The DNA Network |
| Predict a Preterm Delivery: Grants from the March of Dimes [PredictER Blog] Posted: 23 May 2008 05:25 PM CDT The March of Dimes announced today the 10 winners of its 2008 Prematurity Research Initiative grants. The awards were given to "scientists who are trying to stem the growing pace of preterm birth by studying the role genes and heredity play in premature births and how the rate of fetal lung development, infection and other factors may trigger labor". This year's awards include research projects to identify genetic variations associated with preterm delivery, genetic differences in African-American women who gave birth prematurely, a family history study in Scotland, and protein biomarker studies in Israel and Portland, Oregon. In the press release, the need for and goal of these grants are described with happy, eugenic [Gk, eu – gen = "wellborn"] overtones: "Most of the causes of preterm birth remain unknown. There is an urgent purpose for this research," said Dr. Jennifer L. Howse, president of the March of Dimes. "We continue to work toward a future when every baby is born healthy." As the parent of a couple of "preemies", I'm fairly certain that this research wouldn't have helped us; premature twins are not uncommon. From a predictive health angle, I'm not sure how such information would be used. Presumably men will not be so foolish as to screen potential spouses for a premature delivery marker … that'd be a quick way to end an engagement. As for the clinical uses, what interventions would be available to women with increased risks for premature delivery? More anxiety and more bed rest? |
| Insurance and Incentives: Private or Public? [PredictER Blog] Posted: 23 May 2008 05:25 PM CDT [Sam Beasley, a law and bioethics student here at Indiana University, is a new member of the PredictER team. I asked him, as a way of introducing himself to PredictER's readers and friends, to share his thoughts on any topic relevant to the future of predictive health and personalized medicine. I think this is a good post and I hope that we will see more of Sam's contributions to PredictER Blog in the weeks to come. – Jere Odell] Now, before I begin, I need to state upfront that this is the first blog post I have ever written and I am in no way an expert in politics, public policy, health care provision, insurance. I am also new to the PredictER project, and will be working with Jennifer Girod to investigate the legal and policy implications of predictive medicine. I hope that this experience will broaden and deepen my understanding of health care and public policy. Jere asked me to share what's on my mind, so here it is: Following the publication of "Insurance Fears Lead Many to Shun DNA Tests" in The New York Times (24 February 2008), the blogosphere lit up with comments on the need to protect people from discrimination—protection that would be, presumably, provided by S. 358, the Genetic Information Nondiscrimination Act (GINA). A few, like David Dooling of PolITiGenomics, observed that the status-quo of insurance provision in the United States may seriously discourage the progress of medical research and personalized medicine. I'd like to take this discussion and move it an inch or two away from the worthy topic of discrimination. Let's think about the research and health care climate: Which insurance system provides the most incentive to pursue predictive and preventative forms of medicine: a public-funded system or the current private system—one, in which private companies sell insurance to individuals? As I said, I am certainly not an expert on these issues, but it seems to me that the major means of preventing chronic disease are, in large measure, socially, culturally and politically influenced (think food subsidies, health education in public schools, etc.). If eating a healthy diet, exercising regularly, getting scheduled medical exams, and avoiding unhealthy habits such as smoking and drug abuse are indeed foundational in the pursuit of life-long health, then public ownership would seem to be the way to go. Public is superior to private because by spreading the bill for health care over the entire population, you would provide increased incentive for voters to support public programs that promote preventative health measures. In private systems where like-situated individuals are pooled together, the healthy will remain concerned about their own health, and not the health of their neighbors. Only when the health of all affects the individual, will the individual begin to care. And if we've learned anything in America, the quickest way to get people to care is through their wallet. I am not arguing here that this is the "fairest" way to do things, (although my liberal leaning makes me inclined to think that basic health care for all is a social good worth our investment) to the contrary; some may abuse the system and choose not to pursue healthy living practices simply because they know that the cost to them will be subsidized by everyone else. I merely intend to say that if we want to stem the tide of deteriorating health in this country, we have got to find a way to make healthy living a social value. Broad-reaching social programs can do a lot to influence individual practices. If we can teach people to live in a way conducive to health, provide incentives for doing so, and get them the care that they need before minor problems turn into major ones [note: emergency room care will never be the most cost-effective means of providing basic health care needs], then we might be able to turn things around. Of course, this is just one piece in a complicated puzzle, but we have got to do better by ourselves, and if a public health care system is a step in the right direction, then we should pursue it. – Sam Beasley |
