Predicting and validating a model of suppressor of IKKepsilon through biophysical characterization

Suppressor of IKKepsilon (SIKE) is a 207 residue protein that is implicated in the TLR3‐TANK‐binding kinase‐1‐mediated response to viral infection. SIKE's function in this pathway is unknown, but SIKE forms interactions with two distinct cytoskeletal proteins, α‐actinin and tubulin, and SIKE knockout reduces cell migration. As structure informs function and in the absence of solved structural homologs, our studies were directed toward creating a structural model of SIKE through biochemical and biophysical characterization to probe and interrogate SIKE function. Circular dichroism revealed a primarily (73%) helical structure of minimal stability (<T_m > =32°C) but reversibly denatured. Limited proteolysis (LP) and chemical modification identified the N‐terminal 2/3 of the protein as dynamic and accessible, whereas size exclusion chromatography (SEC) confirmed three homo‐oligomeric species. SEC coupled to chemical crosslinking characterized the primary species as dimeric, a secondary hexameric species, and a higher order aggregate/polymer. Fluorescence polarization using intrinsic tryptophan fluorescence contextualized the anisotropy value for the SIKE dimer (molecular weight 51.8 kDa) among proteins of known structure, bovine serum albumin (BSA; 66 kDa), and glutamate dehydrogenase (GDH; 332 kDa). Radii of gyration for BSA and GDH provided exclusionary values for SIKE tertiary and dimeric quaternary models that otherwise conformed to secondary structure, LP, and modification data. Dimeric quaternary models were further culled using acrylamide quenching data of SIKE's single tryptophan that showed a single, protected environment. The low cooperativity of folding and regions of dynamic and potentially disordered structure advance the hypothesis that SIKE forms a conformational ensemble of native states that accommodate SIKE's interactions with multiple, distinct protein‐binding partners.     

Correlates and Consequences of Dominance in a Social Rodent

In harem‐polygynous societies, body condition is often correlated with dominance rank. However, the consequences of dominance are less clear. High‐ranking males do not inevitably have the highest reproductive success, especially in systems where females mate with multiple males. In such societies, we expect male reproductive success to be more highly skewed than female reproductive success, but reproductive skew in females can still arise from rankings established within matrilineal societies. Dominance can also impact life‐history decisions by influencing dispersal patterns in yearlings. To better understand the function of dominance in harem‐polygynous societies, we studied the causes and consequences of dominance in yellow‐bellied marmots (Marmota flaviventris), a social rodent with skewed male reproductive success and female reproductive suppression. Specifically, we examined body condition as a predictor and the probability of breeding, number of offspring, and dispersal as outcomes of dominance. Additionally, we looked at variation in dominance between males and females and adults and yearlings, because marmots can engage in distinct interactions depending on the type of individuals involved. We found that marmots in better body condition have higher dominance rank than those in poorer condition. In addition, adults are dominant over yearlings. Within yearlings, dominance does not influence dispersal, but those in better body condition are less likely to disperse. Within all adults, individuals in better condition produce more offspring per year. Within adult males, more dominant males have greater reproductive success. Despite previous evidence of reproductive suppression in females, we found no effects of dominance rank on female reproductive success in the current study. The function of dominance in female marmots remains enigmatic.     

Roles of N-methyl-d-aspartate receptors and d-amino acids in cancer cell viability

Molecular Biology Reports - N-methyl-d-aspartate (NMDA) receptors, which are widely present in the central nervous system, have also been found to be up-regulated in a variety of cancer cells and...     

