Intersex related gene expression profiles in clams Scrobicularia plana : molecular markers and environmental application

Intersex, the appearance of female characteristics in male gonads, has been identified in several aquatic species. It is a widespread phenomenon in populations of the bivalve, Scrobicularia plana, from the southwest coast of the U.K. Genes previously identified as differentially expressed (ferritin, testicular haploid expressed gene, THEG, proliferating cell nuclear antigen, PCNA; receptor activated protein kinase C, RACK; cytochrome B, CYB; and cytochrome c oxidase 1, COX1) in intersex clams relative to normal male clams, were selected for characterisation and an environmental survey of the Channel region. Transcripts were significantly differentially expressed at sites with varying intersex incidence and contaminant burdens. Significant correlations between specific gene expressions, key contaminants and sampling locations have been identified, though no single gene was associated with intersex incidence. The results highlight the difficulty in understanding the intersex phenomenon in molluscs where there is still a lack of knowledge on the control of normal reproduction

Toxicity of polyelectrolyte-functionalized titania nanoparticles in zebrafish (Danio rerio) embryos

We investigated the effects of short-term exposure of bare TiO2NPs and polyelectrolyte-coated TiO2NPs in the 5-25 nm size range, at relatively high concentrations (of 500 and 1000 mg/L) under light or dark conditions, in D. rerio embryos. The biological endpoints investigated included embryo viability and mRNA transcript levels of antioxidant and membrane transport genes relative to control embryos. The presence of nanoparticles on the surface of embryos was assessed using TEM. The results confirm an accumulation of TiO2NPs on the outer surface (chorion) of the embryo, but not within the embryo. No significant difference in embryo viability was detected following each exposure regime. The expression of antioxidant biomarker, SOD2, was significantly impacted by the type of TiO2NP, with TiO2NPs/PSS/PAH coating exposure showing down regulation; the concentration of the nanoparticles, with down regulation at 500 mg/L; and dark/light condition with down regulation in the light. The expression levels of the hypoxia and membrane markers, HIF1 and Pxmp2, were not significantly impacted by any factor. The study indicates that SOD2 mRNA expression levels may be useful in the detection of apparent oxidative stress induced by the titania nanoparticle build up on the embryo chorion surface

Identification of Reproduction-Specific Genes Associated with Maturation and Estrogen Exposure in a Marine Bivalve Mytilus edulis

Background: While it is established that vertebrate-like steroids, particularly estrogens (estradiol, estrone) and androgens (testosterone), are present in various tissues of molluscs, it is still unclear what role these play in reproductive endocrinology in such organisms. This is despite the significant commercial shellfishery interest in several bivalve species and their decline. Methodology/Principal Findings: Using suppression subtraction hybridisation of mussel gonad samples at two stages (early and mature) of gametogenesis and (in parallel) following controlled laboratory estrogen exposure, we isolate several differentially regulated genes including testis-specific kinases, vitelline lysin and envelope sequences. Conclusions: The differentially expressed mRNAs isolated provide evidence that mussels may be impacted by exogenous estrogen exposure

Insights into technical challenges in the field of microplastic pollution through the lens of early career researchers (ECRs) and a proposed pathway forward

Early career researchers (ECR) face a series of challenges related to the inherent difficulties of starting their careers. Microplastic (MP) research is a topical field attracting high numbers of ECRs with diverse backgrounds and expertise from a wealth of disciplines including environmental science, biology, chemistry and ecotoxicology. In this perspective the challenges that could hinder scientific, professional, or personal development are explored, as identified by an international network of ECRs, all employed in MP research, that was formed following a bilateral workshop for scientists based in the UK and China. Discussions amongst the network were grouped into four overarching themes of technical challenges: in the field, in the laboratory, in the post data collection phase, and miscellaneous. The three key areas of representativeness, access t

Zebrafish Whole-Adult-Organism Chemogenomics for Large-Scale Predictive and Discovery Chemical Biology

