High-resolution complementary chemical imaging of bio-elements in Caenorhabditis elegans

© 2016 The Royal Society of Chemistry. Here, we present a sub-μm multimodal approach to image essential elements in Caenorhabditis elegans. A combination of chemical imaging technologies reveals total metal concentration, chemical state and the protein to which an element is associated. This application of distinct yet complementary chemical imaging techniques provided unique insight into essential and trace elements at the subcellular level

Efficacy and safety of enzyme replacement therapy with BMN 110 (elosulfase alfa) for Morquio A syndrome (mucopolysaccharidosis IVA): a phase 3 randomised placebo-controlled study.

ObjectiveTo assess the efficacy and safety of enzyme replacement therapy (ERT) with BMN 110 (elosulfase alfa) in patients with Morquio A syndrome (mucopolysaccharidosis IVA).MethodsPatients with Morquio A aged ≥5 years (N = 176) were randomised (1:1:1) to receive elosulfase alfa 2.0 mg/kg/every other week (qow), elosulfase alfa 2.0 mg/kg/week (weekly) or placebo for 24 weeks in this phase 3, double-blind, randomised study. The primary efficacy measure was 6-min walk test (6MWT) distance. Secondary efficacy measures were 3-min stair climb test (3MSCT) followed by change in urine keratan sulfate (KS). Various exploratory measures included respiratory function tests. Patient safety was also evaluated.ResultsAt week 24, the estimated mean effect on the 6MWT versus placebo was 22.5 m (95 % CI 4.0, 40.9; P = 0.017) for weekly and 0.5 m (95 % CI -17.8, 18.9; P = 0.954) for qow. The estimated mean effect on 3MSCT was 1.1 stairs/min (95 % CI -2.1, 4.4; P = 0.494) for weekly and -0.5 stairs/min (95 % CI -3.7, 2.8; P = 0.778) for qow. Normalised urine KS was reduced at 24 weeks in both regimens. In the weekly dose group, 22.4 % of patients had adverse events leading to an infusion interruption/discontinuation requiring medical intervention (only 1.3 % of all infusions in this group) over 6 months. No adverse events led to permanent treatment discontinuation.ConclusionsElosulfase alfa improved endurance as measured by the 6MWT in the weekly but not qow dose group, did not improve endurance on the 3MSCT, reduced urine KS, and had an acceptable safety profile

Determination of Cytomegalovirus Prevalence and Glycoprotein B Genotypes Among Ulcerative Colitis Patients in Ahvaz, Iran

Background: The human cytomegalovirus (HCMV) is a common pathogen which usually remains asymptomatic in the healthy adults; however, it can cause a symptomatic disease in the immunocompromised patients. The risk of infection with HCMV increases in ulcerative colitis (UC) patients as a result of receiving immunosuppressive agents. Objectives: This study aimed to determine the prevalence and the glycoprotein B genotypes of HCMV among the patients with HCMV disease superimposed on an UC flare that required hospitalization in Imam Khomeini Hospital in Ahvaz, Iran, during 2010- 2012. Patients and Methods: In this case-control study, formalin-fixed paraffin-embedded intestinal tissue samples were taken from 98 patients with UC disease including 53 males and 45 females (mean age ± standard deviation, 38.95 ± 17.93) and 67 control patients with noninflammatory disease who were referred to Imam Khomeini Hospital during 2010-2012. Detection of HCMV genome in intestinal samples was carried out by seminested polymerase chain reaction. Glycoprotein B genotypes were determined by sequencing. Results: Among 98 patients with UC, only 12 (12.2%) patients were positive for HCMV genome, while the HCMV genome was not detected in any of the controls. (P = 0.002). The distribution of HCMV gB genotypes in 12 CMV-positive UC patients was as follow: gB1, 11 (91.7%) and gB3, 1 (8.3%). The most prevalent genotype in CMV-positive UC patients was gB1. Conclusions: In this study, high prevalence of 91.7% HCMV gB1 genotype was predominant among HCMV-positive UC patients, which suggests that there might be an association between HCMV gB genotype 1 and UC disease

