Endocrine disruption in juvenile roach from English rivers: A preliminary study

Juvenile roach Rutilus rutilus from seven rivers of varying water quality were examined for evidence of endocrine disruption. The majority of roach from five of these rivers had femalelike reproductive ducts. The results suggest that juvenile, rather than adult, fish could be used in studies of endocrine disruption in wild fish populations

ProtocadherinX/Y, a Candidate Gene-Pair for Schizophrenia and Schizoaffective Disorder: A DHPLC Investigation of Gonomic Sequence

Protocadherin X and Protocadherin Y (PCDHX and PCDHY) are cell-surface adhesion molecules expressed predominantly in the brain. The PCDHX/Y gene-pair was generated by an X-Y translocation approximately 3 million years ago (MYA) that gave rise to the Homo sapiens-specific region of Xq21.3 and Yp11.2 homology. Genes within this region are expected to code for sexually dimorphic human characteristics, including, for example, cerebral asymmetry a dimension of variation that has been suggested is relevant to psychosis. We examined differences in patients with schizophrenic or schizoaffective psychosis in the genomic sequence of PCDHX and PCDHY in coding and adjacent intronic sequences using denaturing high performance liquid chromatography (DHPLC). Three coding variants were detected in PCDHX and two in PCDHY. However, neither the coding variants nor the intronic polymorphisms could be related to psychosis within families. Low sequence variation suggests selective pressure against sequence change in modern humans in contrast to the structural chromosomal and sequence changes including fixed X-Y differences that occurred in this region earlier in hominid evolution. Our findings exclude sequence variation in PCDHX/Y as relevant to the aetiology of psychosis. However, we note the unusual status of this region with respect to X-inactivation. Further investigation of the epigenetic control of PCDHX/Y in relation to psychosis is warran

Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis

Background/Aims: Studies in acute liver failure show correlation between evidence of a systemic inflammatory response syndrome (SIRS) and progression of hepatic encephalopathy (HE). We tested the hypothesis that SIRS mediators, such as nitric oxide and proinflammatory cytokines, may exacerbate the neuropsychological effects of hyperammonemia in cirrhosis.Methods: Ten patients with cirrhosis were studied, 24-36 h after admission with clinical evidence of infection, and following its resolution. Hyperammonemia was induced by oral administration of an amino-acid (aa) solution mimicking hemoglobin composition. Inflammatory mediators, nitrate/nitrite, ammonia, aa profiles and a battery of neuropsychological tests were measured.Results: The hyperammonemia generated in response to the aa solution was similar prior to, and after resolution, of the inflammation (P = 0.77). With treatment of the infection there were significant reductions in white blood cell count (WBC), C-reactive protein (CRP), nitrate/nitrite, interleukin-6, interieukin-1beta and tumour necrosis factor alpha. Induced hyperammonemia resulted in significant worsening of the neuropsychological scores when patients showed evidence of SIRS but not after its resolution.Conclusions: The significant deterioration of neuropsychological test scores following induced hyperammonemia during the inflammatory state, but not after its resolution, suggests that the inflammation and its mediators may be important in modulating the cerebral effect of ammonia in liver disease. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved

Distinct emphysema subtypes defined by quantitative CT analysis are associated with specific pulmonary matrix metalloproteinases.

