Date
stringlengths 11
18
| Link
stringlengths 62
62
| Title
stringlengths 16
148
| Summary
stringlengths 1
2.68k
| Body
stringlengths 22
13k
⌀ | Category
stringclasses 20
values | Year
int64 2k
2.02k
|
|---|---|---|---|---|---|---|
February 7, 2014
|
https://www.sciencedaily.com/releases/2014/02/140207083923.htm
|
GMO soybean pollen threatens Mexican honey sales, report finds
|
Mexico is the fourth largest honey producer and fifth largest honey exporter in the world. A Smithsonian researcher and colleagues helped rural farmers in Mexico to quantify the genetically modified organism (GMO) soybean pollen in honey samples rejected for sale in Germany. Their results will appear Feb. 7 in the online journal,
|
David Roubik, senior staff scientist at the Smithsonian Tropical Research Institute, and colleagues developed the ability to identify pollen grains in honey in Panama and in Mexico during the 1980s and 1990s when they studied the effects of the arrival of Africanized bees on native bees. "Nobody else can do this kind of work in the 'big field' environment and be confident that what they are seeing are soybean pollen grains," said Roubik. They found that six honey samples from nine hives in the Campeche region contained soy pollen in addition to pollen from many wild plant species. The pollen came from crops near the bee colonies in several small apiaries.Due to strict European regulations, rural farmers in the Mexican Yucatan face significant price cuts or outright rejection of their honey crop when their product contains pollen from GMO crops that are not for human consumption. The regional agricultural authorities, furthermore, seemed unaware that bees visited flowering soybeans to collect nectar and pollen."As far as we could determine, every kind of GMO soybean grown in Campeche is approved for human consumption," said Roubik. "But honey importers sometimes do no further analysis to match GMO pollen grains with their source."To test the honey for GMO pollen, researchers from the Smithsonian, El Colegio de la Frontera Sur la Universidad Autonoma de Yucatan and el Instituto Nacional de Investigaciones Forestales, Agropecuarias y Pecuarias sent the nine samples to Intertek laboratory in Bremen, Germany, for genetic analysis. Two samples tested positive for GMO pollen."We cautiously interpret these results as significant for elsewhere in Mexico where some five times the GMO soy grown in Campeche is found and beekeeping is alive and well, not to mention the rest of the world," said Roubik. "Bee colonies act as extremely sensitive environmental indicators. Bees from a single colony may gather nectar and pollen resources from flowers in a 200-square-kilometer area. With an economy based on subsistence agriculture associated with honey production, the social implications of this shift in the status of honey are likely to be contentious and have profound implications for beekeeping in general."
|
Genetically Modified
| 2,014 |
February 6, 2014
|
https://www.sciencedaily.com/releases/2014/02/140206133638.htm
|
How our immune system backfires and allows bacteria like Salmonella to grow
|
Our immune system wages an internal battle every day to protect us against a broad range of infections. However, researchers have found that our immune response can sometimes make us vulnerable to the very bacteria it is supposed to protect us from. A study published by Cell Press on February 6th in the journal
|
"Surprisingly, we found that interleukin-22 not only fell short in protecting the host against the spread of To protect against disease-causing pathogens, IL-22 triggers the production of antimicrobial proteins that sequester metal ions such as iron, zinc, and manganese from microbes, starving them of these essential nutrients. But until now, it has been unclear how pathogens such as To address this question, Raffatellu and her team first infected normal mice, and mice genetically engineered to lack IL-22, with The researchers then simultaneously infected the mice with normal Even though IL-22 does not protect against all pathogens, the protein still plays a crucial role in controlling the spread of some harmful microbes. "Blocking interleukin-22 during infection would be too detrimental to the host, so a more promising therapeutic strategy would be to specifically target the alternative pathways used by
|
Genetically Modified
| 2,014 |
February 6, 2014
|
https://www.sciencedaily.com/releases/2014/02/140206111414.htm
|
New, surprising link between chloracne and molecule that protects cells against stress
|
ETH-Zurich researchers have discovered a new, surprising link between chloracne and a molecule that protects cells against stress: if Nrf2 gets out of control, disfiguring cysts form on the skin.
|
The images were seen all over the world and stuck in the minds of many: in the autumn of 2004, former President of the Ukraine, Viktor Yushchenko, was poisoned with a high dose of dioxin. Although he survived the attack, the chloracne caused by the poisoning, officially known as MADISH, left him severely disfigured: his face was peppered with numerous cysts, which left deep scars.Now a team of researchers headed by ETH-Zurich professor Sabine Werner and a senior researcher of her team, Dr. Matthias Schäfer, has stumbled across a link between chloracne and a molecular switch, which causes a comparable skin phenotype in mice after longer and increased activation. The new discovery has just been published in The molecular switch is Nrf2, which the ETH-Zurich researchers have been studying in connection with different skin diseases for some time. Nrf2 is a so-called transcription factor. It activates certain genes that protect cells and help them to survive under stress conditions. The ETH-Zurich scientists had discovered that a moderate activation of Nrf2 protects the skin against UV damage (see ETH Life from 20 May 2010). The molecule activates several genes designed to protect skin cells from aggressive free radicals, which are formed through UV radiation, save them from dying off and prevent damage of the genetic material.Nrf2 is thus an interesting candidate for use in skincare creams and for cancer prevention. Until now, however, the consequences of prolonged Nrf2 activation in the skin had not been characterized. After all, in a previous study Werner and Schäfer realised that the skin of mice became flaky and was thus potentially damaged upon increased activation of Nrf2.For their follow-up study, they used an animal model in which the skin cells of genetically modified mice permanently activated Nrf2. As a result, the animals developed skin changes that were strikingly similar to those in dioxin victims, albeit far less pronounced than in humans. In mice with Nrf2 activation, the sebaceous glands became enlarged and secreted an excessive amount of sebum. The hair follicles were also thickened and callused, which ultimately led to their widening, hair loss and eventually the development of cysts.Consequently, in a second step the scientists tested tissue samples from MADISH patients and discovered that Nrf2 was evidently activated in their skin, causing a strong expression of the same target proteins as in the mouse model. Therefore, it is very likely that the processes that trigger such abnormal skin changes in mice also take place very similarly in humans."We only spotted the link between chloracne and the mouse model in the course of our project -- purely by chance," says Werner. Originally, the aim had been to understand what takes place in the event of an increased activation of Nrf2 in the skin. Hence, the ETH-Zurich researchers are all the more delighted that they identified a major player in the development of chloracne.The issue of which molecular mechanisms take place in an early phase of chloracne still remains unexplored. The researchers simply lack the samples from patients, who have suffered from dioxin poisoning, to address this question. Schäfer stresses how difficult it is to get hold of this kind of sample material. "The patients only go to the doctor once the condition is already quite advanced," he says. "In other words, the early stage goes undetected and is lost."The two researchers believe, however, that therapeutic targeting of Nrf2 in the case of chloracne is problematic. The cells activate Nrf2 in order to accelerate the detoxification of the body. In the event of dioxin poisoning, slowing down or even stopping the body's response with an intervention against Nrf2 could be fatal. Besides, dioxin is a very long-lived toxin that is stored in the body's fatty tissue. It is no coincidence that precisely the sebaceous glands of the facial skin are changed so severely in the case of MADISH: lipids and thus dioxin are stored in them. Consequently, the researchers consider it more sensible to first examine Nrf2's target genes in more detail, so that the amount of activity of specific proteins that are responsible for the symptoms might potentially be influenced.
|
Genetically Modified
| 2,014 |
February 4, 2014
|
https://www.sciencedaily.com/releases/2014/02/140204112125.htm
|
Gene therapy may be possible cure for Hurler syndrome: Mouse Study
|
Researchers used blood platelets and bone marrow cells to deliver potentially curative gene therapy to mouse models of the human genetic disorder Hurler syndrome -- an often fatal condition that causes organ damage and other medical complications.
|
Scientists from Cincinnati Children's Hospital Medical Center and the National Institute of Neurological Disorders and Stroke (NINDS) report their unique strategy for treating the disease the week of Feb. 3-7 in Researchers were able to genetically insert into the cells a gene that produces a critical lysosomal enzyme (called IDUA) and then inject the engineered cells into mice to treat the disorder. Follow up tests showed the treatment resulted in a complete metabolic correction of the disease, according to the authors."Our findings demonstrate a unique and somewhat surprising delivery pathway for lysosomal enzymes," said Dao Pan, PhD, corresponding author and researcher in the Division of Experimental Hematology and Cancer Biology at Cincinnati Children's. "We show proof of concept that platelets and megakaryocytes are capable of generating and storing fully functional lysosomal enzymes, which can lead to their targeted and efficient delivery to vital tissues where they are needed."The mice tested in the study modeled human Hurler syndrome, a subset of disease known as mucopolysaccharidosis type I (MPS I), one of the most common types of lysosomal storage diseases. MPS I is a lysosomal storage disease in which people do not make an enzyme called lysosomal alpha-L-iduronidase (IDUA).IDUA helps break down sugar molecules found throughout the body, often in mucus and fluids around joints, according to the National Library of Medicine/National Institutes of Health. Without IDUA, sugar molecules build up and cause organ damage. Depending on severity, the syndrome can also cause deafness, abnormal bone growth, heart valve problems, joint disease, intellectual disabilities and death.Enzyme replacement therapy can be used to treat the disease, but it is only temporary and not curative. Bone marrow transplant using hematopoietic stem cells also has been tested on some patients with mixed results. The transplant procedure can carry severe risks and does not always work.Pan and her colleagues -- including Roscoe O. Brady, MD, a researcher at NINDS -- report that using platelets and megakaryocytes for gene therapy is effective and could reduce the risk of activating cancer-causing oncogenes in hematopoietic stem cells.The authors said tests showed that human megakaryocytic cells were capable of overexpressing IDUA, revealing their capacity for potential therapeutic benefit. While engineering megakaryocytes and platelets for infusion into their mouse models of Hurler, the scientists report they were able to release IDUA directly into amply sized extracellular spaces or inside micro-particles as the cells matured or activated. The cells were able to produce and package large amounts of functional IDUA and retained the capacity to cross-correct patient cells.After infusing mouse models of Hurler with the genetically modified cells, researchers said this led to long-term normalization of IDUA levels in the animal's blood with versatile delivery routes and on-target preferential distribution to the liver and spleen. The treatment led to a complete metabolic correction of MPS I in most peripheral organs of the mice.Researchers cautioned that study results involving laboratory mouse models do not always translate into clinical treatment of human patients, and that additional research is needed for this prospective therapy.
|
Genetically Modified
| 2,014 |
February 4, 2014
|
https://www.sciencedaily.com/releases/2014/02/140204073821.htm
|
Healthy balance: model for studying cancer, immune diseases
|
The protein STAT1 is involved in defending the body against pathogens and for inhibiting tumor development. If the levels of the protein are out of balance, disease may result. Researchers at the University of Veterinary Medicine, Vienna have developed a mouse whose STAT1 levels can be modified at will, enabling the study of the involvement of STAT1 in various processes. The work has now been published in the online journal
|
STAT1 (signal transducer and activator of transcription 1) is a member of a family of transcription factors, cellular proteins that control whether and when particular genes are active. STAT1 transmits signals from interferons to the immune system. Animals with too little STAT1 suffer from weak immune responses and are prone to develop tumors: human cancer patients frequently have mutations in their STAT1 gene. On the other hand, too much STAT1 causes the immune system to overreact and in humans often results in autoimmune diseases. It is thus vital to ensure the correct dose of STAT1 in the body.Nicole R. Leitner from the Institute of Animal Breeding and Genetics and her colleagues now report the development of a genetically modified mouse where the level of STAT1 can be fine-tuned. The production of STAT1 is under the control of the drug doxycycline, which is added to the drinking water. If less doxycycline is given, STAT1 levels are correspondingly low; adding more doxycycline to the water results in higher STAT1 levels. The system enables the researchers to investigate the precise role of STAT1 in various disease conditions such as breast cancer or infectious diseases."Mice whose STAT1 can be completely switched off, so-called knock-out mice, have been around for some time. The special feature of our model is its ability to produce an exact dose of protein. This will make it possible for us to examine the origins and the course of many diseases and ultimately to test possible cures for them," says Leitner. Mathias Müller, the Director of the Institute, is excited by the model's potential. As he notes, "we are currently investigating the function of STAT1 in various forms of cancer, such as breast cancer and leukemia. In the future it might be possible to use information on the amount of STAT1 in the cell to give an indication about the progression of diseases and thus to guide the choice of therapy."
|
Genetically Modified
| 2,014 |
February 3, 2014
|
https://www.sciencedaily.com/releases/2014/02/140203084612.htm
|
Beneficial insects, nematodes not harmed by genetically modified, insect-resistant crops, studies show
|
A large body of literature has shown that genetically-modified plants that produce proteins from the bacterium
|
In an article in the February 2014 issue of The researchers found that the survival, development, adult mass, fecundity, and fertility of the insect predators in both groups were similar, regardless of whether they consumed caterpillars that fed on Bt plants or non-Bt plants."This research demonstrates that the current Bt proteins used in corn and cotton crops globally do not harm In a similar article appearing in the February 2014 issue of the The researchers found that the virulence, reproductive potential, and time of emergence of the nematodes that consumed Bt-fed caterpillars were not significantly affected, compared to nematodes that did not ingest the Bt protein."This is the first report we are aware of in which a nematode predator has been tested in such detail against a Bt protein," Dr. Shelton said."Together, these two studies add to the scientific literature demonstrating that Bt plants can control targeted insect pests while not harming important natural enemies that help suppress pest species and maintain biodiversity in agricultural systems," Shelton added.
|
Genetically Modified
| 2,014 |
February 3, 2014
|
https://www.sciencedaily.com/releases/2014/02/140203084610.htm
|
First African study on biodiversity in genetically modified maize finds insects abundant
|
Previous studies from China, Spain, and the United States on genetically modified (GM) rice, cotton, and maize have concluded that the biodiversity of insects and related arthropods in GM crop fields was essentially the same as that among conventional crops. Now a new study from South Africa shows similar results.
|
The study is described in an article called "Comparative Diversity of Arthropods on Bt Maize and Non-Bt Maize in two Different Cropping Systems in South Africa," which appears in the February 2014 issue of "The aims of the study were to compile a checklist of arthropods that occur on maize in South Africa and to compare the diversity and abundance of arthropods and functional groups on Bt maize and non-Bt maize," the authors wrote. "Results from this short-term study indicated that abundance and diversity of arthropods in maize and the different functional guilds were not significantly affected by Bt maize, either in terms of diversity or abundance."A total of 8,771 arthropod individuals, comprising 288 morphospecies, were collected from 480 plants sampled from Bt maize and non-Bt maize fields over a two-year period. The researchers found no significant differences in abundance or diversity in detritivores, herbivores, predators, or parasitoids."The results of our study indicate that arthropod diversity, even in high-input farming systems, is as high as in subsistence farming systems" said Dr. Johnnie van den Berg, a professor at North-West University and one of the co-authors of the article. "More recently, surveys of arthropod and plant beta-diversity inside and adjacent to maize fields have been completed during which 30,000 arthropods and 15,000 plant individuals were surveyed along a 1,000 kilometer transect. It seems that maize field diversity is homogenized and field margins had a high beta diversity," he added.
|
Genetically Modified
| 2,014 |
January 31, 2014
|
https://www.sciencedaily.com/releases/2014/01/140131230729.htm
|
Fruit flies reveal normal function of gene mutated in spinocerebellar ataxia type 7
|
Disruptive clumps of mutated protein are often blamed for clogging cells and interfering with brain function in patients with the neurodegenerative diseases known as spinocerebellar ataxias. But a new study in fruit flies suggests that for at least one of these diseases, the defective proteins may not need to form clumps to do harm.
|
The study, published February 1, 2014, in the journal Workman and Abmayr did not set out to study Ataxin-7. For more than a decade, the husband-and-wife team has been investigating how a large protein complex called SAGA, which helps control gene activity in organisms from yeast to humans, influences developmental processes. Workman's lab discovered the complex in yeast in the 1990s. In fruit flies, about 20 different proteins come together to form SAGA, which modifies DNA packaging in multiple ways to influence the activity of thousands of genes.When Vikki Weake, Ph.D., a former postdoctoral researcher in Workman's lab, began investigating the components of the fruit fly SAGA complex, she came across a protein that had not previously been studied in fruit flies. Postdoctoral researcher Ryan Mohan, Ph.D., focused his attention on that novel protein, and by scouring genetic databases, uncovered a resemblance to human Ataxin-7.Ataxin-7 is one of several genes associated with neurodegenerative diseases, including Huntington's disease and other spinocerebellar ataxias. These genes sometimes develop a genetic "stutter" in which a three-letter segment of the DNA code is repeated over and over. "It's not known how that affects that activity of the protein," Abmayr says. "But what is known is that it can cause aggregation." The expansion in the genetic code leads to proteins containing long, redundant strings of a single amino acid called glutamine, she explains. These abnormal proteins are prone to aggregating with one another inside cells.Ataxin-7 was known to aggregate in the cells of patients with SCA-7, but there was no direct evidence linking the aggregates to neurodegeneration. So when the team stumbled across a version of Ataxin-7 in fruit flies, they saw an opportunity to learn more.Mohan says most studies of ataxins and related proteins had focused on the effects of the polyglutamine-expanded versions, rather than the function of the unaltered protein. "I considered that this was part of a larger protein complex that was regulating many, many genes, and I thought it was important to find out what the protein normally does to regulate the complex," he says. "From that position, I could consider what a polyglutamine insertion might do to disturb those functions."Mohan conducted detailed biochemical analyses to better understand how loss of Ataxin-7 affected the SAGA complex. His experiments showed that Ataxin-7 anchors one of the complex's enzymatic modules, which is responsible for removing chemical tags called ubiquitin from DNA-packing proteins. Without Ataxin-7, this module falls off the complex. On its own, the released module becomes overactive, removing too many ubiquitin tags. This can lead to misregulation of genes. The scientists are planning further experiments to find out which genes are affected when Ataxin-7 stops working.Next, Mohan genetically engineered flies without any Ataxin-7. Without the protein, most flies died as embryos. Those that survived to adulthood had movement problems, demonstrated by their inability to climb. When the scientists looked at the structure of the neurons in the insects' brains and eyes, they saw that while the tissue in very young flies was more or less intact, problems developed quickly. "They are initially kind of okay, but after a few days we see massive degeneration in the brain and the eye," Abmayr explains. Similar effects were seen in flies whose Ataxin-7 gene was shut off only in cells in the brain and eyes. The neurodegeneration that the scientists observed was similar to what other researchers had found in flies producing a human Ataxin-7 protein with the polyglutamine expansion."This sheds new light on what we think could be the cause of the SCA7 disease phenotype," Abmayr says. "The problems associated with the disease may be because these polyglutamines actually knock out the function of the Ataxin-7 protein."The fruit fly has the potential to reveal more about Ataxin-7's role in disease, say the scientists, who are now planning to create a mutant fly whose Ataxin-7 contains a polyglutamine expansion. "Hopefully with a combination of biochemistry and genetics we can sort out how much of the neurodegeneration comes from the fact that you don't have the normal Ataxin-7 protein, and how much is because of the aggregated protein," Abmayr says.
|
Genetically Modified
| 2,014 |
January 31, 2014
|
https://www.sciencedaily.com/releases/2014/01/140131130626.htm
|
Protocol developed to harvest mouse cell lines for melanoma research
|
Dartmouth researchers have developed a protocol that permits cells harvested from melanoma tumors in mice to grow readily in cell culture. Their findings were published in an article, Multiple murine BRafV600E melanoma cell lines with sensitivity to PLX4032, in the January 25, 2014 issue of
|
"We anticipate that these cell lines will be extremely useful to many investigators who use mouse melanoma as a model system," said Constance E. Brinckerhoff, PhD, professor of Medicine and of Biochemistry at the Geisel School of Medicine at Dartmouth College and a member of the Norris Cotton Cancer Center (NCCC) Mechanism Research Program.There is a lack of mouse cell lines that harbor the BRAF mutation that is so prevalent in human melanomas, and the cell lines that are available grow slowly in culture and are not representative of human melanoma cell lines. Detailed experiments on molecular mechanisms controlling mouse cell line behavior have been difficult because the currently available mouse cell lines do not grow well in culture.The Geisel researchers are the first to have developed a protocol that permits mouse melanoma cells to be harvested from tumors in the mice and to grow readily in cell culture. Importantly, these cell lines are genetically compatible with a strain of mice that are immunologically competent, while human cells need to be placed into immunologically weakened mice in order to grow. Thus, the ability to study these mouse melanoma cell lines both in culture and in mice with an intact immune system is an experimental advantage.
|
Genetically Modified
| 2,014 |
January 30, 2014
|
https://www.sciencedaily.com/releases/2014/01/140130121607.htm
|
Precise gene editing in monkeys paves the way for valuable human disease models
|
Monkeys are important for modeling diseases because of their close similarities to humans, but past efforts to precisely modify genes in primates have failed. In a study published by Cell Press January 30th in the journal
|
"Our study shows that the CRISPR/Cas9 system enables simultaneous disruption of two target genes in one step without producing off-target mutations," says study author Jiahao Sha of Nanjing Medical University. "Considering that many human diseases are caused by genetic abnormalities, targeted genetic modification in monkeys is invaluable for the generation of human disease models."The CRISPR/Cas9 system is a gene editing tool capable of targeting specific DNA sequences in the genome. Cas9 proteins, which are directed by molecules called single-guide RNAs to specific sites in the genome, generate mutations by introducing double-stranded DNA breaks. Until now, the CRISPR/Cas9 system and other targeted gene editing techniques were successfully applied to mammals such as mice and rats, but not to primates.Sha teamed up with Xingxu Huang of Nanjing University and Weizhi Ji of the Yunnan Key Laboratory of Primate Biomedical Research and Kunming Biomed International. The researchers injected messenger RNA molecules encoding Cas9, in addition to single-guide RNAs designed to target three specific genes, into one-cell-stage embryos of cynomolgus monkeys. After sequencing genomic DNA from 15 embryos, they found that eight of these embryos showed evidence of simultaneous mutations in two of the target genes.The researchers then transferred genetically modified embryos into surrogate females, one of which gave birth to a set of twins. By sequencing the twins' genomic DNA, they found mutations in two of the target genes. Moreover, the CRISPR/Cas9 system did not produce mutations at genomic sites that were not targeted, suggesting that the tool will not cause undesirable effects when applied to monkeys. "With the precise genomic targeting of the CRISPR/Cas9 system, we expect that many disease models will be generated in monkeys, which will significantly advance the development of therapeutic strategies in biomedical research," Ji says.
|
Genetically Modified
| 2,014 |
January 29, 2014
|
https://www.sciencedaily.com/releases/2014/01/140129165415.htm
|
Puzzling question in bacterial immune system answered
|
A central question has been answered regarding a protein that plays an essential role in the bacterial immune system and is fast becoming a valuable tool for genetic engineering. A team of researchers with the Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California (UC) Berkeley have determined how the bacterial enzyme known as Cas9, guided by RNA, is able to identify and degrade foreign DNA during viral infections, as well as induce site-specific genetic changes in animal and plant cells. Through a combination of single-molecule imaging and bulk biochemical experiments, the research team has shown that the genome-editing ability of Cas9 is made possible by the presence of short DNA sequences known as "PAM," for protospacer adjacent motif.
|
"Our results reveal two major functions of the PAM that explain why it is so critical to the ability of Cas9 to target and cleave DNA sequences matching the guide RNA," says Jennifer Doudna, the biochemist who led this study. "The presence of the PAM adjacent to target sites in foreign DNA and its absence from those targets in the host genome enables Cas9 to precisely discriminate between non-self DNA that must be degraded and self DNA that may be almost identical. The presence of the PAM is also required to activate the Cas9 enzyme."With genetically engineered microorganisms, such as bacteria and fungi, playing an increasing role in the green chemistry production of valuable chemical products including therapeutic drugs, advanced biofuels and biodegradable plastics from renewables, Cas9 is emerging as an important genome-editing tool for practitioners of synthetic biology."Understanding how Cas9 is able to locate specific 20-base-pair target sequences within genomes that are millions to billions of base pairs long may enable improvements to gene targeting and genome editing efforts in bacteria and other types of cells," says Doudna who holds joint appointments with Berkeley Lab's Physical Biosciences Division and UC Berkeley's Department of Molecular and Cell Biology and Department of Chemistry, and is also an investigator with the Howard Hughes Medical Institute (HHMI).Doudna is one of two corresponding authors of a paper describing this research in the journal Bacterial microbes face a never-ending onslaught from viruses and invasive snippets of nucleic acid known as plasmids. To survive, the microbes deploy an adaptive nucleic acid-based immune system that revolves around a genetic element known as CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats. Through the combination of CRISPRs and RNA-guided endonucleases, such as Cas9, ("Cas" stands for CRISPR-associated), bacteria are able to utilize small customized crRNA molecules (for CRISPR RNA) to guide the targeting and degradation of matching DNA sequences in invading viruses and plasmids to prevent them from replicating. There are three distinct types of CRISPR-Cas immunity systems. Doudna and her research group have focused on the Type II system which relies exclusively upon RNA-programmed Cas9 to cleave double-stranded DNA at target sites."What has been a major puzzle in the CRISPR-Cas field is how Cas9 and similar RNA-guided complexes locate and recognize matching DNA targets in the context of an entire genome, the classic needle in a haystack problem," says Samuel Sternberg, lead author of the Doudna, Sternberg and their colleagues used a unique DNA curtains assay and total internal reflection fluorescence microscopy (TIRFM) to image single molecules of Cas9 in real time as they bound to and interrogated DNA. The DNA curtains technology provided unprecedented insights into the mechanism of the Cas9 target search process. Imaging results were verified using traditional bulk biochemical assays."We found that Cas9 interrogates DNA for a matching sequence using RNA-DNA base-pairing only after recognition of the PAM, which avoids accidentally targeting matching sites within the bacterium's own genome," Sternberg says. "However, even if Cas9 somehow mistakenly binds to a matching sequence on its own genome, the catalytic nuclease activity is not triggered without a PAM being present. With this mechanism of DNA interrogation, the PAM provides two redundant checkpoints that ensure that Cas9 can't mistakenly destroy its own genomic DNA."
|
Genetically Modified
| 2,014 |
January 28, 2014
|
https://www.sciencedaily.com/releases/2014/01/140128163455.htm
|
Animal model demonstrates role for metabolic enzyme in acute myeloid leukemia
|
In recent years, mutations in two metabolic enzymes, isocitrate dehydrogenase-1 and 2 (IDH1 and IDH2), have been identified in approximately 20 percent of all acute myeloid leukemias (AML). As a result, mutant IDH proteins have been proposed as attractive drug targets for this common form of adult leukemia.
|
Now a scientific team at Beth Israel Deaconess Medical Center (BIDMC) has generated a transgenic mouse model of the most common IDH2 mutation in human AML, and, in the process, answered a central question of whether these mutant IDH proteins are required for leukemia initiation and maintenance in a living organism.Currently published on-line in the journal "The real hope is that we would one day be able to treat IDH2-mutant leukemia patients with a drug that targets this genetic abnormality," explains senior author Pier Paolo Pandolfi, MD, PhD, Director of the Cancer Center and the Cancer Research Institute at BIDMC and the George C. Reisman Professor of Medicine at Harvard Medical School. "Our transgenic animal model has now demonstrated that the IDH mutation contributes to the initiation of acute leukemia in vivo and that mutant IDH is essential for the maintenance of leukemic cells even in a genetic setting where mutant IDH is not required for cancer initiation."IDH1 and IDH2 proteins are critical enzymes in the TCA cycle, which is centrally important to many biochemical pathways. Mutated forms of these proteins gain a novel ability to produce 2-hydroxyglutarate (2HG), a metabolite that has been shown to accumulate at high levels in cancer patients and is therefore described as an "oncometabolite.""Our goal was to generate an animal model of mutant IDH that was both inducible and reversible," explains co-lead author Markus Reschke, PhD, an investigator in BIDMC's Cancer Research Institute and Research Fellow in the Pandolfi laboratory. "This enabled us to address an important unanswered question: Does inhibition of mutant IDH proteins in active disease have an effect on tumor maintenance or progression in a living organism?"Reschke and co-lead author Lev Kats, PhD, also a Research Fellow in the Pandolfi lab, studied two different models: a retroviral transduction model and a genetically engineered model in which IDH mice were crossed to mice harboring other leukemia-relevant mutations.In the first model, the IDH mutation was combined with the oncogenes HoxA9 and Meis1a, two downstream targets of numerous pathways that are deregulated in AML. The results showed evidence of differentiation within two weeks of genetic deinduction of mutant IDH, and two weeks later, six of eight animals showed complete remission with elimination of any detectable leukemic cells.These results, say the authors, were both surprising and encouraging, demonstrating a situation in which IDH mutation occurs as an early event and leukemic transformation occurs as a result of subsequent genetic "hits.""The retroviral model enabled us to observe that mutant IDH2 is essential for the maintenance of HoxA9/Meis1a-induced AML," explains Kats. "But this was still a surrogate model -- this isn't what happens in human patients, per se."The investigators, therefore, went on to develop a transgenic model that more closely recapitulates the genetics of human AML."By crossing the mutant IDH2 animals with other leukemia-relevant mutations, including mutations in the FMS-like tyrosine kinase 3 [FLT3], we observed that compound mutant animals developed acute leukemias," explains Reschke. "This exciting finding told us that mutant IDH2 contributes to leukemia initiation in vivo." As with the retroviral transduction model, genetic deinduction of mutant IDH2 in the context of a cooperating Flt3 mutation resulted in reduced proliferation and/or differentiation of leukemic cells, further demonstrating that mutant IDH2 expression is required for leukemia maintenance."This model has validated mutant IDH proteins as very strong candidates for continued development of targeted anticancer therapeutics," says Pandolfi. "The model will also be of paramount importance to study mechanisms of resistance to treatment that may occur."
|
Genetically Modified
| 2,014 |
January 27, 2014
|
https://www.sciencedaily.com/releases/2014/01/140127093216.htm
|
Immune system drives pregnancy complications after fetal surgery in mice
|
As a fetal surgeon at UC San Francisco, Tippi MacKenzie, MD, has long known that conducting surgery on a fetus to correct a problems such as spina bifida often results in preterm labor and premature birth.
|
Now, MacKenzie and her UCSF colleagues have shown that, in mice at least, pregnancy complications after fetal surgery are triggered by activation of the mother's T cells -- the same T cells that cause the body to reject a donor organ after transplant surgery."Here at UCSF, the birthplace of fetal surgery, preterm labor has been described as the 'Achilles' heel' of the field because it diminishes the benefit of the surgery itself," said MacKenzie, an associate professor of surgery and director of research at the UCSF Fetal Treatment Center. "However, specific treatments have not been developed because until now, the biological triggers responsible for preterm birth have been unknown."If the same fetal rejection mechanism is occurring in humans, she said, "we have the ability to design specific medical treatments to prevent it -- for example, by using medications that target some of the pathways involved in T cell-mediated rejection."The study was published online on January 15, 2014, in the Normally, pregnancy is a robust form of immune tolerance, in which the pregnant mother naturally tolerates a genetically foreign fetus, MacKenzie explained. "This is in contrast to an organ transplant, where you need to administer immunosuppressive drugs to prevent the body from rejecting a foreign graft. Our study supports the idea that fetal intervention breaks this tolerance by activating the mother's immune system, suggesting that the biology behind preterm labor is similar to transplant rejection."In their study, MacKenzie and her team used a mouse model of fetal intervention to show that, after fetal surgery, maternal T cells gather in the uterus. "These are effector T cells, which are the main cells responsible for rejecting a transplanted organ," said MacKenzie. "In a shift from the normal balance in the uterus, they outnumber regulatory T cells, which are usually responsible for suppressing an immune response against the fetus."The scientists next worked with genetically modified mice that had T cells designed to recognize and reject one specific foreign protein. They transferred those T cells into the circulation of pregnant mice whose fetuses expressed that protein because they had inherited the gene from their father. The scientists found that, in mice that had fetal surgery, the transferred T cells multiplied and migrated to the uterus."It's known that in a normal pregnancy T cells that recognize the fetus can circulate in the mother and live in harmony with the fetus," said first author Marta Wegorzewska, DEGREE? a graduate student in the MacKenzie lab. "But when you perform fetal surgery, they get activated and go to the uterus."Although the activated T cells were an important clue, the researchers' next step was to prove that they had a harmful effect on pregnancy. They designed an experiment in which half of the pups carried by a pregnant mouse were genetically identical to their mother -- as is common among experimental mice -- and half were genetically different and expressed foreign proteins inherited from the father. They then injected more of the foreign protein into each fetus in the litter. After this fetal intervention, the scientists observed that there were significantly more deaths among the genetically different pups than among the genetically identical pups.They then repeated the experiment on a group of mice without T cells and found no difference in the rate of death between the two types of pups."This experiment demonstrates that activation of the mother's T cells after fetal surgery can mediate the death of genetically foreign fetuses," concluded MacKenzie.She cautioned that there is a significant difference between her experimental mouse model and human pregnancy: If a mouse pregnancy has complications after fetal surgery, the outcome is not preterm labor but the death of the fetus. "That said, this mouse model is a wonderful tool to study the immune mechanisms of pregnancy complications after surgery," MacKenzie said.The next step for her team, she said, "is to determine to what extent fetal interventions trigger the mother's immune response in humans, or if there is some other cause. Those studies are currently under way."
