Trefoil factors

Trefoil factor family (TFF) peptides have many in vivo and in vitro effects on restitution, wound healing, apoptosis, cell motility, adhesion and vectorial ion pumping, amongst others. (125)I-TFF peptides bind to cell membranes with classical saturable ability. It would be surprising if there were not TFF-protein interactions that would explain these actions, but to date no convincing TFF-binding partner has been shown which unambiguously takes part in any of these functions. Nevertheless, several TFF-binding proteins exist, including the small intestinal CRP-ductin (muclin), which binds TFF2, and the recently described gastric foveolar proteins TFIZ1 (TFF1-binding) and blottin (TFF2-binding), any of which may yet interact in novel ways to elicit TFF-mediated events. This review describes the expression and, where known, the functions of such proteins.     

Barttin is a Cl- channel beta-subunit crucial for renal Cl- reabsorption and inner ear K+ secretion.

Renal salt loss in Bartter's syndrome is caused by impaired transepithelial transport in the loop of Henle. Sodium chloride is taken up apically by the combined activity of NKCC2 (Na+-K--2Cl- cotransporters) and ROMK potassium channels. Chloride ions exit from the cell through basolateral ClC-Kb chloride channels. Mutations in the three corresponding genes have been identified that correspond to Bartter's syndrome types 1-3. The gene encoding the integral membrane protein barttin is mutated in a form of Bartter's syndrome that is associated with congenital deafness and renal failure. Here we show that barttin acts as an essential beta-subunit for ClC-Ka and ClC-Kb chloride channels, with which it colocalizes in basolateral membranes of renal tubules and of potassium-secreting epithelia of the inner ear. Disease-causing mutations in either ClC-Kb or barttin compromise currents through heteromeric channels. Currents can be stimulated further by mutating a proline-tyrosine (PY) motif on barttin. This work describes the first known beta-subunit for CLC chloride channels and reveals that heteromers formed by ClC-K and barttin are crucial for renal salt reabsorption and potassium recycling in the inner ear.     

水平排列硅光二极管色传感器及其特性

简要介绍水平排列硅光二极管色传感器的制作工艺，该器件波长在５００ｎｍ到６５０ｎｍ范围内有一个单调的近于线性的光谱响应。入射光波长为６００ｎｍ时，入射光强度化五个数量级，测出的波长基本不变，器件波长分辨率、最低入射光强、长时间测量的波长漂移以及波长温漂系数等特性的测量结果表明：该类色传感器已达高性能实用要求。     

Ecology drives a global network of gene exchange connecting the human microbiome

Horizontal gene transfer (HGT), the acquisition of genetic material from non-parental lineages, is known to be important in bacterial evolution. In particular, HGT provides rapid access to genetic innovations, allowing traits such as virulence, antibiotic resistance and xenobiotic metabolism to spread through the human microbiome. Recent anecdotal studies providing snapshots of active gene flow on the human body have highlighted the need to determine the frequency of such recent transfers and the forces that govern these events. Here we report the discovery and characterization of a vast, human-associated network of gene exchange, large enough to directly compare the principal forces shaping HGT. We show that this network of 10,770 unique, recently transferred (more than 99% nucleotide identity) genes found in 2,235 full bacterial genomes, is shaped principally by ecology rather than geography or phylogeny, with most gene exchange occurring between isolates from ecologically similar, but geographically separated, environments. For example, we observe 25-fold more HGT between human-associated bacteria than among ecologically diverse non-human isolates (P = 3.0 × 10(-270)). We show that within the human microbiome this ecological architecture continues across multiple spatial scales, functional classes and ecological niches with transfer further enriched among bacteria that inhabit the same body site, have the same oxygen tolerance or have the same ability to cause disease. This structure offers a window into the molecular traits that define ecological niches, insight that we use to uncover sources of antibiotic resistance and identify genes associated with the pathology of meningitis and other diseases.     

Investigation of Sparse Data Mouse Imaging Using Micro-CT with a Carbon-Nanotube-Based X-ray Source

There has been a renewed interest in algorithm development for image reconstruction from highly incomplete data in computed tomography(CT).Such algorithms may lead to reduced imaging dose and time,and to the design of innovative configurations tailored to specific imaging tasks.In recent years,a carbon-nanotube(CNT)-based field-emission x-ray source has been developed,which offers easy electronic control of radiation and thus can be an ideal candidate for gated imaging.We have recently proposed algorithms f...     

Sexual selection enables long-term coexistence despite ecological equivalence

Empirical data indicate that sexual preferences are critical for maintaining species boundaries, yet theoretical work has suggested that, on their own, they can have only a minimal role in maintaining biodiversity. This is because long-term coexistence within overlapping ranges is thought to be unlikely in the absence of ecological differentiation. Here we challenge this widely held view by generalizing a standard model of sexual selection to include two ubiquitous features of populations with sexual selection: spatial variation in local carrying capacity, and mate-search costs in females. We show that, when these two features are combined, sexual preferences can single-handedly maintain coexistence, even when spatial variation in local carrying capacity is so slight that it might go unnoticed empirically. This theoretical study demonstrates that sexual selection alone can promote the long-term coexistence of ecologically equivalent species with overlapping ranges, and it thus provides a novel explanation for the maintenance of species diversity.     

Patterns and rates of exonic de novo mutations in autism spectrum disorders

Autism spectrum disorders (ASD) are believed to have genetic and environmental origins, yet in only a modest fraction of individuals can specific causes be identified. To identify further genetic risk factors, here we assess the role of de novo mutations in ASD by sequencing the exomes of ASD cases and their parents (n = 175 trios). Fewer than half of the cases (46.3%) carry a missense or nonsense de novo variant, and the overall rate of mutation is only modestly higher than the expected rate. In contrast, the proteins encoded by genes that harboured de novo missense or nonsense mutations showed a higher degree of connectivity among themselves and to previous ASD genes as indexed by protein-protein interaction screens. The small increase in the rate of de novo events, when taken together with the protein interaction results, are consistent with an important but limited role for de novo point mutations in ASD, similar to that documented for de novo copy number variants. Genetic models incorporating these data indicate that most of the observed de novo events are unconnected to ASD; those that do confer risk are distributed across many genes and are incompletely penetrant (that is, not necessarily sufficient for disease). Our results support polygenic models in which spontaneous coding mutations in any of a large number of genes increases risk by 5- to 20-fold. Despite the challenge posed by such models, results from de novo events and a large parallel case-control study provide strong evidence in favour of CHD8 and KATNAL2 as genuine autism risk factors.     

Regulation of cancer cell migration and bone metastasis by RANKL

Bone metastases are a frequent complication of many cancers that result in severe disease burden and pain. Since the late nineteenth century, it has been thought that the microenvironment of the local host tissue actively participates in the propensity of certain cancers to metastasize to specific organs, and that bone provides an especially fertile 'soil'. In the case of breast cancers, the local chemokine milieu is now emerging as an explanation for why these tumours preferentially metastasize to certain organs. However, as the inhibition of chemokine receptors in vivo only partially blocks metastatic behaviour, other factors must exist that regulate the preferential metastasis of breast cancer cells. Here we show that the cytokine RANKL (receptor activator of NF-kappaB ligand) triggers migration of human epithelial cancer cells and melanoma cells that express the receptor RANK. RANK is expressed on cancer cell lines and breast cancer cells in patients. In a mouse model of melanoma metastasis, in vivo neutralization of RANKL by osteoprotegerin results in complete protection from paralysis and a marked reduction in tumour burden in bones but not in other organs. Our data show that local differentiation factors such as RANKL have an important role in cell migration and the tissue-specific metastatic behaviour of cancer cells.