The US Food and Drug Administration (FDA) has just approved the drug metreleptin as a therapy for the rare metabolic disease lipodystrophy. Patients with lipodystrophy are deficient in the hormone leptin; meterleptin is a drug form of this hormone. Lipodystrophy is extremely rare, having been reported in 300-500 people internationally. It can be inherited or acquired and is characterised by almost complete absence of fat tissue either from birth or developing during childhood. Despite their extremely lean and muscular body shape, patients paradoxically suffer from diseases such as severe diabetes and high blood pressure due to elevations of triglyceride levels. This leaves them extremely susceptible to cardiovascular disease and stroke.

Standard treatment for lipodystrophy has up until now focused on high-dose insulin to tackle diabetes plus triglyceride- or lipid-lowering medications. The newly approved drug, metreleptin, works by curbing appetite and normalising metabolism. Dr. Abhimanyu Garg, Chief of the Division of Nutrition and Metabolic Diseases at University of Texas (UT) Southwestern initiated the first metreleptin trial in collaboration with the National Institutes of Health (NIH). He says: “Many lipodystrophy patients have benefited from leptin therapy. While it is not a cure, leptin does help manage complications that can include diabetes, high blood lipids, and accumulation of fat in the liver.” Dr Garg’s research first led to identification of mutations in the gene that lipodystrophy.

However, the potential therapeutic potential of leptin was discovered almost by accident due to serendipitous creation of a leptin-deficient mouse model of generalized lipodystrophy by Nobel Laureates Dr. Michael Brown and Dr. Joseph Goldstein while researching cholesterol metabolism. When these mice were injected with leptin, it was discovered that their appetite was suppressed and that their insulin resistance, diabetes, and fatty liver improved. This led to the suggestion that Dr Garg try leptin as a therapeutic in lipodystrophy in humans. The first clinical trial was carried out by UT Southwestern in collaboration with the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases and the pharmaceutical company Amgen. In 2002, the researchers reported that leptin therapy indeed controlled insulin resistance and triglyceride levels in lipodystrophy patients as well as decreasing build-up of fat in the liver. When used in human lipodystrophy patients, an appropriate dose can remove the need for insulin or at least for high-dose insulin treatment.

Dr. Garg, in collaboration with the NIH and Amgen, holds both U.S. and European patents in collaboration for use of leptin for lipodystrophy treatment. Bristpl-Myers Squibb acquired rights to the leptin molecular franchise in 2006 via their subsidiary, Amylin Pharmaceuticals. Dr Gard is currently a consultant for Bristol-Myers Squibb, who make metreleptin in partnership with AstraZeneca.

Source:
UT Southwestern Medical Centre press release; available at http://www.eurekalert.org/pub_releases/2...022514.php

The University of the Basque Country (UPV/EHU) have announced that researchers in their Cell Biology and Histology Department have patented a method for diagnosis and prognosis of cutaneous melanoma, the deadliest form of skin cancer. This method should assist in earlier diagnosis of melanoma and help in developing personalised treatments. The patent has been filed with the Spanish Patents and Trademarks Office, reference P10196ES00.

Melanoma arises from transformation of melanocytes, which are the melanin-synthesising cells of the body. Melanin is essential for protection from harmful effects of solar radiation. Melanoma is one of the less common skin cancers but it has the highest mortality rate due to its high metastatic potential. The key to successful treatment is early diagnosis, as “patients with early-stage melanoma have a survival rate of 95%, while 5-year survival falls to 50% in patients with metastasis,” according to Dr Yoana Arroyo, one of the researchers contributing to the patented method.

The patented method arose from research in the Tumour Markers and New Therapies research group of the Department of Cell Biology and Histology in UPV/EHU. The group were interested in identifying markers which could reliably distinguish between melanoma cells versus normal, untransformed melanocytes. An approach was adopted based on comparing gene expression data, mutational analysis and epigenetic data.

The group were able to confirm that the melanoma cells have characteristic patterns of gene and protein expression which distinguished tumour versus non-tumour status. Furthermore, they have developed a method to identify cells with higher invasive capacity which are most likely to metastasise. Thus the patented method includes new molecular biomarkers that are relevant in melanoma diagnosis, prognosis and susceptibility.

Dr Arroyo concluded: “This diagnosis method is a way of identifying those patients who are more likely to develop metastasis, so that their treatment and survival can be improved. This study could also open up new avenues of research for the development of new, more personalised treatments.”

Source

UPV/EHU press release; available at: http://www.basqueresearch.com/berria_ira...wttJLavnIU [Accessed 24 February 2014].

Human evolution in the genomic era: Origins, populations and phenotypes

Organisers: EMBO; contact Chiara Batini or Mark Jobling (University of Leicester) embo2014humanevolution@gmail.com

Dates: April 1st- 4th, 2014

Location: College Court Conference Centre, Leicester, UK

Website: http://events.embo.org/14-human-evo/
The website gives all the necessary information on abstract submission, fees, registration, conference agenda, hotel, exhibitions and other important facts.

Purpose of the conference

“Molecular studies of human evolution have undergone an extraordinary transformation in the last decade. The analysis of human genetic diversity has shifted from locus-specific to genome-wide, with new molecular techniques and informatic methods, and their application in large-scale collaborative projects. This revolution is providing new insights into the human past, into mutation rates and recombination processes, and into adaptation and the molecular and evolutionary basis of genetic disease. This EMBO Conference aims to provide an accessible opportunity for early-career researchers and PhD students to exchange ideas and knowledge with each other, and with key senior investigators who have contributed some of the major advances. The meeting represents a dynamic and stimulating forum for discussing the state of the art and future of this field.”

Topics:
• Human genome sequence variation
• New frontiers in sequencing technologies
• Processes shaping human genome diversity
• Making inferences from genome diversity
• Humans as apes
• What genetic changes made us human?
• The function of the human genome
• Origins of modern humans
• Crossing disciplinary boundaries
• The global distribution of genome diversity
• Migrating out of Africa
• The impact of agriculture
• Into new-found lands
• Phenotypic variation among humans
• Evolutionary aspects of simple and complex disease
• The personal genome

Confirmed Speakers

Guido Barbujani, Universita' di Ferrara, Italy
Ewan Birney, European Bioinformatic Institute, UK
Carlos Bustamante, Stanford University School of Medicine, USA
Lounes Chikhi, CNRS Toulouse, France
Vincenza Colonna, Institute of Genetics and Biophysics - ABT, Italy
Graham Coop, UC Davis, USA
Anna Di Rienzo, University of Chicago, USA
Richard Durbin, Wellcome Trust Sanger Institute, UK
Pascal Gagneux, UC San Diego, USA
Garrett Hellenthal, University College London, UK
Brenna Henn, Stony Brook University, USA
Turi King, University of Leicester, UK
Tomas Marques-Bonet, Institut Biologia Evolutiva (Universitat Pompeu Fabra/CSIC), Spain
Joanna Mountain, 23andme, US
Mark Pagel, University of Reading, UK
Sohini Ramachandran, Brown University, USA
Aylwyn Scally, University of Cambridge, UK
Mark Shriver, Pennsylvania State University, USA


Who are the organisers?

This is an EMBO conference. The local organisers are Prof Mark Jobling and Dr Chiara Batini of the Department of Genetics in the University of Leicester. They can be contacted at the email address given above. Further details on the organisers and co-organisers can be accessed via the conference website given above.

A new study has described how albumin nanoparticles loaded with an anti-inflammatory drug can be targeted to neutrophils which cause injury by building up at the site of injury while sparing circulating neutrophils. The study from the University of Illinois in Chicago was published online in Nature Nanotechnology on February 23rd. The study could point the way forward to resolve the problem of targeting anti-inflammatory medication effectively to the cells causing damage while allowing other immune cells to remain in circulation to come into play when needed.

Neutrophils are circulating granulocytic cells that accumulate in response to signals at the site of infection and/or injury. When there, they engulf microbes and debris in a process known as phagocytosis, as well as releasing mediators that can help resolve the infection and promote healing. However, in some cases neutrophils can have a damaging effect, for example in chronic and acute inflammatory disease conditions. In these cases, neutrophils can accumulate at the blood vessel wall, sticking both to each other and the endothelium. This can be problematic particularly in some respiratory conditions, for example in the case of acute lung injury when it can lead to severe breathing difficulties and can be fatal if ineffectively treated.

Nanoparticles have risen in prominence in recent years as a way to target therapies in a variety of conditions including some cancers. In this case, the researchers exploited the fact that adhesive neutrophils express cell surface Fcɣ receptors which circulating neutrophils lack or express at a much reduced level. The researchers used a mouse model treated with an inflammatory cytokine called tumour necrosis factor to induce vascular inflammation. The albumin nanoparticles in the study could adhere to the Fcɣ receptors, targeting them to the adherent neutrophils and they were labelled with a fluorescent dye so their location could be studied in real time. The nanoparticles were loaded with an anti-inflammatory tyrosine kinase inhibitor called piceatannol. When delivered to the adherent neutrophils, this drug interfered with the integrin-mediated adhesive signalling pathways inside the neutrophils, causing them to become detached and released into the circulation.

Dr Asrar Malik, senior author on the paper, is confident that this type of nanoparticle technology can improve therapy in inflammatory diseases, which is currently reliant on corticosteroids and non-steroidal anti-inflammatory drugs. These are unselective, broad-range drugs with significant side-effects. Dr Malik concluded: "The nanoparticle is very much like a Trojan horse….It binds to a receptor found only on these activated, sticky neutrophils, and the cell automatically engulfs whatever binds there. Because circulating neutrophils lack these receptors, the system is incredibly precise and targets only those immune cells that are actively contributing to inflammatory disease."

Sources:

Wang,Z., Li, J., Cho, J. and Malik, A.B., 2014. Prevention of vascular inflammation by nanoparticle targeting of adherent neutrophils. Nature Nanotechnology (2014); doi:10.1038/nnano.2014.17

Press release from University of Illinois; available from: http://www.eurekalert.org/pub_releases/2...022114.php [Accessed 24 February 2014].

Protein C (HPC4) tag encodes residues 6 through 17 of the protein C heavy chain. Compared with the His tag, Protein C tag can capture higher purity proteins from

Escherichia coli, yeast, Drosophila, and HeLa extracts.
GenScript has developed highly specific and sensitive Protein C tag antibodies for detection and analysis of fusion proteins with Protein C tag.

---

(02-24-2014, 06:34 PM)Genscriptlorraine Wrote: Protein C (HPC4) tag encodes residues 6 through 17 of the protein C heavy chain. Compared with the His tag, Protein C tag can capture higher purity proteins from

Escherichia coli, yeast, Drosophila, and HeLa extracts.
GenScript has developed highly specific and sensitive Protein C tag antibodies for detection and analysis of fusion proteins with Protein C tag.

---

GenScript has developed highly specific and sensitive Protein C tag antibodies for detection and analysis of fusion proteins with Protein C tag.
http://www.genscript.com/antibody/A01774...c=backlink

Hi,
I have BSc in Biotechnology, but no experience, what courses, certificates are useful for employers ? I want to work in laboratory so I'm looking for courses like ISO 17025 etc. do you know any in UK? what would I need to work in lab in UK?

MazF is an E.coli enzyme that degrades cellular mRNA in a targeted fashion, at the "ACA" sequence. By modifying all "ACA" triplets in the target gene, a study showed that induction of MazF toxin caused degradation of E.coli cellular mRNA but the recombinant gene transcription and protein synthesis continued, causing significant accumulation of high quality target protein.

For years, GenScript has been the industry leader in synthetic DNA technology. As performed in this study, we codon-optimize the target gene to eliminate any unnecessary sequence elements which also helps achieve high levels of soluble expression. With its robust gene-to-protein service offerings, GenScript will be a reliable partner throughout your protein production campaign.



