Modeling Global Warming Scenarios in Greenback Cutthroat Trout (\u3cem\u3eOncorhynchus Clarki Stomias\u3c/em\u3e) Streams: Implications for Species Recovery

Changes in global climate may exacerbate other anthropogenic stressors, accelerating the decline in distribution and abundance of rare species throughout the world. We examined the potential effects of a warming climate on the greenback cutthroat trout (Oncorhynchus clarki stomias), a resident salmonid that inhabits headwater streams of the central Rocky Mountains. Greenbacks are outcompeted at lower elevations by nonnative species of trout and currently are restricted to upper-elevation habitats where barriers to upstream migration by nonnatives are or have been established. We used likelihood-based techniques and information theoretics to select models predicting stream temperature changes for 10 streams where greenback cutthroat trout have been translocated. These models showed high variability among responses by different streams, indicating the usefulness of a stream-specific approach. We used these models to project changes in stream temperatures based on 2°C and 4°C warming of average air temperatures. In these warming scenarios, spawning is predicted to begin from 2 to 3.3 weeks earlier than would be expected under baseline conditions. Of the 10 streams used in this assessment, 5 currently have less than a 50% chance of translocation success. Warming increased the probability of translocation success in these 5 streams by 11.2% and 21.8% in the 2 scenarios, respectively. Assuming barriers to upstream migration by nonnative competitors maintain their integrity, we conclude that an overall habitat improvement results because greenbacks have been restricted through competition with nonnatives to suboptimal habitats, which are generally too cold to be highly productive

Impacts of local human activities on the Antarctic environment

We review the scientific literature, especially from the past decade, on the impacts of human activities on the Antarctic environment. A range of impacts has been identified at a variety of spatial and temporal scales. Chemical contamination and sewage disposal on the continent have been found to be long-lived. Contemporary sewage management practices at many coastal stations are insufficient to prevent local contamination but no introduction of non-indigenous organisms through this route has yet been demonstrated. Human activities, particularly construction and transport, have led to disturbances of flora and fauna. A small number of non-indigenous plant and animal species has become established, mostly on the northern Antarctic Peninsula and southern archipelagos of the Scotia Arc. There is little indication of recovery of overexploited fish stocks, and ramifications of fishing activity oil bycatch species and the ecosystem could also be far-reaching. The Antarctic Treaty System and its instruments, in particular the Convention for the Conservation of Antarctic Marine Living Resources and the Environmental Protocol, provide a framework within which management of human activities take place. In the face of the continuing expansion of human activities in Antarctica, a more effective implementation of a wide range of measures is essential, in order to ensure comprehensive protection of the Antarctic environment, including its intrinsic, wilderness and scientific values which remains a fundamental principle of the Antarctic Treaty System. These measures include effective environmental impact assessments, long-term monitoring, mitigation measures for non-indigenous species, ecosystem-based management of living resources, and increased regulation of National Antarctic Programmes and tourism activities

Increased S-nitrosylation and proteasomal degradation of caspase-3 during infection contribute to the persistence of adherent invasive escherichia coli (AIEC) in immune cells

Adherent invasive Escherichia coli (AIEC) have been implicated as a causative agent of Crohn's disease (CD) due to their isolation from the intestines of CD sufferers and their ability to persist in macrophages inducing granulomas. The rapid intracellular multiplication of AIEC sets it apart from other enteric pathogens such as Salmonella Typhimurium which after limited replication induce programmed cell death (PCD). Understanding the response of infected cells to the increased AIEC bacterial load and associated metabolic stress may offer insights into AIEC pathogenesis and its association with CD. Here we show that AIEC persistence within macrophages and dendritic cells is facilitated by increased proteasomal degradation of caspase-3. In addition S-nitrosylation of pro- and active forms of caspase-3, which can inhibit the enzymes activity, is increased in AIEC infected macrophages. This S-nitrosylated caspase-3 was seen to accumulate upon inhibition of the proteasome indicating an additional role for S-nitrosylation in inducing caspase-3 degradation in a manner independent of ubiquitination. In addition to the autophagic genetic defects that are linked to CD, this delay in apoptosis mediated in AIEC infected cells through increased degradation of caspase-3, may be an essential factor in its prolonged persistence in CD patients

Attitudes to in vitro meat:A survey of potential consumers in the United States

Positivity towards meat consumption remains strong, despite evidence of negative environmental and ethical outcomes. Although awareness of these repercussions is rising, there is still public resistance to removing meat from our diets. One potential method to alleviate these effects is to produce in vitro meat: meat grown in a laboratory that does not carry the same environmental or ethical concerns. However, there is limited research examining public attitudes towards in vitro meat, thus we know little about the capacity for it be accepted by consumers. This study aimed to examine perceptions of in vitro meat and identify potential barriers that might prevent engagement. Through conducting an online survey with US participants, we identified that although most respondents were willing to try in vitro meat, only one third were definitely or probably willing to eat in vitro meat regularly or as a replacement for farmed meat. Men were more receptive to it than women, as were politically liberal respondents compared with conservative ones. Vegetarians and vegans were more likely to perceive benefits compared to farmed meat, but they were less likely to want to try it than meat eaters. The main concerns were an anticipated high price, limited taste and appeal and a concern that the product was unnatural. It is concluded that people in the USA are likely to try in vitro meat, but few believed that it would replace farmed meat in their diet

