369 research outputs found

    The Soviet contributions towards MAP/WINE

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    In the winter of 1983 to 1984, the research institutes of the Soviet Union took an active part in the accomplishment of the project Winter in Northern Europe (MAP/WINE) of the Middle Atmosphere Program. Different methods were used to measure temperature, direction and velocity of wind, turbulence, electron concentration in the lower ionosphere, and radio wave absorption. The study of the stratopheric warmings and the related changes in the mesosphere and lower ionosphere was considered of special importance. The analysis of the obtained data has shown, in particular, that during the stratospheric warmings the western wind in winter time becomes weaker and even reverses. At the same time period the electron concentration and the radio wave absorption in the lower ionosphere are often reduced. It is also observed that the high absorption zones move from west to east. These results confirm the concept about the role of the cyclonic circumpolar vortex in the transport of the auroral air to temperate latitudes and about the appearance of conditions for the winter anomalous radio wave absorption

    The ER morphology-regulating lunapark protein induces the formation of stacked bilayer discs

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    This is the final version of the article. Available from the publisher via the DOI in this recordLunapark (Lnp) is a conserved membrane protein that localizes to and stabilizes three-way junctions of the tubular ER network. In higher eukaryotes, phosphorylation of Lnp may contribute to the conversion of the ER from tubules to sheets during mitosis. Here, we report on the reconstitution of purified Lnp with phospholipids. Surprisingly, Lnp induces the formation of stacked membrane discs. Each disc is a bicelle, with Lnp sitting in the bilayer facing both directions. The interaction between bicelles is mediated by the cytosolic domains of Lnp, resulting in a constant distance between the discs. A phosphomimetic Lnp mutant shows reduced bicelle stacking. Based on these results, we propose that Lnp tethers ER membranes in vivo in a cell cycle–dependent manner. Lnp appears to be the first membrane protein that induces the formation of stacked bicelles.S Wang was supported by a fellowship from the Charles King Trust and RE Powers by a NIGMS T32 training grant (GM008313). We acknowledge the Max Planck Society and University of Exeter for supporting V Gold, in particular Werner Kühlbrandt and Deryck Mills at the Max Planck Institute of Biophysics. TA Rapoport is a Howard Hughes Medical Institute Investigator

    A Relational Event Approach to Modeling Behavioral Dynamics

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    This chapter provides an introduction to the analysis of relational event data (i.e., actions, interactions, or other events involving multiple actors that occur over time) within the R/statnet platform. We begin by reviewing the basics of relational event modeling, with an emphasis on models with piecewise constant hazards. We then discuss estimation for dyadic and more general relational event models using the relevent package, with an emphasis on hands-on applications of the methods and interpretation of results. Statnet is a collection of packages for the R statistical computing system that supports the representation, manipulation, visualization, modeling, simulation, and analysis of relational data. Statnet packages are contributed by a team of volunteer developers, and are made freely available under the GNU Public License. These packages are written for the R statistical computing environment, and can be used with any computing platform that supports R (including Windows, Linux, and Mac).

    BAT3 Guides Misfolded Glycoproteins Out of the Endoplasmic Reticulum

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    Secretory and membrane proteins that fail to acquire their native conformation within the lumen of the Endoplasmic Reticulum (ER) are usually targeted for ubiquitin-dependent degradation by the proteasome. How partially folded polypeptides are kept from aggregation once ejected from the ER into the cytosol is not known. We show that BAT3, a cytosolic chaperone, is recruited to the site of dislocation through its interaction with Derlin2. Furthermore, we observe cytoplasmic BAT3 in a complex with a polypeptide that originates in the ER as a glycoprotein, an interaction that depends on the cytosolic disposition of both, visualized even in the absence of proteasomal inhibition. Cells depleted of BAT3 fail to degrade an established dislocation substrate. We thus implicate a cytosolic chaperone as an active participant in the dislocation of ER glycoproteins.United States. National Institutes of HealthBoehringer Ingelheim Fond

