2,377 research outputs found

    SPG20 protein spartin is recruited to midbodies by ESCRT-III protein Ist1 and participates in cytokinesis.

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    Hereditary spastic paraplegias (HSPs, SPG1-46) are inherited neurological disorders characterized by lower extremity spastic weakness. Loss-of-function SPG20 gene mutations cause an autosomal recessive HSP known as Troyer syndrome. The SPG20 protein spartin localizes to lipid droplets and endosomes, and it interacts with tail interacting protein 47 (TIP47) as well as the ubiquitin E3 ligases atrophin-1-interacting protein (AIP)4 and AIP5. Spartin harbors a domain contained within microtubule-interacting and trafficking molecules (MIT) at its N-terminus, and most proteins with MIT domains interact with specific ESCRT-III proteins. Using yeast two-hybrid and in vitro surface plasmon resonance assays, we demonstrate that the spartin MIT domain binds with micromolar affinity to the endosomal sorting complex required for transport (ESCRT)-III protein increased sodium tolerance (Ist)1 but not to ESCRT-III proteins charged multivesicular body proteins 1-7. Spartin colocalizes with Ist1 at the midbody, and depletion of Ist1 in cells by small interfering RNA significantly decreases the number of cells where spartin is present at midbodies. Depletion of spartin does not affect Ist1 localization to midbodies but markedly impairs cytokinesis. A structure-based amino acid substitution in the spartin MIT domain (F24D) blocks the spartin-Ist1 interaction. Spartin F24D does not localize to the midbody and acts in a dominant-negative manner to impair cytokinesis. These data suggest that Ist1 interaction is important for spartin recruitment to the midbody and that spartin participates in cytokinesis

    A bacteriophage tubulin harnesses dynamic instability to center DNA in infected cells.

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    Dynamic instability, polarity, and spatiotemporal organization are hallmarks of the microtubule cytoskeleton that allow formation of complex structures such as the eukaryotic spindle. No similar structure has been identified in prokaryotes. The bacteriophage-encoded tubulin PhuZ is required to position DNA at mid-cell, without which infectivity is compromised. Here, we show that PhuZ filaments, like microtubules, stochastically switch from growing in a distinctly polar manner to catastrophic depolymerization (dynamic instability) both in vitro and in vivo. One end of each PhuZ filament is stably anchored near the cell pole to form a spindle-like array that orients the growing ends toward the phage nucleoid so as to position it near mid-cell. Our results demonstrate how a bacteriophage can harness the properties of a tubulin-like cytoskeleton for efficient propagation. This represents the first identification of a prokaryotic tubulin with the dynamic instability of microtubules and the ability to form a simplified bipolar spindle

    The prevalence of femoroacetabular impingement anatomy in Division 1 aquatic athletes who tread water

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    Abstract Femoroacetabular impingement (FAI) is a disorder that causes hip pain and disability in young patients, particularly athletes. Increased stress on the hip during development has been associated with increased risk of cam morphology. The specific forces involved are unclear, but may be due to continued rotational motion, like the eggbeater kick. The goal of this prospective cohort study was to use magnetic resonance imaging (MRI) to identify the prevalence of FAI anatomy in athletes who tread water and compare it to the literature on other sports. With university IRB approval, 20 Division 1 water polo players and synchronized swimmers (15 female, 5 male), ages 18–23 years (mean age 20.7 ± 1.4), completed the 33-item International Hip Outcome Tool and underwent non-contrast MRI scans of both hips using a 3 Tesla scanner. Recruitment was based on sport, with both symptomatic and asymptomatic individuals included. Cam and pincer morphology were identified. The Wilcoxon Signed-Rank/Rank Sum tests were used to assess outcomes. Seventy per cent (14/20) of subjects reported pain in their hips yet only 15% (3/20) sought clinical evaluation. Cam morphology was present in 67.5% (27/40) of hips, while 22.5% (9/40) demonstrated pincer morphology. The prevalence of cam morphology in water polo players and synchronized swimmers is greater than that reported for the general population and at a similar level as some other sports. From a clinical perspective, acknowledgment of the high prevalence of cam morphology in water polo players and synchronized swimmers should be considered when these athletes present with hip pain

