220 research outputs found

    Assessing racial and ethnic disparities using a COVID-19 outcomes continuum for New York State

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    Purpose Heightened COVID-19 mortality among Black non-Hispanic and Hispanic communities (relative to white non-Hispanic) is well established. This study aims to estimate the relative contributions to fatality disparities in terms of differences in SARS-CoV-2 infections, diagnoses, and disease severity. Methods We constructed COVID-19 outcome continua (similar to the HIV care continuum) for white non-Hispanic, Black non-Hispanic, and Hispanic adults in New York State. For each stage in the COVID-19 outcome continua (population, infection experience, diagnosis, hospitalization, fatality), we synthesized the most recent publicly available data. We described each continuum using overall percentages, fatality rates, and relative changes between stages, with comparisons between race and ethnicity using risk ratios. Results Estimated per-population COVID-19 fatality rates were 0.03%, 0.18%, and 0.12% for white non-Hispanic, Black non-Hispanic, and Hispanic adults, respectively. The 3.48-fold disparity for Hispanic, relative to white, communities was explained by differences in infection experience, whereas the 5.38-fold disparity for non-Hispanic Black, relative to white, communities was primarily driven by differences in both infection experience and in the need for hospitalization, given infection. Conclusions These findings suggest the most impactful stages on which to intervene with programs and policies to build COVID-19 health equity

    Ubiquitylation of the ER-Shaping Protein Lunapark via the CRL3KLHL12 Ubiquitin Ligase Complex

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    Summary: Cullin-RING ligases (CRLs) control key cellular processes by promoting ubiquitylation of a multitude of soluble cytosolic and nuclear proteins. Subsets of CRL complexes are recruited and activated locally at cellular membranes; however, few CRL functions and substrates at these distinct cellular compartments are known. Here, we use a proteomic screen to identify proteins that are ubiquitylated at cellular membranes and found that Lunapark, an endoplasmic reticulum (ER)-shaping protein localized to ER three-way junctions, is ubiquitylated by the CRL3KLHL12 ubiquitin ligase. We demonstrate that Lunapark interacts with mechanistic target of rapamycin complex-1 (mTORC1), a central cellular regulator that coordinates growth and metabolism with environmental conditions. We show that mTORC1 binds Lunapark specifically at three-way junctions, and lysosomes, where mTORC1 is activated, make contact with three-way junctions where Lunapark resides. Inhibition of Lunapark ubiquitylation results in neurodevelopmental defects indicating that KLHL12-dependent ubiquitylation of Lunapark is required for normal growth and development

    Methods for analysis of brain connectivity : An IFCN-sponsored review

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    The goal of this paper is to examine existing methods to study the "Human Brain Connectome" with a specific focus on the neurophysiological ones. In recent years, a new approach has been developed to evaluate the anatomical and functional organization of the human brain: the aim of this promising multimodality effort is to identify and classify neuronal networks with a number of neurobiologically meaningful and easily computable measures to create its connectome. By defining anatomical and functional connections of brain regions on the same map through an integrated approach, comprising both modern neurophysiological and neuroimaging (i.e. flow/metabolic) brain-mapping techniques, network analysis becomes a powerful tool for exploring structural-functional connectivity mechanisms and for revealing etiological relationships that link connectivity abnormalities to neuropsychiatric disorders. Following a recent IFCN-endorsed meeting, a panel of international experts was selected to produce this current state-of-art document, which covers the available knowledge on anatomical and functional connectivity, including the most commonly used structural and functional MRI, EEG, MEG and non-invasive brain stimulation techniques and measures of local and global brain connectivity. (C) 2019 Published by Elsevier B.V. on behalf of International Federation of Clinical Neurophysiology.Peer reviewe

    Potential effects of oilseed rape expressing oryzacystatin-1 (OC-1) and of purified insecticidal proteins on larvae of the solitary bee Osmia bicornis