    Dimeric SecA Couples the Preprotein Translocation in an Asymmetric Manner

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    The Sec translocase mediates the post-translational translocation of a number of preproteins through the inner membrane in bacteria. In the initiatory translocation step, SecB targets the preprotein to the translocase by specific interaction with its receptor SecA. The latter is the ATPase of Sec translocase which mediates the post-translational translocation of preprotein through the protein-conducting channel SecYEG in the bacterial inner membrane. We examined the structures of Escherichia coli Sec intermediates in solution as visualized by negatively stained electron microscopy in order to probe the oligomeric states of SecA during this process. The symmetric interaction pattern between the SecA dimer and SecB becomes asymmetric in the presence of proOmpA, and one of the SecA protomers predominantly binds to SecB/proOmpA. Our results suggest that during preprotein translocation, the two SecA protomers are different in structure and may play different roles

    Health, not weight loss, focused programmes versus conventional weight loss programmes for cardiovascular risk factors:A systematic review and meta-analysis

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    © 2019 The Authors. Published by BMC. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website:Background: Obesity is a cardiovascular disease risk factor. Conventional weight loss (CWL) programmes focus on weight loss, however 'health, not weight loss, focused' (HNWL) programmes concentrate on improved health and well-being, irrespective of weight loss. What are the differences in CVD risk outcomes between these programmes? Aim: To conduct a systematic review and meta-analysis to compare the effects of HNWL with CWL programmes on cardiovascular disease risk factors. Methods: We searched CENTRAL, MEDLINE, EMBASE, PsycINFO, CINAHL, ASSIA, clinical trial registers, commercial websites and reference lists for randomised controlled trials comparing the two programmes (initially searched up to August 2015 and searched updated to 5 April 2019). We used the Mantel-Haneszel fixed-effect model to pool results. Sub-group and sensitivity analyses that accounted for variations in length of follow-up, enhanced programmes and risk of bias dealt with heterogeneity. Results: Eight randomised controlled trials of 20,242 potential studies were included. Improvements in total cholesterol-HDL ratio (mean difference-0.21 mmol/L, 95% confidence interval [-3.91, 3.50]) and weight loss (-0.28 kg [-2.00, 1.44]) favoured HNWL compared to CWL programmes in the long term (53-104 week follow-up), whereas improvements in systolic (-1.14 mmHg, [-5.84, 3.56]) and diastolic (-0.15 mmHg, [-3.64, 3.34]) blood pressure favoured CWL programmes. These differences did not reach statistical significance. Statistically significant improvements in body satisfaction (-4.30 [-8.32,-0.28]) and restrained eating behaviour (-4.30 [-6.77,-1.83]) favoured HNWL over CWL programmes. Conclusions: We found no long-term significant differences in improved CVD risk factors; however, body satisfaction and restrained eating behaviour improved more with HNWL compared to CWL programmes. Yet firm conclusions cannot be drawn from small studies with high losses to follow-up and data sometimes arising from a single small study.Published versio

    Genome Characteristics of a Novel Phage from Bacillus thuringiensis Showing High Similarity with Phage from Bacillus cereus

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    Bacillus thuringiensis is an important entomopathogenic bacterium belongs to the Bacillus cereus group, which also includes B. anthracis and B. cereus. Several genomes of phages originating from this group had been sequenced, but no genome of Siphoviridae phage from B. thuringiensis has been reported. We recently sequenced and analyzed the genome of a novel phage, BtCS33, from a B. thuringiensis strain, subsp. kurstaki CS33, and compared the gneome of this phage to other phages of the B. cereus group. BtCS33 was the first Siphoviridae phage among the sequenced B. thuringiensis phages. It produced small, turbid plaques on bacterial plates and had a narrow host range. BtCS33 possessed a linear, double-stranded DNA genome of 41,992 bp with 57 putative open reading frames (ORFs). It had a typical genome structure consisting of three modules: the “late” region, the “lysogeny-lysis” region and the “early” region. BtCS33 exhibited high similarity with several phages, B. cereus phage Wβ and some variants of Wβ, in genome organization and the amino acid sequences of structural proteins. There were two ORFs, ORF22 and ORF35, in the genome of BtCS33 that were also found in the genomes of B. cereus phage Wβ and may be involved in regulating sporulation of the host cell. Based on these observations and analysis of phylogenetic trees, we deduced that B. thuringiensis phage BtCS33 and B. cereus phage Wβ may have a common distant ancestor

