Collaborative Course Design in Scientific Writing: Experimentation and Productive Failure

English 3820: Scientific Writing, a writing-intensive (WI) course offered by the Department of English at East Carolina University (ECU), serves primarily science majors. According to the course catalog, it provides students with “practice in assimilation and written presentation of scientific information.� The course asks students to consider the situated nature of scientific writing and also to produce scientific writing for various audiences. Throughout the course, students examine theories, methodologies, and ideologies that undergird scientific writing with an eye to perfecting both critique and imitation of scientific styles

VIP Enhances Phagocytosis of Fibrillar Beta-Amyloid by Microglia and Attenuates Amyloid Deposition in the Brain of APP/PS1 Mice

Vasoactive intestinal peptide (VIP) is a multifunctional neuropeptide with demonstrated immunosuppressive and neuroprotective activities. It has been shown to inhibit Amyloid beta (Aβ)-induced neurodegeneration by indirectly suppressing the production and release of a variety of inflammatory and neurotoxic factors by activated microglia. We demonstrated that VIP markedly increased microglial phagocytosis of fibrillar Aβ42 and that this enhanced phagocytotic activity depended on activation of the Protein kinase C (PKC) signaling pathway. In addition, VIP suppressed the release of tumor necrosis factor alpha (TNF-α) and nitric oxide(NO) from microglia activated by combined treatment with fibrillar Aβ42 and low dose interferon-γ (IFN-γ). We utilized an adenovirus-mediated gene delivery method to overexpress VIP constitutively in the hippocampus of APPswPS1 transgenic mice. The Aβ load was significantly reduced in the hippocampus of this animal model of Alzheimer's disease, possibly due to the accumulation and activation of cd11b-immunoactive microglial cells. The modulation of microglial activation, phagocytosis, and secretion by VIP is a promising therapeutic option for the treatment of Alzheimer's disease(AD)

Chronic Apocynin Treatment Attenuates Beta Amyloid Plaque Size and Microglial Number in hAPP(751)SL Mice

Background: NADPH oxidase is implicated in neurotoxic microglial activation and the progressive nature of Alzheimer’s Disease (AD). Here, we test the ability of two NADPH oxidase inhibitors, apocynin and dextromethorphan (DM), to reduce learning deficits and neuropathology in transgenic mice overexpressing human amyloid precursor protein with the Swedish and London mutations (hAPP(751)SL). Methods: Four month old hAPP(751)SL mice were treated daily with saline, 15 mg/kg DM, 7.5 mg/kg DM, or 10 mg/kg apocynin by gavage for four months. Results: Only hAPP(751)SL mice treated with apocynin showed reduced plaque size and a reduction in the number of cortical microglia, when compared to the saline treated group. Analysis of whole brain homogenates from all treatments tested (saline, DM, and apocynin) demonstrated low levels of TNFa, protein nitration, lipid peroxidation, and NADPH oxidase activation, indicating a low level of neuroinflammation and oxidative stress in hAPP(751)SL mice at 8 months of age that was not significantly affected by any drug treatment. Despite in vitro analyses demonstrating that apocynin and DM ameliorate Ab-induced extracellular superoxide production and neurotoxicity, both DM and apocynin failed to significantly affect learning and memory tasks or synaptic density in hAPP(751)SL mice. To discern how apocynin was affecting plaque levels (plaque load) and microglial number in vivo, in vitro analysis of microglia was performed, revealing no apocynin effects on beta-amyloid (Ab) phagocytosis, microglial proliferation, or microglial survival. Conclusions: Together, this study suggests that while hAPP(751)SL mice show increases in microglial number and plaque load, they fail to exhibit elevated markers of neuroinflammation consistent with AD at 8 months of age, which may be a limitation of this animal model. Despite absence of clear neuroinflammation, apocynin was still able to reduce both plaque size and microglial number, suggesting that apocynin may have additional therapeutic effects independent of anti-inflammatory characteristics

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science

It is well documented that the majority of adults, children and families in need of evidence-based behavioral health interventionsi do not receive them [1, 2] and that few robust empirically supported methods for implementing evidence-based practices (EBPs) exist. The Society for Implementation Research Collaboration (SIRC) represents a burgeoning effort to advance the innovation and rigor of implementation research and is uniquely focused on bringing together researchers and stakeholders committed to evaluating the implementation of complex evidence-based behavioral health interventions. Through its diverse activities and membership, SIRC aims to foster the promise of implementation research to better serve the behavioral health needs of the population by identifying rigorous, relevant, and efficient strategies that successfully transfer scientific evidence to clinical knowledge for use in real world settings [3]. SIRC began as a National Institute of Mental Health (NIMH)-funded conference series in 2010 (previously titled the “Seattle Implementation Research Conference”; $150,000 USD for 3 conferences in 2011, 2013, and 2015) with the recognition that there were multiple researchers and stakeholdersi working in parallel on innovative implementation science projects in behavioral health, but that formal channels for communicating and collaborating with one another were relatively unavailable. There was a significant need for a forum within which implementation researchers and stakeholders could learn from one another, refine approaches to science and practice, and develop an implementation research agenda using common measures, methods, and research principles to improve both the frequency and quality with which behavioral health treatment implementation is evaluated. SIRC’s membership growth is a testament to this identified need with more than 1000 members from 2011 to the present.ii SIRC’s primary objectives are to: (1) foster communication and collaboration across diverse groups, including implementation researchers, intermediariesi, as well as community stakeholders (SIRC uses the term “EBP champions” for these groups) – and to do so across multiple career levels (e.g., students, early career faculty, established investigators); and (2) enhance and disseminate rigorous measures and methodologies for implementing EBPs and evaluating EBP implementation efforts. These objectives are well aligned with Glasgow and colleagues’ [4] five core tenets deemed critical for advancing implementation science: collaboration, efficiency and speed, rigor and relevance, improved capacity, and cumulative knowledge. SIRC advances these objectives and tenets through in-person conferences, which bring together multidisciplinary implementation researchers and those implementing evidence-based behavioral health interventions in the community to share their work and create professional connections and collaborations

