A proteomics study of the response of North Ronaldsay sheep to copper challenge

BACKGROUND: The objective of this proteomics study was to identify proteins that changed expression as a result of copper challenge in the uniquely copper sensitive North Ronaldsay sheep and further, to compare those changes in expression with the more copper tolerant Cambridge breed. Such data gives us a proteome-centered perspective of the pathogenesis of copper-induced oxidative stress in this breed. RESULTS: Many proteins respond to copper challenge, but this study focuses on those exhibiting a differential response between the two breeds, related to liver copper content. As copper accumulated in the tissue, the pattern of expression of several proteins was markedly different, in North Ronaldsay sheep as compared to the Cambridge breed. CONCLUSION: The pattern of changes was consistent with the greatly enhanced susceptibility of North Ronaldsay sheep to copper-induced oxidative stress, focused on mitochondrial disturbance with consequent activation of hepatic stellate cells. The expression profiles were sufficiently complex that the response could not simply be explained as a hypersensitivity to copper in North Ronaldsay sheep

Characterisation of infection associated microRNA and protein cargo in extracellular vesicles of Theileria annulata infected leukocytes

The protozoan parasites, Theileria annulata and T. parva are unique amongst intracellular eukaryotic pathogens as they induce a transformation‐like phenotype in their bovine host cell. T. annulata causes tropical theileriosis, which is frequently fatal, with infected leukocytes becoming metastatic and forming foci in multiple organs resulting in destruction of the lymphoid system. Exosomes, a sub‐set of extracellular vesicles (EV), are critical in metastatic progression in many cancers. Here we characterised the cargo of EV from a control bovine lymphosarcoma cell line (BL20) and BL20 infected with T. annulata (TBL20) by comparative mass spectrometry and miRNA profiling (data available via ProteomeXchange, identifier PXD010713 and NCBI GEO, accession number GSE118456, respectively). Ingenuity Pathway Analysis that many infection‐associated proteins essential to migration and extracellular matrix digestion were upregulated in EV from TBL20 cells compared to BL20 controls. An altered repertoire of host miRNA, many with known roles in tumor and/or infection biology was also observed. Focusing on the tumor suppressor miRNA, bta‐miR‐181a and bta‐miR‐181b, we identified putative mRNA targets and confirmed the interaction of bta‐miR181a with icam‐1. We propose that EV and their miRNA cargo play an important role in the manipulation of the host cell phenotype and the pathobiology of Theileria infection

Influenza Vaccine Effectiveness against Hospitalisation with Confirmed Influenza in the 2010-11 Seasons: A Test-negative Observational Study

Immunisation programs are designed to reduce serious morbidity and mortality from influenza, but most evidence supporting the effectiveness of this intervention has focused on disease in the community or in primary care settings. We aimed to examine the effectiveness of influenza vaccination against hospitalisation with confirmed influenza. We compared influenza vaccination status in patients hospitalised with PCR-confirmed influenza with patients hospitalised with influenza-negative respiratory infections in an Australian sentinel surveillance system. Vaccine effectiveness was estimated from the odds ratio of vaccination in cases and controls. We performed both simple multivariate regression and a stratified analysis based on propensity score of vaccination. Vaccination status was ascertained in 333 of 598 patients with confirmed influenza and 785 of 1384 test-negative patients. Overall estimated crude vaccine effectiveness was 57% (41%, 68%). After adjusting for age, chronic comorbidities and pregnancy status, the estimated vaccine effectiveness was 37% (95% CI: 12%, 55%). In an analysis accounting for a propensity score for vaccination, the estimated vaccine effectiveness was 48.3% (95% CI: 30.0, 61.8%). Influenza vaccination was moderately protective against hospitalisation with influenza in the 2010 and 2011 seasons

Darcin: a male pheromone that stimulates female memory and sexual attraction to an individual male's odour

<p>Abstract</p> <p>Background</p> <p>Among invertebrates, specific pheromones elicit inherent (fixed) behavioural responses to coordinate social behaviours such as sexual recognition and attraction. By contrast, the much more complex social odours of mammals provide a broad range of information about the individual owner and stimulate individual-specific responses that are modulated by learning. How do mammals use such odours to coordinate important social interactions such as sexual attraction while allowing for individual-specific choice? We hypothesized that male mouse urine contains a specific pheromonal component that invokes inherent sexual attraction to the scent and which also stimulates female memory and conditions sexual attraction to the airborne odours of an individual scent owner associated with this pheromone.</p> <p>Results</p> <p>Using wild-stock house mice to ensure natural responses that generalize across individual genomes, we identify a single atypical male-specific major urinary protein (MUP) of mass 18893Da that invokes a female's inherent sexual attraction to male compared to female urinary scent. Attraction to this protein pheromone, which we named darcin, was as strong as the attraction to intact male urine. Importantly, contact with darcin also stimulated a strong learned attraction to the associated airborne urinary odour of an individual male, such that, subsequently, females were attracted to the airborne scent of that specific individual but not to that of other males.</p> <p>Conclusions</p> <p>This involatile protein is a mammalian male sex pheromone that stimulates a flexible response to individual-specific odours through associative learning and memory, allowing female sexual attraction to be inherent but selective towards particular males. This 'darcin effect' offers a new system to investigate the neural basis of individual-specific memories in the brain and give new insights into the regulation of behaviour in complex social mammals.</p> <p>See associated Commentary <url>http://www.biomedcentral.com/1741-7007/8/71</url></p

