Rule-based modeling has become a powerful approach for modeling intracellular networks, which are characterized by rich molecular diversity. Truly comprehensive models of cell behavior, however, must address spatial complexity at both the intracellular level and at the level of interacting populations of cells, and will require richer modeling languages and tools. A recent paper in BMC Systems Biology represents a signifcant step toward the development of a unified modeling language and software platform for the development of multi-level, multiscale biological models.
See research article: http://www.biomedcentral.com/1752-0509/5/166
Cancer cells have different metabolic requirements from their normal counterparts. Understanding the consequences of this differential metabolism requires a detailed understanding of glucose metabolism and its relation to energy production in cancer cells. A recent study in BMC Systems Biology by Vasquez et al. developed a mathematical model to assess some features of this altered metabolism. Here, we take a broader look at the regulation of energy metabolism in cancer cells, considering their anabolic as well as catabolic needs.
See research article: http://www.biomedcentral.com/1752-0509/4/58/
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.
The lag phase of bacterial growth is important from a medical and food safety perspective, but difficult to study due to the low density and metabolic rate of cells. A new study by Alon and colleagues reveals that the gene expression program during early lag phase prioritizes carbon source utilization enzymes over genes responsible for biomass accumulation. This cellular strategy ultimately maximizes growth, making the best long-term use of the new nutrient-rich environment.
See research article: http://www.biomedcentral.com/1752-0509/7/136
Little is known about the genetic mechanisms underlying inducible defenses. Recently, the genome of Daphnia pulex, a model organism for defense studies, has been sequenced. Building on the genome information, recent preliminary studies in BMC Developmental Biology and BMC Molecular Biology have assessed gene response profiles in Daphnia under predation pressure. We review the significance of the findings and highlight future research perspectives.
See research articles http://www.biomedcentral.com/1471-2164/10/527, http://www.biomedcentral.com/1471-2105/6/45, http://www.biomedcentral.com/1471-213X/10/45
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/
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
Recently, there has been an expansion of different forms of systematic review of research and the development of guidance and standards about particular types of review. These reviews can be best understood within a broad framework of the dimensions on which reviews differ, and how the review methodology relates to the methodology of primary research. Similarly, publication standards can be understood in terms of their relation to other standards such as guidance and rules for undertaking reviews and systems for appraising the quality of reviews. This commentary is written with special reference to the publication standards for meta-narrative and realist reviews being published in BMC Medicine.
See related research articles http://www.biomedcentral.com/1741-7015/11/20 and http://www.biomedcentral.com/1741-7015/11/21
Systematic reviews; Meta-narrative; Realist synthesis.
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.
A recent article in BMC Bioinformatics describes new advances in workflow systems for computational modeling in systems biology. Such systems can accelerate, and improve the consistency of, modeling through automation not only at the simulation and results-production stages, but also at the model-generation stage. Their work is a harbinger of the next generation of more powerful software for systems biologists.
See research article: http://www.biomedcentral.com/1471-2105/11/582/abstract/
Ever since the rise of systems biology at the end of the last century, mathematical representations of biological systems and their activities have flourished. They are being used to describe everything from biomolecular networks, such as gene regulation, metabolic processes and signaling pathways, at the lowest biological scales, to tissue growth and differentiation, drug effects, environmental interactions, and more. A very active area in the field has been the development of techniques that facilitate the construction, analysis and dissemination of computational models. The heterogeneous, distributed nature of most data resources today has increased not only the opportunities for, but also the difficulties of, developing software systems to support these tasks. The work by Li et al.  published in BMC Bioinformatics represents a promising evolutionary step forward in this area. They describe a workflow system - a visual software
environment enabling a user to create a connected set of operations to be performed sequentially using seperate tools and resources. Their system uses third-party data resources accessible over the Internet to elaborate and parametrize (that is, assign parameter values to) computational models in a semi-automated manner. In Li et al.'s work, the authors point towards a promising future for computational modeling and simultaneously highlight some of the difficulties that need to be overcome before we get there.
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
The bending of cell sheets plays a major role in multicellular embryonic morphogenesis. Recent advances are leading to a deeper understanding of how the biophysical properties and the force-producing behaviors of cells are regulated, and how these forces are integrated across cell sheets during bending. We review work that shows that the dynamic balance of apical versus basolateral cortical tension controls specific aspects of invagination of epithelial sheets, and recent evidence that tissue expansion by growth contributes to neural retinal invagination in a stem cell-derived, self-organizing system. Of special interest is the detailed analysis of the type B inversion in Volvox reported in BMC Biology by Höhn and Hallmann, as this is a system that promises to be particularly instructive in understanding morphogenesis of any monolayered spheroid system.
See research article: http://www.biomedcentral.com/1741-7007/9/89
The insulin-like growth factor (IGF) system mediates growth, differentiation and developmental processes; it is also involved in various metabolic activities. Deregulation of IGF system expression and action is linked to diverse pathologies, ranging from growth deficits to cancer development. Targeting of the IGF axis emerged in recent years as a promising therapeutic approach in cancer and other medical conditions. Rational use of IGF-I-induced gene signatures may help to identify patients who might benefit from IGF axis-directed therapeutic modalities. In the accompanying research article in BMC Medicine, Rajski et al. show that IGF-I-induced gene expression in primary breast and lung fibroblasts accurately predict outcomes in breast and lung cancer patients.
See the associated research paper by Rajski et al: http://www.biomedcentral.com/1741-7015/8/1
Genome and proteome data from Hydra magnipapillata have opened the way for the molecular analysis of an ancient nervous system, which includes stinging cells, an unusual neurosensory and neurosecretory cell type. They hold some surprises for the mechanisms and evolution of sensory transduction that could not have been anticipated from what has been learned from flies and vertebrates. Research in BMC Biology now implicates the ancient opsin-mediated transduction pathway in the neuronal control of stinging cell discharge.
