development of new antibiotics." Working with colleagues from the Max Delbrück Center for Molecular Medicine MDC) in Berlin and the University of Konstanz, the Charité researchers explored the early stages of ribosome formation to identify points in the process which might serve as targets for new antibacterial and antimicrobial drugs.Ribosomes consist of two subunits: one larger subunit and one smaller one. As part of their latest endeavors, the team, led by Dr. Rainer Nikolay of Charité's Institute for Medical Physics and Biophysics, focused on studying the nature and development of the larger ribosomal subunit in the bacterium E.coli. Hoping to identify a potential target for new antibiotics, the researchers wanted to isolate and visualize the precursor stages of this larger subunit. To do so, they wanted to use the subunit in its unadulterated form, i.e. as close to its natural condition as possible. For the first time, the researchers succeeded in not only isolating one such precursor from bacterial cells (in this case, E. coli), but also visualizing it using cryo-electron microscopy imaging at near-atomic resolution. "We now have a better understanding of the way in which the larger bacterial ribosomal subunit develops at the molecular level, although our understanding remains far from complete," says first author Dr. Nikolay.The research team chose a minimally invasive protocol in order to minimize the degree to which the bacterial cell would need to be manipulated. One of the key agents in the process of ribosome formation, the protein ObgE, was marked using what is known as a 'Strep tag'. This step involves a 'gene knock-in' procedure -- the insertion of genetic information into the bacterial genome. A bacterium thus treated will produce only marked ObgE. After minor processing of the cell, this ObgE can then be visualized using an electron microscope. Strep tagging enabled the researchers to study the entire complex for the first time. This is because the helper protein ObgE effectively carries the precursor of the larger ribosomal subunit on its back. The results came as a surprise, as Dr Nikolay explains: "We found that this precursor is covered in multiple helper proteins, which either interact or directly communicate with one another. The ObgE protein takes on a key role in this process, effectively directing and coordinating it." This could constitute a target for new drugs, which might stop bacterial growth by inhibiting the assembly of functional ribosomes.The team want to use similar strategies to gain further insights into the development of bacterial ribosomal subunits and enhance their understanding of the relevant biological processes at the molecular level. Previous research, conducted at Charité and the Max Planck Institute for Molecular Genetics, had produced valuable information on the fundamental structure of ribosomes and the various steps of the maturation process which these cellular protein factories must undergo. While all of these earlier insights were based on in vitro studies, the researchers knew that the formation of the large chromosomal subunit could only be observed in a living cell. The latest step in their endeavors has therefore been a crucial one: in order to identify new cellular drug targets, it is necessary to understand how the process of ribosome formation seen in bacteria differs from that in human cells. "We have managed to make some headway in that respect," says Dr. Nikolay. "We were able to reveal the existence of both conserved and divergent evolutionary features between prokaryotes -- such as bacteria -- and eukaryotes -- organisms whose genetic information is contained inside a cell nucleus." These findings are important if we are to target features specific to bacteria while also protecting human cells against unwanted side effects.
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Biology
| 2,021 |
March 1, 2021
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https://www.sciencedaily.com/releases/2021/03/210301095945.htm
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Model for wildlife tourism
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Wildlife tourism including white shark cage-diving is growing in popularity, but these industries remain highly contentious amongst tourists, conservationists, and scientists alike.
