300 research outputs found

    High Viral Diversity and Mixed Infections in Cerebral Spinal Fluid From Cases of Varicella Zoster Virus Encephalitis.

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    Background Varicella zoster virus (VZV) may cause encephalitis, both with and without rash. Here we investigate whether viruses recovered from the central nervous system (CNS; encephalitis or meningitis) differ genetically from those recovered from non-CNS samples. Methods Enrichment-based deep sequencing of 45 VZV genomes from cerebral spinal fluid (CSF), plasma, bronchoalveolar lavage (BAL), and vesicles was carried out with samples collected from 34 patients with and without VZV infection of the CNS. Results Viral sequences from multiple sites in the same patient were identical at the consensus level. Virus from vesicle fluid and CSF in cases of meningitis showed low-level diversity. By contrast, plasma, BAL, and encephalitis had higher numbers of variant alleles. Two CSF-encephalitis samples had high genetic diversity, with variant frequency patterns typical of mixed infections with different clades. Conclusions Low viral genetic diversity in vesicle fluid is compatible with previous observations that VZV skin lesions arise from single or low numbers of virions. A similar result was observed in VZV from cases of VZV meningitis, a generally self-limiting infection. CSF from cases of encephalitis had higher diversity with evidence for mixed clade infections in 2 cases. We hypothesize that reactivation from multiple neurons may contribute to the pathogenesis of VZV encephalitis

    Alcohol dehydrogenase 1B (ADH1B) genotype, alcohol consumption and breast cancer risk by age 50 years in a German case–control study

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    In a population-based study of 613 cases and 1082 controls, alcohol dehydrogenase 1B (ADH1B) genotype was not an independent risk factor for breast cancer, athough the possibility was raised that it modifies risk associated with high levels of alcohol consumption (OR 1.1, 95% confidence interval (CI) 0.8–1.6 for ADH1B*1/*1 genotype vs 0.2, 95% CI 0.1–1.0 for ADH1B*2 carriers)

    Genes Associated with Honey Bee Behavioral Maturation Affect Clock-Dependent and -Independent Aspects of Daily Rhythmic Activity in Fruit Flies

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    BACKGROUND: In the honey bee, the age-related and socially regulated transition of workers from in-hive task performance (e.g., caring for young) to foraging (provisioning the hive) is associated with changes in many behaviors including the 24-hour pattern of rhythmic activity. We have previously shown that the hive-bee to forager transition is associated with extensive changes in brain gene expression. In this study, we test the possible function of a subset of these genes in daily rhythmic activity pattern using neural-targeted RNA interference (RNAi) of an orthologous gene set in Drosophila melanogaster. PRINCIPAL FINDINGS: Of 10 genes tested, knockdown of six affected some aspect of locomotor activity under a 12 h:h light:dark regime (LD). Inos affected anticipatory activity preceding lights-off, suggesting a possible clock-dependent function. BM-40-SPARC, U2af50 and fax affected peak activity at dawn without affecting anticipation or overall inactivity (proportion of 15-min intervals without activity), suggesting that these effects may depend on the day-night light cycle. CAH1 affected overall inactivity. The remaining gene, abl, affected peak activity levels but was not clearly time-of-day-specific. No gene tested affected length of period or strength of rhythmicity in constant dark (DD), suggesting that these genes do not act in the core clock. SIGNIFICANCE: Taking advantage of Drosophila molecular genetic tools, our study provides an important step in understanding the large set of gene expression changes that occur in the honey bee transition from hive bee to forager. We show that orthologs of many of these genes influence locomotor activity in Drosophila, possibly through both clock-dependent and -independent pathways. Our results support the importance of both circadian clock and direct environmental stimuli (apart from entrainment) in shaping the bee's 24-hour pattern of activity. Our study also outlines a new approach to dissecting complex behavior in a social animal