Preliminary Characterisation of NP339, a Novel Polyarginine Peptide with Broad Antifungal Activity

FUNDING SOURCE The study was funded by NovaBiotics with support from The UK Governments’ Department of Health and Social Care, delivered by Innovate UK. Shane Smith and Carol Munro’s contribution to the project was funded by a Scottish Universities Life Sciences Alliance Bioskape grant award.Peer reviewedPublisher PD

Matrix metalloproteinase (MMP)-7 in Barrett’s esophagus and esophageal adenocarcinoma : expression, metabolism and functional significance

Supported by grants from North West Cancer Research (Grant number: CR945), The Wellcome Trust (Grant number: 074287/Z/03/Z) and a research studentship (HG) from the Libyan Government.Matrix metalloproteinase (MMP)‐7, unlike many MMPs, is typically expressed in epithelial cells. It has been linked to epithelial responses to infection, injury, and tissue remodeling including the progression of a number of cancers. We have now examined how MMP‐7 expression changes in the progression to esophageal adenocarcinoma (EAC), and have studied mechanisms regulating its expression and its functional significance. Immunohistochemistry revealed that MMP‐7 was weakly expressed in normal squamous epithelium adjacent to EAC but was abundant in epithelial cells in both preneoplastic lesions of Barrett's esophagus and EAC particularly at the invasive front. In the stroma, putative myofibroblasts expressing MMP‐7 were abundant at the invasive front but were scarce or absent in adjacent tissue. Western blot and ELISA revealed high constitutive secretion of proMMP‐7 in an EAC cell line (OE33) that was inhibited by the phosphatidylinositol (PI) 3‐kinase inhibitor LY294002 but not by inhibitors of protein kinase C, or MAP kinase activation. There was detectable proMMP‐7 in cultured esophageal myofibroblasts but it was undetectable in media. Possible metabolism of MMP‐7 by myofibroblasts studied by proteomic analysis indicated degradation via extensive endopeptidase, followed by amino‐ and carboxpeptidase, cleavages. Myofibroblasts exhibited increased migration and invasion in response to conditioned media from OE33 cells that was reduced by MMP‐7 knockdown and immunoneutralization. Thus, MMP‑7 expression increases at the invasive front in EAC which may be partly attributable to activation of PI 3‐kinase. Secreted MMP‐7 may modify the tumor microenvironment by stimulating stromal cell migration and invasion.Publisher PDFPeer reviewe

SHORT COMMUNICATION QCAL-a Novel Standard for Assessing Instrument Conditions for Proteome Analysis

If proteome datasets are to be collated, shared, and merged for higher level proteome analyses, there is a need for generally accepted strategies and reagents for optimization and standardization of instrument performance. At present, there is no single protein or peptide standard set that is capable of assessing instrument performance for peptide separation and analysis in this manner. To create such a standard, we have used the recently described QconCAT methodology to generate an artificial protein, QCAL. This protein, a concatenation of tryptic peptides that is expressed in E. coli, provides a stoichiometrically controlled mixture of peptides that are amenable to analysis by all commonly used instrumentation platforms for proteomics. (J Am Soc Mas

An Interactive Web-Based Lethal Means Safety Decision Aid for Suicidal Adults (Lock to Live): Pilot Randomized Controlled Trial

BACKGROUND: Counseling to reduce access to lethal means such as firearms and medications is recommended for suicidal adults but does not routinely occur. We developed the Web-based Lock to Live (L2L) decision aid to help suicidal adults and their families choose options for safer home storage. OBJECTIVE: This study aimed to test the feasibility and acceptability of L2L among suicidal adults in emergency departments (EDs). METHODS: At 4 EDs, we enrolled participants (English-speaking, community-dwelling, suicidal adults) in a pilot randomized controlled trial. Participants were randomized in a 13:7 ratio to L2L or control (website with general suicide prevention information) groups and received a 1-week follow-up telephone call. RESULTS: Baseline characteristics were similar between the intervention (n=33) and control (n=16) groups. At baseline, many participants reported having access to firearms (33/49, 67%), medications (46/49, 94%), or both (29/49, 59%). Participants viewed L2L for a median of 6 min (IQR 4-10 min). L2L also had very high acceptability; almost all participants reported that they would recommend it to someone in the same situation, that the options felt realistic, and that L2L was respectful of values about firearms. In an exploratory analysis of this pilot trial, more participants in the L2L group reported reduced firearm access at follow-up, although the differences were not statistically significant. CONCLUSIONS: The L2L decision aid appears feasible and acceptable for use among adults with suicide risk and may be a useful adjunct to lethal means counseling and other suicide prevention interventions. Future large-scale studies are needed to determine the effect on home access to lethal means. TRIAL REGISTRATION: ClinicalTrials.gov NCT03478501; https://clinicaltrials.gov/ct2/show/NCT03478501