    O gene do receptor GABA A- γ2 (GABRG2) no transtorno obsessivo-compulsivo

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    OBJECTIVE: The γ-aminobutyric acid type A (GABA A) system may be implicated in obsessive-compulsive disorder, based on its major role in modulation of anxiety and its function as the principal inhibitory neurotransmitter system in the cortex. In addition, glutamatergic/GABAergic mechanisms appear to play a role in the pathophysiology of obsessive-compulsive disorder, making the GABA A receptor-γ2 (GABργ2) gene a good candidate for susceptibility in this disorder. METHOD: 118 probands meeting DSM-IV criteria for primary obsessive-compulsive disorder and their available parents were recruited for participation in this study and informed consent was obtained. An NciI restriction site polymorphism in the second intron was genotyped and data was analyzed using the Transmission Disequilibrium Test. RESULTS: In total, 61 of the participating families were informative (i.e., with at least one heterozygous parent). No biases were observed in the transmission of either of the two alleles (χ2 = 0.016, 1 d.f., p = 0.898) to the affected probands in the total sample. CONCLUSION/DISCUSSION: While these results do not provide support for a major role for the GABA A receptor-γ2 in obsessive-compulsive disorder, further investigations of this gene in larger samples are warranted

    WFPC2 Images of the Central Regions of Early-Type Galaxies - I. The Data

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    We present high resolution R-band images of the central regions of 67 early-type galaxies obtained with the Wide Field and Planetary Camera 2 (WFPC2) aboard the Hubble Space Telescope (HST). Our sample strikingly confirms the complex morphologies of the central regions of early-type galaxies. In particular, we detect dust in 43 percent of all galaxies, and evidence for embedded stellar disks in a remarkably large fraction of 51 percent. In 14 of those galaxies the disk-like structures are misaligned with the main galaxy, suggesting that they correspond to stellar bars in S0 galaxies. We analyze the luminosity profiles of the galaxies in our sample, and classify galaxies according to their central cusp slope. To a large extent we confirm the clear dichotomy found in previous HST surveys: bright, boxy ellipticals with shallow inner cusps (`core' galaxies) on one hand and faint, disky ellipticals with steep central cusps (`power-law' galaxies) on the other hand. The advantages and shortcomings of classification schemes utilizing the extrapolated central cusp slope are discussed, and it is shown that this cusp slope might be an inadequate representation for galaxies whose luminosity profile slope changes smoothly with radius rather than resembling a broken power-law. In fact, we find evidence for an `intermediate' class of galaxies, that cannot unambiguously be classified as either core or power-law galaxies, and which have central cusp slopes and absolute magnitudes intermediate between those of core and power-law galaxies.Comment: 44 pages, 7 Postscript figures. Accepted for publication in the Astronomical Journal. The associated Appendix with figures of luminosity profiles, contour plots and isophotal parameters for all galaxies is available at http://www.astro.washington.edu/rest/centralpro

    Dynamic Oligopoly Pricing: Evidence from the Airline Industry

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    We explore how pricing dynamics in the European airline industry vary with the competitive environment. Our results highlight substantial variations in pricing dynamics that are consistent with a theory of intertemporal price discrimination. First, the rate at which prices increase towards the scheduled travel date is decreasing in competition, supporting the idea that competition restrains the ability of airlines to price-discriminate. Second, the sensitivity to competition is substantially increasing in the heterogeneity of the customer base, reflecting further that restraints on price discrimination are only relevant if there is initial scope for price discrimination. These patterns are quantitatively important, explaining about 83 percent of the total within-flight price dispersion, and explaining 17 percent of the observed cross-market variation of pricing dynamics

