313 research outputs found

    Team-based Classroom Pedagogy Reframed: The Student Perspective

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    Postsecondary learning environments often utilize team-based pedagogical practices to challenge and support student learning outcomes. This manuscript presents the findings of a qualitative research study that analyzed the viewpoints and perceptions of group or team-based projects among undergraduate business students. Results identified five pro-team thematic perspectives of team learners’ views including better deliverables, increased ideas, improved learning experiences, reduced workload, and collective security. Responses from students who preferred to work autonomously resulted in three themes centered on self-sufficiency, social loafing, and schedule challenges. Two situational student responses were identified regarding how and why faculty should utilize group and team projects in consideration of individual efficiency and assignment objectives and outcomes conflicts. This study concludes with research-based recommendations for teaching, learning, and further research

    Contacts between the endoplasmic reticulum and other membranes in neurons

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    The cytoplasm of eukaryotic cells is compartmentalized by intracellular membranes that define subcellular organelles. One of these organelles, the endoplasmic reticulum, forms a continuous network of tubules and cisternae that extends throughout all cell compartments, including neuronal dendrites and axons. This network communicates with most other organelles by vesicular transport, and also by contacts that do not lead to fusion but allow cross-talk between adjacent bilayers. Though these membrane contacts have previously been observed in neurons, their distribution and abundance has not been systematically analyzed. Here, we have carried out such analysis. Our studies reveal new aspects of the internal structure of neurons and provide a critical complement to information about interorganelle communication emerging from functional and biochemical studies

    Insulin-like growth factor binding protein-3 has dual effects on gastrointestinal stromal tumor cell viability and sensitivity to the anti-tumor effects of imatinib mesylate in vitro

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    <p>Abstract</p> <p>Background</p> <p>Imatinib mesylate has significantly improved survival and quality of life of patients with gastrointestinal stromal tumors (GISTs). However, the molecular mechanism through which imatinib exerts its anti-tumor effects is not clear. Previously, we found up-regulation of insulin-like growth factor binding protein-3 (IGFBP3) expression in imatinib-responsive GIST cells and tumor samples. Because IGFBP3 regulates cell proliferation and survival and mediates the anti-tumor effects of a number of anti-cancer agents through both IGF-dependent and IGF-independent mechanisms, we hypothesized that IGFBP3 mediates GIST cell response to imatinib. To test this hypothesis, we manipulated IGFBP3 levels in two imatinib-responsive GIST cell lines and observed cell viability after drug treatment.</p> <p>Results</p> <p>In the GIST882 cell line, imatinib treatment induced endogenous IGFBP3 expression, and IGFBP3 down-modulation by neutralization or RNA interference resulted in partial resistance to imatinib. In contrast, IGFBP3 overexpression in GIST-T1, which had no detectable endogenous IGFBP3 expression after imatinib, had no effect on imatinib-induced loss of viability. Furthermore, both the loss of IGFBP3 in GIST882 cells and the overexpression of IGFBP3 in GIST-T1 cells was cytotoxic, demonstrating that IGFBP3 has opposing effects on GIST cell viability.</p> <p>Conclusion</p> <p>This data demonstrates that IGFBP3 has dual, opposing roles in modulating GIST cell viability and response to imatinib <it>in vitro</it>. These preliminary findings suggest that there may be some clinical benefits to IGFBP3 therapy in GIST patients, but further studies are needed to better characterize the functions of IGFBP3 in GIST.</p

    Predictors and pathways of language and motor development in four prospective cohorts of young children in Ghana, Malawi, and Burkina Faso

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    BackgroundPrevious reviews have identified 44 risk factors for poor early child development (ECD) in low- and middle-income countries. Further understanding of their relative influence and pathways is needed to inform the design of interventions targeting ECD.MethodsWe conducted path analyses of factors associated with 18-month language and motor development in four prospective cohorts of children who participated in trials conducted as part of the International Lipid-Based Nutrient Supplements (iLiNS) Project in Ghana (n&nbsp;=&nbsp;1,023), Malawi (n&nbsp;=&nbsp;675 and 1,385), and Burkina Faso (n&nbsp;=&nbsp;1,122). In two cohorts, women were enrolled during pregnancy. In two cohorts, infants were enrolled at 6 or 9&nbsp;months. In multiple linear regression and structural equation&nbsp;models (SEM), we examined 22 out of 44 factors identified in previous reviews, plus 12 additional factors expected to be associated with ECD.ResultsOut of 42 indicators of the 34 factors examined, 6 were associated with 18-month language and/or motor development in 3 or 4 cohorts: child linear and ponderal growth, variety of play materials, activities with caregivers, dietary diversity, and child hemoglobin/iron status. Factors that were not associated with child development were indicators of maternal Hb/iron status, maternal illness and inflammation during pregnancy, maternal perceived stress and depression, exclusive breastfeeding during 6&nbsp;months postpartum, and child diarrhea, fever, malaria, and acute respiratory infections. Associations between socioeconomic status and language development were consistently mediated to a greater extent by caregiving practices than by maternal or child biomedical conditions, while this pattern for motor development was not consistent across cohorts.ConclusionsKey elements of interventions to ensure quality ECD are likely to be promotion of caregiver activities with children, a variety of play materials, and a diverse diet, and prevention of faltering in linear and ponderal growth and improvement in child hemoglobin/iron status

