241 research outputs found

    Photoswitchable and non-photoswitchable tubulin inhibitors for applications in cell biology

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    Research at the Interface between Chemistry and Virology:  Development of a Molecular Flashlight

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    Although industrial researchers have been involved in interdisciplinary studies pertaining to virology for several decades, the participation of academic chemists has been significantly increased owing to the importance of HIV (human immunodeficiency virus), the virus which leads to the onset of AIDS (acquired immune deficiency syndrome). The Center for Disease Control estimates that almost 20 million people have been infected by HIV worldwide. The compelling need for effective antiviral therapies for HIVinfected persons, together with rapid advances in understanding the molecular mechanisms of virus replication, has resulted in an explosion of interest in antiviral agents and approaches to antiviral therapie

    Doing transnational family im Kontext von Flucht und Krisenmigration: Stand der Forschung

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    In den vergangenen Jahren ist die Zahl gewaltsam Vertriebener stetig gestiegen, und auch die Anzahl der Menschen, die in weiter entfernte Staaten fliehen, hat laut UNHCR weltweit stark zugenommen. In Deutschland wurden im Zeitraum von 2015 bis 2017 fast 1,4 Mio. Asylerstanträge gestellt, hauptsächlich von Menschen aus Syrien, Afghanistan, Irak sowie Eritrea. Aufgrund der Aktualität des Themas hat sich seit Kurzem eine eigen-ständige Forschung zu Flucht und Geflüchteten in Deutschland entwickelt, wobei sich die deutsche Forschungslandschaft über die Disziplinen hinweg vor allem auf die Themen Aufnahme und Teilhabe von Geflüchteten in Deutschland konzentriert. Bisher gibt es nur sehr wenige Arbeiten, die sich mit Familien von Geflüchteten auseinandersetzen, obwohl unbestritten ist, dass Familien sowohl für die Migrationsentscheidung als auch für die Integration und Teilhabe im Zielland eine wichtige Rolle spielen. In Vorbereitung auf eine eigene empirische Studie, die diese Forschungslücke schließen möchte, wurde das vorliegende Working Paper erstellt. Es fasst die internationale Literatur zu den Fragen nach der Entstehung, Beibehaltung und Veränderung von transnationalen Familien, den transnationalen Alltagspraktiken sowie Unterstützungsleistungen und den Konsequenzen von Transnationalität auf die Beziehungsstabilität und -qualität zwischen Partnern, Kindern und Eltern sowie deren (subjektivem) Wohlbefinden, Einstellungen und Geschlechterrollen zusammen. Das Working Paper versucht darüber hinaus, die Anschlussfähigkeit der vorliegenden Studien zu transnationalen Familien auf den Fluchtkontext herzustellen und Forschungslücken im Themenfeld transnationaler Familien und Fluchtmigration aufzuzeigen

    Biomarkers of incident radiographic knee osteoarthritis: Do they vary by chronic knee symptoms?

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    To explore prognostication of incident radiographic knee osteoarthritis (OA) with OA-related biomarkers in a large sample of African-American and Caucasian men and women

    Photoswitchable paclitaxel-based microtubule stabilisers allow optical control over the microtubule cytoskeleton

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    Small molecule inhibitors are prime reagents for studies in microtubule cytoskeleton research, being applicable across a range of biological models and not requiring genetic engineering. However, traditional chemical inhibitors cannot be experimentally applied with spatiotemporal precision suiting the length and time scales inherent to microtubule-dependent cellular processes. We have synthesised photoswitchable paclitaxel-based microtubule stabilisers, whose binding is induced by photoisomerisation to their metastable state. Photoisomerising these reagents in living cells allows optical control over microtubule network integrity and dynamics, cell division and survival, with biological response on the timescale of seconds and spatial precision to the level of individual cells within a population. In primary neurons, they enable regulation of microtubule dynamics resolved to subcellular regions within individual neurites. These azobenzene-based microtubule stabilisers thus enable non-invasive, spatiotemporally precise modulation of the microtubule cytoskeleton in living cells, and promise new possibilities for studying intracellular transport, cell motility, and neuronal physiology

    Creatine and creatinine quantified using nuclear magnetic resonance:A method validation study and clinical associations between circulating creatine and fatigue in kidney transplant recipients

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    Background: A potential contributor to fatigue in kidney transplant recipients (KTR) may be impaired creatine homeostasis. We developed and validated a high-throughput NMR assay allowing for simultaneous measurement of circulating creatine and creatinine, and determined plasma creatine and estimated intramuscular creatine concentrations in KTRs, delineated their determinants and explored their associations with self-reported fatigue.Methods: An NMR assay was developed and validated for measurement of circulating creatinine and creatine concentrations. Plasma creatine and creatinine concentrations were measured in 618 KTR. Fatigue was assessed using the checklist individual strength. Associations of creatine parameters with fatigue was assessed using linear mixed effect models.Results: The NMR-based assay had good sensitivity, precision and demonstrated linearity across a large range of values. Among KTR, the mean age was 56 ± 13 years, 62% were men and eGFR was 54 ± 18 ml/min/1.73 m2. Plasma creatine concentration was 27 [19–39] µmol/L. Estimated intramuscular creatine concentration was 27 ± 7 mmol/kg. Higher plasma creatine concentration and higher estimated intramuscular creatine concentration were independently associated with a lower total fatigue score and less motivation problems.Conclusion: An NMR method for measurement of circulating creatine and creatinine which offers the potential for accurate and efficient quantification was developed. The found associations suggest that improving creatine status may play a beneficial role in mitigating fatigue.</p

    Differences in Multi-joint Symptomatic Osteoarthritis Phenotypes by Race and Gender: The Johnston County Osteoarthritis Project

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    To determine race and gender differences in phenotypes (patterns) of multiple joint symptomatic osteoarthritis (sOA) involvement

    Age-related differences in 1p and 19q deletions in oligodendrogliomas

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    BACKGROUND: Recent reports indicate that anaplastic oligodendrogliomas frequently show allelic losses on chromosome arms 1p and 19q, and that these deletions are associated with better chemotherapeutic response and overall patient survival. Because of the diversified genetic makeup of the population and the centralized provincial referral system for brain tumor patients in Manitoba, the epidemiological features of such tumors sometimes differ from the published data acquired from non-community based settings. In this study, we assessed the prevalence of allelic deletions for chromosome arms 1p and 19q in anaplastic and in low-grade oligodendrogliomas in the Manitoba population. METHODS: Loss of heterozygosity (LOH) analysis of brain tumors was carried out using 4 microsatellite markers (D1S508, D1S2734, D19S219 and D19S412) and a PCR based assay. The tumors were consecutively acquired during the period September 1999–March 2001 and a total of 63 tumors were assessed. RESULTS: We found that allelic loss of chromosome 1p and 19q was higher in oligodendrogliomas than in other diffuse gliomas and that for anaplastic oligodendrogliomas, younger patients exhibited significantly more deletions than older patients (>60 years of age). CONCLUSIONS: These studies suggest that age may be a factor in the genetic alterations of oligodendrogliomas. In addition, these studies demonstrate that this assay can easily be carried out in a cost-effective manner in a small tertiary center
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