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Biotechnology Forums - https://www.biotechnologyforums.com

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    A new study on Danish infants suggests that breastfeeding (and when it is ceased) is the nutritional element with the most significant effect on the development of the child’s gut bacterial population, termed the microbiota. The study, from researchers in the National Food Institute, Technical University of Denmark, and the University of Copenhagen, shows that the child’s intestinal microbiota changes significantly between the ages of 9-18 months, following cessation of breastfeeding and introduction of other foods. However, the evolution of the child’s gut microbiota continues up to the age of three. The study is published in the journal Applied and Environmental Microbiology.

    Previous studies suggest that babies who are breastfed grow marginally more slowly and are a little slimmer than non-breastfed babies. This appears to translate into slightly lower incidence of obesity, allergies, diabetes and inflammatory bowel disease later in life. The composition of the gut microbiota is now recognised to be important in these conditions. The new study suggests that breastfeeding has a beneficial effect on the gut microbiota early in life which could influence how the microbiota evolves and help explain its apparent health benefits.

    In the study, the research team took faecal samples from 330 healthy Danish infants at 9, 18, and 36 months after birth. They used a technique called quantitative PCR to establish the bacterial species present and their relative quantities. The results showed that breastfeeding encouraged the presence of lactobacilli, a type of bacteria that is of benefit in immune system development. Cessation of breastfeeding heralded a change in the microbiota to a population dominated by Clostridium spp. and Bacteroides spp. Evolution and stabilisation of the microbiota continued up until the age of 3 years in many children. Senior author Tine Rask Licht explains the significance of this finding: "The results help to support the assumption that the gut microbiota is not - as previously thought - stable from the moment a child is a year old. According to our study important changes continue to occur right up to the age of three. This probably means that there is a 'window' during those early years, in which intestinal bacteria are more susceptible to external factors than what is seen in adults."

    The results of this study suggest biotechnological advances and public health interventions could be used to develop strategies to promote healthy gut microbiota. Tine Rask Licht explains the possibilities in terms of both breastfeeding and baby formula milk: "The results from the study can be used to support initiatives that can be used to help children develop a type of gut microbiota, which is beneficial for the immune system and for the digestive system . This could for example be advice to mothers about breastfeeding or the development of new types of infant formula to promote the establishment of beneficial bacteria in the gut."

    Sources:

    Bergström, A., Skov, T.H., Bahl, M.I., Roager, H.M., Christensen, L.B., Ejlerskov, K.T., Mølgaard, C., Michaelsen, K.F. and Licht, T.R. (2014). Establishment of Intestinal Microbiota during Early Life: a Longitudinal, Explorative Study of a Large Cohort of Danish Infants. Applied and Environmental Microbiology, Vol. 80, No. 9. (1 May 2014), pp. 2889-2900, doi:10.1128/aem.00342-14

    Press release: Technical University of Denmark; available at http://www.food.dtu.dk/english/News/Nyhe...C24ED68377 [Accessed 8 May 2014]

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    The spider genome has been sequenced for the first time, opening up the possibilities for gaining insights into spider attributes and activities. For example, the venom and silk made by spiders has potential applications for manufacturing of biomaterials or developing pharmacological products. The study establishing the spider genome was carried out by researchers in Aarhus University, Denmark and the Beijing Genomics Institute (BGI) and is published in the journal Nature Communications.

    Spiders are predators which are able to capture large prey by use of their extremely tough silk. They also have a complex venom with which to kill their prey. For the study, the researchers focused on two types of spiders which represent two of the three main spider family groups. One is a small velvet spider, whose genome was completely sequenced and the other is a tarantula, for which there are still some gaps in the genome sequence.

    The team compared the sequences to try to determine if there are genes that define ‘spider’. One of the first authors, Kristian W. Sanggaard, explains: “The idea was that, by comparing their genetic makeup, we’d try to see whether we could say anything in general terms about what makes a spider a spider.” A limited number of similarities were identified, reflecting that fact that it is almost 300 million years since the two types of spiders had a common ancestor. One of the other first authors, Jesper S. Bechsgaard, clarifies: “But we found a number of genes – about two to three hundred – that have only been found in these two types of spiders and not in other organisms. They could be candidates for genes specific to spiders.”

    The results of the study showed that the spider genomes are large with similar structures to mammalian genomes of short, protein-coding exons separated by long, non-coding introns. The sequencing revealed insights into the evolution of the venom genes and suggested that the toxic effect of venom is most likely activated by enzymes called proteases in the venom. The silk genes meanwhile have evolved in a highly dynamic way. The sequencing also revealed new types of silk genes and proteins, and a novel use of aciniform silk.

    The unveiling of the spider genome creates “a tool for everyone interested in spiders,” according to the authors. They point out that: “People can select an aspect or feature of the spider they’re interested in, and then utilise the ‘genetic map’ we published and which we ourselves have used to study silk and venom. This provides completely new opportunities for spider researchers.” Better understanding of the properties of the silk and venom of the spiders, for example, offer major potential in the development of pesticides or medicines or of biomaterials. The paper’s authors plan to use the genome to advance work on the spider’s digestive enzymes and immune system. However, the possibilities are there for anyone interested in other aspects to focus on other genes.

    Sources:
    Sanggaard, K.W., Bechsgaard, J.S. and Fang, X. (2014). Spider genomes provide insight into composition and evolution of venom and silk. Nature Communications, 5(3765); doi:10.1038/ncomms4765

    Press release: Aarhus University; available at http://scitech.au.dk/en/current-affairs/...er-genome/

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    Innovative uses of a promising anti-HIV medication called dapivirine are giving hope that women can be better protected against HIV. The exclusive worldwide rights for dapivirine have been granted to the non-profit organisation The International Partnership for Microbicides (IPM), which is committed to developing HIV prevention tools and other products aimed at women’s sexual and reproductive health and making sure they are accessible to all, particularly to women in developing countries. The rights were granted to IPM by Janssen R&D Ireland under an expanded public-private collaboration with Janssen Pharmaceutical Companies of Johnson & Johnson. This agreement should push forward the development and global availability of dapivirine-based HIV prevention tools for women.

    Despite the advances in recent years in reducing the number of new cases of HIV/AIDS, women have been largely left behind in terms of benefiting from these advances. In parts of sub-Saharan Africa, women in the 15 to 24 year age group are 3-4 times more likely to have HIV infection as their male peers. This drives the imperative to develop tools aimed specifically at women to help give them options to protect themselves. Dr. Zeda F. Rosenberg, chief executive officer of IPM, elaborates: "Women are in a race against time for new HIV prevention methods, and they need innovative tools to protect themselves and help reverse the course of the epidemic….We applaud Janssen's leadership in advancing women's access to new health technologies."