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Many voice concerns about possible negative impacts -- especially when it targets potentially dangerous animals -- while proponents cite the socio-economic benefits to justify wildlife tourism activities.In reality, wildlife tourism is complex, requiring managers to balance the benefits and drawbacks to determine what is acceptable for such industries.To help solve this question of "is wildlife tourism good or bad?," a tool to help managers assess these industries has been created by scientists from Flinders University, the Georgia Aquarium, and Southern Cross University with help from environmental, marine parks, and tourism managers from the South Australian Department for Environment and Water, and a veterinarian/university animal welfare officer.The resulting framework, published in Bringing together these five distinct categories into one framework enables a more comprehensive assessment, combining the various pros and cons typical of wildlife tourism industries."The latest study provides an inventory of relevant factors incorporating a range of different industry sectors, current knowledge, and research needs," says co-author and Flinders Associate Professor Charlie Huveneers.To put the new framework to the test, the authors applied it to the white shark cage-diving industry on South Australia's Eyre Peninsula. Here, three operators host up to 10,000 passengers and generate about $8 million a year.The industry is well regulated with limits on the number of licences, days they can operate, and amount of attractant they can use.Recent research from Dr Meyer found that while food-based attractant (bait and berley) had no impact on white shark diet (they still swim around eating their normal prey items), it can affect the diet of fish and rays that live at these offshore islands.The framework also enabled the comparison of the costs and benefits to white sharks versus the other fish and rays, revealing the wholistic acceptability of the industry and identifying key areas for improvement.The results show that while public opinion varies towards white shark cage-diving, the contribution to public education and awareness, and scientific research is high, Dr Meyer says."The conservation outcomes for target and non-target species is high, owing to the protected status of the Neptune Islands Group Marine Park Sanctuary Zone where the industry operates," she says.Unsurprisingly, the industry offers substantial regional economic benefits, but while the effects on white shark was well managed, the welfare of fishes and rays was identified as requiring further attention.Associate Professor Charlie Huveneers, who has studied shark behaviour and ecology for more than 10 years, including white sharks, says the new framework shows how efficient collaboration between scientists, managers and the industry will help minimise negative effects on white sharks, but it also highlighted areas which could be further improved.Specifically, the framework identified key priorities for future biological, socioeconomic, and cultural heritage research, ensuring comprehensive management of a divisive industry.
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Biology
| 2,021 |
March 1, 2021
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https://www.sciencedaily.com/releases/2021/03/210301091139.htm
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How 'great' was the great oxygenation event?
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Around 2.5 billion years ago, our planet experienced what was possibly the greatest change in its history: According to the geological record, molecular oxygen suddenly went from nonexistent to becoming freely available everywhere. Evidence for the "great oxygenation event" (GOE) is clearly visible, for example, in banded iron formations containing oxidized iron. The GOE, of course, is what allowed oxygen-using organisms -- respirators -- and ultimately ourselves, to evolve. But was it indeed a "great event" in the sense that the change was radical and sudden, or were the organisms alive at the time already using free oxygen, just at lower levels?
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Prof. Dan Tawfik of the Weizmann Institute of Science's Biomolecular Sciences Department explains that the dating of the GOE is indisputable, as is the fact that the molecular oxygen was produced by photosynthetic microorganisms. Chemically speaking, energy taken from light split water into protons (hydrogen ions) and oxygen. The electrons produced in this process were used to form energy-storing compounds (sugars), and the oxygen, a by-product, was initially released into the surroundings.The question that has not been resolved, however, is: Did the production of oxygen coincide with the GOE, or did living organisms have access to oxygen even before that event? One side of this debate states that molecular oxygen would not have been available before the GOE, as the chemistry of the atmosphere and oceans prior to that time would have ensured that any oxygen released by photosynthesis would have immediately reacted chemically. A second side of the debate, however, suggests that some of the oxygen produced by the photosynthetic microorganisms may have remained free long enough for non-photosynthetic organisms to snap it up for their own use, even before the GOE. Several conjectures in between these two have proposed "oases," or short-lived "waves," of atmospheric oxygenation.Research student Jagoda Jabłońska in Tawfik's group thought that the group's focus -- protein evolution -- could help resolve the issue. That is, using methods of tracing how and when various proteins have evolved, she and Tawfik might find out when living organisms began to process oxygen. Such phylogenetic trees are widely used to unravel the history of species, or human families, but also of protein families, and Jabłońska decided to use a similar approach to unearth the evolution of oxygen-based enzymes.To begin the study, Jabłońska sorted through around 130 known families of enzymes that either make or use oxygen in bacteria and archaea -- the sorts of life forms that would have been around in the Archean Eon (the period between the emergence of life, ca. 4 billion years ago, and the GOE). From these she selected around half, in which oxygen-using or -emitting