|
Genetically Modified
| 2,014 |
January 22, 2014
|
https://www.sciencedaily.com/releases/2014/01/140122091950.htm
|
Engineer converts yeast cells into 'sweet crude' biofuel
|
Researchers at The University of Texas at Austin's Cockrell School of Engineering have developed a new source of renewable energy, a biofuel, from genetically engineered yeast cells and ordinary table sugar. This yeast produces oils and fats, known as lipids, that can be used in place of petroleum-derived products.
|
Assistant professor Hal Alper, in the Cockrell School's McKetta Department of Chemical Engineering, along with his team of students, created the new cell-based platform. Given that the yeast cells grow on sugars, Alper calls the biofuel produced by this process "a renewable version of sweet crude."The researchers' platform produces the highest concentration of oils and fats reported through fermentation, the process of culturing cells to convert sugar into products such as alcohol, gases or acids. This work was published in The UT Austin research team was able to rewire yeast cells to enable up to 90 percent of the cell mass to become lipids, which can then be used to produce biodiesel."To put this in perspective, this lipid value is approaching the concentration seen in many industrial biochemical processes," Alper said. "You can take the lipids formed and theoretically use it to power a car."Since fatty materials are building blocks for many household products, this process could be used to produce a variety of items made with petroleum or oils -- from nylon to nutrition supplements to fuels. Biofuels and chemicals produced from living organisms represent a promising portion of the renewable energy market. Overall, the global biofuels market is expected to double during the next several years, going from $82.7 billion in 2011 to $185.3 billion in 2021."We took a starting yeast strain of The biofuel the researchers formulated is similar in composition to biodiesel made from soybean oil. The advantages of using the yeast cells to produce commercial-grade biodiesel are that yeast cells can be grown anywhere, do not compete with land resources and are easier to genetically alter than other sources of biofuel."By genetically rewiring So far, high-level production of biofuels and renewable oils has been an elusive goal, but the researchers believe that industry-scale production is possible with their platform.In a large-scale engineering effort spanning over four years, the researchers genetically modified "Our cells do not require that starvation," Alper said. "That makes it extremely attractive from an industry production standpoint."The team increased lipid levels by nearly 60-fold from the starting point.At 90 percent lipid levels, the platform produces the highest levels of lipid content created so far using a genetically engineered yeast cell. To compare, other yeast-based platforms yield lipid content in the 50 to 80 percent range. However, these alternative platforms do not always produce lipids directly from sugar as the UT Austin technology does.Alper and his team are continuing to find ways to further enhance the lipid production levels and develop new products using this engineered yeast.This research was funded by the Office of Naval Research Young Investigator Program, the DuPont Young Professor Grant and the Welch Foundation under grant F-1753.
|
Genetically Modified
| 2,014 |
January 16, 2014
|
https://www.sciencedaily.com/releases/2014/01/140116085059.htm
|
Stem cells overcome damage in other cells by exporting mitochondria
|
A research team has identified a protein that increases the transfer of mitochondria from mesenchymal stem cells to lung cells. In work published in The EMBO Journal, the researchers reveal that the delivery of mitochondria to human lung cells can rejuvenate damaged cells. The migration of mitochondria from stem cells to epithelial cells also helps to repair tissue damage and inflammation linked to asthma-like symptoms in mice.
|
"Our results show that the movement of mitochondria from stem cells to recipient cells is regulated by the protein Miro1 and is part of a well-directed process," remarked Anurag Agrawal, Professor at the CSIR-Institute of Genomics and Integrative Biology in Delhi, India, and one of the lead authors of the study. "The introduction of mitochondria into damaged cells has beneficial effects on the health of cells and, in the long term, we believe that mesenchymal stem cells could even be engineered to create more effective therapies for lung disease in humans."Earlier work revealed that mitochondria can be transferred between cells through tunneling nanotubes, thread-like structures formed from the plasma membranes of cells that bridge between different types of cells. Stem cells can also use tunneling nanotubes to transfer mitochondria to neighboring cells and the number of these nanotubes increases under conditions of stress.In the study, the protein Miro1 was shown to regulate the transfer of mitochondria from mesenchymal stem cells to epithelial cells. Stem cells that were engineered to have higher amounts of Miro1 were able to transfer mitochondria more efficiently and were therapeutically more effective when tested in mouse models of airway injury and asthma, compared to untreated cells."We hope to determine how this pathway might translate into better stem cell therapies for human disease," added Agrawal.
|
Genetically Modified
| 2,014 |
January 15, 2014
|
https://www.sciencedaily.com/releases/2014/01/140115113518.htm
|
First comprehensive test to detect genetic modification in food
|
As the abundance of genetically modified (GM) foods continues to grow, so does the demand for monitoring and labeling them. The genes of GM plants used for food are tweaked to make them more healthful or pest-resistant, but some consumers are wary of such changes. To help inform shoppers and enforce regulations, scientists are reporting in ACS' journal
|
Li-Tao Yang, Sheng-Ce Tao and colleagues note that by the end of 2012, farmers were growing GM crops on more than 420 million acres of land across 28 countries. That's 100 times more than when commercialization began in 1996. But doubts persist about the potential effects on the environment and human health of these biotech crops, created by changing the plants' genes to make them more healthful or more able to resist pests. In response, policymakers, particularly in Europe, have instituted regulations to monitor GM products. Although researchers have come up with many ways to detect genetic modification in crops, no single test existed to do a comprehensive scan, which is where Yang and Tao come in.They developed a test they call "MACRO," which stands for: multiplex amplification on a chip with readout on an oligo microarray. It combines two well-known genetic methods to flag about 97 percent of the known commercialized modifications, almost twice as many as other tests. It also can be easily expanded to include future genetically modified crops.
|
Genetically Modified
| 2,014 |
January 9, 2014
|
https://www.sciencedaily.com/releases/2014/01/140109143756.htm
|
Capturing a hard-wired variability: What makes some identical twins noticeably different?
|
A Ludwig Cancer Research study has uncovered a phenomenon that alters prevailing views of how the genome is expressed to make and sustain the life of mammals. Published in the journal
|
"We have captured a fundamental randomness at the level of gene expression that has never before been described -- one that persists throughout development and into adulthood," says Ludwig scientist Rickard Sandberg at the Karolinska Institutet in Sweden. The discovery was made possible by a powerful new technique developed by Sandberg's lab for analyzing the global expression of genes in single cells.With the exception of a subset of genes found on sex chromosomes, every mammal inherits one copy of every gene from each of its parents. Each of those copies is known as an allele, and alleles often differ measurably from their genomic siblings -- a fact that accounts for a good deal of human and animal diversity. It has, however, long been unclear whether each allele in any given cell or organism is expressed equally, or whether one allele is favored over the other. The current study finds that only one allele is expressed in between 12 and 24 percent of all such pairs encoded by the mouse genome. Further, the selection of expressed alleles varies randomly from cell to cell, and switches frequently between the two options throughout their lives.Biologists typically assume that most alleles, with a few exceptions, are equally expressed on all chromosomes except those that determine sex. They have long known, however, that "imprinted" genes -- which may be modified to selectively express only one of the two alleles -- are an exception. But such genes only account for 1 percent of the total. "We find that for those genes that are not imprinted, roughly one in five alleles is randomly and dynamically expressed only one at a time," says Sandberg. "And if one allele is being expressed, the other doesn't know about it. There's no coordination between two."This explains in some measure why identical twins -- products of nearly identical genomes -- can be noticeably different from one another in their appearance and propensity for disease. Living things are, after all, built from cells, and each cell is in turn the product of the genes it expresses. Dynamic and random allelic expression can result in different blends of some traits, even in otherwise genetically identical people.The finding also has significant implications for our understanding of some genetic diseases, such as neurofibromatosis, a painful disorder characterized by the systemic proliferation of non-cancerous neural tumors. It has long been a mystery why people who share the mutations that cause this family of diseases are so variably affected by it. The essential randomness of allelic expression might help account for those differences in this disease as well as in others.
|
Genetically Modified
| 2,014 |
January 8, 2014
|
https://www.sciencedaily.com/releases/2014/01/140108123534.htm
|
Color-coded cells reveal patchwork pattern of X chromosome silencing in female brains
|
Producing brightly speckled red and green snapshots of many different tissues, Johns Hopkins researchers have color-coded cells in female mice to display which of their two X chromosomes has been made inactive, or "silenced."
|
Scientists have long known that the silencing of one X chromosome in females -- who have two X chromosomes in every cell -- is a normal occurrence whose consequences can be significant, especially if one X chromosome carries a normal copy of a gene and the other X chromosome carries a mutated copy.By genetically tagging different X chromosomes with genes that code for red or green fluorescent proteins, scientists say they can now peer into different tissue types to analyze genetic diversity within and between individual females at a new level of detail.Published on Jan. 8 in the journal "Calico cats, which are only ever female, have mottled coat colors. They have two different versions of a gene for coat color, which is located on the X chromosome: one version from their mother and the other from their father," explains Jeremy Nathans, M.D., Ph.D., professor of molecular biology and genetics at the Johns Hopkins University and a Howard Hughes Medical Institute investigator. "Their fur is orange or black depending on which X chromosome is silenced in a particular patch of skin cells. X chromosome inactivation actually occurs in all cells in female mammals, including humans, and it affects most of the genes on the X chromosome. Although this phenomenon has been known for over 50 years, it couldn't be clearly visualized in internal organs and tissues until now."Nathans adds that early in the development of most mammals, when a female embryo has only about 1,000 cells, each cell makes a "decision" to inactivate one of the two X chromosomes, a process that silences most of the genes on that chromosome. The choice of which X chromosome to inactivate appears to be random, but when those cells divide, their descendants maintain that initial decision.In the new research, the Johns Hopkins team mated female mice carrying two copies of the gene for green fluorescent protein -- one on each of the two X chromosomes -- with male mice whose single X chromosome carried the gene for a red fluorescent protein. The female offspring from this mating had cells that glowed red or green based on which X chromosome was silenced. Additionally, the team engineered the mice so that not all of their cells were color-coded, since that would make it hard to distinguish one cell from another. Instead, they designed a system that allowed a single cell type in each mouse, such as heart muscle cells, to be color-coded. Their genetic trick resulted in red and green color maps with distinctive patterns for each cell and tissue type that they examined.Nathans explains that the patterns are determined by the way each tissue develops. Some tissues are created from a very small number of "founder cells" in the early embryo; others are created from a large number. Statistically, the larger the group of founder cells, the greater the chances are of having a nearly equivalent number of red and green cells. Although the ratio in the founding group is roughly preserved as the tissue grows, the distribution of those cells is determined by how much movement occurs during the development of the tissue. For example, in a tissue like blood, where the cells move a lot, the red and green cells are finely intermingled. By contrast, in skin, where the cells show little movement, each patch of skin consists of the descendants of a single cell, which share the same inactive X chromosome -- and therefore the same color -- creating a coarse patchwork of red and green.Normally, the pattern of X chromosome inactivation is not easily visualized. This color-coding technique is likely to be valuable for many studies, Nathans says, especially for research on variations caused by changes in the DNA sequence of the X chromosome, referred to as X-linked variation. X-linked genetic variations, such as hemophilia or color blindness, are relatively common, in part because the X chromosome carries many genes -- approximately 1,000, or close to 4 percent of the total.Males who inherit an X-linked disease usually suffer its effects because they have no second X chromosome to compensate for the mutant version of the gene. Female relatives, on the other hand, are more typically "carriers" of X-linked diseases. They have the ability to pass the disease along to their male progeny, but they do not suffer from it themselves due to the normal copy of the gene on their second X chromosome.In the tissues of certain carrier females, however, the cells that have silenced the X chromosome with a mutated gene cannot compensate for the defect in the cells that have silenced the X chromosome with the normal gene. Nathans and his team saw such a pattern when they examined the retinas of mice that were carriers for mutations in the Norrie disease gene, which is located on the X chromosome. The Norrie disease gene codes for a protein, Norrin, which controls blood vessel formation in the retina. Women who are carriers for Norrie disease can have defects in their retinas, but some women are more affected than others, and sometimes one eye is more affected than the other eye in the same individual.The team found that in female mice that were Norrie disease carriers, variation in blood vessel structure corresponded to localized variations in X chromosome inactivation. When the X chromosome carrying the normal copy of the Norrie disease gene was silenced in a group of cells, the blood vessels nearby failed to form properly. In contrast, when the X chromosome carrying the mutated copy of the Norrie disease gene was silenced, the nearby blood vessels developed normally."X chromosome inactivation is a fascinating aspect of mammalian biology," says Nathans. "This new technique for visualizing the pattern of X chromosome inactivation should be particularly useful for looking at the role that this process plays in brain development, including the ways that it contributes to differences between the left and right sides of the female brain, and to differences in brain structure between males and females and among different females, including identical twins."
|
Genetically Modified
| 2,014 |
January 7, 2014
|
https://www.sciencedaily.com/releases/2014/01/140107134312.htm
|
On-demand vaccines possible with engineered nanoparticles
|
Vaccines combat diseases and protect populations from outbreaks, but the life-saving technology leaves room for improvement. Vaccines usually are made en masse in centralized locations far removed from where they will be used. They are expensive to ship and keep refrigerated and they tend to have short shelf lives.
|
University of Washington engineers hope a new type of vaccine they have shown to work in mice will one day make it cheaper and easy to manufacture on-demand vaccines for humans. Immunizations could be administered within minutes where and when a disease is breaking out."We're really excited about this technology because it makes it possible to produce a vaccine on the spot. For instance, a field doctor could see the beginnings of an epidemic, make vaccine doses right away, and blanket vaccinate the entire population in the affected area to prevent the spread of an epidemic," said François Baneyx, a UW professor of chemical engineering and lead author of a recent paper published online in the journal The research was funded by a Grand Challenges Explorations grant from the Bill & Melinda Gates Foundation and the National Institutes of Health.In typical vaccines, weakened pathogens or proteins found on the surface of microbes and viruses are injected into the body along with compounds called adjuvants to prepare a person's immune system to fight a particular disease. But standard formulations don't always work, and the field is seeking ways to manufacture vaccines quicker, cheaper and tailored to specific infectious agents, Baneyx said.The UW team injected mice with nanoparticles synthesized using an engineered protein that both mimics the effect of an infection and binds to calcium phosphate, the inorganic compound found in teeth and bones. After eight months, mice that contracted the disease made threefold the number of protective "killer" T-cells -- a sign of a long-lasting immune response -- compared with mice that had received the protein but no calcium phosphate nanoparticles.The nanoparticles appear to work by ferrying the protein to the lymph nodes where they have a higher chance of meeting dendritic cells, a type of immune cell that is scarce in the skin and muscles, but plays a key role in activating strong immune responses.In a real-life scenario, genetically engineered proteins based on those displayed at the surface of pathogens would be freeze-dried or dehydrated and mixed with water, calcium and phosphate to make the nanoparticles. This should work with many different diseases and be especially useful for viral infections that are hard to vaccinate against, Baneyx said.He cautioned, however, that it has only been proven in mice, and the development of vaccines using this method hasn't begun for humans.The approach could be useful in the future for vaccinating people in developing countries, especially when lead time and resources are scarce, Baneyx said. It would cut costs by not having to rely on refrigeration, and vaccines could be produced with rudimentary equipment in more precise, targeted numbers. The vaccines could be manufactured and delivered using a disposable patch, like a bandage, which could one day lessen the use of trained personnel and hypodermic needles.Co-authors of the paper are Weibin Zhou, Albanus Moguche and David Chiu of the UW, and Kaja Murali-Krishna of Emory University.
|
Genetically Modified
| 2,014 |
January 7, 2014
|
https://www.sciencedaily.com/releases/2014/01/140107112532.htm
|
When germs attack: Lens into molecular dance
|
Researchers at Johns Hopkins have zoomed in on what is going on at the molecular level when the body recognizes and defends against an attack of pathogens, and the findings, they say, could influence how drugs are developed to treat autoimmune diseases.
|
The focus of the research is a pathogen "sensor" known as human IFN inducible protein-16 or IFI16, one of the body's key responders to viruses and bacteria, including herpes, HIV, listeria and salmonella. When IFI16 goes awry, it can prod the immune system to attack its own cells, triggering autoimmune disorders such as lupus and Sjögren syndrome (in which the glands that produce tears and saliva are destroyed). By figuring out how IFI16 operates, biophysicist Jungsan "Jay" Sohn, Ph.D., and his team say they have set the stage for finding ways to stop or limit the damage.For the study, described online at the "By understanding how IFI16 works at this fine molecular level, we may be able to boost this activity to build up immunity or taper down this activity to correct autoimmune disorders," says Sohn, an assistant professor of biophysics and biophysical chemistry.Sohn and his research team first generated genetically engineered IFI16 from bacteria and exposed it to synthetic DNA sequences of varying lengths to see how the protein might react to "foreign," pathogenic DNA. They then observed the IFI16 and DNA interact via electron microscopy. What they saw was surprising.The team expected that IFI16, like other pathogen sensors, would react to foreign DNA if it is long enough to accommodate just one IFI16 molecule. But IFI16 didn't react strongly until the synthetic DNA fragments exceeded 60 base pairs in length, which can accommodate about four IFI16 molecules. It was as if a light went on when the "invading" DNA reached 70 to 100 base pairs, Sohn says. "We call that switch-like behavior."IFI16's preference for long DNA strands explains a longstanding mystery, according to Sohn. Researchers, he explains, have wondered how our bodies' immune systems mostly avoid "friendly fire," or being sent into overdrive and attacking themselves. The new experiments suggest that the length of DNA could be the key: Our DNA is packaged such that there are only short exposed fragments, and IFI16 won't activate in the presence of short DNA, but will in the presence of pathogenic DNA, which typically expose much longer strands."What we found suggests that the sensor uses the length of the naked DNA as a molecular ruler to distinguish self from non-self," Sohn says.Subsequently, Sohn and his team investigated how a sensor like IFI16 was attracted to such long DNA. They found that IFI16 molecules line up along long pathogenic DNA strands to form chains, or filaments. The longer the naked DNA, the longer the chain. What's more, chains of IFI16 then line up and merge to create an even longer chain."The filaments emerge and elongate," Sohn says.But that left the question of how IFI16 molecules were able to find each other and align. In another set of experiments, the team showed that IFI16 contains three protein parts -- HinA, HinB and PYD -- and when they broke up PYD, the chain failed to form.What was surprising, he says, is that PYD doesn't bind directly to the pathogen's DNA. Rather, the Hin domains on IFI16 bind to the DNA, which makes the PYD domains gravitate toward one another. As a result, the PYDs glom together to form a powerful scaffold.Sohn says his work suggests that the PYD-PYD interaction is very specific and a great potential drug target."It's really difficult to develop a drug that's targeting something that binds non-specifically. But PYD-PYD interaction is specific, and it only happens when it encounters DNA. It is what drives the stability of the complex. So if you can disintegrate that, it might alleviate autoimmune disorders," Sohn says. Conversely, developing drugs that bolster the scaffold could enhance immunity, he adds.
|
Genetically Modified
| 2,014 |
January 2, 2014
|
https://www.sciencedaily.com/releases/2014/01/140102113142.htm
|
Research into fruit fly cells could lead to cancer insights
|
New research by scientists at the University of Exeter has shown that cells demonstrate remarkable flexibility and versatility when it comes to how they divide -- a finding with potential links to the underlying causes of many cancers.
|
The study, published today in In order to understand the phenomenon, the authors, including Biosciences researchers Dr. James Wakefield, PhD student Daniel Hayward and Experimental Officer in Image Analysis, Dr. Jeremy Metz, combined highly detailed microscopy and image analysis with genetic and protein manipulation of fruit fly embryos.The innovative research not only describes how the cell can use each pathway in a complementary way, but also that removal of one pathway leads to the cell increasing its use of the others. The researchers also identified that a central molecular complex -- Augmin -- was needed for all of these routes.The authors were the first to identify that each of four pathways of spindle formation could occur in fruit fly embryos.It was previously thought that, in order for chromosomes -- packages containing DNA -- to line up and be correctly separated, microtubules have to extend from specific microtubule-organising centres in the cell, called centrosomes. However, this study found that microtubules could additionally develop from the chromosomes themselves, or at arbitrary sites throughout the main body of the cell, if the centrosomes were missing.All of these routes to spindle formation appeared to be dependent on Augmin -- a protein complex responsible for amplifying the number of microtubules in the cell.Dr. Wakefield said of the project "We have all these different spindle formation pathways working in humans. Because the cell is flexible in which pathway it uses to make the spindle, individuals who are genetically compromised in one pathway may well grow and develop normally. But it will mean they have fewer routes to spindle formation, theoretically predisposing them to errors in cell division as they age."The group is currently investigating cancer links in light of these findings.
|
Genetically Modified
| 2,014 |
December 30, 2013
|
https://www.sciencedaily.com/releases/2013/12/131230170138.htm
|
Field trial with lignin modified poplars shows potential for bio-based economy
|
The results of a field trial with genetically modified poplar trees in Zwijnaarde, Belgium, shows that the wood of lignin modified poplar trees can be converted into sugars in a more efficient way. These sugars can serve as the starting material for producing bio-based products like bio-plastics and bio-ethanol.
|
The results of the field trial have been published in a scientific article in which the results of a field trial of French colleagues of the INRA institute in Orleans have also been incorporated. The article has been published in the online edition of The field trial however also showed that the suppression of the lignin biosynthesis in the trees is variable. In some trees the suppression is stronger than in other trees which is visible through a more pronounced red coloration of the wood beneath the bark. Some branches show almost no red coloration, others a spotty pattern and again other a full red coloration. The branches with the highest red coloration produce 160% more ethanol. On the whole the ethanol yield per gram of wood is 20% higher. This in itself is positive, except for the fact that the modified trees appear to grow somewhat less rapid than non-modified poplar trees.Prof. Wout Boerjan: "The branches with the highest red coloration give us hope that we will be able to achieve our goal in the future. The biosynthesis of lignin is very complex. We will now search for modifications that provide a strong and uniform suppression of the lignin biosynthesis. Because in the meantime we are also getting a pretty good idea of what causes the growth retardation, we immediately will start to work on poplars that grow normal, but still have a stable suppression of the lignin production. It must be possible to improve the ethanol yield per tree with 50 to 100%."In the poplar trees in the field trial in Zwijnaarde in Belgium the so-called 'CCR-enzyme' is suppressed. This enzyme plays a key role in the biosynthesis of lignin, but its suppression apparently does not lead to a uniform lowering of the amount of lignin. In a new field trial that VIB will start in Wetteren, Belgium, in 2014, trees will be tested in which another enzyme has been suppressed: the 'CAD-enzyme'. In these trees also a more modern way of suppression of the enzyme has been used. This new trial therefore fits into the search for modifications that provide a more uniform suppression of the lignin biosynthesis.
|
Genetically Modified
| 2,013 |
December 23, 2013
|
https://www.sciencedaily.com/releases/2013/12/131223181340.htm
|
Library of mutations across all genes
|
Researchers have developed a method to create a comprehensive library of mutations across all genes in the mouse genome. This library can be used to examine the role of every gene in different cell types.
|
CRISPR technology uses the DNA-cutting enzyme Cas9, with the help of a guide RNA sequence, to find and modify genetic targets. Scientists can easily engineer multiple new guide RNAs using standard molecular biology techniques. This makes for a much faster and efficient method to modify the genome of any cell type in any species.The team found that a remarkable 50 of 52 guide RNAs tested successfully cut both copies of the genes. The extremely high success rate for these engineered guide RNAs seems to be consistent across many cell types, which led them to create a library of guide RNAs targeting every gene in the mouse genome."CRISPR technology is revolutionising how we study the behaviour of cells," says Dr Kosuke Yusa, lead author from the Wellcome Trust Sanger Institute. "We've developed a thorough library that can be used by other researchers to study the role of any gene. We can create a library of this type for any cell or any species."The team has engineered a library of nearly 90,000 of these guide RNAs that can be used to target and modify every gene in the mouse genome, and created mutant stem cell libraries. They subjected the mutant libraries to a genetic screen against a bacterial toxin, The team targeted 26 genes that are known to be associated with the synthesis of the receptors of this bacterial toxin. They revealed that 17 of these genes were responsible for resistance. Importantly, they also identified previously unknown genes whose mutations confer with resistance to this toxic agent.The team will now use this library to create mutations in cancer cell lines. A major problem with cancer drugs is that often cells can quickly acquire resistance and reject the treatment. By screening for genes that have lost all function through mutation, the team can determine what genes are involved in acquiring resistance to cancer treatments and thus find a clinical target.
|
Genetically Modified
| 2,013 |
December 19, 2013
|
https://www.sciencedaily.com/releases/2013/12/131219130933.htm
|
Corn pest decline may save farmers money
|
Populations of European corn borer (ECB), a major corn crop pest , have declined significantly in the eastern United States, according to Penn State researchers. The decline suggests that the use of genetically modified, ECB-resistant corn hybrids -- an expensive, yet effective, solution that has been widely adopted by farmers -- may now be unnecessary in some areas.
|
"ECB, which was introduced to North America from Europe in the 1900s, used to be the most important pest of corn in the United States," said John Tooker, assistant professor of entomology. "Not that long ago, it caused crop losses that annually approached $1 billion nationwide, and $35 million in the northeastern United States."According to Tooker, to protect their crops from ECB, many farmers have grown a genetically modified type of corn that expresses insecticidal toxins that kill the worms. These toxins were isolated from the bacterium "These Bt corn hybrids have been widely adopted because they are exceptional for managing ECB -- 99.9 percent of larvae are expected to die when they feed on plants expressing Bt toxins," he said. "Yet a drawback to using these hybrids has been the high cost of purchasing the seeds, which can decrease potential profits."To understand current ECB populations in Pennsylvania field corn, the researchers assessed larval damage in Bt and non-Bt corn hybrids at 29 sites over three years. Specifically, they planted Bt and non-Bt corn hybrids on farm sites across four growing zones in Pennsylvania in 2010, 2011 and 2012. During September of each season, they assessed corn borer damage on 400 random plants at each site. They sliced open stalks, and recorded the number of ECB tunnels and larvae per stalk. They also evaluated corn ears for ECB damage."Our results confirm that we are seeing widespread population declines of ECB in the East, similar to declines that have been found in the Midwestern United States," said Eric Bohnenblust, graduate student in entomology. "With less ECB damage around, non-Bt hybrids in our tests yielded just as well as Bt hybrids, so the decline in ECB populations provides an opportunity for growers to generate greater profits by planting high-yielding non-Bt seed, which is much cheaper than Bt seed. Secondarily, planting more non-Bt corn will reduce the potential for ECB to develop resistance to Bt toxins as corn rootworms have done in about a dozen states so far."The team's results appeared in an early online edition of the journal In addition to investigating the extent of ECB populations and damage in Pennsylvania, the researchers also examined the predictive ability of the PestWatch network, which traps ECB and other moth species and provides data about their prevalence."While traps within the PestWatch network provide insight on ECB population size, where moths are active and periods of ECB activity, their utility as a predictive tool, particularly for field corn, has been limited," Bohnenblust said. "We found that ECB moths captured in the PestWatch network correlate well with in-field populations of ECB in field corn, which means that PestWatch data hold potential to inform decisions about whether Bt or non-Bt hybrids are right for growers in different parts of the state."According to Tooker, growers planting Bt corn hybrids are required to plant set amounts of non-Bt corn as part of a resistance management plan to help prevent evolution of ECB populations that are resistant to the Bt toxins expressed in corn hybrids."Based on our results, we would tell growers to scout their non-Bt acreage toward the end of the growing season," he said. "If they have low ECB populations, and PestWatch reflects low moth captures in their area, we would recommend that in the next season they give competitive non-Bt hybrids a try on some of their acres because they could see better profits from growing non-Bt hybrids."
|
Genetically Modified
| 2,013 |
December 17, 2013
|
https://www.sciencedaily.com/releases/2013/12/131217134714.htm
|
Significant advance reported with genetically modified poplar trees
|
Forest geneticists at Oregon State University have created genetically modified poplar trees that grow faster, have resistance to insect pests and are able to retain expression of the inserted genes for at least 14 years, a report in the
|
The trees are one of the best successes to date in the genetic modification of forest trees, a field that is much less advanced than GMO products in crop agriculture. The advance could prove especially useful in the paper and pulp industries, and in an emerging biofuel industry that could be based on hybrid poplar plantations.Commercial use of such trees could be done with poplars that also had been engineered to be sterile so they would be unlikely to spread their characteristics to other trees, researchers said.Development of male sterile trees has been demonstrated in the field, which can be used for male varieties of poplar. Female sterility has not yet been done but should be feasible, they said. However, it is unclear if regulatory agencies would allow use of these trees, with sterility as a key mitigation factor."In terms of wood yield, plantation health and productivity, these GMO trees could be very significant," said Steven Strauss, a distinguished professor of forest biotechnology in the OSU College of Forestry. "Our field experiments and continued research showed results that exceeded our expectations. And it is likely that we have underestimated the value these trees could have in improved growth and production."A large-scale study of 402 trees from nine "insertion events" tracked the result of placing the All of the trees were removed or cut back at the age of two years before they were old enough to flower and reproduce, in order to prevent any gene flow into wild tree populations, researchers said.With this genetic modification, the trees were able to produce an insecticidal protein that helped protect against insect attack. This method has proven effective as a pest control measure in other crop species such as corn and soybeans, resulting in substantial reductions in pesticide use and a decrease in crop losses."Insect attack not only can kill a tree, it can make the trees more vulnerable to other health problems," said Amy Klocko, an OSU faculty research associate. "In a really bad year of insect attack you can lose an entire plantation."Hybrid poplar trees, which are usually grown in dense rows on flat land almost like a food crop, are especially vulnerable to insect epidemics, the researchers said. Manual application of pesticides is expensive and targets a wide range of insects, rather than only the insects that are attacking the trees.A number of the GMO trees in this study also had significantly improved growth characteristics, the researchers found. Compared to the controls, the transgenic trees grew an average of 13 percent larger after two growing seasons in the field, and in the best case, 23 percent larger.Some of the work also used a drought-tolerant poplar clone, another advantage in what may be a warmer and drier future climate. The research was supported by the Tree Biosafety and Genomics Research Cooperative at OSU.Annual crops such as cotton and corn already are routinely grown as GMO products with insect resistance genes. Trees, however, have to grow and live for years before harvest and are subjected to multiple generations of insect pest attacks. That's why engineered insect protection may offer even greater commercial value, and why extended tests were necessary to demonstrate that the resistance genes would still be expressed more than a decade after planting.Some genetically modified hybrid poplar trees are already being used commercially in China, but none in the United States. The use of GMO trees in the U.S. still faces heavy regulatory obstacles, Strauss said. Agencies are likely to require extensive studies of gene flow and their effects on forest ecosystems, which are difficult to carry out, he said.Strauss said he advocates an approach of engineering sterility genes into the trees as a mechanism to control gene flow, which together with further ecological research might provide a socially acceptable path for commercial deployment.
|
Genetically Modified
| 2,013 |
December 16, 2013
|
https://www.sciencedaily.com/releases/2013/12/131216155012.htm
|
Researchers engineer better method for delivering genetic material into cells
|
Researchers at the Polytechnic Institute of New York University (NYU-Poly) and the NYU College of Dentistry (NYUCD) have developed a carrier in their lab that is five times more efficient in delivering DNA into cells than today's commercial delivery methods -- reagent vectors. This novel complex is a peptide-polymer hybrid, assembled from two separate, less effective vectors that are used to carry DNA into cells.
|
Results of their study, "Long Term Efficient Gene Delivery Using Polyethylenimine with Modified Tat Peptide," were published in Non-viral vectors such as those engineered in this study are used for transfection -- the process of introducing foreign genetic material (in this case, DNA called a plasmid) into a cell. The vectors are essentially vehicles that carry the genetic matter into the cell. But transfection is not as easy. Cells are set up to keep things out of the nucleus. Even if the transported plasmid manages to permeate the cellular membrane, the cytoplasm within the cell has safeguards to stop anything from getting into the nucleus.Traditionally, scientists have engineered viruses to carry out transfection, but viruses are problematic because cells recognize them as foreign and trigger the immune response. Virus transfection is extremely costly and presents numerous difficulties for mass processing. On the other hand, non-viral vectors do not trigger the immune system and are easily manufactured and modified for safe, more effective delivery. Their shortcoming is that they generally are effective only for short periods in transfection, as well as other forms of gene expression.For this project, Yamano and Montclare paired a modified version of CPP HIV-1 (mTat) with PEI -- a non-viral vector particularly effective for delivering oligonucleotides. In combining mTat and PEI, they built a new non-viral vector, more effective than mTat or PEI individually. They tested their reagent vector both The vector may be used in the future for targeted gene therapy.
