BioMed Central Blog
Journal of Molecular Signaling welcomes new co-Editor-in-Chief
Yung Hou Wong, Head of the Section of Biochemistry and Cell Biology, Division of Life Science, at the Hong Kong University of Science and Technology, has recently joined Journal of Molecular Signaling as co-Editor-in-Chief alongside Danny Dhanasekaran. Professor Wong is a leading expert in the molecular pharmacology of G protein-coupled receptors, signal transduction and integration.
Journal of Molecular Signaling was launched in 2006 and encompasses different molecular aspects of cell signaling underlying normal and pathological conditions. The focus of the journal is on the normal or aberrant molecular mechanisms involving receptors, G-proteins, kinases, phosphatases, and transcription factors in regulating cell proliferation, differentiation, apoptosis, and oncogenesis in mammalian cells. This area also covers the genetic and epigenetic changes that modulate the signaling properties of cells and the resultant physiological conditions. A most highly accessed recent article in the journal determines the molecular effect of sulforaphane (SFN, found in cruciferous vegetables) in growth arrest of pancreatic cancer cells.
We would like to welcome Yung Hou Wong to his new role with this growing journal. He says that “Journal of Molecular Signaling is a significant avenue for researchers in the area of cell signaling to share their discoveries and innovations, and contribute towards the advancement of the field. I am excited to be a part of the team and look forward to working with the editorial board to increase its impact as well as its value to the growing readership across the scientific community and around the world.”
Posted by Helen Whitaker at 11:05 Comments (0)
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)
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)
Non-productive transcription in yeast
Studies measuring mRNA abundance, such as those using microarrays, have often been used as a proxy for transcriptional control of gene expression. However, the quantity of a given mRNA at any time is a balance between its production and degradation. In an article recently published in Genome Biology, Oliver Rando and colleagues at the University of Massachusetts have shown that mRNA abundance does not always correlate with the quantity of RNA polymerase on a gene, and thus mRNA abundance is not always a good indicator of transcriptional activity.
Rando and colleagues exposed yeast cells to two different stresses. They then measured mRNA abundance using microarrays and PolII localization using chromatin immunoprecipitation. In general, PolII abundance did explain mRNA abundance, but there were genes which showed an excess or dearth of mRNA per PolII molecule. Interestingly, in many cases those genes were also those showing non-productive transcription - transcription of non-coding genes overlapping the coding genes. Rando concludes that genes not involved in normal growth show non-productive transcription, but that when the cells are stressed the polymerase shifts to the 5' end of the genes to transcribe as they are needed.
Thus, not only has this study shed light on how mRNA levels correlate with PolII activity, it has also revealed a potential new way to regulated gene expression via non-productive transcription.
Posted by Andrew Cosgrove at 10:12 Comments (0)
The fight against crop pathogens
Oomycetes are single celled pathogens of plants; the most widely-known representative of this class is the potato blight pathogen, Phytophthora infestans, which was responsible for the Irish potato famine in the 18th century.
In this issue of Genome Biology, C. Robin Buell and colleagues present the genome and transcriptome of the related plant pathogenic oomycete, Pythium ultimum - a blight pathogen of many ornamental and crop species that is less host-specific than some of its oomycete cousins.
Buell and colleagues compared the genome and transcriptome sequence of P. ultimum with that of P. infestans, the genome sequence of which was recently published in Nature and highlighted in Genome Biology here. Buell and colleagues found that the P. ultimum genome has a very different repertoire of genes involved in pathogenicity compared with P. infestans, including very few Crinkler (cytoplasmic effector proteins) protein-encoding genes, which are abundant in related oomycetes and previously thought to be essential for pathogenicity.
The genome sequence of P. ultimum will increase our understanding of the mechanisms of pathogeniticty in this agriculturally important family of crop pathogens.
You can read the article by Buell and colleagues here.
Posted by Elisabeth Gaskell at 16:06 Comments (0)
In an article recently published in Genome Biology, Michael Rehli and colleagues of the University Hospital Regensburg have identified novel examples of active DNA demethylation that are coupled to the appearance of ‘activating’ histone modifications.
