24 research outputs found

    Sodium Hydroxide Catalyzed Dehydrocoupling of Alcohols with Hydrosilanes

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    An O–Si bond construction protocol employing abundantly available and inexpensive NaOH as the catalyst is described. The method enables the cross-dehydrogenative coupling of an alcohol and hydrosilane to directly generate the corresponding silyl ether under mild conditions and without the production of stoichiometric salt byproducts. The scope of both coupling partners is excellent, positioning the method for use in complex molecule and materials science applications. A novel Si-based cross-coupling reagent is also reported

    Sodium Hydroxide Catalyzed Dehydrocoupling of Alcohols with Hydrosilanes

    Get PDF
    An O–Si bond construction protocol employing abundantly available and inexpensive NaOH as the catalyst is described. The method enables the cross-dehydrogenative coupling of an alcohol and hydrosilane to directly generate the corresponding silyl ether under mild conditions and without the production of stoichiometric salt byproducts. The scope of both coupling partners is excellent, positioning the method for use in complex molecule and materials science applications. A novel Si-based cross-coupling reagent is also reported

    Large-scale comparative genomic ranking of taxonomically restricted genes (TRGs) in bacterial and archaeal genomes

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    BACKGROUND: Lineage-specific, or taxonomically restricted genes (TRGs), especially those that are species and strain-specific, are of special interest because they are expected to play a role in defining exclusive ecological adaptations to particular niches. Despite this, they are relatively poorly studied and little understood, in large part because many are still orphans or only have homologues in very closely related isolates. This lack of homology confounds attempts to establish the likelihood that a hypothetical gene is expressed and, if so, to determine the putative function of the protein. METHODOLOGY/PRINCIPAL FINDINGS: We have developed "QIPP" ("Quality Index for Predicted Proteins"), an index that scores the "quality" of a protein based on non-homology-based criteria. QIPP can be used to assign a value between zero and one to any protein based on comparing its features to other proteins in a given genome. We have used QIPP to rank the predicted proteins in the proteomes of Bacteria and Archaea. This ranking reveals that there is a large amount of variation in QIPP scores, and identifies many high-scoring orphans as potentially "authentic" (expressed) orphans. There are significant differences in the distributions of QIPP scores between orphan and non-orphan genes for many genomes and a trend for less well-conserved genes to have lower QIPP scores. CONCLUSIONS: The implication of this work is that QIPP scores can be used to further annotate predicted proteins with information that is independent of homology. Such information can be used to prioritize candidates for further analysis. Data generated for this study can be found in the OrphanMine at http://www.genomics.ceh.ac.uk/orphan_mine

    Association of mRNA Vaccination With Clinical and Virologic Features of COVID-19 Among US Essential and Frontline Workers

