Analysis of integration error in the ODP-L program and the effect of selenopotential parameters on the solution vector

Analysis of integration error in lunar orbit trajectory program and effect of selenopotential parameters on solution vecto

Differential correction and preliminary orbit determination for lunar satellite orbits

Differential correction and preliminary orbit calculation for lunar satellite orbit

Inflammatory Airway Disease of Horses - Revised Consensus Statement

The purpose of this manuscript is to revise and update the previous consensus statement on inflammatory airway disease (IAD) in horses. Since 2007, a large number of scientific articles have been published on the topic and these new findings have led to a significant evolution of our understanding of IAD

Glutamate Cysteine Ligase-Modulatory Subunit Knockout Mouse Shows Normal Insulin Sensitivity but Reduced Liver Glycogen Storage.

Glutathione (GSH) deficits have been observed in several mental or degenerative illness, and so has the metabolic syndrome. The impact of a decreased glucose metabolism on the GSH system is well-known, but the effect of decreased GSH levels on the energy metabolism is unclear. The aim of the present study was to investigate the sensitivity to insulin in the mouse knockout (KO) for the modulatory subunit of the glutamate cysteine ligase (GCLM), the rate-limiting enzyme of GSH synthesis. Compared to wildtype (WT) mice, GCLM-KO mice presented with reduced basal plasma glucose and insulin levels. During an insulin tolerance test, GCLM-KO mice showed a normal fall in glycemia, indicating normal insulin secretion. However, during the recovery phase, plasma glucose levels remained lower for longer in KO mice despite normal plasma glucagon levels. This is consistent with a normal counterregulatory hormonal response but impaired mobilization of glucose from endogenous stores. Following a resident-intruder stress, during which stress hormones mobilize glucose from hepatic glycogen stores, KO mice showed a lower hyperglycemic level despite higher plasma cortisol levels when compared to WT mice. The lower hepatic glycogen levels observed in GCLM-KO mice could explain the impaired glycogen mobilization following induced hypoglycemia. Altogether, our results indicate that reduced liver glycogen availability, as observed in GCLM-KO mice, could be at the origin of their lower basal and challenged glycemia. Further studies will be necessary to understand how a GSH deficit, typically observed in GCLM-KO mice, leads to a deficit in liver glycogen storage

Hsp27 regulates podocyte cytoskeletal changes in an in vitro model of podocyte process retraction

Nephrotic syndrome (NS) is characterized by structural changes in the actin‐rich foot processes of glomerular podocytes. We previously identified high concentrations of the small heat shock protein hsp27 within podocytes as well as increased glomerular accumulation and phosphorylation of hsp27 in puromycin aminonucleoside (PAN) ‐induced experimental NS. Here we analyzed murine podocytes stably transfected with hsp27 sense, antisense, and vector control constructs using a newly developed in vitro PAN model system. Cell morphology and the microfilament structure of untreated sense and antisense transfectants were altered compared with controls. Vector cell survival, polymerized actin content, cell area, and hsp27 content increased after 1.25 μg/ml PAN treatment and decreased after 5.0 μg/ml treatment. In contrast, sense cells were unaffected by 1.25 μg/ml PAN treatment whereas antisense cells showed decreases or no changes in all parameters. Treatment of sense cells with 5.0 μ g/ml PAN resulted in increased cell survival and cell area whereas antisense cells underwent significant decreases in all parameters. Hsp27 provided dramatic protection against PAN‐induced microfilament disruption in sense > vector > antisense cells. We conclude that hsp27 is able to regulate both the morphological and actin cytoskeletal response of podocytes in an in vitro model of podocyte injury.—Smoyer, W. E., Ransom, R. F. Hsp27 regulates podocyte cytoskeletal changes in an in vitro model of podocyte process retraction. FASEB J. 16, 315–326 (2002)Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154256/1/fsb2fj010681com.pd

Complete analysis of the B-cell response to a protein antigen, from in vivo germinal centre formation to 3-D modelling of affinity maturation

Somatic hypermutation of immunoglobulin variable region genes occurs within germinal centres (GCs) and is the process responsible for affinity maturation of antibodies during an immune response. Previous studies have focused almost exclusively on the immune response to haptens, which may be unrepresentative of epitopes on protein antigens. In this study, we have exploited a model system that uses transgenic B and CD4<sup>+</sup> T cells specific for hen egg lysozyme (HEL) and a chicken ovalbumin peptide, respectively, to investigate a tightly synchronized immune response to protein antigens of widely differing affinities, thus allowing us to track many facets of the development of an antibody response at the antigen-specific B cell level in an integrated system <i>in</i> <i>vivo</i>. Somatic hypermutation of immunoglobulin variable genes was analysed in clones of transgenic B cells proliferating in individual GCs in response to HEL or the cross-reactive low-affinity antigen, duck egg lysozyme (DEL). Molecular modelling of the antibody–antigen interface demonstrates that recurring mutations in the antigen-binding site, selected in GCs, enhance interactions of the antibody with DEL. The effects of these mutations on affinity maturation are demonstrated by a shift of transgenic serum antibodies towards higher affinity for DEL in DEL-cOVA immunized mice. The results show that B cells with high affinity antigen receptors can revise their specificity by somatic hypermutation and antigen selection in response to a low-affinity, cross-reactive antigen. These observations shed further light on the nature of the immune response to pathogens and autoimmunity and demonstrate the utility of this novel model for studies of the mechanisms of somatic hypermutation