Until now, the majority of evidence for active, replication-independent DNA demethylation in mammalian systems has relied upon inhibiting cell division using pharmacological inhibitors and monitoring any subsequent DNA methylation. Here, the authors avoid the use of inhibitors by investigating DNA demethylation in a differentiation system; that of human peripheral blood monocytes into macrophages or dendritic cells in which differentiation proceeds without cell division. By monitoring genome-wide methylation levels during a time course of differentiation, the authors were able to identify novel sites of active demethylation. By analysing histone modifications at these sites, they also found that active DNA demethylation correlated with the increase in ‘activating’ histone modifications.
While the enzymes involved in this active DNA demethylation process remain unknown, the characterisation of active demethylation sites and their associated histone modifications is an important step toward identifying these enzymes.
Posted by Andrew Cosgrove at 16:02 Comments (0)
First articles published in Genome Integrity
Genome Integrity, a new open access journal launched with BioMed Central, published its first articles today. The journal publishes research on all aspects of genome integrity, the cellular processes underlying maintenance of genome stability, and the effects of instability.
In their introductory editorial ‘Genome Integrity – a new open access journal’ Editors-in-Chief Predrag Slijepcevic, Prakash Hande, John Petrini, and Razqallah Hakem discuss the important publishing niche that the journal will fill in the field of DNA damage response and the associated cellular processes behind genome stability maintenance.
“We strongly believe that this new journal will significantly contribute to the understanding of DNA damage response processes” say the Editors-in-Chief.
One of the articles published today with Genome Integrity by Professor Keiji Suzuki et al researches the role of ATM activity in DNA damage checkpoints, and another article by Dr Alireza Senejani and Professor Joann Sweasy discusses the incidence of a novel DNA sequence found within a mouse genomic fragment inserted into a plasmid vector.
For more details on the journal and its articles please visit the journal website. For information on submitting to the journal please see our instructions for authors.
Posted by Genevieve Horne at 12:51 Comments (0)
New thematic series to celebrate 2010 International Year of Biodiversity
To celebrate 2010 as the United Nations’ International Year of Biodiversity and the importance of sharing our knowledge of the diversity of the natural world, we present a cross-journal thematic series on Open Access Biodiversity Research.
The rich diversity of life is essential to our presence on the earth and yet it is at risk of decreasing at an accelerated rate due to human activities. The action of the United Nations, in highlighting biodiversity during 2010, is an important chance to increase our understanding of the vital function of biodiversity and a prompt to act now to reduce its loss. To celebrate this initiative, we feature leading research from different disciplines that share common goals in conserving biodiversity.
A re
cent article published in BMC Ecology by Dr Axel Strauss and colleagues discusses the incidence of functional redundancy in tadpole communities in the species-rich streams in Madagascar, and how this is connected to the accumulation of new traits. Using a very different approach, Dr Clementine Pradal et al, also writing in BMC Ecology, employ a mathematical model to describe the temporal dynamics of an Arctic plant-pollinator network and how climate change could affect these delicate systems. The series also features articles from BMC Biology, BMC Evolutionary Biology, BMC Microbiology and Frontiers in Zoology.
For more information and to read further articles in this series please visit the series webpage.
Posted by Genevieve Horne at 10:46 Comments (0)
Sequence periodicity discovered in human genome
In an article just published in Genome Biology, Charles Hebert and Hugues Roest Crollius of the Ecole Normale Supérieure in Paris have shown the existence of a novel periodicity of nucleotide frequencies in the human genome that may have implications for the positioning of nucleosomes and gene regulation.
In their study, Hebert and Roest Crollius have aligned human genes relative to their transcription start sites and observe a pattern of YY dinucleotides (where Y is either C or T) spaced 10 base pairs apart in phase with the transcription start site. Importantly, analysis of nucleosome-positioning data shows that the nucleosomes are associated with the dinucleotides. The pattern is enriched in genes with binding sites for the EP300 nucleosome-modelling protein. The authors speculate that the repeating pattern may help to position the nucleosomes in such a way that they are easily modified by EP300, thus facilitating their displacement by RNA polymerase, although this model is currently speculative and will require confirmation in future work.
Nevertheless, this work presents an exciting new pattern in the human genome, and has implications for how positioned nucleosomes affect the transcription of genes.