|
Genetically Modified
| 2,013 |
December 12, 2013
|
https://www.sciencedaily.com/releases/2013/12/131212142215.htm
|
Sniffing out danger: Fearful memories can trigger heightened sense of smell
|
Most people -- including scientists -- assumed we can't just sniff out danger.
|
It was thought that we become afraid of an odor -- such as leaking gas -- only after information about a scary scent is processed by our brain.But neuroscientists at Rutgers University studying the olfactory -- sense of smell -- system in mice have discovered that this fear reaction can occur at the sensory level, even before the brain has the opportunity to interpret that the odor could mean trouble.In a new study published today in "What is surprising is that we tend to think of learning as something that only happens deep in the brain after conscious awareness," says McGann. "But now we see how the nervous system can become especially sensitive to threatening stimuli and that fear-learning can affect the signals passing from sensory organs to the brain."McGann and students Marley Kass and Michelle Rosenthal made this discovery by using light to observe activity in the brains of genetically engineered mice through a window in the mouse's skull. They found that those mice that received an electric shock simultaneously with a specific odor showed an enhanced response to the smell in the cells in the nose, before the message was delivered to the neurons in the brain.This new research -- which indicates that fearful memories can influence the senses -- could help to better understand conditions like Post Traumatic Stress Disorder, in which feelings of anxiety and fear exist even though an individual is no longer in danger."We know that anxiety disorders like PTSD can sometimes be triggered by smell, like the smell of diesel exhaust for a soldier," says McGann who received funding from the National Institute of Mental Health and the National Institute on Deafness and Other Communication Disorders for this research. "What this study does is gives us a new way of thinking about how this might happen."In their study, the scientists also discovered a heightened sensitivity to odors in the mice traumatized by shock. When these mice smelled the odor associated with the electrical shocks, the amount of neurotransmitter -- chemicals that carry communications between nerve cells -- released from the olfactory nerve into the brain was as big as if the odor were four times stronger than it actually was.This created mice whose brains were hypersensitive to the fear-associated odors. Before now, scientists did not think that reward or punishment could influence how the sensory organs process information.The next step in the continuing research, McGann says, is to determine whether the hypersensitivity to threatening odors can be reversed by using exposure therapy to teach the mice that the electrical shock is no longer associated with a specific odor. This could help develop a better understanding of fear learning that might someday lead to new therapeutic treatments for anxiety disorders in humans, he says.
|
Genetically Modified
| 2,013 |
December 11, 2013
|
https://www.sciencedaily.com/releases/2013/12/131211185050.htm
|
Modified T cells effective in treating blood-borne cancers, study shows
|
At the 2013 American Society of Hematology meeting in Dec. 2013, James Kochenderfer, M.D., investigator in the Experimental Transplantation and Immunology Branch, NCI, presented findings from two clinical trials evaluating the use of genetically modified immune system T cells as cancer therapy. These studies were performed in close collaboration with Steven A. Rosenberg, M.D., Ph.D., chief of the Surgery Branch, NCI, who is the principle investigator in the first study noted.
|
These reports represent important advances in the understanding of gene therapy for treatment of advanced blood-borne cancers. In the first study, 15 adult patients had their T cells removed, were treated with chemotherapy, and then were given an infusion of their own T cells which had been genetically modified in the lab. The first report of the success of this type of therapy in lymphomas came in 2010 by Kochenderfer and Rosenberg in a patient who remains progression-free over 42 months after treatment. This team has now demonstrated that this same approach is effective in patients with diffuse large B-cell lymphoma, the most common type of non-Hodgkin lymphoma. Six patients in the trial achieved complete remission and six achieved partial remission. This approach offers an option for patients with chemotherapy-resistant large B-cell cancer who are not good candidates for other forms of stem cell transplantation.In the second study, researchers used genetically modified T cells to treat B-cell cancers, such as leukemia and lymphoma, that did not fully respond to transplantation of stem cells from a donor. The study enrolled 10 patients who received no treatment except one infusion of genetically modified T cells that were obtained from related or unrelated stem cell transplant donors. Three of 10 patients experienced significant disease regression, with one patient showing complete remission. Significantly, none of the patients experienced graft-versus-host disease (GVHD). Toxicities were mild, and resolved within two weeks. The results are encouraging because they show that small numbers of modified T cells can cause regression of highly treatment-resistant B-cell cancers without causing GVHD. This finding indicates a possible new treatment approach for patients with aggressive forms of these cancers that have proven resistant to other treatment approaches, including stem cell transplantation from donors.
|
Genetically Modified
| 2,013 |
December 8, 2013
|
https://www.sciencedaily.com/releases/2013/12/131208090339.htm
|
Results from first 59 leukemia patients who received investigational, personalized cellular therapy
|
Three and a half years after beginning a clinical trial which demonstrated the first successful and sustained use of genetically engineered T cells to fight leukemia, a research team from the Perelman School of Medicine at the University of Pennsylvania and the Children's Hospital of Philadelphia will today announce the latest results of studies involving both adults and children with advanced blood cancers that have failed to respond to standard therapies. The findings from the first 59 patients who received this investigational, personalized cellular therapy, known as CTL019, will be presented during the American Society of Hematology's Annual Meeting and Exposition in New Orleans.
|
Two of the first three chronic lymphocytic leukemia (CLL) patients who participated in the study, which started in the summer of 2010, remain in remission, with tests revealing reprogrammed cells still circulating in their bodies, on guard to combat tumor cells that may reappear in the future. Additional highlights of the new research results include an 89 percent complete response rate among adult and pediatric patients with acute lymphoblastic leukemia (ALL)."In a very short time, we've learned so much about how CTL019 works and how powerful it can be," said the research team's leader, Carl H. June, MD, Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine and director of Translational Research in Penn's Abramson Cancer Center. "Our findings show that the human immune system and these modified 'hunter' cells are working together to attack tumors in an entirely new way."The research team, which includes investigators who treat patients at both the Hospital of the University of Pennsylvania and the Children's Hospital of Philadelphia, will announce findings from trials of three different groups of patients:• 15 of 32 adult patients with CLL (47 percent) responded to the therapy, with seven of those experiencing a complete remission of their disease. Results of both the completed pilot study of 14 CLL patients and results thus far of the first 18 patients in a Phase II, dose-optimization trial will be presented.• 19 of 22 pediatric patients with ALL (86 percent) experienced complete remissions. The first pediatric patient treated with the protocol, who is now 8 years old, remains in remission 20 months later. Five patients have relapsed, including one whose tests revealed new tumor cells that do not express the protein targeted by the reprogrammed cells.• All five of the first adult ALL patients treated thus far experienced complete remissions, the longest of which continues six months after treatment. One patient subsequently underwent a bone marrow transplant and remains in remission. One patient relapsed after three months with disease that also tested negative for the engineered cell target.The investigational treatment pioneered by the Penn team begins by removing patients' T cells via an apheresis process similar to blood donation, then reprogramming them in Penn's cell and vaccine production facility with a gene transfer technique using a lentivirus vector. The newly built T cells target tumor cells using an antibody-like protein, called a chimeric antigen receptor (CAR), which is expressed on the surface of the T cells and designed to bind to a protein called CD19, which is found on the surface of the cancerous B cells associated with both CLL and ALL.The modified cells are then infused back into the patient's body following lymphodepleting chemotherapy. In the body, these "hunter" T cells both multiply and attack. A signaling domain built into the CAR promotes rapid growth of these cells, building an army of tumor-killing cells that tests reveal can grow to more than 10,000 new cells for each single engineered cell patients receive. Cells in the patient that do not express CD19 are left untouched by the modified T cells, which limits the prolonged, systemic side effects typically experienced during traditional cancer therapies that harm healthy tissue.Taken together, the newly announced results show promise for a range of tough-to-treat blood cancers. All study patients had exhausted conventional treatment options. In many cases, they were ineligible for bone marrow transplantation or declined that option due to the risks associated with the procedure, which carries at least a 20 percent mortality risk."We are tremendously excited about these results. About half of our CLL patients responded to this therapy, with most of them having several pounds of tumors eradicated by the genetically modified T cells," says study author David L. Porter, MD, the Jodi Fisher Horowitz Professor in Leukemia Care Excellence and director of Blood and Marrow Transplantation in Penn's Abramson Cancer Center, who will present the two CLL trial abstracts during the meeting. "We've now seen remissions lasting for more than three years, and there are clues that the T cells continue to kill leukemia cells in the body for months after treatment: Even in patients who had only a partial response, we often found that all cancer cells disappeared from their blood and bone marrow, and their lymph nodes continued to shrink over time. In some cases, we have seen partial responses convert to complete remissions over several months."The research team is especially encouraged by the early results among ALL patients, since that disease progresses rapidly and is very deadly among those who relapse after standard treatments. About 85 percent of pediatric patients with the disease are cured with first-line therapies, but those whose cancers relapse and/or become refractory have limited options. And while most adults with ALL respond to drug treatment, as many as half ultimately relapse, putting the overall cure rate for the disease among adults at only around 40 percent. New therapies for both these groups of high-risk patients are acutely needed."Our results serve as another important milestone in demonstrating the potential of this treatment for patients who have no other therapeutic options," said study author Stephan A. Grupp, MD, PhD, of the Children's Hospital of Philadelphia and a professor of Pediatrics at the Perelman School of Medicine. "These data also demonstrate that these engineered 'hunter' cells greatly expand and then persist in patients, allowing for long-term disease control. We are looking forward to testing these cells in upcoming multicenter pediatric and adult trials."During the pilot study for CLL, patients received a wide range of cell doses, but the Penn team saw no relationship between the number of cells infused and the responses or toxicities associated with the therapy. To refine the treatment approach, the Penn team launched a randomized Phase II study comparing two different doses, each of which is given as a single outpatient infusion. So far, however, the team has again seen no difference in which amount of cells is more effective or associated with greater toxicities.In the trials for both CLL and ALL, all responding patients experienced a cytokine release syndrome that the researchers now know marks the process of the engineered cells multiplying and attacking tumor cells in the body. During this time, patients typically experience varying degrees of flu-like symptoms, with high fevers, nausea, muscle pain, and in some cases, low blood pressure and breathing difficulties. The team has learned this reaction can be managed, if necessary, using tocilizumab, an immunosuppressant drug which tamps down elevated levels of the inflammatory cytokine IL-6, which have been found to spike during the most robust phase of the engineered cells' expansion in the body.Tests of both CLL and ALL patients who experienced complete remissions also show that normal B cells, which also express the CD19 protein, have been eliminated along with their tumors. The researchers note that persistent loss of normal B cells is a good surrogate marker for continued activity of the gene-modified T cells. In this way, the cells appear to be providing long-term vaccine-like activity preventing B cells -- and presumably tumor cells -- from growing back. B cells are important for the body's immune system to fight infection by making antibodies, though it is possible to replace antibodies with gamma globulin treatments as a preventive measure.
|
Genetically Modified
| 2,013 |
December 5, 2013
|
https://www.sciencedaily.com/releases/2013/12/131205142220.htm
|
Fundamental differences found between human cancers, genetically engineered mouse models
|
Researchers from the Fred Hutchinson Cancer Research Center in Seattle, WA have taken a closer look at existing mouse models of cancer, specifically comparing them to human cancer samples.
|
These genetically engineered mouse models (which usually either overexpress a cancer-causing gene -- or "oncogene" -- or carry a deletion for a "tumor suppressor" gene) have been extensively used to understand human cancer biology in studies of drug resistance, early detection, metastasis, and cancer prevention, as well as for the preclinical development of novel targeted therapeutics.Cancer is a multistep process that involves a complex interplay between genetic and epigenetic alterations. Epigenetic modifications mediate changes in gene expression without altering the DNA sequence. One of those modifications, DNA methylation, was found to be significantly different between mouse models of medulloblastoma and primary medulloblastoma human samples.
|
Genetically Modified
| 2,013 |
December 5, 2013
|
https://www.sciencedaily.com/releases/2013/12/131205141858.htm
|
Protein clumps as memory
|
Yeast has a somewhat complicated love life: on the one hand, a mother cell can produce genetically identical daughter cells through mitosis (cell division); on the other hand, yeast cells, who exist in two different mating types, are able to fuse with cells of the other mating type, thereby combining two different sets of genes. Two yeast cells with a single chromosome set each become a so-called yeast zygote with two sets of chromosomes.
|
To enable two fusion-inclined yeast cells to approach each other, each mating type releases a certain pheromone. If they thereby detect each other, they cease cell division and form a special extension towards each other in a kind of courtship. If these meet, the cells can fuse and form the zygote. If the partners miss, however, they both carry on producing offspring asexually.ETH Zurich researchers Fabrice Caudron and Yves Barral, a professor of biochemistry, have now discovered a previously unknown mechanism that enables yeast cells to memorise "bad experiences" during reproduction. If a mating attempt proves fruitless, the unsuccessful cell develops a molecular memory where the protein Whi3 is transformed and thus deactivated. Once transformed, the modified Whi3 "contaminates" other proteins of the same type. They attach themselves to each other and form aggregates, which the yeast cell can only break apart with great difficulty. The Whi3 aggregates have the effect that future "lovers" have to release a much larger amount of the messenger substance for the cell to respond to it. If the amount is too low, the cell continues to reproduce solely through cell division."Nobody expected to find such a memory in a single-celled organism," explains Yves Barral, stressing the singularity of the discovery. Interestingly, there is a connection between memory and aging. As the cell grows older, the memories accumulate in a cell in the form of these aggregates. "Finding a suitable sexual partner becomes increasingly more difficult with time," says the ETH Zurich professor. After all, the aggregation process is extremely difficult to reverse. Only very rarely is the memory lost when the cell manages to dismantle the aggregates. The daughter cells that a mother cell pinches off do not inherit the memory and the aggregates remain in the mother. As a result, the offspring are not predisposed as the daughter cell is young. How the mother cell retains the protein aggregates is an important mechanism, which Barral and Caudron are currently researching.Research still needs to be conducted into why yeast cells store these (and other) substances. "A memory could thus be useful for the yeast to prevent further unproductive yet energy-intensive mating attempts," says Caudron, who has been researching this phenomenon for the last six years. The yeast faces a dilemma: if it only forms clones, the population will be genetically homogenous and, for instance, could die out in the event of a sudden change in the environmental conditions. While sexual reproduction leads to a genetically variable population, however, the cells have to expend far more energy."Cheating" yeasts are then a problem: if another cell or even a foreign organism produces the pheromone without offering a mating opportunity, a naïve cell would wait in vain for its supposed partner without dividing in the meantime, which rules it out as a competitor for nutrients -- much to its own detriment. Consequently, it is only worth responding to pheromones if successful reproduction is guaranteed. A yeast cell only stands a chance of this if the pheromone is present at high concentrations and indicates the immediate proximity of a partner.With their work, the ETH Zurich scientists demonstrate a form of non-hereditary memory in a single-celled organism for the first time. The system of protein aggregates, however, appears to be universal and relatively old in the history of evolution. Barral also knows of bacteria that grow "old" like yeast cells. They, too, could have a similar memory mechanism, he suspects. Also, one such mechanism has been detected in the fruitfly, Drosophila. Males perform a courtship dance to win the affection of a female. If she has already been fertilised, she does not show any interest and the male memorises this experience in nerve endings, the synapses, with the aid of protein aggregates. For Barral and Caudron, this is an indication that memory processes are very similar in single and multicellular organisms. "Who would have thought that a single-celled organism like yeast could help us to understand how we memorise our experiences?" says Barral.
|
Genetically Modified
| 2,013 |
December 4, 2013
|
https://www.sciencedaily.com/releases/2013/12/131204182217.htm
|
Successful repair of bone defects using novel tissue engineered bone graft
|
Researchers at the Department of Orthopaedics, of the Second Affiliated Hospital of Xi'an Jiaotong University Health Science Center, led by Dr. Kunzheng Wang and Dr. Pei Yang have developed a novel biomimetic tissue engineered bone graft based on rabbit adipose derived stem cells (rASCs), collagen I and a porous beta-tricalcium phosphate (β-TCP) scaffold. Furthermore, the critical-sized bone defects model of rabbits was used to evaluate the efficiency of the construct.
|
This discovery, reported in the December 2013 issue of Although bone has the capacity for regenerative growth and remodeling, these processes are often impaired in clinical situations in which loss of bone is caused by disease, trauma or tumor resection. More than 800,000 patients receive bone graft operations annually around the world. With the rapid development and progress of material and manufacturing sciences, tissue engineered bone grafting has become a promising technique in bone defect treatment. Bone tissue engineering involves three key factors: the seeding cell, growth factors and a porous scaffold. In the present study, rASCs were selected as the cell source for bone tissue engineering based upon the use of autologous ASCs for minimizing immunological rejection and the fact that greater cell numbers can be harvested from the patient with less pain. Collagen I was used to enhance the efficiency of cell adhesion. For the β-TCP scaffold the authors used a pore size of 460.90±78.75 μm and interconnection pore size of 157.66±37.94 μm. These were found to be biocompatible, osteoconductive, and able to be degraded, which facilitate vascularization and rapid bone growth progression. The in vivo experimental results demonstrated that the novel biomimetic tissue engineered bone graft could promote osteogenesis in critically sized defects. Twelve weeks after implantation, the defects were almost completely repaired by the presence of the cortical bone and medullary cavity. The results also suggested that the degeneration of the scaffolds may be accelerated by the interaction of rASCs, collagen I and the biomaterials."We hope to garner new insight into the engineering of rASCs-based bone tissue for clinical application." said Dr. Kunzheng Wang, senior author and Distinguished University Professor, Vice Chairmen of the Chinese Orthopaedic Association (COA).Dr. Steven R. Goodman, Editor-in-Chief of
|
Genetically Modified
| 2,013 |
December 2, 2013
|
https://www.sciencedaily.com/releases/2013/12/131202171926.htm
|
'Designer sperm' inserts custom genes into offspring
|
Get ready: The "new genetics" promises to change faulty genes of future generations by introducing new, functioning genes using "designer sperm."
|
A new research report appearing online in "Transgenic technology is a most important tool for researching all kinds of disease in humans and animals, and for understanding crucial problems in biology," said Anil Chandrashekran, Ph.D., study author from the Department of Veterinary Clinical Sciences at The Royal Veterinary College in North Mimms, United Kingdom.To achieve these results, Chandrashekran and colleagues used lentiviruses to generate transgenic animals via the male germ line. When pseudotyped lentiviral vectors encoding green fluorescent protein (GFP) were incubated with mouse spermatozoa, these sperm were highly successful in producing transgenics. Lentivirally-transduced mouse spermatozoa were used in in vitro fertilization studies and when followed by embryo transfer, at least 42 percent of founders were transgenic for GFP. GFP expression was detected in a wide range of murine tissues, including testis and the transgene was stably transmitted to a third generation of transgenic animals."Using modified sperm to insert genetic material has the potential to be a major breakthrough not only in future research, but also in human medicine," said Gerald Weissmann, M.D., Editor-in-Chief of
|
Genetically Modified
| 2,013 |
November 28, 2013
|
https://www.sciencedaily.com/releases/2013/11/131128141258.htm
|
Fruit flies with better sex lives live longer
|
Sex may in fact be one of the secrets to good health, youth and a longer life -- at least for fruit flies -- suggests a new University of Michigan study that appears in the journal
|
Male fruit flies that perceived sexual pheromones of their female counterparts -- without the opportunity to mate -- experienced rapid decreases in fat stores, resistance to starvation and more stress. The sexually frustrated flies lived shorter lives.Mating, on the other hand, partially reversed the negative effects on health and aging."Our findings give us a better understanding about how sensory perception and physiological state are integrated in the brain to affect long-term health and lifespan," says senior author Scott D. Pletcher, Ph.D, professor in the Department of Molecular and Integrative Physiology at the U-M Medical School and research professor at the U-M Geriatrics Center."The cutting-edge genetics and neurobiology used in this research suggests to us that for fruit flies at least, it may not be a myth that sexual frustration is a health issue. Expecting sex without any sexual reward was detrimental to their health and cut their lives short."U-M scientists used sensory manipulations to give the common male fruit fly, Drosophila melanogaster, the perception that they were in a sexually rich environment by exposing them to genetically engineered males that produced female pheromones. They were also able to manipulate the specific neurons responsible for pheromone perception as well as parts of the brain linked to sexual reward (secreting a group of compounds associated with anxiety and sex drive)."These data may provide the first direct evidence that aging and physiology are influenced by how the brain processes expectations and rewards," Pletcher says. "In this case, sexual rewards specifically promoted healthy aging."Fruit flies have been a powerful tool for studying aging because they live on average 60 days yet many of the discoveries in flies have proven effective in longer-lived animals, such as mice.For decades, one of the most powerful ways to slow aging in different species was by limiting their food intake. In a previous study, Pletcher and his colleagues found that the smell of food alone was enough to speed up aging, offering new context for how dietary restriction works.
|
Genetically Modified
| 2,013 |
November 28, 2013
|
https://www.sciencedaily.com/releases/2013/11/131128103957.htm
|
The heart's own stem cells play their part in regeneration
|
Up until a few years ago, the common school of thought held that the mammalian heart had very little regenerative capacity. However, scientists now know that heart muscle cells constantly regenerate, albeit at a very low rate. Researchers at the Max Planck Institute for Heart and Lung Research in Bad Nauheim, have identified a stem cell population responsible for this regeneration. Hopes are growing that it will be possible in future to stimulate the self-healing powers of patients with diseases and disorders of the heart muscle, and thus develop new potential treatments.
|
Some vertebrates seem to have found the fountain of youth, the source of eternal youth, at least when it comes to their heart. In many amphibians and fish, for example, this important organ has a marked capacity for regeneration and self-healing. Some species in the two animal groups have even perfected this capability and can completely repair damage caused to heart tissue, thus maintaining the organ's full functionality.The situation is different for mammals, whose hearts have a very low regenerative capacity. According to the common school of thought that has prevailed until recently, the reason for this deficit is that the heart muscle cells in mammals cease dividing shortly after birth. It was also assumed that the mammalian heart did not have any stem cells that could be used to form new heart muscle cells. On the contrary: new studies show that aged muscle cells are also replaced in mammalian hearts. Experts estimate, however, that between just one and four percent of heart muscle cells are replaced every year.Scientists in Thomas Braun's Research Group at the Max Planck Institute for Heart and Lung Research have succeeded in identifying a stem cell population in mice that plays a key role in this regeneration of heart muscle cells. Experiments conducted by the researchers in Bad Nauheim on genetically modified mice show that the Sca1 stem cells in a healthy heart are involved in the ongoing replacement of heart muscle cells. The Sca-1 cells increase their activity if the heart is damaged, with the result that significantly more new heart muscle cells are formed.Since, in comparison to the large amount of heart muscle cells, Sca-1 stem cells account for just a tiny proportion of the cells in the heart muscle, searching for them is like searching for a needle in a haystack. "We also faced the problem that Sca-1 is no longer available in the cells as a marker protein for stem cells after they have been changed into heart muscle cells. To prove this, we had to be inventive," says project leader Shizuka Uchida. The Max Planck researchers genetically modified the stem cells to such an extent that, in addition to the Sca-1, they produced another visible marker. Even if Sca-1 was subsequently no longer visible, the marker could still be detected permanently."In this way, we were able to establish that the proportion of heart muscle cells originating from Sca-1 stem cells increased continuously in healthy mice. Around five percent of the heart muscle cells regenerated themselves within 18 months," says Uchida. Moreover, mice suffering from heart disease triggered by the experiment had up to three times more of these newly formed heart muscle cells."The data shows that, in principle, the mammalian heart is able to trigger regeneration and renewal processes. Under normal circumstances, however, these processes are not enough to ultimately repair cardiac damage," says Braun. The aim is to find ways in which the formation of new heart muscle cells from heart stem cells can be improved and thereby strengthen the heart's self-healing powers.
|
Genetically Modified
| 2,013 |
November 25, 2013
|
https://www.sciencedaily.com/releases/2013/11/131125164218.htm
|
Using microRNA fit to a T (Cell)
|
Researchers at the University of California, San Diego School of Medicine have successfully targeted T lymphocytes -- which play a central role in the body's immune response -- with another type of white blood cell engineered to synthesize and deliver bits of non-coding RNA or microRNA (miRNA).
|
The achievement in mice studies, published in this week's online early edition of the "From a practical standpoint, short non-coding RNA can be used for replacement therapy to introduce miRNA or miRNA mimetics into tissues to restore normal levels that have been reduced by a disease process or to inhibit other miRNA to increase levels of therapeutic proteins," said Zanetti."However, the explosive rate at which science has discovered miRNAs to be involved in regulating biological processes has not been matched by progress in the translational arena," Zinetti added. "Very few clinical trials have been launched to date. Part of the problem is that we have not yet identified practical and effective methods to deliver chemically synthesized short non-coding RNA in safe and economically feasible ways."Zanetti and colleagues transfected primary B lymphocytes, a notably abundant type of white blood cell (about 15 percent of circulating blood) with engineered plasmid DNA (a kind of replicating but non-viral DNA), then showed that the altered B cells targeted T cells in mice when activated by an antigen -- a substance that provokes an immune system response."This is a level-one demonstration for this new system," said Zanetti. "The next goal will be to address more complex questions, such as regulation of the class of T cells that can be induced during vaccination to maximize their protective value against pathogens or cancer."There are reasons to believe that the quality of T cells in response to vaccination matters to the efficacy of protection. This could push vaccination aimed at the induction of T cell responses to a new level of accuracy, predictability and ultimately, efficacy."Other potential applications, he said, included targeting and repairing T cells disabled by autoimmune or inflammatory diseases."Another objective will be to further control targeting to tissues other than lymphoid organs. For example, cancer cells," Zanetti said. "There is a world of untapped possibilities out there. We believe that the new idea -- and the technology behind it -- will carry a great distance in a variety of conditions to aid regulation of the immune system or control or prevent disease."
|
Genetically Modified
| 2,013 |
November 13, 2013
|
https://www.sciencedaily.com/releases/2013/11/131113125831.htm
|
Better batteries through biology? Modified viruses boost battery performance
|
MIT researchers have found a way to boost lithium-air battery performance, with the help of modified viruses.
|
Lithium-air batteries have become a hot research area in recent years: They hold the promise of drastically increasing power per battery weight, which could lead, for example, to electric cars with a much greater driving range. But bringing that promise to reality has faced a number of challenges, including the need to develop better, more durable materials for the batteries' electrodes and improving the number of charging-discharging cycles the batteries can withstand.Now, MIT researchers have found that adding genetically modified viruses to the production of nanowires -- wires that are about the width of a red blood cell, and which can serve as one of a battery's electrodes -- could help solve some of these problems.The new work is described in a paper published in the journal The researchers produced an array of nanowires, each about 80 nanometers across, using a genetically modified virus called M13, which can capture molecules of metals from water and bind them into structural shapes. In this case, wires of manganese oxide -- a "favorite material" for a lithium-air battery's cathode, Belcher says -- were actually made by the viruses. But unlike wires "grown" through conventional chemical methods, these virus-built nanowires have a rough, spiky surface, which dramatically increases their surface area.Belcher, the W.M. Keck Professor of Energy and an affiliate of MIT's Koch Institute for Integrative Cancer Research, explains that this process of biosynthesis is "really similar to how an abalone grows its shell" -- in that case, by collecting calcium from seawater and depositing it into a solid, linked structure.The increase in surface area produced by this method can provide "a big advantage," Belcher says, in lithium-air batteries' rate of charging and discharging. But the process also has other potential advantages, she says: Unlike conventional fabrication methods, which involve energy-intensive high temperatures and hazardous chemicals, this process can be carried out at room temperature using a water-based process.Also, rather than isolated wires, the viruses naturally produce a three-dimensional structure of cross-linked wires, which provides greater stability for an electrode.A final part of the process is the addition of a small amount of a metal, such as palladium, which greatly increases the electrical conductivity of the nanowires and allows them to catalyze reactions that take place during charging and discharging. Other groups have tried to produce such batteries using pure or highly concentrated metals as the electrodes, but this new process drastically lowers how much of the expensive material is needed.Altogether, these modifications have the potential to produce a battery that could provide two to three times greater energy density -- the amount of energy that can be stored for a given weight -- than today's best lithium-ion batteries, a closely related technology that is today's top contender, the researchers say.Belcher emphasizes that this is early-stage research, and much more work is needed to produce a lithium-air battery that's viable for commercial production. This work only looked at the production of one component, the cathode; other essential parts, including the electrolyte -- the ion conductor that lithium ions traverse from one of the battery's electrodes to the other -- require further research to find reliable, durable materials. Also, while this material was successfully tested through 50 cycles of charging and discharging, for practical use a battery must be capable of withstanding thousands of these cycles.While these experiments used viruses for the molecular assembly, Belcher says that once the best materials for such batteries are found and tested, actual manufacturing might be done in a different way. This has happened with past materials developed in her lab, she says: The chemistry was initially developed using biological methods, but then alternative means that were more easily scalable for industrial-scale production were substituted in the actual manufacturing.In addition to Oh, Belcher, and Shao-Horn, the work was carried out by MIT research scientists Jifa Qi and Yong Zhang and postdoc Yi-Chun Lu. The work was supported by the U.S. Army Research Office and the National Science Foundation.Video:
|
Genetically Modified
| 2,013 |
November 13, 2013
|
https://www.sciencedaily.com/releases/2013/11/131113125625.htm
|
Tomato therapy: Engineered veggies target intestinal lipids, improve cholesterol
|
UCLA researchers report that tiny amounts of a specific type of lipid in the small intestine may play a greater role than previously thought in generating the high cholesterol levels and inflammation that lead to clogged arteries.
|
The team also found they could reduce the negative effects of these lipids in mice by feeding the animals a new genetically engineered tomato being developed at UCLA that is designed to mimic HDL ("good") cholesterol.The study, published in the December issue of the "These lipids may be a new culprit that we can target in the small intestine in fighting atherosclerosis," said senior author Dr. Alan Fogelman, executive chair of the department of medicine and director of the atherosclerosis research unit at the David Geffen School of Medicine at UCLA.Previously, it was thought that the role of the small intestine in response to a high-fat, high-cholesterol diet was simply to package the fat and cholesterol for transport to the liver. Once delivered to the liver, the large load of fat was thought to cause increased blood levels of LDL ("bad") cholesterol, decreased levels of "good" cholesterol and the rise of systemic inflammation.But that may not be the complete story. The UCLA researchers revealed that LPAs, previously considered very minor because they are found in far smaller amounts in the small intestine than other lipids, like cholesterol, may play a more direct role in contributing to the factors that cause atherosclerosis.Scientists found that mice fed a high-fat, high-cholesterol diet (21 percent fat) showed a two-fold increase in the amount of LPAs in the small intestine over mice fed normal low-fat mouse chow (4 percent fat).When researchers added LPAs at only one part per million (by weight) to the normal low-fat, low-cholesterol mouse chow, they observed the same increase in LPAs in the small intestine as when the mice were fed the high-cholesterol, high-fat diet.Surprisingly, with the addition of LPAs to the low-fat diet, the UCLA team also found alterations in the patterns of gene expression in the small intestine, changes in cholesterol levels (increases in LDL and decreases in HDL) and increases in blood markers of inflammation typically seen when the mice consumed a high-fat, high-cholesterol diet.The findings suggest that some of the factors leading to atherosclerosis occur in the small intestine and not just the liver. Targeting LPAs in the small intestine may be a way to help stop changes in blood cholesterol and inflammation before the load of packaged fat even reaches the liver, the researchers said."Recognizing the importance of these minor lipids in the small intestine may lead to ways to reduce their levels and prevent abnormalities in blood levels of 'good' and 'bad' cholesterol that contribute to heart attack and stroke," Fogelman said.The next step was to test the impact of the genetically engineered tomatoes on reducing the effects of these lipids in the small intestine. The tomatoes, created at UCLA, produce a small peptide called 6F that mimics the action of apoA-1, the chief protein in HDL.Researchers added 2.2 percent (by weight) of freeze-dried tomato powder from the peptide-enhanced tomatoes to low-fat, low-cholesterol mouse chow that was supplemented with LPAs. They also added the same dose of the peptide-enhanced tomatoes to the high-fat high- cholesterol diet.They found that this addition to both diets prevented an increase in the level of LPAs in the small intestine and also stopped increases in "bad" cholesterol, decreases in "good" cholesterol and systemic inflammation. Tomatoes that did not contain the peptide had no effect.According to Fogelman, the peptide-enhanced tomatoes may work in large part by reducing the amount of the LPAs in the small intestine.Future research will focus on identifying the genes in the small intestine that are altered by the LPAs in order to find signaling pathways that may be targets for treatment."Identifying the role of these specific lipids in the small intestine and new ways to target them will hopefully provide new insights and lead to new treatments," said Judith Gasson, a professor of medicine and biological chemistry, director of UCLA's Jonsson Comprehensive Cancer Center, and senior associate dean for research at the Geffen School of Medicine.
