Gut microbes influence animal health and thus, are potential targets for interventions that slow aging. Live E. coli provides the nematode worm Caenorhabditis elegans with vital micronutrients, such as folates that cannot be synthesized by animals. However, the microbe also limits C. elegans lifespan. Understanding these interactions may shed light on how intestinal microbes influence mammalian aging.
Serendipitously, we isolated an E. coli mutant that slows C. elegans aging. We identified the disrupted gene to be aroD, which is required to synthesize aromatic compounds in the microbe. Adding back aromatic compounds to the media revealed that the increased C. elegans lifespan was caused by decreased availability of para-aminobenzoic acid, a precursor to folate. Consistent with this result, inhibition of folate synthesis by sulfamethoxazole, a sulfonamide, led to a dose-dependent increase in C. elegans lifespan. As expected, these treatments caused a decrease in bacterial and worm folate levels, as measured by mass spectrometry of intact folates. The folate cycle is essential for cellular biosynthesis. However, bacterial proliferation and C. elegans growth and reproduction were unaffected under the conditions that increased lifespan.
In this animal:microbe system, folates are in excess of that required for biosynthesis. This study suggests that microbial folate synthesis is a pharmacologically accessible target to slow animal aging without detrimental effects.
aging; microbes; folate; C. elegans; E. coli
Caenorhabditis elegans is a preeminent model organism, but the natural ecology of this nematode has been elusive. A four-year survey of French orchards published in BMC Biology reveals thriving populations of C. elegans (and Caenorhabditis briggsae) in rotting fruit and plant stems. Rather than being simply a 'soil nematode', C. elegans appears to be a 'plant-rot nematode'. These studies signal a growing interest in the integrated genomics and ecology of these tractable animals.
See research article http://www.biomedcentral.com/1741-7007/10/59
Understanding the genetic basis of age-related diseases is a critical step toward developing therapies that promote healthy aging. Numerous genes have been identified that modulate lifespan, but the influence of natural variation in aging has not been well studied. A new report utilizing a transgenic protein aggregation model in Caenorhabditis elegans has provided important tools and insights into the relationship between natural genetic variation, protein aggregation, and age-related pathology.
See research article: http://www.biomedcentral.com/1741-7007/11/100
The nematode Caenorhabditis elegans is a favorite model for the study of aging. A wealth of genetic and genomic studies show that metabolic regulation is a hallmark of life-span modulation. A recent study in BMC Biology identifying metabolic signatures for longevity suggests that amino-acid pools may be important in longevity.
See research article http://www.biomedcentral.com/1741-7007/8/14.
There have been notable advances in the scientific understanding of regeneration within the past year alone, including two recently published in BMC Biology. Increasingly, progress in the regeneration field is being inspired by comparisons with stem cell biology and enabled by newly developed techniques that allow simultaneous examination of thousands of genes and proteins.
See research articles http://www.biomedcentral.com/1741-7007/7/83 and http://www.biomedcentral.com/1741-7007/8/5.
Daphnia pulex is the first crustacean to have its genome sequenced. Availability of the genome sequence will have implications for research in aquatic ecology and evolution in particular, as addressed by a series of papers published recently in BMC Evolutionary Biology and BMC Genomics.
See research articles http://www.biomedcentral.com/1471-2148/9/78, http://www.biomedcentral.com/1471-2164/10/527, http://www.biomedcentral.com/1471-2148/9/79, http://www.biomedcentral.com/1471-2164/10/175, http://www.biomedcentral.com/1471-2164/10/172, http://www.biomedcentral.com/1471-2164/10/169, http://www.biomedcentral.com/1471-2164/10/170 and http://www.biomedcentral.com/1471-2148/9/243.
An international collaborative effort has recently uncovered the genome of the zebra finch, a songbird model that has provided unique insights into an array of biological phenomena.
See research articles http://www.biomedcentral.com/1471-2164/9/131, http://www.biomedcentral.com/1471-2164/11/220/, http://www.biomedcentral.com/1471-2202/11/46/ and http://www.biomedcentral.com/1741-7007/8/28/
ParaHox genes, and their evolutionary sisters the Hox genes, are integral to patterning the anterior-posterior axis of most animals. Like the Hox genes, ParaHox genes can be clustered and exhibit the phenomenon of colinearity - gene order within the cluster matching gene activation. Two new instances of ParaHox clustering provide the first examples of intact clusters outside chordates, with gene expression lending weight to the argument that temporal colinearity is the key to understanding clustering.
See research articles:
Medical student selection is an important but difficult task. Three recent papers by McManus et al. in BMC Medicine have re-examined the role of tests of attainment of learning (A’ levels, GCSEs, SQA) and of aptitude (AH5, UKCAT), but on a much larger scale than previously attempted. They conclude that A’ levels are still the best predictor of future success at medical school and beyond. However, A’ levels account for only 65% of the variance in performance that is found. Therefore, more work is needed to establish relevant assessment of the other 35%.
Please see related research articles http://www.biomedcentral.com/1741-7015/11/242, http://www.biomedcentral.com/1741-7015/11/243 and http://www.biomedcentral.com/1741-7015/11/244.
Medical School Admission; Predictors of performance; Aptitude testing
Mutation of the protein spartin is a cause of one form of spastic paraplegia. Spartin interacts with ubiquitin ligases of the Nedd4 family, and a recent report in BMC Biology now shows that it acts as an adaptor to recruit and activate the ubiquitin ligase AIP4 onto lipid droplets, leading to the ubiquitination and degradation of droplet-associated proteins. A deficiency of spartin apparently causes lipid droplets to accumulate.
