BioMed Central Blog
Facilitating standardized genome annotations
Faster and more reliable genome sequencing has meant that the number of personal genome sequences available is increasing rapidly, yet the analysis of personal human genome sequences has been hampered by the lack of a standard file format to facilitate comparative analyses. In this month’s issue of Genome Biology, Karen Eilbeck and colleagues present GVF, the Genome Variation Format. GVF is an extension of the already widely-used GFF3 standard for describing genome annotations. The utility of GVF is demonstrated by the analysis of the first 10 publicly-available personal human genomes. The authors term this dataset "10Gen" and hope that this will become the standard reference set to facilitate the analysis of future personal genomes.
GVF and the 10Gen dataset are available at http://www.sequenceontology.org/gvf.html and are also included with the article published on the Genome Biology website here.
Posted by Elisabeth Gaskell at 17:27 Comments (0)
Arthritis Research & Therapy – published online only from 2011
The contents of the last regular print edition of Arthritis Research & Therapy will be finalized at the end of 2010, which marks the latest evolution of the journal and reflects the undeniable shift to electronic communication of science in the past decade. The Editors-in-Chief, Prof Peter Lipsky and Prof Sir Ravinder Maini, discuss in an editorial the reasons behind, and opportunities presented by, the journal’s decision to become an exclusively online publication.
Although BioMed Central was the first commercial open access publisher – and the Internet is fundamental to open access – BioMed Central has continued to publish a small but decreasing number of print journals, until now.
Arthritis Research & Therapy, first published by Current Science Ltd in 1999, was conceived with a strategy to take full advantage the benefits of online publishing. It has previously made innovative decisions in the rheumatology community, such as making all research open access and, latterly, publishing only the abstracts of research articles in print to help remove limitations to article length and to reduce publication times. This move to online-only publication will benefit readers, as they will see more cutting-edge review articles, and authors, who will no longer be faced with the choice of paying for color figures in non-research articles, as well as further limiting the environmental impact of the journal.
We expect that more innovations in rheumatology research publishing will be facilitated by the journal’s transfer to BioMed Central’s newly-designed journal platform in the coming months, and we will be communicating with the journal’s registered users via an online survey to establish what other online features would most benefit this rapidly-changing field.
By innovation and investment in new services for our readers, authors and reviewers we hope the journal will continue to readily drive and adapt to the change (or is that disruption?) the Internet has caused to publishing arthritis and rheumatic autoimmune disease research.
Posted by Iain Hrynaszkiewicz at 15:12 Comments (0)
Melatonin therapy effective in treating primary insomnia
Insomnia is a highly prevalent condition, with up to a third of the general adult populace thought to suffer from insomnia at some time. Insomnia is generally associated with a negative impact on day-to-day functioning and has been noted to have co-morbid associations with a variety of psychiatric conditions.
Melatonin, an endogenous sleep regulating hormone, has been mooted as a potential therapy for this debilitating condition. Endogenous melatonin production is known to decrease as a person ages, therefore it has been hypothesised that treatment with this hormone may be efficacious in treating insomnia in the elderly population. However results from studies have often proved contentious, with a lack of consistency in the results seen in differing age groups exposed to melatonin therapy. 
Results from a recently published randomized controlled trial in BMC Medicine have now shed new light on this controversial subject. Wade et al examined the use of prolonged release melatonin (PRM) in sufferers of primary insomnia across a wide range of ages. Their results showed that PRM is particularly effective and well tolerated in patients aged 65 years and over, with the treatment response increasing and being sustained over a 6 month period.
If you wish to learn more about this fascinating result and an array of other high impact articles visit the BMC Medicine website.
Posted by Mick Aulakh at 10:53 Comments (0)
Does genetic test allow prediction of patients’ response to tamoxifen?
Various studies have suggested that a genetic test for the efficacy of the commonly used breast cancer drug, tamoxifen, is an effective predictor of how patients will respond to the drug. Tamoxifen undergoes metabolism upon oral administration, and it is widely accepted that the majority of the anti-proliferative effects of tamoxifen occur via its active metabolites. The CYP2D6 gene plays an important role in these metabolic pathways, and a genetic test is available which establishes which variant of the CYP2D6 gene the patient has. Some experts recommend that this test should be used in clinical practice, particularly in the case of postmenopausal women.