Reduced level of arousal and increased mortality in adult acute medical admissions: a systematic review and meta-analysis

Abstract Background Reduced level of arousal is commonly observed in medical admissions and may predict in-hospital mortality. Delirium and reduced level of arousal are closely related. We systematically reviewed and conducted a meta-analysis of studies in adult acute medical patients of the relationship between reduced level of arousal on admission and in-hospital mortality. Methods We conducted a systematic review (PROSPERO: CRD42016022048), searching MEDLINE and EMBASE. We included studies of adult patients admitted with acute medical illness with level of arousal assessed on admission and mortality rates reported. We performed meta-analysis using a random effects model. Results From 23,941 studies we included 21 with 14 included in the meta-analysis. Mean age range was 33.4 - 83.8 years. Studies considered unselected general medical admissions (8 studies, n=13,039) or specific medical conditions (13 studies, n=38,882). Methods of evaluating level of arousal varied. The prevalence of reduced level of arousal was 3.1%-76.9% (median 13.5%). Mortality rates were 1.7%-58% (median 15.9%). Reduced level of arousal was associated with higher in-hospital mortality (pooled OR 5.71; 95% CI 4.21-7.74; low quality evidence: high risk of bias, clinical heterogeneity and possible publication bias). Conclusions Reduced level of arousal on hospital admission may be a strong predictor of in-hospital mortality. Most evidence was of low quality. Reduced level of arousal is highly specific to delirium, better formal detection of hypoactive delirium and implementation of care pathways may improve outcomes. Future studies to assess the impact of interventions on in-hospital mortality should use validated assessments of both level of arousal and delirium

Dissociable effects of 5-HT2C receptor antagonism and genetic inactivation on perseverance and learned non-reward in an egocentric spatial reversal task

Cognitive flexibility can be assessed in reversal learning tests, which are sensitive to modulation of 5-HT2C receptor (5-HT2CR) function. Successful performance in these tests depends on at least two dissociable cognitive mechanisms which may separately dissipate associations of previous positive and negative valence. The first is opposed by perseverance and the second by learned non-reward. The current experiments explored the effect of reducing function of the 5-HT2CR on the cognitive mechanisms underlying egocentric reversal learning in the mouse. Experiment 1 used the 5-HT2CR antagonist SB242084 (0.5 mg/kg) in a between-groups serial design and Experiment 2 used 5-HT2CR KO mice in a repeated measures design. Animals initially learned to discriminate between two egocentric turning directions, only one of which was food rewarded (denoted CS+, CS−), in a T- or Y-maze configuration. This was followed by three conditions; (1) Full reversal, where contingencies reversed; (2) Perseverance, where the previous CS+ became CS− and the previous CS− was replaced by a novel CS+; (3) Learned non-reward, where the previous CS− became CS+ and the previous CS+ was replaced by a novel CS-. SB242084 reduced perseverance, observed as a decrease in trials and incorrect responses to criterion, but increased learned non-reward, observed as an increase in trials to criterion. In contrast, 5-HT2CR KO mice showed increased perseverance. 5-HT2CR KO mice also showed retarded egocentric discrimination learning. Neither manipulation of 5-HT2CR function affected performance in the full reversal test. These results are unlikely to be accounted for by increased novelty attraction, as SB242084 failed to affect performance in an unrewarded novelty task. In conclusion, acute 5-HT2CR antagonism and constitutive loss of the 5-HT2CR have opposing effects on perseverance in egocentric reversal learning in mice. It is likely that this difference reflects the broader impact of 5HT2CR loss on the development and maintenance of cognitive function

New insights into the classification and nomenclature of cortical GABAergic interneurons.