| The Good News: GINA; The Bad News ... ? [PredictER Blog] Posted: 23 May 2008 05:21 PM CDT A few weeks ago, congress passed the Genetic Information Nondiscrimination Act of 2008 (GINA), a much anticipated piece of legislation, nearly thirteen years in the making. Since the first version of the bill prohibiting genetic discrimination was introduced in Congress in 1995, the legislation has received significant bipartisan support and support from both the Clinton and Bush White Houses. Until recently, however, even in the face of all of that support, just a few members of Congress were able to block the legislation's progress. An agreement has finally been reached, and GINA is now the law of the land; it was signed by President Bush on Wednesday, May 21st. Regular readers of PredictER Blog know that we have been following GINA; now that it has been signed, it's time to kick the tires and to see what we've got. This is the first of a series of posts in which I share what I see as the ups and downs of this legislation. I'll alternate between the good news and the bad news and conclude with an overall "thumbs up" or "thumbs down". For this post, some good news: GINA really is a big deal, in the legislative sense. It provides (at least in theory) significant protection from discrimination based upon genetic information in the employment and health insurance contexts. Studies by the NIH and other institutions have revealed that the vast majority of the American public is afraid of being discriminated against in these arenas and believes that it would be wrong for employers and insurers to do so. Furthermore, additional studies have revealed that a significant number of people who would be likely to benefit medically from genetic tests choose to forgo them for fear that they will lose their job, or health care coverage depending upon the results. Along the same lines, many people are choosing not to participate in important research that requires subjects to undergo genetic testing out of fear of discrimination. Clearly, then, GINA should help to allay public apprehensions and to encourage both the pace of research and the practice of personalized medicine. But … stay tuned for the "bad news". – Sam Beasley |
| Evolutionary Novelties. [T Ryan Gregory's column] Posted: 23 May 2008 04:31 PM CDT Another entry in the "I didn't know about this blog, but I am glad I do now" files: Evolutionary Novelties by Todd Oakley from the University of California, Santa Barbara. Go, read it. Before we start bugging him to blog here instead. :) |
| Pulse-Oximeter in Second Life [ScienceRoll] Posted: 23 May 2008 02:37 PM CDT You may know about the Ann Myers Medical Center in Second Life, the virtual world, where we train medical students and nurses through case presentations. The more realistic these medical simulations are, the more efficiently the education can be. That’s why the new pulse-oximeter in our center could be really helpful during the exercises. Here is a screenshot of the ITU:
What you can edit on the monitor:
And the monitor itself:
Further reading:
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| Down Syndrome Caucus [Mary Meets Dolly] Posted: 23 May 2008 12:31 PM CDT Certainly a step in the right direction. What a cute baby!
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| Officially unemployed [Mary Meets Dolly] Posted: 23 May 2008 12:21 PM CDT Well, I am offcially unemployed. I am not sure how I feel about that. I could yet jump right back in the field in another lab, but I think with four young children, a hiatus from the working world is in order. The upside is that I can blog more!!! I am just gonna start out slow as I catch up on all the happenings is our crazy brave new world. I did see this announcement in the Honolulu News that once again makes my point for me: IVF and cloning go hand in hand. They are sisters. Once you take the act of love out of procreation, anything goes:
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| submit your post for the Molecular & Cell Biology Carnival #3 [the skeptical alchemist] Posted: 23 May 2008 11:53 AM CDT That's right, the time is coming close again, and all submissions should be in by June 7 using this form. We already have a host for this edition - Bertalan over at ScienceRoll will be your host, and I am very happy that he is taking on the MCB Carnival for the upcoming edition. If you are interested in hosting the next edition (July 13), shoot me an e-mail at the address in the sidebar, or leave a comment. You can find out more about the Carnival, how to host it, and how to get a button to put on your site at the official MCB Carnival website. You can also check the official website to find links to all previous editions of the Carnival. So get this science thing going: send a post to Bertalan using that form and/or spread the good news - there is new science carnival in the blogosphere, and it wants you! If the form does not work for you, just e-mail me and I will forward your submission to our host. See you over the week-end with some peer-reviewed blog goodness! P.S. Lest I forget: the latest edition of the Skeptics' Circle is up - in limericks. View blog reactions |
| mtDNA diversity in Southeast Asia and rising sea levels [Yann Klimentidis' Weblog] Posted: 23 May 2008 10:14 AM CDT In this paper, the authors look at mtDNA diversity in Island Southeast Asia and propose that haplogroup E arose "in situ" 35 Kya ago and then there was a dispersal of the haplogroup around the time that the area broke up into islands due to rising sea levels. Climate Change and Postglacial Human Dispersals in Southeast Asia Pedro Soares et al. Molecular Biology and Evolution 2008 25(6):1209-1218 Abstract: Modern humans have been living in Island Southeast Asia (ISEA) for at least 50,000 years. Largely because of the influence of linguistic studies, however, which have a shallow time depth, the attention of archaeologists and geneticists has usually been focused on the last 6,000 years—in particular, on a proposed Neolithic dispersal from China and Taiwan. Here we use complete mitochondrial DNA (mtDNA) genome sequencing to spotlight some earlier processes that clearly had a major role in the demographic history of the region but have hitherto been unrecognized. We show that haplogroup E, an important component of mtDNA diversity in the region, evolved in situ over the last 35,000 years and expanded dramatically throughout ISEA around the beginning of the Holocene, at the time when the ancient continent of Sundaland was being broken up into the present-day archipelago by rising sea levels. It reached Taiwan and Near Oceania more recently, within the last 8,000 years. This suggests that global warming and sea-level rises at the end of the Ice Age, 15,000–7,000 years ago, were the main forces shaping modern human diversity in the region. |
| Around the Blogs [Bitesize Bio] Posted: 23 May 2008 07:24 AM CDT This week is dominated by career-related posts discussing life in science. Check ‘em out! Postdoc Malaise Why It’s So Hard to Get That Course You Need Postdoc Life vs. PI Life What Happens When a PI Dies Your Review is Hereby Summarily Rejected DNA Replication in E. coli: The Solution Why Science Centers Matter |
| Sorry to Coriell, Stay of the New Jersey Turnpike [The Gene Sherpa: Personalized Medicine and You] Posted: 23 May 2008 07:11 AM CDT Sorry to the attendees at Coriell Yesterday. They were ready to start participating in the Delaware Personalized Medicine Project. I was scheduled to speak on the topic of "Patient Centered Genomic... [[ This is a content summary only. Visit my website for full links, other content, and more! ]] |
| Make Music, Boost Brain [Sciencebase Science Blog] Posted: 23 May 2008 07:00 AM CDT
Meanwhile, I took up singing in a choral group (called Big Mouth) and have been compelled to become more adept at reading music in a slightly more disciplined environment than jamming on guitars with friends. Big Mouth formed in the autumn of 2007 and I’ve been with them from about October, so that’s several months of regularly, weekly singing practice and a couple of very low-key gigs. We even put together a last-minute audition video tape for the BBC’s Choir Wars, but didn’t make it through to the heats, unfortunately. Anyway, that’s probably enough detail. The point I wanted to make is that until I joined Big Mouth and began making music regularly with a group, I’d always felt like I was quite useless at remembering people’s names. Like a lot of people I had to make a very conscious effort to retain introducees. However, in the last few months, with no deliberate action on my part, I’ve noticed that I seem to remember stuff like fleeting introductions, the names of people mentioned in conversations, or press releases and other such transient data much better than before. I’m curious as to whether it’s the more formal, group music that’s done something to the wiring in my brain to boost this skill or maybe it’s just the new friends I’ve made joining a new, fairly large social group like this. My suspicions are boulstered somewhat by a recent TED talk from Tod Machover and Dan Ellsey on the power of music A post from David Bradley Science Writer |
| What’s on the web (2008 May 23) [ScienceRoll] Posted: 23 May 2008 06:29 AM CDT
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| Facebook for Scientists: Going Live [ScienceRoll] Posted: 23 May 2008 05:54 AM CDT Can ResearchGATE become a Facebook for researchers? We will get an answer soon because they are now going live.
