Let’s take a look at all seven PLoS journals today. As always, you should rate the articles, post notes and comments and send trackbacks when you blog about the papers. You can now also easily place articles on various social services (CiteULike, Mendeley, Connotea, Stumbleupon, Facebook and Digg) with just one click. Here are my own picks for the week – you go and look for your own favourites:
The 24-hour (h) light-dark (LD) cycle is a fundamental characteristic of Earth’s environment and so its powerful influence on the behaviour and physiology of animals and humans that evolved on this planet is not surprising. In addition to influencing the perception of visual images, light coordinates the temporal rhythms of physiology and behaviour by sending signals to structures in the brain that contain the central circadian clock. These signals are mediated in part by melanopsin, a photopigment found in the retina. Light affects the brain through these nonvisual pathways, and scientists have recently begun to realize just how pervasive these nonvisual effects are. Mounting evidence supports the view that the effects of light on sleep and brain activity during wakefulness, as well as the duration of sleep and the homeostatic response to sleep loss, depend on both melanopsin and circadian time.
In a 2007 article in PLoS Medicine , Holger J. Schünemann and colleagues described a new process used by the World Health Organization for rapidly developing clinical management guidelines in emergency situations. These situations include outbreaks of emerging infectious diseases. The authors discussed how they developed such a “rapid advice” guideline for the pharmacological management of avian influenza A (H5N1) virus infection. The guideline recommends giving the antiviral drug oseltamivir at a dose of 75 mg twice daily for five days. In this Debate, Nicholas White argues that such dosing is inadequate, Robert Webster and Elena Govorkova say that combination antiviral therapy should be used, and Tim Uyeki reminds us that clinical care of patients with H5N1 entails much more than antiviral treatment. These issues may also apply to therapy of patients hospitalized with severe disease due to novel swine-origin influenza A (H1N1) virus infection.
One of the most significant decisions we face as scientists comes at the end of our formal education. Choosing between industry and academia is easy for some, incredibly fraught for others. The author has made two complete cycles between these career destinations, including on the one hand 16 years in academia, as grad student (twice, in biology and in computer science), post-doc, and faculty, and on the other hand 19 years in two different industries (computer and pharmaceutical). The following rules reflect that experience, and my own opinions.
Dobzhansky and Sturtevant provided the first view of the molecular basis of species identity in their 1938 seminal study classifying the chromosome rearrangements that distinguish two Drosophila species . Decades of study of genome architecture from an evolutionary perspective then followed, enriching our knowledge of developmental genetics, gene regulation, human genetic disorders, and cancer, while greatly contributing to the neo-Darwinian view of the divergence of species. The view that has emerged over the last decade, with a sharp acceleration since the publication of the human genome sequence, is of a fluid genomic landscape that is dotted with evidence of both large- and fine-scale chromosome rearrangements. What has remained a mystery are the mechanisms responsible for chromosome rearrangements that karyotypically define species. In this issue of PLoS Genetics, Lucia Carbone et al.  use the northern white-cheeked gibbon (Nomascus leucogenys leucogenys) to address a fascinating problem in evolutionary biology: why are some groups of organisms characterized by a high frequency of chromosome change while others are karyotypically stable?
Measurement of food intake in the fruit fly Drosophila melanogaster is often necessary for studies of behaviour, nutrition and drug administration. There is no reliable and agreed method for measuring food intake of flies in undisturbed, steady state, and normal culture conditions. We report such a method, based on measurement of feeding frequency by proboscis-extension, validated by short-term measurements of food dye intake. We used the method to demonstrate that (a) female flies feed more frequently than males, (b) flies feed more often when housed in larger groups and (c) fly feeding varies at different times of the day. We also show that alterations in food intake are not induced by dietary restriction or by a null mutation of the fly insulin receptor substrate chico. In contrast, mutation of takeout increases food intake by increasing feeding frequency while mutation of ovoD increases food intake by increasing the volume of food consumed per proboscis-extension. This approach provides a practical and reliable method for quantification of food intake in Drosophila under normal, undisturbed culture conditions.