A test of the social cohesion hypothesis: interactive female marmots remain at home

Individuals frequently leave home before reaching reproductive age, but the proximate causes of natal dispersal remain relatively unknown. The social cohesion hypothesis predicts that individuals who engage in more (affiliative) interactions are less likely to disperse. Despite the intuitive nature of this hypothesis, support is both limited and equivocal. We used formal social network analyses to quantify precisely both direct and indirect measures of social cohesion in yellow-bellied marmots. Because approximately 50 per cent of female yearlings disperse, we expected that social relationships and network measures of cohesion would predict dispersal. By contrast, because most male yearlings disperse, we expected that social relationships and cohesion would play a less important role. We found that female yearlings that interacted with more individuals, and those that were more socially embedded in their groups, were less likely to disperse. For males, social interactions were relatively unimportant determinants of dispersal. This is the first strong support for the social cohesion hypothesis and suggests that the specific nature of social relationships, not simply the number of affiliative relationships, may influence the propensity to disperse.     

Regional Amyloid Deposition in Amnestic Mild Cognitive Impairment and Alzheimer's Disease Evaluated by [18F]AV-45 Positron Emission Tomography in Chinese Population

Background

To compare the neocortical amyloid loads among cognitively normal (CN), amnestic mild cognitive impairment (aMCI), and Alzheimer''s disease (AD) subjects with [¹⁸F]AV-45 positron emission tomography (PET).

Materials and Methods

[¹⁸F]AV-45 PET was performed in 11 CN, 13 aMCI, and 12 AD subjects to compare the cerebral cortex-to-whole cerebellum standard uptake value ratios (SUVRs) of global and individual volumes of interest (VOIs) cerebral cortex. The correlation between global cortical [¹⁸F]AV-45 SUVRs and Mini-Mental State Examination (MMSE) scores was analyzed.

Results

The global cortical [¹⁸F]AV-45 SUVRs were significantly different among the CN (1.08±0.08), aMCI (1.27±0.06), and AD groups (1.34±0.13) (p = 0.0003) with amyloidosis positivity rates of 9%, 62%, and 92% in the three groups respectively. Compared to CN subjects, AD subjects had higher SUVRs in the global cortical, precuneus, frontal, parietal, occipital, temporal, and posterior cingulate areas; while aMCI subjects had higher values in the global cortical, precuneus, frontal, occipital and posterior cingulate areas. There were negative correlations of MMSE scores with SUVRs in the global cortical, precuneus, frontal, parietal, occipital, temporal, posterior cingulate and anterior cingulate areas on a combined subject pool of the three groups after age and education attainment adjustment.

Conclusions

Amyloid deposition occurs relatively early in precuneus, frontal and posterior cingulate in aMCI subjects. Higher [¹⁸F]AV-45 accumulation is present in parietal, occipital and temporal gyri in AD subjects compared to the aMCI group. Significant correlation between MMSE scores and [¹⁸F]AV-45 SUVRs can be observed among CN, aMCI and AD subjects.     

Isolation and identification of gastrointestinal microbiota from the short-nosed fruit bat Cynopterus brachyotis brachyotis

Studies on the microbial ecology of gut microbiota in bats are limited and such information is necessary in determining the ecological significance of these hosts. Short-nosed fruit bats (Cynopterus brachyotis brachyotis) are good candidates for microbiota studies given their close association with humans in urban areas. Thus, this study explores the gut microbiota of this species from Peninsular Malaysia by means of biochemical tests and 16S rRNA gene sequences analysis. The estimation of viable bacteria present in the stomach and intestine of C. b. brachyotis ranged from 3.06 × 10¹⁰ to 1.36 × 10¹⁵ CFU/ml for stomach fluid and 1.92 × 10¹⁰ to 6.10 × 10¹⁵ CFU/ml for intestinal fluid. A total of 34 isolates from the stomach and intestine of seven C. b. brachyotis were retrieved. A total of 16 species of bacteria from eight genera (Bacillus, Enterobacter, Enterococcus, Escherichia, Klebsiella, Pantoea, Pseudomonas and Serratia) were identified, Enterobacteriaceae being the most prevalent, contributing 12 out of 16 species isolated. Most isolates from the Family Enterobacteriaceae have been reported as pathogens to humans and wildlife. With the possibility of human wildlife transmission, the findings of this study focus on the importance of bats as reservoirs of potential bacterial pathogens.