Geomorphology and Quaternary History of Shell Valley, Bighorn County, Wyoming

Shell Valley, from the mouth of Shell Canyon, to its junction with the Bighorn Hiver in east-central Bighorn County, Wyoming, was mapped and the fluvial landforms were described in detail. The morphologic features of this valley and its major tributaries are largely the product of structurally-controlled stream erosion and alluviation. Their disposition indicates that they have been produced by lateral planation, slope retreat, simple downcutting, and downcutting accompanied by lateral migration of the stream, all of which are still active. Correlation of the local features with some more regional features, which have been dated, indicates that much of the Erosional history of Shell Valley was confined to the Pleistocene

Therapeutic concentrations of cyclosporine A, but not FK506, increase P-glycoprotein expression in endothelial and renal tubule cells

Therapeutic concentrations of cyclosporine A, but not FK506, increase P-glycoprotein expression in endothelial and renal tubule cells.BackgroundThe immunosuppressive drugs cyclosporine A (CsA) and tacrolimus (FK506) are extruded from cells by the multidrug resistance P-glycoprotein (P-gp), an efflux pump for drugs and xenobiotics, which may limit their therapeutic effectiveness and/or incidence of toxic side effects. In the present study, we investigated the effect of therapeutic concentrations of CsA and FK506 on the expression of P-gp in cultured endothelial and proximal tubule cells.MethodsP-gp expression in human arterial endothelial (HAEC) and rat proximal tubule cells (RPTC) was determined by immunoblotting and immunocytochemistry, and correlated with P-gp-mediated transport by measuring the intracellular accumulation of the fluorescent probe calcein.ResultsFollowing incubation of HAEC with therapeutic concentrations of 0.1 to 1.6 μm CsA up to seven days, P-gp expression increased in a time- and concentration-dependent manner, maximally to 291 ± 42% of controls with 0.8 μm CsA for seven days. Similar effects of CsA were observed in RPTC. In contrast, therapeutic concentrations of FK506 (0.01 to 0.2 μm up to 7days) did not change P-gp expression in either cell type, though at higher, supratherapeutic concentrations of FK506 (0.6 to 1.2 μm) P-gp expression was also increased. Immunocytochemistry revealed increased P-gp expression in the plasma membrane of HAEC and RPTC treated with 0.8 μm CsA, which was reflected by a decrease of P-gp-mediated accumulation of calcein in both cell types.ConclusionsThe data suggest that the induction of P-gp expression in HAEC and RPTC at concentrations of CsA or FK506 above 0.5 μm is part of the protective answer of cells to toxic concentrations of the drugs and could therefore interfere with the therapeutic effectiveness of CsA in vivo

The ring between ring fingers (RBR) protein family

An overview of the large and functionally diverse RBR protein family that mediates protein-protein interactions of various kinds in development and disease

Isolation and functional characterization of calcitonin-like diuretic hormone receptors in <em>Rhodnius prolixus</em>

Several families of diuretic hormones exist in insects, one of which is the calcitonin-like diuretic hormone (CT/DH) family. CT/DH mediates its effects by binding to family B G-protein coupled receptors (GPCRs). Here we isolate and functionally characterize two R. prolixusCT/DH receptor paralogs (Rhopr-CT/DH-R1 and Rhopr-CT/DH-R2) using a novel heterologous assay utilizing a modified human embryonic kidney 293 (HEK293) cell line. Rhopr-CT/DH-R1 is orthologous to the previously characterized D. melanogasterCT/DH receptor (CG17415) while Rhopr-CT/DH-R2 is orthologous to the D. melanogaster receptor (CG4395), an orphan receptor whose ligand was unknown until now. We determine the cDNA sequences of three splice variants encoding Rhopr-CT/DH-R1 (Rhopr-CT/DH-R1-A, Rhopr-CT/DH-R1-B and Rhopr-CT/DH-R1-C) and two splice variants encoding Rhopr-CT/DH-R2 (Rhopr-CT/DH-R2-A and Rhopr-CT/DH-R2-B). Rhopr-CT/DH-R1-A and Rhopr-CT/DH-R2-A encode truncated receptors that lack six and seven of the characteristic seven transmembrane domains, respectively. Rhopr-CT/DH-R1-B and Rhopr-CT/DH-R1-C, which only differ by 2 amino acids in their C-terminal domain, can both be activated by Rhopr-CT/DH at equal sensitivities (EC50 = 200-300 nM). Interestingly, Rhopr-CT/DH-R2-B is much more sensitive to Rhopr-CT/DH (EC50 = 15 nM) compared to Rhopr-CT/DH-R1-B/C and also yields a much greater response (amplitude) in our heterologous assay. This is the first study to reveal that insects possess at least two CT/DH receptors, which may be functionally different. Quantitative PCR demonstrates that Rhopr-CT/DH-R1 and Rhopr-CT/DH-R2 have distinct expression patterns, with both receptors expressed centrally and peripherally. Moreover, the expression analysis also identified novel target tissues for this neuropeptide, including testes, ovaries and prothoracic glands, suggesting a possible role for Rhopr-CT/DH in reproductive physiology and development

Environment sensing and response mediated by ABC transporters

<p>Abstract</p> <p>Background</p> <p>Transporter proteins are one of an organism’s primary interfaces with the environment. The expressed set of transporters mediates cellular metabolic capabilities and influences signal transduction pathways and regulatory networks. The functional annotation of most transporters is currently limited to general classification into families. The development of capabilities to map ligands with specific transporters would improve our knowledge of the function of these proteins, improve the annotation of related genomes, and facilitate predictions for their role in cellular responses to environmental changes.</p> <p>Results</p> <p>To improve the utility of the functional annotation for ABC transporters, we expressed and purified the set of solute binding proteins from <it>Rhodopseudomonas palustris</it> and characterized their ligand-binding specificity. Our approach utilized ligand libraries consisting of environmental and cellular metabolic compounds, and fluorescence thermal shift based high throughput ligand binding screens. This process resulted in the identification of specific binding ligands for approximately 64% of the purified and screened proteins. The collection of binding ligands is representative of common functionalities associated with many bacterial organisms as well as specific capabilities linked to the ecological niche occupied by <it>R. palustris</it>.</p> <p>Conclusion</p> <p>The functional screen identified specific ligands that bound to ABC transporter periplasmic binding subunits from <it>R. palustris</it>. These assignments provide unique insight for the metabolic capabilities of this organism and are consistent with the ecological niche of strain isolation. This functional insight can be used to improve the annotation of related organisms and provides a route to evaluate the evolution of this important and diverse group of transporter proteins.</p

Die volkswirtschaftliche Bedeutung der Familienunternehmen

Das Erkenntnisinteresse vielfältiger empirischer Studien und Untersuchungen richtet sich vornehmlich auf die börsennotierten und i.d.R. großen Unternehmen sowie die kleinen und mittleren Unternehmen. Große Familienunternehmen hingegen werden in der breiten Öffentlichkeit nicht mit einer ähnlich hohen Aufmerksamkeit bedacht, sei es, dass sie selber weniger Medienaufmerksamkeit suchen oder z.B. nicht wie große börsennotierte Unternehmen das Interesse eines breiten Anlegerkreises wecken müssen. Sie stehen daher nicht so sehr im Fokus der Öffentlichkeit und über ihre gesamtwirtschaftliche Leistung ist wenig bekannt. Die vorliegende Untersuchung soll diese Lücke schließen und dazu beitragen, die Informationslage über die volkswirtschaftliche Bedeutung der großen Familienunternehmen zu verbessern. --