T cells develop in the thymus through positive and negative selection, which are responsible for shaping the T cell receptor (TCR) repertoire. To elucidate the molecular mechanisms involved in selection remains an area of intense interest. Here, we identified and characterized a gene product Gasp (Grb2-associating protein, also called Themis) that is critically required for positive selection. Gasp is a cytosolic protein with no known functional motifs that is expressed only in T cells, especially immature CD4/CD8 double positive (DP) thymocytes. In the absence of Gasp, differentiation of both CD4 and CD8 single positive cells in the thymus was severely inhibited, whereas all other TCRinduced events such as -selection, negative selection, peripheral activation, and homeostatic proliferation were unaffected. We found that Gasp constitutively associates with Grb2 via its N-terminal Src homology 3 domain, suggesting that Gasp acts as a thymocytespecific adaptor for Grb2 or regulates Ras signaling in DP thymocytes. Collectively, we have described a gene called Gasp that is critical for positive selection. (2). The fate of individual DP thymocytes is determined by the strength of affinity and longevity of interaction between their TCR and peptide:MHC ligand (3). Although it is known that strong TCR/ligand interaction leads to negative selection and weak association results in positive selection (4), how this quantitative difference of TCR interaction can be converted to the qualitative difference is not known. Therefore, it is important to investigate the difference in molecular mechanisms of positive and negative selection.
The urinary excretion of chiro-inositol was much lower in the diabetic patients (32.3 +/- 16.0 mumol/day, means +/- SD) than in the NGT subjects (96.0 +/- 17.6; P < 0.0001) and IGT subjects (58.9 +/- 11.6; P < 0.0001). SI was much lower in the diabetic patients (3.81 +/- 1.49) than in the NGT subjects 6.30 +/- 1.59, P < 0.0005). SG was much lower in the diabetic patients (2.14 +/- 0.56) than in the NGT subjects (3.07 +/- 0.38, P < 0.0001). There was a significant correlation between urinary chiro-inositol excretion and SI (r = 0.766), as well as a significant correlation between urinary chiro-inositol excretion and SG (r = 0.747).
We investigated the numbers of planktonic and biofilm cells and the expression levels of genes encoding efflux pumps and biofilm-related proteins in 10 clinical isolates of multi-drug resistant Acinetobacter baumannii (MDRA) as well as in its standard strain ATCC 19606 in the presence of colistin (CST), polymyxin B (PMB), minomycin (MIN), and tigecycline (TGC) at their respective sub-MICs. The number of planktonic and biofilm cells of ATCC 19606 decreased in the presence of all aforementioned antibiotics in a dose-dependent manner. Cell number also decreased in two representative MDRA strains, R2 and R3, in the presence of MIN and TGC in a dose-dependent manner. In contrast, the number of biofilm cells in these two strains increased in the presence of CST, while they increased significantly in the presence of PMB in R2 only. Pearson correlation analysis revealed that the number of biofilm cells was positively and significantly correlated with the mRNA levels of genes encoding efflux pumps (adeB and adeG) and autoinducer synthase (abaI) in strain R2 and adeB, adeG, adeJ, poly-acetyl-glucosamine-porin (pgaA), and abaI in strain R3 in the presence of CST. It was positively and significantly correlated with the mRNA levels of genes encoding adeB in strain R2 and an outer membrane protein A (ompA) and biofilm-associated protein (bap) in strain R3 in the presence of PMB. These results provide valuable insights into the biofilm formation potency of clinical isolates of MDRA that depends on efflux pumps and biofilm-related genes and its regulation by antibiotics.
The objective of this study is to identify the dimensions that determine the customers' evaluation of service quality in academic libraries. One university library each in England and Finland and two in Japan were selected to conduct a questionnaire survey based on the GAP theory of SERVQUAL that has led discussions on the assessment of service quality in marketing theory and practice. Since the actual delivery of information as a service outcome is as important as the service process in libraries, attributes inherent to libraries were incorporated into the survey. Subjecting data obtained to exploratory and confirmatory factor analysis showed that library service quality consists of four dimensions: effect of service (personal), library as ba (place), collections and access, and effect of service (organizational), which are different from the five SERVQUAL dimensions: tangibles, reliability, responsiveness, assurance, and empathy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.