BacPower™ Customized service – what's included
> State-of-the-art OptimumGene™ gene design technology
> Sub-cloning and expression optimization
> Pilot scale protein expression and purification
> Protein characterization

---

E.coli mRNA breakdown results

Duckweed, a ‘forever young’ tiny floating plant with one of the smallest known plant genomes, may be about to become big in the field of biofuel production. The complete genome of Greater Duckweed (Spirodela polyrhiza) has this week been detailed and analysed in comparison to other plants such as rice and tomatoes, in a publication from researchers in institutions in the USA and Germany. The study was published in the journal Nature Communications.

Duckweed, a tiny floating plant with a few thin, underwater roots and a single small kidney-shaped leaf, is generally considered to be an annoyingly difficult-to-control weed, growing in ponds and small lakes. It is very fast-growing and can double its population over the course of a couple of days if conditions are favourable. However, it has also been commercially exploited to clean contaminated water and as a pharmaceutical source to produce pharmaceuticals. Its rapid growth, the lack of any need to hold itself upright or transport water from its roots to its leaves and its small content of woody materials like lignin and cellulose make it an ideal candidate for biofuel production. Added to that is its ease of harvesting compared to biofuel-producing microbes.

The sequencing of the Spirodela polyrhiza genome has revealed it to have one of the smallest known plant genomes. There are about 158 million base pairs containing fewer than 20,000 protein-encoding genes. The plant has what senior author Joachim Messing of Rutgers University describes as “a forever-young lifestyle” in which as they mature, they continuously produce cotyledon leaves, that is embryonic leaves inside plant seeds. This prolonging of juvenile traits is called "neoteny." The genome sequencing project revealed that S. polyrhiza had fewer genes to promote and more genes to repress the switch from juvenile to mature growth. This arrest in development allowed the research team to “uncover regulatory networks that are required for differentiation and development," according to Dr Messing.

Importantly in terms of biofuel production, the genome analysis also revealed the molecular basis of the low woody material content of duckweed. The plant lacked many of the genes responsible for cellulose and lignin production in land dwelling plants and had fewer copies of the ones that were present. Meanwhile, genes for compounds associated with cell wall and root growth, called "expansins", were also reduced. Among genes which were retained were those for starch production, probably used for creation of starch-filled turions. These are buds which aquatic plants use to allow them to dwell at the bottom of ponds during winter and revive in warmer weather. Interestingly, S. polyrhiza has more copies of genes for enzymes involved in nitrogen absorption and metabolism than in other plants despite its overall tiny genome. This would contribute to the plant's ability to clean up contaminated water by utilising excess nitrogen.

Overall, the genome analysis will contribute to thorough understanding of the genome and cellular mechanisms of S. polyrhiza and hence to current efforts to recruit duckweed as a biofuel source. Dr Messing estimates that duckweed will be a viable biofuel source as soon as in the next five years. Indeed, he points out that a New Jersey company called Ceres Energy Group is already producing electricity from duckweed. Genome analysis will allow exploitation of traits that are advantageous in biofuel production, such as reduced cellulose or increased starch, in development of new duckweed varieties.

Dr Messing concludes that: "The sequencing of this genome opens new frontiers in the molecular biology of aquatic plants….This publication represents the single largest advance in this field and a new milestone in plant molecular biology and evolution, as previous studies were either classical botany or biochemistry of photosynthesis. The placement of the Spirodela genome as a basal monocot species will serve as a new reference for all flowering plants."

Sources

http://www.eurekalert.org/pub_releases/2...021414.php [DOE/Joint Genome Institute press release; accessed 19 February 2014].

WANG,W., HABERER, G., GUNDLACH, H., GLÄßER, C., NUSSBAUMER, T., LUO, M.C., LOMSADZE, A., BORODOVSKY, M., KERSTETTER, R.A., SHANKLIN, J., BYRANT, D.W., MOCKLER, T.C., APPENROTH, K.J., GRIMWOOD, J., JENKINS, J., CHOW, J., CHOI, C., ADAM, C., CAO, X.H., FUCHS, J., SCHUBERT, I., ROKHSAR, D., SCHMUTZ, J., MICHAEL, T.P., MAYER, K.F.X. and MESSING, J., 2014. The Spirodela polyrhiza genome reveals insights into its neotenous reduction fast growth and aquatic lifestyle. Nature Communications, Vol. 5 (19 February 2014), doi:10.1038/ncomms4311

A new biotechnology company called Voyager Therapeutics was launched this week with the goal of developing gene therapies for diseases of the central nervous system (CNS). The scientific founders of Voyager Therapeutics are experts in the fields of adeno-associated virus (AAV) gene therapy, RNA biology, including RNA interference, and neuroscience. They include the University of Massachusetts researchers Phillip D. Zamore, PhD and Guangping Gao, PhD, Mark Kay, MD, PhD of Stanford University and Krystof Bankiewicz, MD, PhD of the University of California.

Voyager Therapeutics will exploit the expertise of the founders by focusing on an AAV approach to gene therapy. This may transform treatment for a range of devastating CNS disease by allowing one-time therapies. The company will concentrate on sometimes problematic areas in AAV research including vector optimization and engineering, dosing techniques, and process development and production. The company already has multiple clinical and preclinical product programmes underway for CNS diseases, for example an on-going collaborative Parkinson’s disease Phase 1b study with researchers at the University of California and preclinical programmes for a monogenic form of amyotrophic lateral sclerosis (ALS) and Friedreich’s ataxia.

AAV has emerged over the past decade as a promising gene therapy approach, with good safety profiles and effectiveness as a delivery vehicle. Development of AAV vectors that facilitate delivery to the brain and spinal cord means it is well placed for development of CNS disease therapies. AAV production has also become more commercially attractive in recent times, with developments in scalability and cost effectiveness of production.

Voyager’s proposed suite of gene therapies will include both gene replacement and gene knockdown techniques, depending on the disease to be targeted. These techniques can either increase or decrease production of relevant target proteins as appropriate. Thus, the therapy gets to the heart of the disease’s underlying biology.

