The DNA Network |
| Posted: 04 Jun 2008 08:25 PM CDT
After centuries of Principal Assistant to The Grim Reaper, tobacco may be turning over a new leaf. (sorry. couldn’t resist.) Tobacco, as it turns out, is a really efficient medium for scaling up production of viral drug vectors for vaccines. So, instead of addicting people then hip-checking them off this mortal coil, tobacco plants have been conscripted in creating cheaper vaccines for cervical cancer, hepatitis B and more. Could you imagine a world where nobody smoke, and tobacco is just a work-horse for health care? Reminds us of one of our favorite words: Enantiodromia – the process by which things become their opposites. |
| The Onion: Genetic Scientists Develop Sheep With Brain Of A Goat [Think Gene] Posted: 04 Jun 2008 07:47 PM CDT |
| Simple membranes could have allowed nutrients to pass into primitive cells [Think Gene] Posted: 04 Jun 2008 06:53 PM CDT When the first cells developed, how could they bring molecules from the environment into their living interior without the specialized structures found on the modern cell membrane? A research team from Massachusetts General Hospital (MGH) has found that the sort of very simple membrane that may have been present on primitive cells can easily allow small molecules – including the building blocks of RNA and DNA – to pass thorough. Their report will appear in the journal Nature and is receiving early online release. “We have found that membranes made from fatty acids and related molecules – the most likely components of primitive cell membranes – have properties very different from those of the modern cell membrane, which uses specialized pumps, channels or pores to control what gets in and out,” says Jack Szostak, PhD, of the MGH Department of Molecular Biology and Center for Computational and Integrative Biology, the report’s senior author. “Our report shows that very primitive cells may have absorbed nutrients from their environment, rather than having to manufacture needed materials internally, which supports one of two competing theories about fundamental properties of these cells.” How nutrients could get into cells without the specialized mechanisms of the modern cell membrane has been a mystery. The environment in which primitive cells formed probably included many types of fatty acids, which could have been supplied through a couple of scenarios. Fatty-acid molecules could have been formed by the action of heat and minerals deep beneath the earth’s surface and then brought to the surface through deep-sea vents, hot springs or geysers; or they could have come to the earth’s surface on meteorites. No matter the original source, when fatty acids are concentrated in water, they will naturally assemble into membranes which then close into tiny spherical structures called vesicles. Szostak’s team carefully analyzed vesicles comprised of different fatty acid molecules and identified particular features that made membranes more or less permeable to potential nutrient molecules. They found that, while large molecules such as strands of DNA or RNA could not pass through fatty acid membranes, the simple sugar molecules and individual nucleotides that make up larger nucleic acids easily crossed the membrane. To further explore the function of a fatty acid cell membrane, the researchers used activated nucleotides they developed for this study that will copy a DNA template strand without needing the polymerase enzyme usually required for DNA replication. After placing template molecules inside fatty-acid vesicles and adding the activated nucleotides to the external environment, they found that additional DNA was formed within the vesicles, confirming that the nucleotide molecules were passing through the fatty-acid membranes. “Today we have complex cells living in a chemically simple environment, but the primitive environment was chemically very complex, allowing for the synthesis of complex organic chemicals that cannot be formed in today’s environment,” Szostak explains. “We think that the first cells were very simple and assembled from molecules present in localized environments on the early earth.” For many years, Szostak’s team has been working on the development of a ‘protocell’ that would replicate probable features of the earth’s first cells. “The chemistry of nucleic acid replication is the remaining hard part,” he says. “We’re putting a lot of effort into nucleic acid chemistry, but there are also other interesting and important questions – like how cells made the transition from very leaky early membranes to today’s very impermeable membranes – that we are starting to study.” Source: Massachusetts General Hospital Josh says: This reminds me about when I read that Stanley Miller, who demonstrated that organic molecules could have formed from inorganic molecules such as ammonia and cyanide in an early Earth environment. He recently found that when water with cyanide and ammonia is frozen, RNA molecules form and polymerize into chains over a short period of time (25 years). |
| Resveratrol found effective in small doses [Think Gene] Posted: 04 Jun 2008 06:15 PM CDT How, scientists wonder, do the French get away with a clean bill of heart health despite a diet loaded with saturated fats? The answer to the so-called “French paradox” may be found in red wine. More specifically, it may reside in small doses of resveratrol, a natural constituent of grapes, pomegranates, red wine and other foods, according to a new study by an international team of researchers. Writing this week (June 3) in the online, open-access journal Public Library of Science One, the researchers report that low doses of resveratrol in the diet of middle-aged mice has a widespread influence on the genetic levers of aging and may confer special protection on the heart. Specifically, the researchers found that low doses of resveratrol mimic the effects of what is known as caloric restriction - diets with 20-30 percent fewer calories than a typical diet - that in numerous studies has been shown to extend lifespan and blunt the effects of aging. “This brings down the dose of resveratrol toward the consumption reality mode,” says senior author Richard Weindruch, a University of Wisconsin-Madison professor of medicine and a researcher at the William S. Middleton Memorial Veterans Hospital. “At the same time, it plugs into the biology of caloric restriction.” Previous research has shown that resveratrol in high doses extends lifespan in invertebrates and prevents early mortality in mice given a high-fat diet. The new study, conducted by researchers from academia and industry, extends those findings, showing that resveratrol in low doses and beginning in middle age can elicit many of the same benefits as a reduced-calorie diet. “Resveratrol is active in much lower doses than previously thought and mimics a significant fraction of the profile of caloric restriction at the gene expression level,” says Tomas Prolla, a UW-Madison professor of genetics and a senior author of the new report. The group explored the influence of the agent on heart, muscle and brain by looking for changes in gene expression in those tissues. As animals age, gene expression in the different tissues of the body changes as genes are switched on and off. In the new study - which compared the genetic crosstalk of animals on a restricted diet with those fed small doses of resveratrol - the similarities were remarkable, explains lead author Jamie Barger of Madison-based LifeGen Technologies. In the heart, for example, there are at least 1,029 genes whose functions change with age, and the organ’s function is known to diminish with age. In animals on a restricted diet, 90 percent of those heart genes experienced altered gene expression profiles, while low doses of resveratrol thwarted age-related change in 92 percent. The new findings, say the study’s authors, were associated with prevention of the decline in heart function associated with aging. In short, a glass of wine or food or supplements that contain even small doses of resveratrol are likely to represent “a robust intervention in the retardation of cardiac aging,” the authors note. That finding may also explain the remarkable heart health of people who live in some regions of France where diets are soaked in saturated fats but the incidence of heart disease, a major cause of mortality in the United States, is low. In France, meals are traditionally complemented with a glass of red wine. The new resveratrol study is also important because it suggests that caloric restriction, which has been widely studied in animals from spiders to humans, and resveratrol may govern the same master genetic pathways related to aging. “There must be a few master biochemical pathways activated in response to caloric restriction, which in turn activate many other pathways,” explains Prolla. “And resveratrol seems to activate some of these master pathways as well.” The new findings, according to Weindruch and Prolla, provide strong evidence that resveratrol can improve quality of life through its influence on the different parameters of aging such as cardiac function. However, whether the agent can extend lifespan in ways similar to caloric restriction will require further study, according to the new report’s authors. Source: University of Wisconsin-Madison Josh says: I’m not sure how low of a dose is actually effective, but this is certainly a good sign. There has been a lot of research into synthetic, more potent variations of resveratrol produced by Sirtris Pharmaceuticals. At one time I was taking resveratrol pills when the original studies first came out, but stopped once I realized the dose was much too low to be effective. However, if this study is verified, I may end up taking resveratrol again. |
| McCain and Obama on healthcare [Synthesis] Posted: 04 Jun 2008 03:29 PM CDT CNN, which was hotly denying the rumors of Clinton’s concession until as late as last night, has an article up about the policy differences between the Obama and McCain. The article they link to for a critical analysis of the candidates plans is entitled, “Why McCain has the best health-care plan”. Way to be impartial, CNN. Nonetheless, it’s a good article with lots of great detailed information on exactly how the two proposed policies would work, even if the conclusion presented in the title seems a little forced. I’ll summarize the information from the article, and you can see if you come up with my conclusions, or the conclusions of the author. McCainMcCain’s plan would eliminate the employer-paid healthcare plans in favor of a tax credit for buying insurance. He’s not abolishing the employer-paid plans, just making the cost of the plan be considered as taxable income, and offering a credit to offset the extra taxes you’d end up paying. This is thought to lead to via the free market to employers dropping the plans entirely in favor of simply paying employees more, which they can then spend on individual or family plans. It’s also assumed that people would contribute income to an HSA, so combining the increase in income + plus the tax credit would allow people to afford high-deductible, low-premium plans and pay out of pocket for anything else. To apply a little more free-market action to the health insurance industry, he’s going to allow health insurance to be sold across state lines, so a person in Mississippi could buy insurance from a Pennsylvania insurer, subject to Pennsylvania laws. This allows healthy, young people to find cheaper plans which cover less, but would result in increases in the cost of the more comprehensive plans, as they become increasingly composed of the expensive to care for old folks. The overall idea is that insurers will have to compete to get business, and this will make insurers pressure hospitals to reduce costs. ObamaObama’s plan has two components: a private and a public part. The public part is essentially Medicare as we have it today, and the private part is an employer-provided healthcare plan similiar to the federal employee healthcare plan. Employers can choose whether to offer the private plan or pay a tax to fund the public plan. The plans have a wide range of benefits, more than young people need, so the deductible isn’t as low as it could be under a free market system, but it will keep the comprehensive coverage plans from spiking in cost. Supposedly employers will all drop their plans and pay the tax to fund the public program. Under this system, the individual isn’t making much choice about which plan to get, rather it’s the insurance companies that have to figure out a way to lower costs if they want to increase profits. Fortune’s conclusionsMy conclusionsWould it be too cute to say McCain’s plan would make health insurance like the airline industry, whereas Obama’s plan would make it like the public school system? .gif) This post is about health, insurance, McCain, obama, policy, PoliticsRelated posts |
