BioMed Central Blog

sMRI – the most powerful Alzheimer’s disease biomarker?

sMRI is a stable biomarker of AD progression and is useful in measuring disease intensity, however the authors stress that we should not rest on our laurels, but continue to build on it, by looking to develop automated techniques of extracting disease-specific information from images and by integrating it with other existing biomarkers for clinical use.

Posted by Alexander Kroll at 12:26    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)

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 (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)

Foetal testosterone linked to autistic traits in toddlers

Recent reports have confirmed a genetic basis for autism, with new evidence suggesting that autistic traits may be caused by genetic errors first introduced during the formation of the egg and sperm. But autism is a complex disorder. In an article recently published in Molecular Autism, Simon Baron-Cohen and colleagues remind us that many other factors can influence the development of autism, even before birth.

Foetal testosterone and autistic traits in 18 to 24-month-old children
Bonnie Auyeung, Kevin Taylor, Gerald Hackett, Simon Baron-Cohen
Molecular Autism 2010, 1:11

Pre-natal testosterone has been linked to cognitive sex differences, and recent studies have revealed a positive correlation between foetal testosterone and autistic traits in 6 to 10 year old children. In their research, Baron-Cohen and colleagues demonstrate that foetal testosterone levels are also a significant predictor of autistic traits in 18 to 24 month old children.

A consistently positive correlation between levels of foetal testosterone and autistic traits in different age ranges suggests a robust association, and highlights the need for further studies into the genetic factors involved. Further work aimed at identifying the underlying sources of variation in autistic traits will, ultimately, contribute to a greater understanding of the complexities of autism recently highlighted by Martin Raff in BMC Biology.

Jenny Withers
Assistant Journal Development Editor

Posted by Victoria Thompson at 17:49    Comments (0)

Population Health Metrics publishes new thematic series highlighting improvements in mortality statistics

Accurate mortality statistics are fundamental to help guide priorities in public health policy, planning, and resource allocation. Reliable information on levels of mortality and leading causes of death enables decision-makers to strategically design, fund, and implement programs to ensure the greatest possible impact on longevity and quality of life.

The thematic series, “Measuring mortality in Thailand”, published by Population Health Metrics, describes methods and results from what may be the largest-ever national investigation into the validity and quality of cause-of-death statistics in a developing country, using extensive field studies in Thailand to develop reliable estimates of mortality by age, sex, and cause. A commentary by Peter Byass discusses the four research papers by Rao and colleagues and considers methodological assessments and public health implications. The research papers relate to a detailed investigation of cause-specific mortality in Thailand during 2005, integrating a number of different data sources, including empirical investigations, death certification, and the use of verbal autopsy methods.

The research published in this thematic series could serve as a model for additional investigations into the quality of mortality statistics in other developing countries. The series Editor, Dr. Emmanuela Gakidou, is an Associate Editor for Population Health Metrics.

Population Health Metrics is ready to receive manuscripts on all aspects of the measurement of health at the population level.

Posted by Blog Maintenance at 11:58    Comments (0)

Marking 30 years of critical care medicine

The International Symposium on Intensive Care and Emergency Medicine (ISICEM) is celebrating its 30th anniversary in 2010, and to acknowledge this milestone Critical Care has published a related viewpoint article by Editor-in-Chief Professor Jean-Louis Vincent, ISICEM chairman.

This article, co-written by several members of Critical Care’s Editorial Board, is an account of the last 30 years in the field of critical and intensive care medicine. As well as discussing the advances made in specific areas such as sepsis, respiratory failure and cardiovascular disease, the authors are very honest in disclosing that, overall, there have been few major developments in new therapies for intensive care patients. Despite this, notable advances in the process of care and thus patient outcomes are also described.

Looking ahead to the next 30 years the authors speculate that improved communication between research scientists and ICU physicians, better models to test the effect of complex interventions, and improvements to critical care in developing nations will be seen. We congratulate the organisers of ISICEM on this anniversary, and look forward to reporting on the next exciting developments in the field.

Viewpoint articles require a subscription to access. If you are not a subscriber you may sign-up for a free 30-day trial.

Posted by Surayya Johar at 09:44    Comments (0)

Elucidating genetic susceptibility to lupus – credit where credit’s due

“We have way more data than we can possibly analyse”, said Arthritis Research & Therapy Editorial Board member Prof Edward Wakeland, in concluding his keynote address to the 9th International Congress on Systemic Lupus Erythematosus in Vancouver.