    The black hole mass metallicity relation and insights into galaxy quenching

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    One of the most important questions in astrophysics is what causes galaxies to stop forming stars. Previous studies have shown a tight link between quiescence and black hole mass. Other studies have revealed that quiescence is also associated with 'starvation', the halting of gas inflows, which results in the remaining gas being used up rapidly by star formation and in rapid chemical enrichment. In this work we find the final missing link between these two findings. Using a large sample of galaxies, we uncover the intrinsic dependencies of the stellar metallicity on galaxy properties. In the case of the star-forming galaxies, the stellar metallicity is driven by stellar mass. However, for passive galaxies the stellar metallicity is primarily driven by the black hole mass, as traced by velocity dispersion. This result finally reveals the connection between previous studies, where the integrated effect of black hole feedback prevents gas inflows, starving the galaxy, which is seen by the rapid increase in the stellar metallicity, leading to the galaxy becoming passive.Comment: 20 pages, 6 figures, submitted to Nature Astronom

    Association of copy number variation across the genome with neuropsychiatric traits in the general population

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    Copy number variants (CNVs) are associated with psychiatric conditions in clinical populations. The relationship between rare CNV burden and neuropsychiatric traits in young, general populations is underexplored. 6807 children from the Avon Longitudinal Study of Parents and Children (ALSPAC) were studied. CNVs were inferred from SNP-array data using PennCNV. After excluding children with known candidate CNVs for schizophrenia, rare (<1%) CNV burden (total number of genes affected by CNVs, total length of CNVs, and largest CNV carried) was analysed in relation to: psychotic experiences (PEs) and anxiety/depression in adolescence; autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD), ASD and ADHD traits, and cognitive measures during childhood. Outcomes were also assessed in relation to known schizophrenia CNVs. The number of genes affected by rare CNVs was associated with a continuous measure of ASD: the standardised mean difference [SMD] per gene affected was increased by 0.018 [95%CI 0.011,0.025], p=3e-07 for duplications and by 0.021 [95%CI 0.010, 0.032], p=1e-04 for deletions. In line with published results on educational attainment in ALSPAC, IQ was associated with CNV burden: the SMD per gene affected was -0.017 [95%CI -0.025,-0.008] p=1e-04 for duplications and -0.023 [95%CI -0.037, -0.009], p=0.002 for deletions. Associations were also observed for measures of coherence, attention, memory, and social cognition. Schizophrenia-associated deletions were associated with IQ (SMD: -0.617 [95%CI -0.936,-0.298], p=2e-04), but not with PEs or other traits. We found that rare CNV burden and known schizophrenia candidate CNVs are associated with neuropsychiatric phenotypes in a non-clinically ascertained sample of young people

    Mass-flowering crops have a greater impact than semi-natural habitat on crop pollinators and pollen deposition

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    Context: Maximising insect pollination of mass-flowering crops is a widely-discussed approach to sustainable agriculture. Management actions can target landscape-scale semi-natural habitat, cropping patterns or field-scale features, but little is known about their relative effectiveness. Objective: To test how landscape composition (area of mass-flowering crops and semi-natural habitat) and field-scale habitat (margins and hedges) affect pollinator species richness, abundance, and pollen deposition within crop fields. Methods: We surveyed all flower visitors (Diptera, Coleoptera and Hymenoptera) in oilseed rape fields and related them to landscape composition and field features. Flower visitors were classified as bees, non-bee pollinators and brassica specialists. Total pollen deposition by individual taxa was estimated using single visit pollen deposition on stigmas combined with insect abundance. Results: The area of mass-flowering crop had a negative effect on the species richness and abundance of bees in fields, but not other flower visitors. The area of semi-natural habitat in the surrounding landscape had a positive effect on bees, but was not as important as the area of mass-flowering crop. Taxonomic richness and abundance varied significantly between years for non-bee pollinators. Greater cover of mass-flowering crops surrounding fields had a negative effect on pollen deposition, but only when non-bee pollinator numbers were reduced. Conclusions: Management choices that result in landscape homogenisation, such as large areas of mass-flowering crops, may reduce pollination services by reducing the numbers of bees visiting fields. Non-bee insect pollinators may buffer these landscape effects on pollen deposition, and management to support their populations should be considered
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