160 research outputs found

    Virtual Community Health Workers: Outreach Calls During COVID-19

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    The “Clinical Experience” program at the Sidney Kimmel Medical College, established in 2017, provides pre-clerkship students with an opportunity to identify and address patients’ needs for social determinants of health (SDoH). The COVID-19 pandemic led to a suspension of the student program in the clinical environment, but the CHWs continued to address patients’ social needs from a remote setting. In the absence of established best practices regarding patient outreach calls from a remote setting, we sought to develop an effective workflow that would mask the CHWs’ personal cell phones while leading to fewer “unable to reach” scenarios and improved case resolution rates

    Dual TNFα-induced effects on NRF2 mediated antioxidant defence in astrocyte-rich cultures: role of protein kinase activation

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    Tumor necrosis factor-α (TNFα) is a pleiotropic molecule that can have both protective and detrimental effects in neurodegeneration. Here we have investigated the temporal effects of TNFα on the inducible Nrf2 system in astrocyte-rich cultures by determination of glutathione (GSH) levels, γglutamylcysteine ligase (γGCL) activity, the protein levels of Nrf2, Keap1, the catalytic and modulatory subunit of γGCL (γGCL-C and γGCL-M respectively). Astrocyte-rich cultures were exposed for 24 or 72 h to different concentrations of TNFα. Acute exposure (24 h) of astrocyte-rich cultures to 10 ng/mL of TNFα increased GSH, γGCL activity, the protein levels of γGCL-M, γGCL-C and Nrf2 in parallel with decreased levels of Keap1. Antioxidant responsive element (ARE)-mediated transcription was blocked by inhibitors of ERK1/2, JNK and Akt whereas inactivation of p38 and GSK3β further enhanced transcription. In contrast treatment with TNFα for 72 h decreased components of the Nrf2 system in parallel with an increase of Keap1. Stimulation of the Nrf2 system by tBHQ was intact after 24 h but blocked after 72 h treatment with TNFα. This down-regulation after 72 h correlated with activation of p38 MAPK and GSK3β, since inhibition of these signalling pathways reversed this effect. The upregulation of the Nrf2 system by TNFα (24 h treatment) protected the cells from oxidative stress through elevated γGCL activity whereas the down-regulation (72 h treatment) caused pronounced oxidative toxicity. One of the important implications of the results is that in a situation where Nrf2 is decreased, such as in Alzheimer’s disease, the effect of TNFα is detrimental.Fil: Correa, Fernando Gabriel. University Goteborg; Suecia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mallard, Carina. University Goteborg; SueciaFil: Nilsson, Michael. University Goteborg; SueciaFil: Sandberg, Mats. University Goteborg; Sueci

    Subcellular distribution of terminal α-D- and β-D-galactosyl residues in Ehrlich tumour cells studied by lectin-gold techniques

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    We have studied by high resolution in situ light and electron microscopic lectin-gold techniques the subcellular distribution of α- d -Gal residues using the Griffonia simplicifolia I-B 4 isolectin and compared it with that of β- d -Gal residues as detected with the Datura stramonium lectin in Ehrlich tumour cells grown as ascites or monolayer. The microvillar but not the smooth plasma membrane regions were labelled with the Griffonia simplicifolia I-B 4 isolectin whereas both plasma membrane regions were equally well labelled with the Datura stramonium lectin. Elements of the endocytotic/lysosomal system such as coated membrane invaginations and vesicles, early and late endosomes and secondary lysosomes were positive for both α- d -Gal and β- d -Gal residues. A particular feature of Ehrlich tumour cells is an elaborate tubular membrane system located in the pericentriolar region which is labelled throughout by both lectins and represents part of the endosomal system. In the Golgi apparatus labelling with both lectins was observed to commence in trans cisternae which is indirect evidence for a joint distribution of the sequentially acting β1,4 and α1,3-galactosyl-transferases.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45677/1/10719_2004_Article_BF00731358.pd

    Comparative Structural Analysis of Human DEAD-Box RNA Helicases

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    DEAD-box RNA helicases play various, often critical, roles in all processes where RNAs are involved. Members of this family of proteins are linked to human disease, including cancer and viral infections. DEAD-box proteins contain two conserved domains that both contribute to RNA and ATP binding. Despite recent advances the molecular details of how these enzymes convert chemical energy into RNA remodeling is unknown. We present crystal structures of the isolated DEAD-domains of human DDX2A/eIF4A1, DDX2B/eIF4A2, DDX5, DDX10/DBP4, DDX18/myc-regulated DEAD-box protein, DDX20, DDX47, DDX52/ROK1, and DDX53/CAGE, and of the helicase domains of DDX25 and DDX41. Together with prior knowledge this enables a family-wide comparative structural analysis. We propose a general mechanism for opening of the RNA binding site. This analysis also provides insights into the diversity of DExD/H- proteins, with implications for understanding the functions of individual family members

    The associations between Parkinson’s disease and cancer: the plot thickens

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    Long memory estimation for complex-valued time series

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    Long memory has been observed for time series across a multitude of fields and the accurate estimation of such dependence, e.g. via the Hurst exponent, is crucial for the modelling and prediction of many dynamic systems of interest. Many physical processes (such as wind data), are more naturally expressed as a complex-valued time series to represent magnitude and phase information (wind speed and direction). With data collection ubiquitously unreliable, irregular sampling or missingness is also commonplace and can cause bias in a range of analysis tasks, including Hurst estimation. This article proposes a new Hurst exponent estimation technique for complex-valued persistent data sampled with potential irregularity. Our approach is justified through establishing attractive theoretical properties of a new complex-valued wavelet lifting transform, also introduced in this paper. We demonstrate the accuracy of the proposed estimation method through simulations across a range of sampling scenarios and complex- and real-valued persistent processes. For wind data, our method highlights that inclusion of the intrinsic correlations between the real and imaginary data, inherent in our complex-valued approach, can produce different persistence estimates than when using real-valued analysis. Such analysis could then support alternative modelling or policy decisions compared with conclusions based on real-valued estimation
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