    Dapivirine is a member of a class of anti-retroviral agents called non-nucleoside reverse transcriptase inhibitors (NNRTIs). These agents interfere with the ability of HIV to make copies of itself. IPM's most advanced technology dapivirine -based technology is a vaginal ring designed to give a monthly sustained-release of the drug to prevent HIV. This ring is currently in two parallel Phase III trials in Africa; results are expected in late 2015. Other products in the IPM development portfolio include a combination dapivirine -maraviroc ring. There is also a 90-day ring that combines dapivirine with the contraceptive levonogestrel. This would have the double benefit of protection against both HIV and unwanted pregnancy.

    The newly expanded agreement marks another step in a long-established collaboration between Janssen and IPM. Janssen had originally licensed dapivirine to IPM under a royalty-free agreement in 2004 with the intention of having it developed as a microbicide for women in developing countries. The new agreement will ensure women's future access in all countries thanks to affordable pricing strategies. Dr Rosenberg explains the significance of the collaboration: "Our worldwide rights agreement with Janssen is a powerful example of how public-private partnerships can accelerate access to urgently needed, affordable health products…By pooling the expertise of partners across sectors, we can more effectively help women at risk for HIV and, ultimately, end the spread of HIV/AIDS altogether."

    IPM has also been working with other pharmaceutical companies including Bristol-Myers Squibb, Gilead, Merck & Co. and ViiV Healthcare, as well as Janssen since 2004 with royalty-free licenses granted to IPM to develop, manufacture and distribute eight anti-retroviral products in developing countries. This is designed to guarantee affordable access of patients to these drugs where they are most needed. IPM is funded via the Ministry of Foreign Affairs of Denmark, Irish Aid, the Ministry of Foreign Affairs of the Netherlands, the Norwegian Agency for Development Cooperation (Norad), the United Kingdom Department for International Development (DFID), the American people through the United States Agency for International Development (USAID), the Bill and Melinda Gates Foundation, the M.A.C. AIDS Fund and the OPEC Fund for International Development.

    Sources:

    Press release: International Partnership for Microbicides (IPM); available at http://www.eurekalert.org/pub_releases/2...050714.php [Accessed 8 May 2014].

    IPM website: http://www.IPMglobal.org. [Accessed 8 May 2014].

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    An experimental monoclonal antibody hu14.18K322A has shown encouraging results in a Phase I trial on children with advanced neuroblastoma. Of the 31 patients who received two or more rounds of treatment, tumours got smaller or disappeared altogether in 15 patients and progression of the disease was stopped temporarily. The antibody is targeted at the GD2 antigen, which is highly expressed on neuroblastoma tumour cells but with restricted expression on normal cells. The trial was carried out in St. Jude Children's Research Hospital. Results were recently published online ahead of print and will appear in the Journal of Clinical Oncology print edition on May 10th 2014.

    Neuroblastoma affects the sympathetic nervous system. It is the most common cancer in children under the age of one year and accounts for 7-10% of all childhood cancers. The cure rate is high for some patients, especially infants. However, for other high-risk patients, for example those in whom the disease has spread, the prognosis is much poorer. Fewer than half of these achieve long-term, disease-free survival and new therapy development is a priority for these patients.
    The Phase I trial was carried out in order to assess the maximum-tolerated dose and safety profile of hu14.18K322A, a modified antibody. The modification was intended to reduce activation of part of the immune response called the complement cascade and the pain associated with this activation. For the study, 38 patients were recruited whose cancer had returned or who had not responded to standard therapies such as surgery, chemotherapy, radiation and bone marrow transplants. These patients received different doses of hu14.18K322A. The antibody was administered every 28 days in daily doses over 4 days. The object of using this antibody is to mount an immune response specifically against the tumour cells, sparing the normal cells which have limited GD2 expression.

    Of the 31 patients who went on to have two or more rounds of treatment, the disease was stabilised in nine of them. In two patients the tumours got smaller while they became undetectable in four more. First and corresponding author Dr Fariba Navid, added: "Four patients are alive after more than two-and-a-half years without additional therapy." Dr Navid further explained how the efficacy of the treatment was both encouraging and relatively unexpected at this early stage in the trial process: "This was the first time this experimental antibody was tried in patients. We were encouraged with the response…The percentage of patients who benefited from treatment with hu14.18K322A was unusual for a Phase I study."

    Despite the reduction in complement activation, the most common side-effect of hu14.18K322A treatment was pain, with 68% of patients reporting severe pain in the first round of treatment. However, according to Dr Navid, the pain could be managed with medication, generally resolved within 24 hours of antibody administration and became less with additional rounds of treatment.
    Hu14.18K322A is produced in the Children's GMP, LLC. Dr Navid acknowledged that the trial would have been impossible in the absence of GMP, an on-site facility that makes highly specialized pharmaceuticals under US government-approved Good Manufacturing Practices regulations. Clinical trials are on-going with the antibody, with the researchers now examining the impact of weekly dosing and looking at combining hu14.18K322A with other therapies.

    Sources
    Navid, F. et al. (2014) Phase I Trial of a Novel Anti-GD2 Monoclonal Antibody, Hu14.18K322A, Designed to Decrease Toxicity in Children With Refractory or Recurrent Neuroblastoma. Journal of Clinical Oncology, Published online before print April 7, 2014, doi: 10.1200/JCO.2013.50.4423

    Press release: St. Jude Children's Research Hospital; available at http://www.eurekalert.org/pub_releases/2...050814.php

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    Concerns are spreading internationally over a particularly virulent strain of the porcine epidemic diarrhoea virus (PEDv). Thought to have originated in China, this strain of the virus is now suspected to have spread to herds in the USA, Canada, Mexico and Japan. Now BBC News reports that France is planning to stop pig-related imports from infected countries, including live pigs, some by-products and pig sperm. The French action is thought to be a reaction to the perceived lack of decisive action on behalf of the European Union. Agency reports state that French government officials say their suspension has been made while "waiting for a European decision".

    Porcine epidemic diarrhoea is an enteric disease of pigs caused by infection with a virus which is a member of the Coronaviridae family. It causes acute diarrhoea and dehydration in pigs. The disease is not, however, harmful to humans. Porcine epidemic diarrhoea was first observed in 1971 in English fattening pigs and subsequently spread around Europe. This PEDv type I strain was less virulent than the strain currently causing concern and pigs developed immunity to it. Other strains have since evolved and the disease has become problematic in many parts of the world, notably in Asian countries where severe outbreaks have affected new-born pig mortality rates.

    Older pigs can survive PEDv infections but piglets are highly susceptible to the strain that is currently causing concern, with a 80% and 100% mortality rate. While it is not yet certain that the same strain has spread from Asia to the US, this is suspected to be the case. Dr Bernard Vallat, Director-General of the World Organisation for Animal Health (OIE), says: "According to the information from genetic analyses, there is some similarity with a strain from Asia…But the evidence of the crossing from Asia to the US is not yet established. For the moment it is not possible to make a final conclusion on the formal link, it is a suspicion."

    PEDv is spread via faecal matter. Lax biosecurity is suspected to be a factor in the spread of the disease, according to BBC News. For example, a US study carried out in June last year showed that 17% of trucks going into a slaughterhouse were positive for the PEDV infection. According to Dr Zoe Davis of the UK's National Pig Association (NPA): "They also discovered that 11% of the trucks that had been negative when they went into the slaughterhouse were subsequently positive when they left…It's how many animals you are moving around, that's how it’s being spread."

    It is also suspected that the practice of using dried pig blood in feedstuffs for weaned piglets is contributing to the problem. Dr Bernard Vallat explains: "The feed is suspected…Blood from slaughterhouses with insufficient heat treatment is suspected to be the origin. We don't have a scientific publication on that but it is highly suspected.” However, Dr Vallat believes that the history of exposure of European pigs to PEDv may confer some immunity: "It circulated before in Europe but it was a different strain. If there is some remaining circulating virus there is a possibility that animals would be protected - but it is not sure." Dr Zoe Davis disagrees with this optimistic assessment: "Everyone seems to think that because we've had versions of PEDv in the past we will have some immunity to this new strain and we know categorically that this is not the case…We've tested our own herds and we think around 10% of the animals have antibodies to the older strains, we are effectively a naive herd, which is why we are worried."

    The potentially devastating consequences of the disease are evident in the US where 7 million piglets have been killed in the last year due to PEDv infection. In the UK, the NPA claims that all major importers support moves to restrict pigs from infected countries. It says that more than 92% of pigs reared in the UK are not fed on blood products. However, in other EU countries these types of foodstuffs are more common and there is also widespread movement of animals. This increases the risk of the virus becoming established in Europe, with potentially devastating economic consequences for major pig-breeding countries including the Netherlands, Germany and Denmark. The EU has not decided yet on any move to restrict imports. This is thought to have contributed to the French unilateral decision on import restriction and to the thinking in countries such as the UK.

    Another consequence of this outbreak is that the price of pork is likely to rise. Already the US has experienced an increase in pig prices due to the virally-induced piglet losses. Dr Vallat says: "One of the consequences of the problem, the restriction of the products in the market, mean perhaps prices could grow…For the non-infected herds it is good news."

    Sources:

    http://www.bbc.com/news/science-environment-27256466 [Accessed 9 May 2014].

    https://www.avma.org/News/JAVMANews/Pages/130901x.aspx[Accessed 9 May 2014].

    Song, D. & Park, B. 2012, "Porcine epidemic diarrhoea virus: a comprehensive review of molecular epidemiology, diagnosis, and vaccines", Virus genes, vol. 44, no. 2, pp. 167-175.

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    If you are simply beginning a program for waist training, you most likely need to know what to expect in terms of waist training results. The answer to that does, normally, vary according to the individual. However, as long as you are consistent in terms of your corset usage, your healthy eating habits, and your routine workout plan, you can anticipate to recognize some amazing arise from your training. Following the ideas in a waist training guide can also be particularly useful in helping you to attain maximum results from your training.

    In very early outcomes, you will probably see the most remarkable modification. Your first corset must be a high quality one that is produced the specific function of customizing your body. Read about is waist training dangerous. Flex boned corsets that reduce the waist by at least four inches are ideal to begin with. When you first start, you will have to adjust to the corset. While some individuals will put on the corset all the time from the beginning, you might want to adjust yourself more slowly by using it a few hours every day.

    Your waist training corset, when used between two and four hours a day, can begin to yield progressive outcomes. You will wish to slowly raise the quantity of time spent in the waist trainer until you can use all of it day. Lots of people also make use of a lighter type of boned corset to oversleep as they become made use of to the corset. As soon as you are putting on the corset all the time, you can make it tighter using the 2nd clasp set.

    Repeat this process till you are comfortable with this for an entire day each day and then proceed to the next smaller sized set of clasps. Learn about what is waist training right now. Remember, discomfort is a bad indication and you ought to never make yourself injure to do this. Take it as slowly as you have to. You can still anticipate great results, even taking it slow.

    There is no set period where a person will end up being comfortable with a particular level of corset wear and prepare to tighten it, just as there is not a particular time in which you can expect to notice a 6 or 7 inch decrease in your waist. Everyone is distinct. The essential thing to keep in mind is consistency. waist training before and after. Use your corset routinely and slowly up your tolerance. Eat healthy and keep up with a great workout program. This will speed up your waist cincher strategy and you can expect some amazing waist training results if you follow these basic standards. Be healthy and live well.

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    Question by Chikki Renu:

    i just now completed my intermediate 2nd year,and wanted to do biotechhnology so which way should i choose degree or engineering?

    -----------------------------------------------------------------------------------------------------
    -----------------------------------------------------------------------------------------------------
    Dear Renu,
    This is an important decision of your career. So, before you opt for any Major Degree/Course, first set out your career goals. Donot opt for any degree/course blindly. Please answer some of my questions so that I may help you out in whatever capacity I have for the same:

    1. Your specialization (major subjects) in intermediate?
    2. Any competitive exam applied by you?
    3. Your financial condition (how important is it for you to grab a job immediately)
    4. Are you interested in long term research?
    5. Your academic performance in intermediate.

    It's important for me to know answer to these root questions before shedding any blunt advice.

    Best wishes

    Sunil

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    The Worldwide Protein Data Bank (wwPDB), an international partnership which maintains a freely accessible archive of protein and nucleic acid 3-D structures, has announced that they have broken the 100,000 entry mark. The archive was established in 1971 but in recent years it growth has greatly accelerated. It has doubled in size since 2008 and currently releases approximately 200 new structures weekly.

    The archive is made possible by the efforts of the scientific community who deposit their experimentally determined structures. Once submitted, each structure is carefully checked and curated by wwPDB staff. The value to the whole scientific community is maximised by addition of value-added annotations and linking to other important biological data to ensure that it is of use to a wide variety of scientists of different skills, interests and backgrounds. Nobel Laureate Venki Ramakrishnan of the MRC Laboratory of Molecular Biology in Cambridge, UK says: “The PDB is a critical resource for the international community of working scientists which includes everyone from geneticists to pharmaceutical companies interested in drug targets."

    The archive is maintained by PDB data centres in the USA, the UK and Japan. It consists of the Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB; http://rcsb.org) at Rutgers, The State University of New Jersey and the San Diego Supercomputer Center (SDSC) and Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California San Diego and BioMagResBank (BMRB; http://bmrb.wisc.edu) at the University of Wisconsin in the USA, the Protein Data Bank in Europe (PDBe; http://pdbe.org) at the EMBL European Bioinformatics Institute, and the Protein Data Bank Japan (PDBj; http://pdbj.org) at Osaka University.

    They ensure that the data are securely stored, expertly managed, and made freely available. They are advised by community experts in defining deposition and annotation policies, resolution of data representation issues, and implementation of community validation standards. The result is a resource that is accessed hundreds of millions of times every year by researchers, students and educators. They are able to inform themselves on how different proteins might be related as well as gaining insights into how form influences fundamental biological functions and mechanisms. The knowledge gained feeds into new discoveries in biomedicine, agriculture, and ecology.

    The structures of myoglobin and haemoglobin were two of the first to be deposited with the PDB. This week, 219 more structures were deposited, bringing the total to 100,147 entries. There are challenges ahead for the wwPDB as the number of structures as well as size and complexity increases and new hybrid structure determination methods emerge. These use a variety of biophysical, biochemical, and modelling techniques to determine the shapes of biologically relevant molecules which present challenges for data management and representation. Building on its ethos of community-driven enterprise, the wwPDB will continue to strive to meet these challenges.

    Sources:

    Press release: Rutgers University; available at http://www.eurekalert.org/pub_releases/2...051314.php

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    A new study suggests that novel protein fragments (peptides) can protect against Alzheimer’s disease pathology, including the Alzheimer's disease (AD) toxin (amyloid-β 1–42 peptide) and also against tau-like protein tangle formation and cognitive decline in a mouse model of AD. The study, published in the Journal of Alzheimer's Disease, comes from researchers in Tel Aviv University in Israel.

    Alzheimer’s disease is a devastating neurodegenerative condition characterised by amyloid-β 1–42 peptide accumulation and tangles formed from abnormal tau proteins, a marker of cognitive decline. Research is focused on trying to elucidate the pathology as well as harness potential protective or regenerative brain cell properties that could contribute to therapy. AD and other neurodegenerative diseases feature breakdown of the microtubule network. This forms part of all cells in our bodies. In nerve cells it is particularly important for transport of essential proteins and communication between cells. The research in the current study focused on the microtubules, in particular on the microtubule subunit tubulin and in the microtubule associated protein, tau.

    Previously, the researchers in this project had identified a peptide called NAP, which acts to stabilise microtubules and is a drug candidate showing promise in treatment of mild cognitive impairment. In the current study, the research team scanned the protein sequences of tubulin and tau and identified NAP-like homologies. They derived NAP-like peptides called NAT and STPTAIPQ from tubulin, and TAP from tau. These peptides were shown to provide neuroprotection against the Alzheimer's disease (AD) toxin, the amyloid-β 1–42 peptide, in a tissue culture in vitro model. TAP and NAT were more potent than STPTAIPQ . Lead author Prof Ilana Gozes explains: “The newly discovered protein fragments, just like NAP before them, work to protect microtubules, thereby protecting the cell."

    In an in vivo mouse model of AD at 10 months old, both NAT and TAP were able to inhibit the tau-like aggregation that characterises cognitive decline in AD. Further testing of NAT showed that in the AD mouse model, in which there was significantly decreased levels of NAP parent protein, NAT was able to restore NAP levels. Brain-to-body mass ratio, which is an indicator of brain degeneration, was also significantly decreased in the AD mouse model compared to normal mice, but was also restored to normal by NAT treatment. Dr Gozes explains: "We clearly see here the protective effect of the treatment…We witnessed the restorative and protective effects of totally new protein fragments, derived from proteins critical to cell function, in tissue cultures and on animal models."

    Sources

    Gozes, I., Iram, T., Maryanovsky, E., Arviv, C., Rozenberg, L., Schirer, Y., Giladi, E. and Furman-Assaf, S. (2014). Novel Tubulin and Tau Neuroprotective Fragments Sharing Structural Similarities with the Drug Candidate NAP (Davuentide). Journal of Alzheimer's Disease, DOI 10.3233/JAD-131664

    Press release: Tel Aviv University, available at http://www.aftau.org/newsroom?7d56804a-2...cacd9b1135

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    There have been many studies attempting to explain the ‘French Paradox’, that is the relatively low incidence of heart disease in France, despite the high-fat diet consumed by many of its inhabitants. Some researchers had hypothesised that the effect may be explained by moderate consumption of red wine, which along with dark chocolate and berries contains a polyphenol called resveratrol. Resveratrol has been considered to confer antioxidant, anti-inflammatory, and anticancer effects in humans and in some animal studies it contributed to longevity. However, a new study in the journal JAMA Internal Medicine suggests that if there is a health benefit from wine and dark chocolate, it is not due to the levels of resveratrol achievable in the diet.

    The study was carried out in two villages in the Chianti region of Italy between 1998 to 2009 on 783 men and women aged 65 or older. Levels of resveratrol metabolites were measured in the urine of the participants as an indicator of levels of resveratrol consumed in the diet. The primary outcome measure for the study was all-cause mortality, that is death from any cause, and the secondary measures were levels of inflammatory cytokines, cancer and cardiovascular disease. During the course of the study, 268 of the participants died, 174 developed heart disease and 34 got cancer.

    The results of the study indicated that there was no discernable association between levels of resveratrol metabolites and all-cause mortality, incidence of heart disease or cancer or of levels of inflammatory cytokines. Studies in lower organisms had indicated that resveratrol could contribute to longevity, however the doses needed to achieve these effects or the beneficial effects shown in human studies would be impossible to achieve in the diet. Lead author Prof Richard Semba of The Johns Hopkins University School of Medicine says: “The story of resveratrol turns out to be another case where you get a lot of hype about health benefits that doesn't stand the test of time... The thinking was that certain foods are good for you because they contain resveratrol. We didn’t find that at all.”

    However, the results of this relatively small study do not necessarily mean that there is no health benefit to be derived from red wine or dark chocolate. Prof Semba points out that there are many possible ingredients in these substances that could be important and that any benefit, if there is one, must come from another shared ingredient. It is unclear how much wine or chocolate would have to be consumed in order to derive any benefit. Prof. Semba explains: "These are complex foods, and all we really know from our study is that the benefits are probably not due to resveratrol."

    The fact that the levels of resveratrol derived from the diet may be too small to exert any effect also doesn’t mean that in higher doses, resveratrol would not have any beneficial effect. Responding to a BBC News report on the study, Maureen Talbot, senior cardiac nurse at the British Heart Foundation, said: "We recognise the need to learn more about the action of resveratrol though, so are funding research into its reported disease-combating properties and how it affects the heart and circulatory system…This research is vital as it could form the basis of future medicines.”

    Sources:
    Semba, R.D., Luigi Ferrucci, L., Bartali, B., Urpí-Sarda, M., Zamora-Ros, R., Sun, K., Cherubini, A., Bandinelli, S. and Andres-Lacueva, C. (2014). Resveratrol Levels and All-Cause Mortality in Older Community-Dwelling Adults. JAMA Intern Med. Published online May 12, 2014. doi:10.1001/jamainternmed.2014.1582

    http://www.bbc.com/news/health-27371546 [Accessed 15 May 2014]

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    A new study has shed light on factors that cause some species of the trypanosome parasites to be infective of humans while other aren’t. The study, published in the journal PLoS Pathogens, was carried out by researchers in the London School of Hygiene and Tropical Medicine and the University of Dundee.

    African trypanosomes, which are tsetse fly-transmitted protozoan parasites of the genus Trypanosoma, cause devastating diseases in both humans and livestock. The different members of the group are distinguished by their sensitivity to innate immune factors in human serum, which results in different host infectivity. The species Trypanosoma brucei brucei infects cattle, causing the disease nagana, but humans are resistant. On the other hand, the species T. b. gambiense and T. b. rhodesiense infect humans, causing sleeping sickness in Western and Eastern Africa respectively. Distinguishing the factors that cause T. b. brucei to be sensitive to the innate immune response in humans, which is the rapid, first-line immune response, could facilitate development of badly needed new drugs. The existing drugs for sleeping sickness have serious and unpleasant side-effects.

    In the new study, the researchers carried out a comprehensive RNA interference (RNAi) screen of the T. b .brucei genome in order to identify factors that reduced their sensitivity to human serum factors. This entailed use of a library of small T. b. brucei RNA molecules designed to interfere with expression of mRNA from T. b. brucei genes. This strategy enabled the research team to identify four genes that sensitised the trypanosome to human serum factors. These included three previously identified genes, namely the haptoglobin-haemoglobin receptor, a lysosomal membrane protein called p67 and inhibitor of cysteine peptidase (ICP). The fourth gene was a previously unidentified gene predicted to encode a so-called transmembrane channel which might be predicted to take up human defence factors.

    The research team studied ICP in more detail and discovered that it induced sensitivity to human serum innate immunity factors by modulating the activity of an enzyme called cathepsin-L (CATL). CATL is a member of a family of proteins called lysosomal cysteine peptidases, which can degrade proteins and thereby help overcome the immune factors in human serum. CATL modulation by ICP appears to be an important factor in T. b. brucei sensitivity to human immune responses. If ICP was down-regulated, CATL remained fully active and able to degrade human serum immune factors.

    CATL is currently the target of proposed new drugs for sleeping sickness; the results of the current study suggest that it would be an effective strategy. However, the authors of this study urge caution and increased understanding of how CATL interacts with other trypanosomal factors involved in infectivity. Lead author Dr Sam Alsford explains: “CATL is under consideration as a potential drug target, and our results suggest that its inactivation could indeed support the human defense system in fighting off disease-causing trypanosome strains. However, as CATL might also be involved in the generation or break-down of other factors involved in parasite-host interactions, it will be important to develop an improved understanding of the complex interplay of all of these factors in human-infective trypanosomes”.

    Future plans for the researchers include elucidation of the role of the new gene identified as a result of their research. In all, the study increased understanding of the interaction between trypanosomes and the human innate immune system, which can only be of benefit in consideration of new, safe therapeutic strategies.

    Sources:

    Alsford, S., Currier, R.B., Guerra-Assunção, J.A., Clark, G. and Horn, D. (2014) Cathepsin-L Can Resist Lysis by Human Serum in Trypanosoma brucei brucei. PLoS Pathog 10(5): e1004130. doi:10.1371/journal.ppat.1004130

    Press release: PLoS Pathogens

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    A new trial, teaming researchers in Indiana University with Paradigm, a non-profit genomic sequencing and molecular information company, aims to use advanced genomic sequencing technology to tailor personalised therapies to women with intractable triple-negative breast cancer. In a move away from the ‘one-size-fits-all’ model of cancer therapy towards the emerging personalised medicine options, the research team will use next-generation sequencing techniques on DNA from tumours in women who have not responded to standard chemotherapy. In this way, they hope to identify mutations or changes in expression in genes specific to an individual patient’s tumour and then try to identify a drug that might be expected to target that particular tumour.

    Triple-negative breast cancer has a particularly poor prognosis as it is associated with high incidence of recurrence and metastasis to sites such as the brain and lung. Treatment is complicated by the fact that it lacks oestrogen receptor, progesterone receptor and the HER2 protein, all of which are targets for therapy in other forms of breast cancer. This lack of effective therapies for triple-negative breast cancer makes identification of underlying mechanisms and tailored therapies all the more important. The proposed new trial is aimed at testing whether particular tailored treatments can improve survival rates.

    In the trial, 130 women who have received chemotherapy and surgery without the hoped-for outcomes, and who are at high risk of recurrence, will be enrolled. Half of these women will be assigned to the standard of care, while the other half will receive genomic sequencing-directed therapy. Michigan University researchers will enrol the participants and collaborate with Paradigm in analysis of the DNA and RNA of tumours remaining after standard chemotherapy. After discussion of each individual patient’s results, each woman will be assigned a drug selected to be specific to her particular form of triple negative breast cancer.

    Paradigm CEO Dr Robert Penny further explains the significance of the trial: "This trial is one of only a handful in the world that tests, through a controlled scientific study, whether the use of next-generation sequencing (NGS) to identify specific disease drivers -- and the selection of treatments for women based on those genetic markers -- actually improves survival rates for women…Our ability to interrogate the patient's tumour for DNA mutations, DNA copy number variations, chromosomal changes and mRNA gene expression with next-generation sequencing with clinical quality results is a real differentiator in helping to improve patient care.” Meanwhile, Dr Bryan Schneider of Indiana University explains how the sequencing information could lead to identification of the most individually effective drug: "If the mutation is taking place in a certain gene or protein that controls a certain function, and if the mutation has caused damage in that pathway, one can intuitively pick a drug that may also be interacting in that very same pathway to either try to stop or shut down an overly activated pathway."

    While the current trial will focus on triple-negative breast cancer, the research team envisage a time when other cancers can be similarly targeted. Dr Schneider concludes: "We envision a day when we can predict a handful of drugs that will best treat the tumour, derived from the tumour’s unique acquired genetic variability, and then further counsel the patient on which of these might be least toxic based on a person’s unique inherited genetic variability."

    Sources:
    Press release: IU School of Medicine and Indiana University Health; available at http://news.medicine.iu.edu/releases/201...digm.shtml

    http://www.cancer.iu.edu/ [Accessed 16 May 2014].

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    The US Food and Drug Administration (FDA) has been taken by surprise by the high demand for faecal microbiota transplants (FMT), according to a news article published this week in the journal Nature Biotechnology. Concerns over inadequate testing for contaminants such as viruses and lack of long-term safety and efficacy assessments has caused the FDA to take the unusual step of rowing back from earlier draft guidance to doctors and companies to a tighter regulatory stance.

    FMT has shown great efficacy in treatment of intractable Clostridium difficule infections and is accepted as the standard of care for such infections in Europe. It effectively allows the gut microbiome (population of microbes) to be recalibrated. The FMT procedure involves administration of stool by enema, colonoscopy or via nasal tube. The first randomised control trial for its use in antibiotic-resistant C. difficule infections was stopped early as 13 of the 16 patients enrolled were cured after one infusion while the remaining three required only one repeat procedure.

    While the previous FDA regulation exempted many doctors and companies from filing an investigational new drug (IND) application with the FDA before using FMT, the new regulations require that the stool source be known to either the physician or the patient. This has effectively halted the operation of stool banks such as Open Biome which was set up by researchers from Massachusetts Institute of Technology. However, the FDA had envisaged their previous regulations as facilitating use of FMT in emergency situations. Instead, an unforeseen high demand for the procedure ensued and the relatively light regulation meant that meaningful clinical data was not being collected. Furthermore, the sensationalising of the technique in the media and Internet stories of ‘home brew’ FMT prompted the FDA to tighten the regulations.

    The vacillation of the FDA on deciding on FMT regulation has led to some confusion among researchers in the field and disappointment among the initiators of Open Biome, who are now working on an IND to facilitate use of their resource. Various different medications based on stool-based formulations are in development. So far, efficacy has been firmly established for C. difficule infection but researchers are seeking to apply it in a whole host of other conditions from vancomycin-resistant enterococcus to ulcerative colitis and weight loss induction. Long-term safety and efficacy data is lacking for any condition other than C. difficule infection, also contributing to the FDA’s change of mind.

    Despite the new regulatory constraints, the future still looks bright for this therapy, which was first described as far back as 1958. Targeted therapies and development of formulations that can be readily inventories, stored and shipped are predicted to be the way forward by researchers including Lee Jones of Rebiotix and Gerard Honig of Symbiotic Health.

    Source:

    Ratner, M. (2014) Fecal transplantation poses dilemma for FDA. Nature Biotechnology 32, 401–402; doi:10.1038/nbt0514-401

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    Indian Institute of Technology Bombay (IIT Bombay) is the second oldest IIT of the country, established in 1958 with assistance from UNESCO and funded in part by the Soviet Union. Today, it's a world renowned institute of high repute offering a spectrum of courses.

    The Department of Biosciences and Bioengineering (BSBE), IITB is one of the most recognized and most sought after departments offering Undergrad and Graduate courses in the field of Biotechnology in India. Best known for it's research in Biomedical Sciences and Biomedical Engineering, BSBE offers M.Sc. Biotechnology (supported by the Dept. of Biotechnology, Govt. of India), M.Tech Biomedical Engineering, integrated M.Sc. – Ph.D. and Ph.D. programs. Apart from that a nodal divison for Understanding Cell Motility and Cancer Invasion has also been established in BSBE by the name of Wadhwani Research Centre in Biosciences and Bioengineering (WRCBB)

    Key Research Focus:
    Living to it's name in intensive resarch, BSBE has 22 different Research groups! Following is the list (click each to get the details of their heads) of the different research groups of BSBE, IITB:

    1. Autoimmunity and Cancer Immunoengineering Lab

    2. Biomaterials and Bio-interface Lab

    3. Biosensors and Bioinstrumentation Lab

    4. Cell and Tissue Engineering Lab

    5. Cell Biology Lab

    6. Cellular Biophysics Lab

    7. Computational Neuroscience Lab

    8. Gene Regulation Lab

    9. Glycobiology Lab

    10. Mechanistic Structural Biology and Bio-molecular NMR Spectroscopy Lab

    11. Molecular Cell Biology Lab

    12. Metabolic Engineering Lab

    13. Molecular Enzymology Lab

    14. Molecular Genetics Lab

    15. Molecular Immunology Lab

    16. Molecular Parasitology Lab[/align]

    17. Molecular Virology Lab

    18. NanoBios Lab

    19. Physical Biology Lab

    20. Protein Crystallography Lab

    21. Protein Engineering and Neurobiology Lab

    22. Proteomics Lab

    Admissions:
    MSc Program:
    Admission to MSc program is conducted through JOINT ADMISSION (JAM) test FOR M.Sc. The program is sponsored by the Department of Biotechnology, Government of India, with a stipend of Rs. 1200/- pm.
    For details on JAM test, Please Click Here

    M.Tech Program:
    Admission to M.tech program is carried out through GATE (for engineering and science graduates) or AIIMS/MCI/JIPMER/PGI-Chandigarh/AFMC-Pune, DNB Part I national level medical post graduate entrance examinations or GATE Life Sciences for Medical and Biological Sciences.
    Link to GATE basic info

    PhD Program
    The Department of Biosciences and Bioengineering offers PhD in BT (Biotechnology) and BME(Biomedical Engineering) core academic groups.

    Minimum Eligibility for Admission in BIOTECHNOLOGY (BT):

    1. First Class or 60% marks (55% for SC/ST) in M. Sc or equivalent degree in subjects related to Life Sciences/ Physics/ Chemistry OR B.Tech Biotechnology with:

    • a valid GATE score (eligible for Institute TAship/ RAship) OR
    • a valid CSIR/ UGC/ DBT JRF (eligible for FA category) OR
    • a valid ICMR JRF (not linked to ICMR project) (eligible for FA category) OR
    • Two year of relevant post M.Sc research experience (eligible only for project positions) OR UGC/CSIR (Lectureship) eligible only for project position.


