TOM40 Mediates Mitochondrial Dysfunction Induced by α-Synuclein Accumulation in Parkinson's Disease.

Alpha-synuclein (α-Syn) accumulation/aggregation and mitochondrial dysfunction play prominent roles in the pathology of Parkinson's disease. We have previously shown that postmortem human dopaminergic neurons from PD brains accumulate high levels of mitochondrial DNA (mtDNA) deletions. We now addressed the question, whether alterations in a component of the mitochondrial import machinery -TOM40- might contribute to the mitochondrial dysfunction and damage in PD. For this purpose, we studied levels of TOM40, mtDNA deletions, oxidative damage, energy production, and complexes of the respiratory chain in brain homogenates as well as in single neurons, using laser-capture-microdissection in transgenic mice overexpressing human wildtype α-Syn. Additionally, we used lentivirus-mediated stereotactic delivery of a component of this import machinery into mouse brain as a novel therapeutic strategy. We report here that TOM40 is significantly reduced in the brain of PD patients and in α-Syn transgenic mice. TOM40 deficits were associated with increased mtDNA deletions and oxidative DNA damage, and with decreased energy production and altered levels of complex I proteins in α-Syn transgenic mice. Lentiviral-mediated overexpression of Tom40 in α-Syn-transgenic mice brains ameliorated energy deficits as well as oxidative burden. Our results suggest that alterations in the mitochondrial protein transport machinery might contribute to mitochondrial impairment in α-Synucleinopathies

Drones count wildlife more accurately and precisely than humans

Human activities are creating environmental conditions that pose threats and present opportunities for wildlife. In turn, this creates challenges for conservation managers. Some species have benefited from anthropogenic actions. For example, many invasive species profit from human‐assisted dispersal (Banks, Paini, Bayliss, & Hodda, 2015; Hulme, 2009), and mesopredators may thrive following human‐driven loss of top predators (Ritchie & Johnson, 2009). However, in many cases, wildlife populations are undergoing alarming declines, and extinction rates are now as high as 100‐fold greater than the background extinction rate (Ceballos et al., 2015). Ecological monitoring is essential for understanding these population dynamics, and rigorous monitoring facilitates informed management. The effectiveness of management decision‐making is often dependent on the accuracy and timeliness of the relevant ecological data upon which decisions are based, meaning that improvements to data collection methods may herald improved ecological outcomes from management actions

Quantitative imaging of concentrated suspensions under flow

We review recent advances in imaging the flow of concentrated suspensions, focussing on the use of confocal microscopy to obtain time-resolved information on the single-particle level in these systems. After motivating the need for quantitative (confocal) imaging in suspension rheology, we briefly describe the particles, sample environments, microscopy tools and analysis algorithms needed to perform this kind of experiments. The second part of the review focusses on microscopic aspects of the flow of concentrated model hard-sphere-like suspensions, and the relation to non-linear rheological phenomena such as yielding, shear localization, wall slip and shear-induced ordering. Both Brownian and non-Brownian systems will be described. We show how quantitative imaging can improve our understanding of the connection between microscopic dynamics and bulk flow.Comment: Review on imaging hard-sphere suspensions, incl summary of methodology. Submitted for special volume 'High Solid Dispersions' ed. M. Cloitre, Vol. xx of 'Advances and Polymer Science' (Springer, Berlin, 2009); 22 pages, 16 fig

Psychopathology predicts the outcome of medial branch blocks with corticosteroid for chronic axial low back or cervical pain: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Comorbid psychopathology is an important predictor of poor outcome for many types of treatments for back or neck pain. But it is unknown if this applies to the results of medial branch blocks (MBBs) for chronic low back or neck pain, which involves injecting the medial branch of the dorsal ramus nerves that innervate the facet joints. The objective of this study was to determine whether high levels of psychopathology are predictive of pain relief after MBB injections in the lumbar or cervical spine.</p> <p>Methods</p> <p>This was a prospective cohort study. Consecutive patients in a pain medicine practice undergoing MBBs of the lumbar or cervical facets with corticosteroids were recruited to participate. Subjects were selected for a MBB based on operationalized selection criteria and the procedure was performed in a standardized manner. Subjects completed the Brief Pain Inventory (BPI) and the Hospital Anxiety and Depression Scale (HADS) just prior to the procedure and at one-month follow up. Scores on the HADS classified the subjects into three groups based on psychiatric symptoms, which formed the primary predictor variable: <it>Low</it>, <it>Moderate</it>, or <it>High </it>levels of psychopathology. The primary outcome measure was the percent improvement in average daily pain rating one-month following an injection. Analysis of variance and chi-square were used to analyze the analgesia and functional rating differences between groups, and to perform a responder analysis.</p> <p>Results</p> <p>Eighty six (86) subjects completed the study. The <it>Low </it>psychopathology group (n = 37) reported a mean of 23% improvement in pain at one-month while the <it>High </it>psychopathology group (n = 29) reported a mean worsening of -5.8% in pain (p < .001). Forty five percent (45%) of the <it>Low </it>group had at least 30% improvement in pain versus 10% in the <it>High </it>group (p < .001). Using an analysis of covariance, no baseline demographic, social, or medical variables were significant predictors of pain improvement, nor did they mitigate the effect of psychopathology on the outcome.</p> <p>Conclusion</p> <p>Psychiatric comorbidity is associated with diminished pain relief after a MBB injection performed with steroid at one-month follow-up. These findings illustrate the importance of assessing comorbid psychopathology as part of a spine care evaluation.</p