|
Genetically Modified
| 2,013 |
November 5, 2013
|
https://www.sciencedaily.com/releases/2013/11/131105132031.htm
|
Intestinal bacteria linked to rheumatoid arthritis
|
Researchers have linked a species of intestinal bacteria known as
|
Using sophisticated DNA analysis to compare gut bacteria from fecal samples of patients with rheumatoid arthritis and healthy individuals, the researchers found that "Studies in rodent models have clearly shown that the intestinal microbiota contribute significantly to the causation of systemic autoimmune diseases," says Dan R. Littman, MD, PhD, the Helen L. and Martin S. Kimmel Professor of Pathology and Microbiology and a Howard Hughes Medical Institute investigator."Our own results in mouse studies encouraged us to take a closer look at patients with rheumatoid arthritis, and we found this remarkable and surprising association," says Dr. Littman, whose basic science laboratory at NYU School of Medicine's Skirball Institute of Biomolecular Medicine collaborated with clinical investigators led by Steven Abramson, MD, senior vice president and vice dean for education, faculty, and academic affairs; the Frederick H. King Professor of Internal Medicine; chair of the Department of Medicine; and professor of medicine and pathology at NYU School of Medicine."At this stage, however, we cannot conclude that there is a causal link between the abundance of The new findings, reported today in the open-access journal Rheumatoid arthritis, an autoimmune disease that attacks joint tissue and causes painful, often debilitating stiffness and swelling, affects 1.3 million Americans. It strikes twice as many women as men and its cause remains unknown although genetic and environmental factors are thought to play a role.The human gut is home to hundreds of species of beneficial bacteria, including "Expansion of Why To determine if particular bacterial species correlate with rheumatoid arthritis, the researchers sequenced the so-called 16S gene on 44 fecal DNA samples from newly diagnosed patients with rheumatoid arthritis prior to immune-suppressive treatment; 26 samples from patients with chronic, treated rheumatoid arthritis; 16 samples from patients with psoriatic arthritis (characterized by red, flaky skin in conjunction with joint inflammation); and 28 samples from healthy individuals.Seventy-five percent of stool samples from patients newly diagnosed with rheumatoid arthritis carried Rheumatoid arthritis is treated with an assortment of medications, including antibiotics, anti-inflammatory drugs like steroids, and immunosuppressive therapies that tame immune reactions. Little is understood about how these medications affect gut bacteria. This latest research offers an important clue, showing that treated patients with chronic rheumatoid arthritis carry smaller populations of The researchers plan to validate their results in regions beyond New York, since gut flora can vary across geographical regions, and investigate whether the gut flora can be used as a biological marker to guide treatment. "We want to know if people with certain populations of gut bacteria respond better to certain treatment than others," says Dr. Scher. Finally, they hope to study people before they develop rheumatoid arthritis to see whether overgrowth of
|
Genetically Modified
| 2,013 |
October 31, 2013
|
https://www.sciencedaily.com/releases/2013/10/131031124922.htm
|
Researchers model familial amyloidosis in vitro using iPSC technology
|
Researchers from Boston University School of Medicine (BUSM) and Boston Medical Center (BMC) have generated the first known disease-specific induced pluripotent stem cell (iPSC) lines from a patient with familial transthyretin amyloidosis (ATTR). The findings, which are reported in
|
iPSCs are a form of stem cells that come from skin or blood cells reprogrammed into cells that have the ability to become any type of tissue in the body. ATTR is a lethal, autosomal dominant protein-folding disorder caused by one of more than 100 distinct mutations in the transthyretin (TTR) gene. In ATTR, protein secreted from the liver aggregates and forms fibrils in target organs, chiefly the heart and peripheral nervous system, highlighting the need for a model capable of duplicating the multisystem complexity of this clinically variable disease.According to researchers using iPSC technology, cell lines can be established that are genetically identical to the individual from whom they are derived, allowing for disease modeling and development of novel therapeutics in the personalized genetic context of the patient from which they are made.In this study, the researchers used the iPSC to generate liver cells that secrete the disease-specific mutant protein as well as cardiac and neuronal cells, the downstream target tissues of the disease. Upon exposure to the mutant protein, the heart and neuronal cells displayed signs of stress and an increased level of cell death as compared to those exposed to normal protein, thereby recreating essential aspects of the disease in vitro. Furthermore, small molecule stabilizers of the mutant protein that are being tested in clinical trials show efficacy in this model, validating this iPSC-based, patient-specific in vitro system as a platform for testing therapeutic strategies."Our work demonstrates that it is possible to model a complex, multisystem genetic disease in a relatively short space of time, using lineage-specified cells derived from patient stem cells," explained George J. Murphy, PhD, assistant professor of medicine in the section of Hematology and Oncology and co-director of the Center for Regenerative Medicine (CReM) at BUSM and BMC."This is a major breakthrough that will facilitate testing novel targeted therapies that are being developed for ATTR amyloidosis," said coauthor John Berk, MD, clinical director of the Amyloidosis Center at BUSM and BMC, where these rare diseases have been studied for more than 50 years. "Patients and families from all over the world who come to us for treatment may soon benefit from this research."
|
Genetically Modified
| 2,013 |
October 29, 2013
|
https://www.sciencedaily.com/releases/2013/10/131029133554.htm
|
Less toxic metabolites, more chemical product
|
The first dynamic regulatory system that prevents the build-up of toxic metabolites in engineered microbes has been reported by a team of researchers with the U.S. Department of Energy (DOE)'s Joint BioEnergy Institute (JBEI). The JBEI researchers used their system to double the production in
|
Using genome-wide transcriptional analysis, the JBEI researchers identified native regions of DNA -- called "promoters" -- in "Static regulators of toxic metabolite levels have been developed but this is the first metabolite regulator that responds to changes in microbial growth and environmental conditions," says Jay Keasling, CEO of JBEI and ranking authority on synthetic biology, who led this research. "Control systems that can sense and respond to environmental or growth changes are needed for the optimal production of a desired chemical."Keasling, who also serves as Associate Laboratory Director of Biosciences at Lawrence Berkeley National Laboratory (Berkeley Lab), the lead institute in the JBEI partnership, is the corresponding author of a paper describing this research in the journal From life-saving drugs, such as artemisinin, to sustainable, green biofuels, the metabolic engineering of microbes for the production of valuable chemicals continues to grow in importance. To date, the most productive microbial hosts have been those engineered with heterologous pathways for which they have little or no native regulation of the metabolites being expressed. However, such unregulated expression of heterologous enzymes can be toxic to the host, which can limit the production of the target chemical to well below levels that could be obtained."Although synthetic biology has made great strides in creating novel, dynamic genetic circuits, most control systems for heterologous metabolic pathways still rely on inducible or constitutive promoters," Keasling says. "Approaches developed to tailor expression strength by means of promoter libraries, mRNA stability or ribosome-binding are optimized for a particular growth phase or condition in the bioreactor, however, growth and environmental conditions change during the fermentation process."Since the accumulation of intermediate metabolites to toxic levels in a microbe during a fermentation process can lead to a stress response, Keasling and his JBEI colleagues reasoned that it should be possible to tap a host microbe's native stress response system when metabolites accumulate. Transcript profiling of the "Using such promoters to regulate pathway expression in response to the toxic intermediate metabolites creates a link between the cell's metabolic state and the expression of the metabolic pathway," Keasling says. "This enables us to create biosensors that respond to and regulate pathway intermediates. Keasling and his colleagues believe their dynamic approach to metabolite regulation could be extended to higher organisms as well, where constitutive promoters are still commonly used. This holds potential for -- among other things -- improving the accumulation of nutrients in food crops, or decreasing the lignin in energy crops that makes extraction of fuel sugars difficult and expensive."What we're looking at are strategies that could help reduce the problems associated with feeding a larger global population or efficiently converting biomass into renewable fuels," Keasling says.
|
Genetically Modified
| 2,013 |
October 23, 2013
|
https://www.sciencedaily.com/releases/2013/10/131023131702.htm
|
H5N1 bird flu genes show nature can pick worrisome traits
|
In the beginning, all flu viruses came from birds.
|
Over time, the virus evolved to adapt to other animals, including humans, as natural selection favored viruses with mutations that allowed them to more readily infect the cells of new host species. For some strains of bird flu virus, notably the worrisome H5N1 variant, the genetic changes that could make human-to-human transmission a possibility and spark a pandemic are the markers of intense interest to those who track flu as a threat to human health.Now, in a study published in The study used what scientists call "deep sequencing" to identify low-frequency genetic mutations that occur as the virus grows in and transmits between animals. Combing the genetic data from a transmission study in ferrets, a team led by Thomas Friedrich, a professor of pathobiological sciences at the University of Wisconsin-Madison School of Veterinary Medicine, found that during transmission, when one animal is infected by another through sneezing or coughing, the process of natural selection acts strongly on hemagglutinin, the structure the virus uses to attach to and infect host cells.The deep look into the genes of transmitted H5N1 viruses also reveals the surprising degree to which the virus can mutate and genetically diversify in each infected host, a troubling trait for a pathogen that has so far infected 637 people, killing 378. The team's data emphasize the fact that influenza viruses exist in each infected individual -- bird, human or ferret -- as a population or "swarm" of genetically related, but distinct, mutants.A mutation occurs somewhere on the viral genome every time a virus infects a cell, Friedrich explains. "You might think they all have the same sequence, but they don't. We found that this diversity increases over time in essentially all infected individuals we examined."Perhaps their most surprising and troubling discovery was that mutations present in only about 6 percent of the viruses infecting one ferret could be transmitted to another. This suggests that even very rare mutants can be transmitted if they have an evolutionary advantage.Most human infections with H5N1 viruses come directly from birds and are not transmitted to other people. Past studies have identified four key genetic mutations needed for the virus to become transmissible between mammals. Surveillance by public health officials has already identified viruses containing one or more of the required mutations from fowl in Egypt and some Asian countries.The data, Friedrich says, indicate that viruses capable of infecting humans probably already exist in nature, but at very low frequencies. Those findings, he adds, suggest that current surveillance methods may be missing H5N1 viruses capable of making the leap from birds to humans."Traditional sequencing can detect a mutation if it's present in maybe 20 percent or 30 percent of viruses. We were able to detect the transmission of rare mutants in this study only because we used deep sequencing. So there may be a background of transmissible viruses we are missing because surveillance currently relies on older technologies," says Friedrich. "Maybe they've always been there and we just couldn't see them. There may be viruses out there just one or zero mutations away. They just haven't encountered a susceptible host."The new work drew on transmission studies conducted last year in the lab of Yoshihiro Kawaoka, a co-author of the new study and also a professor of pathobiological sciences at the UW-Madison School of Veterinary Medicine. The original studies examined the transmission of an engineered variant of the H5N1 virus between ferrets. Friedrich and his colleagues analyzed the genes of these variant viruses in their new study; no new ferret experiments were performed for the new analysis."Fully avian viruses may act differently in nature," he notes. "But the data suggest to us that it wouldn't take many viruses from a chicken to infect a person, if the right mutations were there -- even if they were a tiny minority of the overall virus population. I suspect that result will hold true."A key aim of the study was to determine how transmission from one host to another affects the virus's genetic makeup. Researchers believed that transmission would reduce the genetic diversity present in the virus, but it was unclear whether genetic changes associated with transmission were random or if natural selection might favor mutations to make it more transmissible. "We found evidence for natural selection occurring. We see it playing a role in which viruses start an infection, creating a genetic bottleneck," Friedrich says.A genetic bottleneck occurs when the survival of an organism with certain traits or mutations is favored over others in the same population, reducing the overall genetic diversity in subsequent generations. "If natural selection is playing a role, it will favor transmission of that one-in-a-million virus," Friedrich notes.
|
Genetically Modified
| 2,013 |
October 23, 2013
|
https://www.sciencedaily.com/releases/2013/10/131023090540.htm
|
Nanopore opens new cellular doorway for drug transport
|
A living cell is built with barriers to keep things out -- and researchers are constantly trying to find ways to smuggle molecules in. Professor Giovanni Maglia (Biochemistry, Molecular and Structural Biology, KU Leuven) and his team have engineered a biological nanopore that acts as a selective revolving door through a cell's lipid membrane. The nanopore could potentially be used in gene therapy and targeted drug delivery.
|
All living cells are enclosed by a lipid membrane that separates the interior of the cell from the outside environment. The influx of molecules through the cell membrane is tightly regulated by membrane proteins that act as specific doorways for the trafficking of ions and nutrients. Membrane proteins can also be used by cells as weapons. Such proteins attack a cell by making holes -- nanopores -- in 'enemy' cell membranes. Ions and molecules leak from the holes, eventually causing cell death.Researchers are now trying to use nanopores to smuggle DNA or proteins across membranes. Once inside a cell, the DNA molecule could re-programme the cell for a particular action. Professor Maglia explains: "We are now able to engineer biological nanopores, but the difficult part is to precisely control the passage of molecules through the nanopores' doorways. We do not want the nanopore to let everything in. Rather, we want to limit entry to specific genetic information in specific cells."Professor Maglia and his team succeeded in engineering a nanopore that works like a revolving door for DNA molecules. "We have introduced a selective DNA revolving door atop of the nanopore. Specific DNA keys in solution hybridise to the DNA door and are transported across the nanopore. A second DNA key on the other side of the nanopore then releases the desired genetic information. A new cycle can then begin with another piece of DNA -- as long as it has the correct key. In this way, the nanopore acts simultaneously as a filter and a conveyor belt.""In other words, we have engineered a selective transport system that can be used in the future to deliver medication into the cell. This could be of particular use in gene therapy, which involves introducing genetic material into degenerated cells in order to disable or re-programme them. It could also be used in targeted drug delivery, which involves administering medication directly into the cell. The possibilities are promising."The researchers' findings were published in a recent edition of
|
Genetically Modified
| 2,013 |
October 20, 2013
|
https://www.sciencedaily.com/releases/2013/10/131020160735.htm
|
Large-scale deep re-sequencing reveals cucumber's evolutionary enigma
|
In a collaborative study published online today in
|
Cucumber is a major vegetable crop consumed worldwide as well as a model system for sex determination and plant vascular biology. In 2009, cucumber became the seventh plant to have its genome sequence published, following the well-studied model plant As a part of these efforts, researchers from CAAS and BGI re-sequenced 115 cucumber lines sampled from 3,342 accessions worldwide, and also conducted de novo sequencing on a wild cucumber. In total, they detected more than 3.3 million SNPs, over 0.33 million small insertion and deletions (indels), and 594 presence-absence variations (PAVs), and then constructed a comprehensive variation map of cucumber.Furthermore, researchers did a suite of model-based analyses of population structure and phylogenetic reconstruction. The results indicated that the three cultivated groups (Eurasian, East Asian, and Xishuangbanna) each are monophyletic and genetically quite homogeneous, but the Indian group shows clear evidence of substructure and genetic heterogeneity. Their further analysis also provide evidence on the ancestral status of the Indian group, which holds great potential for introducing new alleles into the cultivated gene pool.To understand the population bottlenecks during domestication, researchers made a comparison analysis between vegetable and grain food crops. The comparison result indicated that the three vegetable crops (cucumber, watermelon, and tomato) probably underwent narrower bottleneck events during domestication than the grain food crops (rice, maize, and soybean). In addition, they also identified 112 putative domestication sweeps in the cucumber genome. These findings provide additional impetus for the use of wild germplasm in future vegetable breeding.Wild cucumber is an extremely bitter fruit. An essential step in the domestication of the wild cucumber into a eatable vegetable must have degenerated its bitter taste. Two genetic loci, Bi and Bt, are known to confer bitterness in cucumber. In this study, researchers found that the Bt locus was delimited to a 442-kb region on chromosome 5 that harbors 67 predicted genes.They further investigated the genomic basis of divergence among the cultivated populations for identifying genes controlling important traits. The most obvious trait is the orange endocarp, which distinguishes the Xishuangbanna group from the other groups. This trait is caused by the accumulation of large amounts of β-carotene that was reported to be controlled by a single recessive gene ore. In this study, researchers discovered a key natural variation in a β-carotene hydroxylase gene that could be used to breed cucumber with enhanced nutritional value.Xin Liu, Project Manager from BGI, said "This study not only generates valuable genomic resource including additional wild reference genome, genome-wide variations for further studies and breeding applications on cucumber, but also gave us a better picture about how the cucumber genome evolved during domestication. It is also a good example for studies on vegetable or other economic crops. Large scale sequencing approach and genome wide analysis can be applied on different economic crops for better understanding their evolutionary process and specific traits, providing unique opportunities for further applications."
|
Genetically Modified
| 2,013 |
October 18, 2013
|
https://www.sciencedaily.com/releases/2013/10/131018132248.htm
|
Researchers delve into the behavior of cohesins
|
Understanding the regulation of cohesins can improve diagnosis and treatment for some cancer patients or those suffering from Cornella de Lange Syndrome. New research shows that Pds5 proteins modulate the behavior of cohesins to ensure the proper division of cells.
|
Cohesins are protein complexes that join the two copies of each chromosome -- called sister chromatids -- to ensure that they are shared fairly between the daughter cells during cell division. In this way, each daughter cell receives exactly the same genetic information from the parent cell.Pds5 is a protein associated with cohesins; it binds cohesins along different chromosome regions. In vertebrates there are two variants of Pds5, Pds5A and Pds5B, not very well characterised to date. Scientists from the Spanish National Cancer Research Centre (CNIO), led by Ana Losada, from the Chromosome Dynamics Group, have discovered -- by using genetically-modified mice (knock-out mice for Pds5A and Pds5B) -- that the two Pds5 variants are not equivalent, as both are necessary for cell proliferation and for embryo development to take place correctly.The results, published today in the online version of Illnesses such as Cornella de Lange Syndrome, which affects 1/30,000 newborns and which is characterised by serious physical abnormalities and cognitive impairments, have their origin in the abnormal function of cohesins. Cohesin mutations have recently been identified in some types of tumours, such as bladder cancer or acute myeloid leukemia (AML). "If we understand the function and regulation of the cohesins, we can improve the diagnosis and treatment for affected patients," says Losada."In this context, we have seen that both forms of Pds5 stabilise the binding of cohesins to the arms and distal regions of chromosomes, whilst only Pds5B does so in the centromeres -- the chromosomal regions that are most critical for chromosome separation during cell division," explains Losada.But Pds5 proteins not only stabilise cohesins, they can also have the opposite effect when they bind to the Wapl protein. "In this case, Pds5 contributes to destabilising the binding of cohesins to chromosomes, which can sometimes be important for activating essential genes at the right moment, as well as for allowing an efficient separation of the sister chromatids during cell division."
|
Genetically Modified
| 2,013 |
October 17, 2013
|
https://www.sciencedaily.com/releases/2013/10/131017144628.htm
|
Researchers advance toward engineering 'wildly new genome'
|
In two parallel projects, researchers have created new genomes inside the bacterium
|
In one project, researchers created a novel genome -- the first-ever entirely genomically recoded organism -- by replacing all 321 instances of a specific "genetic three-letter word," called a codon, throughout the organism's entire genome with a word of supposedly identical meaning. The researchers then reintroduced a reprogramed version of the original word (with a new meaning, a new amino acid) into the bacteria, expanding the bacterium's vocabulary and allowing it to produce proteins that do not normally occur in nature.In the second project, the researchers removed every occurrence of 13 different codons across 42 separate "The first project is saying that we can take one codon, completely remove it from the genome, then successfully reassign its function," said Marc Lajoie, a Harvard Medical School graduate student in the lab of George Church. "For the second project we asked, 'OK, we've changed this one codon, how many others can we change?'"Of the 13 codons chosen for the project, all could be changed."That leaves open the possibility that we could potentially replace any or all of those 13 codons throughout the entire genome," Lajoie said.The results of these two projects appear today in Recoded genomes can confer protection against viruses -- which limit productivity in the biotech industry -- and help prevent the spread of potentially dangerous genetically engineered traits to wild organisms."In science we talk a lot about the 'what' and the 'how' of things, but in this case, the 'why' is very important," Church said, explaining how this project is part of an ongoing effort to improve the safety, productivity and flexibility of biotechnology."These results might also open a whole new chemical toolbox for biotech production," said Isaacs. "For example, adding durable polymers to a therapeutic molecule could allow it to function longer in the human bloodstream."But to have such an impact, the researchers said, large swaths of the genome need to be changed all at once."If we make a few changes that make the microbe a little more resistant to a virus, the virus is going to compensate. It becomes a back and forth battle," Church said. "But if we take the microbe offline and make a whole bunch of changes, when we bring it back and show it to the virus, the virus is going to say 'I give up.' No amount of diversity in any reasonable natural virus population is going to be enough to compensate for this wildly new genome."In the first study, with just a single codon removed, the genomically recoded organism showed increased resistance to viral infection. The same potential "wildly new genome" would make it impossible for engineered genes to escape into wild populations, Church said, because they would be incompatible with natural genomes. This could be of considerable benefit with strains engineered for drug or pesticide resistance, for example. What's more, incorporating rare, non-standard amino acids could ensure strains only survive in a laboratory environment.Since a single genetic flaw can spell death for an organism, the challenge of managing a series of hundreds of specific changes was daunting, the researchers said. In both projects, the researchers paid particular attention to developing a methodical approach to planning and implementing changes and troubleshooting the results."We wanted to develop the ability to efficiently build the desired genome and to very quickly identify any problems -- from design flaws or from undesired mutations -- and develop workarounds," Lajoie said.The team relied on number oftechnologies developed in the Church lab and the Wyss Institute and with partners in academia and industry, including next-generation sequencing tools, DNA synthesis on a chip, and MAGE and CAGE genome editing tools. But one of the most important tools they used was the power of natural selection, the researchers added."When an engineering team designs a new cellphone, it's a huge investment of time and money. They really want that cell phone to work," Church said. "With
|
Genetically Modified
| 2,013 |
October 17, 2013
|
https://www.sciencedaily.com/releases/2013/10/131017080348.htm
|
Genetically modified bacteria became efficient sugar producers
|
The production of rare sugars has been very costly until now. A recent doctoral study indicates that their production can be made significantly more efficient with the help of genetically modified bacteria. This reduces prices and allows for their more versatile use in medicine, for example, says doctoral candidate Anne Usvalampi from the Aalto University in Finland.
|
Industry is already making use of rare sugars as low-calorie sweeteners, and as precursors of anti-cancer and antiviral medicines. However, their high cost has impeded research and use: it is not possible to isolate significant amounts of rare sugars directly from nature, and consequently their production has been expensive.The efficiency of sugar production can be increased through gene technology. In her recent doctoral dissertation Anne Usvalampi, Lic.Sc. (Tech.), studied the microbial production of three rare sugars -- xylitol, l-xylulose and l-xylose with the help of genetically modified bacteria."We added certain genes to the bacteria, making them produce the enzymes that we wanted, and with their help, the desired rare sugars. The results were promising. The production of xylitol was considerably more efficient than what has previously been achieved by using bacteria, and L-xylose was manufactured for the first time without large amounts of by-products. Compared with chemical synthesis, bacteria proved to be significantly better in the production of l-xylulose and l-xylose," Anne Usvalampi says.Genetic engineering has taken great strides in the past decade, but it is still not simple."On paper the process looks good: the DNA is isolated and the desired gene is replicated and attached to a vector which is used to transform bacteria. It sounds straightforward, but things do not always go like one would expect," she admits.As a precursor Usvalampi and her group used d-xylose, which is a part of hemicellulose, which can be extracted from hardwoods. It was used for the manufacture of xylitol with the help of So is it true that xylitol, which is familiar to all Finns, does not come directly from birch?"It does not," Anne Usvalampi notes with a smile."The idea, nurtured in Finland, of xylitol as birch sugar is incorrect. The precursor d-xylose can be extracted from birch, but it can come from other hardwoods, and also from maize, for instance."Xylitol is known for its preventive effect against caries, but new studies indicate that it is also useful in preventing ear infections in children. Anne Usvalampi believes that plenty of new uses can be found for rare sugars, especially in the pharmaceutical industry, once their prices can be brought down thanks to new and more efficient methods of production. Already now there is evidence that the rare sugar mannose can be used in the treatment of various infections and wounds.
|
Genetically Modified
| 2,013 |
October 17, 2013
|
https://www.sciencedaily.com/releases/2013/10/131017093505.htm
|
Activating proteins in brain by shining LED light on them
|
With the flick of a light switch, researchers at the Salk Institute for Biological Studies can change the shape of a protein in the brain of a mouse, turning on the protein at the precise moment they want. This allows the scientists to observe the exact effect of the protein's activation. The new method, described in the October 16 issue of the journal
|
"What we are now able to do is not only control neuronal activity, but control a specific protein within a neuron," says senior study author Lei Wang, an associate professor in Salk's Jack H. Skirball Center for Chemical Biology and Proteomics and holder of the Frederick B. Rentschler Developmental Chair.If a scientist wants to know what set of neurons in the brain is responsible for a particular action or behavior, being able to turn the neurons on and off at will gives the researcher a targeted way to test the neurons' effects. Likewise, if they want to know the role of a certain protein inside the cells, the ability to activate or inactivate the protein of interest is key to studying its biology.Over the past decade, researchers have developed a handful of ways of activating or inactivating neurons using light, as part of the burgeoning field of so-called optogenetics. In optogenetic experiments, mice are genetically engineered to have a light-sensitive channel from algae integrated into their neurons. When exposed to light, the channel opens or closes, changing the flow of molecules into the neuron and altering its ability to pass an electrochemical message through the brain. Using such optogenetic approaches, scientists can pick and choose which neurons in the brain they want turned on or off at any given time and observe the resulting change in the engineered mice."There's no question that this is a great way to control neuronal activity, by borrowing light-responsive channels or pumps from other organisms and putting them in neurons," says Wang. "But rather than put a stranger into neurons, we wanted to control the activity of proteins native to neurons."To make proteins respond to light, Wang's team harnessed a photo-responsive amino acid, called Cmn, which has a large chemical structure. When a pulse of light shines on the molecule, Cmn's bulky side chain breaks off, leaving cysteine, a smaller amino acid. Wang's group realized that if a single Cmn was integrated into the right place in the structure of a protein, the drastic change in the amino acid's size could activate or inactivate the entire protein.To test their idea, Wang and his colleagues engineered new versions of a potassium channel in neurons, adding Cmn to their sequence."Basically the idea was that when you put this amino acid in the pore of the channel, the bulky side chain entirely blocks the passage of ions through the channel," explains Ji-Yong Kang, a graduate student who works in Wang's group, and first author of the new paper. "Then, when the bond in the amino acid breaks in response to light, the channel is opened up."The method worked in isolated cells: After trial and error, the scientists found the ideal spot in the channel to put Cmn, so that the channel was initially blocked, but opened when light shone on it. They were able to measure the change to the channel's properties by recording the electrical current that flowed through the cells before and after exposure to light.But to apply the technique to living mice, Wang and his colleagues needed to change the animals' genetic code -- -- the built-in instructions that cells use to produce proteins based on gene sequences. The normal genetic code doesn't contain information on Cmn, so simply injecting Cmn amino acids into mice wouldn't lead to the molecules being integrated into proteins. In the past, the Wang group and others have expanded the genetic codes of isolated cells of simple organisms like bacteria, or yeast, inserting instructions for a new amino acid. But the approach had never been successful in mammals. Through a combination of techniques and new tricks, however, Wang's team was able to provide embryonic mice with the instructions for the new amino acid, Cmn. With the help from Salk Professor Dennis O'Leary and his research associate Daichi Kawaguchi, they then integrated the new Cmn-containing channel into the brains of the developing mice, and showed that by shining light on the brain tissue they could force the channel open, altering patterns of neuron activity. It was not only a first for expanding the genetic code of mammals, but also for protein control.At the surface, the new approach has the same result as optogenetic approaches to studying the brain -- -neurons are silenced at a precise time in response to light. But Wang's method can now be used to study a whole cadre of different proteins in neurons. Aside from being used to open and close channels or pores that let ions flow in and out of brain cells, Cmn could be used to optically regulate protein modifications and protein-protein interactions."We can pinpoint exactly which protein, or even which part of a protein, is crucial for the functioning of targeted neurons," says Wang. "If you want to study something like the mechanism of memory formation, it's not always just a matter of finding what neurons are responsible, but what molecules within those neurons are critical."Earlier this year, President Obama announced the multi-billion dollar Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, a ten-year project to map the activity of the human brain. Creating new ways to study the molecules in the brain, such as using light-responsive amino acids to study neuronal proteins, will be key to moving forward on this initiative and similar efforts to understand the brain, says Wang. His lab is now working to develop ways to not only activate proteins, but inactive them using light-sensitive amino acids, and applying the technique to proteins other than Kir2.1.Other researchers on the study were Daichi Kawaguchi, Irene Coin, Zheng Xiang, Dennis D. M. O'Leary the Salk Institute for Biological Studies, and Paul A. Slesinger of the Icahn School of Medicine at Mount Sinai.The work was supported a Salk Innovation Grant, a Marie Curie Fellowship from the European Commission, and grants from the California Institute for Regenerative Medicine and the U.S. National Institutes of Health.
|
Genetically Modified
| 2,013 |
October 14, 2013
|
https://www.sciencedaily.com/releases/2013/10/131014094119.htm
|
Genetically modified tobacco plants are viable for producing biofuels
|
In her PhD thesis Ruth Sanz-Barrio, an agricultural engineer of the NUP/UPNA-Public University of Navarre and researcher at the Institute of Biotechnology (mixed centre of the CSIC-Spanish National Research Council, Public University of Navarre and the Government of Navarre), has demonstrated, for the first time, the viability of using specific tobacco proteins (known as thioredoxins) as biotechnological tools in plants. Specifically, she has managed to increase the amount of starch produced in the tobacco leaves by 700% and fermentable sugars by 500%. "We believe that these genetically modified plants," she explained, "could be a good alternative to food crops for producing biofuels, and could provide an outlet for the tobacco-producing areas in our country that see their future in jeopardy owing to the discontinuing of European grants for this crop."
|
Thioredoxins (Trxs) are small proteins present in most living organisms. In the course of her research Ruth Sanz demonstrated the capacity of the thioredoxinsHuman albumin is the most widely used intravenous protein in the world for therapeutic purposes. It is used to stabilize blood volume and prevent the risk of infarction, and its application in operating theatres is almost a daily occurrence. It is also used in burns, surgical operations, haemorrhages, or when the patient is undernourished or dehydrated, and in the case of chronic infections and renal or hepatic diseases.Although commercial albumin is extracted from blood, the lack of a sufficient volume in reserve has prompted many researchers to seek new formulas for obtaining this protein on a large scale economically and safely. "We have come up with an easier, cheaper procedure for producing it in the tobacco plant and extracting it. By fusing the genes encoding the TrxsAs the research progressed, thioredoxinOnce the regulating function of TrxGenetically enhanced tobacco could be an alternative source of biomass in areas like Extremadura and Andalusia, the traditional tobacco producers. The estimated calculations of the starch production of these enhanced varieties would be the equivalent to those of crops like barley or wheat. "As cereals are currently being used as the raw material to produce bioethanol, genetically enhanced tobacco could be an alternative source of biomass and for obtaining clean energies."
|
Genetically Modified
| 2,013 |
October 10, 2013
|
https://www.sciencedaily.com/releases/2013/10/131010142754.htm
|
New antiviral response discovered in mammals
|
Many viral infections are nipped in the bud by the innate immune response. This involves specific proteins within the infected cell that recognize the virus and trigger a signalling cascade -- the so-called interferon response. This activates a protective mechanism in neighbouring cells and often results in the death of the primarily infected cell.
|
In plants and invertebrates another mechanism is known to function in antiviral immune response: the so-called RNA interference (RNAi) pathway. RNAi uses an intermediate of the viral proliferation process to build a weapon against the virus. Although RNAi also exists in mammals, researchers have until now thought it to be involved in other cellular processes required for gene regulation but not in antiviral immunity. Evidence that RNAi does indeed contribute to mammalian antiviral defence is now published in The researchers infected mouse embryonic stem cells with two viruses, the encephalomyocarditis virus (EMCV) and the Nodamura virus (NoV). Subsequently, they were able to detect short RNA molecules of about 22 nucleotides in length within the cells. The sequence of these RNA clearly corresponded to the viral genome and they displayed all the characteristics of the main effector molecules of RNAi called the small interfering or siRNAs. This provided evidence that the virus infection had activated the RNAi machinery of mammalian cells.The trigger for RNAi is an unusual RNA molecule that arises when the viral genome is copied: a long, double-stranded RNA molecule. This double-stranded RNA is cut into shorter pieces to produce siRNAs, which subsequently serve as a homing device. Since they are derived from the viral RNA and thus correspond perfectly to its sequence, they guide molecular scissor proteins to the viral RNA. The latter is subsequently cut into harmless pieces. Thus, the virus can no longer proliferate.Voinnet provides two reasons why the role of RNAi in antiviral immunity in mammals has been overlooked for so long: first, studies conducted in plants (notably by the Voinnet group) and later in invertebrates have shown that many viruses have developed counter-defences to inhibit the RNAi machinery of infected cells. If such counter-defences existed also in mammalian viruses, they would likely mask antiviral RNAi. Second, most scientists have looked for antiviral RNAi in differentiated cells in which the interferon response makes up the majority of the innate immune response. In contrast, Voinnet and his colleagues have focused on stem cells.Stem and presumably progenitor cells cannot produce an interferon response and thus do not possess a classical innate immunity. This makes sense, says Voinnet, as the interferon response results in the death of the infected cell. Since whole differentiated cell populations arise from the progenitor cells, they would be eliminated along with the latter. Similarly, virus infections in a stem cell would be very detrimental, as all its descendant cell lineages would be infected as well. "RNAi is therefore perfectly suited to protect progenitor cells from viruses. It may actually be the only form of immunity these cells can mount against viruses," Voinnet says. He adds: "However, I would not want to put into people's mind that antiviral RNAi operates only in stem and progenitor cells: we show in our paper that we can detect it in differentiated stem cells as well, although at a significantly lower level."In order to provide further evidence for a function of RNAi in mammalian antiviral immunity, the researchers modified the Nodamura Virus genetically to eliminate what they thought was its counter-defence mechanism against RNAi. Subsequently, they infected mouse stem cells with the modified virus and observed that the cells could fend off this virus much better than the original NoV. Moreover, only upon infection with the engineered virus did the scientists detect siRNAs derived from the virus genome. These results show that RNAi is the mechanism that held NoV at bay, but this mechanism became only visible when the RNAi antagonist encoded by NoV was removed. "Thus, identical frameworks of antiviral defence and counter-defence operate in mammals, plants and invertebrates," Voinnet concludes.Work conducted in parallel and published back-to-back by Voinnet's colleague and collaborator Shou Wei Ding (University of Riverside, USA) show that siRNAs could be also detected in tissues of newborn mice infected with the modified NoV. Remarkably these siRNAs were identical to those found by Voinnet and colleagues in cultured mouse stem cells and they provided the suckling mice a near-complete immunity against the virus. "This was important proof to show that antiviral RNAi exists in a living organism and not just in stem cell cultures," explains Voinnet.Thus, the researchers have revealed an important and so far hidden part of innate immunity in mammals. "The beauty of this system is its simplicity, and, we can now say it, its universality," says Voinnet. "The RNAi machinery is part of the cells' normal life, but it acquires its function as an antiviral weapon thanks to the RNA that is produced by the virus to be eliminated. Since the specificity of the response is provided by the virus itself, the mechanism can basically adapt to any virus. Immunity could not be more innate than that!" he concludes.
