The Oxytocin Receptor (OXTR) Contributes to Prosocial Fund Allocations in the Dictator Game and the Social Value Orientations Task

Background: Economic games observe social decision making in the laboratory that involves real money payoffs. Previously we have shown that allocation of funds in the Dictator Game (DG), a paradigm that illustrates costly altruistic behavior, is partially determined by promoter-region repeat region variants in the arginine vasopressin 1a receptor gene (AVPR1a). In the current investigation, the gene encoding the related oxytocin receptor (OXTR) was tested for association with the DG and a related paradigm, the Social Values Orientation (SVO) task. Methodology/Principal Findings: Association (101 male and 102 female students) using a robust-family based test between 15 single tagging SNPs (htSNPs) across the OXTR was demonstrated with both the DG and SVO. Three htSNPs across the gene region showed significant association with both of the two games. The most significant association was observed with rs1042778 (p = 0.001). Haplotype analysis also showed significant associations for both DG and SVO. Following permutation test adjustment, significance was observed for 2–5 locus haplotypes (p,0.05). A second sample of 98 female subjects was subsequently and independently recruited to play the dictator game and was genotyped for the three significant SNPs found in the first sample. The rs1042778 SNP was shown to be significant for the second sample as well (p = 0.004, Fisher’s exact test). Conclusions: The demonstration that genetic polymorphisms for the OXTR are associated with human prosocial decisio

Heat Shock Proteins and Amateur Chaperones in Amyloid-Beta Accumulation and Clearance in Alzheimer’s Disease

The pathologic lesions of Alzheimer’s disease (AD) are characterized by accumulation of protein aggregates consisting of intracellular or extracellular misfolded proteins. The amyloid-β (Aβ) protein accumulates extracellularly in senile plaques and cerebral amyloid angiopathy, whereas the hyperphosphorylated tau protein accumulates intracellularly as neurofibrillary tangles. “Professional chaperones”, such as the heat shock protein family, have a function in the prevention of protein misfolding and subsequent aggregation. “Amateur” chaperones, such as apolipoproteins and heparan sulfate proteoglycans, bind amyloidogenic proteins and may affect their aggregation process. Professional and amateur chaperones not only colocalize with the pathological lesions of AD, but may also be involved in conformational changes of Aβ, and in the clearance of Aβ from the brain via phagocytosis or active transport across the blood–brain barrier. Thus, both professional and amateur chaperones may be involved in the aggregation, accumulation, persistence, and clearance of Aβ and tau and in other Aβ-associated reactions such as inflammation associated with AD lesions, and may, therefore, serve as potential targets for therapeutic intervention

Controversies in the management of advanced prostate cancer

For advanced prostate cancer, the main hormone treatment against which other treatments are assessed is surgical castration. It is simple, safe and effective, however it is not acceptable to all patients. Medical castration by means of luteinizing hormone-releasing hormone (LH-RH) analogues such as goserelin acetate provides an alternative to surgical castration. Diethylstilboestrol, previously the only non-surgical alternative to orchidectomy, is no longer routinely used. Castration reduces serum testosterone by around 90%, but does not affect androgen biosynthesis in the adrenal glands. Addition of an anti-androgen to medical or surgical castration blocks the effect of remaining testosterone on prostate cells and is termed combined androgen blockade (CAB). CAB has now been compared with castration alone (medical and surgical) in numerous clinical trials. Some trials show advantage of CAB over castration, whereas others report no significant difference. The author favours the view that CAB has an advantage over castration. No study has reported that CAB is less effective than castration. Of the anti-androgens which are available for use in CAB, bicalutamide may be associated with a lower incidence of side-effects compared with the other non-steroidal anti-androgens and, in common with nilutamide, has the advantage of once-daily dosing. Only one study has compared anti-androgens within CAB: bicalutamide plus LH-RH analogue and flutamide plus LH-RH analogue. At 160-week follow-up, the groups were equivalent in terms of survival and time to progression. However, bicalutamide caused significantly less diarrhoea than flutamide. Withdrawal and intermittent therapy with anti-androgens extend the range of treatment options. © 1999 Cancer Research Campaig

Targeted disruption of the extracellular polymeric network of Pseudomonas aeruginosa biofilms by alginate oligosaccharides