Proposed Role for COUP-TFII in Regulating Fetal Leydig Cell Steroidogenesis, Perturbation of Which Leads to Masculinization Disorders in Rodents

Reproductive disorders that are common/increasing in prevalence in human males may arise because of deficient androgen production/action during a fetal ‘masculinization programming window’. We identify a potentially important role for Chicken Ovalbumin Upstream Promoter-Transcription Factor II (COUP-TFII) in Leydig cell (LC) steroidogenesis that may partly explain this. In rats, fetal LC size and intratesticular testosterone (ITT) increased ∼3-fold between e15.5-e21.5 which associated with a progressive decrease in the percentage of LC expressing COUP-TFII. Exposure of fetuses to dibutyl phthalate (DBP), which induces masculinization disorders, dose-dependently prevented the age-related decrease in LC COUP-TFII expression and the normal increases in LC size and ITT. We show that nuclear COUP-TFII expression in fetal rat LC relates inversely to LC expression of steroidogenic factor-1 (SF-1)-dependent genes (StAR, Cyp11a1, Cyp17a1) with overlapping binding sites for SF-1 and COUP-TFII in their promoter regions, but does not affect an SF-1 dependent LC gene (3β-HSD) without overlapping sites. We also show that once COUP-TFII expression in LC has switched off, it is re-induced by DBP exposure, coincident with suppression of ITT. Furthermore, other treatments that reduce fetal ITT in rats (dexamethasone, diethylstilbestrol (DES)) also maintain/induce LC nuclear expression of COUP-TFII. In contrast to rats, in mice DBP neither causes persistence of fetal LC COUP-TFII nor reduces ITT, whereas DES-exposure of mice maintains COUP-TFII expression in fetal LC and decreases ITT, as in rats. These findings suggest that lifting of repression by COUP-TFII may be an important mechanism that promotes increased testosterone production by fetal LC to drive masculinization. As we also show an age-related decline in expression of COUP-TFII in human fetal LC, this mechanism may also be functional in humans, and its susceptibility to disruption by environmental chemicals, stress and pregnancy hormones could explain the origin of some human male reproductive disorders

Challenges in multidisciplinary cancer care among general surgeons in Canada

<p>Abstract</p> <p>Background</p> <p>While many factors can influence the way that cancer care is delivered, including the way that evidence is packaged and disseminated, little research has evaluated how health care professionals who manage cancer patients seek and use this information to identify whether and how this could be supported. Through interviews we identified that general surgeons experience challenges in coordinating care for complex cancer patients whose management is not easily addressed by guidelines, and conducted a population-based survey of general surgeon information needs and information seeking practices to extend these findings.</p> <p>Methods</p> <p>General surgeons with privileges at acute care hospitals in Ontario, Canada were mailed a questionnaire to solicit information needs (task, importance), information seeking (source, frequency of and reasons for use), key challenges and suggested solutions. Non-responders received up to three reminder packages. Significant differences among sub-groups (age, setting) were examined statistically (Kruskal Wallis, Mann Whitney, Chi Square). Standard qualitative methods were used to thematically analyze open-ended responses.</p> <p>Results</p> <p>The response rate was 44.2% (170/385) representing all 14 health regions. System resource constraints (60.4%), comorbidities (56.4%) and physiologic factors (51.8%) were top-ranked issues creating information needs. Local surgical colleagues (84.6%), other local colleagues (82.2%) and the Internet (81.1%) were top-ranked sources of information, primarily due to familiarity and speed of access. No resources were considered to be highly applicable to patient care. Challenges were related to limitations in diagnostics and staging, operative resources, and systems to support multidisciplinary care, together accounting for 76.0% of all reported issues. Findings did not differ significantly by surgeon age or setting of care.</p> <p>Conclusion</p> <p>General surgeons appear to use a wide range of information resources but they may not address the complex needs of many cancer patients. Decision-making is challenged by informational and logistical issues related to the coordination of multidisciplinary care. This suggests that limitations in system capacity may, in part, contribute to variable guideline compliance. Further research is required to evaluate the appropriateness of information seeking, and both concurrent and consecutive mechanisms by which to achieve multidisciplinary care.</p

Glucose-Dependent Regulation of NR2F2 Promoter and Influence of SNP-rs3743462 on Whole Body Insulin Sensitivity

