Vaspin inhibits kallikrein 7 by serpin mechanism

The molecular target of the adipokine vaspin (visceral adipose tissue-derived serpin; serpinA12) and its mode of action are unknown. Here, we provide the vaspin crystal structure and identify human kallikrein 7 (hK7) as a first protease target of vaspin inhibited by classical serpin mechanism with high specificity in vitro. We detect vaspin–hK7 complexes in human plasma and find co-expression of both proteins in murine pancreatic β-cells. We further demonstrate that hK7 cleaves human insulin in the A- and B-chain. Vaspin treatment of isolated pancreatic islets leads to increased insulin concentration in the media upon glucose stimulation without influencing insulin secretion. By application of vaspin and generated inactive mutants, we find the significantly improved glucose tolerance in C57BL/6NTac and db/db mice treated with recombinant vaspin fully dependent on the vaspin serpin activity and not related to vaspin-mediated changes in insulin sensitivity as determined by euglycemic-hyperinsulinemic clamp studies. Improved glucose metabolism could be mediated by increased insulin plasma concentrations 150 min after a glucose challenge in db/db mice, supporting the hypothesis that vaspin may inhibit insulin degradation by hK7 in the circulation. In conclusion, we demonstrate the inhibitory serpin nature and the first protease target of the adipose tissue-derived serpin vaspin, and our findings suggest hK7 inhibition by vaspin as an underlying physiological mechanism for its compensatory actions on obesity-induced insulin resistance.     

Morpho-sedimentary unit signatures associated with micro-estuaries in Barnegat Bay national estuary, New Jersey, the USA

Incorporation of the Barnegat Bay into the US National Estuary Program has triggered collection and collation of basic data sets appropriate to estuarine management. Gathering of water quality and quantity as well as basic geological data is adding to the knowledge of the complexity of the bay. An ongoing program of systematic sampling of bottom sediments in the large bay and intense sampling in the many micro-estuaries along the mainland margin is demonstrating the presence of localized mor-pho-sedimentological units related to the interaction of the fluvial, tidal, and wave processes active in the bay. Mean grain sizes and standard deviation measures assist in the development of signatures of bottom sediment types.     

A filament of dark matter between two clusters of galaxies

It is a firm prediction of the concordance cold-dark-matter cosmological model that galaxy clusters occur at the intersection of large-scale structure filaments. The thread-like structure of this 'cosmic web' has been traced by galaxy redshift surveys for decades. More recently, the warm–hot intergalactic medium (a sparse plasma with temperatures of 10(5) kelvin to 10(7) kelvin) residing in low-redshift filaments has been observed in emission and absorption. However, a reliable direct detection of the underlying dark-matter skeleton, which should contain more than half of all matter, has remained elusive, because earlier candidates for such detections were either falsified or suffered from low signal-to-noise ratios and unphysical misalignments of dark and luminous matter. Here we report the detection of a dark-matter filament connecting the two main components of the Abell 222/223 supercluster system from its weak gravitational lensing signal, both in a non-parametric mass reconstruction and in parametric model fits. This filament is coincident with an overdensity of galaxies and diffuse, soft-X-ray emission, and contributes a mass comparable to that of an additional galaxy cluster to the total mass of the supercluster. By combining this result with X-ray observations, we can place an upper limit of 0.09 on the hot gas fraction (the mass of X-ray-emitting gas divided by the total mass) in the filament.     

Drosophila and the genetics of the internal milieu

'Homeostasis', from the Greek words for 'same' and 'steady', refers to ways in which the body acts to maintain a stable internal environment despite perturbations. Recent studies in Drosophila exemplify the conservation of regulatory mechanisms involved in metabolic homeostasis. These new findings underscore the use of Drosophila as a model for the study of various human disorders.     

Re-evaluation of the phylogenetic position of the genus Dexiotrichides (Protozoa, Ciliophora, Scuticociliatida) inferred from stomatogenetic and molecular information for Dexiotrichides pangi

The divisional process and systematic position of the marine scuticociliate Dexiotrichides pangi are studied. Based on both stomatogenetic data and 18S rDNA gene sequences, the phylogeny and morphogenetic characteristics of this taxon, and of other related genera, are analyzed and discussed. Both the divisionary events and the molecular biological data indicate that this speciesgenus, together with certain other genera in the Dexiotricha-complex, occupies an intermediate position between the tetrahymenids and the “typical” scuticociliate, which suggests that the Dexiotricha-like taxa should be excluded from the “true” scuticociliates. As a further contribution, the process of stomatogenesis in D. pangi can be summarized as follows: (1) The oral primordia in the opisthe are formed only by the proliferation of basal bodies in the scutica field, which subsequently develop into three membranelles, while the new paroral membrane seems to be generated by the sub-anterior portion of somatic kinety 1 (the 1st postoral intercalary kinety). The latter character exhibits a mode similar to Tetrahymena. (2) In the proter the parental membranelles are retained and remain unchanged throughout the entire division process; only the old paroral membrane is disassembled and differentiated into the anlage, which then gives rise to the new paroral membrane and the scutica of the proter. The 18S rRNA gene sequence reported here is the first one for a ciliate in the Dexiotricha-complex.     

Identification of renal Cd36 as a determinant of blood pressure and risk for hypertension

To identify renally expressed genes that influence risk for hypertension, we integrated expression quantitative trait locus (QTL) analysis of the kidney with genome-wide correlation analysis of renal expression profiles and blood pressure in recombinant inbred strains derived from the spontaneously hypertensive rat (SHR). This strategy, together with renal transplantation studies in SHR progenitor, transgenic and congenic strains, identified deficient renal expression of Cd36 encoding fatty acid translocase as a genetically determined risk factor for spontaneous hypertension.     

Exploiting position effects and the gypsy retrovirus insulator to engineer precisely expressed transgenes

A major obstacle to creating precisely expressed transgenes lies in the epigenetic effects of the host chromatin that surrounds them. Here we present a strategy to overcome this problem, employing a Gal4-inducible luciferase assay to systematically quantify position effects of host chromatin and the ability of insulators to counteract these effects at phiC31 integration loci randomly distributed throughout the Drosophila genome. We identify loci that can be exploited to deliver precise doses of transgene expression to specific tissues. Moreover, we uncover a previously unrecognized property of the gypsy retrovirus insulator to boost gene expression to levels severalfold greater than at most or possibly all un-insulated loci, in every tissue tested. These findings provide the first opportunity to create a battery of transgenes that can be reliably expressed at high levels in virtually any tissue by integration at a single locus, and conversely, to engineer a controlled phenotypic allelic series by exploiting several loci. The generality of our approach makes it adaptable to other model systems to identify and modify loci for optimal transgene expression.