| Busy busy busy… [Mailund on the Internet] Posted: 04 Jun 2008 03:05 PM CDT If you’re wondering why I haven’t been writing on my blog the last couple of days, let me explain. This has been “one of those weeks”. I’ve had three review reports coming in for papers I submitted ages ago, all of which I have had to respond to and figure out how to proceed with my papers (one I prefer to submit to another journal, if I can convince my co-authors; two will be resubmitted after some additional experiments). Experiments I’ve been running to show how great one of my new multi-locus association mapping methods is, turned out to show that it did about as good — but not quite — as the simplest single marker tests. Bummer. On top of that, I’ve been preparing a talk I’m giving at CLC Bio this Friday and a talk I’m giving next Wednesday at the Danish Society of Computer Science in Copenhagen. About the latter, I’m a bit confused about what is expected exactly … in the program, I have an hour and a half to give a talk just before a dinner, but that seems like a lot of time … not that I cannot fill it, but still… Anyway, I just wanted to add a quick post here to let you know that I am not quite dead yet, just caught up in work :) |
| Kin selection, even in big groups with low r? [Yann Klimentidis' Weblog] Posted: 04 Jun 2008 02:55 PM CDT The underlying question here is: does kin selection offer a benefit (even small) to cooperation even in large groups such as elephant seal colonies where coefficients of relatedness are likely to be small. The comparison to humans are obvious and interesting since most people dismiss small coefficients of relatedness as insignificant in the case of kin selection operating among human groups... in other words, this paper would suggest that: the degree of relatedness, however small, may still factor into the costs and benefits of cooperative behavior... as opposed to: once you get beyond cousins, there is no effect of kin selection. also, from the conclusion: Genetic structure—inferred by both genetic relatedness coefficients and pedigree relationships—coincided with 'social communities', an intermediate tier of the social network that closely corresponds to spatial relationships among individuals. This finding supports the idea that kin structure can arise as an emergent property of limited dispersal alone and need not imply any targeted, beneficial interactions among kin. These results are consistent with many studies showing that philopatry is a powerful mechanism by which genetic structure can accumulate as a by-product...Kin in space: social viscosity in a spatially and genetically substructured network Jochen B.W. Wolf, Fritz Trillmich Proceedings of the Royal Society London B Early online Abstract: Population substructuring is a fundamental aspect of animal societies. A growing number of theoretical studies recognize that who-meets-whom is not random, but rather determined by spatial relationships or illustrated by social networks. Structural properties of large highly dynamic social systems are notoriously difficult to unravel. Network approaches provide powerful ways to analyse the intricate relationships between social behaviour, dispersal strategies and genetic structure. Applying network analytical tools to a colony of the highly gregarious Galápagos sea lion (Zalophus wollebaeki), we find several genetic clusters that correspond to spatially determined 'network communities'. Overall relatedness was low, and genetic structure in the network can be interpreted as an emergent property of philopatry and seems not to be primarily driven by targeted interactions among highly related individuals in family groups. Nevertheless, social relationships between directly adjacent individuals in the network were stronger among genetically more similar individuals. Taken together, these results suggest that even small differences in the degree of relatedness can influence behavioural decisions. This raises the fascinating prospect that kin selection may also apply to low levels of relatedness within densely packed animal groups where less obvious co-operative interactions such as increased tolerance and stress reduction are important. |
| How to Promote Your Bio/Genetic Website [Think Gene] Posted: 04 Jun 2008 02:53 PM CDT Free website help for non-techy DNA Network members! (see below) We here at Think Gene are officially releasing news.thinkgene.com, a social site for the genomics community.
Social news sites are a better alternative to news feeds for more a bigger, more general communities because content is sorted by what’s most interesting each day by the community and contributions aren’t limited to web producing members. We’ve created a widgets on the sidebar to integrate into your browser and site to help better promote your own or your favorite biology websites. What to SubmitAnything that intelligent people interested about genetics, genomics, and biology would appreciate. Submitting your own website, business, or press releases is encouraged, but do not game the system or you and your websites will be banned. Rules
QuestionsFor more information, help integrating news.thinkgene widgets on your website, or moderator applications, please email Andrew Yates at andrew@thinkgene.com. HelpFree for DNA Network members! Need help integrating news.thinkgene widgets and other web tools to promote your website? Email us, and we will help you install the software on your website for free. If you are not a member of the DNA Network but still would like help, email us anyways, and we may be able to help you if your website is a fit for our genomics community. |
| Soylent Vaccines are Made Out of People! [Bayblab] Posted: 04 Jun 2008 02:39 PM CDT Jenny McCarthy, mom-celebre and current pin-up girl for the anti-vaccination movement, is descending on Washington DC today for a 'Green Our Vaccines' rally. There's been some buzz in the skeptical blogosphere about the rally, most notably Orac (of course) with a discussion about the Orwellian nature of the new slogan. The Green Our Vaccines campaign isn't about making vaccines more environmentally friendly, it's about removing toxins. Anti-vaxers, beginning to realize that their former pet thimerosal isn't a vaccine hazard, have moved to the more nebulous 'toxins' as the real danger of vaccines. Their list:  It's easy to pick apart this list (sucrose in vaccines is a toxin?), as some people have done. Some of that list probably isn't even present in more than trace amounts: fetal bovine serum, for example, is a cell culture supplement for growing cells to produce vaccine not an additive to the vaccines, and it's purified out. Anti-vaxers are eager to blur the line between vaccine ingredients and components of vaccine production.One of the items on the list is human diploid cells (from aborted fetal tissue). Sometimes this is listed simply as aborted fetal tissue. While it's understandable that people might not want to inject themselves with aborted fetal tissue (though, I'm not sure it's necessarily toxic), there are still a couple of problems with that inclusion on the list: 1) Vaccine makers aren't grinding up aborted fetuses and injecting them. Nor are they generating new fetal cell lines from them every time a vaccine is made. The 'human diploid cells (from aborted fetal tissue)' are one of two cell lines derived in the 60s and 70s: WI-38 and MRC-5. 