Mark Levin, interim chief executive officer of Voyager and partner at Third Rock, is optimistic about the future of gene therapy in general. He says: “We believe the time is right for gene therapy, and we have assembled the expertise, technology and strategies to translate the promise of AAV gene therapy into breakthrough treatments for patients with these devastating CNS diseases.”

Voyager’s future will be bolstered by licencing agreements with the University of Massachusetts, the University of California and Stanford University, which allows the fledgling company to access relevant technology and data. This includes intellectual property on RNA interference technology discovered at the University of Massachusetts, Parkinson’s disease clinical data from the University of California and AAV intellectual property at Stanford.

Source
http://www.umassmed.edu/news/2014/resear...apies.aspx [UMass Medical School press release; accessed 19 February 2014].

A new digital publication called ‘Mosaic’ will be launched on 4th March by the charitable foundation, the Wellcome Trust. ‘Mosaic’ aims to explore the science of life and will tell the story of biomedical research via features, articles and films to an audience interested in science, with or without specialised knowledge. ‘Mosaic’ articles will be free to read and text features will be published under a Creative Commons licence. This means they can be reproduced and freely distributed via other platforms such as paid-for websites and magazines and publications that are funded by advertising, as well as independent blogs.

The development of ‘Mosaic’ is partially in response to the lack of space in mainstream print publications. It aims to give a home to in-depth science writing, with scope for the contributing writers to explore their topic in depth over an article of up to several hundred words. The Wellcome Trust sees this as an opportunity to fill a gap in how science is conveyed in print to the general public and allow interested readers to learn more about a subject from different angles. The Creative Commons licencing arrangement is consistent with the Trust’s commitment to open access in science and biomedical publishing and will allow the content of ‘Mosaic’ to be available to the widest possible audience.

‘Mosaic’ has commissioned several well-known journalists and writers to contribute pieces. These include Carl Zimmer, Rose George, Virginia Hughes, Ed Yong and Jenny Diski. While Wellcome Trust funded research in the fields of biomedical science and medical humanities will be covered, the content of ‘Mosaic’ will not be limited to this research. Editorial policy will be established to ensure there is transparency if Trust-funded research is featured.

Mark Henderson, Head of Communications at the Wellcome Trust said: "The Wellcome Trust is committed to engaging the public with the areas of research we support and encouraging discussion around the contributions and challenges they bring. Digital technology now gives us the chance to do this by supporting great journalism and sharing it with the large but poorly-served general audience with an affinity for science. We hope Mosaic will help to give life science, and the many issues it raises, a more central place in the national and international conversation."

Source
http://www.eurekalert.org/pub_releases/2...021714.php [Wellcome Trust press release; accessed 19 February 2014].

A new study published in the journal Respirology shows that walking 3-6 km per day significantly reduced the risk of patients with chronic obstructive pulmonary disease (COPD) being hospitalised for exacerbations of their COPD. This is another demonstration of the benefits of even moderate physical activity for health.

COPD is a distressing respiratory condition resulting from long-term lung damage, for example due to cigarette smoking. The term includes chronic bronchitis and emphysema. COPD patients eventually develop breathing difficulties and if symptoms become severe (eCOPD) can suddenly lose lung function altogether, which is life-threatening.

In the Respirology study, five hundred forty-three ambulatory clinic patients being treated for COPD were identified from five Spanish respiratory clinics. Subjects were included who were followed up for at least two years after study enrolment. The researchers monitored the patients’ exercise levels based on the distance they walked during the course of a week. They then matched this information to records on the database of Bilbao’s Hospital Galdakao-Usansolo to determine which patients were hospitalised due to eCOPD.

The results of the study showed that patients with a lower level of physical activity had an increased risk of being hospitalised for eCOPD, while patients who had the highest level of physical activity then decreased their physical activity in the follow-up also had an increasing rate of hospitalisations. Increasing physical activity to a higher level or maintaining a moderate or high level of physical activity over time, for example with low intensity activity such as walking for at least 3–6 km/day, reduced the rate of hospitalisations for eCOPD.

The lead author on the study, Dr. Cristóbal Esteban, concluded: “COPD patients are less likely to engage in regular physical activity than healthy individuals. However, regular exercise has been associated with reduced risk of hospitalization for exacerbated COPD and mortality among patients with COPD….Indeed, even a low level of physical activity such as walking a minimum of 2 hours per week has been associated with decreased risk of hospitalization for exacerbated COPD.”

Sources

http://eu.wiley.com/WileyCDA/PressReleas...10311.html [Accessed 18 February 2014].

ESTEBAN, C., AROSTEGUI, I., ABURTO, M., MORAZA, J., QUINTANA, J. M., AIZPIRI, S., BASUALDO, L. V. and CAPELASTEGUI, A., 2014. Influence of changes in physical activity on frequency of hospitalization in chronic obstructive pulmonary disease. Respirology. doi: 10.1111/resp.12239

247th American Chemical Society (ACS) National Meeting & Exposition

Organisers: American Chemical Society

Dates: March 16th -20th, 2014

Location: Dallas, Texas, USA

Website: http://www.acs.org/content/acs/en/meetin...-2014.html

The website gives all the necessary information on conference agenda, hotel, exhibitions and other important facts. The conference brochure including preliminary programme is attached.

Major theme
“Chemistry & Materials for Energy”

Reasons to attend?
 ACS meetings & expositions each year attract 11,000 to 13,000 chemists, chemical engineers, academicians, graduate and undergraduate students, and other related professionals.
 Scientists present new multidisciplinary research, hear the latest information in their areas of professional interest, and network with colleagues.
 Programming is planned by our 33 technical divisions that cover all scientific fields, secretariats that focus on multidisciplinary programming, and ACS committees.
 Each meeting will feature more than 7,000 presentations organized into technical symposia that highlight important research advances.