Lack of knowledge about sexually transmitted infections among women in North rural Vietnam

<p>Abstract</p> <p>Background</p> <p>The serious long-term complications of sexually transmitted infections (STI) in women and newborns are well-documented. Particularly, STI imply considerable social consequences for women. Low STI knowledge has been shown to be associated with unsafe sex. In Vietnam, misconceptions regarding STI exist, and rural women delay seeking care for STI. The aim of the study was to investigate knowledge of STI among women aged 15 to 49 years in a rural district of Vietnam and to evaluate possible associations between socioeconomic factors and STI knowledge.</p> <p>Methods</p> <p>A cross-sectional population-based study using face-to-face interviews was carried out between March and May 2006 in a demographic surveillance site in rural Vietnam. In total, 1805 women aged 15–49 years were randomly selected to participate in the study. The interviews were based on a structured questionnaire including questions on sociodemographic characteristics of the women and their knowledge about STI. Each correct answer was scored 1, incorrect or do not know answer was scored 0. Multivariate analyses were applied to examine associations between socio-economic conditions and STI knowledge. Intra-cluster correlation was calculated to examine similarities of STI knowledge within clusters.</p> <p>Results</p> <p>Of the 1,805 respondents, 78% (73% married vs. 93% unmarried, p < 0.001) did not know any symptoms of STI, 50% could not identify any cause of STI, 59% (54% married vs. 76% unmarried, p < 0.001) did not know that STI can be prevented. Only 31% of the respondents (36% married vs. 14% unmarried, p < 0.001) answered that condom use could protect against STI, and 56% considered partner treatment necessary. Of 40 possible correct answers, the mean knowledge score was 6.5 (range 0–26, median 6). Young, unmarried women and women who lived in the highlands or mountainous areas demonstrated very low levels of STI knowledge (regression coefficients -1.3 and -2.5, respectively, p < 0.001). Experience of an induced abortion was significantly associated with a higher level of knowledge.</p> <p>Conclusion</p> <p>The low levels of STI knowledge found among women of reproductive age in a rural district of Vietnam indicate an urgent need of health education interventions, of which, young and unmarried women should be specifically targeted.</p

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Trans Fatty Acids Induce Vascular Inflammation and Reduce Vascular Nitric Oxide Production in Endothelial Cells

Intake of trans fatty acids (TFA), which are consumed by eating foods made from partially hydrogenated vegetable oils, is associated with a higher risk of cardiovascular disease. This relation can be explained by many factors including TFA's negative effect on endothelial function and reduced nitric oxide (NO) bioavailability. In this study we investigated the effects of three different TFA (2 common isomers of C18 found in partially hydrogenated vegetable oil and a C18 isomer found from ruminant-derived—dairy products and meat) on endothelial NF-κB activation and nitric oxide (NO) production. Human endothelial cells were treated with increasing concentrations of Elaidic (trans-C18:1 (9 trans)), Linoelaidic (trans-C18:2 (9 trans, 12 trans)), and Transvaccenic (trans-C18:1 (11 trans)) for 3 h. Both Elaidic and Linoelaidic acids were associated with increasing NF-κB activation as measured by IL-6 levels and phosphorylation of IκBα, and impairment of endothelial insulin signaling and NO production, whereas Transvaccenic acid was not associated with these responses. We also measured superoxide production, which has been hypothesized to be necessary in fatty acid-dependent activation of NF-κB. Both Elaidic acid and Linoelaidic acid are associated with increased superoxide production, whereas Transvaccenic acid (which did not induce inflammatory responses) did not increase superoxide production. We observed differential activation of endothelial superoxide production, NF-κB activation, and reduction in NO production by different C18 isomers suggesting that the location and number of trans double bonds effect endothelial NF-κB activation

Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews

BACKGROUND: Our objective was to develop an instrument to assess the methodological quality of systematic reviews, building upon previous tools, empirical evidence and expert consensus. METHODS: A 37-item assessment tool was formed by combining 1) the enhanced Overview Quality Assessment Questionnaire (OQAQ), 2) a checklist created by Sacks, and 3) three additional items recently judged to be of methodological importance. This tool was applied to 99 paper-based and 52 electronic systematic reviews. Exploratory factor analysis was used to identify underlying components. The results were considered by methodological experts using a nominal group technique aimed at item reduction and design of an assessment tool with face and content validity. RESULTS: The factor analysis identified 11 components. From each component, one item was selected by the nominal group. The resulting instrument was judged to have face and content validity. CONCLUSION: A measurement tool for the 'assessment of multiple systematic reviews' (AMSTAR) was developed. The tool consists of 11 items and has good face and content validity for measuring the methodological quality of systematic reviews. Additional studies are needed with a focus on the reproducibility and construct validity of AMSTAR, before strong recommendations can be made on its use

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente