“Systems biology approach provides insulin resistance insights - Science Centric” plus 4 more |
- Systems biology approach provides insulin resistance insights - Science Centric
- The Biology Behind the Milk of Human Kindness - Tuscaloosa News
- Charles Darwin Debate Rages On 150 Years After "Origin" - Post Chronicle
- Biology Under the Influence - Monthly Review
- Synthetic biology offers new opportunities for interdisciplinary ... - Genetic Engineering News
| Systems biology approach provides insulin resistance insights - Science Centric Posted: 24 Nov 2009 06:54 AM PST Researchers from the University of California, San Diego recently offered the sharpest-yet picture of how core biochemical pathways in skeletal muscle cells and fat cells are altered in people who suffer from insulin resistance - a primary defect in type 2 diabetes and obesity. Taking a systems biology approach, the bioengineers and medical researchers also determined how a common class of drugs for treating insulin resistance - TZDs - alter these same core pathways. This led the team to uncover previously unknown effects of TZDs and insights that could lead to improved drug therapies for insulin resistance. The team - led by investigators from the UC San Diego Jacobs School of Engineering and School of Medicine - recently published their findings in the journal Proceedings of the National Academy of Sciences (PNAS). 'When you are insulin resistant, your metabolism suffers. If you take a TZD for your insulin resistance, will the drug fix the dysfunction in muscle and fat tissues? Will these changes be functionally related to drug efficacy? These are some of the questions we addressed in our new study,' say UC San Diego faculty members Dr Shankar Subramaniam and Dr Dorothy Sears, co-corresponding authors of the new paper. The collaborative project involved Dr Subramaniam's Bioinformatics and Systems Biology laboratory in the Department of Bioengineering at the Jacobs School of Engineering, Dr Sears and her colleagues in the Department of Medicine, and Pfizer, Inc. By combining human subject clinical information with multi-tissue, genome-wide gene expression analyses, the researchers determined that TZDs do in fact alter expression of metabolic pathways, as expected, in insulin resistant subjects. Further, they discovered distinct pathway alterations that correlated with improved insulin sensitivity after TZD treatment. In fat tissue, for example, the TZDs reduced inflammation and enhanced branched chain amino acid metabolism pathways in subjects who responded to drug treatment, i.e., became more insulin sensitive. 'Our analyses have uncovered what is happening in both muscle and fat tissues - from a biochemical pathway perspective - in patients who are insulin resistant. We have also discovered specific functional pathway alterations in the subjects who responded favourably to insulin-sensitising drugs. These findings present new targets for the development of improved drug therapies,' said Dr Sears, Assistant Professor of Medicine in the Division of Endocrinology and Metabolism at the UCSD School of Medicine. 'One surprise of the study was that insulin resistant subjects whose insulin sensitivity improved after TZD treatment showed increased fat markers in their skeletal muscle. The insulin resistant subjects exhibited elevated muscle fat at baseline which was further increased with TZD-induced insulin sensitisation. This finding is an example of the kind of drug effects that we can uncover with our systems biology approach,' said Subramaniam, holder of the Joan and Irwin Jacobs Endowed Chair in Bioengineering and Systems Biology at UC San Diego. The U.S. Food and Drug Administration (FDA) and pharmaceutical companies are very interested in system-wide drug effects, explained Subramaniam. 'In the coming decade, researchers, drug developers and clinicians will use systems biology to discover exactly which drug-induced functional changes are related to therapeutic efficacy and which are unrelated to efficacy,' said Subramaniam. The side effects of statins - a class of cholesterol-lowering drugs - provide an example of the kinds of non-therapeutic effects that researchers hope to uncover during the drug development process. 'These are the kinds of problems we believe we can identify early on, by taking a system-wide approach,' said Subramaniam. The team's systems biology approach could also help doctors quickly determine if a specific patient is likely to respond to a drug, based on their personal gene expression profile and basic phenotypic information. In the new study, the researchers uncovered markers for identifying which patients will respond to TZD treatment with improved insulin sensitivity - and which patients will not respond. Methodologies developed in Subramaniam's lab make it possible to say what is and is not significant from mountains of gene expression data. 'This study is built on our variance modelling approach. Gene expression gives you thousands of transcription data points, and we devised a way to tease out what is significant and what is not significant. We are looking at gene expression profiles and their relevance to function,' said Gene Hsiao, a Ph.D. candidate in bioengineering at UCSD and an author on the PNAS paper. 'I think this is one of the first successful examples of 'systems medicine' - which is the application of systems biology to medicine,' said Subramaniam, who explained that this systems approach can be applied to many other diseases and drugs. His team is currently investigating both cell death and stem cell differentiation using similar strategies. Source: UCSD News CentreThis content has passed through fivefilters.org. | |