Attendees will have the opportunity to:
• Discover New Research and Publish Your Work
• Advance Your Career
• Network with your peers
• Learn about New Technologies

Meeting topics

The conference brochure, including preliminary programme is attached and includes information on symposia relevant to biotechnologists. Meeting topics will also include:
• Catalysis for clean energy technologies:
biomass conversion; reduced emissions;
electrocatalysts for batteries, fuel cells, and artificial photosynthesis
• Harnessing the energy of the sun:
photovoltaic; solar thermal; solar fuels; artificial
photosynthesis, biomass conversion
• Materials for extremes:
corrosion resistant materials; materials for high T/P; next generation lightweight materials for transportation and other applications (e.g., carbon fiber, polymers, etc.)
• Nuclear materials and fuels:
fuel cladding, fuel recycle, radiation resistant materials (structural materials and concrete)
• Energy storage materials:
batteries and capacitors
• New materials and systems for the grid:
superconductivity; rare earths (substitutes,
recovery); grid-scale storage; generation technologies
• Materials for energy efficiency:
thermoelectrics, solid state lighting, building materials (insulation, coatings, roofing, windows)
• New technologies for enhanced recovery of fossil fuels
• CO2 sequestration and conversion

Is your child a ‘hearty eater’ who finds it hard to resist tempting food and has difficulty knowing when they are ‘full’? Two studies in the journal JAMA Pediatrics suggest that childhood obesity could be related to these key aspects of appetite. The studies, led by researchers in the UCL Health Behaviour Research Centre in the UK, looked at weight gain in relation to both lower satiety responsiveness (a reduced urge to eat in response to internal 'fullness' signals) and higher food responsiveness (an increased urge to eat in response to the sight or smell of nice food). The studies suggested that both of these elements correlated with weight and risk of obesity.

Childhood obesity is a major public health concern in westernised nations, to the point of being termed an epidemic. Public health campaigns focus on trying to educate parents to pay attention to portion sizes, frequency of giving treats, avoiding sugary drinks and making sure children take enough exercise. The two current studies shed light on what elements of appetite place children at risk of developing obesity and stress that problems can be identified in infancy.

The first study examined non-identical, same-sex twins born in the UK in 2007. Twins were assessed for differences in their satiety responsiveness (SR) and food responsiveness (FR) at three months of age, then their growth was monitored up to fifteen months. It was observed that within a twin pair, the child with greater food responsiveness or lower satiety responsiveness grew faster than their twin, potentially increasing their chance of developing childhood obesity.

Professor Jane Wardle, the lead author on the study from the UCL Health Behaviour Research Centre said: "Identifying factors that promote or protect against weight gain could help identify targets for obesity intervention and prevention in future. These findings are extremely powerful because we were comparing children of the same age and same sex growing up in the same family in order to reveal the role that appetite plays in infant growth…It might make life easy to have a baby with a hearty appetite, but as she grows up, parents may need to be alert for tendencies to be somewhat over-responsive to food cues in the environment, or somewhat unresponsive to fullness. This behaviour could put her at risk of gaining weight faster than is good for her."

In the second paper, data from 2258 ten-year old children born in the UK between 1994 and 1996 was examined. Researchers calculated a ‘polygenic obesity risk score’ (PRS) to figure out genetic susceptibility of each individual child to obesity by adding up the number of obesity-risk alleles from a panel of 28 obesity-related genes. A high PRS indicated an increased genetic predisposition to obesity. The researchers then matched the PRS to children's satiety responsiveness and adiposity (body fatness) to figure out if these was any correlation. They found that children with higher PRS tended to have higher BMI and waist circumference. But even more importantly, they confirmed that higher PRS also correlated with lower satiety responsiveness.

Dr Clare Llewellyn, lead author from the UCL Health Behaviour Research Centre said: "This suggests that satiety sensitivity could be targeted for pharmacological and behavioural interventions, to prevent or treat obesity. For example, children with lower satiety sensitivity could be taught techniques that might improve their fullness signals when eating, such as slowing their eating speed. Another approach might be to provide better advice to parents and children about appropriate portion sizes, limiting access to 'second helpings' and ensuring tempting treats are out of sight between meals."

Sources

Press release: http://www.eurekalert.org/pub_releases/2...021414.php [Accessed 18 February 2014].

LLEWELLYN, C.H., TRZASKOWSKI, M., VAN JAARSVELD, C.M., PLOMIN, R. and WARDLE, J., 2014. Satiety Mechanisms in Genetic Risk of Obesity. JAMA Pediatr. 2014;(): doi:10.1001/jamapediatrics.2013.4944

VAN JAARSVELD, C.M., BONIFACE, D., LLEWELLYN, C.H. and WARDLE J., 2014. Appetite and Growth: A Longitudinal Sibling Analysis. JAMA Pediatr. 2014;():. doi:10.1001/jamapediatrics.2013.4951

According to a new international study published online in Nature on February 16th, over-use of fertilisers is having an adverse effect on the number of species thriving in grasslands. According to one of the study’s co-authors, Johannes M.H. Knop of the University of Nebraska: "More nitrogen means more production, but it's less stable….There are more good years and more bad years. Not all years are going to be good and the bad years are going to be worse."

The three year study analysed diversity–stability relationships from 41 grasslands on five continents, in Germany, the USA, Switzerland, Tanzania and China, and looked to see how chronic fertilisation could affect these relationships. Such a concerted, long-term international effort is a relatively new development. Chronic fertilisation has been identified as one of the strongest international drivers of species loss. There were common trends observed across the range of grasslands. A process known as species asynchrony in natural, unfertilised grasslands, in which decreases in the biomass of some species are compensated for by increases in others resulted in a variety of grass species with more stability. However, use of fertiliser resulted in reduction of asynchrony and hence weakened the positive effect of diversity on stability due to the decline in the number of species.

It would not be common for farmers to directly fertilise rangeland and pastures, however grasslands would be affected by nitrogen deposition due to, for example, run-off from nearby fertilised crops and ammonia volatilization from cropland. According to Dr Knops, the effects of fertiliser overuse on species asynchrony could exacerbate the impact of events such as droughts on grasslands, such as devastated the cattle herd in Texas and Oklahoma in 2011-2013. It could also increase erosion due to reduction in plant cover, hence decreasing water filtration and carbon sequestration benefits of grasslands. This large international project emphasises the importance of a comprehensive consideration of how drivers of global change interact with each other to affect ecosystems and their diversity.