Research published in Breast Cancer Research sheds new light on the matter. The study looked at 6640 breast cancer patients from the United Kingdom and evaluated the association between genotype and breast cancer specific survival (BCSS), finding weak evidence that the poor-metaboliser variant, CYP2D6*6, is associated with decreased BCSS. This suggests that the use of this test in a clinical setting should be avoided until larger studies confirming any associations are available.
There are currently 500,000 women in the U.S.A. taking tamoxifen, so this outcome has the potential to affect hundreds of thousands of people. This fresh evidence reflects recent doubts about the test, as an editorial published recently in the Journal of Clinical Oncology stated that "routine use should await more reliable evidence from well-designed studies."
Anita Bock
Assistant Editor - Breast Cancer Research
Posted by Surayya Johar at 11:56 Comments (0)
Hereditary Angioedema: Management Consensus 2010 – a thematic series
Allergy, Asthma and Clinical Immunology has published its first thematic series, reviewing the current consensus on the treatment of the potentially fatal condition, hereditary angioedema.
Hereditary angioedema is a rare genetic disease that causes the rapid swelling of the limbs, face, intestinal tract, larynx or trachaea. The disease, which affects 1 in 50,000 people globally, is caused when a protein called C1 inhibitor is either deficient or non-functional. The symptoms of the disease cannot be controlled by conventional treatment with antihistamines or corticosteroids, and can lead to sudden death. The thematic series reviews the current international approach to the diagnosis, treatment and management of the disease. This includes investigating the management of the disease in children, which represents 50 % of clinical cases, and in women, who are more susceptible to the symptoms because of hormonal factors. The series also incorporates a comprehensive review of past, current and potential therapies for the disease.
The articles in the series were presented at the Toronto Consensus meeting organized by the Canadian Hereditary Angioedema Network, the Canadian Society of Allergy and Clinical Immunology and the University of Calgary. A final consensus document outlining the current global guidelines for the management of hereditary angioedema was agreed and authored by scientists who attended the meeting in Toronto.
Posted by Srimathy Sriskantharajah at 09:17 Comments (0)
BioMed Central to take on Nature in 10K charity run
On September 14th, a team of runners from BioMed Central will be taking part in a 10K race against our friends (and rivals) at Nature Publishing Group. BioMed Central’s team will be raising money for our partner charity Computer Aid International, which works to recycle computer equipment for use in developing countries.
You can support BioMed Central’s open access David as we take on the traditional publishing Goliath by sponsoring us via the BioMed Central team’s fundraising page.
Our plucky open access mascot turtle Gulliver is already in training, and he will be joined by around 15 BioMed Central staff, all of whom are aiming to complete the course in under an hour. For the latest updates on Gulliver’s progress, or to sponsor him, see his blog and/or Facebook page.
About Computer Aid and BioMed Central
Computer Aid International provides professionally refurbished computers for reuse in education, health and not-for-profit organizations in developing countries.
Computer Aid has provided over 170,000 PCs to where they are most needed in more than 100 countries across Africa and South America, and is the world's largest and most experienced ICT for Development provider.
BioMed Central has supported Computer Aid for some time, and the funds we have raised will be used to send a container-load of reconditioned computer equipment to Kenyatta University in Nairobi later this summer. You can also support Computer Aid by buying a BioMed Central journal T-shirt.
Read more about Computer Aid’s activities in this recent guest blog post by Computer Aid’s Stephen Campbell.
Posted by Matthew Cockerill at 10:47 Comments (0)
Approaching technical hurdles to iPS technology
Producing induced pluripotent stem cells (iPS) has the potential to revolutionize drug discovery and regenerative medicine. These cells have an advantage over embryonic stem cells, which face both ethical concerns and the technical difficulties isolating cells from human embryos.