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    Despite their importance as pollinators in crops and wild plants, solitary bees have not previously been included in non-target testing of insect-resistant transgenic crop plants. Larvae of many solitary bees feed almost exclusively on pollen and thus could be highly exposed to transgene products expressed in the pollen. The potential effects of pollen from oilseed rape expressing the cysteine protease inhibitor oryzacystatin-1 (OC-1) were investigated on larvae of the solitary bee Osmia bicornis (= O. rufa). Furthermore, recombinant OC-1 (rOC-1), the Bt toxin Cry1Ab and the snowdrop lectin Galanthus nivalis agglutinin (GNA) were evaluated for effects on the life history parameters of this important pollinator. Pollen provisions from transgenic OC-1 oilseed rape did not affect overall development. Similarly, high doses of rOC-1 and Cry1Ab as well as a low dose of GNA failed to cause any significant effects. However, a high dose of GNA (0.1%) in the larval diet resulted in significantly increased development time and reduced efficiency in conversion of pollen food into larval body weight. Our results suggest that OC-1 and Cry1Ab expressing transgenic crops would pose a negligible risk for O. bicornis larvae, whereas GNA expressing plants could cause detrimental effects, but only if bees were exposed to high levels of the protein. The described bioassay with bee brood is not only suitable for early tier non-target tests of transgenic plants, but also has broader applicability to other crop protection products

    Using Heat to Characterize Streambed Water Flux Variability in Four Stream Reaches

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    Estimates of streambed water fl ux are needed for the interpretation of streambed chemistry and reactions. Continuous temperature and head monitoring in stream reaches within four agricultural watersheds (Leary Weber Ditch, IN; Maple Creek, NE; DR2 Drain, WA; and Merced River, CA) allowed heat to be used as a tracer to study the temporal and spatial variability of fluxes through the streambed. Synoptic methods (seepage meter and differential discharge measurements) were compared with estimates obtained by using heat as a tracer. Water flux was estimated by modeling one-dimensional vertical flow of water and heat using the model VS2DH. Flux was influenced by physical heterogeneity of the stream channel and temporal variability in stream and ground-water levels. During most of the study period (April–December 2004), flux was upward through the streambeds. At the IN, NE, and CA sites, high-stage events resulted in rapid reversal of flow direction inducing short-term surface-water flow into the streambed. During late summer at the IN site, regional ground-water levels dropped, leading to surface-water loss to ground water that resulted in drying of the ditch. Synoptic measurements of flux generally supported the model flux estimates. Water flow through the streambed was roughly an order of magnitude larger in the humid basins (IN and NE) than in the arid basins (WA and CA). Downward flux, in response to sudden high streamflows, and seasonal variability in flux was most pronounced in the humid basins and in high conductivity zones in the streambed

    BRCA1 mutations and other sequence variants in a population-based sample of Australian women with breast cancer

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    The frequency, in women with breast cancer, of mutations and other variants in the susceptibility gene, BRCA1, was investigated using a population-based case–control-family study. Cases were women living in Melbourne or Sydney, Australia, with histologically confirmed, first primary, invasive breast cancer, diagnosed before the age of 40 years, recorded on the state Cancer Registries. Controls were women without breast cancer, frequency-matched for age, randomly selected from electoral rolls. Full manual sequencing of the coding region of BRCA1 was conducted in a randomly stratified sample of 91 cases; 47 with, and 44 without, a family history of breast cancer in a first- or second-degree relative. All detected variants were tested in a random sample of 67 controls. Three cases with a (protein-truncating) mutation were detected. Only one case had a family history; her mother had breast cancer, but did not carry the mutation. The proportion of Australian women with breast cancer before age 40 who carry a germline mutation in BRCA1 was estimated to be 3.8% (95% Cl 0.3–12.6%). Seven rare variants were also detected, but for none was there evidence of a strong effect on breast cancer susceptibility. Therefore, on a population basis, rare variants are likely to contribute little to breast cancer incidence. © 1999 Cancer Research Campaig
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