A systematic classification and accepted nomenclature of neuron types is much needed but is currently lacking. This article describes a possible taxonomical solution for classifying GABAergic interneurons of the cerebral cortex based on a novel, web-based interactive system that allows experts to classify neurons with pre-determined criteria. Using Bayesian analysis and clustering algorithms on the resulting data, we investigated the suitability of several anatomical terms and neuron names for cortical GABAergic interneurons. Moreover, we show that supervised classification models could automatically categorize interneurons in agreement with experts' assignments. These results demonstrate a practical and objective approach to the naming, characterization and classification of neurons based on community consensus

Ecosystem service provision by marine habitats in Southeast Asia

Southeast Asia is an area of rich marine biodiversity providing a host of ecosystem services that contribute to the well-being of coastal communities and beyond. Sustainable management of ecosystems and the services they provide requires a good understanding of their underlying ecological functions and processes. This understanding can be gained through the rigorous assessment of studies identifying and quantifying ecological functions and ecosystem services. The aims of this study were to review the ecosystem services provided by marine and coastal habitats in Southeast Asia. The ecosystem service potential was scored for each habitat. The review was focused on nine key marine and coastal habitats, identified across four case study sites in Southeast Asia, contributing 18 marine relevant ecosystem services. The approach comprised a literature review supplemented with observations from experts from the case study areas. The four case study sites consist of three Man and Biosphere Reserves in Southeast Asia: Palawan in the Philippines, Cu Lao Cham- Hoi An in Viet Nam, Take-Bonerate Kepulauan Selayar in Indonesia, and a recently gazetted marine protected area, the Tun Mustapha Marine Park in Malaysia (Figure 1). The nine key habitats (eight benthic and one pelagic) covered in this review, identified as highly relevant for most case study sites, were mangrove forests, coral reefs, seagrass meadows, sand, mud, rock, coarse substratum, pelagic and modified habitats. Further division of these habitats into sub-habitats on the basis of biological type and substrate type was used to capture data on differential provision of ecosystem services within the broad habitat types. To ensure relevance in the four case study sites, firstly an ecosystem services typology was created tailored to these sites. After exploring several ecosystem service typologies, our final classification was adapted from the Common International Classification of Ecosystem services (CICES) V4.3 because it was considered to be most relevant to the objectives of this task. Provisioning, regulation and maintenance, and cultural services were assessed. Provisioning services focused on food for consumption by humans from plants, pelagic animals, demersal fish and invertebrates; energy from harvested plants; other materials from plants and animals, such as fibres, building and housing materials, medicines, decoration, handicrafts and souvenirs; and genetic material from plants and animals (including seeds, spat, spores, whole plants or animals, individual genes), for example seed or brood-stock collection for aquaculture and mangrove replanting and new plantations. Regulation and maintenance services assessed were treatment and assimilation of wastes or toxic substances; coastal erosion control; water flow regulation contributing to dampening the intensity of storm, floods, tsunamis, and hurricanes and the maintenance of localized water flows such as coastal current structures; maintenance of nursery,reproduction and feeding habitats; maintenance of critical habitats for charismatic species such as turtles, dugongs, cetaceans, sharks, seahorses, bats, fireflies, birds, monkeys, orchids and other epiphytes; and climate regulation through impacts on the hydrological cycle, temperature regulation, and the contribution to regulation of climate-influencing gases in the atmosphere, for example through carbon sequestration and long-term, decadal storage. Cultural services examined included uses of habitats as places for active and passive recreation; ceremonial activities; creative activities; and knowledge-based activities, such as educational activities, and citizen science or community environmental activities. The comprehensive literature review included peer-reviewed scientific research literature as well as grey literature such as government and other reports. To ensure a wide breadth of coverage, the research focused on studies from Southeast Asia. When no evidence was found in the literature, evidence was sought from experts, and where useful, was accompanied by observations from the authors in their respective case study sites. The evidence gathered was used to assess the potential of each habitat to provide an ecosystem service, rather than to assess the actual provision of ecosystem services from each case study site. This important distinction allows the differentiation between services provided by the ecosystem (i.e. the potential supply of ecosystem services that a habitat could deliver) and (achieved or used) benefits (i.e. the demand for ecosystem services). The knowledge gained from the literature, local and regional reports, together with observations from the study team and experts, was critically assessed using a robust methodology that captured different types of information together with a confidence score for the supporting evidence. The contribution of each habitat to each ecosystem service was then scored relative to other habitats. Our objective was to provide baseline information to enable better understanding of the ecosystem services arising from marine and coastal habitats in SE Asia. This provides a foundation for future assessments of natural capital and ecosystem services which may be used to inform sustainable management. The report will serve as a useful reference to many different readers. Regulators, managers of marine sites and policy makers might use this report to inform their management choices. This should enable more sustainable use of the marine environment and maximise the ecosystem service provision of all types of services addressed in this study. Stakeholders of the marine environment such as fisherfolk or residents might use this report to help them engage in management processes, to gain deeper understanding of the marine environment or confirm their observations of the marine environment. Academics can use it as a reference source or a base for further studies, in particular for valuation studies or when considering the trade-offs between ecosystem services in marine and coastal habitats. Finally, it is hoped that this report may bring a new appreciation and understanding of the marine environment and the life support it provides to society and inspire readers to improve management of the marine environment. This report is one of the outputs of the UK Research and Innovation’s Global Challenges Research Fund (UKRI GCRF) Blue Communities Programme (GCRF Blue Communities Global Challenges Research Fund via the United Kingdom Research and Innovation (UKRI) under grant agreement reference NE/P021107/1, www.blue-communities.org), which aims to “build capacity for sustainable interactions with marine ecosystems for the benefit of the health, well-being, food security and livelihoods of coastal communities in SE Asia”. GCRF Blue Communities is developing interdisciplinary research capability and lasting collaborations that can facilitate innovative application of integrated planning in the marine environment and respond to the UN Sustainable Development Goals of ‘no poverty’, ‘zero hunger’, ‘good health and well-being’ for coastal communities as well as ‘conserve and sustainably use the oceans, seas and marine resources for sustainable development’ through the sustainable use of marine resources