    Pathogenic nontuberculous mycobacteria resist and inactivate cathelicidin: implication of a novel role for polar mycobacterial lipids

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    Includes bibliographic references.Nontuberculous mycobacteria (NTM) are a large group of environmental organisms with worldwide distribution, but only a relatively few are known to be pathogenic. Chronic, debilitating lung disease is the most common manifestation of NTM infection, which is often refractory to treatment. The incidence and prevalence of NTM lung disease are increasing in the United States and in many parts of the world. Hence, a more complete understanding of NTM pathogenesis will provide the foundation to develop innovative approaches to treat this recalcitrant disease. Herein, we domonstrate that several species of NTM show broad resistance to the antimicrobial peptide, cathelicidin (LL-37). Resistance to LL-37 was not significantly different between M. avium that contain serovar-specific glycopeptidolipid (GPL, M. aviumˢˢᴳᴾᴸ) and M.avium that do not (M. aviumᐞˢˢᴳᴾᴸ). Similarly, M. Abscessus containing non-specific GPL (M. abscessusⁿˢᴳᴾᴸ⁽⁺⁾) or lacking nsGPL (M. abscessusⁿˢᴳᴾᴸ⁽⁻⁾) remained equally resistant to LL-37. These findings would support the notion that GPL are not the components responsible for NTM resistance to LL-37. Unexpectedly, the growth of M. abscessusⁿˢᴳᴾᴸ⁽⁻⁾ increased with LL-37 or scrambled LL-37 peptide in a dose-dependent fashion. We also discovered that LL-37 exposed to NTM had reduced antimicrobial activity, and initial work indicates that this is likely due to inactivation of LL-37 by lipid component(s) of the NTM cell envelope. We conclude that pathogenic NTM resist and inactivate LL-37. The mechanism by which NTM circumvent the antimicrobial activity of LL-37 remains to be determined

    Convergence of Agriculture and Energy: II. Producing Cellulosic Biomass for Biofuels

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    Global energy demand is increasing as known global petroleum supplies are decreas¬ing. Calls to supplement or replace the current fossil-based energy system with new, envi¬ronmentally and economically sustainable strategies continue to increase, especially in light of more expensive traditional energy sources. Various governmental agencies and working groups have set aggressive targets and timelines for decreasing fossil fuel consumption by substituting bio-based energy (Bush 2007; Foust et al. 2007; Perlack et al. 2005; Smith et al. 2004). The alignment and continuity of these goals is illustrated in Figure 1. Current biofuel production in the United States relies primarily on corn grain conver¬sion to ethanol, but future systems are expected to depend more intensively on plant biomass than on grain as a feedstock for production of ethanol and other biofuels. In addition, current cropping systems generally are designed to optimize grain production and are not designed to harvest all the aboveground portion of the plant for cellulose-containing biomass. Significant, immediate national investments are needed, along with changes in policy, to address chal¬lenges limiting the sustainable production and efficient use of cellulosic biomass as a fuel feedstock to meet anticipated U.S. demand. The Bush Administration outlined a portfolio of recommended technologies, pro¬cesses, and practices for bio-based energy production that targets improved rates of feedstock conversion and greater efficiency in energy use. The plan also states that a significant portion of the nation’s 2017 energy supply, especially transportation fuel, will come from conversion of biomass feedstock to liquid fuels. Considering just the biomass-derived fuels contribution, roughly 250 million tons or more of grain and cellulosic biomass per year will be needed to reach the 10-year goal, and 650 to 700 million tons per year of biomass to reach the 2025 goal (Figure 1)

    Bicarbonate-responsive “soluble” adenylyl cyclase defines a nuclear cAMP microdomain

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    Bicarbonate-responsive “soluble” adenylyl cyclase resides, in part, inside the mammalian cell nucleus where it stimulates the activity of nuclear protein kinase A to phosphorylate the cAMP response element binding protein (CREB). The existence of this complete and functional, nuclear-localized cAMP pathway establishes that cAMP signals in intracellular microdomains and identifies an alternate pathway leading to CREB activation

    The “Soluble” Adenylyl Cyclase in Sperm Mediates Multiple Signaling Events Required for Fertilization

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    SummaryMammalian fertilization is dependent upon a series of bicarbonate-induced, cAMP-dependent processes sperm undergo as they “capacitate,” i.e., acquire the ability to fertilize eggs. Male mice lacking the bicarbonate- and calcium-responsive soluble adenylyl cyclase (sAC), the predominant source of cAMP in male germ cells, are infertile, as the sperm are immotile. Membrane-permeable cAMP analogs are reported to rescue the motility defect, but we now show that these “rescued” null sperm were not hyperactive, displayed flagellar angulation, and remained unable to fertilize eggs in vitro. These deficits uncover a requirement for sAC during spermatogenesis and/or epididymal maturation and reveal limitations inherent in studying sAC function using knockout mice. To circumvent this restriction, we identified a specific sAC inhibitor that allowed temporal control over sAC activity. This inhibitor revealed that capacitation is defined by separable events: induction of protein tyrosine phosphorylation and motility are sAC dependent while acrosomal exocytosis is not dependent on sAC
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