Nras loss induces metastatic conversion of Rb1-deficient neuroendocrine thyroid tumor

Mutations in the gene encoding the retinoblastoma tumor suppressor predispose humans and mice to tumor development. Here we have assessed the effect of Nras loss on tumor development in Rb1 heterozygous mice. Loss of one or two Nras alleles is shown to significantly reduce the severity of pituitary tumors arising in Rb1(+/-) animals by enhancing their differentiation. By contrast, C-cell thyroid adenomas occurring in Rb1(+/-) mice progress to metastatic medullary carcinomas after loss of Nras. In Rb1(+/-)Nras(+/-) animals, distant medullary thyroid carcinoma metastases are associated with loss of the remaining wild-type Nras allele. Loss of Nras in Rb1-deficient C cells results in elevated Ras homolog family A (RhoA) activity, and this is causally linked to the invasiveness and metastatic behavior of these cells. These findings suggest that the loss of the proto-oncogene Nras in certain cellular contexts can promote malignant tumor progression.     

Coral mucus functions as an energy carrier and particle trap in the reef ecosystem

Zooxanthellae, endosymbiotic algae of reef-building corals, substantially contribute to the high gross primary production of coral reefs, but corals exude up to half of the carbon assimilated by their zooxanthellae as mucus. Here we show that released coral mucus efficiently traps organic matter from the water column and rapidly carries energy and nutrients to the reef lagoon sediment, which acts as a biocatalytic mineralizing filter. In the Great Barrier Reef, the dominant genus of hard corals, Acropora, exudes up to 4.8 litres of mucus per square metre of reef area per day. Between 56% and 80% of this mucus dissolves in the reef water, which is filtered through the lagoon sands. Here, coral mucus is degraded at a turnover rate of at least 7% per hour. Detached undissolved mucus traps suspended particles, increasing its initial organic carbon and nitrogen content by three orders of magnitude within 2 h. Tidal currents concentrate these mucus aggregates into the lagoon, where they rapidly settle. Coral mucus provides light energy harvested by the zooxanthellae and trapped particles to the heterotrophic reef community, thereby establishing a recycling loop that supports benthic life, while reducing loss of energy and nutrients from the reef ecosystem.     

近百年来大冶湖流域洪涝灾害研究

利用大冶湖流域1901年～2000年近百年来的历史洪水资料,对该流域洪涝灾害发生的时间特征、灾害等级进行分析,并利用Matlab小波分析方法对洪涝灾害等级的周期变化规律及特征进行分析.结果表明：大冶湖流域在前期洪涝灾害发生频率较低,到后期洪涝灾害发生越来越频繁;流域发生的洪涝灾害具有明显的季节性和集中性,主要集中发生在夏季;中后期主要以重度洪涝灾害为主,中度洪涝灾害和特大洪涝灾害也比较频繁;各等级洪涝灾害的周期变化与规律有很大差异性.针对大冶湖流域洪涝灾害的特征,分析了成灾原因,并提出了防治措施.     

The substrate degradome of meprin metalloproteases reveals an unexpected proteolytic link between meprin β and ADAM10

The in vivo roles of meprin metalloproteases in pathophysiological conditions remain elusive. Substrates define protease roles. Therefore, to identify natural substrates for human meprin α and β we employed TAILS (terminal amine isotopic labeling of substrates), a proteomics approach that enriches for N-terminal peptides of proteins and cleavage fragments. Of the 151 new extracellular substrates we identified, it was notable that ADAM10 (a disintegrin and metalloprotease domain-containing protein 10)—the constitutive α-secretase—is activated by meprin β through cleavage of the propeptide. To validate this cleavage event, we expressed recombinant proADAM10 and after preincubation with meprin β, this resulted in significantly elevated ADAM10 activity. Cellular expression in murine primary fibroblasts confirmed activation. Other novel substrates including extracellular matrix proteins, growth factors and inhibitors were validated by western analyses and enzyme activity assays with Edman sequencing confirming the exact cleavage sites identified by TAILS. Cleavages in vivo were confirmed by comparing wild-type and meprin^?/? mice. Our finding of cystatin C, elafin and fetuin-A as substrates and natural inhibitors for meprins reveal new mechanisms in the regulation of protease activity important for understanding pathophysiological processes.     

Exogenous cAMP upregulates the expression of glnII and glnK-amtB genes in Sinorhizobium meliloti 1021

Sinorhizobium meliloti is a soil-borne bacterium that can lead a symbiosis life with leguminous host plants. Successful symbiont establishment requires specific recognition and progressive differentiation of both bac- teria and host cells. Once inside the plant cells of root nodules, the bacteria differentiate into non-dividing cells called bacteroids. Bacteroids obtain carbon source from the plant and, in return, they provide the plant with ammonium, and/or amino acid, as fixed nitrogen. Sign…     

The irreducibility of value-freedom to theory assessment

The current ideal of value-freedom holds non-cognitive values to be illegitimate in theory appraisal but legitimate in earlier stages of the research process, for example, when affecting the selection of topics or the generation of hypotheses. Respective decisions are often considered as part of a context of discovery and as irrelevant for the justification and assessment of theories. I will argue that this premise of an epistemic independence of theory appraisal, though often taken for granted, is false. Due to the possibility of value-laden blind spots, decisions in discovery can have an indirect impact on theory assessment that the value-free ideal cannot deal with. This argument is illustrated by a case study from women's health research, namely the assessment of hormone replacement therapy as a prevention of coronary heart diseases. In consequence, the epistemic trustworthiness of science is promoted more by a pluralism of non-cognitive values than by their exclusion; and a normative philosophy of science needs to enlarge its focus to include the context of discovery as well as the social conditions of science.     

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.