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| Books About DNA: DNA: Promise and Peril [Eye on DNA] Posted: 23 May 2008 03:01 AM CDT
Here is Kathy Johnston’s impression of the book as originally posted at GENEALOGY-DNA: As I am sitting here thumbing through the book, I get the impression that it is well written. It touches on forensics, ethics, race, gender, patents, cloning, reproductive medicine, gene testing, engineering and health insurance policies. However, I think they completely missed the impact that genetic genealogy is having right now and will have in the future as more of us order tests on ourselves. Dr. Edward McCabe is a co-director for the UCLA Center for Society and Genetics so if anyone should know about the social impact that amateur DNA research is having, he should know. But I think they missed the boat on this one. The authors stressed that recreational DNA research represents “an extremely small part of the genome” but I don’t think they realize how many tests are actually being ordered on extended family members. These academicians never seem to get it when it comes to understanding pedigree collapse, extended family and surname research projects and how the Internet and globalization will be revolutionizing genealogy through DNA search engines and pedigrees as more and more people are tested. Think of all the retired people who are spending their money on this hobby and helping labs to build branches on the phylogenetic trees that previously only universities could do. In addition, I should think a major university with a huge public policy department like UCLA would be looking at the social and medical impact of genetic genealogy. Well, it may be good thing that we are not on their radar screen right now. We can grow undisturbed. This is what the McCabes think about genealogy DNA testing:
I was just surprised that they have not seen the explosion of DNA studies being performed by us so-called amateurs. Genealogy will eventually make its way into the academic circles as the researchers figure out they need better pedigrees to help them figure out the more complicated mechanisms of inheritance especially when they look more at epigenetics. |
| TGG Accepted To The 9rules Network [The Genetic Genealogist] Posted: 23 May 2008 02:00 AM CDT And don’t forget that starting next Tuesday I’m starting a great nine-part series of interviews with some of the biggest names in the field of genetic genealogy! |
| Major ‘missed’ biochemical pathway emerges as important in virtually all cells [Think Gene] Posted: 22 May 2008 11:17 PM CDT A new study by Duke University researchers provides more evidence that the nitric oxide (NO) system in the life of a cell plays a key role in disease, and the findings point to ways to improve treatment of illnesses such as heart disease and cancer. The nitric oxide system in cells is "a major biological signaling pathway that has been missed with regard to the way it controls proteins," and it is linked to cancer and other diseases when the system goes awry, said Jonathan Stamler, M.D., a professor of medicine and biochemistry at Duke University Medical Center who worked on the study. In the body, nitric oxide plays a role in the transport of oxygen to tissues and physiological activities such as the transmission of nerve impulses, and the beating of the heart. When things go awry with the nitric oxide system, bad things can happen in bodies, according to recent studies. For instance, there may be too little nitric oxide in atherosclerosis and there may be too much in Parkinson's disease; there may not be enough nitric oxide in sickle cell disease and there may be too much in some types of diabetes, Stamler said. The new findings, which Stamler said change understanding of how the nitric oxide system is controlled, appear in the May 23 issue of the journal Science. "What we see now for the first time in the Science paper is that there are enzymes that are removing NO from proteins to control protein activity," Stamler said. "This action has a broad-based effect, frankly, and probably happens in virtually all cells and across all protein classes. Nitric oxide is implicated in many disease processes. Sepsis, asthma, cystic fibrosis, Parkinson's disease, heart failure, malignant hyperthermia — all of these diseases are linked to aberrant nitric-oxide-based signaling." An important factor that previously wasn't appreciated, he said, is that the target of nitric oxide in disease is different in every case. The finding of how nitric oxide binding to proteins is regulated opens the field for new refinement in biochemical research, said Stamler, who has been studying nitric oxide in cells for 15 years. "Now we will need to study whether the aberrant cell signals are a matter of too much NO being produced and added to proteins or not enough being removed from proteins," he said. "It is not simply a matter of too much or too little NO being in cells, but rather how much is being added or taken away from specific proteins, which is quite a different thing." First author on the paper, Moran Benhar, Ph.D., and co-author Douglas Hess, Ph.D., are both in the Duke Department of Medicine. Co-author Michael Forrester is a graduate student in the Duke Department of Biochemistry. The research explains that the enzymes thioredoxin 1 and thioredoxin 2 remove nitric oxide from the amino acid cysteine within mammalian cells, thereby regulating several different actions in cells. One result of this removal is the activation of molecules that begin apoptosis, which is the normal programmed death of a cell. This process has potential importance for many diseases, including inflammatory diseases, heart failure and cancer. Because thioredoxins are established targets of drug therapy for arthritis, the research suggests potential therapeutic applications of the process. The nitric oxide system is analogous to the