Inbuilt Mechanisms for Overcoming Functional Problems Inherent in Hepatic Microlobular Structure

This paper is funded by an MRC/EPSRC Discipline Bridging Initiative Grant (G0502256-77947) to W. Wan

Avoidance of vitamin D deficiency in pregnancy in the United Kingdom: the case for a unified approach in National policy

Prevalence of hypovitaminosis D in Western populations is high; pregnant women are identified as a high-risk group, especially if dark skinned. Consequences of severe clinical vitamin D deficiency in pregnancy can be life threatening to the newborn, while lesser degrees of hypovitaminosis D may have important long-term implications for offspring health. Past experiences with routine provision of 10 mu g/d (4001U/d) to all pregnant mothers suggest that this dose is sufficient to prevent overt neonatal complications of vitamin D deficiency. Recent data suggest that supplementation with dosages above 10 mu g/d may be required for optimal health in the mother and child; however, further research is required for the assessment of the benefits and safety of supplementation with higher dosages. Lack of unified advice on vitamin D supplementation of pregnant mothers in the UK hinders the implementation of primary prevention strategies and is likely to leave some deficient mothers without supplementation

Response Inhibition and Error Monitoring during a Visual Go/No-Go Task in Inuit Children Exposed to Lead, Polychlorinated Biphenyls, and Methylmercury

Background: Lead (Pb) and polychlorinated biphenyls (PCBs) are neurotoxic contaminants that have been related to impairment in response inhibition

Elevated Paracellular Glucose Flux across Cystic Fibrosis Airway Epithelial Monolayers Is an Important Factor for Pseudomonas aeruginosa Growth.

People with cystic fibrosis (CF) who develop related diabetes (CFRD) have accelerated pulmonary decline, increased infection with antibiotic-resistant Pseudomonas aeruginosa and increased pulmonary exacerbations. We have previously shown that glucose concentrations are elevated in airway surface liquid (ASL) of people with CF, particularly in those with CFRD. We therefore explored the hypotheses that glucose homeostasis is altered in CF airway epithelia and that elevation of glucose flux into ASL drives increased bacterial growth, with an effect over and above other cystic fibrosis transmembrane conductance regulator (CFTR)-related ASL abnormalities. The aim of this study was to compare the mechanisms governing airway glucose homeostasis in CF and non-CF primary human bronchial epithelial (HBE) monolayers, under normal conditions and in the presence of Ps. aeruginosa filtrate. HBE-bacterial co-cultures were performed in the presence of 5 mM or 15 mM basolateral glucose to investigate how changes in blood glucose, such as those seen in CFRD, affects luminal Ps. aeruginosa growth. Calu-3 cell monolayers were used to evaluate the potential importance of glucose on Ps. aeruginosa growth, in comparison to other hallmarks of the CF ASL, namely mucus hyperviscosity and impaired CFTR-dependent fluid secretions. We show that elevation of basolateral glucose promotes the apical growth of Ps. aeruginosa on CF airway epithelial monolayers more than non-CF monolayers. Ps. aeruginosa secretions elicited more glucose flux across CF airway epithelial monolayers compared to non-CF monolayers which we propose increases glucose availability in ASL for bacterial growth. In addition, elevating basolateral glucose increased Ps. aeruginosa growth over and above any CFTR-dependent effects and the presence or absence of mucus in Calu-3 airway epithelia-bacteria co-cultures. Together these studies highlight the importance of glucose as an additional factor in promoting Ps. aeruginosa growth and respiratory infection in CF disease

Increased insolation threshold for runaway greenhouse processes on Earth like planets

Because the solar luminosity increases over geological timescales, Earth climate is expected to warm, increasing water evaporation which, in turn, enhances the atmospheric greenhouse effect. Above a certain critical insolation, this destabilizing greenhouse feedback can "runaway" until all the oceans are evaporated. Through increases in stratospheric humidity, warming may also cause oceans to escape to space before the runaway greenhouse occurs. The critical insolation thresholds for these processes, however, remain uncertain because they have so far been evaluated with unidimensional models that cannot account for the dynamical and cloud feedback effects that are key stabilizing features of Earth's climate. Here we use a 3D global climate model to show that the threshold for the runaway greenhouse is about 375 W/m$^2$, significantly higher than previously thought. Our model is specifically developed to quantify the climate response of Earth-like planets to increased insolation in hot and extremely moist atmospheres. In contrast with previous studies, we find that clouds have a destabilizing feedback on the long term warming. However, subsident, unsaturated regions created by the Hadley circulation have a stabilizing effect that is strong enough to defer the runaway greenhouse limit to higher insolation than inferred from 1D models. Furthermore, because of wavelength-dependent radiative effects, the stratosphere remains cold and dry enough to hamper atmospheric water escape, even at large fluxes. This has strong implications for Venus early water history and extends the size of the habitable zone around other stars.Comment: Published in Nature. Online publication date: December 12, 2013. Accepted version before journal editing and with Supplementary Informatio

Different Verbal Learning Strategies in Autism Spectrum Disorder: Evidence from the Rey Auditory Verbal Learning Test

The Rey Auditory Verbal Learning Test, which requires the free recall of the same list of 15 items over 5 trials, was administered to a group of highfunctioning adolescents and adults with autism spectrum disorder (PDD) and a group of matched typical individuals. Overall levels of free recall were comparable in the two groups, as were the rates of learning over trials. Both groups also subjectively organised their recall to a similar extent. However, the serial position curve of the PDD participants, although similar to that of the comparison group on the first trial, became flatter on subsequent trials and was characterised by a slower growth in the primacy effect. Growth in the middle and recency portions of the curve was comparable in both groups. The findings are discussed in the light of current models of serial position effects and their implications for memory in ASD

