217 research outputs found

    The digital media lab at Bainbridge College

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    This project describes the development of an audio and video production facility at Bainbridge College, a small community college in Bainbridge, Georgia. The Digital Media Lab provides faculty, staff, and students with the ability to create audio and video resources for classroom use, research, training, and outreach. The principal steps of this project were a literature review, a needs analysis, the equipment selection process, and implementation. The literature review included examples of how video is used in higher education, information about current trends in technology, and faculty development strategies. The needs analysis determined that the facility should support both analog and digital media and that a facility where users could work independently was most practical. A list of equipment, user guidelines, outlines of current workshops, and samples of quick reference materials used in the lab are also included in this report

    Elevated circulating amyloid concentrations in obesity and diabetes promote vascular dysfunction

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    Diabetes, obesity and Alzheimer’s disease (AD) are associated with vascular complications and impaired nitric oxide (NO) production. Furthermore, increased β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), APP and β-amyloid (Aβ) are linked with vascular disease development and raised BACE1 and Aβ accompany hyperglycemia and hyperlipidemia. However, the causal relationship between obesity and diabetes, raised Aβ and vascular dysfunction is unclear. We report that diet-induced obesity (DIO) in mice raised plasma and vascular Aβ42 that correlated with decreased NO bioavailability, endothelial dysfunction and raised blood pressure. Genetic or pharmacological reduction of BACE1 activity and Aβ42 prevented and reversed, respectively, these outcomes. In contrast, expression of human mutant APP in mice or Aβ42 infusion into control diet-fed mice to mimic obese levels impaired NO production, vascular relaxation and raised blood pressure. In humans, raised plasma Aβ42 correlated with diabetes and endothelial dysfunction. Mechanistically, higher Aβ42 reduced endothelial NO synthase (eNOS), cyclic GMP and protein kinase G (PKG) activity independently of diet whereas endothelin-1 was increased by diet and Aβ42. Lowering Aβ42 reversed the DIO deficit in the eNOS-cGMP-PKG pathway and decreased endothelin-1. Our findings suggest that BACE1 inhibitors may have therapeutic value in the treatment of vascular disease associated with diabetes

    Retention of perylene diimide optical properties in solid-state materials through tethering to nanodiamonds

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    The synthesis of nanodiamond-perylene diimide composites is reported. Suitably hydroxyl-functionalised perylene diimides (PDIs) are reacted with carboxylic acid functionalised nanodiamonds (NDs) through ester formation. The ND-PDI nanocomposite materials were characterised using a variety of different techniques confirming retention of the ND cores and interestingly the dye properties of the PDIs. In particular, fluorescence measurements suggest that PDIs tethered to NDs retain the characteristics of solution-phase PDIs rather than the optical properties associated with solid-state PDIs which are typically modified due to aggregation. Our relatively simple approach provides a mechanism for maintaining the solution-phase properties of PDIs in solid-state materials

    Strip‐Bark Morphology and Radial Growth Trends in Ancient Pinus sibirica Trees From Central Mongolia

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    Some of the oldest and most important trees used for dendroclimatic reconstructions develop strip‐bark morphology, in which only a portion of the stem contains living tissue. Yet the ecophysiological factors initiating strip bark and the potential effect of cambial dieback on annual ring widths and tree‐ring estimates of past climate remain poorly understood. Using a combination of field observations and tree‐ring data, we investigate the causes and timing of cambial dieback events in Pinus sibirica strip‐bark trees from central Mongolia and compare the radial growth rates and trends of strip‐bark and whole‐bark trees over the past 515 years. Results indicate that strip bark is more common on the southern aspect of trees, and dieback events were most prevalent in the 19th century, a cold and dry period. Further, strip‐bark and whole‐bark trees have differing centennial trends, with strip‐bark trees exhibiting notably large increases in ring widths at the beginning of the 20th century. We find a steeper positive trend in the strip‐bark chronology relative to the whole‐bark chronology when standardizing with age‐dependent splines. We hypothesize that localized warming on the southern side of stems due to solar irradiance results in physiological damage and dieback and leads to increasing tree‐ring increment along the living portion of strip‐bark trees. Because the impact of cambial dieback on ring widths likely varies depending on species and site, we suggest conducting a comparison of strip‐bark and whole‐bark ring widths before statistically treating ring‐width data for climate reconstructions

    The HAND-Q : Psychometrics of a New Patient-reported Outcome Measure for Clinical and Research Applications

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    Background: The perspective of the patient in measuring the outcome of their hand treatment is of key importance. We developed a hand-specific patient-reported outcome measure to provide a means to measure outcomes and experiences of care from the patient perspective, that is, HAND-Q. Methods: Data were collected from people with a broad range of hand conditions in hand clinics in six countries between April 2018 and January 2021. Rasch measurement theory analysis was used to perform item reduction and to examine reliability and validity of each HAND-Q scale. Results: A sample of 1277 patients was recruited. Participants ranged in age from 16 to 89 years, 54% were women, and a broad range of congenital and acquired hand conditions were represented. Rasch measurement theory analysis led to the refinement of 14 independently functioning scales that measure hand appearance, health-related quality of life, experience of care, and treatment outcome. Each scale evidenced reliability and validity. Examination of differential item functioning by age, gender, language, and type of hand condition (ie, nontraumatic versus traumatic) confirmed that a common scoring algorithm for each scale could be implemented. Conclusions: The HAND-Q was developed following robust psychometric methods to provide a comprehensive modular independently functioning set of scales. HAND-Q scales can be used to assess and compare evidence-based outcomes in patients with any type of hand condition.Peer reviewe