The Wakeland Laboratory are generating data that should help elucidate the genetic basis for human susceptibility to lupus. They aim to sequence the genome of 600 patients with systemic lupus erythematosus (SLE) – a disease thought to affect more than 250,000 US citizens  – in the next 16 months. They have sequenced 107 patients so far and are on track to achieve their goal, facilitated by modern ‘deep sequencing’ technology. Control data for the project are being provided by the 1000 Genomes Project.

But generating terabytes of sequence data is just the beginning.  Prof Wakeland explained that there are 89 genomic segments of potential interest but this is more than one lab is able to analyse, and on the second day of the congress he offered the data out to the community to collaborate with his group.

The web-based interface by which the Wakeland lab will make its data available to collaborators is not yet completed, but the proposal seems to be another example of genomic researchers being ahead of the curve in scientific data sharing.

Indeed, collaboration on – and driving – future research is one of the many benefits of openly sharing research data, and the potential for collaboration with large genomic datasets is vast. And where researchers must publish or perish, offering co-authorship on articles to collaborators might seem logical. However, by contributing data alone researchers will not meet the authorship criteria of the ICMJE, which are endorsed by many journals including BioMed Central’s. Moreover, researchers might not want to endorse the findings of every article resulting from their data.

So is it time for a rethink? Authorship criteria offer protection as well as a means of giving academic credit, so ambitious projects such as the Wakeland group’s instead add to the urgent need for data sharing to be recognised by academic institutions and the broader scientific community, particularly as plans for sharing data are increasingly a requirement of research funding agencies, such as the NIH and Wellcome Trust.

Prof Wakeland explained that his group have had a policy for sharing data from the outset. “All of the sequencing data was generated in my laboratory, using samples predominantly obtained from the OMRF. The size of the data set is mammoth already and we are unable to analyze all of the gene segments that are available,” he said.

Posted by Iain Hrynaszkiewicz at 13:01    Comments (0)

Uncovering the role of proteases in neurodegeneration

Alzheimer’s disease (AD) is associated with a progressive accumulation of senile plaques (containing β-amyloid (Aβ)) and neurofibrillary tangles, but the underlying pathology is still, to a large extent, a mystery. Nevertheless, there is growing evidence that matrix metalloproteinases (MMPs), molecules produced by neurons and glial cells, may play an important, but complex, role. 

In an article published last week in Alzheimer’s Research & Therapy, Stomrud and colleagues examined MMP, tissue inhibitor of metalloproteinase-1 (TIMP-1), Aβ and tau protein levels in the cerebrospinal fluid (CSF) of Alzheimer’s patients and found that compared to individuals with no cognitive dysfunction, AD patients had higher CSF levels of certain MMPs. Interestingly, cognitively healthy individuals with risk markers for the future, such as the presence of the APOE-ε4 allele, also had higher MMP levels when compared to healthy individuals with no risk markers.

The results indicate that MMPs could be associated with neuronal degeneration, even in individuals who are yet to develop any evident cognitive dysfunction.

Posted by Alexander Kroll at 09:28    Comments (2)

Transcriptional regulation of miRNA-21

According to research recently published in Genome Medicine, a complex of transcription factors which includes p53, NF-kappa-B and STAT3 is responsible for regulation of miRNA-21 expression. This microRNA is significantly upregulated in stressed heart muscle and has previously been suggested as a therapeutic target in a mouse model of heart failure.  

Roger Foo and colleagues used chromatin immunoprecipitation assays and high-throughput sequencing to examine transcription factor binding at the miRNA-21 locus.  They found that p53 acts as a cofactor, forming a protein complex with NF-kappa-B (RELA), and that STAT3 is also required for the complex to associate with the cis-element controlling mir-21 expression.  This may be a more general mechanism of control in other genes whose promoters lack a p53 consensus sequence.

The authors suggest that understanding the interactions of DNA binding proteins and regulatory elements in miRNA-21 expression will further inform future drug design.

Posted by Rebecca Furlong at 10:53    Comments (0)

Time to put biomarkers to the test in myocardial infarction?

Have you ever asked yourself exactly what a biomarker is, and what this term really means?  It can be confusing, since biomarkers themselves are discussed in a number of different contexts including: aiding diagnosis, predicting response and monitoring response to therapy, or helping to identify candidates that will benefit from therapy.