BACKGROUND: Emphysema is characterised by distinct pathological sub-types, but little is known about the divergent underlying aetiology. Matrix-metalloproteinases (MMPs) are proteolytic enzymes that can degrade the extracellular matrix and have been identified as potentially important in the development of emphysema. However, the relationship between MMPs and emphysema sub-type is unknown. We investigated the role of MMPs and their inhibitors in the development of emphysema sub-types by quantifying levels and determining relationships with these sub-types in mild-moderate COPD patients and ex/current smokers with preserved lung function. METHODS: Twenty-four mild-moderate COPD and 8 ex/current smokers with preserved lung function underwent high resolution CT and distinct emphysema sub-types were quantified using novel local histogram-based assessment of lung density. We analysed levels of MMPs and tissue inhibitors of MMPs (TIMPs) in bronchoalveolar lavage (BAL) and assessed their relationship with these emphysema sub-types. RESULTS: The most prevalent emphysema subtypes in COPD subjects were mild and moderate centrilobular (CLE) emphysema, while only small amounts of severe centrilobular emphysema, paraseptal emphysema (PSE) and panlobular emphysema (PLE) were present. MMP-3, and -10 associated with all emphysema sub-types other than mild CLE, while MMP-7 and -8 had associations with moderate and severe CLE and PSE. MMP-9 also had associations with moderate CLE and paraseptal emphysema. Mild CLE occurred in substantial quantities irrespective of whether airflow obstruction was present and did not show any associations with MMPs. CONCLUSION: Multiple MMPs are directly associated with emphysema sub-types identified by CT imaging, apart from mild CLE. This suggests that MMPs play a significant role in the tissue destruction seen in the more severe sub-types of emphysema, whereas early emphysematous change may be driven by a different mechanism. TRIAL REGISTRATION: Trial registration number NCT01701869

Online scan of FASD prevention and health promotion resources for Aboriginal and Torres Strait Islander communities

© 2017 The Authors. Health Promotion Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of Australian Health Promotion Association Issue addressed: Foetal Alcohol Spectrum Disorder (FASD) includes a range of life-long impairments caused by alcohol exposure in utero. Health professionals are vital to preventing FASD but many are hesitant to discuss FASD with clients due to their need for additional resources to aid the conversation. This scan sought to identify the scope and gaps in publicly available FASD prevention and health promotion resources, and assess their cultural appropriateness for use among five key groups of Indigenous Australian people including: (i) pregnant women, (ii) women of childbearing age, (iii) grandmothers and aunties, (iv) men, and (v) health professionals. Methods: Relevant resources published 1995-2017 were identified through the Australian Indigenous HealthInfoNet, FASD organisation websites, grey literature, Google searches, and field experts. Results were screened by inclusion and cultural appropriateness criteria developed and piloted by the research team, and further screened by health professionals attending FASD training workshops. Results: 115 of the 2146 identified resources were eligible. Relevant resources were found for all five key groups; however, no resources were specifically designed for men, grandmothers or aunties. Conclusions: A range of high-quality, culturally appropriate resources were identified, however, health professionals attending the training workshops were not aware of their availability. Further resource development is suggested for men, grandmothers and aunties. So what?: Prioritisation of active dissemination and implementation strategies is suggested to increase awareness and use of future resource developments. The inclusion of a resource trial among health professionals is a recommended strategy to increase awareness and use of newly developed resources

GLP-1 action in the mouse bed nucleus of the stria terminalis

Glucagon-like peptide-1 (GLP-1) injected into the brain reduces food intake. Similarly, activation of preproglucagon (PPG) cells in the hindbrain which synthesize GLP-1, reduces food intake. However, it is far from clear whether this happens because of satiety, nausea, reduced reward, or even stress. Here we explore the role of the bed nucleus of the stria terminalis (BNST), an area involved in feeding control as well as stress responses, in GLP-1 responses. Using cre-expressing mice we visualized projections of NTS PPG neurons and GLP-1R-expressing BNST cells with AAV-driven Channelrhodopsin-YFP expression. The BNST displayed many varicose YFP+ PPG axons in the ventral and less in the dorsal regions. Mice which express RFP in GLP-1R neurons had RFP+ cells throughout the BNST with the highest density in the dorsal part, suggesting that PPG neuron-derived GLP-1 acts in the BNST. Indeed, injection of GLP-1 into the BNST reduced chow intake during the dark phase, whereas injection of the GLP-1 receptor antagonist Ex9 increased feeding. BNST-specific GLP-1-induced food suppression was less effective in mice on high fat (HF, 60%) diet, and Ex9 had no effect. Restraint stress-induced hypophagia was attenuated by BNST Ex9 treatment, further supporting a role for endogenous brain GLP-1. Finally, whole-cell patch clamp recordings of RFP+ BNST neurons demonstrated that GLP-1 elicited either a depolarizing or hyperpolarizing reversible response that was of opposite polarity to that under dopamine. Our data support a physiological role for BNST GLP-1R in feeding, and suggest complex cellular responses to GLP-1 in this nucleus