Sources

HAUTIER, Y., SEABLOOM, E.W., BORER, E.T., ADLER, P.B., HARPOLE, W.S., HILLEBRAND, H., LIND, E.M., MACDOUGALL, A.S., STEVENS, C.J., BAKKER, J.D., BUCKLEY, Y.M., CHU, C., COLLINS, S.L., DALEO, P., DAMSCHEN, E.I., DAVIES, K..F, FAY, P.A., FIRN, J., GRUNER, D.S., JIN, V.L., KLEIN, J.A., KNOPS, J.M.H., LA PIERRE, K.J., LI, W., MCCULLEY, R.L, MELBOURNE, B.A., MOORE, J.L., O’HALLORAN, L.R., PROBER, S.M., RISCH, A.C., SANKARAN, M., SCHUETZ M. and HECTOR, A., 2014. Eutrophication weakens stabilizing effects of diversity in natural grasslands. Nature (16 February 2014), doi:10.1038/nature13014

http://www.eurekalert.org/pub_releases/2...021414.php [Accessed 17 February 2014]

Organisers: European Molecular Biology Laboratory (EMBL):
Scientific Organisers: A. Berns, P. Pandolfi, B. Pauly

Dates: 7th May - 10th May 2014

Location: EMBL Heidelberg, Germany

Website: http://www.embo-embl-symposia.org/sympos...index.html

The website gives all the necessary information on abstract submission, fees, registration, conference agenda, hotel, exhibitions and other important facts. Although the abstract submission date has officially passed, the organisers request that if you still wish to submit an abstract please contact events@embl.de. Registration and payment deadline is 27th March 2014.

Purpose of the conference

This symposium brings together researchers from complementary fields to enhance understanding of the communication between cancer cells and their microenvironment. Important open questions are: Which signals do cancer cells transmit to and receive from the stroma and how do these signals promote malignant growth? What roles does the extracellular matrix play during neoplastic transformation? What is the contribution of immune cells to tumor progression? How is the inflammatory response of the tumour microenvironment regulated by the microbiota?

Session topics:

• Tumor Microenvironment
• Signalling pathways in stroma and cancer
• Therapeutical implications: from bench to bedside
• Cancer Stem Cells
• Cancer & the immune system
• Animal models in cancer

Confirmed Speakers:

• Kari Alitalo, University of Helsinki, Finland
• Frances Balkwill, Barts Cancer Institute, United Kingdom
• Mariano Barbacid, Spanish National Cancer Research Centre, Spain
• Eduard Batlle, Institute for Research in Biomedicine (IRB), Spain
• Joan Brugge, Harvard Medical School, USA
• Vincenzo Cerundolo, University of Oxford, United Kingdom
• Mike Clarke, Stanford University, USA
• Maria Pia Cosma, CRG Barcelona, Spain
• Karin de Visser, Netherlands Cancer Institute, The Netherlands
• Bruce Edgar, German Research Center (DKFZ), Gremany
• Mikala Egeblad, Cold Spring Harbor Laboratory, USA
• Rudi Grosschedl, Max Planck Institute of Immunobiology and Epigenetics, Germany
• Joerg Huelsken, Swiss Institute of Technology Lausanne (EPFL), ISREC, Switzerland
• Lisa Johnson, BC Cancer Agency, Canada
• Jos Jonkers, Netherlands Cancer Institute, The Netherlands
• Chris Marshall, The Institute of Cancer Research, United Kingdom
• Jan Paul Medema, Academic Medical Center, The Netherlands
• Luis Parada, UT Southwestern, USA
• Emmanuelle Passegué, UCSF, USA
• Catrin Pritchard, University of Leister, United Kingdom
• Andreas Trumpp, German Cancer Research Centre (DKFZ), Germany
• David Tuveson, Cold Spring Harbor Laboratory, USA
• Terry van Dyke, National Cancer Institute, USA
• Karen Vousden, The Beatson Institute for Cancer Research, United Kingdom
• Zena Werb, University of San Francisco, USA

Small non-coding RNAs, long dismissed as 'transcriptional noise' due to their apparently random distribution and lack of any discernible link to known functions, may actually be predictive of individuals who may develop breast cancer. That’s according to a study published today in EMBO Reports from researchers who contribute to The Cancer Genome Atlas project. This project is one of the largest available resources for small non-coding RNAs. The researchers are from the BC Cancer Agency, Simon Fraser University and the University of British Columbia, all in Vancouver, and Harvard Medical School.

Small non-coding RNAs, as the name suggests, do not give rise to protein products but may have other cellular functions. They are often found near transcriptional start sites but their function is often unclear. In the current study, the researchers were interested in distinguishing between the many different small non-coding RNAs that are found near the transcriptional start sites of genes in healthy individuals versus patients with breast invasive carcinoma. They used a computational technique to filter away some of the ‘transcriptional noise’ and arrived at a subset of small non-coding RNAs which were rich in CpG islands, i.e. in cytosine and guanine residues. They were also negatively correlated with methylation status. These small non-coding RNAs were mapped to specific DNA sequence locations and the researchers then looked to see if there was any relationship between strongly-expressed non-coding RNAs and the disease status of the patients from whom the tissue samples had been taken. Importantly, they used the information generated to try to predict the presence of disease in other tissue samples from breast cancer patients and found that they could efficiently predict the correct disease status for these samples. Thus these RNAs could potentially be used to classify cancer patients according to different survival outcomes.

Dr Steven Jones, the senior author on the study concluded that: "This is the first time that small non-coding RNAs near the transcription start site of genes have been associated with disease….Further work is required but based on our data we believe there is considerable diagnostic potential for these small non-coding RNAs as a predictive tool for cancer. In addition, they may help us understand better the mechanisms underlying oncogenesis at the epigenetic level and lead to potential new drugs employing small non-coding RNAs."