2) These cell lines aren't ingredients. They are used to produce viruses used for vaccines. They are removed during the production process (a simple spin will separate the cells from the virus-rich supernatant, which is then further processed). That needs to be stressed, because it applies to many of the "toxins" on the list: tools used for production of vaccines aren't ingredients. Of course there is a potential moral objection to the use of aborted fetal cells in production, even if they aren't in the vaccine itself. The Catholic Church, for example, encourages the use of alternative vaccines where they exist and to press pharmaceutical companies to develop such alternatives. However even the Church, which is normally rigid in its stance, allows the use of vaccines derived from fetal cells in the absence of an alternative. This is made clear in their official position: "we find, in such a case, a proportional reason, in order to accept the use of these vaccines in the presence of the danger of favouring the spread of the pathological agent, due to the lack of vaccination of children." They go even further than this with regards to the German measles vaccine, adding This is particularly true in the case of vaccination against German measles, because of the danger of Congenital Rubella Syndrome. This could occur, causing grave congenital malformations in the foetus, when a pregnant woman enters into contact, even if it is brief, with children who have not been immunized and are carriers of the virus. In this case, the parents who did not accept the vaccination of their own children become responsible for the malformations in question, and for the subsequent abortion of foetuses, when they have been discovered to be malformed.That having been said, the stand taken by the 'Green Our Vaccines' group does not seem to stem from moral objections, but rather they're clear that it's about the fearful toxins. It seems that they're either unsure of how vaccines are produced or willfully misusing charged words (eg. aborted human fetus) to drum up vaccine opposition. Soylent green may be made out of people, but vaccines aren't. |
| Pepper viruses populate people poop [Discovering Biology in a Digital World] Posted: 04 Jun 2008 01:07 PM CDT Have you ever wondered what kinds of viruses can be found in human waste? Mya Breitbart and team have been sequencing nucleic acids from fecal samples in order to find out. You might expect that we'd find viruses that infect humans or viruses that infect the bacteria in our gut. I wouldn't have expected to learn the result that they found. Read the rest of this post... | Read the comments on this post... |
| Histone lysine methyltransferases and demethylases in Plasmodium falciparum. [Epigenetics News] Posted: 04 Jun 2008 12:58 PM CDT Cui L, Fan Q, Cui L, Miao J Dynamic histone lysine methylation, regulated by methyltransferases and demethylases, plays fundamental roles in chromatin structure and gene expression in a wide range of eukaryotic organisms. A large number of SET-domain-containing proteins make up the histone lysine methyltransferase (HKMT) family, which catalyses the methylation of different lysine residues with relatively high substrate specificities. Another large family of Jumonji C (JmjC)-domain-containing histone lysine demethylases (JHDMs) reverses histone lysine methylation with both lysine site and methyl-state specificities. Through bioinformatic analysis, at least nine SET-domain-containing genes were found in the malaria parasite Plasmodium falciparum and its sibling species. Phylogenetic analysis separated these putative HKMTs into five subfamilies with different putative substrate specificities. Consistent with the phylogenetic subdivision, methyl marks were found on K4, K9 and K36 of histone H3 and K20 of histone H4 by site-specific methyl-lysine antibodies. In addition, most SET-domain genes and histone methyl-lysine marks displayed dynamic changes during the parasite asexual erythrocytic cycle, suggesting that they constitute an important epigenetic mechanism of gene regulation in malaria parasites. Furthermore, the malaria parasite and other apicomplexan genomes also encode JmjC-domain-containing proteins that may serve as histone lysine demethylases. Whereas prokaryotic expression of putative active domains of four P. falciparum SET proteins did not yield detectable HKMT activity towards recombinant P. falciparum histones, two protein domains expressed in vitro in a eukaryotic system showed HKMT activities towards H3 and H4, respectively. With the discovery of these Plasmodium SET- and JmjC-domain genes in the malaria parasite genomes, future efforts will be directed towards elucidation of their substrate specificities and functions in various cellular processes of the parasites. |
| Posted: 04 Jun 2008 12:58 PM CDT Zheng L, Song J, Li Z, Fan Y, Zhao Z, Chen Y, Deng F, Hu Y Mechanical strain is one of the important epigenetic factors that cause deformation and differentiation of skeletal muscles. This research was designed to investigate how myoblast deformation occurs after cyclic strain loading. Myoblasts were passaged three times and harvested; various cyclic strains (2.5kPa, 5kPa and 10kPa) were then loaded using a pulsatile mechanical system. The adaptive response of the myoblasts was observed at different time points (0.5h, 1h, 6h and 12h) post-loading. At the early stage of cyclic strain loading (<1h), almost no visible morphological changes were observed in the myoblasts. The actin cytoskeleton showed a disordered arrangement and a weak fluorescence expression; there was little expression of talin. At 6h and 12h post-loading, the myoblasts changed their orientation to parallel (in the 2.5kPa and 5kPa groups) or perpendicular (in the 10kPa group) to the direction of strain. Fluorescence expression of both the actin cytoskeleton and talin was significantly increased. The results suggest that cyclic strain has at least two ways to regulate adaptation of myoblasts: (1) by directly affecting actin cytoskeleton at an early stage post-loading to cause depolymerization; and (2) by later chemical signals transmitted from the extracellular side to intracellular side to initiate repolymerization. |