Takahashi and Yamanaka's breakthrough study in 2006 showed that pluripotent stem cells could be directly generated from fibroblast cultures, and significant progress has been made since then to improve their technique. In a review published in Stem Cell Research & Therapy Sommer and Mostoslavsky summarize current reprogramming methods, focusing on the production of genetically unmanipulated induced pluripotent stem cells. They highlight important technical details that could influence the biological properties of these cells and outline techniques worth additional investigation.
Despite some criticism of the iPS approach, there have been many improvements to both the safety and efficiency of reprogramming methodologies. Sommer and Mostoslavsky are positive about the way forward, concluding that "Given the rapid pace of the field, further optimization of the protocols coupled with a thorough analysis of the iPSC lines generated will facilitate the clinical translation of this technology."
Posted by Frances Mulvany at 12:53 Comments (0)
Computer gamers solve medical problems
As a core area of molecular biology, the study of protein structure is integral to elucidating pathological processes. Protein structure prediction has become one of the most important goals of pharmaceutical and biochemical industries.
With the correctly folded 3D structure of a protein often being integral to its function, the demand for the development of new and improved techniques for computational protein structure prediction is forever on the up.
Every two years a worldwide experiment: Critical Assessment of Techniques for Protein Structure Prediction (CASP), provides hundreds of researchers worldwide with the opportunity to test their structure predictions and delivers information on the latest modelling techniques and software available.
Now, solutions being entered to CASP are originating from another type of computing project. Foldit is a computer game that presents a series of puzzles in which the user manipulates a graphical representation of an unfolded protein to create a final 3D structure, with the accuracy of the process being measured by a “score” which is calculated as the user modifies the protein.
Created by researchers at the University of Washington (UW), Foldit attempts to apply the human brain’s instinctive abilities to the problem of protein structure prediction. By analyzing the way our minds intuitively approach 3D shapes and patterns, researchers hope to offer new dynamics on the problems presented by the limitations of existing algorithmic software. Following the success of Foldit, researchers in other fields are now considering using this approach to enhance their research.
Reflecting on the aims of the project and the concept of citizen science, UW professor Zoran Propovic, comments on some high scoring individuals: “They can't even explain what they're doing, but somehow they're able to do it. We're hopefully going to change the way science is done, and who it's done by ".
For further information on Foldit or to have a go at the game yourself, please visit the Foldit website.
Posted by Sally Robertson at 13:39 Comments (3)
Sequencing of a tumor and its metastases
In an article just published in Genome Biology, Steven Jones and colleagues at the British Columbia Cancer Agency have used next generation sequencing to monitor the development of a tumor as it metastasized and used the genomic information to inform treatment.
Cancers are known to accumulate mutations as they progress, and there are several mutations characteristic of metastases. However, even the most well-characterised of tumor types show genetic heterogeneity, and there are few data available for rare tumor types. The recent advent of next generation sequencing technology, allowing rapid and inexpensive genome sequencing, has made it possible to explore the genomic landscape of tumors in more detail.
In this study, a man presented with an unusual cancer of the tongue. He received surgery and radiotherapy, but was subsequently found to have metastases in the lungs. The patient was initially treated with the EGFR inhibitor erlotinib, but the lung metastases continued to grow. Sequencing of the metastases uncovered amplification of the RET oncogene, which explained the resistance to erlotinib, and also suggested the use of the RET inhibitor sunitinib. This drug reduced the size of the lung lesions for a few months, before they started to grow again. A skin metastasis was also detected, and sequencing uncovered seven new mutations that were present in neither the lung metastases nor the original tongue tumor. It appeared that the tumor had upregulated the AKT signalling pathway to compensate for the inhibition of the RET pathway.
This eloquent study demonstrates nicely both how tumors respond to treatment with compensatory changes and also how genomics can be used to guide medical treatment.
Posted by Andrew Cosgrove at 11:29 Comments (0)
Eastern moles evolve different haemoglobin to facilitate fast tunnelling
Most moles spend the vast majority of their lives underground and consequently have evolved numerous adaptations to facilitate this. Over time this has included the development of large, broad front paws with strong claws for digging, and the gradual loss of their eyesight as it is not selected for in the dark conditions. Different species of mole have also been shown to have further diversified in their adaptations to their environment, as in the case of the Star-nosed mole which has developed an intricately shaped nose in order to feed on small prey items in the wet lowland areas in which it lives. 
