Ecology: the proximate cause of frog declines?

Pounds et al. argue that global warming contributes to amphibian declines by encouraging outbreaks of the chytrid fungus Batrachochytrium dendrobatidis. Although our findings agree with the climate-linked epidemic hypothesis, this pathogen is probably not the only proximate factor in such cases: in the Trasimeno Lake area of Umbria in central Italy, for example, the water frog Rana lessonae first declined in the late 1990s, yet chytridiomycosis was not observed until 2003 (refs 5, 6). Here we show that the chytrid was common there throughout 1999-2002, in a previously unknown form that did not cause disease. We therefore think that the focus by Pounds et al. on a single pathogen is hard to justify because the host-parasite ecology is at present so poorly understood.     

Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human

Free fatty acids provide an important energy source as nutrients, and act as signalling molecules in various cellular processes. Several G-protein-coupled receptors have been identified as free-fatty-acid receptors important in physiology as well as in several diseases. GPR120 (also known as O3FAR1) functions as a receptor for unsaturated long-chain free fatty acids and has a critical role in various physiological homeostasis mechanisms such as adipogenesis, regulation of appetite and food preference. Here we show that GPR120-deficient mice fed a high-fat diet develop obesity, glucose intolerance and fatty liver with decreased adipocyte differentiation and lipogenesis and enhanced hepatic lipogenesis. Insulin resistance in such mice is associated with reduced insulin signalling and enhanced inflammation in adipose tissue. In human, we show that GPR120 expression in adipose tissue is significantly higher in obese individuals than in lean controls. GPR120 exon sequencing in obese subjects reveals a deleterious non-synonymous mutation (p.R270H) that inhibits GPR120 signalling activity. Furthermore, the p.R270H variant increases the risk of obesity in European populations. Overall, this study demonstrates that the lipid sensor GPR120 has a key role in sensing dietary fat and, therefore, in the control of energy balance in both humans and rodents.     

Joint power and spectrum allocation algorithm in cognitive radio networks

The spectrum sharing problem between primary and cognitive users is mainly investigated.Since the interference for primary users and the total power for cognitive users are constrained,based on the well-known water-filling theorem,a novel one-user water-filling algorithm is proposed,and then the corresponding simulation results are given to analyze the feasibility and validity.After that this algorithm is used to solve the communication utility optimization problem subject to the power constraints in cognitive radio network.First,through the gain to noise ratio for cognitive users,a subcarrier and power allocation algorithm based on the optimal frequency partition is proposed for two cognitive users.Then the spectrum sharing algorithm is extended to multiuser conditions such that the greedy and parallel algorithms are proposed for spectrum sharing.Theory and simulation analysis show that the subcarrier and power allocation algorithms can not only protect the primary users but also effectively solve the spectrum and power allocation problem for cognitive users.     

Impacts of biodiversity on the emergence and transmission of infectious diseases

Current unprecedented declines in biodiversity reduce the ability of ecological communities to provide many fundamental ecosystem services. Here we evaluate evidence that reduced biodiversity affects the transmission of infectious diseases of humans, other animals and plants. In principle, loss of biodiversity could either increase or decrease disease transmission. However, mounting evidence indicates that biodiversity loss frequently increases disease transmission. In contrast, areas of naturally high biodiversity may serve as a source pool for new pathogens. Overall, despite many remaining questions, current evidence indicates that preserving intact ecosystems and their endemic biodiversity should generally reduce the prevalence of infectious diseases.     

Role of vasostatin-1 C-terminal region in fibroblast cell adhesion

Fibroblast adhesion can be modulated by proteins released by neuroendocrine cells and neurons, such as chromogranin A (CgA) and its N-terminal fragment vasostatin-1 (VS-1, CgA_1–78). We have investigated the mechanisms of the interaction of VS-1 with fibroblasts and of its pro-adhesive activity and have found that the proadhesive activity of VS-1 relies on its interaction with the fibroblast membrane via a phospholipid-binding amphipathic α-helix located within residues 47–66, as well as on the interaction of the adjacent C-terminal region 67–78, which is structurally similar to ezrin–radixin–moesin-binding phosphoprotein 50 (a membrane-cytoskeleton adapter protein), with other cellular components critical for the regulation of cell cytoskeleton.     

Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease

More than 1,000 susceptibility loci have been identified through genome-wide association studies (GWAS) of common variants; however, the specific genes and full allelic spectrum of causal variants underlying these findings have not yet been defined. Here we used pooled next-generation sequencing to study 56 genes from regions associated with Crohn's disease in 350 cases and 350 controls. Through follow-up genotyping of 70 rare and low-frequency protein-altering variants in nine independent case-control series (16,054 Crohn's disease cases, 12,153 ulcerative colitis cases and 17,575 healthy controls), we identified four additional independent risk factors in NOD2, two additional protective variants in IL23R, a highly significant association with a protective splice variant in CARD9 (P < 1 × 10(-16), odds ratio ≈ 0.29) and additional associations with coding variants in IL18RAP, CUL2, C1orf106, PTPN22 and MUC19. We extend the results of successful GWAS by identifying new, rare and probably functional variants that could aid functional experiments and predictive models.     

Composition and functional role of the mucus layers in the intestine

In discussions on intestinal protection, the protective capacity of mucus has not been very much considered. The progress in the last years in understanding the molecular nature of mucins, the main building blocks of mucus, has, however, changed this. The intestinal enterocytes have their apical surfaces covered by transmembrane mucins and the whole intestinal surface is further covered by mucus, built around the gel-forming mucin MUC2. The mucus of the small intestine has only one layer, whereas the large intestine has a two-layered mucus where the inner, attached layer has a protective function for the intestine, as it is impermeable to the luminal bacteria.     

Selective killing of cancer cells by a small molecule targeting the stress response to ROS

Malignant transformation, driven by gain-of-function mutations in oncogenes and loss-of-function mutations in tumour suppressor genes, results in cell deregulation that is frequently associated with enhanced cellular stress (for example, oxidative, replicative, metabolic and proteotoxic stress, and DNA damage). Adaptation to this stress phenotype is required for cancer cells to survive, and consequently cancer cells may become dependent upon non-oncogenes that do not ordinarily perform such a vital function in normal cells. Thus, targeting these non-oncogene dependencies in the context of a transformed genotype may result in a synthetic lethal interaction and the selective death of cancer cells. Here we used a cell-based small-molecule screening and quantitative proteomics approach that resulted in the unbiased identification of a small molecule that selectively kills cancer cells but not normal cells. Piperlongumine increases the level of reactive oxygen species (ROS) and apoptotic cell death in both cancer cells and normal cells engineered to have a cancer genotype, irrespective of p53 status, but it has little effect on either rapidly or slowly dividing primary normal cells. Significant antitumour effects are observed in piperlongumine-treated mouse xenograft tumour models, with no apparent toxicity in normal mice. Moreover, piperlongumine potently inhibits the growth of spontaneously formed malignant breast tumours and their associated metastases in mice. Our results demonstrate the ability of a small molecule to induce apoptosis selectively in cells that have a cancer genotype, by targeting a non-oncogene co-dependency acquired through the expression of the cancer genotype in response to transformation-induced oxidative stress.     

Social exclusion in academia through biases in methodological quality evaluation: On the situation of women in science and philosophy

Empirical studies show that academia is socially exclusive. I argue that this social exclusion works, at least partly, through the systematic methodological disqualification of contributions from members of underrepresented social groups. As methodological quality criteria are underdetermined their interpretation and weighting can be biased with relation to gender, race, social background, etc. Such biased quality evaluation can take place on a local or global level. The current situation of women in academic philosophy illuminates this. I conclude that only mechanical solutions can effectively change the situation.