| Posted: 04 Jun 2008 12:58 PM CDT Liao X, Siu MK, Chan KY, Wong ES, Ngan HY, Chan QK, Li AS, Khoo US, Cheung AN Epigenetic aberration is known to be important in human carcinogenesis. Promoter methylation status of RAS effector related genes, RASSF1A, RASSF2A, hDAB2IP (m2a and m2b regions) and BLU, was evaluated in 76 endometrial carcinomas and their non-neoplastic endometrial tissue by methylation specific PCR. Hypermethylation of at least one of the 5 genes was detected in 73.7% of carcinomas. There were significant correlations between methylation of hDAB2IP and RASSF1A, RASSF2A (p = 0.042, p = 0.012, respectively). Significantly, more frequent RASSF1A hypermethylation was found in Type I endometrioid carcinomas than Type II carcinomas (p = 0.049). Among endometrioid cancers, significant association between RASSF1A hypermethylation and advanced stage, as well as between methylation of hDAB2IP at m2a region with deep myometrial invasion (p < 0.05) was observed. mRNA expression of RASSF1A, RASSF2A and BLU in endometrial cancer cell lines significantly increased after treatment with the demethylating agent 5-Aza-2′-deoxycytidine supporting the repressive effect of hypermethylation on their transcription. Immunohistochemical study of DNMT1 on eight normal endometrium, 16 hyperplastic endometrium without atypia, 40 atypical complex hyperplasia and 79 endometrial carcinomas showed progressive increase in DNMT1 immunoreactivity from normal endometrium to endometrial hyperplasia and endometrioid carcinomas (p = 0.001). Among carcinomas, distinctly higher DNMT1 expression was observed in Type I endometrioid carcinomas (p < 0.001). DNMT1 immunoreactivity correlated with RASSF1A and RASSF2A methylation (p < 0.05). The data suggested that hypermethylation of RAS related genes, particularly RASSF1A, was involved in endometrial carcinogenesis with possible divergent patterns in different histological types. DNMT1 protein overexpression might contribute to such aberrant DNA hypermethylation of specific tumor suppressor genes in endometrial cancers. |
| Posted: 04 Jun 2008 12:58 PM CDT Kimura S, Sawatsubashi S, Ito S, Kouzmenko A, Suzuki E, Zhao Y, Yamagata K, Tanabe M, Ueda T, Fujiyama S, Murata T, Matsukawa H, Takeyama K, Yaegashi N, Kato S Histone arginine methylation is an epigenetic marker that regulates gene expression by defining the chromatin state. Arginine methyltransferases, therefore, serve as transcriptional co-regulators. However, unlike other transcriptional co-regulators, the physiological roles of arginine methyltransferases are poorly understood. Drosophila arginine methyltransferase 1 (DART1), the mammalian PRMT1 homologue, methylates the arginine residue of histone H4 (H4R3me2). Disruption of DART1 in Drosophila by imprecise P-element excision resulted in low viability during metamorphosis in the pupal stages. In the pupal stage, an ecdysone hormone signal is critical for developmental progression. DART1 interacted with the nuclear ecdysone receptor (EcR) in a ligand-dependent manner, and co-repressed EcR in intact flies. These findings suggest that DART1, a histone arginine methyltransferase, is a co-repressor of EcR that is indispensable for normal pupal development in the intact fly. |
| Oxidative stress, DNA methylation and carcinogenesis. [Epigenetics News] Posted: 04 Jun 2008 12:58 PM CDT Franco R, Schoneveld O, Georgakilas AG, Panayiotidis MI Transformation of a normal cell to a malignant one requires phenotypic changes often associated with each of the initiation, promotion and progression phases of the carcinogenic process. Genes in each of these phases acquire alterations in their transcriptional activity that are associated either with hypermethylation-induced transcriptional repression (in the case of tumor suppressor genes) or hypomethylation-induced activation (in the case of oncogenes). Growing evidence supports a role of ROS-induced generation of oxidative stress in these epigenetic processes and as such we can hypothesize of potential mode(s) of action by which oxidative stress modulates epigenetic regulation of gene expression. This is of outmost importance given that various components of the epigenetic pathway and primarily aberrant DNA methylation patterns are used as potential biomarkers for cancer diagnosis and prognosis. |
| Posted: 04 Jun 2008 12:58 PM CDT Toepoel M, Joosten PH, Knobbe CB, Afink GB, Zotz RB, Steegers-Theunissen RP, Reifenberger G, van Zoelen EJ Aberrant expression of the platelet-derived growth factor alpha-receptor (PDGFRA) gene has been associated with various diseases, including neural tube defects and gliomas. We have previously identified 5 distinct haplotypes for the PDGFRA promoter region, designated H1, H2alpha, H2beta, H2gamma and H2delta. Of these haplotypes H1 and H2alpha are the most common, whereby H1 drives low and H2alpha high transcriptional activity in transient transfection assays. Here we have investigated the role of these PDGFRA promoter haplotypes in gliomagenesis at both the genetic and cellular level. In a case-control study on 71 glioblastoma patients, we observed a clear underrepresentation of H1 alleles, with pH1 = 0.141 in patients and pH1 = 0.211 in a combined Western European control group (n = 998, p < 0.05). Furthermore, in 3 out of 4 available H1/H2alpha heterozygous human glioblastoma cell lines, H1-derived mRNA levels were more than 10-fold lower than from H2alpha, resulting at least in part from haplotype-specific epigenetic differences such as DNA methylation and histone acetylation. Together, these results indicate that PDGFRA promoter haplotypes may predispose to gliomas. We propose a model in which PDGFRA is upregulated in a haplotype-specific manner during neural stem cell differentiation, which affects the pool size of cells that can later undergo gliomagenesis. |