Nucleosome rotational setting is associated with transcriptional regulation in promoters of tissue-specific human genes
Charles Hebert and Hugues Roest Crollius, Genome Biology 2010, 11:R51
http://genomebiology.com/2010/11/5/R51
Posted by Andrew Cosgrove at 12:27 Comments (2)
Transcriptional control in flies
In a paper recently published in Genome Biology, Boris Adryan (Cambridge University) and Sarah Teichmann (LMB) have presented evidence that calls in to question currently-held beliefs about how transcription factors (TFs) coordinate gene expression during development to specify the fates of the different tissues in the body.
It has been assumed that transcription factors are expressed in the manner of a cascade, with one TF turning on the expression of others resulting in groups of TFs acting in a cooperative manner to specify cell fate. In this study, Adryan and Teichmann have analysed gene expression data from Drosophila melanogaster development to investigate when every transcription factor is expressed. 95% of TFs were expressed at some time during embryonic development.
Perhaps the most important finding of the study is the combinatorial complexity of TF expression. The vast majority of the 69,500 possible combinations of pairs of TFs are expressed in at least one tissue at one time. Thus, the co-expression of TFs is extremely plastic. Rather than having tissue-specific TFs dictating the cell fate in different organs, what actually appears to happen is that the specific combination of TFs at a given point is what determines the cells' fates, with different combinations of the same set of TFs determining different tissue types.
You can read Uwe Ohler’s commentary on the paper, also in Genome Biology, here
Posted by Andrew Cosgrove at 17:56 Comments (0)
Bona fide ancient DNA sequence from Neandertal bone
An article published in Genome Biology assesses the pitfalls of sequencing ancient DNA and presents a new approach for improved identification of ancient DNA sequences.
The DNA sequence of extinct species are of enormous value in determining evolutionary relationships to living species. However, ancient DNA from fossil is notoriously difficult to sequence due to the presence of bacterial contamination and DNA damage. Kay Prüfer and colleagues at the Max-Planck Institute for Evolutionary Anthropology investigated the biases inherent in short read sequencing of ancient DNA samples with an analysis of Neandertal (Homo neanderthalensis) DNA, generated as part of the Neandertal genome project, from 38,000-year-old fossil bone. The full draft Neandertal genome sequence is published today in Science by the Neandertal Genome Analysis Consortium.
To identify the endogenous Neandertal sequence from the contaminating bacterial sequences Prüfer and colleagues perform pairwise comparisons of the sequence data to the genomes of closely related living primate and mammalian species. The authors discuss other ancient extinct species to which their approach for ancient DNA shotgun sequencing could be applied, such as mammoth, cave bear, sabre tooth cat and ground sloth. It could also be used to study living species when no reference genome sequence is available.
Read the Prüfer and colleagues method here in Genome Biology.
Posted by Emma Ralph at 12:20 Comments (0)
Sloth fur has symbiotic relationship with green algae
Sloth hair is long and coarse and depending on the species can contain either a number of grooves or irregular transverse cracks that increase in number and size with the age of the animal. These features are ideal for inhabitation by a wide variety of organisms, ranging from moths, beetles, and cockroaches to ciliates, fungi, and algae. It is a popular assumption that algae in particular form a symbiotic relationship with the sloth, obtaining shelter and a good supply of water as sloth fur absorbs water extremely readily, and providing in return camouflage and extra nutrients via diffusion and absorption through the hair and skin.
Until now, there has been no good evidence to support this hypothesis. New research published recently in BMC Evolutionary Biology is the first to use molecular methods to explore evolutionary relationships among the algae inhabiting the fur of all six sloth species.
Research article
Molecular evidence for a diverse green algal community growing in the hair of sloths and a specific association with Trichophilus welckeri (Chlorophyta, Ulvophyceae)
Milla Suutari, Markus Majaneva, David P Fewer, Bryson Voirin, Annette Aiello, Thomas Friedl, Adriano G Chiarello, Jaanika Blomster
BMC Evolutionary Biology 2010, 10:86 (30 March 2010)
[Abstract] [Provisional PDF] [PubMed] [Related articles]
Milla Suutari and colleagues found that the predominant algae inhabiting sloth fur was Trichophilus welckeri. It is passed directly from mother to offspring and young sloths gain the algae and other parasites by the time they are a few weeks old. This species of algae is host specific and has not been found to occur in any other environment. This finding adds strong support to the hypothesis that there is a co-evolutionary relationship between the sloths and the algae of the genus Trichophilus, which may well only exist as a symbiont.