    A Single Polar Residue and Distinct Membrane Topologies Impact the Function of the Infectious Bronchitis Coronavirus E Protein

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    The coronavirus E protein is a small membrane protein with a single predicted hydrophobic domain (HD), and has a poorly defined role in infection. The E protein is thought to promote virion assembly, which occurs in the Golgi region of infected cells. It has also been implicated in the release of infectious particles after budding. The E protein has ion channel activity in vitro, although a role for channel activity in infection has not been established. Furthermore, the membrane topology of the E protein is of considerable debate, and the protein may adopt more than one topology during infection. We previously showed that the HD of the infectious bronchitis virus (IBV) E protein is required for the efficient release of infectious virus, an activity that correlated with disruption of the secretory pathway. Here we report that a single residue within the hydrophobic domain, Thr16, is required for secretory pathway disruption. Substitutions of other residues for Thr16 were not tolerated. Mutations of Thr16 did not impact virus assembly as judged by virus-like particle production, suggesting that alteration of secretory pathway and assembly are independent activities. We also examined how the membrane topology of IBV E affected its function by generating mutant versions that adopted either a transmembrane or membrane hairpin topology. We found that a transmembrane topology was required for disrupting the secretory pathway, but was less efficient for virus-like particle production. The hairpin version of E was unable to disrupt the secretory pathway or produce particles. The findings reported here identify properties of the E protein that are important for its function, and provide insight into how the E protein may perform multiple roles during infection

    Discordant effect of body mass index on bone mineral density and speed of sound

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    BACKGROUND: Increased BMI may affect the determination of bone mineral density (BMD) by dual X-ray absorptiometry (DXA) and speed of sound (SOS) measured across bones. Preliminary data suggest that axial SOS is less affected by soft tissue. The purpose of this study is to evaluate the effect of body mass index (BMI) on BMD and SOS measured along bones. METHODS: We compared axial BMD determined by DXA with SOS along the phalanx, radius and tibia in 22 overweight (BMI > 27 kg/m(2)), and 11 lean (BMI = 21 kg/m(2)) postmenopausal women. Serum bone specific alkaline phosphatase and urinary deoxypyridinoline excretion determined bone turnover. RESULTS: Mean femoral neck – but not lumbar spine BMD was higher in the overweight – as compared with the lean group (0.70 ± 0.82, -0.99 ± 0.52, P < 0.00001). Femoral neck BMD in the overweight – but not in the lean group highly correlated with BMI (R = 0.68. P < 0.0001). Mean SOS at all measurement sites was similar in both groups and did not correlate with BMI. Bone turnover was similar in the two study groups. CONCLUSIONS: The high BMI of postmenopausal women may result in spuriously high BMD. SOS measured along bones may be a more appropriate means for evaluating bones of overweight women

    Structure of clathrin coat with bound Hsc70 and auxilin: mechanism of Hsc70-facilitated disassembly

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    The chaperone Hsc70 drives the clathrin assembly–disassembly cycle forward by stimulating dissociation of a clathrin lattice. A J-domain containing co-chaperone, auxilin, associates with a freshly budded clathrin-coated vesicle, or with an in vitro assembled clathrin coat, and recruits Hsc70 to its specific heavy-chain-binding site. We have determined by electron cryomicroscopy (cryoEM), at about 11 Å resolution, the structure of a clathrin coat (in the D6-barrel form) with specifically bound Hsc70 and auxilin. The Hsc70 binds a previously analysed site near the C-terminus of the heavy chain, with a stoichiometry of about one per three-fold vertex. Its binding is accompanied by a distortion of the clathrin lattice, detected by a change in the axial ratio of the D6 barrel. We propose that when Hsc70, recruited to a position close to its target by the auxilin J-domain, splits ATP, it clamps firmly onto its heavy-chain site and locks in place a transient fluctuation. Accumulation of the local strain thus imposed at multiple vertices can then lead to disassembly
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