Tributyltin (TBT) and the decline of the Norfolk Broads

This is the final report to the Department for Environment, Food & Rural Affairs (DEFRA) on the contract "Tributyltin (TBT) and the decline of the Norfolk Broads"

Common mental disorders and mortality in the West of Scotland Twenty-07 Study: comparing the General Health Questionnaire and the Hospital Anxiety and Depression Scale

Background While various measures of common mental disorders (CMD) have been found to be associated with mortality, a comparison of how different measures predict mortality may improve our understanding of the association. This paper compares how the Hospital Anxiety and Depression Scale (HADS) and the 30-item General Health Questionnaire (GHQ-30) predict all cause and cause-specific mortality. Methods Data on 2547 men and women from two cohorts, aged approximately 39 and 55 years, from the West of Scotland Twenty-07 Study who were followed up for mortality over an average of 18.9 (SD 5.0) years. Scores were calculated for HADS depression (HADS-D), HADS Anxiety (HADS-A) and GHQ-30. Cox Proportional Hazards Models were used to determine how each CMD measure predicted mortality. Results After adjusting for serious physical illness, smoking, social class, alcohol, obesity, pulse rate and living alone, HRs (95% CI) per SD increase in score for all-cause mortality were: 1.15 (1.07 to 1.25) for HADSD; 1.13 (1.04 to 1.23) for GHQ-30 and 1.05 (0.96 to 1.14) for HADS-A. After the same adjustments, cardiovascular disease mortality was also related to HADS-D (HR 1.24 (1.07 to 1.43)), to GHQ-30 (HR 1.24 (1.11 to 1.40)) and to HADS-A (HR 1.15 (1.01 to 1.32)); respiratory mortality to GHQ-30 (HR 1.33 (1.13 to 1.55)) and mortality from other causes, excluding injuries, to HADS-D (HR 1.28 (1.05 to 1.55)). Conclusions There were associations between CMD and both all-cause and cause-specific mortality which were broadly similar for GHQ-30 and HADS-D and were still present after adjustment for important confounders and mediators

Quantum Correlations in Multipartite Quantum Systems

We review some concepts and properties of quantum correlations, in particular multipartite measures, geometric measures and monogamy relations. We also discuss the relation between classical and total correlationsComment: to be published as a chapter of the book "Lectures on general quantum correlations and their applications" edited by F. Fanchini, D. Soares-Pinto, and G. Adesso (Springer, 2017

Blood Cholinesterases from Washington State Orchard Workers

Court-ordered monitoring of blood cholinesterases (ChEs) from orchard workers in Washington State is underway. In 2008, the mean red blood cell acetylcholinesterase (AChE, EC 3.1.1.7) activity was 9.65 ± 1.11 μmoles/min/ml (n = 1,793) and the mean serum (BChE, 3.1.1.6) activity was 5.19 ± 0.90 μmoles/min/ml (n = 1,811). Determinations were made using the Ellman assay and automated equipment of Pathology Associates Medical Laboratories (PAML), Spokane, Washington

Latent Epstein-Barr Virus Can Inhibit Apoptosis in B Cells by Blocking the Induction of NOXA Expression

Latent Epstein-Barr virus (EBV) has been shown to protect Burkitt's lymphoma-derived B cells from apoptosis induced by agents that cause damage to DNA, in the context of mutant p53. This protection requires expression of the latency-associated nuclear proteins EBNA3A and EBNA3C and correlates with their ability to cooperate in the repression of the gene encoding the pro-apoptotic, BH3-only protein BIM. Here we confirm that latent EBV in B cells also inhibits apoptosis induced by two other agents – ionomycin and staurosporine – and show that these act by a distinct pathway that involves a p53-independent increase in expression of another pro-apoptotic, BH3-only protein, NOXA. Analyses employing a variety of B cells infected with naturally occurring EBV or B95.8 EBV-BAC recombinant mutants indicated that the block to NOXA induction does not depend on the well-characterized viral latency-associated genes (EBNAs 1, 2, 3A, 3B, 3C, the LMPs or the EBERs) or expression of BIM. Regulation of NOXA was shown to be at least partly at the level of mRNA and the requirement for NOXA to induce cell death in this context was demonstrated by NOXA-specific shRNA-mediated depletion experiments. Although recombinant EBV with a deletion removing the BHRF1 locus – that encodes the BCL2-homologue BHRF1 and three microRNAs – partially abrogates protection against ionomycin and staurosporine, the deletion has no effect on the EBV-mediated block to NOXA accumulation