    2. First Class or 60% marks (55% for SC/ST) in M.Tech or equivalent degree in Biotechnology


    Minimum Eligibility for Admission in BIOMEDICAL ENGINEERING (BME) :

    First Class or 60% marks (55% for SC/ST) in :
    • M.Tech/M.E. or B.Tech/B.E. in Biomedical, Chemical, Computer Science, Electrical, Electronics, Telecommunications, Instrumentation & Mechanical Engineering, and Engineering Physics OR
    • M.Sc. or equivalent in Biochemistry, Biophysics, Biotechnology, ceramics, Chemistry, Electronics, Egronomics, Material Science, Mathematics, Molecular Biology, Physics and Physiology. OR
    • First class/division in MBBS degree in occupational Physiotherapy, with AIMS (PG Entrance Test) / MCI entrance examination for MD/MS (for Medical graduate)/MBBS with MD/MS OR M.Pharm

    For both BT and BME admissions in PhD, if one requires Institute financial support, then it is expected that he/she should have cleared GATE (for engineering and science graduates) or AIIMS/MCI/GIPMER/PGI-Chandigarch/ AFMC-Pune post graduate entrance examinations.

    These were the major updates about BSBE IITB. Keep watching this space for further updates.

    Best wishes
    Sunil

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    Three proteins, namely matrix metalloproteinase-3 (MMP3), Rac1b and KRAS work together to drive progression and tumourigenesis in pancreatic cancer. This pathway provides a therapeutic target for this notoriously difficult to treat cancer. These are the main findings of a new study in the journal Molecular Cancer Research from researchers in the Mayo Clinic and Unikliniken Marburg Und Giessen.

    Pancreatic cancer features genetic alterations in a cancer-associated oncogene called KRAS. Tumours are also supported by their microenvironment which is characterised by influx of immune cells. Cells that surround the tumour make matrix metalloproteinases such as MMP3. These are enzymes that break cell adhesions and in the cancer context allow tumour cells to move away from the tumour to other sites, a process known as metastasis. The RAC1 protein superfamily of proteins are important in regulation of cell growth and cell movement. Some forms of these proteins, such as Rac1b, had been previously implicated in other cancers but not in pancreatic cancer.

    In the current study, the research team wanted to establish what drives the expression of MMP3 in pancreatic cancer. They used several strategies, including examination of a cohort of pancreatic cancer tissue biopsy samples, transgenic mouse models and in vitro studies of cultured pancreatic cancer cells.

    The biopsy samples revealed that both MMP3 and Rac1b are expressed in pancreatic cancer cells. Their expression was correlated and the location of the Rac1b in the cells was associated with the patient’s prognosis. The transgenic mouse models studies showed that co-expressing MMP3 with activated KRAS in pancreatic cells stimulated development of the tumour microenvironment. Finally, using pancreatic cancer cells in culture and exposing them to recombinant MMP3 directly stimulated Rac1b expression and also increased the invasiveness of the cells and their expression of cancer-associated genes.

    The results suggest that Rac1b is associated with the aggressiveness of pancreatic cancer and may provide a drug target for pancreatic cancer, especially in patients who do not respond well to other therapies. Dr Derek Radisky, senior investigator on the study, further explains the significance of the findings: "The implication from our research is that Rac1b is activating unique pathways in pancreatic tumours that make this cancer aggressive. If we can therapeutically target that pathway, we may be able to have an impact on this very difficult-to-treat disease."

    However, targeting Rac1b directly would be difficult as it is involved in many normal biological processes. Thus, the research team are now undertaking some scientific detective work to identify targets among the cancer-causing pathways activated by Rac1b. Dr Radisky concludes: "Pancreatic cancer is not uniformly aggressive — some patients have a relatively better outcome. This work allows us to hone in on those patients who don't do as well, and who would most benefit from more targeted therapies.”

    Sources

    Mehner, C., Miller, E., Khauv, D., Nassar, A., Oberg, A.L., Bamlet, W.R., Zhang, L., Waldmann, J., Radisky, E.S., Crawford, H.C. and Radisky, D.C. (2014). Tumor Cell-derived MMP-3 Orchestrates Rac1b and Tissue Alterations that Promote Pancreatic Adenocarcinoma. Molecular Cancer Research (21 May 2014). doi: 10.1158/1541-7786.MCR-13-055

    Press release: Mayo Clinic

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    AIMS AND OBJECTIVES:
    The Bioinformatics course aims to provide students with high-quality training in bioinformatics. The course provides a strong foundation for the development of essential bioinformatics knowledge and skills within the context of academic and industrial research, as well as an introduction to the emerging fields of Bio-inspired Computing & Systems biology. Some key themes are:
     Genomics
     Databases
     Functional & Structural Proteomics
     Phylogenetic Analysis
     Metabolomics
     Bio-inspired Computing
     Systems Biology

    TARGET AUDIENCES:
    Graduates (B.Sc, B-Tech, B.E) and Postgraduates (M.Sc, M-Tech, M.E) from the disciplines of Life sciences, Biotechnology, Computer Science, Bioinformatics, Biomedical Engineering, Genetics, Chemistry.

    MODE OF SELECTION:
    First Come First Serve Basis

    PERIOD OF COURSE COMMENCEMENT/IMPLEMENTATION:
    09/06/2014 – 20/06/ 2014 (Batch – 1)
    23/06/2014 – 04/07/2014 (Batch – 2)

    COURSE COORDINATOR:
    Mr. Karthik Kalyan

    CO-COORDINATORS:
    Mr. Sandeepan Mukherjee
    Dr. Ritwik Dahake
    Dr. Usha Padmanabhan

    All Participants shall work on LIVE projects through the course of the workshop. Participants who make a significant contribution to data generation and analysis shall be given an authorship in publications coming out of such research.

    Registration Charges: Rs: 10,000/- (Ten Thousand Rupees Only) Payable by Cash/ Demand Draft (Drawn in favour of “The Director, Haffkine Institute” Payable at Mumbai.

    A fee once paid is non-refundable & non-transferable. Registration forms are available on Haffkine Institute Website.

    For further information please visit the following links:
    http://www.haffkineinstitute.org/BAIT-20...CATION.pdf
    https://www.facebook.com/BAITATHAFFKINE

    .pdf  BAIT-2014 NOTIFICATION.pdf (Size: 383.35 KB / Downloads: 1)

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    Calorific restriction reduces metastasis (spreading to secondary sites) of tumours in a mouse model of triple-negative breast cancer. This effect is augmented by ionising radiation. While the effect is mediated partially by reduction in expression of microRNAs, calorific restriction is likely to have many molecular targets and could form part of the therapeutic arsenal aimed at reducing triple negative breast cancer metastasis. These are the findings of a new study from researchers in Thomas Jefferson University in Philadelphia and the National Cancer Institute, NIH, Bethesda. The study is published in the journal Breast Cancer Research and Treatment.