Background: The Nuclear Receptor 2F2 (NR2F2/COUP-TFII) heterozygous knockout mice display low basal insulinemia and enhanced insulin sensitivity. We previously established that insulin represses NR2F2 gene expression in pancreatic β-cells. The cis-regulatory region of the NR2F2 promoter is unknown and its influence on metabolism in humans is poorly understood. The present study aimed to identify the regulatory regions that control NR2F2 gene transcription and to evaluate the effect of NR2F2 promoter variation on glucose homeostasis in humans. Methodology/Principal Findings: Regulation of the NR2F2 promoter was assessed using gene reporter assays, ChIP and gel shift experiments. The effects of variation at SNP rs3743462 in NR2F2 on quantitative metabolic traits were studied in two European prospective cohorts. We identified a minimal promoter region that down-regulates NR2F2 expression by attenuating HNF4α activation in response to high glucose concentrations. Subjects of the French DESIR population, who carried the rs3743462 T-to-C polymorphism, located in the distal glucose-responsive promoter, displayed lower basal insulin levels and lower HOMA-IR index. The C-allele at rs3743462 was associated with increased NR2F2 binding and decreased NR2F2 gene expression. Conclusions/Significance: The rs3743462 polymorphism affects glucose-responsive NR2F2 promoter regulation and thereby may influence whole-body insulin sensitivity, suggesting a role of NR2F2 in the control of glucose homeostasis in humans. © 2012 Boutant et al

Chromosomes 4 and 8 implicated in a genome wide SNP linkage scan of 762 prostate cancer families collected by the ICPCG

BACKGROUND In spite of intensive efforts, understanding of the genetic aspects of familial prostate cancer (PC) remains largely incomplete. In a previous microsatellite‐based linkage scan of 1,233 PC families, we identified suggestive evidence for linkage (i.e., LOD ≥ 1.86) at 5q12, 15q11, 17q21, 22q12, and two loci on 8p, with additional regions implicated in subsets of families defined by age at diagnosis, disease aggressiveness, or number of affected members. METHODS In an attempt to replicate these findings and increase linkage resolution, we used the Illumina 6000 SNP linkage panel to perform a genome‐wide linkage scan of an independent set of 762 multiplex PC families, collected by 11 International Consortium for Prostate Cancer Genetics (ICPCG) groups. RESULTS Of the regions identified previously, modest evidence of replication was observed only on the short arm of chromosome 8, where HLOD scores of 1.63 and 3.60 were observed in the complete set of families and families with young average age at diagnosis, respectively. The most significant linkage signals found in the complete set of families were observed across a broad, 37 cM interval on 4q13–25, with LOD scores ranging from 2.02 to 2.62, increasing to 4.50 in families with older average age at diagnosis. In families with multiple cases presenting with more aggressive disease, LOD scores over 3.0 were observed at 8q24 in the vicinity of previously identified common PC risk variants, as well as MYC , an important gene in PC biology. CONCLUSIONS These results will be useful in prioritizing future susceptibility gene discovery efforts in this common cancer. Prostate 72:410–426, 2012. © 2011 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90245/1/21443_ftp.pd

Global Changes in Staphylococcus aureus Gene Expression in Human Blood

Staphylococcus aureus is a leading cause of bloodstream infections worldwide. In the United States, many of these infections are caused by a strain known as USA300. Although progress has been made, our understanding of the S. aureus molecules that promote survival in human blood and ultimately facilitate metastases is incomplete. To that end, we analyzed the USA300 transcriptome during culture in human blood, human serum, and trypticase soy broth (TSB), a standard laboratory culture media. Notably, genes encoding several cytolytic toxins were up-regulated in human blood over time, and hlgA, hlgB, and hlgC (encoding gamma-hemolysin subunits HlgA, HlgB, and HlgC) were among the most highly up-regulated genes at all time points. Compared to culture supernatants from a wild-type USA300 strain (LAC), those derived from an isogenic hlgABC-deletion strain (LACΔhlgABC) had significantly reduced capacity to form pores in human neutrophils and ultimately cause neutrophil lysis. Moreover, LACΔhlgABC had modestly reduced ability to cause mortality in a mouse bacteremia model. On the other hand, wild-type and LACΔhlgABC strains caused virtually identical abscesses in a mouse skin infection model, and bacterial survival and neutrophil lysis after phagocytosis in vitro was similar between these strains. Comparison of the cytolytic capacity of culture supernatants from wild-type and isogenic deletion strains lacking hlgABC, lukS/F-PV (encoding PVL), and/or lukDE revealed functional redundancy among two-component leukotoxins in vitro. These findings, along with a requirement of specific growth conditions for leukotoxin expression, may explain the apparent limited contribution of any single two-component leukotoxin to USA300 immune evasion and virulence

Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families.

BACKGROUND: Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive. METHODS: Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed. RESULTS: Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2-3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded. CONCLUSIONS: Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2-3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage signals. Our results suggest that the genetic basis for prostate cancer in our families is much more complex than a single susceptibility locus on the X chromosome, and that future explorations of the Xq27-28 region should focus on the subset of families identified here with the strongest evidence of linkage to this region.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are