Host,Pathogen, and Environmental Characteristics Predict White-Nose Syndrome Mortality in Captive Little Brown Myotis (Myotis lucifugus)

An estimated 5.7 million or more bats died in North America between 2006 and 2012 due to infection with the fungus Pseudogymnoascus destructans (Pd) that causes white-nose syndrome (WNS) during hibernation. The behavioral and physiological changes associated with hibernation leave bats vulnerable to WNS, but the persistence of bats within the contaminated regions of North America suggests that survival might vary predictably among individuals or in relation to environmental conditions. To investigate variables influencing WNS mortality, we conducted a captive study of 147 little brown myotis (Myotis lucifugus) inoculated with 0, 500, 5 000, 50 000, or 500 000 Pd conidia and hibernated for five months at either 4 or 10°C. We found that female bats were significantly more likely to survive hibernation, as were bats hibernated at 4°C, and bats with greater body condition at the start of hibernation. Although all bats inoculated with Pd exhibited shorter torpor bouts compared to controls, a characteristic of WNS, only bats inoculated with 500 conidia had significantly lower survival odds compared to controls. These data show that host and environmental characteristics are significant predictors of WNS mortality, and that exposure to up to 500 conidia is sufficient to cause a fatal infection. These results also illustrate a need to quantify dynamics of Pd exposure in free-ranging bats, as dynamics of WNS produced in captive studies inoculating bats with several hundred thousand conidia may differ from those in the wild.     

The Role of Hormones in the Differences in the Incidence of Breast Cancer between Mongolia and the United Kingdom

Background

There are striking differences in breast cancer incidence between Asian and western women. Rates vary substantially within Asia also, with Mongolia''s even lower than China''s. These profound differences have been speculated to be due in part to diet, mediated by circulating hormone concentrations.

Methods

Sex steroid hormone concentrations were measured in women living in Ulaanbaatar, Mongolia and the United Kingdom (U.K.). Diet was obtained by interview and national survey data. Mean hormone differences were compared by country, and systematic variation by number of days since last menstrual period was modeled and adjusted for age and parity; difference in overall area under the curves was assessed.

Findings

The diet in Mongolia was higher in meat and dairy than in the U.K. Mean testosterone concentrations were 18.5% lower (p<0.0001) while estradiol concentrations were 19.1% higher (p = 0.02) in Mongolian than British women, adjusted for age and parity. Progesterone was almost 50% higher in Mongolian women (p = 0.04), particularly during the follicular phase and early luteal surge. Hormone concentrations generally were similar in Mongolian women born in Ulaanbaatar compared with those born in rural areas, although there was a decreasing progesterone trend by degree of westernization (rural Mongolia; urban Mongolia; U.K.). Mean hormone differences were similar when restricted to parous women, and with further adjustment for body mass index, height, and smoking status.

Interpretation

These data augment accumulating evidence that circulating estrogens are unlikely to explain reduced breast cancer rates in Asia compared with the west, and suggest casting a wider net with respect to biomarkers. Lower testosterone and higher progesterone in Mongolian women raise the possibility that these hormones may be important to consider. In addition, the almost exclusive dietary reliance of Mongolians on meat and dairy argues against beneficial effects of a low-fat diet on circulating hormones explaining international breast cancer differences.     

Altered Activation of Protein Kinase PKR and Enhanced Apoptosis in Dystonia Cells Carrying a Mutation in PKR Activator Protein PACT

PACT is a stress-modulated activator of the interferon-induced double-stranded RNA-activated protein kinase (PKR). Stress-induced phosphorylation of PACT is essential for PACT''s association with PKR leading to PKR activation. PKR activation leads to phosphorylation of translation initiation factor eIF2α inhibition of protein synthesis and apoptosis. A recessively inherited form of early-onset dystonia DYT16 has been recently identified to arise due to a homozygous missense mutation P222L in PACT. To examine if the mutant P222L protein alters the stress-response pathway, we examined the ability of mutant P222L to interact with and activate PKR. Our results indicate that the substitution mutant P222L activates PKR more robustly and for longer duration albeit with slower kinetics in response to the endoplasmic reticulum stress. In addition, the affinity of PACT-PACT and PACT-PKR interactions is enhanced in dystonia patient lymphoblasts, thereby leading to intensified PKR activation and enhanced cellular death. P222L mutation also changes the affinity of PACT-TRBP interaction after cellular stress, thereby offering a mechanism for the delayed PKR activation in response to stress. Our results demonstrate the impact of a dystonia-causing substitution mutation on stress-induced cellular apoptosis.     

Diet and feeding habits of the small catfish,Clarias liocephalus in wetlands of Western Uganda

Clarias liocephalus is an air‐breathing catfish inhabiting wetland and river systems in East Africa. This catfish is in high demand for sale as live bait in the Nile perch fishery of Lake Victoria and equally important in the diet of local communities in the lake basin. Wetland loss and increasing fishing pressure potentially threaten the persistence of C. liocephalus; however, little information exists on the ecology of this species to permit evaluation of current threats. This study quantified dietary characteristics of C. liocephalus from heavy and lightly fished wetlands in Western Uganda using numeric, gravimetric and volumetric indices on 492 stomach samples collected over one year. Clarias liocephalus was significantly smaller in three heavily fished sites, relative to the one in‐park site, likely a reflection of a size‐selective fishery. Across sites, C. liocephalus was a generalist feeder whose diet was dominated by aquatic dipteran larvae and plant material. The broad niche gives C. liocephalus an ecological advantage to forage effectively on a wide selection of prey. The significant presence of plant material shows that the species may utilize plant protein, an important consideration of diet requirements should the species be selected for aquaculture.     