Reconstruction of Lamb weather type series back to the eighteenth century

The Lamb weather type series is a subjective catalogue of daily atmospheric patterns and flow directions over the British Isles, covering the period 1861–1996. Based on synoptic maps, meteorologists have empirically classified surface pressure patterns over this area, which is a key area for the progression of Atlantic storm tracks towards Europe. We apply this classification to a set of daily pressure series from a few stations from western Europe, in order to reconstruct and to extend this daily weather type series back to 1781. We describe a statistical framework which provides, for each day, the weather types consistent enough with the observed pressure pattern, and their respective probability. Overall, this technique can correctly reconstruct almost 75% of the Lamb daily types, when simplified to the seven main weather types. The weather type series are described and compared to the original series for the winter season only. Since the low frequency variability of synoptic conditions is directly related to the North Atlantic Oscillation (NAO), we derive from the weather type series an NAO index for winter. An interesting feature is a larger multidecadal variability during the nineteenth century than during the twentieth century

Epidermal growth factor suppresses induction by progestin of the adhesion protein desmoplakin in T47D breast cancer cells

INTRODUCTION: Although the effects of progesterone on cell cycle progression are well known, its role in spreading and adhesion of breast cancer cells has not attracted much attention until recently. Indeed, by controlling cell adhesion proteins, progesterone may play a direct role in breast cancer invasion and metastasis. Progesterone has also been shown to modulate epidermal growth factor (EGF) effects in neoplasia, although EGF effects on progesterone pathways and targets are less well understood. In the present study we identify an effect of EGF on a progesterone target, namely desmoplakin. METHODS: Initially flow cytometry was used to establish the growing conditions and demonstrate that the T47D breast cancer cell line was responding to progesterone and EGF in a classical manner. Differential display RT-PCR was employed to identify differentially expressed genes affected by progesterone and EGF. Western and Northern blotting were used to verify interactions between EGF and progesterone in three breast cancer cell lines: T47D, MCF-7, and ZR-75. RESULTS: We found the cell adhesion protein desmoplakin to be upregulated by progesterone – a process that was suppressed by EGF. This appears to be a general but not universal effect in breast cancer cell lines. CONCLUSION: Our findings suggest that progesterone and EGF may play opposing roles in metastasis. They also suggest that desmoplakin may be a useful biomarker for mechanistic studies designed to analyze the crosstalk between EGF and progesterone dependent events. Our work may help to bridge the fields of metastasis and differentiation, and the mechanisms of steroid action