The ability to perform large-scale, expression-based chemogenomics on whole adult organisms, as in invertebrate models (worm and fly), is highly desirable for a vertebrate model but its feasibility and potential has not been demonstrated. We performed expression-based chemogenomics on the whole adult organism of a vertebrate model, the zebrafish, and demonstrated its potential for large-scale predictive and discovery chemical biology. Focusing on two classes of compounds with wide implications to human health, polycyclic (halogenated) aromatic hydrocarbons [P(H)AHs] and estrogenic compounds (ECs), we generated robust prediction models that can discriminate compounds of the same class from those of different classes in two large independent experiments. The robust expression signatures led to the identification of biomarkers for potent aryl hydrocarbon receptor (AHR) and estrogen receptor (ER) agonists, respectively, and were validated in multiple targeted tissues. Knowledge-based data mining of human homologs of zebrafish genes revealed highly conserved chemical-induced biological responses/effects, health risks, and novel biological insights associated with AHR and ER that could be inferred to humans. Thus, our study presents an effective, high-throughput strategy of capturing molecular snapshots of chemical-induced biological states of a whole adult vertebrate that provides information on biomarkers of effects, deregulated signaling pathways, and possible affected biological functions, perturbed physiological systems, and increased health risks. These findings place zebrafish in a strategic position to bridge the wide gap between cell-based and rodent models in chemogenomics research and applications, especially in preclinical drug discovery and toxicology

Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial

Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects. Methods FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762. Findings Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months. Interpretation Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function. Funding UK Stroke Association and NIHR Health Technology Assessment Programme

Community nurses', home carers' and patients' perceptions of factors affecting venous leg ulcer recurrence and management of services

The definitive version is available at www3.interscience.wiley.com Copyright Blackwell [Full text of this article is not available in the UHRA]Aim: This study examines the feasibility of utilizing social service home carers (SSHC) to provide a collaborative approach with community nurses for the provision of leg ulcer aftercare in four National Health Service (NHS) Trusts. The purpose of this study was to gain insight into what community nurses and people with healed venous leg ulcers felt influenced leg ulcer recurrence. Background: Studies have demonstrated that provision of community-based leg ulcer clinics has improved healing rates of venous leg ulcers, yet recurrence remains a problem. The reasons for this are far from clear, and further research is required before unequivocal support can be given to one approach to the provision of care for this client group. Collaborative approaches to the provision of leg ulcer aftercare are beginning to receive more attention. It has been recognized that social service health carers could be co-opted to provide essential aftercare once healing has occurred, although the logistics of this approach have not been fully explored. Methods: This study was conducted in four NHS Trusts. Stage one used focus groups to explore the perceptions of district nurses (n = 15) and social service health carers (n = 15) of a leg ulcer shared care project and to gain insight into factors that they felt influenced recurrence. The second stage used semistructured interviews (n = 12) to explore the perceptions that people with healed leg ulcers have about factors influencing ulcer recurrence. Findings: Key themes emerging from this study were: health promotion is perceived by community nurses and patients to be ineffective and leg ulcer aftercare services are fragmented. Organizational factors such as time constraints and limited resources were cited by community nurses and home carers as being responsible for high leg ulcer recurrence rates. Community nurses expressed a desire to delegate preventative aspects of leg ulcer care to home carers rather than participate in health promotion strategies to support healing behaviours. Conclusions: A strategy aimed at supporting healing behaviour in elderly people has the potential to reduce the recurrence of leg ulceration and improve quality of life. The findings suggest that such a strategy needs to rationalize delivery of leg ulcer aftercare to provide seamless care. It needs to improve carers' and patients' understanding of factors influencing leg ulcer recurrence and facilitate development of a more balanced professional–patient relationship.Peer reviewe

The provision of leg ulcer services by practice nurses

Original article can be found at: http://nursingstandard.rcnpublishing.co.uk/ Copyright RCN Publishing Company Limited [Full text of this article is not available in the UHRA]Peer reviewe