Sources

ZOVOILIS, A., MUNGALL, A.J., MOORE, R., VARHOL, R., CHU, A., WONG, T., MARRA, M. and JONES, S.J.M., 2014. The expression level of small non‐coding RNAs derived from the first exon of protein‐coding genes is predictive of cancer status. EMBO Reports, 2014. DOI: 10.1002/embr.201337950 |Published 17.02.2014

http://www.eurekalert.org/pub_releases/2...021314.php [Accessed 17 February 2014].

Scientists from Harvard University have discovered that prostaglandin E2 (PGE2) is the key that unlocks stem cells to differentiate into either liver or pancreas cells. Both these cell types are derived from a common endodermal stem cell progenitor and the trigger that decides which cell fate is followed has been poorly understood up until now. This study, published in the journal Developmental Cell, may help in making it easier to generate liver and pancreas cells in the lab, with benefits for transplant patients and/or future cell therapies.

The study was initiated in zebrafish embryos, where it was observed that there was a gradient of PGE2 in the area where stem cells differentiate into the internal organs. Studies were expanded to include mouse endodermal progenitor cells. It was found that both the PGE2 synthetic enzyme cox2a and one of its receptors, ep2a, are arranged in such a way that cells closest to PGE2 synthesis become liver cells, whereas more distant cells become pancreatic. It cooperates with another cell signalling pathway, the bmp2b pathway, to favour liver versus pancreatic fate. Further experiments in mouse cells showed that PGE2 could also enhance liver growth and regeneration of liver cells. At later developmental stages, PGE2 acting via another of its receptors, the ep4a receptor, to promote both liver and pancreatic outgrowth.

Dr Wolfram Goessling, senior author on the study, said that: “This is the first time that prostaglandin is being reported as a factor that can lead this fate switch and essentially instruct what kind of identity a cell is going to be….Prostaglandin might be a master regulator of cell growth in different organs.” The researchers now plan to develop knowledge in the laboratory as to how PGE2 instructs induced pluripotent stem cells—mature cells that have been reprogrammed into a stem-like state—to become liver or pancreas cells in order to benefit transplant patients and/or future cell therapies.

Sources

NISSIM, S. et al., 2014. Prostaglandin E2 Regulates Liver versus Pancreas Cell-Fate Decisions and Endodermal Outgrowth. Developmental Cell - 13 February 2014; 10.1016/j.devcel.2014.01.006

http://www.hsci.harvard.edu/newsroom/har...r-pancreas [Accessed 17 February 2014].

A new study published in the journal Cancer Cell suggests that a nuclear protein known as Twist may point to a potential way forward in treatment of the clinically aggressive triple-negative form of breast cancer. Triple-negative breast cancer is characterised by an activated programme of epithelial-mesenchymal transition (EMT), a process that allows cells to adapt to stressful environments. This is positive when contributing to processes such as embryonic development and wound healing but is unfortunately ‘hijacked’ by tumour cells to facilitate metastasis to secondary sites. It also makes tumour cells resemble stem cells, effectively ‘hiding’ them from therapeutic interventions. Twist is an accelerant of EMT, prompting the interest of researchers in the University of Kentucky Markey Cancer Centre to study it with respect to triple-negative breast cancer.

Triple-negative breast cancer is a particularly unpleasant form of this cancer, featuring high incidence of recurrence and metastasis to sites such as the brain and lung, factors which impact negatively on five year survival statistics. There is a lack of effective therapies for this form of breast cancer, making studies to elucidate its mechanisms even more important.

While Twist was known to be a transcriptional activator of EMT, the mechanism by which Twist exerts this activation was unclear. The Cancer Cell study revealed that Twist acts in an analogous manner to DNA viruses such as papillomaviruses. When these viruses enter the cell, they hijack host cell machinery for their own purposes to allow them to replicate and synthesis their viral DNA and proteins. A favourite target of DNA viruses is a nuclear transcriptional regulator called BRD4. Results of the Cancer Cell study showed that Twist similarly targets BRD4. Twist contains a histone H4-like domain which can bind to a bromodomain of BRD4. This creates a transcription-activating complex (Twist/BRD4/P-TEFb/RNA-Pol II) which targets transcription of the gene WNT5A. This in turn directs production of the protein Wnt-5a, which is implicated in oncogenesis. This process enhanced invasion and stem cell properties of triple-negative cancer cells. Pharmacological inhibition of BRD4 using the known inhibitors JQ1 and MS417 suppressed invasion, stem cell properties and tumourigenicity of these cells. Thus this study identifies a previously unrecognised interaction with BRD4 in directing oncogenic function of Twist in triple-negative breast cancer cells and provides a potential avenue for future drug development to treat this devastating disease. Dr Peter Zhou, the senior author of this paper, concluded that: "This finding has significant clinical ramification, because drugs that can target the Twist-BRD4 interaction provide a new hope for treating life-threatening triple-negative breast cancer."

Sources

University of Kentucky Markey Cancer Center: http://uknow.uky.edu/content/new-uk-stud...st-cancers [Accessed 12 February 2014].

Shi, J. et al, 2014. Disrupting the Interaction of BRD4 with Diacetylated Twist Suppresses Tumorigenesis in Basal-like Breast Cancer. Cancer Cell, 25 (2) 10 February 2014, Pages 210–225

Agatha Christie’s famous fictional detective Hercule Poirot was fond of ascribing his formidable intelligence to his ‘little grey cells’. A new study from an international team of scientists, led by a group in King’s College London, UK, suggests that he may have been partly right. These researchers have identified a gene which links thickness of the ‘grey matter’, i.e. the cerebral cortex which forms the outermost layer of the human brain, to intelligence. The study, published in today’s Molecular Psychiatry may shed light on the biological mechanisms underlying some forms of intellectual impairment.

The study describes the results of analysis of DNA samples and MRI brain scans from 1,583 healthy 14 year old teenagers, part of the IMAGEN cohort. The MRI and DNA results were correlated with the results of tests to determine their verbal and non-verbal intelligence. According to Dr Sylvane Desrivières, from King's College London's Institute of Psychiatry and lead author of the study, the object was to "find out how structural differences in the brain relate to differences in intellectual ability. The genetic variation we identified is linked to synaptic plasticity – how neurons communicate. This may help us understand what happens at a neuronal level in certain forms of intellectual impairments, where the ability of the neurons to communicate effectively is somehow compromised." Dr Desrivières cautioned that the gene identified in the study “explains a tiny proportion of the differences in intellectual ability, so it's by no means a 'gene for intelligence'."