Eastern moles in particular prefer moist, invertebrate-rich soil in which they can construct their extensive burrow networks. As a result they are constantly exposed to hypoxic and hypercapnic environments due to the reduced gas exchange of the damp soils with the surface air. Moles are fast burrowers and this incurs high metabolic costs in terms of respiration, which are exacerbated by the re-breathing of expired air when tunnelling.
Recent research published in BMC Evolutionary Biology shows that in order to cope with this, the Eastern mole has undergone adaptive modifications in its haemoglobin function.
Research article
Molecular basis of a novel adaptation to hypoxic-hypercapnia in a strictly fossorial mole
Kevin L Campbell, Jay F Storz, Anthony V Signore, Hideaki Moriyama, Kenneth C Catania, Alexander P Payson, Joseph Bonaventura, Joerg Stetefeld, Roy E Weber
BMC Evolutionary Biology 2010, 10:214 (16 July 2010)
[Abstract] [Full Text] [PDF] [PubMed] [Related articles]
Mammalian haemoglobin generally falls into two discrete categories; haemoglobin with very high oxygen affinity that has a high reactivity to concentrations of allosteric effectors such as 2,3-diphosphoglycerate (DPG) in the red blood cell and so is stabilised by these, and haemoglobin with low oxygen affinity which has much lower concentrations of DPG in the red blood cells and reacts weakly to these. DPG modulates haemoglobin’s oxygen binding inside the red blood cell and in this article by Dr Kevin Campbell et al, it is shown that the haemoglobin of the Eastern mole has evolved to a position where the key sites which usually bind to DPG are deleted, and so this allows for additional binding from carbon dioxide molecules. This research suggests that this unique haemoglobin enhances carbon dioxide carrying capacity in the Eastern mole’s red blood cells and is specifically designed to facilitate burst tunnelling activities in gas-exchange impeded burrows.
Posted by Genevieve Horne at 13:07 Comments (0)
The Centre for the AIDS Programme of Research in South Africa (CAPRISA) announced the ground-breaking results of a clinical trial of a new microbicidal vaginal gel at the XVIII International AIDS Conference in Vienna. The efficacy trial provides evidence that the antiretroviral-based microbicides can reduce the risk of sexual transmission of HIV and genital herpes in women by up to 50%. This could translate into preventing over half a million new HIV infections over the next ten years in South Africa alone.
The microbicide, which contains 1% tenofovir, an antiretroviral agent that is frequently used for therapeutic proposes, is the first antiretroviral-based microbicide that has been proven to prevent HIV infection in a clinical trial setting.
Microbicides could be considered effective prevention options for women, as they provide a female-initiated prevention tool for those unable to negotiate other forms of protection with their sexual partners.
The results of the CAPRISA 004 trial were publicized at the XVIII International AIDS Conference; a biennial conference organized by the International AIDS Society, sponsor of the Journal of the International AIDS Society. World leaders including US President Barack Obama, former US president Bill Clinton, Archbishop Tutu and many more addressed the conference, calling for ongoing support of HIV and AIDS research.
Posted by Srimathy Sriskantharajah at 09:27 Comments (0)
Regulating drug based enhancement - where's the line?
Drug-based enhancement is no longer an underground phenomenon but is now firmly focused within the mainstream consciousness.
Performance-enhancing drugs are no longer used solely for personal gratification, but also for competitive advantage in a gamut of fields - ranging from the highest academic circles through to elite sporting events.
In a new commentary published in BMC Medicine, Morten Hesse argues that public health interventions should not focus on which 
aspects of human behaviour it is acceptable to enhance; instead they should target and regulate the relevant harms associated with the use of these substances.
Providing eloquent examples to argue his case, Hesse provides a fascinating discussion into why we should not necessarily be looking to limit access to these substances, but rather be looking at reducing any associated burden of illness connected with substance use.
Visit the BMC Medicine website to learn more about this controversial and often polarising topic.
