Displacement of plasma protein and conduction velocity in rats under action of acceleration forces and hypokinesia

The permeability of capillary vessels was investigated in order to determine if acceleration alone or following prolonged hypokinesia would induce changes in the vascular wall leading to the penetration by l-albumins and/or proteins with larger molecules. In rats undergoing action of +5 Gz accelerations, no increase in vascular permeability, as tested with the use of (Cr-5k)-globulin, was demostrated. In rats immobilized for 4 weeks before centrifugation, rather weak migration of (Cr-51)-globulin from the vessels was observed. Immobilization resulted also in lowering of conduction velocity in the sciatic nerve

E2F8 is a nonreceptor activator of heterotrimeric G proteins

BACKGROUND: Heterotrimeric G proteins are important for numerous signaling events in eukaryotes, serving primarily to transduce signals that are initiated by G protein-coupled receptors. It has recently become clear that nonreceptor activators can regulate the level of heterotrimeric G protein signaling and, in some cases, drive cycles of receptor-independent G protein activation. In this study, we used a yeast expression cloning strategy to identify novel nonreceptor activators of heterotrimeric G proteins in a human adipocyte cDNA library. RESULTS: The human transcription factor E2F8 was found to activate heterotrimeric G proteins, suggesting a specific biological role for this recently described member of the E2F family. Epistasis studies showed that E2F8 acted at the level of G proteins and was specific for Gα(i )over Gpa1. E2F8 augmented receptor-driven signaling, but also activated G proteins in the absence of a receptor. The GTPase-activating protein RGS4 antagonized the effect of E2F8, showing that E2F8's effect on Gα involved nucleotide turnover. The entire E2F8 protein was required for full activity, but the majority of the signaling activity appeared to reside in the first 200 residues. CONCLUSION: In yeast, E2F8 is a guanine nucleotide exchange factor (GEF) for the α subunit of heterotrimeric G proteins. The molecular mechanism and biological significance of this effect remain to be determined

A repeat sales index for office buildings in New York City, 1900-2000

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Urban Studies and Planning, 2002.Includes bibliographical references.This paper comments on one of the real estate and financial world's most common adages: that real estate is a safe long-term investment that will perform equal to or exceed other common investments, particularly over long stretches of time. With data drawn from a wide range of primary and secondary sources, a repeat sales index of large (250,000+ square foot) commercial building sales in the Midtown and Downtown sub-markets of New York City is created to illustrate how these properties have performed as an inflation-adjusted investment from 1900 through 2000. It differs from other papers that focused on hedonic modeling of building attributes and locational characteristics or that created appraisal-, lease- or property-share returns indices. Although our findings were not statistically significant, appreciation is found to be rather flat over time, appreciating on average between 1/4 to 2/3 percent per year and mirrors the findings of Eichholtz 1997 and Eichholtz & Geltner 2002. This suggests that while commercial office properties may provide investment opportunities when purchased and sold at the right points in the cycle, it tends to under-perform other investment options when carried over time.by Cesarina A. Templeton and Mark S. Baranski.S.M

Determination of oxygen tension in the subcutaneous tissue of cosmonauts during the Salyut-6 mission

A polarographic technique was used to measure the oxygen tension in subcutaneous tissue of the forearm of a cosmonaut prior to, after, and on the fourth day of a space mission performed by Salut-6. A drop in the oxygen exchange rate in the peripheral tissues during weightlessness was observed. The mechanisms of this change are studied, taking into consideration the blood distribution in the organism and microcirculation disorders reflected by a decreased blood flow rate in arterial-venous junctions

Investigation of cooling properties of the gaseous medium of a space station

An investigation of cooling properties of the gaseous medium was performed in the biosatellite Kosmos-936 as well as in the orbital complexes Soyuz-28/Salyut-6 and Soyuz-30/Salyut-6 with the aid of an especially constructed electric dynamic catathermometer. In this instrument current was measured which was necessary to keep a steady settled temperature of the sensing device. The investigation was performed because of the disturbed heat exhange of the human body caused by lack of natural convection in weightlessness. The instrument also enabled objective estimation of the temperature of the cosmonaut's ody in six optionally selected regions. The results obtained by means of the catathermometer will also enable defining the appropriate hygienic conditions of the gaseous medium of space stations