In a new review published this month in BMC Medicine, Daniel Chan and Leong Ng from the University of Leicester (UK), outline what makes a good biomarker in the context of myocardial infarction.  Further, they talk about the different biomarkers that have been investigated for use in earlier diagnosis and prediction of prognosis in myocardial infarction, a condition that leads to significant mortality and morbidity.

Chan and Ng posit that a rich host of biomarkers have been identified for use in myocardial infarction diagnosis and treatment. However, our knowledge of the underlying science remains weak, and many of them are not ready to be used in wider clinical practice; this highlights the need to validate many of these markers in well-designed randomized trials.

Visit the BMC Medicine website to read the full review and explore the authors’ insights into this serious condition.  While you’re there, why not sign up for article alerts for BMC Medicine, and check out the high quality research that we are publishing?

Posted by Robin Cassady-Cain at 14:20    Comments (0)

Molecular classification for biliary atresia

A molecular signature for biliary atresia classifies samples into inflammation or fibrosis stages at diagnosis and will be valuable for personalized clinical management of this disease, according to research recently published in Genome Medicine.

Biliary atresia is a blockage or absence of the bile duct usually diagnosed soon after birth.  The cause of this condition is not well understood, but the management of the resulting liver fibrosis is well-studied due to its importance for prognosis.  In their study 'Staging of biliary atresia at diagnosis by molecular profiling of the liver', Jorge Bezerra and colleagues asked whether liver gene expression levels at diagnosis could be used to predict disease severity, the response to surgical reconstruction of the bile duct (portoenterostomy), and survival at 2 years of age.  

Differential profiling of liver biopsies showed that a unique molecular signature was associated with each of the histological features of inflammation and fibrosis, and that this signature could be used to classify otherwise ambiguous biopsies into one of the two groups. This signature may relate to the stage of disease at the time of diagnosis, and infants classified with the fibrosis signature (possibly indicating a more advanced stage of disease) had decreased transplant-free survival.  This information may be valuable for clinical management and personalised therapy for this rare congenital condition.

Posted by Rebecca Furlong at 09:59    Comments (0)

Diagnosing Alzheimer's disease - how good is neuropathology?

Advances in clinical diagnostics, such as neuroimaging, as well as the development of new biomarkers, have raised questions as to whether neuropathological assessment is both accurate and specific enough to diagnose Alzheimer's disease (AD).  Two articles published last week in Alzheimer's Research & Therapy address this issue and make up a pro/con debate discussing whether neuropathology can confirm the exact diagnosis of AD.

Arguing the case for, Margaret Esiri stresses that neuropathology is still the gold standard by which to reach a reliable diagnosis of AD and suggests that because diseases change and evolve over time, only this tool is in a position to provide a concrete distinction between pathological processes.  Esiri acknowledges that novel clinical diagnostics will have a part to play in the future, but that until our understanding of AD improves neuropathology still has a future in elucidating the molecular and cellular mechanisms involved.

In his counter viewpoint, Kurt Jellinger argues that although neuropathology has provided us with a large amount of data on the pathogenesis and pathophysiology of AD, there are a number of drawbacks associated with it (such as a quantitative nature and the existence of co-existing confounding processes in aged brains) and we should increasingly be focusing on using harmonised techniques to improve the accuracy and reproducibility of AD diagnosis.  Only this, he stresses, will allow us to devise successful neuroprotective and treatment strategies for the future.

Alex Kroll - Senior Assistant Editor, Alzheimer's Research & Therapy

Posted by Frances Mulvany at 09:38    Comments (0)

Novel format for gene variant reporting

The Locus Reference Genomic (LRG) sequence format, recently reported in Genome Medicine, allows a single fixed record containing a reference DNA sequence and all relevant transcripts and protein sequences to be associated with an updateable layer of gene variant coordinates, which should reduce errors in reporting and lead to improved communication about genomic variants.

Nature Genetics this month stated that the LRG agreement has provided a platform which allows the editors to adjust journal policy, mandating the use of Human Genome Variation Society (HGVS) allele naming conventions in manuscripts submitted to Nature Genetics.

Dalgleish and colleagues propose that variants associated with human genetic disease can be documented using this format, which was designed for the specific purpose of gene variant reporting and which builds upon the NCBI RefSeqGene project.  LRG records will have long-term stability, being created and maintained by the NCBI and the EBI, as well as flexibility, which will allow their use as an up-to-date reference for clinical genetic tests even as more disease variants are discovered. 

Posted by Rebecca Furlong at 15:27    Comments (0)