A novel isolator-based system promotes viability of human embryos during laboratory processing

In vitro fertilisation (IVF) and related technologies are arguably the most challenging of all cell culture applications. The starting material is a single cell from which one aims to produce an embryo capable of establishing a pregnancy eventually leading to a live birth. Laboratory processing during IVF treatment requires open manipulations of gametes and embryos, which typically involves exposure to ambient conditions. To reduce the risk of cellular stress, we have developed a totally enclosed system of interlinked isolator-based workstations designed to maintain oocytes and embryos in a physiological environment throughout the IVF process. Comparison of clinical and laboratory data before and after the introduction of the new system revealed that significantly more embryos developed to the blastocyst stage in the enclosed isolator-based system compared with conventional open-fronted laminar flow hoods. Moreover, blastocysts produced in the isolator-based system contained significantly more cells and their development was accelerated. Consistent with this, the introduction of the enclosed system was accompanied by a significant increase in the clinical pregnancy rate and in the proportion of embryos implanting following transfer to the uterus. The data indicate that protection from ambient conditions promotes improved development of human embryos. Importantly, we found that it was entirely feasible to conduct all IVF-related procedures in the isolator-based workstations

Suppression of the ATP-binding cassette transporter ABCC4 impairs neuroblastoma tumour growth and sensitises to irinotecan in vivo

The ATP-binding cassette transporter ABCC4 (multidrug resistance protein 4, MRP4) mRNA level is a strong predictor of poor clinical outcome in neuroblastoma which may relate to its export of endogenous signalling molecules and chemotherapeutic agents. We sought to determine whether ABCC4 contributes to development, growth and drug response in neuroblastoma in vivo. In neuroblastoma patients, high ABCC4 protein levels were associated with reduced overall survival. Inducible knockdown of ABCC4 strongly inhibited the growth of human neuroblastoma cells in vitro and impaired the growth of neuroblastoma xenografts. Loss of Abcc4 in the Th-MYCN transgenic neuroblastoma mouse model did not impact tumour formation; however, Abcc4-null neuroblastomas were strongly sensitised to the ABCC4 substrate drug irinotecan. Our findings demonstrate a role for ABCC4 in neuroblastoma cell proliferation and chemoresistance and provide rationale for a strategy where inhibition of ABCC4 should both attenuate the growth of neuroblastoma and sensitise tumours to ABCC4 chemotherapeutic substrates

The microaerophilic microbiota of de-novo paediatric inflammatory bowel disease: the BISCUIT study

