327 research outputs found

    Genome sequence of a gammaherpesvirus from a common bottlenose dolphin (Tursiops truncatus)

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    A herpesvirus genome was sequenced directly from a biopsy specimen of a rectal lesion from a female common bottlenose dolphin. This genome sequence comprises a unique region (161,235 bp) flanked by multiple copies of a terminal repeat (4,431 bp) and contains 72 putative genes. The virus was named common bottlenose dolphin gammaherpesvirus 1

    Effects of cardiotrophin on adipocytes

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    Cardiotrophin (CT-1) is a naturally occurring protein member of the interleukin (IL)-6 cytokine family and signals through the gp130/leukemia inhibitory factor receptor (LIFR) heterodimer. The formation of gp130/ LIFR complex triggers the auto/trans-phosphorylation of associated Janus kinases, leading to the activation of Janus kinase/STAT and MAPK (ERK1 and -2) signaling pathways. Since adipocytes express both gp130 and LIFR proteins and are responsive to other IL-6 family cytokines, we examined the effects of CT-1 on 3T3-L1 adipocytes. Our studies have shown that CT-1 administration results in a dose- and time-dependent activation and nuclear translocation of STAT1, -3, -5A, and -5B as well as ERK1 and -2. We also confirmed the ability of CT-1 to induce signaling in fat cells in vivo. Our studies revealed that neither CT-1 nor ciliary neurotrophic factor treatment affected adipocyte differentiation. However, acute CT-1 treatment caused an increase in SOCS-3 mRNA in adipocytes and a transient decrease in peroxisome proliferator-activated receptor γ (PPARγ) mRNA that was regulated by the binding of STAT1 to the PPARγ2 promoter. The effects of CT-1 on SOCS-3 and PPARγ mRNA were independent of MAPK activation. Chronic administration of CT-1 to 3T3-L1 adipocytes resulted in a decrease of both fatty acid synthase and insulin receptor substrate-1 protein expression yet did not effect the expression of a variety of other adipocyte proteins. Moreover, chronic CT-1 treatment resulted in the development of insulin resistance as judged by a decrease in insulin-stimulated glucose uptake. In summary, CT-1 is a potent regulator of signaling in adipocytes in vitro and in vivo, and our current efforts are focused on determining the role of this cardioprotective cytokine on adipocyte physiology

    Impact Of Redesigning A Large-Lecture Introductory Earth Science Course To Increase Student Achievement And Streamline Faculty Workload

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    A Geological Perspective is a general education survey course for non-science majors at a large southwestern research extensive university.  The class has traditionally served 600 students per semester in four 150-student lectures taught by faculty, and accompanied by optional weekly study groups run by graduate teaching assistants.  We radically redesigned the course to 1) improve student learning and, simultaneously, 2) reduce faculty effort.   Previously optional study groups were replaced by weekly mandatory break-out sessions, run largely by undergraduate peer mentors.  Twice weekly, lectures are brief with a large portion of class time allocated to active learning in small groups.  Completing quizzes on-line reduced grading and allowed students more flexibility.  Evaluation of the redesign (mixed methods, quasi-experimental, two-group, pre-test-post-test, multiple-measures study design) revealed no significant improvements in learner outcomes insofar as the instruments could measure. However, qualitative results reveal that overall students greatly valued their learning experience under the redesign.  In addition, the redesign reduced the departmental cost of the class offering per student by more than half.

    Modeling instrumental field-dependent aberrations in the NIRC2 instrument on the Keck II telescope

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    We present a model of field-dependent aberrations arising in the NIRC2 instrument on the W. M. Keck II telescope. We use high signal-to-noise phase diversity data employing a source in the Nasmyth focal plane to construct a model of the optical path difference as a function of field position and wavelength. With a differential wavefront error of up to 190 nm, this effect is one of the main sources of astrometric and photometric measurement uncertainties. Our tests of temporal stability show sufficient reliability for our measurements over a 20-month period at the field extrema. Additionally, while chromaticity exists, applying a correction for field-dependent aberrations provides overall improvement compared to the existing aberrations present across the field of view

    Variation in thromboembolic complications among patients undergoing commonly performed cancer operations

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    ObjectiveThere is widespread evidence that cancer confers an increased risk of deep venous thrombosis (DVT). This risk is thought to vary among different cancer types. The purpose of this study is to better define the incidence of thrombotic complications among patients undergoing surgical treatment for a spectrum of prevalent cancer diagnoses in contemporary practice.MethodsAll patients undergoing one of 11 cancer surgical operations (breast resection, hysterectomy, prostatectomy, colectomy, gastrectomy, lung resection, hepatectomy, pancreatectomy, cystectomy, esophagectomy, and nephrectomy) were identified by Current Procedural Terminology and International Classification of Diseases, Ninth Revision codes using the American College of Surgeons National Surgical Quality Improvement Program database (2007-2009). The study endpoints were DVT, pulmonary embolism (PE), and overall postoperative venous thromboembolic events (VTE) within 1 month of the index procedure. Multivariate logistic regression was utilized to calculate adjusted odds ratios for each endpoint.ResultsOver the study interval, 43,808 of the selected cancer operations were performed. The incidence of DVT, PE, and total VTE within 1 month following surgery varied widely across a spectrum of cancer diagnoses, ranging from 0.19%, 0.12%, and 0.28% for breast resection to 6.1%, 2.4%, and 7.3%, respectively, for esophagectomy. Compared with breast cancer, the incidence of VTE ranged from a 1.31-fold increase in VTE associated with gastrectomy (95% confidence interval, 0.73-2.37; P = .4) to a 2.68-fold increase associated with hysterectomy (95% confidence interval, 1.43-5.01; P = .002). Multivariate logistic regression revealed that inpatient status, steroid use, advanced age (≥60 years), morbid obesity (body mass index ≥35), blood transfusion, reintubation, cardiac arrest, postoperative infectious complications, and prolonged hospitalization were independently associated with increased risk of VTE.ConclusionsThe incidence of VTE and thromboembolic complications associated with cancer surgery varies substantially. These findings suggest that both tumor type and resection magnitude may impact VTE risk. Accordingly, such data support diagnosis and procedural-specific guidelines for perioperative VTE prophylaxis and can be used to anticipate the risk of potentially preventable morbidity