Posted by Mick Aulakh at 10:08 Comments (0)
Skewed X inactivation in mammals
In an article just published in Genome Biology, Andrew Clark and his colleagues at Cornell describe an intriguing bias that they have found in transcription from the X chromosome.
In mammals, females have two X chromosomes whereas males only have one. This means that if expression from the two X chromosomes was equal, females would have twice as much gene product from the X chromosome, with potentially toxic results. To get around this, females only express genes from one of their X chromosomes and up until now it had been believed that the choice of which X chromosome is active and which is silenced is a random decision in placental mammals. Using a technique that allowed them to differentiate expression from the two X chromosomes, Clark's group has used pyrosequencing to measure transcription in the brains of embryonic mice. They found a small but statistically significant preference for expression from the maternal chromosome, meaning that there is a slight bias towards inactivation of the paternal X. They speculate that this has so far gone undetected because of a lack of sufficiently sensitive methods.
It remains to be seen if this bias is observed in other tissues, or at other developmental stages, or in mammals other than mice, and the mechanism by which this bias occurs is still to be elucidated. Nevertheless, this is an exciting result that could potentially lead to a new way of understanding how dosage compensation is achieved in mammals.
Posted by Andrew Cosgrove at 14:37 Comments (0)
Preliminary findings in BMC Research Notes cause a stir
In a first step towards establishing whether or not performance in cognitive tests is related to differences in brain structure, researchers writing in BMC Research Notes recently used brain scans from 40 volunteers to find out how well the results of eight vocational guidance tests correlated to the distribution of gray matter in their brains. Despite the preliminary nature of the findings, the story has been widely covered in the press with some news sites claiming that brain scans could soon be used to determine a person's ideal career alongside - or even instead of - vocational guidance tests.
Taking a closer look at the research itself, the study did yield some interesting preliminary results. The research team were looking for associations between test results and brain structure and were also keen to see whether narrower tests of specific abilities could be more useful than tests of broader factors like general intelligence. In the 40 individuals studied, the gray matter correlates for the broad and narrow test types were different. Interpreting their results, the authors suggest that cognitive tests could potentially help to identify brain networks related to cognitive abilities beyond a general intelligence factor.
It is perhaps not surprising that this study received considerable attention – both positive and negative – in the media. After all, if researchers could unequivocally demonstrate a robust association between different cognitive abilities and brain structure, the job of the school careers adviser would suddenly become a great deal easier.
But, as emphasized in BioMed Central's press release, these are preliminary findings. Acknowledging the study's limited power, the authors do not draw firm conclusions but instead suggest that their results form a basis for further investigation into the relationship between cognitive abilities and brain structure. The potential for brain scans to become the vocational guidance tool of choice may exist, but we are not there yet.
Posted by Victoria Thompson at 11:18 Comments (0)
Skeletal Muscle is now accepting submissions!
BioMed Central is delighted to announce Skeletal Muscle, a new open access journal that focuses on the molecular mechanisms underlying the biology of skeletal muscle is now accepting submissions.
Skeletal Muscle is overseen by co-Editors-in-Chief Kevin P. Campbell (University of Iowa), David J. Glass (Novartis Institute for Biomedical Research) and Michael A. Rudnicki (Ottawa Hospital Research Institute), who are supported by an expert Editorial Board.
Our new journal aims to provide a venue for the publication of novel, cutting-edge research on a wide range of skeletal muscle biology and to answer questions relevant to the understanding of skeletal muscle.
The scope of the journal includes:
- Differentiation of skeletal muscle
- Atrophy and hypertrophy of skeletal muscle
- Aging of skeletal muscle
- Regeneration and degeneration of skeletal muscle
- Biology of satellite and satellite-like cells
- Maintenance of neuromuscular junctions
- Roles of ryanodine receptors and calcium signaling in skeletal muscle
- Roles of nuclear receptors in skeletal muscle
- Roles of GPCRs and GPCR signaling in skeletal muscle
Why not register for updates keeping you abreast of any journal developments?
For more information on submitting an article, please visit www.skeletalmusclejournal.com or contact the Editorial Office.
Posted by Emma Pettengale at 15:41 Comments (0)