112 research outputs found

    The Lies You Tell: Disrupting the Dominant Depiction of Black Women in Film

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    Hollywood negatively depicts Black women, often minimizing or ignoring their character’s developmental milestones or self-actualization. Using Black Feminist Thought, an oppositional gaze was used to analyze their development in film

    Unveiling Strategies: Empowering Autistic Adult Learners in Higher Education through Inclusive Research Practices

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    This qualitative research investigates strategies of autistic adult learners in higher education through participatory methods. Findings reveal nuanced experiences, emphasizing the need for inclusive research to support diverse learners effectively

    International Law in Crisis: Foreword

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    International Law in Crisis: Foreword

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    Diagnostic and Prognostic Significance of Complement in Patients with Alcohol-associated Hepatitis

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    BACKGROUND and AIMS: Given the lack of effective therapies and high mortality in acute alcohol-associated hepatitis (AH), it is important to develop rationally-designed biomarkers for effective disease management. Complement, a critical component of the innate immune system, contributes to uncontrolled inflammatory responses leading to liver injury, but is also involved in hepatic regeneration. Here we investigated if a panel of complement proteins and activation products would provide useful biomarkers for severity of AH and aid in predicting 90 days mortality. APPROACH and RESULTS: Plasma samples collected at time of diagnosis from 254 patients with moderate and severe AH recruited from four medical centers and 31 healthy individuals were used to quantify complement proteins by ELISA and Luminex arrays. Components of the classical and lectin pathways, including complement factors C2, C4b and C4d, as well as complement factor I (CFI) and C5, were reduced in AH patients compared to healthy individuals. In contrast, components of the alternative pathway, including complement factor Ba (CFBa) and factor D (CFD), were increased. Markers of complement activation were also differentially evident, with C5a increased and the soluble terminal complement complex (sC5b9) decreased in AH. Mannose binding lectin (MBL), C4b, CFI, C5 and sC5b9 were negatively correlated with model for end-stage liver disease (MELD) score, while CFBa and CFD were positively associated with disease severity. Lower CFI and sC5b9 were associated with increased 90-day mortality in AH. CONCLUSIONS: Taken together, these data indicate that AH is associated with a profound disruption of complement. Inclusion of complement, especially CFI and sC5b9, along with other laboratory indicators, could improve diagnostic and prognostic indications of disease severity and risk of mortality for AH patients

    Extramedullary Hematopoiesis in the Sinonasal Cavity: A Case Report and Review of the Literature

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    Approximately 1 in 600 African-Americans are homozygous for the sickle cell gene.1 This commonly inherited hematologic disorder causes sickling of red blood cells (RBCs), prompting rapid hemolysis. A common clinical manifestation of sickle cell disease (SCD) is chronic anemia. The body responds by increasing hematopoiesis. RBC production classically occurs in the bone marrow of the long bones, pelvis, spine, and sternum. With chronically elevated erythropoietin levels, organs such as the spleen and liver help augment the body’s RBC supply. These organs are areas of fetal erythropoiesis that do not typically contribute to physiologic RBC production in adults. Other, less commonly involved organs that have been documented as sites of extramedullary hematoposesis (EMH) include lymph nodes, paravertebral regions, intra-spinal canal, pre-sacral region, nasopharynx, and paranasal sinuses

    Biomarkers Signal Contaminant Effects on the Organs of English Sole (Parophrys vetulus) from Puget Sound

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    Fish living in contaminated environments accumulate toxic chemicals in their tissues. Biomarkers are needed to identify the resulting health effects, particularly focusing on early changes at a subcellular level. We used a suite of complementary biomarkers to signal contaminant-induced changes in the DNA structure and cellular physiology of the livers and gills of English sole (Parophrys vetulus). These sediment-dwelling fish were obtained from the industrialized lower Duwamish River (DR) in Seattle, Washington, and from Quartermaster Harbor (QMH), a relatively clean reference site in south Puget Sound. Fourier transform–infrared (FT-IR) spectroscopy, liquid chromatography/mass spectrometry (LC/MS), and gas chromatography/mass spectrometry (GC/MS) identified potentially deleterious alterations in the DNA structure of the DR fish livers and gills, compared with the QMH fish. Expression of CYP1A (a member of the cytochrome P450 multigene family of enzymes) signaled changes in the liver associated with the oxidation of organic xenobiotics, as previously found with the gill. The FT-IR models demonstrated that the liver DNA of the DR fish had a unique structure likely arising from exposure to environmental chemicals. Analysis by LC/MS and GC/MS showed higher concentrations of DNA base lesions in the liver DNA of the DR fish, suggesting that these base modifications contributed to this discrete DNA structure. A comparable analysis by LC/MS and GC/MS of base modifications provided similar results with the gill. The biomarkers described are highly promising for identifying contaminant-induced stresses in fish populations from polluted and reference sites and, in addition, for monitoring the progress of remedial actions

    Isolation and Characterization of Intestinal Stem Cells Based on Surface Marker Combinations and Colony-Formation Assay

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    Identification of intestinal stem cells (ISCs) has relied heavily on the use of transgenic reporters in mice, but this approach is limited by mosaic expression patterns and difficult to directly apply to human tissues. We sought to identify reliable surface markers of ISCs and establish a robust functional assay to characterize ISCs from mouse and human tissues

    Lessons learned and study results from HIVCore, an HIV implementation science initiative

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138261/1/jia21261.pd

    MrkH, a Novel c-di-GMP-Dependent Transcriptional Activator, Controls Klebsiella pneumoniae Biofilm Formation by Regulating Type 3 Fimbriae Expression

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    Klebsiella pneumoniae causes significant morbidity and mortality worldwide, particularly amongst hospitalized individuals. The principle mechanism for pathogenesis in hospital environments involves the formation of biofilms, primarily on implanted medical devices. In this study, we constructed a transposon mutant library in a clinical isolate, K. pneumoniae AJ218, to identify the genes and pathways implicated in biofilm formation. Three mutants severely defective in biofilm formation contained insertions within the mrkABCDF genes encoding the main structural subunit and assembly machinery for type 3 fimbriae. Two other mutants carried insertions within the yfiN and mrkJ genes, which encode GGDEF domain- and EAL domain-containing c-di-GMP turnover enzymes, respectively. The remaining two isolates contained insertions that inactivated the mrkH and mrkI genes, which encode for novel proteins with a c-di-GMP-binding PilZ domain and a LuxR-type transcriptional regulator, respectively. Biochemical and functional assays indicated that the effects of these factors on biofilm formation accompany concomitant changes in type 3 fimbriae expression. We mapped the transcriptional start site of mrkA, demonstrated that MrkH directly activates transcription of the mrkA promoter and showed that MrkH binds strongly to the mrkA regulatory region only in the presence of c-di-GMP. Furthermore, a point mutation in the putative c-di-GMP-binding domain of MrkH completely abolished its function as a transcriptional activator. In vivo analysis of the yfiN and mrkJ genes strongly indicated their c-di-GMP-specific function as diguanylate cyclase and phosphodiesterase, respectively. In addition, in vitro assays showed that purified MrkJ protein has strong c-di-GMP phosphodiesterase activity. These results demonstrate for the first time that c-di-GMP can function as an effector to stimulate the activity of a transcriptional activator, and explain how type 3 fimbriae expression is coordinated with other gene expression programs in K. pneumoniae to promote biofilm formation to implanted medical devices
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