| Posted: 04 Jun 2008 12:58 PM CDT Kim JC, Cho YK, Roh SA, Yu CS, Gong G, Jang SJ, Kim SY, Kim YS Clinicopathologic features of sporadic colorectal adenocarcinomas were compared using integrated data from 244 patients subjected to curative resection. Individual steps in the tumorigenesis pathway, that is, adenomatosis polyposis coli (APC), Wnt-activated, base excision repair mutations, mismatch repair defects, RAF-mediated, transforming growth factor (TGF)-beta-suppressed, bone morphogenic protein (BMP)-suppressed, and p53 alterations, were examined in terms of genetic and epigenetic changes, as well as protein expression. Genetic and molecular alterations of right colon cancers were distinct from those of left colon and rectal cancers. Rectal cancers showed the attenuated phenotype of left colon cancers. Tumors most frequently displayed either TGF-beta- or BMP-suppressed alterations (81.2%), followed by RAF-mediated alterations (78.6%), and mismatch repair defects (38.4%), constituting a total of 24 integrated pathways. Tumors lacking APC mutations or carrying the RAF alteration (V600E) were frequently associated with lymphovascular invasion and lymph node metastasis (P < 0.05). Poorly differentiated or mucinous adenocarcinomas were generally associated with high level microsatellite instability, Axin2 suppression, TGF-beta1 or BMPR1A suppression, loss of heterozygosity of D18S46 or D18S474, and absence of base excision repair mutations (P < 0.0001-0.05). Early tumor recurrence was significantly correlated with lack of APC mutations (P = 0.036). Moreover, tumors that concurrently displayed APC/Wnt-activated, TGF-beta/BMP-suppressed, and p53 alterations were significantly predisposed to early recurrence (P = 0.026). Our data clearly indicate that particular steps or pathways of colorectal tumorigenesis are closely associated with characteristic clinicopathologic features that, in turn, determine biological behavior, such as tumor growth, invasion, and recurrence. |
| Cell Phones and Cancer Yet Again [adaptivecomplexity's column] Posted: 04 Jun 2008 11:45 AM CDT The NY Times has another story about a possible link between cell phones and brain cancer. Apparently, this controversy has flared up not because of any new scientific research, but because several neurosurgeons told Larry King that they don't hold cell phones to their ears. |
| Flash animations of Sanger DNA Sequencing [Discovering Biology in a Digital World] Posted: 04 Jun 2008 10:30 AM CDT I'm in Berkeley right now at the annual Bio-Link Summer Fellows forum. We're getting to hear talks from people in the biotech industry, listen to enthusiastic instructors describe their biotech programs and ideas, and try out new educational materials. Yesterday, two speakers (Damon Tighe and Jason Baumohl) from the Joint Genome Institute in Walnut Creek, CA, gave a fun talk about DNA sequencing and sequence assembly. They also showed some very nice Flash animations, made by Damon Tighe, at the JGI, that illustrate how DNA sequencing is done. There's no sound, but the animations are quite nice. The site also has some step by step diagrams describing the process. I think the animations and diagrams would be a great help to students who are engaged in DNA sequencing projects. |
| ASM Phylogenomics Notes [The Tree of Life] Posted: 04 Jun 2008 08:41 AM CDT Well, I just gave my talk on phylogenomic and functional predictions and am going to try and catch up with blogging. In my talk I discussed how an understanding of function and prediction of function requires an understanding of how functions have evolved. Patricia Babbitt gave a talk after mine on another aspect of phylogenomics and functional predictions. She has done some really interesting studies (see her lab site here) of functional diversifications and the molecular level by integrating genomic, structural, biochemical and phylogenetic analyses. She showed some really nice tools for clustering and visualization protein families that, although not phylogenetic, seemed to be very useful for the onslaught of genome data. Unfortunately, most of her publications are not in OA journals so I cannot use any of the figures here and am not going to bother linking to the papers. Kimmen Sjolander is talking now about her phylogenomic studies. She is discussion "Phylofacts" which are precomputer phylogenetic trees of gene families from across the tree of life. One great thing about her work - most of it is published in OA journals and most of her software is available for free download.  More detail on Phylofacts is available in her Genome Biology paper here. Kimmen has done some really great work on automating phylogenomic functional predictions and this is one example. Also see her Flower Power and Sci-Phy and Satchmo and Intrepid and Phylo builder other tools (downlaods and other information are available at her website here.) Gretta Serres will be speaking next. She is discussing "linking metabolic diversity to protein families" os something to that effect. She discussed something I never have thought of doing which is the following - take genomes, identify the size of protein families in each genome and then cluster genomes by their similarity of the protein family size. I assume some others must have done this but it seems like a good way to identify similar duplication pressures on distantly related organisms. This posting includes an audio/video/photo media file: Download Now |
| Great Speech [The Daily Transcript] Posted: 04 Jun 2008 08:40 AM CDT |
| Hawks on Handling Exponential Growth in Demographic Models [HENRY » genetics] Posted: 04 Jun 2008 08:34 AM CDT John Hawks has a nicely detailed discussion about handling exponential growth in demographic models. Very interesting, and hopefully he’ll keep them coming:
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| The Future of Cell Biology - Part II - The Sweet Life [The Daily Transcript] Posted: 04 Jun 2008 08:07 AM CDT With the sequencing of the human genome, the public at large has been told that biologists now have a full picture of how biological life works. This is far from the truth. In this series of posts I'll try to outline what we don't know - in other words gaps in our knowledge. Today we'll look at how proteins acquire sugar modifications, aka glycosylation. Look at any eukaryotic cell and you'll notice that one of the main differences between it and its prokaryotic cousins is its elaborate systems of membranes and its complicated secretion machinery. Unlike prokaryotes, which inject secreted proteins directly into the extracellular (or periplasmic) space, eukaryotes pump newly made secreted and membrane bound proteins into the endoplasmic reticulum (ER). These proteins are then extensively modified by that same elaborate systems of membranes that characterize eukaryotes. The modification that occurs in these organelles is called glycosylation. In other words, long sugars chains are added to certain asparagine, serine or threonine residues found in the newly synthesized polypeptide.