In vitro assessment of the antimicrobial activity of new N-acyl-thiourea derivatives

The qualitative screening of the susceptibility spectra of different microbial strains to the newly synthesized substances complexes was performed by adapted disk diffusion techniques, while the quantitative assay of the minimal inhibitory concentration (M.I.C., microg/cm3) value was based on liquid medium serial microdilutions. The compounds were solubilized in dimethylsulfoxide (DMSO). The in vitro biological screening effects were tested against a microbial inoculum of approximately 1.5 x 10(8) UFC/cm3, corresponding to 0.5 McFarland standard density, obtained from Gram positive (Staphylococcus aureus, Bacillus subtilis), Gram negative bacteria (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa) and fungal strains (Candida albicans). In order to investigate the influence of the subinhibitory concentration of the tested substances on the expression of different virulence features, the strains were incubated overnight in the presence of the newly synthesized thiourea derivatives (vol:vol) and different virulence features were investigated, i.e: adherence capacity to the cellular substrate represented by HeLa cells and to inert substrata quantified by slime test and soluble enzymatic virulence factors (haemolysins and other pore-forming toxins, proteases activity, DN-ase and siderophores production). The cytotoxicity was assessed microscopically, by observing the effect of the tested compounds on the cellular substratum integrity.     

A mechanical model of cell segregation driven by differential adhesion

From simulations that begin with a random mix of two cell types, we monitor progress towards segregation driven by contact-mediated linkage of model cells, which is equivalent to the cell-cell adhesion of real cells. In comparison with real cell experiments, we show that this mechanical model can account for the observed extent of segregation obtained by differential adhesion in a 2D cell culture assay of cells with differentially expressed cadherin molecules. Calibration of virtual to real time allowed us to estimate a time course for these experiments that was within 50% agreement for the simulations compared to differential adhesion of cells. In contrast, simulations of differential adhesion do not account for the rate of segregation driven by interactions between EphB2 receptor and ephrinB1 expressing cells which occurs an order of magnitude faster. The latter result suggests that mechanisms additional or alternative to differential adhesion contribute to Eph-ephrin mediated cell segregation.     

Sex differences and similarities in the neuroendocrine regulation of social behavior in an African cichlid fish

An individual's position in a social hierarchy profoundly affects behavior and physiology through interactions with community members, yet little is known about how the brain contributes to status differences between and within the social states or sexes. We aimed to determine sex-specific attributes of social status by comparing circulating sex steroid hormones and neural gene expression of sex steroid receptors in dominant and subordinate male and female Astatotilapia burtoni, a highly social African cichlid fish. We found that testosterone and 17β-estradiol levels are higher in males regardless of status and dominant individuals regardless of sex. Progesterone was found to be higher in dominant individuals regardless of sex. Based on pharmacological manipulations in males and females, progesterone appears to be a common mechanism for promoting courtship in dominant individuals. We also examined expression of androgen receptors, estrogen receptor α, and the progesterone receptor in five brain regions that are important for social behavior. Most of the differences in brain sex steroid receptor expression were due to sex rather than status. Our results suggest that the parvocellular preoptic area is a core region for mediating sex differences through androgen and estrogen receptor expression, whereas the progesterone receptor may mediate sex and status behaviors in the putative homologs of the nucleus accumbens and ventromedial hypothalamus. Overall our results suggest sex differences and similarities in the regulation of social dominance by gonadal hormones and their receptors in the brain.     

Business‐to‐Business Information Technology User Practices at End of Life in the United Kingdom,Germany, and France

Business‐to‐business (B2B) electronics account for a significant volume of the electrical and electronic equipment (EEE) put on the market. Very little B2B waste electrical and electronic equipment (WEEE) is reported as collected in the European Union (EU) in compliance with the WEEE Directive, which uses the policy principle of extended producer responsibility (EPR) to ensure that WEEE is managed correctly. This presents a barrier to parties looking for access to the waste. Company practice dictates the channels into which B2B WEEE flows following primary use. This article presents a study that engaged with company actors directly to get a better understanding of business information technology (IT) EEE asset management. Data were collected to determine the barriers current practice could present to the collection of B2B IT EEE at end of life and the implications of these for the development of policies and strategies for EPR. A questionnaire was developed and data were gathered from organizations in three EU countries—the United Kingdom, Germany, and France—stratified by size. Some notable findings were that there are several routes by which end‐of‐life B2B WEEE can flow. The recycling and refurbishment of B2B IT units at end of use was shown to be commonplace, but it is likely that these units enter streams where they are not reported. The actors disposing of their units did not have information on the management or disposition of these streams. It is concluded that to achieve the goals of EPR for B2B IT WEEE, the networks and the operational practices of these streams need to be better understood when developing strategies and policies.