NFATc1 in cardiac valve development and EPDC invasion

Congenital malformations are the most common cause of death in infancy in the United States. Of these birth defects, most are malformations of cardiac valvuloseptal structures and a significant number are coronary vessel malformations. Therefore, identifying molecular mechanisms that regulate cardiac valve and coronary artery development is of great clinical importance. Cardiac valve morphogenesis begins with growth of endocardial cushions in the atrioventricular canal and outflow tract regions of the looping heart. After growth, endocardial cushions are remodeled into thin leaflets, characteristic of mature heart valves. Nuclear Factor of Activated T-cells cytoplasmic 1 (NFATc1) is a transcription factor necessary for heart valve development. The studies detailed here demonstrate that Vascular Endothelial Growth Factor A (VEGF)/ NFATc1 pathway function promotes endocardial cushion growth, while Receptor Activator of NFκB (RANKL)/ NFATc1 pathway function is associated with valve remodeling. These studies further demonstrate that NFATc1 serves as a nodal point in the transition from endocardial cushion growth to valve remodeling via ERK1/2 or JNK1/2 copathway activation. In the course of these studies NFATc1 expression by PE, epicardium, and EPDCs was discovered. During heart looping, PE cells migrate onto the myocardium and proliferate to form the epicardium. A subset of epicardial cells undergo epithelial-tomesenchymal transformation (EMT) and invade the subepicardium and myocardium as epicardium-derived cells (EPDCs). EPDCs differentiate into coronary endothelial and smooth muscle cells, as well as adventitial fibroblasts that produce the fibrous matrix. Studies detailed in this dissertation demonstrate that conditional loss of NFATc1 expression in EPDCs in mice causes embryonic death by E18.5 with reduced coronary vessel and fibrous matrix penetration into myocardium. These studies further demonstrate that RANKL/NFATc1 pathway components are expressed in EPDCs and loss of NFATc1 in EPDCs causes loss of CtsK expression in the myocardial interstitium in vivo. Likewise, RANKL treatment induces CtsK expression in PE-derived cell cultures via a calcineurin-dependent mechanism. In chicken embryo hearts, RANKL treatment increases the distance of EPDC invasion into myocardium, and this response is calcineurin-dependent. Together, these data demonstrate a critical role for the RANKL/ NFATc1 signaling pathway in promoting invasion of EPDCs into myocardium by induction of extracellular matrix-degrading enzyme gene expression

Collaborative Course Design in Scientific Writing: Experimentation and Productive Failure

"English 3820: Scientific Writing , a writing-intensive (WI) course offered by the Department of English at East Carolina University (ECU) , serves primarily science majors. According to the course catalog , it provides students with ""practice in assimilation and written presentation of scientific information."" The course asks students to consider the situated nature of scientific writing and also to produce scientific writing for various audiences. Throughout the course , students examine theories , methodologies , and ideologies that undergird scientific writing with an eye to perfecting both critique and imitation of scientific styles.

The Early Effects of the Coronavirus Disease-19 Pandemic on Pediatric Resident Education: A National Assessment

PurposeResidency programs must ensure resident competence for independent practice. The coronavirus disease-19 (COVID-19) pandemic disrupted health care delivery, impacting pediatric residencies. This study examines the impact on pediatric resident education.MethodsThe authors conducted a mixed methods national survey of pediatric residency program directors (PDs) from May 2020 to July 2020. Data analysis included descriptive statistics, chi-square, and Wilcoxon rank sum tests. Multivariable modeling identified factors associated with resident preparation for more senior roles. Thematic analysis was performed on open-ended questions about PD COVID-19 pandemic recommendations to peers, Accreditation Council for Graduate Medical Education and American Board of Pediatrics.ResultsResponse rate was 55% (110/199). PDs reported the COVID-19 pandemic negatively affected inpatient (n = 86, 78.2%), and outpatient education (n = 104, 94.5%), procedural competence (n = 64; 58.2%), and resident preparation for more senior roles (n = 50, 45.5%). In bivariate analyses, increasingly negative impacts on inpatient and outpatient education were associated with an increasingly negative impact on resident preparation for more senior roles (P = .03, P = .008), these relationships held true in multivariable analysis. Qualitative analysis identified 4 themes from PD recommendations: 1) Clear communication from governing bodies and other leaders; 2) Flexibility within programs and from governing bodies; 3) Clinical exposure is key for competency development; 4) Online platforms are important for education, communication, and support.ConclusionsThe COVID-19 pandemic negatively impacted inpatient and outpatient education. When these were more negatively impacted, resident preparation for more senior roles was worse, highlighting the importance of competency based medical education to tailor experiences ensuring each resident is competent for independent practice