What do I mean by this? Take a the first layer, called the cis-Golgi cisternae. In this model, vesicles from the ER would fuse together and with vesicles that contain enzymes that are normally found in this Golgi layer to form a new cis-Golgi cisternae. Over time the enzymes are replaced - the cis-Golgi enzymes are packed into vesicles that bud off of this compartment and are replaced by medial-Golgi enzymes that are found in vesicles that fuse with the same layer. Our cis-Golgi cisternae slowly transforms into a medial-Golgi and a new cis-Golgi is assembled beneath it. Because each Golgi cisternae contains different sugar pruning and sugar growing enzymes the glycosylation patterns on each processed protein slowly changes as the cisternae matures. In some late Golgi compartments we even get some new glycosylation on serine and threonine residues. By the end of the process, different proteins acquire different sugar trees. Some proteins gain gigantic sugar trees while other proteins are barely touched. Eventually the proteins that were synthesized in the ER end up in the last (or most mature) cisternae, the trans-Golgi, which is really not a continuous layer, but instead a loose connection larger vessicles found after the last true Golgi cisternae. In the trans-Golgi, proteins are packed into vesicles and shipped to different parts of the cell such as the endosome, the plasma membrane etc. |
| 14 years and still no good genes! [The Gene Sherpa: Personalized Medicine and You] Posted: 04 Jun 2008 07:58 AM CDT I am preparing a talk for the Connecticut Geriatric Society and I am just can't get over it. We haven't found good genes for Late Onset Alzheimer's Disease since 1994. Sure we have SORL1, GALP and... [[ This is a content summary only. Visit my website for full links, other content, and more! ]] |
| Vive la difference? [genomeboy.com] Posted: 04 Jun 2008 07:45 AM CDT
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| Nutraceutical News [Sciencebase Science Blog] Posted: 04 Jun 2008 07:00 AM CDT
Apparently, nutraceuticals promote wellbeing and underpin public health by providing a supposedly natural way to lower raised cholesterol levels, help unblock clogged arteries, ward off otherwise inevitable cancers, and ease the machinations of the over-sensitive gut. All this, without anyone having to resort to pharmaceutical products and double-blind placebo-controlled clinical trials. It’s the opening paragraphs of the paper that were the most interesting with regard to the state of play when it comes to the gradual public acceptance of the marketing hype surrounding nutraceuticals: Consider this domestic scene: it is a typical Sunday morning in an English household in the city of Westminster, London. Mrs Jones is preparing breakfast for her family. Like most mothers, she is concerned about her family’s nutritional status and tries to cook healthy meals. This morning it is an English breakfast, but not just an ordinary one. Personally, I doubt there are many such domestic goddesses around these days, particularly in Westminster, but more to the point, I think many families these days rush breakfast with at best a quick splash of synthetic fruit juice, and some artificially flavoured cereal rather than feasting on the great English breakfast. But, that aside, the researchers then describe the menu: The wholemeal bread was made out of grains to increase dietary fibre intake and essential micronutrients, thus helping bowl [sic] movement and support the gastrointestinal tract. The omega 3-enriched eggs will enhance the immune system, reduce the risk of cardiovascular diseases (CVD) and blood clotting. The sugar-free orange juice has added vitamins and antioxidant nutrients, believed to reduce the risk of diabetes, CVD and cancer. The extra virgin olive oil she uses to fry the eggs [You shouldn't use extra virgin to fry, it degrades rapidly at high temperatures, db] has been chosen to help lowering her mother-in-law high cholesterol. Agreed, wholemeal bread is probably better for bowel movements than bland and bleached white bread, but wholemeal, while functional, is not the breakthrough health product. After all, my grandmother extolled the virtues of roughage to me decades ago. The mention of omega acids and antioxidants is possibly valid, but there are no wide-scale trials yet to backup some of the wilder claims made in the popular press. Indeed, adding to one’s diet excessive amounts of antioxidants could Next, the team suggests that the breakfast sausages with “less than 1% fat” will somehow eliminate any risk of CVD posed by saturated fatty acids. Well, 1% might be described as low fat, but I’d prefer the term reduced, but again, I am not sure how functional are reduced-fat sausages. One of my many pet peeves regards the claims surrounding so-called organic foods. The jury is still well and truly out on whether there are any benefits and as for the lack of pesticides and fertilisers requires some of those used by organic practitioners are already known to be more hazardous. The beans, tomatoes and mushrooms being “organically grown” also does not take into account the fact that just because Mrs Jones in Westminster can afford the luxury of organic this does not mean organic is better for the world. Energy expenditure for organic farming on a large enough scale to feed the world could be significantly greater than in non-organic methods. Finally, the salt used by hubby was specially manufactured to help minimise his high blood pressure. Well, yes, I’d concede that’s a functional food. But, whether or not a sprinkle of non-sodium salt is going to benefit Mr Jones’ blood pressure is not beyond doubt; alcohol consumed, cigarettes smoked, processed foods eaten, and genes inherited, play a much bigger role. More to the point, given that the sausages will have been made with salt, why not simply not use salt at all, those organic foods are claimed as more flavoursome anyway, so no need to enhance with salt. The researchers end their introduction with the thought that this Westminster breakfast is not a scene from 'Balanced-Nutrition' program on national television, it is the era of medicinal and functional foods and it is happening as we read this paper in many parts of the world. This is not just food this is ‘functional foods’. Well, I am not so sure, most of what they describe is not functional in the conventional sense, although elsewhere in the paper they list dozens of functional foods and herbal supplements such as ginseng and Gingko biloba. There may certainl dozens, if not hundreds, of food products now on the market that claim some kind of health functionality. But, the whole notion of a supplemented diet that might improve wellbeing has been stacked very high in recent years. There are shelves full of milky probiotic drinks full of microbes that supposedly repopulate your intestine with good bacteria, products with plant steroids to reduce cholesterol, ward off the menopause, and dozens of herbal extracts each one of which is seemingly a cure-all for a wide range of disparate health conditions. As long ago as 2001, uber-skeptic of the alternative medicine movement, Edzard Ernst of Exeter University, asked whether functional foods, neutraceuticals, and designer foods are simply Almost a decade later, there is still a lot of health hype in those lifestyle magazines and supermarket shelves are increasingly stacked with organic produce, with its premium price tag, and healthstores are packed with botanical products from all corners of the globe. Is this food fad just a cynical marketing exercise, not only for food manufacturers, who can charge more by making dubious health claims for their products, but also for the pharmaceutical and health-care product companies who are now, as blockbuster pipelines dry up, providing the ingredients for the functional diets we are all being told we must consider. I suspect, once the advertising revenues dwindle and the lifestyle magazines become necessarily bored with the functional food fad, that ultimately many will be left on the shelf while the next moneyspinner rings the changes at the checkout. A post from David Bradley Science Writer |