Natural selection at a population level requires phenotypic diversity, which at the molecular level arises by mutation of the genome of each individual. What kinds of changes at the level of the DNA are most important for the generation of phenotypic differences remains a fundamental question in evolutionary biology. One well-studied source of phenotypic diversity is mutation in gene regulatory regions that results in changes in gene expression, but what proportion of phenotypic diversity is due to such mutations is not entirely clear. We investigated the relative contribution to phenotypic diversity of mutations in protein-coding regions compared to mutations in gene regulatory sequences. Given the important regulatory role played by phosphorylation across biological systems, we focused on mutations in protein-coding regions that alter protein-protein interactions involved in the binding of kinases to their substrate proteins. We studied the evolution of this “phosphoregulation” by analyzing the in vivo complement of phosphorylated proteins (the “phosphoproteome”) in three highly diverged yeast species–the budding yeast Saccharomyces cerevisiae, the pathogenic yeast Candida albicans, and the fission yeast Schizosaccharomyces pombe–and integrating those data with existing data on thousands of known genetic interactions from S. cerevisiae and Sc. pombe. We show that kinase-substrate interactions are altered at a rate that is at most two orders of magnitude slower than the alteration of transcription factor (TF)-promoter interactions, whereas TFs and kinases both show a faster than average rate of functional divergence estimated by the cross-species analysis of genetic interactions. Our data provide a quantitative estimate of the relative frequencies of different kinds of functionally relevant mutations and demonstrate that, like mutations in gene regulatory regions, mutations that result in changes in kinase-substrate interactions are an important source of phenotypic diversity.
Over the past three years, PLoS Pathogens has become a definitive choice of the wider pathogens research community as a place to publish its best work in the field of microbial pathogenesis. True to our vision, we have freely distributed, worldwide, outstanding original articles that significantly advance the understanding of pathogens and how they interact with their host organisms, and it is our goal to continue to do so. As part of our development, we have decided to expand the content of the journal. Building on the strength of the Opinions and Reviews, which, like our research articles, are well read and well received by the community, we are pleased to introduce Pearls.
Global fisheries are in crisis: marine fisheries provide 15% of the animal protein consumed by humans, yet 80% of the world’s fish stocks are either fully exploited, overexploited or have collapsed. Several international initiatives have sought to improve the management of marine fisheries, hoping to reduce the deleterious ecological and socioeconomic consequence of the crisis. Unfortunately, the extent to which countries are improving their management and whether such intervention ensures the sustainability of the fisheries remain unknown. Here, we surveyed 1,188 fisheries experts from every coastal country in the world for information about the effectiveness with which fisheries are being managed, and related those results to an index of the probable sustainability of reported catches. We show that the management of fisheries worldwide is lagging far behind international guidelines recommended to minimize the effects of overexploitation. Only a handful of countries have a robust scientific basis for management recommendations, and transparent and participatory processes to convert those recommendations into policy while also ensuring compliance with regulations. Our study also shows that the conversion of scientific advice into policy, through a participatory and transparent process, is at the core of achieving fisheries sustainability, regardless of other attributes of the fisheries. These results illustrate the benefits of participatory, transparent, and science-based management while highlighting the great vulnerability of the world’s fisheries services. The data for each country can be viewed at http://as01.ucis.dal.ca/ramweb/surveys/fishery_assessment .
Biomedical research is benefiting from the wealth of new data generated in the laboratory through new instrumentation, greater computational resources, and massive repositories of public domain data. Using these data to make scientific discoveries is sometimes straightforward, but can be complicated by the number and breadth of public sources available to the researcher as well as by the plethora of tools from which to choose. Complex searches, analyses, or even storage needs require more computational expertise than that available within an individual laboratory. As biomedical researchers develop more computational skills, this may change over time. Having a centralized group of experts in computational biology can be of great value to the experimental biologist, and, recognizing this, many organizations have invested in building a team of computational biologists, bioinformaticists, and research IT services to address the needs of the investigators. This Editorial presents our views on the benefits and challenges of centralizing these activities.
DNA methylation is defined as an epigenetic modification because it can be inherited across cell division. Since variations in DNA methylation can affect gene expression and be inherited across generations, they can provide a source of heritable phenotypic variation that is not caused by changes in the DNA sequence. However, the extent to which this type of phenotypic variation occurs in natural or experimental populations is unknown, partly because of the difficulty in teasing apart the effect of DNA methylation variants (epialleles) from that of the DNA sequence variants also present in these populations. To overcome this problem, we have derived a population of epigenetic recombinant inbred lines in the plant Arabidopsis thaliana, using parents with few DNA sequence differences but contrasting DNA methylation profiles. This population showed variation and a high degree of heritability for two complex traits, flowering time and plant height. Multiple parental DNA methylation differences were also found to be stably inherited over eight generations in this population. These findings reveal the potential impact of heritable DNA methylation variation on complex traits and demonstrate the importance of integrating epigenetic information in population genetics studies.
Centralized Bioinformatics Core Facilities provide shared resources for the computational and IT requirements of the investigators in their department or institution. As such, they must be able to effectively react to new types of experimental technology. Recently faced with an unprecedented flood of data generated by the next generation of DNA sequencers, these groups found it necessary to respond quickly and efficiently to the informatics and infrastructure demands. Centralized Facilities newly facing this challenge need to anticipate time and design considerations of necessary components, including infrastructure upgrades, staffing, and tools for data analyses and management.