406 research outputs found

    Venus lower atmosphere heat balance

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    Pioneer Venus observations of temperatures and radiative fluxes are examined in an attempt to understand the thermal balance of the lower atmosphere. If all observations are correct and the probe sites are typical of the planet, the second law of thermodynamics requires that the bulk of the lower atmosphere heating must come from a source other than direct sunlight or a thermally driven atmospheric circulation. Neither the so-called greenhouse models nor the mechanical heating models are consistent with this interpretation of the observations. One possible interpretation is that two out of the three probe sites are atypical of the planet. Additional lower atmosphere heat sources provide another possible interpretation. These include a planetary heat flux that is 250 times the earth's, a secular cooling of the atmosphere, and a chemically energetic rain carrying solar energy from the clouds to the surface. Other data make these interpretations seem unlikely, so measurement error remains a serious possibility

    Tiotropium Respimat® add-on therapy to inhaled corticosteroids in patients with symptomatic asthma improves clinical outcomes regardless of baseline characteristics

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    BACKGROUND: Despite currently available therapies and detailed treatment guidelines, many patients with asthma remain symptomatic. Tiotropium delivered by the soft mist inhaler Respimat®, as add-on therapy to medium-dose inhaled corticosteroids (ICS), has been shown to improve lung function and asthma control in patients with symptomatic moderate asthma. OBJECTIVE: To determine whether the efficacy of tiotropium Respimat® in asthma differs by patients' study baseline characteristics. METHODS: Two replicate Phase III, randomized, double-blind, placebo-controlled, parallel-group studies (MezzoTinA-asthma®; NCT01172808 and NCT01172821) of once-daily tiotropium Respimat 5 μg and 2.5 μg add-on to ICS were conducted in patients with symptomatic asthma despite treatment with medium-dose ICS with or without additional controllers. Subgroup analyses of peak forced expiratory volume in 1 s (FEV1), trough FEV1, risk of severe asthma exacerbation and Asthma Control Questionnaire responder rate were performed to determine whether results were influenced by patients' baseline characteristics. RESULTS: In this analysis, 523 patients received placebo while 517 and 519 patients received the 5 μg and 2.5 μg dose of tiotropium Respimat, respectively. The magnitude of the improvements in lung function and asthma control, as well as the reduced risk of severe exacerbation with both doses of tiotropium Respimat versus placebo, was independent of a broad range of baseline characteristics. CONCLUSIONS: Once-daily tiotropium Respimat as add-on to ICS is a beneficial treatment option for patients with asthma who remain symptomatic despite at least medium-dose ICS, regardless of baseline characteristics

    Neuroligin 1 is dynamically exchanged at postsynaptic sites

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    Neuroligins are postsynaptic cell adhesion molecules that associate with presynaptic neurexins. Both factors form a transsynaptic connection, mediate signaling across the synapse, specify synaptic functions, and play a role in synapse formation. Neuroligin dysfunction impairs synaptic transmission, disrupts neuronal networks, and is thought to participate in cognitive diseases. Here we report that chemical treatment designed to induce long-term potentiation or long-term depression (LTD) induces neuroligin 1/3 turnover, leading to either increased or decreased surface membrane protein levels, respectively. Despite its structural role at a crucial transsynaptic position, GFP-neuroligin 1 leaves synapses in hippocampal neurons over time with chemical LTD-induced neuroligin internalization depending on an intact microtubule cytoskeleton. Accordingly, neuroligin 1 and its binding partner postsynaptic density protein-95 (PSD-95) associate with components of the dynein motor complex and undergo retrograde cotransport with a dynein subunit. Transgenic depletion of dynein function in mice causes postsynaptic NLG1/3 and PSD-95 enrichment. In parallel, PSD lengths and spine head sizes are significantly increased, a phenotype similar to that observed upon transgenic overexpression of NLG1 (Dahlhaus et al., 2010). Moreover, application of a competitive PSD-95 peptide and neuroligin 1 C-terminal mutagenesis each specifically alter neuroligin 1 surface membrane expression and interfere with its internalization. Our data suggest the concept that synaptic plasticity regulates neuroligin turnover through active cytoskeleton transport

    Gene content evolution in the arthropods

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    Arthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from and recorded in adaptive changes in the genome. Dissection of the genomic record of sequence change enables broad questions regarding genome evolution to be addressed, even across hyper-diverse taxa within arthropods. Using 76 whole genome sequences representing 21 orders spanning more than 500 million years of arthropod evolution, we document changes in gene and protein domain content and provide temporal and phylogenetic context for interpreting these innovations. We identify many novel gene families that arose early in the evolution of arthropods and during the diversification of insects into modern orders. We reveal unexpected variation in patterns of DNA methylation across arthropods and examples of gene family and protein domain evolution coincident with the appearance of notable phenotypic and physiological adaptations such as flight, metamorphosis, sociality, and chemoperception. These analyses demonstrate how large-scale comparative genomics can provide broad new insights into the genotype to phenotype map and generate testable hypotheses about the evolution of animal diversity