| Thoughts on Industry Jobs [Bitesize Bio] Posted: 04 Jun 2008 04:46 AM CDT
I’m sure though that PhD’s with more of a background in applied research might not face these problems. In the life sciences, food science is one such applied field, that might suit the shift from academia to industry better, or more clinically-oriented fields. Any field, however, with a focus on the fundamental nature of things, promotes the sort of arrogance that Sandra describes - correct me if I’m wrong. Regardless however, plenty of PhD’s find the employment market ultra-competitive, and must find the humility to find work where they can. They have to find a way to enjoy such work even if they previously had lofty dreams of making great discoveries someday. That’s just life. |
| What does DNA mean to you? #8 [Eye on DNA] Posted: 04 Jun 2008 03:02 AM CDT
Reader Doug tells us what he thinks of DNA:
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| Thinness vs. obesity not directly linked to eating habits, study suggests [Think Gene] Posted: 04 Jun 2008 12:18 AM CDT Whether you are fat or thin isn't directly determined by your eating habits, suggest researchers who report new findings made in worms in the June issue of Cell Metabolism, a publication of Cell Press. While both feeding and fat in worms depends on serotonin levels in the nervous system, they found evidence that the nerve messenger acts through independent channels to control whether you eat versus what to do with those calories once you’ve eaten them. “It says that the nervous system is a key regulator coordinating all energy-related processes through distinct molecular pathways,” said Kaveh Ashrafi of the University of California, San Francisco. “The nervous system makes a decision about its state leading to effects on behavior, reproduction, growth and metabolism. These outputs are related, but they are not consequences of each other. It’s not that feeding isn’t important, but the neural control of fat is distinct from feeding.” If the results in worms can be extrapolated to humans, as Ashrafi suspects at a fundamental level they can given serotonin's ancient evolutionary origins, then the finding may have clinical implications. “From a clinical perspective, this may mean you could develop therapeutic strategies to manipulate fat metabolism independently of what you eat,” he said. “Now, the focus is primarily on feeding behavior. As important as that is, it’s only part of the story. If the logic of the system is conserved across species, a strategy that focuses solely on behavior can only go so far. It may be one reason diets fail.” While fat regulation is at one level a relatively simple balance between energy intake and expenditure, the physiology is nonetheless quite complex, Ashrafi said. It was the researchers goal in the new study to dissect that complexity using the worm C. elegans, an organism that is much simpler to work with in comparison to mammals. They found in the worms that control of feeding by serotonin involves receptors whose function is not required for fat control. Rather, the nerve messenger’s effects on fat depend on a separate neural channel and receptor that spark signals leading to the breakdown of fat. The byproducts of that process generated in fat then come "full circle" and control feeding behavior, Ashrafi said. The findings show that, as in mammals, C. elegans feeding behavior depends on cues in the environment as well as internal cues. Moreover, the researchers said, “obesity and thinness are not solely determined by feeding behavior. Rather, feeding behavior and fat metabolism are coordinated but independent responses of the nervous system to the perception of nutrient availability.” In both the worm C. elegans and in mammals, high serotonin levels are already known to lead to fat loss while low serotonin levels lead to fat accumulation, the researchers noted. However, there are some differences. In C. elegans, when serotonin goes up, feeding goes up and fat goes down. On the other hand, high serotonin leads people to eat less and shed fat. Since C. elegans directly match their feeding rates to increasing and decreasing food concentrations, serotonin’s effects on fat and feeding in the worms are consistent with the nerve messenger’s role as a sensory gauge of nutrient availability, the researchers said. When resources are scarce, worms build up their fat reserves. Thus, the perception of food scarcity leads them to shift to a metabolic state favoring conservation of energy and the direction of nutrients to fat stores. Despite those differences, Ashrafi said, given the contributions of the serotonin pathway to energy balance across species, “we speculate that human counterparts of feeding-independent fat regulatory genes identified in our study may similarly regulate energy balance.” Source: Cell Press Josh says: I had no idea that serotonin played a role in food consumption and fat storage. I wonder if this is any reason why when people get depressed, they sometimes tend to eat a lot of “comfort foods”, since their serotonin levels are lower. This is of course just speculation. |
| The online life science community is on a roll [business|bytes|genes|molecules] Posted: 03 Jun 2008 10:24 PM CDT When I started the Life Scientists room, it was mostly meant to try out the new rooms functionality and wasn’t sure if anyone would sign up. It is safe to say that the room has exceeded expectations and has even led to further activity. Where will it all end up? No idea, but the future certainly looks bright. I am sure reality will kick in at some points and we will have momentum killers from time to time. Lets not forget Twitter in all this. Conversations there have led to ideas for books and a BioBarCamp (August 6-7 at the Institute for the Future in Palo Alto). Further reading Technorati Tags: Friendfeed, Twitter, BioBarCamp |
I discovered a rather intriguing perspective on the world of wellbeing, health and nutrition in the latest issue of the journal World Review of Science, Technology and Sustainable Development (
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