<p>Introduction: Children presenting for the first time with inflammatory bowel disease (IBD) offer a unique opportunity to study aetiological agents before the confounders of treatment. Microaerophilic bacteria can exploit the ecological niche of the intestinal epithelium; Helicobacter and Campylobacter are previously implicated in IBD pathogenesis. We set out to study these and other microaerophilic bacteria in de-novo paediatric IBD.</p> <p>Patients and Methods: 100 children undergoing colonoscopy were recruited including 44 treatment naïve de-novo IBD patients and 42 with normal colons. Colonic biopsies were subjected to microaerophilic culture with Gram-negative isolates then identified by sequencing. Biopsies were also PCR screened for the specific microaerophilic bacterial groups: Helicobacteraceae, Campylobacteraceae and Sutterella wadsworthensis.</p> <p>Results: 129 Gram-negative microaerophilic bacterial isolates were identified from 10 genera. The most frequently cultured was S. wadsworthensis (32 distinct isolates). Unusual Campylobacter were isolated from 8 subjects (including 3 C. concisus, 1 C. curvus, 1 C. lari, 1 C. rectus, 3 C. showae). No Helicobacter were cultured. When comparing IBD vs. normal colon control by PCR the prevalence figures were not significantly different (Helicobacter 11% vs. 12%, p = 1.00; Campylobacter 75% vs. 76%, p = 1.00; S. wadsworthensis 82% vs. 71%, p = 0.312).</p> <p>Conclusions: This study offers a comprehensive overview of the microaerophilic microbiota of the paediatric colon including at IBD onset. Campylobacter appear to be surprisingly common, are not more strongly associated with IBD and can be isolated from around 8% of paediatric colonic biopsies. S. wadsworthensis appears to be a common commensal. Helicobacter species are relatively rare in the paediatric colon.</p&gt

Looking to Score: The Dissociation of Goal Influence on Eye Movement and Meta-Attentional Allocation in a Complex Dynamic Natural Scene

Several studies have reported that task instructions influence eye-movement behavior during static image observation. In contrast, during dynamic scene observation we show that while the specificity of the goal of a task influences observers’ beliefs about where they look, the goal does not in turn influence eye-movement patterns. In our study observers watched short video clips of a single tennis match and were asked to make subjective judgments about the allocation of visual attention to the items presented in the clip (e.g., ball, players, court lines, and umpire). However, before attending to the clips, observers were either told to simply watch clips (non-specific goal), or they were told to watch the clips with a view to judging which of the two tennis players was awarded the point (specific goal). The results of subjective reports suggest that observers believed that they allocated their attention more to goal-related items (e.g. court lines) if they performed the goal-specific task. However, we did not find the effect of goal specificity on major eye-movement parameters (i.e., saccadic amplitudes, inter-saccadic intervals, and gaze coherence). We conclude that the specificity of a task goal can alter observer’s beliefs about their attention allocation strategy, but such task-driven meta-attentional modulation does not necessarily correlate with eye-movement behavior

Metabolic Profiling of Hypoxic Cells Revealed a Catabolic Signature Required for Cell Survival

Hypoxia is one of the features of poorly vascularised areas of solid tumours but cancer cells can survive in these areas despite the low oxygen tension. The adaptation to hypoxia requires both biochemical and genetic responses that culminate in a metabolic rearrangement to counter-balance the decrease in energy supply from mitochondrial respiration. The understanding of metabolic adaptations under hypoxia could reveal novel pathways that, if targeted, would lead to specific death of hypoxic regions. In this study, we developed biochemical and metabolomic analyses to assess the effects of hypoxia on cellular metabolism of HCT116 cancer cell line. We utilized an oxygen fluorescent probe in anaerobic cuvettes to study oxygen consumption rates under hypoxic conditions without the need to re-oxygenate the cells and demonstrated that hypoxic cells can maintain active, though diminished, oxidative phosphorylation even at 1% oxygen. These results were further supported by in situ microscopy analysis of mitochondrial NADH oxidation under hypoxia. We then used metabolomic methodologies, utilizing liquid chromatography–mass spectrometry (LC-MS), to determine the metabolic profile of hypoxic cells. This approach revealed the importance of synchronized and regulated catabolism as a mechanism of adaptation to bioenergetic stress. We then confirmed the presence of autophagy under hypoxic conditions and demonstrated that the inhibition of this catabolic process dramatically reduced the ATP levels in hypoxic cells and stimulated hypoxia-induced cell death. These results suggest that under hypoxia, autophagy is required to support ATP production, in addition to glycolysis, and that the inhibition of autophagy might be used to selectively target hypoxic regions of tumours, the most notoriously resistant areas of solid tumours