Tryptophan fluorescence check details measurements were used to monitor unfolding as a function of temperature and indicate that the loop involved in domain swapping does not unfold below 60 degrees C. The domain-swapping is not directly responsible
for the affinity loss, but is likely a side-effect of the structural instability which may contribute to affinity loss. A second round of design was successful in eliminating the dimerization through mutation of a residue (Leu51Ser) at the joint of the domain-swapped loop.”
“Bluetongue is a seasonal midge-borne disease of ruminants with economic consequences on herd productivity and animal trade. Recently, two new modes of transmission have been demonstrated in cattle for Bluetongue virus serotype 8 (BTV8): vertical and pseudo-vertical transmission. Our objective was to model the seasonal spread of BTV8 over several years in a homogeneous population of cattle, and to evaluate the effectiveness of vaccination strategies. We built a deterministic mathematical model accounting for the seasonality in vector abundance and all the modes of transmission. We proposed a counterpart
of the basic reproduction number (R(0)) in a seasonal context (R(S)). Set A(t) is the number of secondary cases produced by a primary case selleck introduced at time t. R(S) is the average of A(t). It is a function of midge abundance and vaccination strategy. We also used A*, the maximum of A(t), as an indicator of the risk of an epidemic. Without vaccination, the model predicted a large first epidemic peak followed by smaller annual peaks if R(S) > 1.
When R(S) < 1, small epidemics could occur if A* > 1. Vaccination reduced R(S) and A* to less than one, but almost perfect vaccine efficacy and coverage were required to ensure no epidemics occurred. However, a lower coverage resulting in R(S) > 1 could decrease infection prevalence. A further step would be to optimize vaccination strategies by targeting an appropriate period of the year to implement the vaccination. (C) 2011 Elsevier Ltd. All rights reserved.”
“Hypoxia inducible factors (HIFs) are master-regulators of cellular responses Histone demethylase to hypoxia, and thus are crucial for survival. HIFs also play a role in regulating cellular processes in beta-cells, liver, muscle, and adipose tissue, have effects on the regulation of weight, and play a role in type 2 diabetes (T2D). Indeed, in people with T2D the HIF pathway is dyregulated in major metabolic tissues involved in the pathogenesis of diabetes. This review covers the contrasting, complementary and conflicting effects of decreasing and increasing HIFs in various tissues, and shows that a delicate balance exists between HIF levels and optimal metabolic function. We propose that increasing the activity of HIFs might be a potential therapeutic strategy for treating T2D.