| The Biology Behind the Milk of Human Kindness - Tuscaloosa News Posted: 24 Nov 2009 04:38 AM PST Be thankful that, on at least one occasion, your mother did not fend off your father with a pair of nunchucks, but instead allowed enough contact to facilitate your happy conception. Be thankful that when you go to buy a pale, poultrylike entity, the grocery clerk will accept your credit card in good faith and even return it with a heroic garble of your last name. Be grateful for the empathetic employee working the United Airlines ticket counter the day after Thanksgiving, who understands why you must leave town today, this very minute, lest someone pull out the family nunchucks. Above all, be thankful for your brain's supply of oxytocin, the small, celebrated peptide hormone that, by the looks of it, helps lubricate our every prosocial exchange, the thousands of acts of kindness, kind-of kindness and not-as-nakedly-venal-as-I-could-have-been kindness that make human society possible. Scientists have long known that the hormone plays essential physiological roles during birth and lactation, and animal studies have shown that oxytocin can influence behavior too, prompting voles to cuddle up with their mates, for example, or to clean and comfort their pups. Now a raft of new research in humans suggests that oxytocin underlies the twin emotional pillars of civilized life, our capacity to feel empathy and trust. Reporting this month in The Proceedings of the National Academy of Sciences, researchers found that genetic differences in people's responsiveness to the effects of oxytocin were linked to their ability to read faces, infer the emotions of others, feel distress at others' hardship and even to identify with characters in a novel or "Doonesbury." "I came into this research as a big skeptic," said Sarina M. Rodrigues of Oregon State University, an author of the new report, "but the results had me floored." Oxytocin may also be a capitalist tool. In a series of papers that appeared in Nature, Neuron and elsewhere, Ernst Fehr, director of the Institute for Empirical Research in Economics at the University of Zurich, and his colleagues showed that the hormone had a remarkable effect on the willingness of people to trust strangers with their money. In the Nature study, 58 healthy male students were given a single nasal squirt of either oxytocin or a placebo solution and, 50 minutes later, were instructed to start playing rounds of the Trust Game with each other, using monetary units they could either invest or withhold. The researchers found that the oxytocin-enhanced subjects were significantly more likely than the placebo players to trust their financial partners: whereas 45 percent of the oxytocin group agreed to invest the maximum amount of money possible, just 21 percent of the control group proved so amenable. Moreover, the researchers showed that the oxytocin boost didn't simply make subjects more willing to take risks and throw their money around. When participants knew they were playing against a computer rather than a human being, there was no difference in investment strategy between the groups. Trust, it seems, is a strictly wetware affair. Yet the hormone doesn't turn you into a sucker. In the Nov. 1 issue of Biological Psychiatry, Simone Shamay-Tsoory of the University of Haifa and her colleagues reported that when participants in a game of chance were pitted against a player they considered arrogant, a nasal spritz of oxytocin augmented their feelings both of envy whenever the haughty one won and of schadenfreudian gloating when their opponent lost. As a rule, though, oxytocin is a joiner not a splitter. Analogues of the molecule are found in fish, perhaps to help facilitate the delicate business of fertilization, by inhibiting a fish's natural tendency to flee from other fish. The more elaborate grew the social demands, the more roles oxytocin assumed, reaching its apotheosis in mammals. If you're going to give birth to a litter of needy young, why not let the same signal that helped push those mewlers into the world give you tips on their care and feeding? And if you're a human, bent on turning everything into an extended family affair, here is oxytocin again to cheerlead and teleprompt. C. Sue Carter of the University of Illinois at Chicago, a pioneer in the study of oxytocin, suspects that the association between the hormone and childbirth long kept scientists from taking it seriously. "But now that it's been brought into the world of economics and finance," Dr. Carter said, "suddenly it's very hot." Oxytocin acts as a hormone, traveling through the bloodstream to affect organs far from its origin