Identification of Giardia lamblia DHHC Proteins and the Role of Protein S-palmitoylation in the Encystation Process

Protein S-palmitoylation, a hydrophobic post-translational modification, is performed by protein acyltransferases that have a common DHHC Cys-rich domain (DHHC proteins), and provides a regulatory switch for protein membrane association. In this work, we analyzed the presence of DHHC proteins in the protozoa parasite Giardia lamblia and the function of the reversible S-palmitoylation of proteins during parasite differentiation into cyst. Two specific events were observed: encysting cells displayed a larger amount of palmitoylated proteins, and parasites treated with palmitoylation inhibitors produced a reduced number of mature cysts. With bioinformatics tools, we found nine DHHC proteins, potential protein acyltransferases, in the Giardia proteome. These proteins displayed a conserved structure when compared to different organisms and are distributed in different monophyletic clades. Although all Giardia DHHC proteins were found to be present in trophozoites and encysting cells, these proteins showed a different intracellular localization in trophozoites and seemed to be differently involved in the encystation process when they were overexpressed. dhhc transgenic parasites showed a different pattern of cyst wall protein expression and yielded different amounts of mature cysts when they were induced to encyst. Our findings disclosed some important issues regarding the role of DHHC proteins and palmitoylation during Giardia encystation.Fil: Merino, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Zamponi, Nahuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Vranych, Cecilia Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Touz, Maria Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Ropolo, Andrea Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentin

Awareness of vitamin D deficiency among at-risk patients

<p>Abstract</p> <p>Background</p> <p>Vitamin D deficiency is a significant problem for a growing proportion of the UK population. Individuals with dark or covered skin are at particularly high risk due to ethno-cultural, environmental and genetic factors. We assessed the level of awareness of vitamin D deficiency among at-risk patients in order to identify groups most in need of education.</p> <p>Findings</p> <p>A cross-sectional survey using a piloted questionnaire was conducted among consecutive at-risk patients without a diagnosis of Vitamin D deficiency arriving at a large inner city general practice in the North West of England over a five day period. The survey was completed by 221 patients. The mean age was 35 years. 28% of them (n = 61) had never heard about vitamin D. Older patients (p = 0.003) were less likely to have heard about vitamin D. 54% of participants were unaware of the commonest symptoms of vitamin D deficiency. 34% did not expose their skin other than their face in the last one year, and 11% did not include vitamin D rich foods in their diet.</p> <p>Conclusion</p> <p>The majority of at-risk patients are aware of vitamin D; nevertheless, there is a significant lack of knowledge among older people, who have higher morbidity. A programme of targeted education of the at-risk population is recommended.</p

Free Recall Learning of Hierarchically Organised Lists by Adults with Asperger's Syndrome: Additional Evidence for Diminished Relational Processing

The Task Support Hypothesis (TSH, Bowler et al. Neuropsychologia 35:65–70 1997) states that individuals with autism spectrum disorder (ASD) show better memory when test procedures provide support for retrieval. The present study aimed to see whether this principle also applied at encoding. Twenty participants with high-functioning ASD and 20 matched comparison participants studied arrays of 112 words over four trials. Words were arranged either under hierarchically embedded category headings (e.g. Instruments—String—Plucked—Violin) or randomly. Both groups showed similar overall recall and better recall for the hierarchically organised words. However, the ASD participants made less use of information about relations between words and more use of item-specific information in their recall, confirming earlier reports of relational difficulties in this population

Effects of betel nut on cardiovascular risk factors in a rat model

Background: Areca nut (commonly known as betel nut) chewing has been shown to be associated with metabolic syndrome and cardiovascular disease (CVD). The mechanism by which betel nut ingestion could lead to development of CVD is not precisely known; however, dyslipidemia, hyperhomocysteinemia, hypertriglyceridemia and inflammation could be some of the potential risk factors. This study was undertaken to investigate the effects of two dosages of betel nut on homocysteinemia, inflammation and some of the components of metabolic syndrome, such as hypertriglyceridemia, low HDL-cholesterol, obesity and fasting hyperglycemia in a rat model.Methods: Thirty-six adult female Sprague Dawley rats, aged 10–12 weeks were divided into three equal groups. Group-1 served as the control group (n = 12) and received water, whereas groups 2 and 3 were given water suspension of betel nut orally in two dosages, 30 mg and 60 mg, respectively for a period of 5 weeks. At the end of the fifth week, the animals were weighed and sacrificed, blood was collected and liver, kidney, spleen and stomach were removed for histological examination. Plasma/serum was analyzed for glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, homocysteine, folate, vitamin B12 and N-acetyl-β-D-glucosaminidase (NAG) – a marker of inflammation.Results: When the mean concentration values of 3 groups were compared using one way ANOVA followed by Tukey’s HSD-test, there was a significant increase in the concentration of total cholesterol (p = 0.04) in the group receiving 30 mg/day betel nut compared to the control group. However, administration of a higher dose of betel nut (60 mg/day) had no significant effect on the serum concentrations of glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol, and NAG. Histological examination of spleen revealed a dose-dependent extramedullary hematopoiesis. No other remarkable change in the tissues (liver, kidney and stomach) was observed. Mean serum/plasma levels of folate, vitamin B12 and homocysteine were not found to be significantly different in all the groups. Betel nut ingestion had no effect on the mean body weights of rats.Conclusions: Low dosage of betel nut is found to be associated with hypercholesterolemia. However, betel nut ingestion is not associated with hyperhomocysteinemia, hypertriglyceridemia, hyperglycemia, inflammation and increase in body weight in a rat model