Regulation of rat renal (Na(+) + K+)-adenosine triphosphatase mRNA levels by corticosterone.

We investigated the mechanisms for glucocorticoid regulation of rat renal NaK-ATPase activity. Our findings suggest that the magnitudes of corticosterone-induced increases in alpha 1 mRNA and beta 1 mRNA levels are similar in the kidney of the adult adrenalectomized rats. The results also suggest that corticosterone restores NaK-ATPase activity in adrenalectomized rats prior to any enhanced sodium delivery.     

In vivo imaging of Treg cells providing immune privilege to the haematopoietic stem-cell niche

Stem cells reside in a specialized regulatory microenvironment or niche, where they receive appropriate support for maintaining self-renewal and multi-lineage differentiation capacity. The niche may also protect stem cells from environmental insults including cytotoxic chemotherapy and perhaps pathogenic immunity. The testis, hair follicle and placenta are all sites of residence for stem cells and are immune-suppressive environments, called immune-privileged sites, where multiple mechanisms cooperate to prevent immune attack, even enabling prolonged survival of foreign allografts without immunosuppression. We sought to determine if somatic stem-cell niches more broadly are immune-privileged sites by examining the haematopoietic stem/progenitor cell (HSPC) niche in the bone marrow, a site where immune reactivity exists. We observed persistence of HSPCs from allogeneic donor mice (allo-HSPCs) in non-irradiated recipient mice for 30?days without immunosuppression with the same survival frequency compared to syngeneic HSPCs. These HSPCs were lost after the depletion of FoxP3 regulatory T (T(reg)) cells. High-resolution in vivo imaging over time demonstrated marked co-localization of HSPCs with T(reg) cells that accumulated on the endosteal surface in the calvarial and trabecular bone marrow. T(reg) cells seem to participate in creating a localized zone where HSPCs reside and where T(reg) cells are necessary for allo-HSPC persistence. In addition to processes supporting stem-cell function, the niche will provide a relative sanctuary from immune attack.     

Bayesian structure selection for vector autoregression model

A vector autoregression (VAR) model is powerful for analyzing economic data as it can be used to simultaneously handle multiple time series from different sources. However, in the VAR model, we need to address the problem of substantial coefficient dimensionality, which would cause some computational problems for coefficient inference. To reduce the dimensionality, one could take model structures into account based on prior knowledge. In this paper, group structures of the coefficient matrices are considered. Because of the different types of VAR structures, corresponding Markov chain Monte Carlo algorithms are proposed to generate posterior samples for performing inference of the structure selection. Simulation studies and a real example are used to demonstrate the performances of the proposed Bayesian approaches.     

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P?相似文献   

Solid-liquid iron partitioning in Earth's deep mantle

Melting processes in the deep mantle have important implications for the origin of the deep-derived plumes believed to feed hotspot volcanoes such as those in Hawaii. They also provide insight into how the mantle has evolved, geochemically and dynamically, since the formation of Earth. Melt production in the shallow mantle is quite well understood, but deeper melting near the core-mantle boundary remains controversial. Modelling the dynamic behaviour of deep, partially molten mantle requires knowledge of the density contrast between solid and melt fractions. Although both positive and negative melt buoyancies can produce major chemical segregation between different geochemical reservoirs, each type of buoyancy yields drastically different geodynamical models. Ascent or descent of liquids in a partially molten deep mantle should contribute to surface volcanism or production of a deep magma ocean, respectively. We investigated phase relations in a partially molten chondritic-type material under deep-mantle conditions. Here we show that the iron partition coefficient between aluminium-bearing (Mg,Fe)SiO(3) perovskite and liquid is between 0.45 and 0.6, so iron is not as incompatible with deep-mantle minerals as has been reported previously. Calculated solid and melt density contrasts suggest that melt generated at the core-mantle boundary should be buoyant, and hence should segregate upwards. In the framework of the magma oceans induced by large meteoritic impacts on early Earth, our results imply that the magma crystallization should push the liquids towards the surface and form a deep solid residue depleted in incompatible elements.     

Effects of cholesterol-derived photoproducts on the incorporation of14C-acetate into human skin lipids

Zusammenfassung Hautbestrahlung beim Menschen mit Xenon- oder UV-Licht und die dabei beobachteten chemischen Vorgänge (Hemmung von 1-¹⁴C-Azetat und Einbau in die Gesamtlipide) legen eine mögliche Relation zwischen Photoproduktbildung und lichtinduzierter Hemmung der Lipogenese nahe.

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Supported in part by The Robert A. Welch Foundation Grant No. Q-253 and USPHS Grant No. EC00110-83.     

Monoclonal antibody production by receptor-mediated electrically induced cell fusion

Fusion of myeloma cells and B lymphocytes to form hybridomas which produce monoclonal antibodies has been a major advance, but the poor efficiency and randomness of viral or polyethylene glycol fusion techniques generally gives poor yields of specific, high affinity antibodies. High voltage electrical fields with dielectrophoresis to ensure cell alignment can fuse a limited number of cells under direct microscopic examination, but it is not possible to identify B-cells destined to secrete relevant antibodies. However, B-cells express, on their surface, antigen receptor immunoglobulins of the same antigenic specificity as the secreted antibodies. Binding of antigen to surface immunoglobulins stimulates proliferation and differentiation of B-cells into plasma cells. Here we report the use of the selective, high affinity interaction of antigen with surface immunoglobulins on B-cells to facilitate a close adherence to myeloma cells. The antigen, covalently conjugated to avidin, binds to the surface immunoglobulins on B-cells. This B-cell-antigen-avidin complex binds to biotin covalently attached to the surface of myeloma cells. An intense electric field across a bulk cell suspension then produces selective fusion of cells in contact, that is, of myeloma cells with B-cells which make the appropriate antibody. We have used this technique with several antigens, and all resultant hybridomas secrete appropriate antibodies with very high affinity.     

Protein degradation and protection against misfolded or damaged proteins

The ultimate mechanism that cells use to ensure the quality of intracellular proteins is the selective destruction of misfolded or damaged polypeptides. In eukaryotic cells, the large ATP-dependent proteolytic machine, the 26S proteasome, prevents the accumulation of non-functional, potentially toxic proteins. This process is of particular importance in protecting cells against harsh conditions (for example, heat shock or oxidative stress) and in a variety of diseases (for example, cystic fibrosis and the major neurodegenerative diseases). A full understanding of the pathogenesis of the protein-folding diseases will require greater knowledge of how misfolded proteins are recognized and selectively degraded.