activity was found in most or all of the family members and seemed to be the founding function. That is, the very first family member would have emerged as an oxygen enzyme. From these, she selected 36 whose evolutionary history could be traced conclusively. "Of course, it was far from simple," says Tawfik. "Genes can be lost in some organisms, giving the impression they evolved later in members in which they held on. And microorganisms share genes horizontally, messing up the phylogenetic trees and leading to an overestimation of the enzyme's age. We had to correct for the latter, especially."The phylogenetic trees the researchers ultimately obtained showed a burst of oxygen-based enzyme evolution about 3 billion years ago -- something like half a billion years before the GOE. Examining this time frame further, the scientists found that rather than coinciding with the takeover of atmospheric oxygen, this burst dated to the time that bacteria left the oceans and began to colonize the land. A few oxygen-using enzymes could be traced back even farther. If oxygen use had coincided with the GOE, the enzymes that use it would have evolved later, so the findings supported the scenario in which oxygen was already known to many life forms by the time the GOE took place.The scenario that Jabłońska and Tawfik propose looks something like this: Oxygen is one of the most chemically reactive elements around. Like one end of a battery, it readily accepts electrons, thus providing extra metabolic power. That makes it extremely useful to many life forms, but also potentially damaging. So photosynthetic organisms as well as other organisms living in their vicinity had to quickly develop ways to efficiently dispose of oxygen. This would account for the emergence of oxygen-utilizing enzymes that would remove molecular oxygen from cells. One microorganism's waste, however, is another's potential source of life. Oxygen's unique reactivity enabled organisms to break down and use "resilient" molecules such as aromatics and lipids, so enzymes that take up and use oxygen likely began evolving soon after.Tawfik: "This confirms the hypothesis that oxygen appeared and persisted in the biosphere well before the GOE. It took time to achieve the higher GOE level, but by then oxygen was widely known in the biosphere."Jabłońska: "Our research presents a completely new means of dating oxygen emergence, and one that helps us understand how life as we know it now evolved."Prof. Dan Tawfik's research is supported by the Zuckerman STEM Leadership Program. Prof. Tawfik is the incumbent of the Nella and Leon Benoziyo Professorial Chair.
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Biology
| 2,021 |
March 4, 2021
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https://www.sciencedaily.com/releases/2021/03/210304100415.htm
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New insights into an ancient protein complex
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Cells rely on membranes to protect themselves from the outside world. But these membranes can't be fully closed because nutrients and other molecules have to be able to pass through. To achieve this, cell membranes have many types of channels and pores. Also, there are receptors, antennas if you like, imbedded in the membrane that continuously monitor the outside world and signal to the cell interior. Extensive collaboration between five VIB groups resulted in a better understanding of the machinery that plants use to regulate the protein composition of their outer membrane. This discovery, published in
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Complex life has complex cells, also known as eukaryotic cells. Unlike bacteria, for example, the cells of complex life have many distinct internal compartments known as organelles. These organelles exchange material among themselves. To do so, the organelles have a few tricks. One of those tricks is vesicle trafficking. This means that they use a part of their own membrane as a bag for the goods to be exchanged.A recent discovery showed that plants heavily rely on a protein complex named the TPLATE complex to do so. This complex is not only present in plants, but also in a wide range of other eukaryotes, which suggests it is evolutionary very old and part of a protein complex family of which all other members are intensively studied. However, because this particular complex is not present in the most-studied model organisms (animals and yeasts), its existence and function remained under the radar for a very long time.In this study, VIB teams (the groups of Bert De Rybel, Geert De Jaeger, and Daniël Van Damme from the VIB-UGent Center for Plant Systems Biology, Remy Loris from the VIB-VIB Center for Structural Biology, and Savvas Savvides from the VIB-UGent Center for Inflammation Research) reveal TPLATE's molecular architecture for the very first time. They achieved this by crosslinking mass spectrometry and computer simulations. These new insights revealed the orientation of this complex towards the membrane as well as the delicate relationship between the different domains of its subunits.These findings are important to increase our knowledge of crucial eukaryotic processes. Indeed, the structure of this complex now allows us to compare it with known structures of its close relatives that are present in all eukaryotes including animals and yeasts and this allows us to visualize the evolution of these trafficking complexes.To obtain both structural and functional insight into this enigmatic complex an integrative, collaborative approach was needed. Five VIB research groups and one group from the Czech Republic contributed within their specific expertise to perform experiments ranging from lipid-binding studies to structural biology approaches.The novel structural insight was mostly generated based on crosslinking mass spectrometry, performed with the help of the VIB Proteomics core facility.'A major benefit of working at VIB is that it greatly encourages and facilitates access to knowledge and expertise that allows research groups to successfully embark on joint projects that lie far beyond their comfort zone.' -- Prof. Daniel Van DammeThis study will form the foundation of further scientific work and will open doors for the generation of novel and safer herbicides or modulation of stress responses in plants.