in the brain, and as a kind of neurotransmitter, allowing brain cells to communicate. Unlike most neurotransmitters, oxytocin seems to deliver its signal through just one receptor, one protein designed to recognize its shape and shudder accordingly when clasped; dopamine and serotonin, by contrast, each have five or more receptors assigned to their care. Yet the precise contours of oxytocin's hardworking receptor differ among individuals, to apparently noticeable effect. In their new study, Dr. Rodrigues and Laura R. Saslow and Dacher Keltner of the University of California, Berkeley, looked at how two variants in the genetic code for the receptor might influence a person's capacity for empathy, as measured by a standard empathy questionnaire ("I really get involved with the feelings of the characters in a novel") and a behavioral task called "Reading the Mind in the Eyes." In it, participants looked at 36 black-and-white photographs of people's eyes and were asked to choose the word that best described each subject's mood. Uneasy, defiant, contemplative, playful? In a related measure of oxytocin's presumed calming effects, subjects were also tested for how strongly they reacted to the stress of hearing a series of loud noises. In their sample of 192 male and female college students, the researchers found that those carrying the so-called A version of the oxytocin receptor, which previous reports had associated with autism and poor parenting skills, scored significantly lower on the eye-reading task and higher on the stress-prone test than did subjects with the G variant of the receptor. "We're all different, and that's a good thing," Dr. Rodrigues said. "If everyone were gooey and lovey-dovey, it would be an obnoxious world." As she drolly admitted, she herself is Type A. This content has passed through fivefilters.org. | |
| Charles Darwin Debate Rages On 150 Years After "Origin" - Post Chronicle Posted: 24 Nov 2009 07:44 AM PST Even 150 years after it first appeared in print, Charles Darwin's "On The Origin of Species" still fuels clashes between scientists convinced of its truth and critics who reject its view of life without a creator. This "Darwin Year" -- so named because February 12 was the 200th anniversary of the British naturalist's birth and November 24 the 150th anniversary of his book -- has seen a flood of books, articles and conferences debating his theory of evolution. While many covered well-trodden ground, some have taken new paths. But no consensus is in sight, probably because Darwinian evolution is both a powerful scientific theory describing how life forms develop through natural selection and a basis for philosophies and social views that often include atheism. "People are encountering and rejecting evolution not so much as a science but as a philosophy," Nick Spencer, director of studies at the public theology think-tank Theos in London, told Reuters. "Today's most eloquent Darwinians often associate evolution with atheism ... amorality (and) the idea there is no design or purpose in the universe." He said many people had embraced anti-evolution views in the United States and Britain in recent decades "not so much because they are rejecting evolution as a science, although that is often how that sentiment is articulated, but because they're rejecting it as a philosophy about life." "It's quite possible to be an evolutionist and not to hold that philosophy about life, to be an evolutionist and still believe in God and purpose and design," he said. MUSLIM DOUBTS ABOUT DARWIN Creationism, the idea God made the world as described in the Bible, and the "intelligent design" view positing an unnamed creator are usually linked to conservative U.S. Protestant groups in the United States. A conference last week in Alexandria, Egypt, focused on how widespread anti-evolution views also are in the Muslim world, where believers cite the Koran's account of creation -- somewhat similar to the Bible's -- to reject Darwinism as atheist. Nidhal Guessoum, an Algerian astrophysicist at the American University of Sharjah in the United Arab Emirates, said 62 percent of the Muslim students and professors on his campus said in a recent survey that evolution was "just an unproven theory." Only 10 percent of non-Muslim professors agreed. He also cited a poll saying 80 percent of Pakistani students doubted evolution and many teachers misunderstood the scientific theory. "It will take a long, sustained effort, and a compassionate approach" to convince such Muslims that evolution need not negate faith, he said. "'More biology' does not improve the situation much (and) 'more science' does not work." EVOLUTION BEYOND DARWIN In Paris on Monday, a conference at UNESCO (the United Nations Educational, Scientific and Cultural Organization) heard several scientists who accept evolution argue Darwin could not explain underlying order and patterns found in nature. "We have to differentiate between evolution and Darwinism," said French philosopher of science Jean Staune, author of the new book "Au-dela de Darwin" (Beyond Darwin). "Of course there is adaptation. But like physics and chemistry, biology is also subject to its own laws." Michael