Glutathionylation of the p50 subunit of NF-kappaB: a mechanism for redox-induced inhibition of DNA binding.

The cellular redox status can modify the function of NF-kappaB, whose DNA-binding activity can be inhibited by oxidative, nitrosative, and nonphysiological agents such as diamide, iodoacetamide, or N-ethylmaleimide. This inhibitory effect has been proposed to be mediated by the oxidation of a conserved cysteine in its DNA-binding domain (Cys62) through unknown biochemical mechanisms. The aim of this work was to identify new oxidative modifications in Cys62 involved in the redox regulation of the NF-kappaB subunit p50. To address this problem, we exposed p50, both the native form (p50WT) and its corresponding mutant in Cys62 (C62S), to changes in the redox pair glutathione/glutathione disulfide (GSH/GSSG) ratio ranging from 100 to 0.1, which may correspond to intracellular (patho)physiological states. A ratio between 1 and 0.1 resulted in a 40-70% inhibition of the DNA binding of p50WT, having no effect on the C62S mutant. Mass spectrometry studies, molecular modeling, and incorporation of (3)H-glutathione assays were consistent with an S-glutathionylation of p50WT in Cys62. Maximal incorporation of (3)H-glutathione to the p50WT and C62S was of 0.4 and 0.1 mol of (3)H-GSH/mol of protein, respectively. Because this covalent glutathione incorporation did not show a perfect correlation with the observed inhibition in the DNA-binding activity of p50WT, we searched for other modifications contributing to the maximal inhibition. MALDI-TOF and nanospray-QIT studies revealed the formation of sulfenic acid as an alternative or concomitant oxidative modification of p50. In summary, these data are consistent with new oxidative modifications in p50 that could be involved in redox regulatory mechanisms for NF-kappaB. These postranslational modifications could represent a molecular basis for the coupling of pro-oxidative stimuli to gene expression.     

Rhesus macaques build new social connections after a natural disaster

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Studies on Disaccharide Nucleoside Synthesis. Mechanism of the Formation of Trisaccharide Purine Nucleosides

Abstract

The unexpected formation of trisaccharide nucleosides during synthesis of purine 5′-O-β-D-ribofuranosylnucleosides in the presence of Lewis acids was observed.     

Indoor Tracking to Understand Physical Activity and Sedentary Behaviour: Exploratory Study in UK Office Buildings

Little is known of the patterns of physical activity, standing and sitting by office workers. However, insight into these behaviours is of growing interest, notably in regard to public health priorities to reduce non-communicable disease risk factors associated with high levels of sitting time and low levels of physical activity. With the advent and increasing availability of indoor tracking systems it is now becoming possible to build detailed pictures of the usage of indoor spaces. This paper reports initial results of indoor tracking used in conjunction with the ActivPAL activity monitoring device. In this paper we give an overview of the usage of the tracking system and its installation and illustrate some of the resultant data. We also provide preliminary results that investigate the relationship between location, light physical activity and sitting in a small sample of office workers (n=33) from two separate office environments in order to demonstrate the relevance and explanatory power of the technique.     

Explaining geographical variation in the isotope composition of mouse lemurs (Microcebus)

Aim We sought to quantify geographical variation in the stable isotope values of mouse lemurs (Microcebus) and to determine whether this variation reflects trophic differences among populations or baseline isotopic differences among habitats. If the latter pattern is demonstrated, then Microcebus can become a proxy for tracking baseline habitat isotopic variability. Establishing such a baseline is crucial for identifying niche partitioning in modern and ancient communities. Location We studied five species of Microcebus from eight distinct habitats across Madagascar. Methods We compared isotopic variation in C₃ plants and Microcebus fur within and among localities. We predicted that carbon and nitrogen isotope values of Microcebus should: (1) vary as a function of abiotic variables such as rainfall and temperature, and (2) covary with isotopic values in plants. We checked for trophic differences among Microcebus populations by comparing the average difference between mouse lemur and plant isotope values for each locality. We then used multiple regression models to explain spatial isotope variation in mouse lemurs, testing a suite of explanatory abiotic variables. Results We found substantial isotopic variation geographically. Ranges for mean isotope values were similar for both Microcebus and plants across localities (carbon 3.5–4.0‰; nitrogen 10.5–11.0‰). Mean mouse lemur and plant isotope values were lowest in cool, moist localities and highest in hot, dry localities. Rainfall explained 58% of the variation in Microcebus carbon isotope values, and mean plant nitrogen isotope values explained 99.7% of the variation in Microcebus nitrogen isotope values. Average differences between mouse lemur and plant isotope values (carbon 5.0‰; nitrogen 5.9‰) were similar across localities. Main conclusions Isotopic data suggest that trophic differences among Microcebus populations were small. Carbon isotope values in mouse lemurs were negatively correlated with rainfall. Nitrogen isotope values in Microcebus and plants covaried. Such findings suggest that nitrogen isotope values for Microcebus are a particularly good proxy for tracking baseline isotopic differences among habitats. Our results will facilitate future comparative research on modern mouse lemur communities, and ecological interpretations of extinct Holocene communities.