    A mutation in the mitochondrial fission gene Dnm1l leads to cardiomyopathy

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    Mutations in a number of genes have been linked to inherited dilated cardiomyopathy (DCM). However, such mutations account for only a small proportion of the clinical cases emphasising the need for alternative discovery approaches to uncovering novel pathogenic mutations in hitherto unidentified pathways. Accordingly, as part of a large-scale N-ethyl-N-nitrosourea mutagenesis screen, we identified a mouse mutant, Python, which develops DCM. We demonstrate that the Python phenotype is attributable to a dominant fully penetrant mutation in the dynamin-1-like (Dnm1l) gene, which has been shown to be critical for mitochondrial fission. The C452F mutation is in a highly conserved region of the M domain of Dnm1l that alters protein interactions in a yeast two-hybrid system, suggesting that the mutation might alter intramolecular interactions within the Dnm1l monomer. Heterozygous Python fibroblasts exhibit abnormal mitochondria and peroxisomes. Homozygosity for the mutation results in the death of embryos midway though gestation. Heterozygous Python hearts show reduced levels of mitochondria enzyme complexes and suffer from cardiac ATP depletion. The resulting energy deficiency may contribute to cardiomyopathy. This is the first demonstration that a defect in a gene involved in mitochondrial remodelling can result in cardiomyopathy, showing that the function of this gene is needed for the maintenance of normal cellular function in a relatively tissue-specific manner. This disease model attests to the importance of mitochondrial remodelling in the heart; similar defects might underlie human heart muscle disease

    An affordable, quality-assured community-based system for high-resolution entomological surveillance of vector mosquitoes that reflects human malaria infection risk patterns.

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    ABSTRACT: BACKGROUND: More sensitive and scalable entomological surveillance tools are required to monitor low levels of transmission that are increasingly common across the tropics, particularly where vector control has been successful. A large-scale larviciding programme in urban Dar es Salaam, Tanzania is supported by a community-based (CB) system for trapping adult mosquito densities to monitor programme performance. Methodology An intensive and extensive CB system for routine, longitudinal, programmatic surveillance of malaria vectors and other mosquitoes using the Ifakara Tent Trap (ITT-C) was developed in Urban Dar es Salaam, Tanzania, and validated by comparison with quality assurance (QA) surveys using either ITT-C or human landing catches (HLC), as well as a cross-sectional survey of malaria parasite prevalence in the same housing compounds. RESULTS: Community-based ITT-C had much lower sensitivity per person-night of sampling than HLC (Relative Rate (RR) [95% Confidence Interval (CI)] = 0.079 [0.051, 0.121], P < 0.001 for Anopheles gambiae s.l. and 0.153 [0.137, 0.171], P < 0.001 for Culicines) but only moderately differed from QA surveys with the same trap (0.536 [0.406,0.617], P = 0.001 and 0.747 [0.677,0.824], P < 0.001, for An. gambiae or Culex respectively). Despite the poor sensitivity of the ITT per night of sampling, when CB-ITT was compared with QA-HLC, it proved at least comparably sensitive in absolute terms (171 versus 169 primary vectors caught) and cost-effective (153USversus187US versus 187US per An. gambiae caught) because it allowed more spatially extensive and temporally intensive sampling (4284 versus 335 trap nights distributed over 615 versus 240 locations with a mean number of samples per year of 143 versus 141). Despite the very low vectors densities (Annual estimate of about 170 An gambiae s.l bites per person per year), CB-ITT was the only entomological predictor of parasite infection risk (Odds Ratio [95% CI] = 4.43[3.027,7. 454] per An. gambiae or Anopheles funestus caught per night, P =0.0373). Discussion and conclusion CB trapping approaches could be improved with more sensitive traps, but already offer a practical, safe and affordable system for routine programmatic mosquito surveillance and clusters could be distributed across entire countries by adapting the sample submission and quality assurance procedures accordingly

    HIV-1 Vpu Protein Mediates the Transport of Potassium in Saccharomyces cerevisiae

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    Human immunodeficiency virus type 1 (HIV-1) Vpu is an integral membrane protein that belongs to the viroporin family. Viroporins interact with cell membranes, triggering membrane permeabilization and promoting release of viral particles. In vitro electrophysiological methods have revealed changes in membrane ion currents when Vpu is present; however, in vivo the molecular mechanism of Vpu at the plasma membrane is still uncertain. We used the yeast Saccharomyces cerevisiae as a genetic model system to analyze how Vpu ion channel impacts cellular homeostasis. Inducible expression of Vpu impaired cell growth, suggesting that this viral protein is toxic to yeast cultures. This toxicity decreased with extracellular acidic pH. Also, Vpu toxicity diminished as the extracellular K(+) concentration was increased. However, expression of the Vpu protein suppresses the growth defect of K(+) uptake-deficient yeast (Δtrk1,2). The phenotype rescue of these highly hyperpolarized cells was almost total when they were grown in medium supplemented with high concentrations of KCl (100 mM) at pH 7.0 but was significantly reduced when the extracellular K(+) concentration or pH was decreased. These results indicate that Vpu has the ability to modify K(+) transport in both yeast strains. Here, we show also that Vpu confers tolerance to the aminoglycoside antibiotic hygromycin B in Δtrk1,2 yeast. Our results suggest that Vpu interferes with cell growth of wild-type yeast but improves proliferation of the hyperpolarized trk1,2 mutant by inducing plasma membrane depolarization. Furthermore, evaluation of the ion channel activity of the Vpu protein in Δtrk1,2 yeast could aid in the development of a high-throughput screening assay for molecules that target the retroviral protein.This study was supported by Grants PI PI05/00013 and PI08/0912 from Fondo de Investigación Sanitaria. L.H. and N.M. were holders of Predoctoral Fellowships from Instituto de Salud Carlos III.S
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