The data indicate that many of these residues may be hot spot Microtubule Associated inhibitor residues. Most remarkably, two residues, R83 and R133, were observed to shift the oligomerization state to 50% dimer. Based on the hypothesis that these two residues constitute a “”hot strip,” located at the ferritin-like threefold axis, the double mutant was generated which completely shuts down detectable formation of 12-mer in solution, favoring a cooperatively folded dimer. The fact that this effect logically builds upon the single mutants emphasizes that complex self-assembly has the potential

to be manipulated rationally. This study should have an impact on the fundamental understanding of the assembly of DPS protein cages specifically and protein quaternary structure in general. In addition, as there is much interest in applying these and similar systems to the templation of nano-materials and drug delivery, the ability to control this ferritin’s oligomerization state and stability could prove especially valuable.”
“Background. Frailty and p38 MAPK inhibitor hyperhomocysteinemia are common in the older population. The researchers’ objectives were to determine whether elevated homocysteine (tHcy) is associated with frailty and mortality.

Methods. The researchers conducted a prospective cohort study. tHcy was measured by immunoassay in 4,248 community-dwelling men aged 70-88 years. Frailty was assessed with the Fatigue, Resistance, Ambulation, Illness and

Loss of weight (FRAIL) scale. Mortality was determined from selleck the death registry.

Results. At baseline, 1,117 men (26.3%) had high tHcy (>= 15 mu mol/L) and 685 (16.2%) were frail (ie, having three or more deficits in the FRAIL scale). There were 749 deaths during

a follow-up duration of 5.1 +/- 1.3 years. In cross-sectional analysis, high tHcy was associated with increased prevalent frailty (odds ratio 1.49, 95% CI 1.22-1.81) after adjusting for confounding factors. After a period of 5.3 +/- 0.8 years, the longitudinal relationship between high tHcy and frailty was weakened in multivariate analysis (hazards ratio 1.25, 95% CI 0.95-1.65). When assessing the relationship between tHcy and incident frailty, the odds of being frail at follow-up for men with high tHcy and having zero deficit at baseline (ie, FRAIL scale = 0) were 1.59 (95% CI 0.88-2.89) in adjusted analysis. High tHcy also predicted all-cause mortality (hazards ratio 1.25, 95% CI 1.06-1.48) after adjusting for frailty and other covariates.

Conclusions. Hyperhomocysteinemia is associated with the prevalence of frailty. It is also predictive of all-cause mortality, independent of frailty. The results suggest that the association between tHcy and mortality is largely not mediated through the occurrence of frailty.”
“Major histocompatibility complex (MHC) II proteins bind peptide fragments derived from pathogen antigens and present them at the cell surface for recognition by T cells.