Treatment of nephrotic syndrome with adrenocorticotropic hormone (ACTH) gel

Andrew S Bomback1, James A Tumlin2, Joel Baranski3, James E Bourdeau4, Anatole Besarab5, Alice S Appel1, Jai Radhakrishnan1, Gerald B Appel11Department of Medicine, Division of Nephrology, Columbia University College of Physicians and Surgeons, New York, NY, USA; 2Department of Internal Medicine, Division of Nephrology, University of Tennessee College of Medicine in Chattanooga, Chattanooga, TN, USA; 3Balboa Nephrology Medical Group, San Diego, CA, USA; 4Nephrology Specialists of Oklahoma, Tulsa, OK, USA; 5Department of Medicine, Division of Nephrology and Hypertension, Henry Ford Health System, Detroit, MI, USAPurpose: A synthetic adrenocorticotropin (ACTH) analog has shown efficacy in Europe as primary and secondary therapy for nephrotic syndrome, but there is no published experience using the natural, highly purified ACTH gel formulation, available in the United States, for nephrotic syndrome. We therefore investigated the use of ACTH gel for nephrotic syndrome in the United States.Patients and methods: Twenty-one patients with nephrotic syndrome treated with ACTH gel outside of research settings in the United States, with initiation of therapy by December 31, 2009, allowing a minimum 6 months follow-up. We defined complete remission as stable renal function with proteinuria falling to <500 mg/day, and partial remission as stable renal function with >50% reduction in proteinuria from 500 to 3500 mg/day.Results: Twenty-one patients with nephrotic syndrome were treated: 11 with idiopathic membranous nephropathy (iMN), 4 with membranoproliferative glomerulonephritis (MPGN), 1 with focal segmental glomerulosclerosis (FSGS), 1 with minimal change disease (MCD), 1 with immunoglobulin A (IgA) nephropathy, 1 with class V systemic lupus erythematosus (SLE) glomerulonephritis, 1 with monoclonal diffuse proliferative glomerulonephritis, and 1 with unbiopsied nephrotic syndrome. ACTH was used as primary therapy for 3 patients; the remaining patients had previously failed a mean 2.3 immunosuppressive regimens. Eleven patients achieved a complete or partial remission, with 4 (19%) in complete remission. Of the 11 patients who achieved remission, 9 had iMN, 1 had FSGS, and 1 had IgA nephropathy. Of the 11 patients with iMN, 3 (27%) achieved complete remission and 6 (55%) achieved partial remission despite having previously failed a mean 2.4 therapies. Five patients reported steroid-like adverse effects, but there were no severe infections. The limitations were retrospective data analysis with short-term follow-up.Conclusion: ACTH gel may be a viable treatment option for resistant nephrotic syndrome due to membranous nephropathy. Short-term data suggest that remission rates may approach 80%.Keywords: nephrotic syndrome, membranous nephropathy, chronic kidney diseas

A Drosophila functional evaluation of candidates from human genome-wide association studies of type 2 diabetes and related metabolic traits identifies tissue-specific roles for dHHEX

BACKGROUND: Genome-wide association studies (GWAS) identify regions of the genome that are associated with particular traits, but do not typically identify specific causative genetic elements. For example, while a large number of single nucleotide polymorphisms associated with type 2 diabetes (T2D) and related traits have been identified by human GWAS, only a few genes have functional evidence to support or to rule out a role in cellular metabolism or dietary interactions. Here, we use a recently developed Drosophila model in which high-sucrose feeding induces phenotypes similar to T2D to assess orthologs of human GWAS-identified candidate genes for risk of T2D and related traits. RESULTS: Disrupting orthologs of certain T2D candidate genes (HHEX, THADA, PPARG, KCNJ11) led to sucrose-dependent toxicity. Tissue-specific knockdown of the HHEX ortholog dHHEX (CG7056) directed metabolic defects and enhanced lethality; for example, fat-body-specific loss of dHHEX led to increased hemolymph glucose and reduced insulin sensitivity. CONCLUSION: Candidate genes identified in human genetic studies of metabolic traits can be prioritized and functionally characterized using a simple Drosophila approach. To our knowledge, this is the first large-scale effort to study the functional interaction between GWAS-identified candidate genes and an environmental risk factor such as diet in a model organism system

Quantitative trait loci and genes associated with salmonid alphavirus load in Atlantic salmon:implications for pancreas disease resistance and tolerance

publishedVersio

A linkage map of the Atlantic salmon (Salmo salar) based on EST-derived SNP markers

<p>Abstract</p> <p>Background</p> <p>The Atlantic salmon is a species of commercial and ecological significance. Like other salmonids, the species displays residual tetrasomy and a large difference in recombination rate between sexes. Linkage maps with full genome coverage, containing both type I and type II markers, are needed for progress in genomics. Furthermore, it is important to estimate levels of linkage disequilibrium (LD) in the species. In this study, we developed several hundred single nucleotide polymorphism (SNP) markers for the Atlantic salmon, and constructed male and female linkage maps containing SNP and microsatellite markers. We also investigated further the distribution of male and female recombination events across the genome, and estimated levels of LD between pairs of markers.</p> <p>Results</p> <p>The male map had 29 linkage groups and was 390 cM long. The female map had 30 linkage groups as was 1983 cM long. In total, the maps contained 138 microsatellite markers and 304 SNPs located within genes, most of which were successfully annotated. The ratio of male to female recombination events was either close to zero or very large, indicating that there is little overlap between regions in which male and female crossovers occur. The female map is likely to have close to full genome coverage, while the majority of male linkage groups probably lack markers in telomeric regions where male recombination events occur. Levels of r²increased with decreasing inter-marker distance in a bimodal fashion; increasing slowly from ~60 cM, and more rapidly more from ~12 cM. Long-ranging LD may be consequence of recent admixture in the population, the population being a 'synthetic' breeding population with contributions from several distinct rivers. Levels of r²dropped to half its maximum value (above baseline) within 15 cM, and were higher than 0.2 above baseline for unlinked markers ('useful LD') at inter-marker distances less than 5 cM.</p> <p>Conclusion</p> <p>The linkage map presented here is an important resource for genetic, comparative, and physical mapping of the Atlantic salmon. The female map is likely to have a map coverage that is not far from complete, whereas the male map length is likely to be significantly shorter than the true map, due to suboptimal marker coverage in the apparently small physical regions where male crossovers occur. 'Useful LD' was found at inter-marker distances less than 5 cM.</p