much more studied phosphorylation system, in which phosphates are added and removed from proteins, the paper said. Changes in phosphorylation are among the most common causes of disease, and proteins that regulate phosphorylation are major drug targets, Stamler said. "Aberrant dephosphosphorylation causes disease. Expect the same for denitrosylation," Stamler said. Similar research at Duke that was published in the journal Nature on March 16 supports Stamler's findings. Christopher Counter, an associate professor in the Duke Department of Pharmacology and Cancer Biology, and colleagues found that eNOS (endothelial nitric oxide synthase), an enzyme that enhances the creation of nitric oxide, promoted tumor development and tumor maintenance in mice. "The Chris Counter work is especially exciting because he shows that a nitric oxide synthase is linked to cancer, and he specifically identifies the protein that is the target of the nitric oxide, the protein that gets turned on through S-nitrosylation," Stamler said. Blocking S-nitrosylation of this protein prevented cancer. The steady stream of new papers on nitric oxide seems to underscore Stamler's long-held belief that nitric oxide affects cells in bigger ways than many had appreciated. "When we began our studies two decades ago, we hypothesized that nitric oxide was part of a significant, broad-based system," Stamler said. "Our hypothesis never changed." Source: Duke University Medical Center Josh says: I found this shocking, because in my studies we were never even told that nitric oxide is sometimes bound to cystine. I suppose this could be because no one thought it was important. It reminds me of lecture I attended on the use of ubiquitin for regulation rather than targetting proteins for degredation. I’m looking forward to seeing the upcoming research in this area. |
| ThinkGene is Upgrading! [Think Gene] Posted: 22 May 2008 10:42 PM CDT Hi everyone, The good news is that ThinkGene has gotten quite popular recently. So popular that we’ve had to upgrade our servers. The bad news is that we may experience the odd error or unexpected downtime as we make the transition. Thank you for your understanding. Also, if you notice a bug or outage, please contact us so that we may fix it promptly. Thanks! |
| This is How We Teach Critical Thinking?! My Kid's Science Homework [adaptivecomplexity's column] Posted: 22 May 2008 10:18 PM CDT Not teaching evolution isn't the only problem in America's science classrooms. The evidence for this for this came home today in the form of my third grader's homework. My daughter's third grade class is learning about plant life cycles, from a textbook whose publisher I will, out of mercy, refuse to name. This textbook attempts to teach eager young students about some of the critical thinking skills scientists use, including making predictions, making inferences or drawing conclusions, and making comparisons. Teaching critical thinking skills - it sounds great, right? The problem though, is that this textbook drums home these key words without making any distinction whatsoever between them. |
| Tell me Everything: How To Use SNPedia for 23andMe and deCODEme [Think Gene] Posted: 22 May 2008 10:17 PM CDT Services like 23andMe and deCODEme test for hundreds of thousands of SNPs (genetic datapoints). Yet, these services only attempt to interpret less than 100 traits in their web reports. [1] Fortunately, these services allow you to download the raw data from your test to be interpreted elsewhere. For example, recently Mike Cariaso “creatively profiled” Lilly Mendel (23andMe’s female demo user) using the public SNPedia database and Promethease software to win the 23andMe Win Your Genome Contest.
These tools are not yet user friendly, and they certainly exist beyond the general consumer. However, I purchased a 23andMe test a couple months ago, and as a power user, I wanted ALL the data. Yes, I know that the research is new, the interpretations can be highly speculative, and 23andMe is making a laudable effort to make the best research accessible. But hey, I spent $1000; I want to know everything. Further, while these services do not report many high-penetrance genes like BRCA (breast cancer) for legal reasons [2], some of that information is in the raw test data “for your own interpretation.” If 23andMe is the Apple I of genomics, this is the box of parts for garage assembly. Enjoy! How To Use SNPedia for 23andMe and deCODEme1) Get Data Download your test results. If you do not have a 23andMe or deCODEme account, you may download a sample dataset from 23andMe’s trial users. (deCODEme’s trial user does not yet support data download) Download Lilly Mendel’s raw data from ThinkGene 23andMe:
Here is what raw 23andMe data looks like from my genome: # rsid chromosome position genotype rs3094315 1 742429 AA rs12562034 1 758311 GG rs3934834 1 995669 CC rs9442372 1 1008567 AA rs3737728 1 1011278 AG rs11260588 1 1011521 GG rs6687776 1 1020428 CC rs9651273 1 1021403 AG rs4970405 1 1038818 AA rs12726255 1 1039813 AA rs11807848 1 1051029 CT rs9442373 1 1052501 CC ... and so on for over 570,000 lines. Raw deCODEme data looks like this: Name,Variation,Chromosome,Position,Strand,YourCode rs2278544,A/G,2,136262580,+,AG rs4954633,C/T,2,136263105,+,CC rs3213890,A/G,2,136268658,+,AG rs1807356,A/G,2,136271954,-,AA rs2015532,A/C,2,136271995,-,AC rs2322659,C/T,2,136272129,+,CT rs3769013,A/G,2,136272652,-,AG rs2304371,C/T,2,136278027,-,CT rs2304370,C/T,2,136278205,-,CT rs3739022,C/T,2,136278942,-,CC rs12988076,A/C,2,136286318,+,AC rs6719488,G/T,2,136291669,+,GT ... and so on for over 1,000,000 lines. 2) Get Software Download Promethease (windows only, version 0.1.14) from SNPepida. Also, see Promethease’s homepage. 3) Run Software Launch Promethease and select your data file. Select your race. Begin Analysis. Note that Promethease automatically detects which service generated your SNP data.