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Biology
| 2,021 |
February 27, 2021
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https://www.sciencedaily.com/releases/2021/02/210227083248.htm
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Oahu marine protected areas offer limited protection of coral reef herbivorous fishes
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Marine protected areas (MPAs) around Oahu do not adequately protect populations of herbivorous reef fishes that eat algae on coral reefs. That is the primary conclusion of a study published in
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There are over 20 species of herbivorous fishes and ten species of herbivorous urchins commonly observed on Hawaiian reefs. These species eat algae that grows on reefs, a process called herbivory, that contributes to the resilience of coral reefs by preventing algae dominance that can lead to overgrowth of corals.The team of researchers found that of the four marine protected areas around Oahu they assessed in the study, three did not provide biologically significant benefits for herbivorous fish populations compared to reefs outside the areas."Marine protected areas are a fishery management tool to limit or prevent fishing to help the recovery and maintenance of fish abundance and biomass inside the MPA," said senior author Erik Franklin, Associate Research Professor at the Hawaii Institute of Marine Biology in SOEST. "An effective MPA should lead to a considerably higher abundance and biomass of fishes inside the MPA boundaries that would otherwise be caught by fishers but that wasn't what our study found."Other factors influencing the biomass of herbivorous fishes included habitat complexity and depth, suggesting that environmental characteristics of coral reefs may have had a greater impact on herbivorous fish populations than MPA protection.As part of the Sustainable Hawaii Initiative, the State of Hawaii's Division of Aquatic Resources leads the Marine 30x30 Initiative, which committed to effectively manage Hawaii's nearshore waters with 30 percent established as marine management areas by 2030. Currently, five percent of waters within state jurisdiction, which is within three nautical miles of shore, have some form of marine management, but no-take MPAs that ban fishing only make up less than one-half of one percent of the nearshore waters. To attain the stated goal of the 30x30 Initiative would require an expansion of marine managed areas to include an additional 25 percent of Hawaii state waters."Our results suggest that prior to an expansion of MPAs in Hawaiian waters, more effort should be directed to effectively manage the existing MPAs to see if they meet the desired management objectives," said lead author and UH Manoa's Marine Biology Graduate Program graduate student Noam Altman-Kurosaki. "The addition of more MPAs throughout the state that have similar performance to the Oahu MPAs would just lead to a series of paper parks that don't provide biologically significant conservation benefits while decreasing fishing opportunities."Franklin said the research resulted in a comparative analysis of herbivorous fish and urchin populations inside and outside of Oahu MPAs that demonstrated biologically insignificant differences in fish biomass between the MPAs and reference areas, except for one site, Hanauma Bay. The analyses used statistical methods to assess the effects of protecting population within MPAs and the influence that differences in benthic habitats contributed to the results.
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Biology
| 2,021 |
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