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    IMPORTANCE: Data on the epidemiology of mild to moderately severe COVID-19 are needed to inform public health guidance. OBJECTIVE: To evaluate associations between 2 or 3 doses of mRNA COVID-19 vaccine and attenuation of symptoms and viral RNA load across SARS-CoV-2 viral lineages. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of essential and frontline workers in Arizona, Florida, Minnesota, Oregon, Texas, and Utah with COVID-19 infection confirmed by reverse transcriptase-polymerase chain reaction testing and lineage classified by whole genome sequencing of specimens self-collected weekly and at COVID-19 illness symptom onset. This analysis was conducted among 1199 participants with SARS-CoV-2 from December 14, 2020, to April 19, 2022, with follow-up until May 9, 2022, reported. EXPOSURES: SARS-CoV-2 lineage (origin strain, Delta variant, Omicron variant) and COVID-19 vaccination status. MAIN OUTCOMES AND MEASURES: Clinical outcomes included presence of symptoms, specific symptoms (including fever or chills), illness duration, and medical care seeking. Virologic outcomes included viral load by quantitative reverse transcriptase-polymerase chain reaction testing along with viral viability. RESULTS: Among 1199 participants with COVID-19 infection (714 [59.5%] women; median age, 41 years), 14.0% were infected with the origin strain, 24.0% with the Delta variant, and 62.0% with the Omicron variant. Participants vaccinated with the second vaccine dose 14 to 149 days before Delta infection were significantly less likely to be symptomatic compared with unvaccinated participants (21/27 [77.8%] vs 74/77 [96.1%]; OR, 0.13 [95% CI, 0-0.6]) and, when symptomatic, those vaccinated with the third dose 7 to 149 days before infection were significantly less likely to report fever or chills (5/13 [38.5%] vs 62/73 [84.9%]; OR, 0.07 [95% CI, 0.0-0.3]) and reported significantly fewer days of symptoms (10.2 vs 16.4; difference, -6.1 [95% CI, -11.8 to -0.4] days). Among those with Omicron infection, the risk of symptomatic infection did not differ significantly for the 2-dose vaccination status vs unvaccinated status and was significantly higher for the 3-dose recipients vs those who were unvaccinated (327/370 [88.4%] vs 85/107 [79.4%]; OR, 2.0 [95% CI, 1.1-3.5]). Among symptomatic Omicron infections, those vaccinated with the third dose 7 to 149 days before infection compared with those who were unvaccinated were significantly less likely to report fever or chills (160/311 [51.5%] vs 64/81 [79.0%]; OR, 0.25 [95% CI, 0.1-0.5]) or seek medical care (45/308 [14.6%] vs 20/81 [24.7%]; OR, 0.45 [95% CI, 0.2-0.9]). Participants with Delta and Omicron infections who received the second dose 14 to 149 days before infection had a significantly lower mean viral load compared with unvaccinated participants (3 vs 4.1 log10 copies/μL; difference, -1.0 [95% CI, -1.7 to -0.2] for Delta and 2.8 vs 3.5 log10 copies/μL, difference, -1.0 [95% CI, -1.7 to -0.3] for Omicron). CONCLUSIONS AND RELEVANCE: In a cohort of US essential and frontline workers with SARS-CoV-2 infections, recent vaccination with 2 or 3 mRNA vaccine doses less than 150 days before infection with Delta or Omicron variants, compared with being unvaccinated, was associated with attenuated symptoms, duration of illness, medical care seeking, or viral load for some comparisons, although the precision and statistical significance of specific estimates varied

    Measurement of Socio-Scientific Reasoning (SSR) and Exploration of SSR as a Progression of Competencies

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    Socio-scientific reasoning (SSR) is key to helping students take informed positions around socio-scientific issues (SSI). SSR comprises four competencies: recognising complexity of SSI’s, multiple perspectives around SSI’s, the need for ongoing inquiry around SSI’s, and skepticism around different parties’ claims made about SSI’s. The Quantitative Assessment of SSR (QuASSR) provides a promising measurement framework, but there are still important questions around the ability of this instrument to measure transfer across different scenarios and change in SSR over an intervention. Further, prior work suggests that the four competencies may constitute a progression. We explored the ability of the QuASSR to measure transfer of SSR across three different SSI’s using 2-faceted and multi-faceted Rasch models. We used path analysis to test the hypothesis that competencies associated with SSR formed a progression. We found transfer or neartransfer of SSR across the three scenarios, and that the competencies comprise a unidimensional hierarchy. Perspective-taking is a necessary bridge between students’ understanding of complexity and the higher-level competencies of inquiry and skepticism. Inquiry and skepticism were found to be conditionally independent upon accounting for perspective-taking, supporting the idea that seeing multiple perspectives around SSI’s is central to development of the other SSR competencies. (PsycInfo Database Record (c) 2021 APA, all rights reserved

    Measurement of Socio-Scientific Reasoning (SSR) and Exploration of SSR as a Progression of Competencies

    No full text
    Socio-scientific reasoning (SSR) is key to helping students take informed positions around socio-scientific issues (SSI). SSR comprises four competencies: recognising complexity of SSI’s, multiple perspectives around SSI’s, the need for ongoing inquiry around SSI’s, and skepticism around different parties’ claims made about SSI’s. The Quantitative Assessment of SSR (QuASSR) provides a promising measurement framework, but there are still important questions around the ability of this instrument to measure transfer across different scenarios and change in SSR over an intervention. Further, prior work suggests that the four competencies may constitute a progression. We explored the ability of the QuASSR to measure transfer of SSR across three different SSI’s using 2-faceted and multi-faceted Rasch models. We used path analysis to test the hypothesis that competencies associated with SSR formed a progression. We found transfer or neartransfer of SSR across the three scenarios, and that the competencies comprise a unidimensional hierarchy. Perspective-taking is a necessary bridge between students’ understanding of complexity and the higher-level competencies of inquiry and skepticism. Inquiry and skepticism were found to be conditionally independent upon accounting for perspective-taking, supporting the idea that seeing multiple perspectives around SSI’s is central to development of the other SSR competencies. (PsycInfo Database Record (c) 2021 APA, all rights reserved