|
Genetically Modified
| 2,013 |
October 7, 2013
|
https://www.sciencedaily.com/releases/2013/10/131007094508.htm
|
Genetically modified sweet corn can reduce insecticide use
|
A new study finds that genetically-modified sweet corn is better for the environment and safer for farm workers
|
Since 1996, corn containing a gene that allows it to create a protein that is toxic to certain insects, yet safe for human consumption, has been grown in the United States. However, most of this "Bt corn" has been used for animal feed or processed into corn meal, starch, or other products. Although varieties of sweet corn (corn on the cob) have existed since the late 1990s, relatively few acres have been planted.Due to pressure from activist groups, some grocery stores have refused to carry Bt sweet corn. However, a new study published in the Journal of Economic Entomology suggests that Bt sweet corn is better for the environment because it requires fewer pesticide applications than conventional corn."Our data suggest that using Bt sweet corn will dramatically reduce the use of traditional insecticides," the authors wrote. "Based on the performance of Bt field corn, growers should realize increased profits and there will be less risk to nontarget organisms, including natural enemies that help suppress pest densities."The study, "Multi-State Trials of Bt Sweet Corn Varieties for Control of the Corn Earworm (Lepidoptera: Noctuidae)," analyzed the performance of Bt sweet corn, comparing its rate of infestation and marketability to genetically identical varieties that lacked Bt proteins. In 2010 and 2011, sweet corn trials were conducted in New York, Minnesota, Maryland, Ohio and Georgia, locations that differ in climate, management practices and pest pressure. The authors found that for pest management of the corn earworm, Bt sweet corn consistently performed better than its non-Bt counterparts, even those that were sprayed with conventional insecticides."Across multiple states and multiple years, Bt sweet corn performed better and required fewer sprays to meet market standards," said Cornell entomology professor Anthony Shelton. "One of the most spectacular examples occurred in New York plots in 2010: the Bt sweet corn had 99 to 100 percent marketable ears without any sprays and, even with eight conventional insecticide sprays, the non-Bt corn had only 18 percent marketable ears. This wasn't much better than the 6 percent marketable ears produced in the plots that received no sprays at all."The authors predict that growers could realize increased profits with Bt sweet corn because of lower inputs and higher marketability, while simultaneously conserving populations of beneficial insects that keep damaging pests at bay."The use of Bt vegetables could significantly reduce the use of conventional insecticides and, in turn, reduce occupational and environmental risks that arise from intensive insecticide use," Shelton said.
|
Genetically Modified
| 2,013 |
October 3, 2013
|
https://www.sciencedaily.com/releases/2013/10/131003142704.htm
|
Genetics used to sort out poorly known -- and hunted -- whale species
|
Saving the whales often means knowing -- sometimes genetically -- one group of whales from another, say researchers attempting to define populations of a medium-sized and poorly understood baleen whale that is sometimes targeted by Japan's scientific whaling program. In a new study, scientists from Wildlife Conservation Society, the American Museum of Natural History, Columbia University, NOAA, and other groups are working to define separate groups and subspecies of the Bryde's whale in the Indian and western Pacific Oceans.
|
By generating genetic information that allowed the team to discriminate among different Bryde's whales (almost akin to a 'bar code'), the research has confirmed the existence of two subspecies, one which is larger in size and inhabits offshore waters, and one that is smaller in size and frequents more coastal marine habitats. The study now appears in the latest edition of the "Very little is known about Bryde's whales in terms of where populations are distributed, the extent of their range, or even relationships among them at the population, sub-species and species levels," said Columbia University researcher Francine Kershaw, lead author of the study. "Our genetic research will help define these groups and identify populations in need of additional protection.""The ability to delineate different populations and subspecies of Bryde's whales -- particularly ones threatened by low numbers and genetic diversity -- will help management authorities prevent the loss of unique and distinct genetic lineages and distinct populations," said Dr. Howard Rosenbaum, the paper's senior author and director of the Wildlife Conservation Society's Ocean Giants Program.Named after Norwegian whaler and entrepreneur Johan Bryde, the Bryde's whale (pronounced BREW-dus) grows up to 50 feet in length. The species occurs in tropical, subtropical, and warm temperate waters of the Atlantic, Pacific, and Indian Oceans. In addition to scientific whaling, threats to Bryde's whale populations include ship strikes, fisheries bycatch, hydrocarbon exploration, and development in coastal waters.The lack of knowledge on the Bryde's whale -- how many species and populations there are -- presents marine managers with a conservation dilemma. The species is considered "Data Deficient" by the International Union for Conservation of Nature, and the International Whaling Commission grants Japan an annual take of Bryde's whales in the northwest Pacific Ocean through the provisions of special scientific permit. The quota for the 2012/2013 season was 34 Bryde's whales.Working to fill in these knowledge gaps, the research team conducted an analysis of Bryde's whale populations in the Indian and Pacific Oceans by examining new genetic samples from 56 individual whales from the waters of Oman, Maldives, and Bangladesh. The team also used published data sets from Java, the coast of Japan, and the northwest Pacific in the study.Specifically, the team examined nine diagnostic characters from the mitochondrial DNA material from each of the samples. In most instances, the researchers harmlessly collected skin samples from living whales using small biopsy darts launched from crossbows. Other samples were collected from beached whales and individuals killed in ship strikes.The research team then examined the genetic material gathered from skin samples with a technique called polymerase chain reaction (PCR), used in this study to amplify specific regions of mitochondrial DNA (passed on through maternal lines of a population). They then carried out a statistical analysis to measure how genetically different individuals were.The results of the genetic analysis confirmed the existence of two subspecies or types of Brydes whales, one coastal and one offshore, underlining the need to designate both subspecies as separate conservation units, with specific management needs for each type.Further, the study revealed significant population structure for each subspecies between regions. According to the analysis, the larger offshore Bryde's whale populations in Maldives, Java, and the Northwest Pacific were genetically distinct from one another. The authors recommend that each population be considered a separate conservation unit.The smaller coastal form of Bryde's whale showed extremely low genetic diversity, the lowest ever measured with baleen whale populations. Only a single maternal line or haplotype was detected in the 45 individual whales sampled in Bangladesh and Oman. This population, insist the authors, must be considered a conservation unit independent from coastal Bryde's whales found off Japan.
|
Genetically Modified
| 2,013 |
October 3, 2013
|
https://www.sciencedaily.com/releases/2013/10/131003132242.htm
|
Innovative approach could ultimately end deadly disease of sleeping sickness
|
A tag team of two bacteria, one of them genetically modified, has a good chance to reduce or even eliminate the deadly disease African trypanosomiasis, or sleeping sickness, researchers at Oregon State University conclude in a recent mathematical modeling study.
|
African trypanosomiasis, caused by a parasite carried by the tsetse fly, infects 30,000 people in sub-Saharan Africa each year and is almost always fatal without treatment. In a 2008 epidemic, 48,000 people died.In this research, scientists evaluated the potential for success of a new approach to combat the disease -- creating a genetically modified version of the When that's done, the GMO version of "There are a few 'ifs' necessary for this to succeed, but none of them look like an obstacle that could not be overcome," said Jan Medlock, an assistant professor in the OSU Department of Biomedical Sciences, and lead author on the new report."If everything goes right, and we are optimistic that it will, this could be enormously important," Medlock said. "There's a potential here to completely solve this disease that has killed many thousands of people, and open new approaches to dealing with even more serious diseases such as malaria."Some of the "ifs" include: the transgenic The research shows that dealing with all of those obstacles should be possible. If so, this might spell the end of a tropical disease that has plagued humans for hundreds, possibly thousands of years. African trypanosomiasis causes serious mental and physical deterioration -- including the altered sleep patterns that give the disease its name -- and is fatal without treatment. It's still difficult to treat, and neurologic damage is permanent.Past efforts to control the disease, including insect traps, insecticide spraying, and use of sterile insects have been of some value, but only in limited areas and the effects were not permanent.The strength of the new approach, researchers say, is that once the process begins it should spread and be self-sustaining -- it should not be necessary to repeatedly take action in the huge geographic areas of Africa. Due to some genetic manipulation, the flies carrying the As the flies carrying transgenic bacteria continue to dominate and their populations spread, trypanosomiasis should fairly rapidly disappear. Whether the mechanism of control could wane in effectiveness over time is an issue that requires further study, scientists said.Work has begun on the GMO version of Medlock, an expert in modeling the transmission of various diseases -- including human influenza -- says the analysis is clear that this approach has significant promise of success. Because of the relatively low infectiousness of the parasite and the ability of Accomplishing a similar goal with diseases such as malaria may be more difficult, he said, because that disease historically has shown a remarkable ability to mutate and overcome many of the approaches used to attack it. However, at least some near-term gains may be possible, he said.
|
Genetically Modified
| 2,013 |
October 2, 2013
|
https://www.sciencedaily.com/releases/2013/10/131002185245.htm
|
Certain type of fat could help humans lose weight
|
A diet high in a certain type of fat may actually increase metabolism, according to recent research by Texas Tech University nutrition scientists.
|
After studying genetically modified mice, the discovery could lead to supplements and a diet regimen that will increase metabolism and decrease muscle fatigue in humans. The research was published in the peer reviewed journal, Chad Paton, an assistant professor of nutritional biochemistry in the Department of Nutrition, Hospitality and Retailing, said he and colleagues were curious why skeletal muscles of obese people contained a certain type of enzyme that breaks down saturated fats. To test what that enzyme did, Paton's lab and colleagues from the University of Wisconsin -- Madison genetically modified mice so that their muscles would constantly produce the enzyme."We used a transgenic mouse model, and we took the gene that makes the enzyme that's not normally expressed and took away it's regulation to make it active all the time," Paton said. "What we found in those animals is they had a hypermetabolic rate compared to the wild mice, increased energy consumption and greatly increased these animals' exercise capacity."The enzyme, called SCD1, converts saturated fat into monounsaturated fat, which is easier to metabolize. The liver will produce this enzyme depending on the fat content of the food consumed, he said. Fatty adipose tissue produces it all the time as a way of regulating itself.Only in heavily exercised muscle tissue or in the case of obesity does skeletal muscle produce the enzyme, he said.After looking at skeletal muscles of the genetically modified mice compared to that of the wild mice, Paton and his team discovered higher levels of polyunsaturated fats, particularly linoleic acid, gotten only through diet.Higher levels of linoleic acid could only mean one thing -- the modified mice were eating more food. But Paton's team found that the modified mice weighed less than the wild mice. On top of that, their ability to exercise increased."We found in the genetically modified animals that they had a hypermetabolic rate," he said. "They were increasing their energy consumption, and they experienced greatly increased exercise capacity. For example, on the exercise wheels, normal mice fatigue after 7 to 10 minutes. These genetically modified animals wouldn't fatigue for about 70 minutes. So they were running a lot longer. Sedentary mice looked more like exercise-trained mice. That really made us look in a lot more detail what was happening in the skeletal muscle." By looking at the muscle tissues, Paton and his team members discovered a trend.More of the SCD1 enzyme and a greater appetite by the mice meant more linoleic acid in the tissues. The linoleic acid switched on part of the muscle cell's DNA that encouraged the cells to make more mitochondria and to turn on a protein that encouraged the cell to burn off excess energy from the extra food as heat -- a process called uncoupling.Humans store unused energy as fat, Paton said. And while that helped our ancestors survive, it can lead to obesity for some people in today's world of plentiful food.While genetically modifying humans isn't an option, Paton said this experiment could hold useful information for supplementing human diets to achieve the same results."That's where we have taken our research from this," he said. "You can't change the human genome, but that gives us insight if you could activate the same part of the DNA in human in skeletal muscles that burn off excess energy as heat instead of storing it. Perhaps it's a supplement people could take that will turn on the cells' metabolic machinery burn off energy and increase mitochondria."
|
Genetically Modified
| 2,013 |
October 1, 2013
|
https://www.sciencedaily.com/releases/2013/10/131001090012.htm
|
Link found between high-fat, high-calorie diet and pancreas cancer
|
Researchers at UCLA's Jonsson Comprehensive Cancer Center (JCCC) have found that mice made obese by being given high-calorie, high-fat diets (HFCD) developed abnormally high numbers of lesions known as pancreatic intraepithelial neoplasias (PanINs), which are known to be precursors to pancreas cancer. This is the first study to show a direct causative link in an animal model between obesity and risk of this deadly cancer.
|
The study was led by Dr. Guido Eibl, JCCC member and professor -in-residence in the department of surgery at David Geffen School of Medicine. It was published in the journal Cancer of the pancreas (scientifically known as pancreatic ductal adenocarcinoma or PaCa) is one of the most deadly forms of the disease in humans. Overall five-year survival rates are approximately three to five percent and the average survival period after diagnosis is just four to six months. It is a particularly aggressive disease and often beyond the point of effective treatment by the time symptoms appear. Current treatments are limited in number and effectiveness, thus researchers are turning to prevention strategies to try to make headway against the disease before it reaches advanced stages. Previous research in the study of the disease in large populations has strongly supported a positive association between obesity and increased risk of PaCa, but no studies recapitulated human PaCa in animals. The availability of genetically engineered model mice that have the same genetic mutation found in human pancreas cancer patients (the KR as mutation) has made study of the possible causes more feasible, because changes in the mouse metabolism caused by obesity are similar to those in humans.Dr. Eibl and colleagues set out to develop diet-induced obesity and development of pancreas cancer in a set of mice and then compare them to another set of mice that are genetically identical but not given a high-fat, high-calorie diet. Obesity in these mice resembles several important clinical features of human obesity such as weight gain and disturbance of metabolism, and this mouse model was ideal for unraveling any underlying biological mechanisms of pancreas cancer that are put in motion by obesity.The researchers also set parameters to assess the impact of the effects of the high-fat, high-calorie diet on mouse pancreas tissue, such as increased inflammation and other biological signs that indicate pancreas problems. These indicators were measured and used to create an overall score (pancreatitis score) to indicate negative effects on the pancreas. They then conducted pathology tests on mouse pancreas tissue to determine how many PanIN precursor lesions had developed.Mice that ate the normal diet gained an average of approximately 7.2 grams, plus or minus approximately 2.8 grams over 14 months. Mice that ate the high-fat, high-calorie diet gained an average of 15.9 grams, plus or minus 3.2 grams. Mice fed the normal diet had mostly normal pancreases with very few scattered PanIN lesions. Mice fed the high-fat, high-calorie diet had significantly more PanIN lesions and fewer overall healthy pancreases.The study showed that the mice fed a diet high in fats and calories gained significantly more weight, had abnormalities of their metabolism and increased insulin levels, and had marked pancreatic tissue inflammation and development of PanIN lesions. These observations strongly suggest that such a diet leads to weight gain, metabolism disturbances, can cause pancreas inflammation and promotes pancreas lesions that are precursors to cancer."The development of these lesions in mice is very similar to what happens in humans," Dr. Eibl said. "These lesions take a long time to develop into cancer, so there is enough time for cancer preventive strategies, such as changing to a lower fat, lower calorie diet, to have a positive effect."This research was supported by the National Institutes of Health, the US Department of Veterans Affairs, and Hirshberg Foundation for Pancreatic Cancer Research.UCLA's Jonsson Comprehensive Cancer Center has more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2013, the Jonsson Cancer Center was named among the top 12 cancer centers nationwide by U.S. News & World Report, a ranking it has held for 14 consecutive years. For more information on the Jonsson Cancer Center, visit our website at
|
Genetically Modified
| 2,013 |
September 30, 2013
|
https://www.sciencedaily.com/releases/2013/09/130930162415.htm
|
New metabolic pathway to more efficiently convert sugars into biofuels
|
UCLA chemical engineering researchers have created a new synthetic metabolic pathway for breaking down glucose that could lead to a 50 percent increase in the production of biofuels.
|
The new pathway is intended to replace the natural metabolic pathway known as glycolysis, a series of chemical reactions that nearly all organisms use to convert sugars into the molecular precursors that cells need. Glycolysis converts four of the six carbon atoms found in glucose into two-carbon molecules known acetyl-CoA, a precursor to biofuels like ethanol and butanol, as well as fatty acids, amino acids and pharmaceuticals. However, the two remaining glucose carbons are lost as carbon dioxide.Glycolysis is currently used in biorefinies to convert sugars derived from plant biomass into biofuels, but the loss of two carbon atoms for every six that are input is seen as a major gap in the efficiency of the process. The UCLA research team's synthetic glycolytic pathway converts all six glucose carbon atoms into three molecules of acetyl-CoA without losing any as carbon dioxide.The research is published online Sept. 29 in the peer-reviewed journal The principal investigator on the research is James Liao, UCLA's Ralph M. Parsons Foundation Professor of Chemical Engineering and chair of the chemical and biomolecular engineering department. Igor Bogorad, a graduate student in Liao's laboratory, is the lead author."This pathway solved one of the most significant limitations in biofuel production and biorefining: losing one-third of carbon from carbohydrate raw materials," Liao said. "This limitation was previously thought to be insurmountable because of the way glycolysis evolved."This synthetic pathway uses enzymes found in several distinct pathways in nature.The team first tested and confirmed that the new pathway worked in vitro. Then, they genetically engineered E. coli bacteria to use the synthetic pathway and demonstrated complete carbon conservation. The resulting acetyl-CoA molecules can be used to produce a desired chemical with higher carbon efficiency. The researchers dubbed their new hybrid pathway non-oxidative glycolysis, or NOG."This is a fundamentally new cycle," Bogorad said. "We rerouted the most central metabolic pathway and found a way to increase the production of acetyl-CoA. Instead of losing carbon atoms to CO2, you can now conserve them and improve your yields and produce even more product."The researchers also noted that this new synthetic pathway could be used with many kinds of sugars, which in each case have different numbers of carbon atoms per molecule, and no carbon would be wasted."For biorefining, a 50 percent improvement in yield would be a huge increase," Bogorad said. "NOG can be a nice platform with different sugars for a 100 percent conversion to acetyl-CoA. We envision that NOG will have wide-reaching applications and will open up many new possibilities because of the way we can conserve carbon."The researchers also suggest this new pathway could be used in biofuel production using photosynthetic microbes.The paper's other author is Tzu-Shyang Lin, who recently received a bachelor's degree from UCLA in chemical engineering.
|
Genetically Modified
| 2,013 |
September 26, 2013
|
https://www.sciencedaily.com/releases/2013/09/130926204433.htm
|
Cell powerhouses shape one's risk of heart disease
|
Genes in mitochondria, the "powerhouses" that turn sugar into energy in human cells, shape each person's risk for heart disease and diabetes, according to a study published recently by researchers at the University of Alabama at Birmingham in the
|
Researchers have long sought to determine disease risk by looking at diet and variations in nuclear genes, leaving out differences in mitochondrial genes, the second kind of DNA in every cell.Research in recent years revealed that miscues in mitochondrial energy production create too many particles called oxidants and free radicals that cause cells to self-destruct as part of heart disease, diabetes and cancer."Having been in this field for decades, I remember when mitochondrial DNA variations were thought to play a role only in the rarest of genetic syndromes," said Scott Ballinger, Ph.D., professor in the Division of Molecular and Cellular Pathology within the UAB School of Medicine, and corresponding study author. "Today, there is a growing consensus that variations in mitochondrial DNA alone make a substantial contribution to each person's risk for heart disease, and ours is the first study to directly confirm it in a living mammal."Ballinger's study results reflect the theory that our ancient, one-celled ancestors "swallowed" the bacterial forbears of what are now mitochondria. The newcomers gave their hosts the ability to convert sugar from food into about 15 times as much cellular energy as they could before by using oxygen. Evolution favored the match, and mitochondria became permanent sub-compartments of human cells.For that reason, each human cell now has two genomes, the long stretches of DNA that encode the blueprint for the human body: one set inherited from both parents in a centrally located nucleus, and a separate, smaller set in each mitochondrion passed down from mom thanks to details of cell division.The theory that maternally inherited, mitochondrial DNA shape disease risk has been hard to prove. The field has struggled to genetically engineer mice that would enable researchers to separate the impact of one gene set from the other. Additionally, the human nuclear genome contains more than 30,000 genes compared to a mere 13 energy-related genes in mitochondria, so few researchers paid them much attention.Swapping mitochondriaTo determine if mitochondrial DNA variations drive disease risk independent of an individual's nuclear DNA, the research team started with two varieties of mice; the C57 mouse known to be vulnerable to diseases associated with diet, and the C3H mouse, which is resistant. The study authors then used a technique called nuclear transfer to remove the nucleus from an embryo in each mouse line and switch them.Because mitochondria reside in the cytoplasm (not in the switched nuclei), the new embryos grew into mice whose cells had their own mitochondrial DNA and the nuclear DNA from the other line. That enabled researchers to compare mice with the same nuclear DNA, but different mitochondrial DNA, isolating the latter's distinct contribution to risk.In general, the data showed that replacing mitochondrial DNA alone could increase or decrease a given mouse's susceptibility to a model of heart failure.In addition, putting disease-vulnerable C57 mitochondria in a cell with a C3H nucleus made that cell take on the energy characteristics of the original, more energy efficient C57 strain. This came with a 15 percent decrease in the amount of oxygen needed to make the same amount of cellular energy in the form of adenosine triphosphate. In a mixed bag, mice with efficient C57 mitochondrial DNA also generated 200 percent more oxidants than their disease-resistant counterparts with C3H mtDNA.Another study underway in Ballinger's lab is comparing mitochondrial DNA variations in people of African versus northern European ancestry. Evidence suggests that mitochondria carrying African mitochondrial DNA get more energy from the same amount of oxygen and sugar, perhaps reflecting an evolutionary history of food scarcity. Early migrating humans may have found more food in Europe, but would also have had to brave the cold. Thus, Euro mitochondria appear to be less efficient, perhaps because a byproduct of such inefficiency is the increased generation of body heat. More efficient mitochondria, with their greater oxidant production, may explain, in part, higher incidents of heart disease and diabetes among those of African ancestry in the face of modern, high-calorie diets.
|
Genetically Modified
| 2,013 |
September 26, 2013
|
https://www.sciencedaily.com/releases/2013/09/130926143147.htm
|
Mucus useful in treating IBD, ulcerative colitis and Crohn's disease
|
Imagine mucus -- which most people find unpleasant -- actually helping your body maintain its equilibrium, prevent inflammation, and reduce food allergy problems.
|
Researchers from the Icahn School of Medicine at Mount Sinai's Immunology Institute foresee a day when mucus could be manufactured and given to sick people to help them fight inflammation and increase immunity. For the first time ever, they report that mucus in the large intestine provides a valuable anti-inflammatory and self-regulating immune function. In fact, they propose that mucus may one day prove valuable in treating gut diseases, such as inflammatory bowel disease (IBD), Crohn's disease, as well as cancer.The research is published online September 26 in the peer-reviewed journal "We asked ourselves whether dendritic cells in the gut could capture mucus, as well as bacteria and food antigens," said Andrea Cerutti, MD, PhD, the study's senior author and Professor in the Department of Medicine at the Immunology Institute at the Icahn School of Medicine. Dendritic cells are a type of immune cell found in the mucosa that launch an immune response. "We found that whenever mucus was present, it was stimulating the production of anti-inflammatory cytokines [regulatory proteins released by the cells of the immune system that act to regulate an immune response]," he added. The mucus prevented bacteria from inducing a damaging immune response.Put another way, intestinal mucus not only acted as a barrier against bacteria and dietary toxins, but also stopped the onset of inflammatory reactions against these agents. "This important property of mucus was unknown until now," said Meimei Shan, MD, PhD, the study's lead author, and Assistant Professor in the Department of Medicine at the Immunology Institute at Icahn School of Medicine at Mount Sinai.In this research, mucus was isolated and analyzed from the intestine of healthy mice, from pigs, and from a human intestinal cell line. A number of techniques involving cellular immunology and molecular biology were used to demonstrate the anti-inflammatory properties of mucus. In addition, genetically engineered mice lacking intestinal mucus and mice with colitis were given mucus from healthy mice.Under normal conditions, people release about one liter of mucus every single day. Mucus is normally secreted by mucosal tissues throughout the body, according to the researchers. The large intestine carries 80 percent of the body's immune cells. In inflammatory gastrointestinal disorders, such as Crohn's disease and inflammatory bowel disease, people may have alterations of intestinal mucus that impede the generation of a protective anti-inflammatory response."Future research will focus on further exploring the mechanisms to synthesize gut mucus or an equivalent drug-like compound for oral administration," said Dr. Shan. "We hope to artificially synthesize mucus or an equivalent compound for oral use."Besides helping to treat inflammatory gut diseases, the researchers see ramifications in treating cancer. Dr. Cerutti explained: "Several aggressive tumors, such as colon, ovarian, and breast cancers produce mucous, including MUC2. Mucus produced by malignant cells may prevent protective immune responses against the malignant cells." As researchers gain a better understanding of the properties of mucus, it could also have a positive effect in treating tumors.
|
Genetically Modified
| 2,013 |
September 24, 2013
|
https://www.sciencedaily.com/releases/2013/09/130924113452.htm
|
Adjusting bacteria in intestines may lead to obesity treatments
|
A drug that appears to target specific intestinal bacteria in the guts of mice may create a chain reaction that could eventually lead to new treatments for obesity and diabetes in humans, according to a team of researchers.
|
Mice fed a high-fat diet and provided tempol, an anti-oxidant drug that may help protect people from the effects of radiation, were significantly less obese than those that did not receive the drug, according to Andrew Patterson, assistant professor of molecular toxicology, Penn State, who worked with Frank J. Gonzalez, laboratory metabolism chief, and James B. Mitchell, radiation biology branch chief, both of the National Cancer Institute."The two interesting findings are that the mice that received tempol didn't gain as much weight and the tempol somehow impacted the gut microbiome of these mice," said Patterson. "Eventually, we hope that this can lead to a new line of therapeutics to treat obesity and diabetes."The microbiome is the biological environment of microorganisms within the human body.The researchers, who reported their findings in the current issue of "The study suggests that inhibiting FXR in the intestine might be a potential target for anti-obesity drugs," said Gonzalez.The researchers said that tempol may help treat type 2 diabetes symptoms. In addition to lower weight gain, the tempol-treated mice on a high-fat diet had lower blood glucose and insulin levels."Previously, Dr. Mitchell observed a significant difference in weight gain in mice on tempol-containing diet," said Patterson. "He approached us to help figure out what was going on, and it had been an interesting journey wading through the complexities of the microbiome."Other studies hinted at the relationship between tempol, the gut microbiome and obesity, but did not focus on why the drug seemed to control weigh gain, according to Patterson.The researchers said these studies are demonstrating how integrated the 100 trillion microbes that make up the human microbiome are with metabolism and health and how the microbiome may provide more pathways to treating other disorders."There is a tremendous interest in how the microbiome can be manipulated in a therapeutic way," said Patterson. "And we need to look at these microbiome management techniques in a good, unbiased way."In the study, the researchers dissolved the tempol in drinking water, or delivered it directly to the mice. Within three weeks, tempol reduced the weight gain for the mice in that group. The mice showed significant reduction in weight gain even after 16 weeks.To further test the role of FXR in obesity, the researchers placed mice that were genetically modified so that they lack FXR on the same high-fat diet. This group was resistant to the effects of tempol and taura-beta-muricholic acid, which further strengthened the importance of FXR in mediating the anti-obesity effect.Gonzalez said that there are indications that FXR plays a similar role in human obesity and diabetes.The researchers must now test the treatments to ensure it is effective in humans, as well as check for any potential side effects, including cancer.
|
Genetically Modified
| 2,013 |
September 23, 2013
|
https://www.sciencedaily.com/releases/2013/09/130923143528.htm
|
Modifying rice crops to resist herbicide prompts weedy neighbors' growth spurt
|
Rice containing an overactive gene that makes it resistant to a common herbicide can pass that genetic trait to weedy rice, prompting powerful growth even without a weed-killer to trigger the modification benefit, new research shows.
|
Previously, scientists have found that when a genetically modified trait passes from a crop plant to a closely related weed, the weed gains the crop’s engineered benefit – resistance to pests, for example – only in the presence of the offending insects.This new study is a surprising example of gene flow from crops to weeds that makes weeds more vigorous even without an environmental trigger, researchers say.The suspected reason: This modification method enhances a plant’s own growth control mechanism, essentially making it grow faster – an attractive trait in crops but a recipe for potential problems with weedy relatives that could out-compete the crop.“Our next question is whether this method of enhancing plant growth could be developed for any crop. We want to know whether growers could get higher yields in the crop and then, if it happened to cross with a related weed, whether it might make the weed more prolific as well,” said Allison Snow, professor of evolution, ecology and organismal biology at The Ohio State University and a lead author of the paper.“It’s unusual for any transgene to have such a positive effect on a wild relative and even more so for herbicide resistance,” she said. “But we think we know why: It’s probably because the pathway regulated by this gene is so important to the plant.”The work is the result of Snow’s longtime collaboration with senior author Bao-Rong Lu, a professor at Fudan University in Shanghai. Their publication appears online in the journal The weed-killer glyphosate, sold under the brand name Roundup, kills plants by inhibiting a growth-related pathway activated by the epsps gene. Biotech companies have inserted mutated forms of a similar gene from microbes into crop plants, producing “Roundup Ready” corn and soybeans that remain undamaged by widespread herbicide application.But in this study, the researchers used a different method, boosting activation of the native epsps gene in rice plants – a process called overexpressing – to give the plants enough strength to survive an application of herbicide. Because companies that genetically modify commercial crops don’t fully disclose their methods, Snow and her colleagues aren’t sure how prevalent this method might be, now or in the future.“This is a relatively new way to get a trait into a crop: taking the plant’s own gene and ramping it up,” Snow said. “We don’t know yet if our findings are going to be generalizable, but if they are, it’s definitely going to be important.”To overexpress the native gene in rice, the scientists attached a promoter to it, giving the plant an extra copy of its own gene and ensuring that the gene is activated at all times.The researchers conducted tests in rice and four strains of a relative of the same species, weedy rice, a noxious plant that infests rice fields around the world. By crossing genetically altered herbicide-resistant rice with weedy rice to mimic what happens naturally in the field, the researchers created crop-weed hybrids that grew larger and produced more offspring than unaltered counterparts – even without any herbicide present.In regulated field experiments, the hybrids containing the overexpressed gene produced 48 percent to 125 percent more seeds per plant than did hybrid plants with no modified genes. They also had higher concentrations of a key amino acid, greater photosynthetic rates and better fledgling seed growth than controls – all presumed signs of better fitness in evolutionary terms.“Fitness is a hard thing to measure, but you can conclude that if a gene gives you a lot more seeds per plant compared to controls, it’s likely to increase the plants’ fitness because those genes would be represented at a higher percentage in future generations,” Snow said.When Snow and Lu set out to study this new genetic engineering method, they didn’t know what to expect.“Our colleagues developed this novel transgenic trait in rice and we didn’t know if it would have a fitness benefit, or a cost, or be neutral,” Snow said. “With most types of herbicide resistant genes, there’s no benefit to a wild plant unless the herbicide is sprayed. A lot of transgenes in crop plants are either selectively neutral in wild plants or, if they have a benefit, it depends on environmental factors like insects, diseases or herbicides being present.”Snow has a history in this area of research. She has found that genes from crop plants can persist in related weeds over many generations. In 2002, she led a study that was the first to show that a gene artificially inserted into crop plants to fend off pests could migrate to weeds in a natural environment and make the weeds stronger. She also has served on national panels that monitor and make recommendations about the release of genetically engineered species into the environment.She is interested in identifying new possible outcomes of the growth of crop-weed hybrids that contain genetic modifications, but she doesn’t take sides about possible risks and benefits of genetically modified crops.“It’s not always the end of the world if a weed starts to become a lot more common after acquiring a new trait – there may be effective ways to manage that weed,” Snow said. “You just can’t make sweeping generalizations about genetic engineering, and knowledge from ecological studies like ours can help inform risk assessment and biosafety oversight.”