See research article: http://www.biomedcentral.com/1741-7007/8/72/
A recent study in BMC Biology has determined that the immature stage of the bed bug (the nymph) signals its reproductive status to adult males using pheromones and thus avoids the trauma associated with copulation in this species. The success of this nymphal strategy of deterrence is instructive. Against the background of increasing problems with bed bugs, this research raises the question whether pheromones might be used to control them.
See research article http://www.biomedcentral.com/1741-7007/8/121
This article is a response to Klütsch and Crapon de Caprona
See correspondence article http://www.biomedcentral.com/1741-7007/8/119 and our original research article http://www.biomedcentral.com/1741-7007/8/16.
This article is a response to Wang and Luo.
See correspondence article http://www.biomedcentral.com/1741-7007/10/30/ [WEBCITE] and the original research article http://www.biomedcentral.com/1741-7007/9/24 [WEBCITE].
This article is a response to Wang and Luo.
See correspondence article http://www.biomedcentral.com/1741-7007/10/30 and the original research article http://www.biomedcentral.com/1741-7007/9/24.
This article is a response to Vibranovski et al.
See correspondence article http://www.biomedcentral.com/1741-7007/10/49 and the original research article http://www.biomedcentral.com/1741-7007/9/29
We have previously reported a high propensity of testis-expressed X-linked genes to activation in meiotic cells, a similarity in global gene expression between the X chromosome and autosomes in meiotic germline, and under-representation of various types of tissue-specific genes on the X chromosome. Based on our findings and a critical review of the current literature, we believe that there is no global and severe silencing of the X chromosome in the meiotic male germline of Drosophila. The term 'meiotic sex chromosome inactivation' (MSCI) therefore seems misleading when used to describe the minor underexpression of the X chromosome in the testis of Drosophila, because this term erroneously implies a profound and widespread silencing of the X-linked genes, by analogy to the well-studied MSCI system in mammals, and therefore distracts from identification and analysis of the real mechanisms that orchestrate gene expression and evolution in this species.
A recent article in BMC Biology illustrates the use of a systems-biology approach to integrate data across the transcriptome, proteome and metabolome of budding yeast in order to dissect the relationship between nutrient conditions and cell growth.
See research article http://jbiol.com/content/6/2/4 and http://www.biomedcentral.com/1741-7007/8/68
Current interest in proteasome inhibitors for cancer therapy has stimulated considerable research efforts to identify the molecular pathway to their cytotoxicity with a view to identifying the mechanisms of sensitivity and resistance as well as informing the development of new drugs. Zhao and Vuori describe this month in BMC Biology experiments indicating a novel role of the adaptor protein p130Cas in sensitivity to apoptosis induced not only by proteasome inhibitors but also by the unrelated drug doxorubicin.
See research article: http:// http://www.biomedcentral.com/1741-7007/9/73
How much functional specialization can one component histone confer on a single nucleosome? The histone variant H2A.Z seems to be an extreme example. Genome-wide distribution maps show non-random (and evolutionarily conserved) patterns, with localized enrichment or depletion giving a tantalizing suggestion of function. Multiple post-translational modifications on the protein indicate further regulation. An additional layer of complexity has now been uncovered: the vertebrate form is actually encoded by two non-allelic genes that differ by expression pattern and three amino acids.
See research articles http://www.biomedcentral.com/1741-7007/7/86 and http://www.biomedcentral.com/1471-2148/9/31.
Several recent papers illustrate the importance of migration and gene flow in molding the patterns of genetic variation observed in humans today. We place the varied demographic processes covered by these terms into a more general framework, and discuss some of the challenges facing attempts to reconstruct past human mobility and determine its influence on our genetic heritage.
See research articles: http://www.biomedcentral.com/1741-7007/8/15 and http://www.biomedcentral.com/1471-2156/11/18
Important advances in the field of tissue engineering are arising from increased interest in novel biomaterial designs with bioactive components that directly influence cell behavior. Following the recent work of Mitchell and co-workers published in BMC Biology, we review how spatial and temporal control of signaling molecules in a matrix material regulates cellular responses for tissue-specific applications.
See research article http://www.biomedcentral.com/1741-7007/8/57
The complexity of the core promoter transcription machinery has emerged as an additional level of transcription regulation that is used during vertebrate development. Recent studies, including one published in BMC Biology, provide mechanistic insights into how the TATA binding protein (TBP) and its vertebrate-specific paralog TBP2 (TRF3) switch function during the transition from the oocyte to the embryo.
See research article http://www.biomedcentral.com/1741-7007/7/45
Bioinformatics-based searches for correlations between subcellular localization and pI or charge distribution of proteins have failed to detect meaningful correlations. Recent work published in BMC Biology finds that a physicochemical metric of charge distribution correlates better with subcellular pH than does pI.
See research article http://www.biomedcentral.com/1741-7007/7/69
A study in the current issue of BMC Biology has identified a mouse major urinary protein as a pheromone that attracts female mice to male urine marks and induces a learned attraction to the volatile urinary odor of the producer. See research article http://www.biomedcentral.com/1741-7007/8/75
The identification of an increasing number of cancer genes is opening up unexpected scenarios in cancer genetics. When analyzed for their systemic properties, these genes show a general fragility towards perturbation. A recent paper published in BMC Biology shows how the founder domains of known cancer genes emerged at two macroevolutionary transitions - the advent of the first cell and the transition to metazoan multicellularity.
See research article http://www.biomedcentral.com/1741-7007/8/66
The basis for transcriptional fidelity by RNA polymerase is not understood, but the 'trigger loop', a conserved structural element that is rearranged in the presence of correct substrate nucleotides, is thought to be critical. A study just published in BMC Biology sheds new light on the ways in which the trigger loop may promote selection of correct nucleotide triphosphate substrates.
See research article http://www.biomedcentral.com/1741-7007/8/54