Caribbean Lecturers’ Self-Efficacy and Their Perceived Barriers to Technology Adoption

Educational technology is a learning tool that helps lecturers enhance learning through instructional practices; however, it is unclear why lecturers have difficulties adopting technology. The purpose of this study was to examine how lecturers’ self-efficacy at one college in Antigua and Barbuda influenced their technology adoption in terms of their instructional practices, including perceived barriers and supports for technology use. The conceptual frameworks for this study were Bandura’s self-efficacy theory and Rogers’ diffusion of innovation. The study included nine lecturers from a Caribbean college in Antigua and Barbuda as participants. Data were collected through interviews and analyzed using open coding and thematic analysis. Findings from the study were that college lecturers’ beliefs regarding technology were positive and technology held value in terms of the learning process. However, the results established that not all lecturers were comfortable adopting technology within their instructional practice and faced barriers when attempting to adopt technology. Lecturers indicated the need for professional training, institutional support, and observational learning of others which would assist with lecturers’ pedagogy, content knowledge, and technology adoption. The results of the study may lead to social change by revealing potential barriers that lecturers face during technology use. The study can also provide both lecturers and stakeholders with data that is Caribbean-specific and can provide the most effective plan to support lecturers’ adoption of technology

Identification of the protein kinases Pyk3 and Phg2 as regulators of the STATc-mediated response to hyperosmolarity

Cellular adaptation to changes in environmental osmolarity is crucial for cell survival. In Dictyostelium, STATc is a key regulator of the transcriptional response to hyperosmotic stress. Its phosphorylation and consequent activation is controlled by two signaling branches, one cGMP- and the other Ca(2+)-dependent, of which many signaling components have yet to be identified. The STATc stress signalling pathway feeds back on itself by upregulating the expression of STATc and STATc-regulated genes. Based on microarray studies we chose two tyrosine-kinase like proteins, Pyk3 and Phg2, as possible modulators of STATc phosphorylation and generated single and double knock-out mutants to them. Transcriptional regulation of STATc and STATc dependent genes was disturbed in pyk3(-), phg2(-), and pyk3(-)/phg2(-) cells. The absence of Pyk3 and/or Phg2 resulted in diminished or completely abolished increased transcription of STATc dependent genes in response to sorbitol, 8-Br-cGMP and the Ca(2+) liberator BHQ. Also, phospho-STATc levels were significantly reduced in pyk3(-) and phg2(-) cells and even further decreased in pyk3(-)/phg2(-) cells. The reduced phosphorylation was mirrored by a significant delay in nuclear translocation of GFP-STATc. The protein tyrosine phosphatase 3 (PTP3), which dephosphorylates and inhibits STATc, is inhibited by stress-induced phosphorylation on S448 and S747. Use of phosphoserine specific antibodies showed that Phg2 but not Pyk3 is involved in the phosphorylation of PTP3 on S747. In pull-down assays Phg2 and PTP3 interact directly, suggesting that Phg2 phosphorylates PTP3 on S747 in vivo. Phosphorylation of S448 was unchanged in phg2(-) cells. We show that Phg2 and an, as yet unknown, S448 protein kinase are responsible for PTP3 phosphorylation and hence its inhibition, and that Pyk3 is involved in the regulation of STATc by either directly or indirectly activating it. Our results add further complexities to the regulation of STATc, which presumably ensure its optimal activation in response to different environmental cues

Preface

The University of Pennsylvania Working Papers in Linguistics (PWPL) is an occasional series published by the Penn Linguistics Club, the graduate student organization of the Linguistics Department of the University of Pennsylvania. The series has included volumes of previously unpublished work, or work in progress, by linguists with an ongoing affiliation with the Department, as well as volumes of papers from the NWAVE conference and the Penn Linguistics Colloquium. The current PWPL series editors are Jim Alexander, Alexis Dimitriadis, Na-­‐Rae Han, Elsi Kaiser, Michelle Minnick Fox, Christine Moisset, and Alexander Williams