|
Genetically Modified
| 2,013 |
September 19, 2013
|
https://www.sciencedaily.com/releases/2013/09/130919122254.htm
|
How lethal bird flu viruses evolved
|
Deadly H7N9 avian flu viruses infected people for the first time earlier this year in China, but little is known about how they evolved to become harmful to humans. In a study published by Cell Press on September 19 in
|
"A deep understanding of how the novel H7N9 viruses were generated is of critical importance for formulating proper measures for surveillance and control of these viruses and other potential emerging influenza viruses," says senior study author Taijiao Jiang of the Chinese Academy of Sciences.First detected in people in late March, H7N9 viruses have resulted in more than 130 human infections and at least 44 deaths. Most of these infections occurred after exposure to infected poultry or contaminated environments rather than person-to-person contact, but these viruses could evolve to become more readily transmissible among humans. This possible threat highlights the importance of understanding the evolutionary history of H7N9 viruses for developing appropriate strategies to monitor and control outbreaks.To address this problem, Jiang teamed up with Daxin Peng of Yangzhou University and their collaborators to analyze whole-genome sequences of avian flu viruses from humans, poultry, and wild birds from China. They discovered that H7N9 viruses are genetically diverse, suggesting that complex genetic events were involved in their evolution.Their analysis revealed that the new H7N9 viruses emerged through a two-step process involving the exchange of genetic material between distinct viruses. In the first step, which took place in wild birds, genetic material from H9N2 viruses and unspecified H7 and N9 viruses was mixed to create precursor H7N9 viruses. The second step, which occurred in domestic birds in eastern China early last year, involved the exchange of genetic material between the precursor H7N9 viruses and other H9N2 viruses to create new, genetically diverse H7N9 viruses."Our work not only re-enforces the important role of wild birds in the emergence of novel influenza viruses but also highlights the necessity of integrating data from infections in humans, poultry, and wild birds for effective influenza surveillance," Jiang says.
|
Genetically Modified
| 2,013 |
September 5, 2013
|
https://www.sciencedaily.com/releases/2013/09/130905160515.htm
|
Blue-green algae a five-tool player in converting waste to fuel
|
"In the baseball world, a superstar can do five things exceptionally well: hit, hit for power, run, throw and field," said Fuzhong Zhang.
|
In the parallel universe of the microbiological world, there is a current superstar species of blue-green algae that, through its powers of photosynthesis and carbon dioxide fixation, or uptake, can produce (count 'em) ethanol, hydrogen, butanol, isobutanol and potentially biodiesel. Now that's some five-tool player.In baseball, you call that player Willie Mays or Mike Trout. In microbiology, it goes by In addition, genetically engineered Granted, that's mostly in laboratories, on the liter scale. Because of its versatility and potential, this microscopic organism is one of the most studied of its kind since it was discovered in 1968. But just as in baseball, where "can't miss" five-tool prospects are signed yearly with great expectations and never achieve their promise, Fuzhong Zhang, PhD, assistant professor of energy, environmental & chemical engineering at Washington University in St. Louis, works with Zhang says the biotech world has to overcome several challenges to put the engineered microbes in the applications stage. Zhang will be in the thick of them."My goal is to engineer microbes and turn them into microfactories that produce useful chemicals," Zhang says. "Traditional chemical production requires high pressure and temperatures and literally tons of chemical solvents, but the microbial approach is very eco-friendly: Once the engineered cyanobacteria start to grow, all they need are water, basic salts and the COIn an academic "scouting report" of Current industry specifications for potentially scalable chemical production are roughly 100 grams per liter of fuel or chemicals. Presently, the laboratory production is generally less than 1 gram per liter, and the efficiency is very low.Zhang says the research community needs better tools to control gene expression. For example, promoters -- little stretches of DNA before genes of interest that help control gene expression -- with predictable strength are needed. They also need better cellular biosensors that can sense key metabolites and control the production of vital proteins that create the desired chemicals.And they need to engineer the organisms' circadian rhythms (day/night) to someday produce organisms that work around the clock making a fuel or chemical. Natural The natural circadian rhythm has to be rewired to make a biofuel 24 hours a day.Zhang's research includes developing gene expression tools, new chemical biosynthetic pathways and circadian control tools for cyanobacteria."I'm confident that in two or three years we will have more potent tools to engineer gene expression levels and timing, which will speed up the process more accurately and efficiently," he says.Also, his group has been working to develop dynamical control systems in microbes that function like meters and valves in a traditional chemical production plant -- the meters calculate pressure and flow, and the valves control them."It's a biological version of the valve-and-meter model to control the flow of metabolites that make the production of fuel and chemicals more efficiently," he says.
|
Genetically Modified
| 2,013 |
September 4, 2013
|
https://www.sciencedaily.com/releases/2013/09/130904132457.htm
|
TB and Parkinson's disease linked by unique protein
|
A protein at the center of Parkinson's disease research now also has been found to play a key role in causing the destruction of bacteria that cause tuberculosis, according to scientists led by UC San Francisco microbiologist and tuberculosis expert Jeffery Cox, PhD.
|
The protein, named Parkin, already is the focus of intense investigation in Parkinson's disease, in which its malfunction is associated with a loss of nerve cells. Cox and colleagues now report that Parkin also acts on tuberculosis, triggering destruction of the bacteria by immune cells known as macrophages. Results appear online today (September 4, 2013) in the journal The finding suggests that disease-fighting strategies already under investigation in pre-clinical studies for Parkinson's disease might also prove useful in fighting tuberculosis, according to Cox. Cox is investigating ways to ramp up Parkin activity in mice infected with tuberculosis using a strategy similar to one being explored by his UCSF colleague Kevan Shokat, PhD, as a way to ward off neurodegeneration in Parkinson's disease.Globally, tuberculosis kills 1.4 million people each year, spreading from person to person through the air. Parkinson's disease, the most common neurodegenerative movement disorder, also affects millions of mostly elderly people worldwide.Cox homed in on the enzyme Parkin as a common element in Parkinson's and tuberculosis through his investigations of how macrophages engulf and destroy bacteria. In a sense the macrophage -- which translates from Greek as "big eater" -- gobbles down foreign bacteria, through a process scientists call xenophagy.The battle between macrophage and mycobacterium can be especially intense. The cells of non-bacterial organisms ranging in complexity from baker's yeast to humans also use a similar mechanism -- called autophagy -- to dispose of their own unneeded molecules or worn out cellular components. Among the most abundant and crucial of these components are the cell's mitochondria, metabolic powerhouses that convert food molecules into a source of energy that the cell can readily use to carry out its everyday housekeeping chores, as well as its more specialized functions.Like other cellular components, mitochondria can wear out and malfunction, and often require replacement. The process through which mitochondria are disposed of, called mitophagy, depends on Parkin.Cox became curious about the enzyme when he learned that specific, naturally occurring variations in the Parkin gene, called polymorphisms, are associated with increased susceptibility to tuberculosis infection."Because of the commonalities between mitophagy and the xenophagy of intracellular mycobacteria, as well as the links between Parkin gene polymorphisms and increased susceptibility to bacterial infection in humans, we speculated that Parkin may also be recruited to In both mouse and human macrophages infected with The involvement of Parkin in targeting both damaged mitochondria and infectious mycobacteria arose long ago in evolution, Cox argues. As part of the Looking back more than 1 billion years, Cox noted that mitochondria evolved from bacteria that were taken up by cells in a symbiotic relationship.In the same way that the immune system recognizes infectious bacteria as foreign, Cox said, "The evolutionary origin of mitochondria from bacteria suggests that perhaps mitochondrial dysfunction triggers the recognition of a mitochondrian as non-self."Having now demonstrated the importance of Parkin in fighting mycobacterial infection, Cox has begun working with Shokat to find a way to boost Parkin activity against cell-invading bacteria. "We are exploring the possibility that small-molecule drugs could be developed to activate Parkin to better fight tuberculosis infection," Cox said.
|
Genetically Modified
| 2,013 |
September 3, 2013
|
https://www.sciencedaily.com/releases/2013/09/130903193923.htm
|
Promiscuity and sperm selection improves genetic quality in birds
|
New research from the University of East Anglia has shown that females can maximise the genetic quality of their offspring by being promiscuous.
|
Researchers studied red junglefowl (the wild ancestor of the domestic chicken) in a collaborative project with the University of Oxford, Stockholm University and Linköping University.Findings published today in the journal This is down to 'cryptic female choice' -- where an internal mechanism in their reproductive tract favours the sperm from males that are most genetically different to them.The genes in question (Major Histocompatibility Complex; MHC) play a key role in detecting and fighting infections. By biasing fertilisation in favour of MHC-dissimilar males, females increase the diversity of MHC within their offspring, providing them with better disease resistance.The findings will be important for animal breeders as well as conservation projects because they show that allowing multiple matings will produce the most disease resistant and genetically healthy offspring.Prof David S Richardson, from UEA's school of Biological Sciences, said: "Our research has shown that the females don't need to choose between males to produce the most healthy offspring. Rather by mating with multiple males, they allow their internal choice mechanism to favour the most genetically different sperm."This could be the case in other animals -- including humans, however the practicality of testing this in mammals would be very difficult, and obviously impossible in humans for ethical reasons."The research investigated both experimentally controlled natural matings and artificial inseminations and found that the effect observed in natural matings was lost during artificial insemination."To optimise the quality of offspring produced in breeding programs we may need to make sure that females mate with multiple males and that they avoid artificial insemination, which could lead to the genetic health of bred stocks being weaker."Many breeding programmes for livestock and conservation use artificial insemination. But our research suggests that this may not produce the best quality offspring."This is because the effect appears to require the subconscious female assessment of the male by some cue during actual mating."So having correct cues during mating, perhaps the smell of the male, can affect a females' chances of being fertilised. And the cues from different males may not work equally well on different females. This is something that needs to be explored further in various animals including humans."The research was funded by Natural Environmental Research Council (NERC), the Biotechnology and Biological Sciences Research Council (BBSRC), Stockholm University, the Schwartz' foundation, Lars Hierta's foundation, Knut & Alice Wallenberg's foundation, the Royal Swedish Academy of Science, and the Royal Swedish Academy of Agriculture and Forestry.
|
Genetically Modified
| 2,013 |
September 3, 2013
|
https://www.sciencedaily.com/releases/2013/09/130903123041.htm
|
Aging really is 'in your head:' Scientists answer hotly debated questions about how calorie restriction delays aging process
|
Among scientists, the role of proteins called sirtuins in enhancing longevity has been hotly debated, driven by contradictory results from many different scientists. But new research at Washington University School of Medicine in St. Louis may settle the dispute.
|
Reporting Sept. 3 in The Japanese philosopher and scientist Ekiken Kaibara first described the concept of dietary control as a method to achieve good health and longevity in 1713. He died the following year at the ripe old age of 84 -- a long life for someone in the 18th century.Since then, science has proven a link between a low-calorie diet (without malnutrition) and longevity in a variety of animal models. In the new study, Imai and his team have shown how Sirt1 prompts neural activity in specific areas of the hypothalamus of the brain, which triggers dramatic physical changes in skeletal muscle and increases in vigor and longevity."In our studies of mice that express Sirt1 in the brain, we found that the skeletal muscular structures of old mice resemble young muscle tissue," said Imai. "Twenty-month-old mice (the equivalent of 70-year-old humans) look as active as five-month-olds."Imai and his team began their quest to define the critical junctures responsible for the connection between dietary restriction and longevity with the knowledge from previous studies that the Sirt1 protein played a role in delaying aging when calories are restricted. But the specific mechanisms by which it carried out its function were unknown.Imai's team studied mice that had been genetically modified to overproduce Sirt1 protein. Some of the mice had been engineered to overproduce Sirt1 in body tissues, while others were engineered to produce more of the Sirt1 protein only in the brain."We found that only the mice that overexpressed Sirt1 in the brain (called BRASTO) had significant lifespan extension and delay in aging, just like normal mice reared under dietary restriction regimens," said Imai, an expert in aging research and a professor in the departments of Developmental Biology and Medicine.The BRASTO mice demonstrated significant life span extension without undergoing dietary restriction. "They were free to eat regular chow whenever they wished," he said.In addition to positive skeletal muscle changes in the BRASTO mice, the investigators also observed significant increases in nighttime physical activity, body temperature and oxygen consumption compared with age-matched controls.Mice are characteristically most active at night. The BRASTO mice also experienced better or deeper sleep, and both males and females had significant increases in longevity.The median life span of BRASTO mice in the study was extended by 16 percent for females and 9 percent for males. Translated to humans, this could mean an extra 13 or 14 years for women, making their average life span almost 100 years, Shin said. For men, this would add another seven years, increasing their average life span to the mid-80s.Delay in cancer-dependent death also was observed in the BRASTO mice relative to control mice, the researchers noted.Imai said that the longevity and health profile associated with the BRASTO mice appears to be the result of a shift in the onset of aging rather than the pace of aging. "What we have observed in BRASTO mice is a delay in the time when age-related decline begins, so while the rate of aging does not change, aging and the risk of cancer has been postponed."Having narrowed control of aging to the brain, Imai's team then traced the control center of aging regulation to two areas of the hypothalamus called the dorsomedial and lateral hypothalamic nuclei. They then were able to identify specific genes within those areas that partner with Sirt1 to kick off the neural signals that elicit the physical and behavioral responses observed."We found that overexpression of Sirt1 in the brain leads to an increase in the cellular response of a receptor called orexin type 2 receptor in the two areas of the hypothalamus," said first author Akiko Satoh, PhD, a postdoctoral staff scientist in Imai's lab."We have demonstrated that the increased response by the receptor initiates signaling from the hypothalamus to skeletal muscles," said Satoh. She noted that the mechanism by which the signal is specifically directed to skeletal muscle remains to be discovered.According to Imai, the tight association discovered between Sirt1-prompted brain activation and the regulation of aging and longevity raises the tantalizing possibility of a "control center of aging and longevity" in the brain, which could be manipulated to maintain youthful physiology and extend life span in other mammals as well.
|
Genetically Modified
| 2,013 |
September 3, 2013
|
https://www.sciencedaily.com/releases/2013/09/130903091044.htm
|
Scientists discover new bat species in West Africa
|
An international team of scientists, including biologists from, the University of York, has discovered five new species of bats in West Africa.
|
The team, which also included researchers from the Czech University of Life Sciences and the Academy of Sciences, Charles University in the Czech Republic, discovered a wealth of unexpected diversity among Vesper bats in Senegal.During seven expeditions to the Niokolo-Koba National Park in south-eastern Senegal, and subsequent genetic analysis, the scientists discovered that five species of bats looked similar to other populations in Africa, but differed significantly genetically from them.Taxonomists are now working on describing formally these new species -- Vesper bats (Vespertilionidae) are already the largest family of bats with more than 400 known species. The research is published in The researchers studied 213 vespertilionid bats from Senegal and identified ten species, five of which were significantly genetically different from their nominate species -- One of the research team, Nancy Irwin, of the Department of Biology at York, says: "The fact that these Senegalese bats are unrelated and are different to their cousins in other parts of Africa, suggests that West Africa may have been isolated in the past and formed a refugium, where populations gradually diverged and even acquired new chromosomal configurations."This exciting finding confirms that West Africa may represent an underestimated bio-geographic hotspot with many more species to discover."
|
Genetically Modified
| 2,013 |
August 29, 2013
|
https://www.sciencedaily.com/releases/2013/08/130829124011.htm
|
Single gene change increases mouse lifespan by 20 percent
|
By lowering the expression of a single gene, researchers at the National Institutes of Health have extended the average lifespan of a group of mice by about 20 percent -- the equivalent of raising the average human lifespan by 16 years, from 79 to 95. The research team targeted a gene called mTOR, which is involved in metabolism and energy balance, and may be connected with the increased lifespan associated with caloric restriction.
|
A detailed study of these mice revealed that gene-influenced lifespan extension did not affect every tissue and organ the same way. For example, the mice retained better memory and balance as they aged, but their bones deteriorated more quickly than normal.This study appears in the Aug. 29 edition of "While the high extension in lifespan is noteworthy, this study reinforces an important facet of aging; it is not uniform," said lead researcher Toren Finkel, M.D., Ph.D., at NIH's National Heart, Lung, and Blood Institute (NHLBI). "Rather, similar to circadian rhythms, an animal might have several organ-specific aging clocks that generally work together to govern the aging of the whole organism."Finkel, who heads the NHLBI's Laboratory of Molecular Biology in the Division of Intramural Research, noted that these results may help guide therapies for aging-related diseases that target specific organs, like Alzheimer's. However, further studies in these mice as well as human cells are needed to identify exactly how aging in these different tissues is connected at the molecular level.The researchers engineered mice that produce about 25 percent of the normal amount of the mTOR protein, or about the minimum needed for survival. The engineered mTOR mice were a bit smaller than average, but they otherwise appeared normal.The median lifespan for the mTOR mice was 28.0 months for males and 31.5 months for females, compared to 22.9 months and 26.5 months for normal males and females, respectively. The mTOR mice also had a longer maximal lifespan; seven of the eight longest-lived mice in this study were mTOR mice. This lifespan increase is one of the largest observed in mice so far.While the genetically modified mTOR mice aged better overall, they showed only selective improvement in specific organs. They generally outperformed normal mice of equivalent age in maze and balance tests, indicating better retention of memory and coordination. Older mTOR mice also retained more muscle strength and posture. However, mTOR mice had a greater loss in bone volume as they aged, and they were more susceptible to infections at old age, suggesting a loss of immune function.In addition to the NHLBI, this study was carried out by intramural researchers at the NIH's National Cancer Institute; National Institute of Diabetes and Digestive and Kidney Diseases; and National Institute on Aging.
|
Genetically Modified
| 2,013 |
August 29, 2013
|
https://www.sciencedaily.com/releases/2013/08/130829093030.htm
|
More efficient production of biofuels from waste with the help of modified yeasts
|
A significant portion of the petroleum consumed by the transport sector must be replaced in the long term by renewable energy. Therefore, it is of the utmost economic and ecological importance to optimise the production of biofuels from renewable raw materials. Researchers from VIB who are associated with KU Leuven have developed yeast strains that produce bio-ethanol from waste with an unprecedented efficiency. As a result, they are well placed to become important players on a global scale in this burgeoning industry.
|
Johan Thevelein (VIB/KU Leuven): "Our new yeast strains come at a good moment because the entire industry of second-generation biofuels has now clearly come quite a bit closer to becoming economically viable. We are working at full capacity to further improve our yeast strains in order to continue to increase the efficiency of the fermentations, and in this way we hope to further strengthen our leadership position in this burgeoning industrial sector."The production of bio-ethanol from waste streams, post-harvest waste (e.g., straw, wheat bran, empty corn husks or corn stalks) and wood (waste) is generally considered to be one of the most sustainable and climate-friendly technologies for producing fuels for the transport sector (road and air traffic). This sector is responsible for more than 10% of the energy consumed in Flanders. In 2011, the portion of energy that was renewable was only 4%, with bio-diesel as the predominant source (86%), followed by bio-ethanol (12%) and then green electricity (2%). In the future, the portion of renewable energy should increase even further to reach the minimum targeted level of 10% renewable energy by 2020.Yeasts are used in the production of bio-ethanol from waste streams. Until recently, there were a number of important obstacles to making efficient bio-ethanol production attainable. One of these was the fact that no one single strain of yeast was capable of converting all of the sugars in the biomass into ethanol. The pentose sugars, in particular, posed a big problem. In recent years, a great deal of progress has been made with genetically modified yeast strains that are also able to ferment pentose sugars, but these laboratory strains did not prove to be entirely suitable for industrial fermentation processes.Mekonnen Demeke and Johan Thevelein (VIB/KU Leuven) have now cleared this obstacle out of the way. They did this by changing the DNA of the best industrial strains of yeast used for bio-ethanol production in such a way that the modified yeast strains were also able to very easily ferment pentose sugars while at the same time becoming even more robust than they were. Their new yeast strains have also proved to efficiently and quickly ferment various types of biomass into bio-ethanol in real conditions, outside of the lab. The interest in this new strain from the industry itself is great, because the efficiency with which these yeast strains make bio-ethanol from waste is unprecedented.
|
Genetically Modified
| 2,013 |
August 28, 2013
|
https://www.sciencedaily.com/releases/2013/08/130828211142.htm
|
Biodiversity in Ontario's Great Lakes region may be greater than we thought
|
Branched Bartonia (
|
Populations of a species are commonly separated by relatively short distances, yet sometimes there is a leap of several hundred kilometres between a species' core set of populations and a subset of populations that are known as disjuncts. In Ontario, Canada, numerous species at risk occur as disjunct populations, most commonly around the Great Lakes region."Though many of these populations are considered regionally threatened because they harbour a relatively small number of individuals, they may not be considered globally threatened because individuals in the core set of populations (usually further south) are often abundant," explains Claudia Ciotir, a co-author of the study and researcher in the Department of Environmental and Life Sciences at Trent University in Peterborough, Ontario. "This means that the core populations can downgrade the conservation status of the disjunct populations, but this downgrading assumes that the disjunct and core populations are closely related to one another.""Our findings provide evidence that the accumulated genetic novelty between disjuncts and their central populations is important and we recommend that genetic novelty should be factored into future conservation policies of Canadian disjunct populations. We show that comparative genetic assessments of disjunct and central populations can provide information that is critical to decisions about conservation management."This divergent evolutionary history may be relevant to a suite of 62 species of disjunct populations residing along the Great Lakes shores. The study "Evolutionary history and conservation value of disjunct
|
Genetically Modified
| 2,013 |
August 27, 2013
|
https://www.sciencedaily.com/releases/2013/08/130827091629.htm
|
Long-term memory stored in the cortex
|
'Where' and 'how' memories are encoded in a nervous system is one of the most challenging questions in biological research. The formation and recall of associative memories is essential for an independent life. The hippocampus has long been considered a centre in the brain for the long-term storage of spatial associations. Now, Mazahir T. Hasan at the Max Planck Institute for Medical Research and José Maria Delgado-Garcìa at the University Pablo de Olavide of Seville, Spain, were able to provide first experimental evidence that a specific form of memory associations is encoded in the cerebral cortex and is not localized in the hippocampus as described in most neuroscience textbooks. The new study is a game changer since it strongly suggests that the motor cortical circuits itself, and not the hippocampus, is used as memory storage.
|
Henry Molaison, known widely as H.M., is a famous name in memory research. Large parts of the American's hippocampus -- the region of the brain that is a major element in learning and memory processes -- were removed in the 1950s in an attempt to cure his epileptic seizures. He subsequently suffered severe memory lapses and was no longer able to remember virtually anything new he had learned. Most scientists thereby concluded that the hippocampus is the site of long-term memory.However, the extent of H.M.'s brain damage was obviously underestimated, because other regions in addition to the hippocampus were also removed or damaged in the surgical procedure. The researchers from Heidelberg and Seville have therefore investigated the learning behaviour of genetically modified mice in which NMDA receptors are turned off only in the motor cerebral cortex. NMDA receptors bind the neurotransmitter glutamate to the synapses and become active when several signals feed into one synapse at the same time. They are the central molecular elements of learning processes, being involved in increasing or decreasing transmission of the signals to synapses.As the new study shows, in the motor cortex this so-called synaptic plasticity no longer functions without the NMDA receptors. The scientists were thus able to rule out the hippocampus or other regions as the cause for their observations. Based on the new findings, it is the cerebral cortex, not the hippocampus that is the storage site for some forms of memory.In behaviour tests, so called eyeblink conditioning, animals with and without NMDA receptors in the primary motor cortex had to learn to link a tone with a subsequent electrical stimulus of the eyelid. This association of two sensory inputs involves the cerebellum which coordinates the necessary movements, as well as the hippocampus and the cerebral cortex, which are important learning and memory centres. "After a learning phase, the animals' reflex is to close their eye when they hear just the tone. Without NMDA receptors in the primary motor cerebral cortex, the genetically modified mice on the other hand cannot remember the connection between the tone and electrical stimulus, and therefore they keep their eyes open despite the tone," explains Mazahir T. Hasan of the Max Planck Institute for Medical Research.The researchers have thus complemented the findings of their Heidelberg-based colleagues that the hippocampus is not the seat of memory. In July 2012, Rolf Sprengel and Peter Seeburg from the Max Planck Institute for Medical Research discovered that mice without NMDA receptors in the hippocampus are still quite capable of learning. "We now think that the hippocampus provides the necessary environmental cues, which are transmitted to the cortex where learning-dependent associations take place. Memories are thus stored at various sites in the cerebral cortex on a long-term basis," explains Hasan.The findings of Hasan and Delgado-Garcìa thus represent a paradigm-shift in memory research as they make clear that the cerebral cortex is the brain region where memory associations are linked and stored -- not the hippocampus. An advanced and detailed knowledge of the mechanisms for the acquisition, consolidation, and recall of associations in the brain is the prerequisite for a therapeutic treatment of the devastating effects of memory loss in various neurological diseases, such as amnesia, Alzheimer`s disease and dementia.
|
Genetically Modified
| 2,013 |
August 15, 2013
|
https://www.sciencedaily.com/releases/2013/08/130815145034.htm
|
New possibilities for efficient biofuel production
|
Limited availability of fossil fuels stimulates the search for different energy resources. The use of biofuels is one of the alternatives. Sugars derived from the grain of agricultural crops can be used to produce biofuel but these crops occupy fertile soils needed for food and feed production.
|
Fast growing plants such as poplar, eucalyptus, or various grass residues such as corn stover and sugarcane bagasse do not compete and can be a sustainable source for biofuel. An international collaboration of plant scientists from VIB and Ghent University (Belgium), the University of Dundee (UK), The James Hutton Institute (UK) and the University of Wisconsin (USA) identified a new gene in the biosynthetic pathway of lignin, a major component of plant secondary cell walls that limits the conversion of biomass to energy.These findings published online in this week's issue of"This exciting, fundamental discovery provides an alternative pathway for altering lignin in plants and has the potential to greatly increase the efficiency of energy crop conversion for biofuels," said Sally M. Benson, director of Stanford University's Global Climate and Energy Project. "We have been so pleased to support this team of world leaders in lignin research and to see the highly successful outcome of these projects."To understand how plant cells can deliver fuel or plastics, a basic knowledge of a plant's cell wall is needed. A plant cell wall mainly consists of lignin and sugar molecules such as cellulose. Cellulose can be converted to glucose which can then be used in a classical fermentation process to produce alcohol, similar to beer or wine making. Lignin is a kind of cement that embeds the sugar molecules and thereby gives firmness to plants. Thanks to lignin, even very tall plants can maintain their upright stature. Unfortunately, lignin severely reduces the accessibility of sugar molecules for biofuel production. The lignin cement has to be removed via an energy-consuming and environmentally unfriendly process. Plants with a lower amount of lignin or with lignin that is easier to break down can be a real benefit for biofuel and bioplastics production. The same holds true for the paper industry that uses the cellulose fibres to produce paper.For many years researchers have been studying the lignin biosynthetic pathway in plants. Increasing insight into this process can lead to new strategies to improve the accessibility of the cellulose molecules. Using the model plant Arabidopsis thaliana, an international research collaboration between VIB and Ghent University (Belgium), the University of Dundee (UK), the James Hutton Institute (UK) and the University of Wisconsin (USA) has now identified a new enzyme in the lignin biosynthetic pathway. This enzyme, caffeoyl shikimate esterase (CSE), fulfils a central role in lignin biosynthesis. Knocking-out the CSE gene, resulted in 36% less lignin per gram of stem material. Additionally, the remaining lignin had an altered structure. As a result, the direct conversion of cellulose to glucose from un-pretreated plant biomass increased four-fold, from 18% in the control plants to 78% in the cse mutant plants.These new insights, published this week online in Science Express, can now be used to screen natural populations of energy crops such as poplar, eucalyptus, switchgrass or other grass species for a non-functional CSE gene. Alternatively, the expression of CSE can be genetically engineered in energy crops. A reduced amount of lignin or an adapted lignin structure can contribute to a more efficient conversion of biomass to energy.This research was co-financed by the multidisciplinary research partnership 'Biotechnology for a sustainable economy' of Ghent University, the DOE Great Lakes Bioenergy Research Center and the 'Global Climate and Energy Project' (GCEP). Based at Stanford University, the Global Climate and Energy Project is a worldwide collaboration of premier research institutions and private industry that supports research on technologies that significantly reduce emissions of greenhouse gases, while meeting the world's energy needs.
|
Genetically Modified
| 2,013 |
August 15, 2013
|
https://www.sciencedaily.com/releases/2013/08/130815105152.htm
|
Researchers report a critical role for the complement system in early macular degeneration
|
In a study published on line this week in the journal
|
Macular degenerations, which occur in several forms, are important causes of vision loss. Juvenile or early-onset macular degeneration includes several inherited disorders that can affect children and young adults. In contrast, age-related macular degeneration (AMD) affects older individuals; it is the leading cause of blindness for individuals over 65 years of age in developed countries, and its prevalence is increasing worldwide. Both inherited macular degeneration and AMD lead to the loss of central vision. While therapies exist for some forms of late AMD, and nutritional supplements can slow the progression of early AMD for some patients, improved therapies to prevent vision loss from these disorders are needed.This is the first report to demonstrate a role for the complement system in an inherited macular degeneration. Previous genetic studies have shown that variants in the genes that encode several complement system components are important risk factors for AMD. Based on this, drugs that inhibit specific complement system activities are being tested clinically as treatments for AMD. However, it is not entirely clear how alterations in complement system components lead to AMD.The new results reported suggest that complement activation by abnormalities in the extracellular matrix or the scaffold secreted by retinal cells plays an important role in the formation of basal deposits, one of the earliest stages of macular degeneration. Basal deposits are precursors of drusen, which appear as spots in the retina on clinical examination, and are accumulations of proteins and lipids outside the retinal cells; their presence is the first clinical indication of a risk of developing macular degeneration.The findings are important because they suggest that inherited macular degenerations share common features with AMD, such as a complement-mediated response to abnormal extracellular matrix. The results also suggest that alterations in the activity of the complement system are involved in the earliest stages of disease pathogenesis. This finding has important implications for the use of drugs that modulate the complement system for treating macular degenerations.For these studies, the investigators used a mouse model of the inherited macular dystrophy Doyne Honeycomb Retinal Dystrophy/Malattia Leventinese (DHRD/ML) which is caused by the p.Arg345Trp mutation in the EFEMP1 gene. This mutation leads to extensive drusen in patients with DHRD/ML, and the gene targeted Efemp1R345W/R345W mice develop extensive basal deposits.As a first step in their studies, Dr. Garland and colleagues used proteomic techniques to identify the proteins present in the basal deposits of the Efemp1R345W/R345W mice. Like they do in people, these deposits form between the retinal pigment epithelial cells and their basement membrane, which is called Bruch's membrane and is composed of extracellular matrix. These studies showed that the basal deposits are composed of normal extracellular matrix components that are present in abnormal amounts. This is logical because the EFEMP1 protein is secreted by retinal cells and is thought to be required for maturation of elastin fibers, which are part of Bruch's membrane.The proteomic analyses also suggest that the altered extracellular matrix stimulates a local immune response, including activation of the complement system. The complement system is part of our innate immune system, and helps fend off infections, but under certain circumstances can also lead to cell and tissue damage.The Mass. Eye and Ear team applied the power of mouse genetics to study the role of complement in basal deposit formation, and generated Efemp1R345W/R345W:C3-/- double mutant mice, which have the disease-causing mutation in Efemp1 and also lack the key complement component C3. Without C3, the complement system cannot be activated. In contrast to their single mutant Efemp1-R345W cousins, the double mutant Efemp1R345W/R345W:C3-/- mice did not develop basal deposits, demonstrating that the complement system is required for formation of basal deposits.The investigators plan to continue their studies to help identify additional treatments to prevent vision loss from macular degenerations.