    Triple-negative breast cancer lacks oestrogen receptor, progesterone receptor and the HER2 protein. These are therapeutic targets in other forms of breast cancer and their absence makes it all the more difficult to develop effective therapies to triple-negative breast cancer. New strategies are desperately needed as this form of breast cancer features high incidence of recurrence and metastasis to sites such as the brain and lung. Calorific restriction is a form of dieting in which food intake is carefully reduced by a specified percentage and has been previously shown to induce tumour regression in mouse models of triple-negative breast cancer. The treatments given to breast cancer patients, such as hormonal therapy to reduce tumour growth and steroids to counteract chemotherapy side-effects, themselves contribute to the weight gain often experienced by women being treated for breast cancer. Too much weight has been shown to reduce the effectiveness of standard breast cancer therapies, inspiring the research team to look at metabolism and calorific restriction in women with breast cancer.

    In the current study the researchers examined whether this regression was mediated by a type of small, regulatory RNA called microRNA (miR). These miRs exert their cellular effects by altering expression of other genes. The researchers examined miRarrays from mice which had been subjected to calorific restriction compared to mice which were given free access to food. The results showed that calorific restriction reduced the expression of miR-17/miR-20a. These have been previously shown to be up-regulated in patients with metastasising triple-negative breast cancer. The research team further investigated how these miRs might be regulating the response to calorific restriction. They discovered that the gene targets were related to the extracellular matrix, which would be highly relevant to tumour metastasis. Senior author Dr Nicole Simon explains the significance of this finding: “Calorie restriction promotes epigenetic changes in the breast tissue that keep the extracellular matrix strong…A strong matrix creates a sort of cage around the tumour, making it more difficult for cancer cells to escape and spread to new sites in the body."

    Identification of the link to miR-17/miR-20a should be helpful in identifying triple-negative breast cancer patients whose cancer is more likely to metastasise and may suggest a potential new drug target. However, Dr Simon stresses that the effects of calorific restriction, especially when used to augment ionising radiation treatment, are likely to be more widespread than simply a targeted effect on miR-17/miR-20a. Triple negative breast cancers differ genetically between patients. Calorific restriction has the potential to ‘hit’ a large group of genes simultaneously, thus offering non-toxic benefits to patients whose cancers have different genetic bases.
    To test this, Dr Simon is currently enrolling triple-negative breast cancer patients in a trial called CaReFOR (Calorie Restriction for Oncology Research). In this trial, women receiving radiation therapy for their breast cancer will also receive nutritional counselling and guidance in weight loss as they progress through their treatment.

    Sources

    L. Jin, et al., "The metastatic potential of triple-negative breast cancer is decreased via caloric restriction-mediated reduction of the miR-17~92 cluster," Breast Cancer Research and Treatment[/u][/i]. DOI 10.1007/s10549-014-2978-7, 2014.

    Press release: Thomas Jefferson University. Available at http://www.eurekalert.org/pub_releases/2...052114.php

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    International Conference on: Urban Planning and Architectural Design for Sustainable Development (http://www.ierek.com)

    We have the honor to invite you to attend our international conference on: “Urban Planning and Architectural Design for Sustainable Development”
    This conference is planned to be held on The Kore University of Enna, Italy.
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  • 05/28/14--05:23: Fermentation / EMF
  • I'm hoping someone can direct me to someone who may know whether EMF (electromagnetic radiation) has been used in any commercial fermentation processes as a way to promote growth.

    The reason for my question actually has to do with the effect of pulsed EMF (PEMF), which is a low-frequency EMF therapy used to promote tissue healing, on microbiota.

    Online I've found only a few relevant studies and articles, such as:

    http://www.researchgate.net/profile/Andr...ion_detail

    http://www.ncbi.nlm.nih.gov/pubmed/23046211

    Thanks very much for your help.

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    Use of high-throughput DNA sequencing techniques has revealed that the underlying genetic cause of schizophrenia appears to lie in damage to several genes rather than being pinpointed to a single gene. The number and types of mutations also influences severity of this devastating psychiatric disorder. These are the main findings of a study published in the journal Neuron from researchers in Columbia University Medical Centre and Pretoria University.

    Schizophrenia is a psychiatric disorder characterised by hallucinations, delusions and cognitive issues. With an incidence of 1 in 100, it is relatively common and the risk of schizophrenia is increased in people with a family history of the disease. Previous studies have attempted to identify single genes that could lie behind schizophrenia. However, the rise of high-throughput sequencing techniques means that a more far-reaching approach can be taken, as in the current study.

    The research team recruited 231 schizophrenia patients and their non-schizophrenic parents and applied the high-throughput DNA sequencing techniques to the ‘exome’ of these individuals. This means the part of the genome that actually encodes proteins rather than any intervening regions. The results indicated that the schizophrenia patients had DNA damage extending over several genes. The types of mutations were also examined and the research team observed that there was a higher than expected incidence of so-called ‘loss-of-function’ mutations which were not inherited from the patients’ parents. These types of mutations are rare but, as their name implies, have a more severe effect on gene function than other types of mutation.

    The team turned their attention to the identities of some of the genes that were mutated and found that there was a preponderance of mutations in genes encoding proteins involved in a process called chromatin regulation. This process dictates how DNA is packaged and how genes are regulated. Alterations in chromatin regulation genes have recently been observed in other psychiatric disorders. In particular, the researchers noted two loss-of-function mutations in a gene called SETD1A, which encodes a subunit of the protein histone methyltransferase, a key enzyme in chromatin regulation.

    Study author Dr Joseph Gogos explained the clinical significance of these findings: “A clinical implication of this finding is the possibility of using the number and severity of mutations involved in chromatin regulation as a way to identify children at risk of developing schizophrenia and other neurodevelopmental disorders…Exploring ways to reverse alterations in chromatic modification and restore gene expression may be an effective path toward treatment." The research team is now seeking to identify further genes associated with schizophrenia and identify common functions of these genes.

    Sources

    Takata, A. et al. (2014). Loss-of-Function Variants in Schizophrenia Risk and SETD1A as a Candidate Susceptibility Gene. Neuron 82(4): 773-780. http://dx.doi.org/10.1016/j.neuron.2014.04.043

    Press release: Columbia University Medical Centre

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