Acquisition of a mucoid phenotype by Pseudomonas sp. in the lungs of cystic fibrosis (CF) patients, with subsequent over-production of extracellular polymeric substance (EPS), plays an important role in mediating the persistence of multi-drug resistant (MDR) infections. The ability of a low molecular weight (Mn=3200 g mol-1) alginate oligomer (OligoG CF-5/20) to modify biofilm structure of mucoid Pseudomonas aeruginosa (NH57388A) was studied in vitro using scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM) with Texas Red (TxRd®)-labelled OligoG and EPS histochemical staining. Structural changes in treated biofilms were quantified using COMSTAT image-analysis software of CLSM z-stack images, and nanoparticle diffusion. Interactions between the oligomers, Ca2+ and DNA were studied using molecular dynamics simulations (MDS), Fourier transform infrared spectroscopy (FTIR) and isothermal titration calorimetry (ITC). Imaging demonstrated that OligoG treatment (>0.5%) inhibited biofilm formation, demonstrating a significant reduction in both biomass and biofilm height (17.8 vs. 5.5 µm; P <0.05). TxRd®-labelled oligomers readily diffused into established (24 h) biofilms. OligoG treatment (≥2%) induced alterations in the EPS of established biofilms; significantly reducing the structural quantities of sugar residues, and extracellular (e)DNA (P <0.05) with a corresponding increase in nanoparticle diffusion (P<0.05) and antibiotic efficacy against established biofilms. ITC demonstrated an absence of rapid complex formation between DNA and OligoG and confirmed the interactions of OligoG with Ca2+ evident in FTIR and MDS. The ability of OligoG to diffuse into biofilms, potentiate antibiotic activity, disrupt DNA-Ca2+-DNA bridges and biofilm EPS matrix highlights its potential for the treatment of biofilm-related infections

Designing a network of critical zone observatories to explore the living skin of the terrestrial Earth

The critical zone (CZ), the dynamic living skin of the Earth, extends from the top of the vegetative canopy through the soil and down to fresh bedrock and the bottom of the groundwater. All humans live in and depend on the CZ. This zone has three co-evolving surfaces: the top of the vegetative canopy, the ground surface, and a deep subsurface below which Earth's materials are unweathered. The network of nine CZ observatories supported by the US National Science Foundation has made advances in three broad areas of CZ research relating to the co-evolving surfaces. First, monitoring has revealed how natural and anthropogenic inputs at the vegetation canopy and ground surface cause subsurface responses in water, regolith structure, minerals, and biotic activity to considerable depths. This response, in turn, impacts aboveground biota and climate. Second, drilling and geophysical imaging now reveal how the deep subsurface of the CZ varies across landscapes, which in turn influences aboveground ecosystems. Third, several new mechanistic models now provide quantitative predictions of the spatial structure of the subsurface of the CZ.Many countries fund critical zone observatories (CZOs) to measure the fluxes of solutes, water, energy, gases, and sediments in the CZ and some relate these observations to the histories of those fluxes recorded in landforms, biota, soils, sediments, and rocks. Each US observatory has succeeded in (i) synthesizing research across disciplines into convergent approaches; (ii) providing long-term measurements to compare across sites; (iii) testing and developing models; (iv) collecting and measuring baseline data for comparison to catastrophic events; (v) stimulating new process-based hypotheses; (vi) catalyzing development of new techniques and instrumentation; (vii) informing the public about the CZ; (viii) mentoring students and teaching about emerging multidisciplinary CZ science; and (ix) discovering new insights about the CZ. Many of these activities can only be accomplished with observatories. Here we review the CZO enterprise in the United States and identify how such observatories could operate in the future as a network designed to generate critical scientific insights. Specifically, we recognize the need for the network to study network-level questions, expand the environments under investigation, accommodate both hypothesis testing and monitoring, and involve more stakeholders. We propose a driving question for future CZ science and a hubs-and-campaigns model to address that question and target the CZ as one unit. Only with such integrative efforts will we learn to steward the life-sustaining critical zone now and into the future

Nécrologie. Jean Brissaud (1854-1904)

Nécrologie. Jean Brissaud (1854-1904). In: Annales du Midi : revue archéologique, historique et philologique de la France méridionale, Tome 17, N°65, 1905. pp. 121-123

Using genetics in the conservation management of the American black bear (Ursus americanus) in Missouri

By the early 1900s, black bears were believed to be almost extinct in Missouri and Arkansas, presumably due to extensive logging and overharvest. To reestablish Arkansas populations, the Arkansas Game and Fish Commission conducted a translocation program from 1958 to 1968, moving 254 bears from Minnesota and Manitoba, Canada, to the Ozark and Ouachita National Forests. This remains one of the most successful large mammal translocations ever conducted, and the Arkansas population grew rapidly into the thousands. However, bear sightings and nuisance reports suggested that 50 years after the translocations, populations in Missouri were small, and densities were low. We conducted a spatially explicit genetic capture-recapture study to estimate the size and density of the black bear population in south-centralMissouri.We genotyped hair samples collected over two years using 15 microsatellite loci and estimated the population size at 279 ± 54 (SE) and the density at 1.7 bears/km2. To infer the source of bears colonizing Missouri, we analyzed the resulting genotypes in the Bayesian clustering program STRUCTURE along with genotypes from Arkansas, Oklahoma, and source populations. The results revealed unique genetic clusters in the Ouachitas, the Ozarks, and the source populations and found that Missouri bears were divided between those that clustered with the Ozarks and a unique cluster. The presence of the unique cluster in Missouri supports the hypothesis that black bears in the Missouri Ozarks were not extirpated but were reduced to very low densities during European settlement and have subsequently become admixed with bears that trace their ancestry to the reintroduction. While some might suggest that the unique Missouri population should be designated as a separate management unit, we caution that this might not be beneficial to the preservation of the Missouri bear population as we have no evidence that it is ecologically or geographically distinct, it has low genetic diversity, and the genetic differentiation may not be related to adaptive differences