|
Genetically Modified
| 2,013 |
August 8, 2013
|
https://www.sciencedaily.com/releases/2013/08/130808124044.htm
|
Scientists watch live brain cell circuits spark and fire
|
Scientists used fruit flies to show for the first time that a new class of genetically engineered proteins can be used to watch electrical activity in individual brain cells in live brains. The results, published in
|
Brain cells use electricity to control thoughts, movements and senses. Ever since the late nineteenth century, when Dr. Luigi Galvani induced frog legs to move with electric shocks, scientists have been trying to watch nerve cell electricity to understand how it is involved in these actions. Usually they directly mo nitor electricity with cumbersome electrodes or toxic voltage-sensitive dyes, or indirectly with calcium detectors. This study, led by Michael Nitabach, Ph.D., J.D., and Vincent Pieribone, Ph.D., at the Yale School of Medicine, New Haven, CT, shows that a class of proteins, called genetically encoded fluorescent voltage indicators (GEVIs), may allow researchers to watch nerve cell electricity in a live animal.Dr. Pieribone and his colleagues helped develop ArcLight, the protein used in this study. ArcLight fluoresces, or glows, as a nerve cell's voltage changes and enables researchers to watch, in real time, the cell's electrical activity. In this study, Dr. Nitabach and his colleagues engineered fruit flies to express ArcLight in brain cells that control the fly's sleeping cycle or sense of smell. Initial experiments in which the researchers simultaneously watched brain cell electricity with a microscope and recorded voltage with electrodes showed that ArcLight can accurately monitor electricity in a living brain. Further experiments showed that ArcLight illuminated electricity in parts of the brain that were previously inaccessible using other techniques. Finally, ArcLight allowed the researchers to watch brain cells spark and fire while the flies were awakening and smelling. These results suggest that in the future neuroscientists may be able to use ArcLight and similar GEVIs in a variety of ways to map brain cell circuit activity during normal and disease states.This study was supported by grants from NINDS (NS055035, NS056443, NS083875, NS057631, NS083875) and NIGMS (GM098931).GEVIs and other sensors are being developed by a group of NINDS-funded researchers who are part of the Fluorogenetic Voltage Sensors Consortium. The consortium was partly funded with grants from the American Recovery and Reinvestment Act.For more information go to: Video:
|
Genetically Modified
| 2,013 |
August 5, 2013
|
https://www.sciencedaily.com/releases/2013/08/130805152420.htm
|
Could discovery lead to end of sunburn pain?
|
The painful, red skin that comes from too much time in the sun is caused by a molecule abundant in the skin's epidermis, a new study shows.
|
Blocking this molecule, called TRPV4, greatly protects against the painful effects of sunburn. The results were published the week of Aug. 5 in the "We have uncovered a novel explanation for why sunburn hurts," said Wolfgang Liedtke, M.D., Ph.D., one of the senior authors of the study and associate professor of neurology and neurobiology at Duke University School of Medicine. "If we understand sunburn better, we can understand pain better because what plagues my patients day in and day out is what temporarily affects otherwise healthy people who suffer from sunburn."The vast majority of sunburns are caused by ultraviolet B or UVB radiation. In moderation, this component of sunlight does the body good, giving a daily dose of vitamin D and perhaps improving mood. But if people get too much, it can damage the DNA in their skin cells and increase their susceptibility to cancer. Sunburns are nature's way of telling people to go inside and avoid further damage.Liedtke worked together with a multi-institutional team of researchers: Elaine Fuchs, Ph.D., a professor at Rockefeller University and an investigator with the Howard Hughes Medical Institute and skin biologist; and Martin Steinhoff, M.D., Ph.D., professor of dermatology and surgery at the University of California in San Francisco who is known for his studies on sensory function of skin in health and disease. Together, they investigated whether the TRPV4 molecule, which is abundant in skin cells and has been shown to be involved in other pain processes, might play a role in the pain and tissue damage caused by UVB over-exposure. TRPV4 is an ion channel, a gateway in the cell membrane that rapidly lets in positively charged ions such as calcium and sodium.First, the researchers built a mouse model that was missing TRPV4 only in the cells of the epidermis, the outermost layer of the skin. They took these genetically engineered mice and their normal counterparts and exposed their hind paws -- which most resemble human skin -- to UVB rays. The hind paws of the normal mice became hypersensitive and blistered in response to the UVB exposure, while those of the mutant mice showed little sensitization and tissue injury.Next, they used cultured mouse skin cells to dissect the activities of TRPV4. Using a device engineered by Nan Marie Jokerst, Ph.D., a professor of electrical and computer engineering at Duke's Pratt School of Engineering, the researchers showed that UVB caused calcium to flow into the skin cells, but only when the TRPV4 ion channel was present.Further molecular analysis uncovered the entire sequence of events in this pathway, with each event affecting the next: UVB exposure activates TRPV4, which causes the influx of calcium ions, which brings in another molecule called endothelin, which triggers TRPV4 to send more calcium into the cells. Endothelin is known to cause pain in humans and also evokes itching, which could explain the urge sunburned patients feel to scratch their skin.To test whether these findings in mice and mouse cells have human relevance, the researchers used human skin samples to successfully demonstrate increased activation of TRPV4 and endothelin in human epidermis after UVB exposure.To see if they could block this novel pain pathway, the researchers used a pharmaceutical compound called GSK205 that selectively inhibits TRPV4. They dissolved this compound into a solution of alcohol and glycerol -- basically, skin disinfectant -- and then applied it to the hind paws of normal mice. The researchers found that the mice treated with the compound were again largely resistant to the pain-inducing and skin-disrupting effects of sunburn. Similarly, when they administered the compound to mouse skin cells in culture, they found that it stopped the UV-triggered influx of calcium ions into the cells."The results position TRPV4 as a new target for preventing and treating sunburn, and probably chronic sun damage including skin cancer or skin photo-aging, though more work must be done before TRPV4 inhibitors can become part of the sun defense arsenal, perhaps in new kinds of skin cream, or to treat chronic sun damage," said Steinhoff, co-senior author of the study."I think we should be cautious because we want to see what inhibition of TRPV4 will do to other processes going on in the skin," Liedtke added. "Once these concerns will be addressed, we will need to adapt TRPV4 blockers to make them more suitable for topical application. I could imagine it being mixed with traditional sunblock to provide stronger protections against UVB exposure."The research was supported by grants from the National Institutes of Health (DE018549, DE018549S1,DE018549S2, AR059402, AR31737, AR050452, and P41 EB015897), and the German Research Foundation (DFG; DFG STE 1014/2-2, DFG Ce165/1-1, DFG Ke1672/1-1).
|
Genetically Modified
| 2,013 |
July 31, 2013
|
https://www.sciencedaily.com/releases/2013/07/130731105600.htm
|
Insect-inspired super rubber moves toward practical uses in medicine
|
The remarkable, rubber-like protein that enables dragonflies, grasshoppers and other insects to flap their wings, jump and chirp has major potential uses in medicine, scientists conclude in an article in the journal
|
Kristi Kiick and colleagues explain that scientists discovered resilin a half-century ago in the wing hinges of locusts and elastic tendons of dragonflies. The extraordinary natural protein tops the best synthetic rubbers. Resilin can stretch to three times its original length, for instance, and then spring back to its initial shape without losing its elasticity, despite repeated stretching and relaxing cycles. That's a crucial trait for insects that must flap or jump millions of times over their lifetimes. Scientists first synthesized resilin in 2005 and have been striving to harness its properties in medicine.Kiick's team describes how their own research and experiments by other scientists are making major strides toward practical applications of resilin. Scientists have modified resilin with gold nanoparticles for possible use in diagnostics, engineered mosquito-based resin to act like human cartilage and developed a hybrid material for cardiovascular applications. "This increasing amount of knowledge gained from studies on natural resilin and resilin-like polypeptides continues to inspire new designs and applications of recombinant resilin-based biopolymers in biomedical and biotechnological applications," the scientists state.
|
Genetically Modified
| 2,013 |
July 25, 2013
|
https://www.sciencedaily.com/releases/2013/07/130725152138.htm
|
Broad-scale genome tinkering with help of an RNA guide: Biotechnology tool borrowed from pathogenic bacteria
|
Duke researchers have devised a way to quickly and easily target and tinker with any gene in the human genome. The new tool, which builds on an RNA-guided enzyme they borrowed from bacteria, is being made freely available to researchers who may now apply it to the next round of genome discovery.
|
The new method also has obvious utility for gene therapy and for efforts to reprogram stem or adult cells into other cell types -- for example, to make new neurons from skin cells."We have the genome sequence and we know what all the parts are, but we are still in need of methods to manipulate it easily and precisely," says assistant professor Charles Gersbach, of Duke's Pratt School of Engineering and the Duke Institute for Genome Sciences & Policy. "That's where this engineering tool comes in."Gersbach's team had already been in the business of tinkering with the genome using specially engineered proteins, but the process was difficult and slow. It was hard to imagine how to scale it up for the investigation of hundreds or even thousands of genes in the way genome scientists really wanted to do. "That's where the conversation always broke down," he says.Then, he and post-doctoral researcher Pablo Perez-Pinera found out about an RNA-guided protein called Cas9 found in a Streptococcus bacteria. The bacteria rely on Cas9 as part of an adaptive immune system to defend themselves against infection by viruses, cutting out a piece of the viral DNA and inserting it into their own genome for recognition of future infection. Other scientists then showed that those immune system components could function inside human cells.Gersbach's team recognized the RNA-guided nature of this system as a potential game-changer for the gene engineering work they do.In the study now reported in In other words, it works, and it works on genes that matter from a clinical perspective. In principle, the RNA-guided tool could be used to modify or influence any gene anywhere in the genome.Gersbach now hopes to apply the new tool along with collaborators in the IGSP to investigate the functions of thousands of sites across the genome. With tissue engineer Farshid Guilak, a professor of engineering and orthopaedic surgery, he will continue to work on its application in the fight against inflammatory and autoimmune diseases such as arthritis."This simple and versatile tool makes it easy for anyone to do this," Gersbach says.
|
Genetically Modified
| 2,013 |
July 18, 2013
|
https://www.sciencedaily.com/releases/2013/07/130718101343.htm
|
This fungus cell only looks like the 405 freeway
|
No, those are not cars darting along a busy highway. The glowing specks you're seeing in this video are millions of nuclei flowing through the tube-like filaments, or hyphae, of a single fungus cell.
|
The "It's complex, beautiful and so dynamic," said Roper, an assistant professor of mathematics and the lead author of two new studies that cast light on how cells ingeniously adapt to physical challenges.The research, conducted with a group led by UC Berkeley life scientist Louise Glass, focused on the fungus Having genetically different nuclei within a single cell benefits a fungus by making it more infectious, Roper said. However, this advantage only works if each part of the fungus contains a mixture of each type of genetically different nuclei.This is where the traffic-like flow comes in. As the cell's tubular filaments containing the nuclei grow, the flow process continuously distributes the different nuclei throughout the fungus cell, keeping them well mixed for maximum advantage."The fungus is keeping all of its nuclei very well mixed. If the nuclei weren't all traveling along complex highways, they would separate out as the fungus grows," Roper said. "As you go deeper into the colony, the flow gets more complicated. It's like a traffic system. It starts to look like the 405 Freeway. As the nuclei move around, sometimes they find shortcuts. Sometimes there are traffic jams."But what, precisely, conducts this nuclear traffic?The flow, Roper and his colleagues discovered, is "propelled by pressure gradients across the colony in a complicated, mutely-directional network." By demonstrating how a variety of different pressures throughout the colony determine the speed and direction of flow, Roper illustrates how the apparently random network of tubes is actually exquisitely engineered to optimally mix the nuclei."To understand whether this mixing is engineered into the fungus, we need to figure out mathematically what the alternatives are," said Roper, who received an Alfred P. Sloan Foundation Research Fellowship last year.To that end, the researchers studied the geometry of the network and then compared it to alternative, mathematically generated networks to see whether the fungus' natural network was optimal for mixing the genetically different nuclei. They found that it was.To confirm their finding, they muted a gene in the fungus cell, changing the network. They found that in the genetically altered network, the nuclei tended to segregate out -- that is, nuclei that were the same genetically tended to group together rather than mix."The flow helps the fungus tolerate being genetically diverse within itself," Roper said. "That is not something any other class of organism does. There are millions of species of fungi, and many of them have this internal genetic diversity. In a person, we have a word for genetic diversity: cancer. But the fungus doesn't mind; it helps the fungus."Roper's goal is to apply mathematics to make new discoveries about how cells solve physical challenges. Those challenges -- and the solutions organisms have found for them -- have left deep imprints on how life has evolved.For instance, how and why did multicellular life arise? To help answer that, Roper has been studying an organism in a family known as the choanoflagellates -- the closest single-celled cousins of multicellular animals. Scientists believe that something remarkable must have happened following the divergence of choanoflagellates from the multicellular animals to create conditions favoring complex multicellular life.Interestingly, it was recently discovered that one species of the single-celled choanoflagellates -- "It's like watching a fish walk onto land -- seeing evolution in action," he said. "If we can understand the conditions that make this transition occur, maybe we can understand why multicellularity arose among animals in the first place."Is there any advantage to A single cell's tail, or flagellum, allows the cell to swim and helps bring toward the cell fluid containing the bacteria on which it feeds. Generally, multicellular organisms can swim faster and therefore encounter more food.But multicellular Although this "multiple oars" chaos does hinder the colony's ability to swim, Roper said, it actually helps to bring distant bacteria-containing fluid to the colony much faster than is possible with a single-celled "It is not at all obvious from the biology that there would be any benefit to being multicellular," Roper said. "But we found a benefit."Co-authors of this research are Patrick Hickey, a postdoctoral scholar in Roper's group at UCLA; Anna Simonin of Australia's University of Western Sydney; and Abby Leeder, N. Louise Glass, Mark J. Dayel, Rachel E. Pepper and M.A.R. Koehl of UC Berkeley.
|
Genetically Modified
| 2,013 |
July 16, 2013
|
https://www.sciencedaily.com/releases/2013/07/130716080026.htm
|
RNA-interference pesticides will need special safety testing
|
Standard toxicity testing is inadequate to assess the safety of a new technology with potential for creating pesticides and genetically modifying crops, according to a Forum article published in the August issue of
|
RNA interference is a natural process that affects the level of activity of genes in animals and plants. Agricultural scientists have, however, successfully devised artificial "interfering RNAs" that target genes in insect pests, slowing their growth or killing them. The hope is that interfering RNAs might be applied to crops, or that crops might be genetically engineered to make interfering RNAs harmful to their pests, thus increasing crop yields.The safety concern, as with other types of genetic modification and with pesticides generally, is that the artificial interfering RNAs will also harm desirable insects or other animals. And the way interfering RNA works means that simply testing for lethality might not detect important damaging effects. For example, an interfering RNA might have the unintended effect of suppressing the action of a gene needed for reproduction in a beneficial species. Standard laboratory testing would detect no harm, but there could be ecological disruption in fields because of the effects on reproduction.Lundgren and Duan suggest that researchers investigating the potential of interference RNA pesticides create types that are designed to be unlikely to affect non-target species. They also suggest a research program to evaluate how the chemicals move in real-life situations. If such steps are taken, Lundgren and Duan are optimistic that the "flexibility, adaptability, and demonstrated effectiveness" of RNA interference technology mean it will have "an important place in the future of pest management."
|
Genetically Modified
| 2,013 |
July 14, 2013
|
https://www.sciencedaily.com/releases/2013/07/130714160607.htm
|
Sexual reproduction only second choice for powdery mildew
|
Genetically, powdery mildew is perfectly adapted to its host plants. Evidently, sexual reproduction and new combinations of genetic material usually prove disadvantageous for the fungus. Asexual reproduction, however, is considerably more successful for mildew, as plant biologists from the University of Zurich and the Max Planck Institute for Plant Breeding Research in Cologne demonstrate. Nonetheless, the fungus still allows itself a sexual reproduction cycle.
|
Powdery mildew is one of the most dreaded plant diseases: The parasitic fungus afflicts crops such as wheat and barley and is responsible for large harvest shortfalls every year. Beat Keller and Thomas Wicker, both plant biologists from the University of Zurich, and their team have been analyzing the genetic material of wheat mildew varieties from Switzerland, England and Israel while the team headed by Paul Schulze-Lefert at the Max Planck Institute for Plant Breeding Research in Cologne studies the genetic material of barley mildew.The results recently published in Like other fungi, mildew reproduces in two ways: Sexually, where the genetic material is recombined, and asexually, where the offspring and the mother fungus are genetically identical. The researchers now demonstrate that the success of the two reproduction methods could not be more different: "Mildew fungi detected on afflicted host plants have only successfully reproduced sexually every few centuries, primarily reproducing asexually instead," explains Wicker.This baffling fact has more deep-rooted causes: In order to infect the host plant, the mildew fungus needs to be able to successfully disable the plant's defense mechanisms -- the parasite has to be perfectly adapted to its host. "In a parasite-host situation, new combinations of genetic material are a disadvantage for the parasite as the adaptation to the host and its defense mechanisms deteriorates as a result." Genetically identical offspring of successful mildew fungi that have already been able to infect the host plant, however, have the ideal genetic prerequisites to be able to attack a host themselves. According to Schulze-Lefert, wheat and barley mildew offspring from asexual reproduction are normally more successful than their sexually reproduced counterparts. Asexual reproduction as a success model seems to be characteristic of many parasitic fungi, including those that afflict humans, such as athlete's foot.Based on the gene analyses, the scientists were also able to prove that mildew already lived parasitically on the ancestral form of wheat 10,000 years ago, before wheat were actually domesticated as crops. None of the subsequent genetic changes in the crops due to breeding or spontaneous mutations was ever able to keep the mildew fungus away from wheat in the longer term. And this is precisely where the advantage of sexual reproduction lies and why the usually unsuccessful sexual reproduction cycle is still worthwhile for the mildew fungus: Wheat and mildew are embroiled in a permanent evolutionary arms race. "If wheat improves its defense mechanisms against the parasites, the fungus has to be able to follow suit or it has lost," explains Wicker. "That's only possible by recombining the genetic material; in other words, sexual reproduction."Evidently, a sexual exchange and mixtures of the genetic material of different mildew varieties have occurred several times in the course of the millennia, giving rise to new mildew varieties that were able to attack new sorts of wheat. The scientists suspect that the grain trade in the ancient world was partly responsible for the emergence of new mildew varieties.
|
Genetically Modified
| 2,013 |
June 30, 2013
|
https://www.sciencedaily.com/releases/2013/06/130630145008.htm
|
Different neuronal groups govern right-left alternation when walking
|
Scientists at Karolinska Institutet in Sweden have identified the neuronal circuits in the spinal cord of mice that control the ability to produce the alternating movements of the legs during walking. The study, published in the journal
|
Most land animals can walk or run by alternating their left and right legs in different coordinated patterns. Some animals, such as rabbits, move both leg pairs simultaneously to obtain a hopping motion. In the present study, the researchers Adolfo Talpalar and Julien Bouvier together with professor Ole Kiehn and colleagues, have studied the spinal networks that control these movement patterns in mice. By using advanced genetic methods that allow the elimination of discrete groups of neurons from the spinal cord, they were able to remove a type of neurons characterized by the expression of the gene Dbx1."It was classically thought that only one group of nerve cells controls left right alternation," says Ole Kiehn who leads the laboratory behind the study at the Department of Neuroscience. "It was then very interesting to find that there are actually two specific neuronal populations involved, and on top of that that they each control different aspect of the limb coordination."Indeed, the researchers found that the gene Dbx1 is expressed in two different groups of nerve cells, one of which is inhibitory and one that is excitatory. The new study shows that the two cellular populations control different forms of the behaviour. Just like when we change gear to accelerate in a car, one part of the neuronal circuit controls the mouse's alternating gait at low speeds, while the other population is engaged when the animal moves faster. Accordingly, the study also show that when the two populations are removed altogether in the same animal, the mice were unable to alternate at all, and hopped like rabbits instead.There are some animals, such as desert mice and kangaroos, which only hop. The researchers behind the study speculate that the locomotive pattern of these animals could be attributable to the lack of the Dbx1 controlled alternating system.
|
Genetically Modified
| 2,013 |
June 26, 2013
|
https://www.sciencedaily.com/releases/2013/06/130626183932.htm
|
Hold the medicinal lettuce
|
In 2011 and 2012, research from China's Nanjing University made international headlines with reports that after mice ate, bits of genetic material from the plants they'd ingested could make it into their bloodstreams intact and turn the animals' own genes off. The surprising results from Chen-Yu Zhang's group led to speculation that genetic illness might one day be treated with medicinal food, but also to worry that genetically modified foods might in turn modify consumers in unanticipated ways.
|
Now, though, a research team at Johns Hopkins reports that Zhang's results were likely a false positive that resulted from the technique his group used. The new study, the Johns Hopkins group says, bolsters the case of skeptics who argued that genetic material from food would have little chance of surviving the digestive system, much less crossing the intestinal lining to enter the bloodstream. The study appears in the July issue of "It's disappointing in a sense -- it would open up so many therapeutic possibilities if microRNAs from food really could get into our blood and regulate our genes," says Kenneth Witwer, Ph.D., of the Johns Hopkins University School of Medicine's Institute for Basic Biomedical Sciences, who led the new study. But beyond the fact that people won't be picking up prescription lettuce at the pharmacy anytime soon, he adds, the larger lesson is that scientific research's capacity for self-correction is alive and well.Witwer said his group was intrigued by the earlier results, in which Zhang's group focused on microRNAs, molecules that are a chemical cousin of DNA. Rather than storing genetic information as DNA does, their primary role is to intervene in so-called "gene expression," the process of using genes' blueprints to build proteins. Because they affect whether and how much genes are actually used, microRNAs wield tremendous power, Witwer notes, "so it was startling to think that microRNAs from plants could get into the bloodstream, get into tissues, and regulate genes in those tissues."Witwer teamed up with colleagues to check the results with a similar experiment of their own. They bought soy-based smoothies at a grocery store and tested their microRNA content, then fed the smoothies to macaques and took samples of the animals' blood.Knowing that the concentrations of any plant microRNAs in the blood would be too low to measure directly, they used a common technique called polymerase chain reaction (PCR) to bring up the concentration of the genetic material. PCR is designed so that only certain fragments of genetic material in a sample -- the ones researchers choose to target -- will be copied. Zhang's studies had also used PCR to look for plant microRNAs.Just as Zhang had, the Johns Hopkins team found what appeared to be the targeted plant microRNAs in the macaques' blood. But when they ran the experiment several times, they got highly variable results: Sometimes the microRNAs were present in low concentrations, and sometimes not at all. In addition, the samples from before the macaques drank the smoothies were just as likely to have the microRNAs as were the post-smoothie samples -- a result that just didn't make sense if the source of the microRNAs was the plant material in the drinks.To Witwer, the results indicated that what he was seeing was not the targeted plant microRNAs, but fragments of the macaques' own genetic material that were similar enough to the targeted segments that the PCR copied them at low levels.To test this, the team used a new technique in which PCR takes place in tiny aerosolized droplets rather than in a test tube. The advantage, Witwer says, is that by effectively running tens or hundreds of thousands of reactions at the same time, researchers can see whether the outcomes of those reactions are consistent -- in other words, whether the results are meaningful or just a fluke. In this case, the results were all over the place, indicating that plant microRNAs weren't really present.At the same time, Witwer cautions, it remains possible that very low levels of microRNAs could enter the blood. Even if this happened, though, he says it is unlikely that such small numbers of molecules could affect gene expression. Additional studies will be needed to determine whether low-level transfer occurs and whether any plant RNAs serve a function in the body.
|
Genetically Modified
| 2,013 |
June 26, 2013
|
https://www.sciencedaily.com/releases/2013/06/130626153920.htm
|
Cloning mice: For the first time, a donor mouse has been cloned using a drop of peripheral blood from its tail
|
From obesity to substance abuse, from anxiety to cancer, genetically modified mice are used extensively in research as models of human disease. Researchers often spend years developing a strain of mouse with the exact genetic mutations necessary to model a particular human disorder. But what if that mouse, due to the mutations themselves or a simple twist of fate, was infertile?
|
Currently, two methods exist for perpetuating a valuable strain of mouse. If at least one of the remaining mice is male and possesses healthy germ cells, the best option is intracytoplasmic sperm injection (ICSI), an in vitro fertilization procedure in which a single sperm is injected directly into an egg.However, if the remaining mice cannot produce healthy germ cells, or if they are female, researchers must turn to cloning. Somatic-cell nuclear transfer (SCNT) produces cloned animals by replacing an oocyte's nucleus with that of an adult somatic cell. An early version of this process was used to produce Dolly the sheep in 1996.Since then, SCNT techniques have continued to advance. Earlier this year, researchers at the RIKEN Center for Developmental Biology in Kobe, Japan, even devised a technique to avoid the diminishing returns of recloning the same cell; success rates increased from the standard three percent in first-generation clones to ten percent in first-generation and 14 percent in higher-generation clones.The type of somatic cell used for this process is critical and depends largely on its efficiency in producing live clones, as well as its ease of access and readiness for experimental use. While cumulus cells, which surround oocytes in the ovarian follicle and after ovulation, are currently the preferred cell type, Drs. Satoshi Kamimura, Atsuo Ogura, and colleagues at the RIKEN BioResource Center in Tsukuba, Japan, questioned whether white blood cells (a.k.a., leukocytes) collected from an easily accessed site, such as a tail, would be effective donor cells. Such cells would allow for repeated sampling with minimal risk to the donor mouse.There are five different types of white blood cells and, as expected, the researchers found that lymphocytes were the type that performed the most poorly: only 1.7 percent of embryos developed into offspring. The physically largest white blood cells, and thus the easiest to filter from the blood sample, were granulocytes and monocytes. The nuclei of these cells performed better, with 2.1 percent of the embryos surviving to term, compared to 2.7 percent for the preferred cell type, cumulus cells.The granulocytes' performance was poorer than expected due to a much higher rate of fragmentation in early embryos (22.6 percent): twofold higher than that of lymphocyte cloning and fivefold higher than cumulus cell cloning. The researchers were unable to determine what could be causing the fragmentation and intend to perform further studies to improve the performance of granulocyte donor cells.Although the blood cells tested did not surpass the success rate of cumulus cells in this study, the researchers have demonstrated, for the first time, that mice can be cloned using the nuclei of peripheral blood cells. These cells may be used for cloning immediately after collection with minimal risk to the donor, helping to generate genetic copies of mouse strains that cannot be preserved by other assisted reproduction techniques.
|
Genetically Modified
| 2,013 |
June 20, 2013
|
https://www.sciencedaily.com/releases/2013/06/130620111232.htm
|
'Forrest Gump' mice show too much of a good thing, can be bad
|
A line of genetically modified mice that Western University scientists call "Forrest Gump" because, like the movie character, they can run far but they aren't smart, is furthering the understanding of a key neurotransmitter called acetylcholine (ACh). Marco Prado, PhD, and his team at Robarts Research Institute say the mice show what happens when too much of this neurotransmitter becomes available in the brain. Boosting ACh is a therapeutic target for Alzheimer's disease because it's found in reduced amounts when there's cognitive failure.
|
Prado's research is published in the "We wanted to know what happens if you have more of the gene which controls how much acetylcholine is secreted by neurons," says Prado, a Robarts scientist and professor in the Departments of Physiology and Pharmacology and Anatomy and Cell Biology at Western's Schulich School of Medicine & Dentistry. "The response was the complete opposite of what we expected. It's not a good thing. Acetylcholine release was increased threefold in these mice, which seemed to disturb cognitive function. But put them on a treadmill and they can run twice as far as normal mice before tiring. They're super-athletes." In addition to its function in modulating cognitive abilities, ACh drives muscle contraction which allowed for the marked improvement in motor endurance.One of the tests the scientists, including first author Benjamin Kolisnyk, used is called the touch screen test for mice (video is available showing the test) which uses technology similar to a tablet. After initiating the test, the mice have to scan five different spots on the touch screen to see a light flash, and then run and touch that area. If they get it right they get a reward. Compared to the control mice, the "Forrest Gump" mice failed miserably at the task. The researchers found the mice, which have the scientific name ChAT-ChR2-EYFP, had terrible attention spans, as well as dysfunction in working memory and spatial memory.Prado interprets the research as showing ACh is very important for differentiating cues. So if your brain is presented with a lot of simultaneous information, it helps to pick what's important. But when you flood the brain with ACh, your brain loses the ability to discern what's relevant. This study was funded mainly by the Canadian Institutes of Health Research.
|
Genetically Modified
| 2,013 |
June 12, 2013
|
https://www.sciencedaily.com/releases/2013/06/130612132532.htm
|
Fingernails reveal clues to limb regeneration
|
Mammals possess the remarkable ability to regenerate a lost fingertip, including the nail, nerves and even bone. In humans, an amputated fingertip can sprout back in as little as two months, a phenomenon that has remained poorly understood until now. In a paper published today in the journal
|
"Everyone knows that fingernails keep growing, but no one really knows why," says lead author Mayumi Ito, PhD, assistant professor of dermatology in the Ronald O. Perelman Department of Dermatology at NYU School of Medicine. Nor is much understood about the link between nail growth and the regenerative ability of the bone and tissue beneath the nail. Now, Dr. Ito and team have discovered an important clue in this process: a population of self-renewing stem cells in the nail matrix, a part of the nail bed rich in nerve endings and blood vessels that stimulate nail growth. Moreover, the scientists have found that these stem cells depend upon a family of proteins known as the "Wnt signaling network" -- the same proteins that play a crucial role in hair and tissue regeneration -- to regenerate bone in the fingertip."When we blocked the Wnt-signaling pathway in mice with amputated fingertips, the nail and bone did not grow back as they normally would," says Dr. Ito. Even more intriguing, the researchers found that they could manipulate the Wnt pathway to stimulate regeneration in bone and tissue just beyond the fingertip. "Amputations of this magnitude ordinarily do not grow back," says Dr. Ito. These findings suggest that Wnt signaling is essential for fingertip regeneration, and point the way to therapies that could help people regenerate lost limbs. An estimated 1.7 million people in the U.S. live with amputations.The team's next step is to zoom in on the molecular mechanisms that control how the Wnt signaling pathway interacts with the nail stem cells to influence bone and nail growth.
|
Genetically Modified
| 2,013 |
June 10, 2013
|
https://www.sciencedaily.com/releases/2013/06/130610152127.htm
|
Biotech crops vs. pests: Successes and failures from the first billion acres
|
Since 1996, farmers worldwide have planted more than a billion acres (400 million hectares) of genetically modified corn and cotton that produce insecticidal proteins from the bacterium Bacillus thuringiensis, or Bt for short. Bt proteins, used for decades in sprays by organic farmers, kill some devastating pests but are considered environmentally friendly and harmless to people. However, some scientists feared that widespread use of these proteins in genetically modified crops would spur rapid evolution of resistance in pests.
|
A team of experts at the University of Arizona has taken stock to address this concern and to figure out why pests became resistant quickly in some cases, but not others. Bruce Tabashnik and Yves Carrière in the department of entomology at the College of Agriculture and Life Sciences together with visiting scholar Thierry Brévault from the Center for Agricultural Research for Development (CIRAD) in France scrutinized the available field and laboratory data to test predictions about resistance. Their results are published in the journal "When Bt crops were first introduced, the main question was how quickly would pests adapt and evolve resistance," said Tabashnik, head of the UA department of entomology who led the study. "And no one really knew, we were just guessing.""Now, with a billion acres of these crops planted over the past 16 years, and with the data accumulated over that period, we have a better scientific understanding of how fast the insects evolve resistance and why."Analyzing data from 77 studies of 13 pest species in eight countries on five continents, the researchers found well-documented cases of field-evolved resistance to Bt crops in five major pests as of 2010, compared with only one such case in 2005. Three of the five cases are in the United States, where farmers have planted about half of the world's Bt crop acreage. Their report indicates that in the worst cases, resistance evolved in 2 to 3 years; but in the best cases, effectiveness of Bt crops has been sustained more than 15 years.According to the paper, both the best and worst outcomes correspond with predictions from evolutionary principles."The factors we found to favor sustained efficacy of Bt crops are in line with what we would expect based on evolutionary theory," said Carrière, explaining that conditions are most favorable if resistance genes are initially rare in pest populations; inheritance of resistance is recessive -- meaning insects survive on Bt plants only if have two copies of a resistance gene, one from each parent -- and abundant refuges are present. Refuges consist of standard, non-Bt plants that pests can eat without ingesting Bt toxins."Computer models showed that refuges should be especially good for delaying resistance when inheritance of resistance in the pest is recessive," explained Carrière.Planting refuges near Bt crops reduces the chances that two resistant insects will mate with each other, making it more likely they will breed with a susceptible mate, yielding offspring that are killed by the Bt crop. The value of refuges has been controversial, and in recent years, the EPA has relaxed its requirements for planting refuges in the U.S."Perhaps the most compelling evidence that refuges work comes from the pink bollworm, which evolved resistance rapidly to Bt cotton in India, but not in the U.S.," Tabashnik said. "Same pest, same crop, same Bt protein, but very different outcomes."He explained that in the southwestern U.S., scientists from the EPA, academia, industry and the USDA worked with growers to craft and implement an effective refuge strategy. In India, on the other hand, the refuge requirement was similar, but without the collaborative infrastructure, compliance was low.One of the paper's main conclusions is that evaluating two factors can help to gauge the risk of resistance before Bt crops are commercialized. "If the data indicate that the pest's resistance is likely to be recessive and resistance is rare initially, the risk of rapid resistance evolution is low," Tabashnik said. In such cases, setting aside a relatively small area of land for refuges can delay resistance substantially. Conversely, failure to meet one or both of these criteria signifies a higher risk of resistance.When higher risk is indicated, Tabashnik describes a fork in the road, with two paths: "Either take more stringent measures to delay resistance such as requiring larger refuges, or this pest will probably evolve resistance quickly to this Bt crop."Two leading experts on Bt crops welcomed publication of the study. Kongming Wu, director of the Institute for Plant Protection at the Chinese Academy of Agricultural Sciences in Beijing said, "This review paper will be very helpful for understanding insect resistance in agricultural systems and improving strategies to sustain the effectiveness of Bt crops." Fred Gould, professor of entomology at North Carolina State University, commented: "It's great to have an up-to-date, comprehensive review of what we know about resistance to transgenic insecticidal crops."Although the new report is the most comprehensive evaluation of pest resistance to Bt crops so far, Tabashnik emphasized that it represents only the beginning of using systematic data analyses to enhance understanding and management of resistance."These plants have been remarkably useful and in most cases, resistance has evolved slower than expected," Tabashnik said. "I see these crops as an increasingly important part of the future of agriculture. The progress made provides motivation to collect more data and to incorporate it in planning future crop deployments. We've also started exchanging ideas and information with scientists facing related challenges, such as herbicide resistance in weeds and resistance to drugs in bacteria, HIV and cancer."But will farmers ever be able to prevent resistance altogether? Tabashnik said he doesn't think so."You're always expecting the pest to adapt. It's almost a given that preventing the evolution of resistance is not possible."