The gene variation identified, from a genetic detective exercise involving examination of over 54,000 genetic variants possibly involved in brain development, was in the NPTN gene. This gene encodes the synaptic cell adhesion glycoprotein neuroplastin, which filled the criterion of influencing how neurons communicate. The study results showed that in participants who carried the particular gene variant, there was a thinner cortex in the left cerebral hemisphere, particularly in the frontal and temporal lobes. Importantly, these participants also had lower performance on the intelligence tests.

To extend and confirm these findings, the researchers carried out analysis of the NPTN gene both in mouse and human brain cells. Results indicated differential NPTN activity in the left versus the right brain hemispheres. The impact of these differences would result in the left hemisphere being more sensitive to NPTN mutation than the right. The findings suggest that reduction of NPTN function in the left hemisphere of the brain may contribute to compromising of intellectual ability. While this NPTN variation would account for no more than approximately 0.5% of variation in intelligence, it could still have major implications for beginning to tease out the biological mechanisms behind diseases featuring cognitive impairment, including schizophrenia and autism.

Sources
http://www.eurekalert.org/pub_releases/2...021014.php [Accessed 11 February 2014].

Desrivières, S. et al., 2014. Single nucleotide polymorphism in the neuroplastin locus associates with cortical thickness and intellectual ability in adolescents. Molecular Psychiatry advance online publication 11 February 2014; doi: 10.1038/mp.2013.197

In the first clinical trial of a drug intended to slow onset of Huntington’s disease (HD) symptoms, a study from Massachusetts General Hospital has provided evidence that the nutritional supplement creatine slows progression of brain atrophy in Huntington’s disease (HD) patients as well we being safe and well-tolerated by most study participants. The phase II PRECREST trial also pioneered a novel design that allowed participants- who were recruited as they were at potential genetic risk of HD due to family history- to enrol in the study without having to find out whether or not they were carriers of the HD mutation.

HD is a devastating a hereditary neurological disorder that causes brain cell degeneration. It is caused by an autosomal dominant mutation in the Huntingtin gene, resulting in a mutated form of the huntingtin protein. The disease causes physical, cognitive and emotional decline and can typically be associated with symptoms such as involuntary movements and speech impairment. Symptoms are most commonly first noticed between the ages of 30 and 45. The corresponding author of the study, Dr H. Diana Rosas, pointed out that: "More than 90 percent of those in the United States who know they are at risk for HD because of their family history have abstained from genetic testing, often because they fear discrimination or don't want to face the stress and anxiety of knowing they are destined to develop such a devastating disease." Thus the option offered in the trial of not finding out their HD status while still gaining access to a potentially helpful drug was attractive to many participants.

One mode of action of mutated huntingtin protein in HD is interference with brain cell energy production. This leads to depletion of ATP. This is where the creatine comes in, as it is known to help restore ATP and hence maintain cellular energy. Animal studies had previously shown that creatine can increase brain ATP and ward off neurodegeneration. However, previous human trials in HD patients had been limited as the daily dosage was low at only 10 g or less and did not indicate potential clinical efficacy. The PRECREST trial, by contrast, used daily dosages of up to 30 g. The researchers recruited sixty-four eligible consenting participants. These were randomly allocated to 15 g twice daily of creatine monohydrate or placebo for a 6-month double-blind phase followed by a 12-month open-label extension. Of the study subjects, 19 already knew they carried the HD mutation. The other 45 were at risk due to family history; of these 26 were found to be pre-symptomatic carriers of the mutated gene. Thus the final tally for the study was a total of 47 participants with pre-symptomatic HD and 17 controls. Primary outcomes for the trial were safety and tolerability of the creatine. Exploratory endpoints included fine motor, visuospatial, and memory performance, MRI brain scans and selected blood markers; these were measured at the beginning of the trial, at the end of the six month first phase and at the end of the trial.

Participants were regularly monitored for adverse events throughout the trial, with dosage levels being modified as necessary. The majority of the participants (more than two-thirds) tolerated the 30 g dosage. A total of fifteen participants stopped creatine because of factors including, gastrointestinal discomfort, the taste of the drug, inconvenience, or the stress of being constantly reminded of their HD risk. The most common adverse events were gastrointestinal. However, MRI neuroimaging demonstrated treatment-related slowing of cortical and striatal atrophy at 6 months in the creatine-treated participants versus the placebo-treated. At the 18 months trial endpoint, the rate of brain atrophy had also slowed in pre-symptomatic participants that started taking creatine after 6 months on placebo.

These results suggest both that creatine could slow the progression of HD and that neuroimaging may provide a useful biomarker of disease modification in studies of other potential treatments. A note of caution may be sounded by the fact that during the time period covered by the trial, there was no evidence of creatine having a positive effect on cognitive tests. The researchers noted that this may possibly be because the tests were not sensitive enough to detect subtle changes that might occur during such a brief time period. Senior author on the study, Dr Steven Hersch, concluded that: "The results of this trial suggest that the prevention or delay of HD symptoms is feasible, that at-risk individuals can participate in clinical trials – even if they do not want to learn their genetic status – and that useful biomarkers can be developed to help assess therapeutic benefits.”

Sources

http://www.eurekalert.org/pub_releases/2...020514.php [Accessed 11 February 2014].

ROSAS, H. D., DOROS, G., GEVORKIAN, S., MALARICK, K., REUTER, M., COUTU, J.-P., TRIGGS, T. D., WILKENS, P. J., MATSON, W., SALAT, D. H. and HERSCH. S. M., 2014. PRECREST: A phase II prevention and biomarker trial of creatine in at-risk Huntington disease. Neurology, 2014; DOI: 10.1212/WNL.0000000000000187

http://www.huntingtons.ie/ [Accessed 11 February 2014].