    Smoking in film in New Zealand: measuring risk exposure

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    BACKGROUND: Smoking in film is a risk factor for smoking uptake in adolescence. This study aimed to quantify exposure to smoking in film received by New Zealand audiences, and evaluate potential interventions to reduce the quantity and impact of this exposure. METHODS: The ten highest-grossing films in New Zealand for 2003 were each analysed independently by two viewers for smoking, smoking references and related imagery. Potential interventions were explored by reviewing relevant New Zealand legislation, and scientific literature. RESULTS: Seven of the ten films contained at least one tobacco reference, similar to larger film samples. The majority of the 38 tobacco references involved characters smoking, most of whom were male. Smoking was associated with positive character traits, notably rebellion (which may appeal to adolescents). There appeared to be a low threshold for including smoking in film. Legislative or censorship approaches to smoking in film are currently unlikely to succeed. Anti-smoking advertising before films has promise, but experimental research is required to demonstrate cost effectiveness. CONCLUSION: Smoking in film warrants concern from public health advocates. In New Zealand, pre-film anti-smoking advertising appears to be the most promising immediate policy response

    A New Paradigm for Large Earthquakes in Stable Continental Plate Interiors

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    Large earthquakes within stable continental regions (SCR) show that significant amounts of elastic strain can be released on geological structures far from plate boundary faults, where the vast majority of the Earth's seismic activity takes place. SCR earthquakes show spatial and temporal patterns that differ from those at plate boundaries and occur in regions where tectonic loading rates are negligible. However, in the absence of a more appropriate model, they are traditionally viewed as analogous to their plate boundary counterparts, occuring when the accrual of tectonic stress localized at long-lived active faults reaches failure threshold. Here we argue that SCR earthquakes are better explained by transient perturbations of local stress or fault strength that release elastic energy from a pre-stressed lithosphere. As a result, SCR earthquakes can occur in regions with no previous seismicity and no surface evidence for strain accumulation. They need not repeat, since the tectonic loading rate is close to zero. Therefore, concepts of recurrence time or fault slip rate do not apply. As a consequence, seismic hazard in SCRs is likely more spatially distributed than indicated by paleoearthquakes, current seismicity, or geodetic strain rates

    Facilitating Adolescent Well-Being: A Review of the Challenges and Opportunities and the Beneficial Roles of Parents, Schools, Neighborhoods, and Policymakers

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    Adolescents face exceptional challenges and opportunities that may have a lifelong impact on their consumption and personal and societal well-being. Parents, community members (schools and neighborhoods), and policymakers play major roles in shaping adolescents and influencing their engagement in consumption behaviors that are either developmentally problematic (e.g., drug use and unhealthy eating) or developmentally constructive (e.g., academic pursuits and extracurricular activities). In this article, we discuss two main topics: (a) the challenges and opportunities that characterize adolescence, based primarily on research in epidemiology and neuroscience, and (b) the ways that parents, community members, and policymakers can facilitate positive adolescent development, based on research from many disciplines including marketing, psychology, sociology, communications, public health, and education. Our goal is to summarize the latest scientific findings that can be used by various stakeholders to help adolescents navigate this turbulent period and become well-adjusted, thriving adults

    Defining the Specificity of Cotranslationally Acting Chaperones by Systematic Analysis of mRNAs Associated with Ribosome-Nascent Chain Complexes

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    Polypeptides exiting the ribosome must fold and assemble in the crowded environment of the cell. Chaperones and other protein homeostasis factors interact with newly translated polypeptides to facilitate their folding and correct localization. Despite the extensive efforts, little is known about the specificity of the chaperones and other factors that bind nascent polypeptides. To address this question we present an approach that systematically identifies cotranslational chaperone substrates through the mRNAs associated with ribosome-nascent chain-chaperone complexes. We here focused on two Saccharomyces cerevisiae chaperones: the Signal Recognition Particle (SRP), which acts cotranslationally to target proteins to the ER, and the Nascent chain Associated Complex (NAC), whose function has been elusive. Our results provide new insights into SRP selectivity and reveal that NAC is a general cotranslational chaperone. We found surprising differential substrate specificity for the three subunits of NAC, which appear to recognize distinct features within nascent chains. Our results also revealed a partial overlap between the sets of nascent polypeptides that interact with NAC and SRP, respectively, and showed that NAC modulates SRP specificity and fidelity in vivo. These findings give us new insight into the dynamic interplay of chaperones acting on nascent chains. The strategy we used should be generally applicable to mapping the specificity, interplay, and dynamics of the cotranslational protein homeostasis network
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