In fact, most of the varied eukaryote organisms living in the individuals’ fur differ between sloth species and this is suggested to reflect the divergence of the sloth genera about 20 million years ago, which may have led to the separation of the cohabiting communities.
Posted by Genevieve Horne at 14:53 Comments (0)
Journal of Biomedical Semantics publishes first articles
Journal of Biomedical Semantics was launched today, aiming to address the barriers to access and integration of data in the public domain that can hinder reanalysis. Semantics are essential for mining and analyzing data and the ability to manage semantic representations is vital for making computational approaches productive for a large community. The first articles published in the journal today reflect this.
In their introductory editorial ‘BioMedical Semantics: the hub for Biomedical Research’ Dietrich Rebholz-Schuhmann and Goran Nenadic
discuss the importance and history of biomedical semantics as an emerging field and examine the aims of this timely new journal. Also published today, Dr Nigel Collier addresses the issue of systematically evaluating online health news to support automatic alerting, and an article from Ms Kristina Hettne and colleagues highlights the importance of applying rewrite and suppression rules for the identification of terms in biomedical text mining and recommends a useful software tool for this.
“We aspire to provide authors and readers with opportunities to semantically enrich their publications so that they can become part of an integrated semantics network of biomedicine” say Editors-in-Chief Dietrich Rebholz-Schuhmann and Goran Nenadic.
For more details on the journal and its articles please visit the journal website. For information on submitting to the journal please see our instructions for authors.
Posted by Genevieve Horne at 16:24 Comments (2)
False duplications in genome assemblies
David Kelley and Steven Salzberg at the University of Maryland have developed a pipeline to correct misassembles due to false duplications, in a study published today in Genome Biology. Diploid genomes harbour a significant amount of variation between homologous chromosomes. This causes problems for genome assembly algorithms which may construct two DNA sequences corresponding to one divergent region and incorporate both into an assembly as a false segmental duplication.
Their approach is to align DNA sequence fragments to the surrounding sequence, using mate pair information, to determine whether duplicated segments should be merged into one copy. Mate pairs are two sequence reads derived from the same region of DNA and this study is the first time in which mate pair reads have been used to detect duplications. Kelley and Salzberg apply their pipeline to the cow, chimpanzee, dog and chicken genomes and they identify many single copy regions that have been falsely incorporated as segmental duplications in these genome assemblies, which also allows previously undetected polymorphisms to be identified. This promises to be a valuable method for correcting existing errors in many genome assemblies and to control for misassembly errors in future genome sequencing efforts.
Posted by Emma Ralph at 11:50 Comments (0)
Genome Biology recently published an article from Alicia Oshlack and colleagues in which they describe an approach for performing Gene Ontology analysis on RNA-seq data. RNA-seq is an emerging technology for monitoring gene expression levels by directly sequencing the mRNA molecules in a sample, and is likely to overtake microarrays as the technique of choice for gene expression profiling. Now, Genome Biology has published another innovative method, this time for normalizing RNA-seq data. This method is much needed and will be embraced by the genomics community as, until now, methods for normalizing RNA-seq data have often relied on tools that were based on those developed for microarray data.
A common approach for normalizing RNA-seq data has been to consider the expression of an individual gene relative to the global gene expression levels. In her latest paper, Oshlack, at the Walter and Eliza Hall Institute in Melbourne, Australia, shows that this is not always appropriate. In particular, if one tissue has a small number of genes that are significantly differentially expressed compared with another tissue then these can affect whether or not other genes in the sample are determined as being differentially expressed, often leading to implausible results. The paper demonstrates again the need for new statistical techniques to fully exploit the powerful RNA-seq technology, as well as providing a useful tool for doing this.
Posted by Andrew Cosgrove at 17:32 Comments (0)