    Depressed Synaptic Transmission and Reduced Vesicle Release Sites in Huntington\u27s Disease Neuromuscular Junctions

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    Huntington\u27s disease (HD) is a progressive and fatal degenerative disorder that results in debilitating cognitive and motor dysfunction. Most HD studies have focused on degeneration of the CNS. We previously discovered that skeletal muscle from transgenic R6/2 HD mice is hyperexcitable due to decreased chloride and potassium conductances. The progressive and early onset of these defects suggest a primary myopathy in HD. In this study, we examined the relationship between neuromuscular transmission and skeletal muscle hyperexcitability. We used an ex vivo preparation of the levator auris longus muscle from male and female late-stage R6/2 mice and age-matched wild-type controls. Immunostaining of the synapses and molecular analyses revealed no evidence of denervation. Physiologically, we recorded spontaneous miniature endplate currents (mEPCs) and nerve-evoked EPCs (eEPCs) under voltage-clamp, which, unlike current-clamp records, were independent of the changes in muscle membrane properties. We found a reduction in the number of vesicles released per action potential (quantal content) in R6/2 muscle, which analysis of eEPC variance and morphology indicate is caused by a reduction in the number of vesicle release sites (n) rather than a change in the probability of release (prel). Furthermore, analysis of high-frequency stimulation trains suggests an impairment in vesicle mobilization. The depressed neuromuscular transmission in R6/2 muscle may help compensate for the muscle hyperexcitability and contribute to motor impersistence.SIGNIFICANCE STATEMENT Recent evidence indicates that Huntington\u27s disease (HD) is a multisystem disorder. Our examination of neuromuscular transmission in this study reveals defects in the motor nerve terminal that may compensate for the muscle hyperexcitability in HD. The technique we used eliminates the effects of the altered muscle membrane properties on synaptic currents and thus provides hitherto the most detailed analysis of synaptic transmission in HD. Clinically, the striking depression of neurotransmission we found may help explain the motor impersistence in HD patients. Therapies that target the highly accessible peripheral nerve and muscle system provide a promising new avenue to lessen the debilitating motor symptoms of HD

    Depressed Synaptic Transmission and Reduced Vesicle Release Sites in Huntington\u27s Disease Neuromuscular Junctions

    No full text
    Huntington\u27s disease (HD) is a progressive and fatal degenerative disorder that results in debilitating cognitive and motor dysfunction. Most HD studies have focused on degeneration of the CNS. We previously discovered that skeletal muscle from transgenic R6/2 HD mice is hyperexcitable due to decreased chloride and potassium conductances. The progressive and early onset of these defects suggest a primary myopathy in HD. In this study, we examined the relationship between neuromuscular transmission and skeletal muscle hyperexcitability. We used an ex vivo preparation of the levator auris longus muscle from male and female late-stage R6/2 mice and age-matched wild-type controls. Immunostaining of the synapses and molecular analyses revealed no evidence of denervation. Physiologically, we recorded spontaneous miniature endplate currents (mEPCs) and nerve-evoked EPCs (eEPCs) under voltage-clamp, which, unlike current-clamp records, were independent of the changes in muscle membrane properties. We found a reduction in the number of vesicles released per action potential (quantal content) in R6/2 muscle, which analysis of eEPC variance and morphology indicate is caused by a reduction in the number of vesicle release sites (n) rather than a change in the probability of release (prel). Furthermore, analysis of high-frequency stimulation trains suggests an impairment in vesicle mobilization. The depressed neuromuscular transmission in R6/2 muscle may help compensate for the muscle hyperexcitability and contribute to motor impersistence.SIGNIFICANCE STATEMENT Recent evidence indicates that Huntington\u27s disease (HD) is a multisystem disorder. Our examination of neuromuscular transmission in this study reveals defects in the motor nerve terminal that may compensate for the muscle hyperexcitability in HD. The technique we used eliminates the effects of the altered muscle membrane properties on synaptic currents and thus provides hitherto the most detailed analysis of synaptic transmission in HD. Clinically, the striking depression of neurotransmission we found may help explain the motor impersistence in HD patients. Therapies that target the highly accessible peripheral nerve and muscle system provide a promising new avenue to lessen the debilitating motor symptoms of HD
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