WARNING: generating a report with Promethease may take hours. If there is demand (and time), I’ll write / help write better Open SNP software. Please contact me if this interests you. 4) View Report MY REPORT: Andrew Yates’s SNPedia report via Promethease [3] Promethease outputs a final report of about SNP 1300 entries as an HTML file to your desktop. It’s not pretty or easy to read —let alone understand as actionable medical information. But this is the best that Open SNP software has to offer today. See Interpreting Promethease / SNPedia Results for help understanding your Promethease report. 5) Report Reflection While my SNPedia report contained more information about my SNPs, I didn’t learn anything worth knowing that 23andMe (or deCODEme) didn’t already tell me. Further, running and understanding my “open SNP” report, while interesting, took hours. While much potential exists for community efforts to understand our genome, SNPedia is not yet ready for the majority of genetics enthusiasts, let alone the general public. Notes [1] 23andMe and deCODEme officially report less than one hundred traits, plus ancestry. 23andMe tests for about 500,000 SNPs; deCODE tests for about 1,000,000. However, the useful information in both tests is about the same (for now). [2] The industry line is that users shouldn’t know about some high-penetrance genes for reasons including “it’s for your own good” and “high penetrance genes are not common enough,” but the real reason is that these genes are defended by walls of patents, expensive licenses, and litigious companies. See "Low penetrance genes v high penetrance genes" [3] At first, I was leery about posting my genome online, but then I realized: hey, if I’m ever discriminated against (and I can easily check my server logs to see who has viewed my genome report), maybe I’ll get to participate in a landmark judicial case! |
| Anti-HIV drugs reduce the cause of some forms of vision loss [Think Gene] Posted: 22 May 2008 10:06 PM CDT A potential new therapeutic use for anti-HIV drugs known as protease inhibitors has been suggested by a team of researchers from Harvard Medical School, Boston, and Inserm U848, France, as a result of their work in a mouse model of retinal detachment. An important cause of vision loss in many diseases of the eye is the death (by a process known as apoptosis) of nerve cells in the eye (known as photoreceptors) after retinal detachment. In the study, administration of HIV protease inhibitors by mouth markedly decreased photoreceptor apoptosis in the mouse model of retinal detachment. Mechanistic analysis in mouse retinal cell cultures and in mice expressing decreased amounts of specific proteins established that the HIV protease inhibitors disrupted two molecular pathways that cause apoptotic cell death, both of which affect the cell compartments known as mitochondria. As the same apoptotic cell death–inducing pathways were shown to be activated in human retinas after retinal detachment, the authors suggest that although the HIV protease inhibitors cannot reattach the retina, they might be of clinical benefit through their ability to prevent the photoreceptor apoptosis that has a central role in vision loss after retinal detachment. Source: Journal of Clinical Investigation Josh says: It makes me uneasy to disrupt apoptosis this way, as it could also contribute to cancer. However, certainly it would help in cases of retinal detachment. Perhaps there is a way to localize it to the retina. |
| Long-awaited ubiquitin receptor on the proteasome found [Think Gene] Posted: 22 May 2008 09:43 PM CDT Insulin, a hormone released in large quantities when food is consumed, is reduced by 50% only three to five minutes later. However, if the cell's internal waste disposal system malfunctions, illnesses such as Alzheimer's or Parkinson's disease may occur. To prevent this from happening, the complex process of protein degradation first needs to be fully understood at an atomic level so that appropriate drugs can be developed. Biochemists at Frankfurt University, collaborating with an international team of scientists have just taken an important step towards unravelling the workings of this mechanism. In the current edition of the scientific journal "Nature" they report finding the long-awaited receptor for ubiquitin on the proteasome. This receptor may well turn out to have a key role in fighting tumors. "A discovery of this kind happens only once in a researcher's lifetime" comments Professor Ivan Dikic, in whose group at the Institute for Biochemistry the significant finding was made. The editors of "Nature" agree and have accepted two manuscripts describing this discovery: an article (leading manuscript in the issue) and a letter (regular publication). The