    Trim17, novel E3 ubiquitin-ligase, initiates neuronal apoptosis

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    Accumulating data indicate that the ubiquitin-proteasome system controls apoptosis by regulating the level and the function of key regulatory proteins. In this study, we identified Trim17, a member of the TRIM/RBCC protein family, as one of the critical E3 ubiquitin ligases involved in the control of neuronal apoptosis upstream of mitochondria. We show that expression of Trim17 is increased both at the mRNA and protein level in several in vitro models of transcription-dependent neuronal apoptosis. Expression of Trim17 is controlled by the PI3K/Akt/GSK3 pathway in cerebellar granule neurons (CGN). Moreover, the Trim17 protein is expressed in vivo, in apoptotic neurons that naturally die during post-natal cerebellar development. Overexpression of active Trim17 in primary CGN was sufficient to induce the intrinsic pathway of apoptosis in survival conditions. This pro-apoptotic effect was abolished in Bax(-/-) neurons and depended on the E3 activity of Trim17 conferred by its RING domain. Furthermore, knock-down of endogenous Trim17 and overexpression of dominant-negative mutants of Trim17 blocked trophic factor withdrawal-induced apoptosis both in CGN and in sympathetic neurons. Collectively, our data are the first to assign a cellular function to Trim17 by showing that its E3 activity is both necessary and sufficient for the initiation of neuronal apoptosis. Cell Death and Differentiation (2010) 17, 1928-1941; doi: 10.1038/cdd.2010.73; published online 18 June 201

    Co-designing Indices for Tailored Seasonal Climate Forecasts in Malawi

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    In central and southern Malawi, climate variability significantly impacts agricultural production and food availability owing to a high dependence on rain-fed maize production. Seasonal climate forecast information has the potential to inform farmers' agricultural planning, thereby improving preparedness to extreme events. In this paper we describe and evaluate an approach to co-designing and testing agro-climatic indices for use in seasonal forecasts that are tailored to farmer-defined decision-making needs in three districts of central and southern Malawi. Specifically, we aim to (a) identify critical maize specific agro-climatic indices by engaging key stakeholders and farmers; (b) compare and triangulate these indices with the historical climate record in study districts; and (c) analyze empirical relationships between seasonal total rainfall and maize specific indices in order to assess the potential for forecasting them at appropriate seasonal timescales. The identified agro-climatic indices include critical temperature/rainfall thresholds that are directly associated with phenological stages of maize growth with direct implications for maize yield and quality. While there are statistically significant relationships between observed wet season rainfall totals and several agro-climatic indices (e.g., heavy rainfall days and dry spell), the forecast skill of the UK Met Office's coupled initialized global seasonal forecasting system (GloSea5) over Malawi is currently low to provide confident predictions of total wet season rainfall and the agro-climatic indices correlated with it. We reflect on some of the opportunities and challenges associated with integrating farmers' information needs into a seasonal forecast process, through the use of agro-climatic indices

    Global analysis of gene expression in NGF-deprived sympathetic neurons identifies molecular pathways associated with cell death

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    Developing sympathetic neurons depend on nerve growth factor (NGF) for survival and die by apoptosis after NGF withdrawal. This process requires de novo gene expression but only a small number of genes induced by NGF deprivation have been identified so far, either by a candidate gene approach or in mRNA differential display experiments. This is partly because it is difficult to obtain large numbers of sympathetic neurons for in vitro studies. Here, we describe for the first time, how advances in gene microarray technology have allowed us to investigate the expression of all known genes in sympathetic neurons cultured in the presence and absence of NGF

    An integrated 1D–2D hydraulic modelling approach to assess the sensitivity of a coastal region to compound flooding hazard under climate change

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    Coastal regions are dynamic areas that often lie at the junction of different natural hazards. Extreme events such as storm surges and high precipitation are significant sources of concern for flood management. As climatic changes and sea-level rise put further pressure on these vulnerable systems, there is a need for a better understanding of the implications of compounding hazards. Recent computational advances in hydraulic modelling offer new opportunities to support decision-making and adaptation. Our research makes use of recently released features in the HEC-RAS version 5.0 software to develop an integrated 1D–2D hydrodynamic model. Using extreme value analysis with the Peaks-Over-Threshold method to define extreme scenarios, the model was applied to the eastern coast of the UK. The sensitivity of the protected wetland known as the Broads to a combination of fluvial, tidal and coastal sources of flooding was assessed, accounting for different rates of twenty-first century sea-level rise up to the year 2100. The 1D–2D approach led to a more detailed representation of inundation in coastal urban areas, while allowing for interactions with more fluvially dominated inland areas to be captured. While flooding was primarily driven by increased sea levels, combined events exacerbated flooded area by 5–40% and average depth by 10–32%, affecting different locations depending on the scenario. The results emphasise the importance of catchment-scale strategies that account for potentially interacting sources of flooding

    Adverse childhood experiences and prescription drug use in a cohort study of adult HMO patients

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    <p>Abstract</p> <p>Background</p> <p>Prescription drugs account for approximately 11% of national health expenditures. Prior research on adverse childhood experiences (ACEs), which include common forms of child maltreatment and related traumatic stressors, has linked them to numerous health problems. However, data about the relationship of these experiences to prescription drug use are scarce.</p> <p>Method</p> <p>We used the ACE Score (an integer count of 8 different categories of ACEs) as a measure of cumulative exposure to traumatic stress during childhood. We prospectively assessed the relationship of the Score to prescription drug use in a cohort of 15,033 adult HMO patients (mean follow-up: 6.1 years) and assessed mediation of this relationship by documented ACE-related health and social problems.</p> <p>Results</p> <p>Nearly 1.2 million prescriptions were recorded; prescriptions rates increased in a graded fashion as the ACE Score increased (p for trend < 0.0001). Compared to persons with an ACE Score of 0, persons with a Score ≥ 5 had rates increased by 40%; graded relationships were seen for all age groups (18–44, 45–64, and 65–89 years) (p for trend < 0.01). Graded relationships were observed for the risk of being in the upper decile of number of classes of drugs used; persons with scores of ≥ 5 had this risk increased 2-fold. Adjustment for ACE-related health problems reduced the strength of the associations by more than 60%.</p> <p>Conclusion</p> <p>ACEs substantially increase the number of prescriptions and classes of drugs used for as long as 7 or 8 decades after their occurrence. The increases in prescription drug use were largely mediated by documented ACE-related health and social problems.</p

    Development of a Halotolerant Community in the St. Lucia Estuary (South Africa) during a Hypersaline Phase

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    Background: The St. Lucia Estuary, Africa’s largest estuarine lake, is currently experiencing unprecedented freshwater deprivation which has resulted in a northward gradient of drought effects, with hypersaline conditions in its northern lakes. Methodology/Principal Findings: This study documents the changes that occurred in the biotic communities at False Bay from May 2010 to June 2011, in order to better understand ecosystem functioning in hypersaline habitats. Few zooplankton taxa were able to withstand the harsh environmental conditions during 2010. These were the flatworm Macrostomum sp., the harpacticoid copepod Cletocamptus confluens, the cyclopoid copepod Apocyclops cf. dengizicus and the ciliate Fabrea cf. salina. In addition to their exceptional salinity tolerance, they were involved in a remarkably simple food web. In June 2009, a bloom of an orange-pigmented cyanobacterium (Cyanothece sp.) was recorded in False Bay and persisted uninterruptedly for 18 months. Stable isotope analysis suggests that this cyanobacterium was the main prey item of F. cf. salina. This ciliate was then consumed by A. cf. dengizicus, which in turn was presumably consumed by flamingos as they flocked in the area when the copepods attained swarming densities. On the shore, cyanobacteria mats contributed to a population explosion of the staphylinid beetle Bledius pilicollis. Although zooplankton disappeared once salinities exceeded 130, many taxa are capable of producing spores or resting cysts to bridge harsh periods. The hypersaline community was disrupted by heavy summer rains in 2011, which alleviated drought conditions and resulted in a sharp increase in zooplankton stock an
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