|
Genetically Modified
| 2,013 |
June 5, 2013
|
https://www.sciencedaily.com/releases/2013/06/130605090524.htm
|
Personality is the result of nurture, not nature, suggests study on birds
|
Personality is not inherited from birth parents says new research on zebra finches.
|
External factors are likely to play a bigger part in developing the personality of an individual than the genes it inherits from its parents, suggests the study.Researchers at the University of Exeter and the University of Hamburg investigated how personality is transferred between generations. They found that foster parents have a greater influence on the personalities of fostered offspring than the genes inherited from birth parents.Dr Nick Royle from Biosciences at the University of Exeter said: "This is one of the first experiments to show that behaviour can be non-genetically transmitted from parents to offspring. Our study shows that in zebra finches, personality traits can be transmitted from one generation to another through behaviour not just genetics."The research, published in the journal Although this study considers personality inheritance in zebra finches, it raises questions about the inheritance of personality in other species, including humans. Do adopted children inherit the personality characteristics of their birth parents or their adoptive parents? Is the environment more important than genetic inheritance in the development of personality?The results of this study indicate that non-genetic transmission of behaviour can play an important role in shaping animal personality. Further studies will build on this research to assess how widespread behavioural inheritance is for personality traits across other species.This work was funded by the European Social Fund and the Natural Environment Research Council.
|
Genetically Modified
| 2,013 |
May 29, 2013
|
https://www.sciencedaily.com/releases/2013/05/130529133151.htm
|
Genetic engineering alters mosquitoes' sense of smell
|
In one of the first successful attempts at genetically engineering mosquitoes, HHMI researchers have altered the way the insects respond to odors, including the smell of humans and the insect repellant DEET. The research not only demonstrates that mosquitoes can be genetically altered using the latest research techniques, but paves the way to understanding why the insect is so attracted to humans, and how to block that attraction. "The time has come now to do genetics in these important disease-vector insects.
|
I think our new work is a great example that you can do it," says Leslie Vosshall, an HHMI investigator at The Rockefeller University who led the new research, published May 29, 2013 in the journal In 2007, scientists announced the completion of the full genome sequence of Vosshall's first target: a gene called orco, which her lab had deleted in genetically engineered flies 10 years earlier. "We knew this gene was important for flies to be able to respond to the odors they respond to," says Vosshall. "And we had some hints that mosquitoes interact with smells in their environment, so it was a good bet that something would interact with orco in mosquitoes."Vosshall's team turned to a genetic engineering tool called zinc-finger nucleases to specifically mutate the orco gene in When given a choice between a human and any other animal, normal Aedes aegypti will reliably buzz toward the human. But the mosquitoes with orco mutations showed reduced preference for the smell of humans over guinea pigs, even in the presence of carbon dioxide, which is thought to help mosquitoes respond to human scent. "By disrupting a single gene, we can fundamentally confuse the mosquito from its task of seeking humans," says Vosshall. But they don't yet know whether the confusion stems from an inability to sense a "bad" smell coming from the guinea pig, a "good" smell from the human, or both. Next, the team tested whether the mosquitoes with orco mutations responded differently to DEET. When exposed to two human arms -- one slathered in a solution containing 10 percent DEET, the active ingredient in many bug repellants, and the other untreated -- the mosquitoes flew equally toward both arms, suggesting they couldn't smell the DEET. But once they landed on the arms, they quickly flew away from the DEET-covered one. "This tells us that there are two totally different mechanisms that mosquitoes are using to sense DEET," explains Vosshall. "One is what's happening in the air, and the other only comes into action when the mosquito is touching the skin." Such dual mechanisms had been discussed but had never been shown before.Vosshall and her collaborators next want to study in more detail how the orco protein interacts with the mosquitoes' odorant receptors to allow the insects to sense smells. "We want to know what it is about these mosquitoes that makes them so specialized for humans," she says. "And if we can also provide insights into how existing repellants are working, then we can start having some ideas about what a next-generation repellant would look like."
|
Genetically Modified
| 2,013 |
May 28, 2013
|
https://www.sciencedaily.com/releases/2013/05/130528100238.htm
|
New 1-step process for designer bacteria
|
A simpler and faster way of producing designer bacteria used in biotechnology processes has been developed by University of Adelaide researchers.
|
The researchers have developed a new one-step bacterial genetic engineering process called 'clonetegration', published in the journal Led by Dr Keith Shearwin, in the University's School of Molecular and Biomedical Sciences, the research facilitates faster development of designer bacteria used in therapeutic drug development, such as insulin, and other biotechnology products.Designer bacteria are produced by integrating extra pieces of genetic material into the DNA of bacteria, in this case E. coli, so that the bacteria will make a desired product."E. coli strains are commonly used workhorses for biotechnology and metabolic engineering," Dr Shearwin says."For example, new genes or even the genetic material for whole metabolic pathways are inserted into the bacteria's chromosome so that they produce compounds or proteins not normally produced. Insulin is an example of a therapeutic product produced in this way.""The existing process for integrating new genes is inefficient, taking several days. Our new process can be completed overnight."As well as speeding up the process, 'clonetegration' enables multiple rounds of genetic engineering on the same bacteria, and simultaneous integration of multiple genes at different specific locations."This will become a valuable technique for facilitating genetic engineering with sequences that are difficult to clone as well as enable the rapid construction of synthetic biological systems," Dr Shearwin says.The research was a collaboration with Stanford University, California. The molecular tools needed for the clonetegration process will be made freely available for ongoing research and development.
|
Genetically Modified
| 2,013 |
May 22, 2013
|
https://www.sciencedaily.com/releases/2013/05/130522131210.htm
|
Fast new, one-step genetic engineering technology
|
A new, streamlined approach to genetic engineering drastically reduces the time and effort needed to insert new genes into bacteria, the workhorses of biotechnology, scientists are reporting. Published in the journal
|
Keith Shearwin and colleagues explain that placing, or integrating, a piece of the genetic material DNA into a bacterium's genome is critical for making designer bacteria. That DNA can give microbes the ability to churn out ingredients for medication, for instance, or substances that break down oil after a big spill. But current genetic engineering methods are time-consuming and involve many steps. The approaches have other limitations as well. To address those drawbacks, the researchers sought to develop a new, one-step genetic engineering technology, which they named "clonetegration," a reference to clones or copies of genes or DNA fragments.They describe development and successful laboratory tests of clonetegration in The authors acknowledge funding from the China Scholarship Council, the National Science Foundation Synthetic Biology Engineering Research Center, the Human Frontier Science Program, the Australian Research Council and a William H. Elliott Biochemistry Fellowship.
|
Genetically Modified
| 2,013 |
May 20, 2013
|
https://www.sciencedaily.com/releases/2013/05/130520095106.htm
|
Archaeological genetics: It's not all as old as it at first seems
|
Genomic analyses suggest that patterns of genetic diversity which indicate population movement may not be as ancient as previously believed, but may be attributable to recent events. This study published in BioMed Central's open access journal
|
Looking at more than 400,000 SNPs (genetic variations) of almost 1000 people across the Netherlands, this study found that the genomic diversity across the Netherlands follows a southeast to northwest gradient and that the Dutch population could be separated out genetically into four geographic groups (south, north, central-west and central-north).These results could be explained by invoking movement of ancient, Paleolithic-Neolithic humans, similar to that proposed to explain the genetic diversity across central entire Europe. However the data also fits a model involving movement of people within the last 70 generations of modern Dutch, for which there is a wealth of archaeological evidence.Prof Manfred Kayser from the Erasmus University Medical Center in Rotterdam, who led the study, commented, "Because of the overwhelming geological and archaeological records for strong genetic discontinuities we explain our findings by recent rather than ancient events in Dutch population history. Our results not only are of epidemiological and forensic relevance but additionally highlight that future population history studies need to take into account recent demography before assuming all genetic variation observed is due to ancient events."
|
Genetically Modified
| 2,013 |
May 19, 2013
|
https://www.sciencedaily.com/releases/2013/05/130519191102.htm
|
Bacteria use hydrogen, carbon dioxide to produce electricity
|
Researchers have engineered a strain of electricity-producing bacteria that can grow using hydrogen gas as its sole electron donor and carbon dioxide as its sole source of carbon.
|
Researchers at the University of Massachusetts, Amherst report their findings at the 113th General Meeting of the American Society for Microbiology."This represents the first result of current production solely on hydrogen," says Amit Kumar, a researcher on the study who, along with his co-authors are part of the Lovley Lab Group at the university.Under the leadership of Derek Lovley the lab group has been studying Geobacter bacteria since Lovley first isolated Kumar and his colleagues studied a relative of "The adapted strain readily produced electrical current in microbial fuel cells with hydrogen gas as the sole electron donor and no organic carbon source," says Kumar, who notes that when the hydrogen supply to the microbial fuel cell was intermittently stopped electrical current dropped significantly and cells attached to the electrodes did not generate any significant current.This research was supported by funding by the U.S. Department of Energy and the Office of Naval Research.
|
Genetically Modified
| 2,013 |
May 9, 2013
|
https://www.sciencedaily.com/releases/2013/05/130508213250.htm
|
Engineered spider toxin could be the future of anti-venom vaccines
|
New engineered spider protein could be the start of a new generation of anti-venom vaccines, potentially saving thousands of lives worldwide. The new protein, created from parts of a toxin from the reaper spider, is described today in the Elsevier journal
|
The researchers behind the study, from the Universidade Federal de Minas Gerais in Brazil, say that the engineered protein may be a promising candidate for developing therapeutic serums or vaccines against other venoms.Reaper spiders, or brown spiders, are a family of species found all over the world that produce harmful venoms. The toxic bite of these spiders causes skin around the bite to die, and can lead to more serious effects like kidney failure and haemorrhaging. These Loxosceles spiders are most prevalent in Brazil, where they cause almost 7,000 human accidents every year.The new study describes an engineered protein made of three pieces of a venom toxin from the Loxosceles intermedia spider. The engineered protein is not itself toxic, and gives effective protection against the effects of the pure spider venom in animal models."In Brazil we see thousands of cases of people being bitten by Loxosceles spiders, and the bites can have very serious side-effects," said Dr. Chávez-Olortegui, corresponding author of the study. "Existing anti-venoms are made of the pure toxins and can be harmful to people who take them. We wanted to develop a new way of protecting people from the effects of these spider bites, without having to suffer from side-effects."Current approaches to protecting against venom involve giving the venom to animals, and taking the resulting antibodies for the serum. These antibodies enable the human immune system to prepare to neutralize venom from bites. Although they are somewhat effective, the production of anti-venoms like these is problematic because animals are required to produce them, and these animals suffer from the effects of the venom.The new protein is engineered in the lab, without the need for the venomous animals. It is made up of three proteins, so it can protect against more than one kind of toxin at a time. The protein is not harmful to the immunized animal that produces the antibodies. It is also more effective than existing approaches, and easier to produce than preparing crude venom from spiders."It's not easy taking venom from a spider, a snake or any other kind of venomous animal," said Chávez-Olortegui. "With our new method, we would be able to engineer the proteins in the lab without having to isolate whole toxins from venom. This makes the whole process much safer."The researchers tested their new protein on rabbits: all immunized animals showed an immune response similar to the way they respond to the whole toxin. The engineered protein was effective for venom of the L. intermedia and L. gaucho sub-species, which have similar toxins. Immunized rabbits were protected from skin damage at the site of venom injection, and from haemorrhaging.This engineered protein may be a promising candidate for therapeutic serum development or vaccination in the future.
|
Genetically Modified
| 2,013 |
May 8, 2013
|
https://www.sciencedaily.com/releases/2013/05/130508114307.htm
|
Soy and tomato may be effective in preventing prostate cancer
|
Tomatoes and soy foods may be more effective in preventing prostate cancer when they are eaten together than when either is eaten alone, said a University of Illinois study.
|
"In our study, we used mice that were genetically engineered to develop an aggressive form of prostate cancer. Even so, half the animals that had consumed tomato and soy had no cancerous lesions in the prostate at study's end. All mice in the control group -- no soy, no tomato -- developed the disease," said John Erdman, a U of I professor of food science and nutrition.From the time they were 4 to 18 weeks old, the animals were fed one of four diets: (1) 10 percent whole tomato powder; (2) 2 percent soy germ; (3) tomato powder plus soy germ; and (4) a control group that ate neither tomato nor soy.The 4- to 18-week time frame modeled an early and lifelong exposure to the bioactive components in these foods, he said."Eating tomato, soy, and the combination all significantly reduced prostate cancer incidence. But the combination gave us the best results. Only 45 percent of mice fed both foods developed the disease compared to 61 percent in the tomato group, and 66 percent in the soy group," he said.Prostate cancer is the most frequently diagnosed cancer in men, but the disease has nearly a 100 percent survival rate if it's caught early. In older men, it is often a slow-growing cancer, and these men often choose watchful waiting over radiation and surgical treatments that have unwelcome side effects, said Krystle Zuniga, co-author of the paper.Soy isoflavone serum and prostate levels in the mice are similar to those found in Asian men who consume one to two servings of soy daily. In countries where soy is eaten regularly, prostate cancer occurs at significantly lower levels, Erdman noted.How much soy and tomato should a 55-year-old man concerned about prostate health eat in order to receive these benefits?"The results of the mouse study suggest that three to four servings of tomato products per week and one to two servings of soy foods daily could protect against prostate cancer," Zuniga said.According to the scientists, these findings reinforce the recommendation that we should all eat a wide variety of whole fruits and vegetables."It's better to eat a whole tomato than to take a lycopene supplement. It's better to drink soy milk than to take soy isoflavones. When you eat whole foods, you expose yourself to the entire array of cancer-fighting, bioactive components in these foods," Erdman said.The researcher's whole-food recommendation is bolstered by the way soy germ performed in this study. He noted that soy germ has a very different isoflavone profile than the rest of the soybean."Of the isoflavones, genistein gets most of the attention. But soy germ is very high in the other isoflavones, daidzein and glycitein, and low in genistein," he said.It was interesting for the scientists to see that the soy product they used, although low in genistein, was still very effective at reducing cancer incidence.
|
Genetically Modified
| 2,013 |
May 6, 2013
|
https://www.sciencedaily.com/releases/2013/05/130506181609.htm
|
New technique to track cell interactions in living bodies developed
|
Researchers at Stanford University School of Medicine have developed a new technique to see how different types of cells interact in a living mouse. The process uses light-emitting proteins that glow when two types of cells come close together.
|
Using the technique, the team was able to pinpoint where in the body metastatic cancer cells ended up after they broke off from an initial tumor site, using readily available lab reagents. The team chose chemicals that are easily available in most life sciences laboratories because they wanted to develop a technique that could be widely used.The study was published online May 6 in the Until now, the best way to see cells interacting inside a living animal or person was to implant a microscope. But predicting all the places metastatic cancer cells will proliferate is nearly impossible. "There are currently no great ways to look at early metastasis, where metastases are finding their micro-environments and setting up shop," said Mark Sellmyer, MD, PhD, the study's lead author, who developed the technique as a graduate student working jointly for Christopher Contag, PhD, professor of pediatrics and of microbiology and immunology, and Tom Wandless, PhD, associate professor of chemical and systems biology.Sellmyer, who begins a research residency in radiology at the University of Pennsylvania this summer, worked closely with Jennifer Prescher, PhD, a former postdoctoral scholar in Contag's lab who is now an assistant professor at the University of California-Irvine. "I think it really expands our capabilities, expands the tool box," Prescher said. "We're always beholden to the tools available for us in terms of what we can observe. Any time we have a new vantage point -- a new technology -- it can open doors to understanding new aspects of biology."Sellmyer and Prescher genetically altered immune cells and cancer cells -- what they call activator and reporter cells, respectively -- so the cells would produce two different enzymes. The activator immune cells created the enzyme B-galactosidase, which can convert a common biological probe called a "caged luciferin" into luciferin, a molecule naturally found in animals like fireflies. The reporter cancer cells created the enzyme luciferase, which splits the luciferin molecule in a chemical reaction that emits light.After demonstrating the process could work in a cell culture in a petri dish, they used the same method in living mice. The mice were implanted with genetically altered bone marrow cells that generated activator immune cells. An experimental group of 10 mice had tumors made of cancer cells genetically altered to serve as reporters implanted into their abdomens. For comparison, a control group of four additional mice were implanted with unaltered bone marrow cells. After several weeks, the researchers injected a compound that would be converted to light-emitting luciferin.The researchers could easily see where populations of immune cells got close to metastatic cancer cell populations because those parts of the mouse body would glow and take a picture of the pattern of light emitted by the mouse's body. Among other metastasis sites, researchers were surprised to find that in several mice, small populations of cancer cells had started to grow in their noses and just under their lower jaws.Currently, the technique can't be used in people, but the researchers hope it will be used to study a variety of cell interactions in laboratory mice. Contag is planning to use the technique to study how immune cells migrate to sites of infection. Cell-cell communication is important for a variety of biological processes," he said. "Knowing the proximity of one cell type to another in the context of the living tissue is key for understanding biology."The technique requires a minimum population of 1,000 cells for both the activator and reporter cells to work. Prescher is working on improving the precision of the method so that smaller populations with fewer cells can be tracked.Both Contag and Wandless noted that Sellmyer's and Prescher's interdisciplinary approach was key to developing the technique. "Their training in biology allowed them to identify an important problem in the area of in vivo imaging, and their ability to incorporate chemistry allowed Mark and Jenn to design and develop a new technique that would be out-of-reach to the majority of classical biology labs," Wandless said.Other Stanford authors of the study include postdoctoral scholar Laura Bronsart, PhD, and visiting scholar Hiroshi Imoto, PhD.The study was supported by the National Institutes of Health (grants GM073046 and P50CA114747), the NIH Medical Scientist Training Program and the Susan G. Komen Foundation.
|
Genetically Modified
| 2,013 |
May 2, 2013
|
https://www.sciencedaily.com/releases/2013/05/130502131716.htm
|
Scientists revolutionize creation of genetically altered mice to model human disease
|
Whitehead Institute Founding Member Rudolf Jaenisch, who helped transform the study of genetics by creating the first transgenic mouse in 1974, is again revolutionizing how genetically altered animal models are created and perhaps even redefining what species may serve as models.
|
"This new method is a game changer," says Jaenisch, who is also a professor of biology at MIT. "We can now make a mouse with five mutations in just three to four weeks, whereas the conventional way would take three to four years. And it's rather straightforward, probably even easier than the conventional way."Scientists create models in mice by altering specific genes that have been associated with a given disease. The models allow for the study of the development and course of the disease and the effects of various interventions, including genetic and chemical. For the past 20 years, the creation of such models has remained relatively unchanged: scientists insert a piece of DNA into a mouse embryonic stem (ES) cell, inject the modified cell into a very early-stage embryo, called a blastocyst, then implant this developing ball of cells into a foster female mouse. The whole process can take years and tens of thousands of dollars to establish a mouse strain with, for example, a single copy of a gene "knocked out." Such knockouts can only be created in very few species, including mice and rats, whose ES cells can be grown and modified reliably.The new approach used by scientists in Jaenisch's lab bypasses ES cells to quickly and efficiently produce mice with mutations in both copies of multiple genes. In next week's issue of the journal This is the first time that the system, known as CRISPR (for "clustered regularly interspaced short palindromic repeat")/Cas (for "CRISPR-associated"), has been used to alter multiple genes in a single multicellular organism. Shivalila says the process is so accessible that he expects other labs to adopt it quickly."For any institution or university with a core facility, we think this will be the way they will start making mice carrying specific mutations because it's a lot faster and so efficient," says Shivalila, one of Jaenisch's graduate students. "We were surprised that we could get two genes 'knocked out' at four loci very, very efficiently, about 80% efficiency. If we used TALENs, a more recent and complicated development in genetic engineering, we got 30% efficiency for just one gene."Because the CRISPR/Cas technique can generate mutant mice even without using ES cells, a limitation of the conventional method for making models, genetic research may no longer be confined to a limited list of model organisms -- those for which ES cells exist."This breaks down the definition of model organism," says Wang, a postdoctoral researcher in Jaenisch's lab. "So now, even with limited resources, any animal with established embryo manipulation procedures could be the subject of genome engineering. With many of the animals' genomes that have been sequenced, we could use this technology to establish efficient genetic manipulations in more species, to study the unique biology of each, and to learn more about evolution."Thus, Wang, Yang, and Shivalila have used CRISPR/Cas to create mouse models only, but the team is excited broaden its application to other animals."We also need to see if the CRISPR/Cas system has any unexpected, undesired off-target effects, changes to the genome that we don't want," says Yang, a postdoctoral researcher in the Jaenisch lab. "So we need study this further to establish the fidelity of the system. But I think this will be the way to go."This research was supported by Damon Runyon Cancer Research Foundation, Croucher Foundation, National Institutes of Health (NIH) grants R37-HD045022 and R01-CA084198. Jaenisch is an adviser to Stemgent and a cofounder of Fate Therapeutics.
|
Genetically Modified
| 2,013 |
April 25, 2013
|
https://www.sciencedaily.com/releases/2013/04/130425132612.htm
|
Europe needs genetically engineered crops, scientists say
|
The European Union cannot meet its goals in agricultural policy without embracing genetically engineered crops (GMOs). That's the conclusion of scientists who write in
|
"Failing such a change, ultimately the EU will become almost entirely dependent on the outside world for food and feed and scientific progress, ironically because the outside world has embraced the technology which is so unpopular in Europe, realizing this is the only way to achieve sustainable agriculture," said Paul Christou of the University of Lleida-Agrotecnio Center and Institució Catalana de Recerca i Estudis Avançats in Spain."Many aspects of the EU agricultural policy, including those concerning GMOs, are internally inconsistent and actively obstruct what the policy sets out to achieve," Christou and his colleagues continued.For instance, the Lisbon Strategy aims to create a knowledge-based bioeconomy and recognizes the potential of GMOs to deliver it, but EU policy on the cultivation of GMOs has created an environment that makes this impossible. In reality, there is a de facto moratorium in Europe on the cultivation of genetically engineered crops such as maize, cotton, and soybean, even as the same products are imported because there is insufficient capacity to produce them by conventional means at home.Subsidies designed to support farmers now benefit large producers at the expense of family farms, Christou says. The EU has also banned its farmers from using many pesticides and restricted them from other nonchemical methods of pest control, while allowing food products produced in the same ways to be imported."EU farmers are denied freedom of choice -- in essence, they are prevented from competing because EU policies actively discriminate against those wishing to cultivate genetically engineered crops, yet exactly the same crops are approved for import," Christou says.
|
Genetically Modified
| 2,013 |
April 19, 2013
|
https://www.sciencedaily.com/releases/2013/04/130419132607.htm
|
Quest for edible malarial vaccine leads to other potential medical uses for algae
|
Can scientists rid malaria from the Third World by simply feeding algae genetically engineered with a vaccine?
|
That's the question biologists at UC San Diego sought to answer after they demonstrated last May that algae can be engineered to produce a vaccine that blocks malaria transmission. In a follow up study, published online today in the scientific journalIn their most recent study, which the authors made freely available on the The result? The mice developed Immunoglobulin A (IgA) antibodies to both the malarial parasite protein and to a toxin produced by the cholera bacteria. Because IgA antibodies are produced in the gut and mucosal linings, they don't protect against the malarial parasites, which are injected directly into the bloodstream by mosquitoes. But their study suggests that similar fusion proteins might protect against infectious diseases that affect mucosal linings using their edible freeze-dried algae."Many bacterial and viral infections are caused by eating tainted food or water," says Stephen Mayfield, a professor of biology at UC San Diego who headed the study. "So what this study shows is that you can get a really good immune response from a recombinant protein in algae that you feed to a mammal. In this case, it happens to be a mouse, but presumably it would also work in a human. That's really encouraging for the potential for algae-based vaccines in the future."The scientists say bacterial infections caused byPart of the difficulty in creating a vaccine against malaria is that it requires a system that can produce structurally complex proteins that resemble those made by the parasite, thus eliciting antibodies that disrupt malaria transmission. Most vaccines created by engineered bacteria are relatively simple proteins that stimulate the body's immune system to produce antibodies against bacterial invaders.Three years ago, a UC San Diego team of biologists headed by Mayfield, who is also the director of the San Diego Center for Algae Biotechnology, a research consortium seeking to develop transportation fuels from algae, published a landmark study demonstrating that many complex human therapeutic proteins, such as monoclonal antibodies and growth hormones, could be produced by the common algae"It's too costly to vaccinate two billion people using current technologies," explained Mayfield. "Realistically, the only way a malaria vaccine will ever be used in the developing world is if it can be produced at a fraction of the cost of current vaccines. Algae have this potential because you can grow algae any place on the planet in ponds or even in bathtubs."Collaborating with Joseph Vinetz, a professor of medicine at UC San Diego and a leading expert in tropical diseases who has been working on developing vaccines against malaria, the researchers showed in their earlier study, published in the open access journal PLoS ONE last May that the proteins produced by the algae, when injected into laboratory mice, made antibodies that blocked malaria transmission from mosquitoes.The next step was to see if they could immunize mice against malaria by simply feeding the genetically engineered algae. "We think getting oral vaccines in which you don't have to purify the protein is the only way in which you can make medicines dramatically cheaper and make them available to the developing world," says Mayfield. "The Holy Grail is to develop an orally delivered vaccine, and we predict that we may be able to do it in algae, and for about a penny a dose. Our algae-produced malarial vaccine works against malarial parasites in mice, but it needs to be injected into the bloodstream."Although an edible malarial vaccine is not yet a reality, he adds, "this study shows that you can make a pretty fancy protein using algae, deliver it to the gut and get IgA antibodies that recognize that protein. Now we know we have a system that can deliver a complex protein to the right place and develop an immune response to provide protection."Mayfield is also co-director of the Center for Food & Fuel for the 21st Century, a new research unit that has brought together researchers from across the campus to develop renewable ways of improving the nation's food, fuel, pharmaceutical and other bio-based industries and is this week hosting a major symposium on the subject at the Institute of the Americas at UC San Diego.
|
Genetically Modified
| 2,013 |
April 15, 2013
|
https://www.sciencedaily.com/releases/2013/04/130415182505.htm
|
Plant protein shape puzzle solved by molecular 3-D model
|
Researchers from North Carolina State University believe they have solved a puzzle that has vexed science since plants first appeared on Earth.
|
In a groundbreaking paper published online this week in New understanding of the structure of the modeled plant enzyme, a cellulose synthase, may allow researchers to genetically engineer plants and trees for better cotton fibers or stronger wood, for example. From a materials engineering perspective, the findings can also be used to create beneficial nanocrystals with desired properties and functions."This structural model gives us insight into how cellulose synthesis works," said Dr. Yaroslava Yingling, an NC State materials science and engineering professor who is the corresponding author on the study. "In the long term, it could result in new genetically modified plants that can be tweaked to induce specific engineered properties of cellulose."The study examined the structure of one cellulose synthase found in cotton fibers. The researchers compared their model with the structure of a similar enzyme in bacteria and found that the proteins were similarly folded in key regions required for cellulose synthesis. In the lab rat of the plant family -- Arabidopsis thaliana, or mustard weed -- the researchers identified potential causes for defective cellulose synthesis in mutant plants by making analogies to the modeled cotton cellulose synthase."Without the enzyme structure, you can't make strategically designed, rational projections about how to make beneficial changes to the proteins -- but now you can," said Dr. Candace Haigler, an NC State crop scientist and plant biologist who co-authored the study. "In the future we could make cellulose easier to break down into biofuels while ensuring that the plants themselves are able to grow well."Latsavongsakda Sethaphong, an NC State doctoral student, co-authored the study, as did researchers from Penn State University, the University of Virginia, the University of Ontario Institute of Technology and the University of Kentucky. The computational research was supported as part of The Center for LignoCellulose Structure and Formation, an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science.
|
Genetically Modified
| 2,013 |
April 11, 2013
|
https://www.sciencedaily.com/releases/2013/04/130411105822.htm
|
Molecular 'superglue' based on flesh-eating bacteria
|
In a classic case of turning an enemy into a friend, scientists have engineered a protein from flesh-eating bacteria to act as a molecular "superglue" that promises to become a disease fighter. And their latest results, which make the technology more versatile, were the topic of a report in New Orleans on April 11 at the 245th National Meeting & Exposition of the American Chemical Society.
|
"We've turned the tables and put one kind of flesh-eating bacterium to good use," said Mark Howarth, Ph.D., who led the research. "We have engineered one of its proteins into a molecular superglue that adheres so tightly that the set-up we used to measure the strength actually broke. It resists high and low temperatures, acids and other harsh conditions and seals quickly. With this material we can lock proteins together in ways that could underpin better diagnostic tests -- for early detection of cancer cells circulating in the blood, for instance. There are many uses in research, such as probing how the forces inside cells change the biochemistry and affect health and disease."Howarth's team at the University of Oxford in the United Kingdom genetically engineered the glue from a protein, FbaB, that helps They split FbaB into two parts, a larger protein and a smaller protein subunit, termed a peptide. Abbreviating In an advance reported at the meeting, Howarth described how Jacob Fierer, a graduate student on the research team, greatly reduced the size of the SpyCatcher part of the technology. That achievement makes the technology more flexible, enabling scientists to connect proteins into new architectures, he said.One of the applications on the horizon involves testing the technology as a new way to detect "circulating tumor cells," or CTCs. Tumors shed these cells into the bloodstream, where they may act as seeds, spreading or metastasizing cancer from the original site to other parts of the body. That spreading is the reason why cancer is such a serious health problem. Detecting CTCs is an active area of research worldwide because of its potential for early diagnosis of cancer -- from blood samples rather than biopsies -- and determining when new treatments may be needed to prevent the disease from spreading.Howarth said that the Spy technology has advantages over other molecular gluing systems that are available. SpyCatcher and SpyTag, for instance, can glue two proteins together at any point in the protein. "That flexibility allows us many different ways to label proteins and gives us new approaches to assemble proteins together for diagnostic tests," Howarth explained.Howarth and colleagues are working with Isis Innovation, the University of Oxford's technology transfer company, to find potential partners to bring the Spy system to the market.The researchers acknowledge funding from the Clarendon Fund.
|
Genetically Modified
| 2,013 |
April 8, 2013
|
https://www.sciencedaily.com/releases/2013/04/130408184727.htm
|
Couch potatoes may be genetically predisposed to being lazy, rat study suggests
|
Studies show 97 percent of American adults get less than 30 minutes of exercise a day, which is the minimum recommended amount based on federal guidelines. New research from the University of Missouri suggests certain genetic traits may predispose people to being more or less motivated to exercise and remain active. Frank Booth, a professor in the MU College of Veterinary Medicine, along with his post-doctoral fellow Michael Roberts, were able to selectively breed rats that exhibited traits of either extreme activity or extreme laziness. They say these rats indicate that genetics could play a role in exercise motivation, even in humans.
|
"We have shown that it is possible to be genetically predisposed to being lazy," Booth said. "This could be an important step in identifying additional causes for obesity in humans, especially considering dramatic increases in childhood obesity in the United States. It would be very useful to know if a person is genetically predisposed to having a lack of motivation to exercise, because that could potentially make them more likely to grow obese."In their study published in the Once the researchers created their "super runner" and "couch potato" rats, they studied the levels of mitochondria in muscle cells, compared body composition and conducted thorough genetic evaluations through RNA deep sequencing of each rat."While we found minor differences in the body composition and levels of mitochondria in muscle cells of the rats, the most important thing we identified were the genetic differences between the two lines of rats," Roberts said. "Out of more than 17,000 different genes in one part of the brain, we identified 36 genes that may play a role in predisposition to physical activity motivation."Now that the researchers have identified these specific genes, they plan on continuing their research to explore the effects each gene has on motivation to exercise.Frank Booth also is a professor in the Department of Physiology in the MU School of Medicine as well as a research investigator in the Dalton Cardiovascular Research Center at MU. This research also featured Kevin Wells, an assistant professor of genetics in the College of Agriculture, Food and Natural Resources Division of Animal Sciences.
|
Genetically Modified
| 2,013 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.