Adoptive transfer of P14 TCR transgenic cells demonstrated that the increased expansion of effector cells was T cell autonomous. After rechallenge, effector CD8(+)

T cells in mutant animals were more skewed to memory phenotype than cells from wild-type mice, resulting in a larger secondary memory CD8(+) T cell pool. During chronic find more viral infection, increased antigen-specific CD8(+) T cells accumulated in the spleens of PrdxII mutant mice, causing mortality. These results demonstrate that PrdxII controls effector CD8(+) T cell expansion, secondary memory generation, and immunopathology.”
“Which of the newer drugs is best for a patient with diabetes who needs to get her glycated hemoglobin level down to 7.0%? See our latest Clinical Decisions article on managing complicated diabetes; vote and comment at NEJM.org. StageAgnes is a 51-year-old widow with hypertension who received a diagnosis of type 2 diabetes a decade ago. She has been worried about her diabetes since then because she has not been able to gain complete control over it. Her glycated hemoglobin level was 7.0% for 1 year but gradually increased to 9.0%. For the

past 2 years, she has been taking metformin. She is maintaining her weight at 165 pounds (75 kg), but she is not able to lose weight. Agnes goes to the gym and walks on a treadmill three times a week, but she jokes …”
“The entry of the enveloped Rift Valley fever virus (RVFV) into its host cell is mediated by the viral glycoproteins Gn and Gc. We investigated the RVFV entry process and, in particular, its Selleck Z-IETD-FMK pH-dependent activation mechanism using our recently developed nonspreading-RVFV-particle system. Entry of the virus into the host cell was efficiently inhibited by lysosomotropic agents that prevent endosomal acidification and

by compounds that interfere with dynamin-and clathrin-dependent endocytosis. Exposure of plasma membrane-bound virions to an acidic pH (<pH 6) equivalent to the pH of late 8-Bromo-cAMP datasheet endolysosomal compartments allowed the virus to bypass the endosomal route of infection. Acid exposure of virions in the absence of target membranes triggered the class II-like Gc fusion protein to form extremely stable oligomers that were resistant to SDS and temperature dissociation and concomitantly compromised virus infectivity. By targeted mutagenesis of conserved histidines in Gn and Gc, we demonstrated that mutation of a single histidine (H857) in Gc completely abrogated virus entry, as well as acid-induced Gc oligomerization. In conclusion, our data suggest that after endocytic uptake, RVFV traffics to the acidic late endolysosomal compartments, where histidine protonation drives the reorganization of the Gc fusion protein that leads to membrane fusion.