Denton, a geneticist with New Zealand's University of Otago, said Darwinian "functionalists" believed life forms adapted to the outside world while his "structuralist" view also saw an internal logic driving this evolution down certain paths. His view, which he called "extraordinarily foreign to modern biology," explained why many animals developed eyes like human ones and why proteins, one of the building blocks of life, fold into structures unchanged for three billion years. Denton said he was a religious agnostic seeking answers to unresolved scientific questions. "Our knowledge of biology is actually very limited," he said. "I have no axe to grind -- I'll leave it to science to find this out." (Editing by Jon Boyle) This content has passed through fivefilters.org. | |
| Biology Under the Influence - Monthly Review Posted: 23 Nov 2009 07:41 PM PST
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| Synthetic biology offers new opportunities for interdisciplinary ... - Genetic Engineering News Posted: 23 Nov 2009 01:14 PM PST Nov 23 2009, 4:20 PM EST Synthetic biology offers new opportunities for interdisciplinary collaborationEUREKALERT Contact: Maureen O'Learynews@nas.edu 202-334-2138 National Academy of Sciences $1 million in research grants to be awardedIRVINE, Calif. -- More than 160 participants gathered this week for the seventh annual National Academies Keck FUTURES INITIATIVE conference. This year's topic, "Synthetic Biology," brought together scientists, engineers, and medical researchers to explore the engineering, scientific, and social issues surrounding the emerging field of synthetic biology. Bonnie L. Bassler, professor of molecular biology at Princeton University and this year's conference chair, challenged the attendees to work at bridging the gap between what synthetic biology already has achieved and what it may someday make possible. "The promise of synthetic biology" Bassler said, "could come from engineering new ways to fight disease, producing renewable energy sources, or synthesizing materials more cheaply and efficiently. For scientists, the excitement will come from pushing the boundaries, moving the field forward in unexpected ways, and in doing so, discovering new principles." To encourage further interdisciplinary work, the National Academies announced the availability of $1 million in seed grants up to $100,000 each for new lines of research identified at the conference. Recipients of the competitive grants will be announced next April. To help participants overcome differences in terminology used in various fields, the organizers offered a number of podcast "tutorials" focusing on many aspects of synthetic biology. The podcasts were created by NPR News science correspondent Joe Palca and feature interviews with experts in the field. These tutorials are available online at www.keckfutures.org. During the conference, researchers participated in one of 12 research teams to explore diverse challenges. Among the challenges were to identify technologies and tools that would make biology easier to engineer; how to understand natural genetic circuits using synthetic biology; how to design communities of cells; how to move beyond genetics to engage chemical and physical approaches to synthetic biology; and the role of evolution and evolvability in synthetic biology. Representatives from public and private funding organizations, government, industry, graduate writing students, and the media also participated. Researchers also presented posters describing their latest research. 2009 COMMUNICATION AWARDS Encouraging better communication among scientists in various fields and between scientists and the public is another key component of the FUTURES INITIATIVE. During the conference, the National Academies held an awards dinner to honor their 2009 Communication Awards winners:
The awards recognize excellence in communicating science, engineering, and medicine to the public. The winners of the four $20,000 cash prizes spoke to conference attendees about their experiences communicating science. Launched in 2003 by the National Academies and the W.M. Keck Foundation, the FUTURES INITIATIVE is a 15-year effort to stimulate interdisciplinary inquiry and to enhance communication among researchers, funding agencies, universities, and the general public. The initiative builds on three pillars of vital and sustained research: interdisciplinary encounters that counterbalance specialization and isolation; exploration of new questions; and bridging languages, cultures, habits of thought, and institutions through communication. For more information on the FUTURES INITIATIVE, visit www.keckfutures.org. The National Academies comprise the National Academy of Sciences, National Academy of Engineering, Institute of Medicine, and National Research Council. They are private, nonprofit institutions that provide science, technology, and health policy advice under a congressional charter. For more information, visit www.national-academies.org. [ This news release is available at http://national-academies.org ] This content has passed through fivefilters.org. |
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