See research article http://www.biomedcentral.com/1741-7007/10/17
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
Small nucleolar RNAs (snoRNAs) are among the most evolutionarily ancient classes of small RNA. Two experimental screens published in BMC Genomics expand the eukaryotic snoRNA catalog, but many more snoRNAs remain to be found.
See research articles http://www.biomedcentral.com/1471-2164/10/515 and http://www.biomedcentral.com/1471-2164/11/61.
Chemosensory receptor genes encode G protein-coupled receptors with which animals sense their chemical environment. The large number of chemosensory receptor genes in the genome and their extreme genetic variability pose unusual challenges for understanding their evolution and function. Two articles in BMC Genomics explore the genetic variation of chemosensory receptor gene repertoires in humans and mice and provide unparalleled insight into the causes and consequences of this variability.
See research articles http://www.biomedcentral.com/1471-2164/13/414 and http://www.biomedcentral.com/1471-2164/13/415
Selection and constraints put limits on morphological evolution. Mammalian teeth are no exception, and the need for them to meet precisely exerts exacting constraints on a staggering array of developmental and functional factors that must be integrated to maintain their performance as they evolve. A study in BMC Evolutionary Biology demonstrates that mandibular movement is an important component of this integration, and one that should not be neglected in the quantitiative study of the evolution of tooth morphology.
See research article http://www.biomedcentral.com/1471-2148/12/146/
dental occlusion; evolutionary constraints; morphological integration; complexity; orientation patch counts
Bistability, the capacity to achieve two distinct stable steady states in response to a set of external stimuli, arises within biological systems ranging from the λ phage switch in bacteria to cellular signal transduction pathways in mammalian cells. On the other hand, more and more experimental evidence in the form of bimodal population distribution has indicated that noise plays a very important role in the switching of bistable systems. However, the physiological mechanism underling noise-induced switching behaviors remains to be fully understood.
In this paper, we investigate the effect of noises on switching in single and coupled genetic toggle switch systems in Escherichia coli. In the case of the single toggle switch, we show that the multiplicative noises resulting from stochastic fluctuations in degradation rates can induce switching. In the case of the toggle switches interfaced by a quorum-sensing signaling pathway, we find that stochastic fluctuations in degradation rates inside cells, i.e., intracellular noises, can induce synchronized switching, whereas the extracellular noise additive to the common medium can not only entrain all the individual systems to switch in a synchronous manner but also enhance this ordering behavior efficiently, leading a robust collective rhythm in this interacting system.
These insights on the effect of noises would be beneficial to understanding the basic mechanism of how living systems optimally facilitate to function under various fluctuated environments.
Often considered an 'aging' hormone due to its role in accelerating such developmental processes as ripening, senescence, and abscission, the plant hormone ethylene also regulates many aspects of growth and development throughout the life cycle of the plant. Multiple mechanisms have been identified by which transcriptional output from the ethylene signaling pathway can be tailored to meet the needs of particular developmental pathways. Of special interest is the report by Lumba et al. in BMC Biology on how vegetative transitions are regulated through the effect of the transcription factor FUSCA3 on ethylene-controlled gene expression, providing an elegant example of how hormonal control can be integrated into a developmental pathway.
See research article http://www.biomedcentral.com/1741-7007/10/8
One of the amazing qualities of plants is their phenotypic plasticity. Consider, for example, how a pine tree will grow to a towering hundreds of feet in height in Yosemite Valley, but to only a gnarled few feet in height up near the timberline. This diversity of form, though originating from the same genotype, points to the degree to which plant growth and development can be modulated. Much of this control is mediated by a small group of plant hormones that include auxin, cytokinin, gibberellin, abscisic acid, brassinosteroid, jasmonic acid, and ethylene . These are often considered 'classical' plant hormones because they were discovered decades ago; indeed, the presence of some was inferred over a century ago. Their early discovery is no doubt due in part to their general function throughout the life cycle of the plant. More recently, and in the remarkably short period of time since the advent of Arabidopsis as a genetic model, key elements in the primary signaling pathways of these plant hormones have been uncovered. The important question is no longer simply how are these hormones perceived, but how are the hormonal signals integrated into the control of particular developmental pathways? In pursuing such a question, Lumba et al.  have now uncovered a role for the plant hormone ethylene in regulating the conversion of juvenile to adult leaves. These new data, in combination with prior research implicating the plant hormones abscisic acid and gibberellin in this transition , form an important step in defining how a hormonal network regulates a key developmental process.
The regulation of gene expression in trypanosomes is unique. In the absence of transcriptional control at the level of initiation, a subset of Trypanosoma brucei genes form post-transcriptional regulons in which mRNAs are co-regulated in response to differentiation signals.
See research articles http://www.biomedcentral.com/1471-2164/10/427, http://www.biomedcentral.com/1471-2164/10/482 and http://www.biomedcentral.com/1471-2164/10/495.
Genome-wide association studies (GWAS) look for correlations between traits of interest and genetic markers spread throughout the genome. A recent study in BMC Genetics has found that populations of the malaria parasite Plasmodium vivax should be amenable to GWAS searching for a genetic basis of parasite pathogenicity. Geographical substructure in populations may, however, prove a problem in interpreting the results.
See research article http://www.biomedcentral.com/1471-2156/11/65
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
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.
Population genetic analyses of Eurasian wolves published recently in BMC Evolutionary Biology suggest that a major genetic turnover took place in Eurasian wolves after the Pleistocene. These results add to the growing evidence that large mammal species surviving the late Pleistocene extinctions nevertheless lost a large share of their genetic diversity.
See research article http://www.biomedcentral.com/1471-2148/10/104