Institute's director Professor Werner Müller-Esterl states "We are delighted by his success of a member of our Cluster of Excellence on Macromolecular complexes. This sort of recognition is only achieved by one in a thousand scientists". However, things were looking very different only a year ago when it appeared that the research groups involved in this project - in Frankfurt, Munich, Minnesota and Harvard - were treading water. The scientists were hoping to solve structure of the portal protein from yeast using protein crystallography but the protein refused to crystallize. However, Koraljka Husnjak, a postdoctoral researcher found a way to isolate the ubiquitin binding domain in the mammalian protein, that was amenable for rapid crystallization and subsequent determination of its structure. Already some 30 years ago, the basic mechanism of cellular waste disposal was elucidated by three scientists, Aaron Ciechanover, Avram Hershko, and Irwin Rose, for which they won Nobel Prize in Chemistry in 2004. Since then it has been known that proteins due for disposal are marked with ubiquitin molecules, which are present throughout the cell. They reach the barrel-like proteasome complex via 'shuttle' molecules or through diffusion. On the upper side of the proteasome there is a kind of gatekeeper's lodge with a narrow entrance leading to an inner chamber, where aggressive enzymes cleave the protein. But first the protein is subjected to a strict control procedure to ensure that it is indeed destined for the shredder. If the gatekeeper - a receptor - recognizes that the protein is tagged with ubiquitin, the tagged protein is unfolded and can then pass through the narrow opening. While this takes place the ubiquitin separates from the protein, ready to be re-used. Until now, only one such gatekeeper, a proteasomal receptor called Rpn 10, was known. The scientists then conducted experiments to genetically remove Rpn 10 from the cell and were surprised to discover that the proteasome continued to function normally. This led them to suspect that there must be an additional protein in the cell, which compensates in the absence of Rpn 10 and serves a similar purpose. This has now been discovered: protein Rpn 13. According to Koraljka Husnjak the first breakthrough occurred about four years ago, when they found out that ubiquitin binds to a subunit in the gatekeeper's lodge. "So it became clear to us that the proteasome subunit might act as ubiquitin receptor on the proteasome. But first of all we had to clarify this binding site's function and understand the details of the binding process at an atomic level". Ivan Dikic then asked other leading international groups for their expertise in helping to solve this complex research problem. The X-ray structural analysis was carried out by Prof. Michael Groll and his group at the Technical University in Munich, and a group led by Prof. Kylie Walters at the University of Minnesota, Minneapolis undertook the NMR structure work. As soon as the binding mechanism had been understood at an atomic level, Professor Finley and his group at Harvard Medical School conducted experiments with various yeast strains in which they were able to prove that in living cells the process was indeed identical to that already suggested by the structural model. The discovery of this second receptor on the proteasome is of particular significance in cancer research since it has the potential to be blocked by specific drugs. This would then prevent the proteins in the cell from being broken down. Since developing cancer cells depend on the breakdown of specific proteins in signaling cascades, which appear critical for tumor cell survival and proliferation, the cancer cells would no longer be able to multiply. It is likely that both these receptors react selectively to certain groups of proteins. So even if one is blocked, the other continues to ensure that the proteins that are no longer needed nevertheless still gain access to the proteasome. Source: Goethe University Frankfurt Josh says: This is a HUGE discovery. Understanding the function of the proteasome is crucial to our further understanding of biology, and finding ubiquitin receptors on it brings us one step closer… |
I’ve played guitar - classical, acoustic, electric - for three decades, ever since I pilfered my sister’s nylon string at the age of 12, although even before that, I’d had a couple of those mini toy guitars with real strings at various points in my childhood. I eventually learned to follow music and guitar tablature, but was only really any good at keeping up with a score if I had heard someone else play the music I was hoping to make myself.
The Genetic Genealogist has been 
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