    Qualitative evaluation of barriers and facilitators to hepatocellular carcinoma care in North Carolina

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    Background Many patients with hepatocellular carcinoma (HCC) never receive cancer-directed therapy. In order to tailor interventions to increase access to appropriate therapy, we sought to understand the barriers and facilitators to HCC care. Methods Patients with recently diagnosed HCC were identified through the University of North Carolina (UNC) HCC clinic or local hospital cancer registrars (rapid case ascertainment, RCA). Two qualitative researchers conducted in-depth, semi-structured interviews. Interviews were audiotaped, transcribed, and coded. Results Nineteen interviews were conducted (10 UNC, 9 RCA). Key facilitators of care were: physician knowledge; effective communication regarding test results, plan of care, and prognosis; social support; and financial support. Barriers included: lack of transportation; cost of care; provider lack of knowledge about HCC; delays in scheduling; or poor communication with the medical team. Participants suggested better coordination of appointments and having a primary contact within the healthcare team. Limitations We primarily captured the perspectives of those HCC patients who, despite the challenges they describe, were ultimately able to receive HCC care. Conclusions This study identifies key facilitators and barriers to accessing care for HCC in North Carolina. Use of the RCA system to identify patients from a variety of settings, treated and untreated, enabled us to capture a broad range of perspectives. Reducing barriers through improving communication and care coordination, assisting with out-of-pocket costs, and engaging caregivers and other medical providers may improve access. This study should serve as the basis for tailored interventions aimed at improving access to appropriate, life-prolonging care for patients with HCC

    What are the impacts of within-field farmland management practices on the flux of greenhouse gases from arable cropland in temperate regions? A systematic map protocol

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    Background: Reducing greenhouse gas emissions is a vital step in limiting climate change and meeting the goals outlined in the COP 21 Paris Agreement of 2015. Studies have suggested that agriculture accounts for around 11% of total greenhouse gas emissions and the industry has a significant role in meeting international and national climate change reduction objectives. However, there is currently little consensus on the mechanisms that regulate the production and assimilation of greenhouse gases in arable land and the practical factors that affect the process. Practical advice for farmers is often overly general, and models based on the amount of nitrogen fertiliser applied, for example, are used despite a lack of knowledge of how local conditions affect the process, such as the importance of humus content and soil types. Here, we propose a systematic map of the evidence relating to the impact on greenhouse gas flux from the agricultural management of arable land in temperate regions. Methods: Using established methods for systematic mapping in environmental sciences we will search for, collate and catalogue research studies relating to the impacts of farming in temperate systems on greenhouse gas emissions. We will search 6 bibliographic databases using a tested search string, and will hand search a web-based search engine and a list of organisational web sites. Furthermore, evidence will be sought from key stakeholders. Search results will then be screened for relevance at title, abstract and full text levels according to a predefined set of eligibility criteria. Consistency checking will be employed to ensure the criteria are being applied accurately and consistently. Relevant studies will then be subjected to coding and meta-data extraction, which will be used to populate a systematic map database describing each relevant study's settings, methods and measured outcomes. The mapping process will help to identify knowledge gaps (subjects lacking in evidence warranting further primary research) and knowledge clusters (subjects with sufficient studies to allow a useful full systematic review), and will highlight best and suboptimal research methods

    CRISPR-delivery particles targeting nuclear receptor-interacting protein 1 (Nrip1) in adipose cells to enhance energy expenditure

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    RNA-guided, engineered nucleases derived from the prokaryotic adaptive immune system CRISPR-Cas represent a powerful platform for gene deletion and editing. When used as a therapeutic approach, direct delivery of Cas9 protein and single-guide RNA (sgRNA) could circumvent the safety issues associated with plasmid delivery and therefore represents an attractive tool for precision genome engineering. Gene deletion or editing in adipose tissue to enhance its energy expenditure, fatty acid oxidation, and secretion of bioactive factors through a browning process presents a potential therapeutic strategy to alleviate metabolic disease. Here, we developed CRISPR-delivery particles, denoted CriPs, composed of nano-size complexes of Cas9 protein and sgRNA that are coated with an amphipathic peptide called Endo-Porter that mediates entry into cells. Efficient CRISPR-Cas9-mediated gene deletion of ectopically expressed GFP by CriPs was achieved in multiple cell types, including a macrophage cell line, primary macrophages, and primary pre-adipocytes. Significant GFP loss was also observed in peritoneal exudate cells with minimum systemic toxicity in GFP-expressing mice following intraperitoneal injection of CriPs containing Gfp-targeting sgRNA. Furthermore, disruption of a nuclear co-repressor of catabolism, the Nrip1 gene, in white adipocytes by CriPs enhanced adipocyte browning with a marked increase of uncoupling protein 1 (UCP1) expression. Of note, the CriP-mediated Nrip1 deletion did not produce detectable off-target effects. We conclude that CriPs offer an effective Cas9 and sgRNA delivery system for ablating targeted gene products in cultured cells and in vivo, providing a potential therapeutic strategy for metabolic disease
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