523 research outputs found

    Core level spectroscopies locate hydrogen in the proton transfer pathway – identifying quasi-symmetrical hydrogen bonds in the solid state

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    Short, strong hydrogen bonds (SSHBs) have been a source of interest and considerable speculation over recent years, culminating with those where hydrogen resides around the midpoint between the donor and acceptor atoms, leading to quasi-covalent nature. We demonstrate that X-ray photoelectron spectroscopy (XPS) and near-edge X-ray absorption fine structure (NEXAFS) spectroscopy provide deep insight into the electronic structure of the short OHN hydrogen bond of 3,5-pyridinedicarboxylic acid, revealing for the first time distinctive spectroscopic identifiers for these quasi-symmetrical hydrogen bonds. An intermediate nitrogen (core level) chemical shift occurs for the almost centrally located hydrogen compared to protonated (ionic) and non-ionic analogues, and it reveals the absence of two-site disorder. This type of bonding is also evident through broadening of the nitrogen 1s photoemission and 1s → 1π* peaks in XPS and NEXAFS, respectively, arising from the femtosecond lifetimes of hydrogen in the potential wells slightly offset to either side of the centre. The line-shape of the core level excitations are thus related to the population occupancies, reflecting the temperature-dependent shape of the hydrogen potential energy well. Both XPS and NEXAFS provide a distinctive identifier for these quasi-symmetrical hydrogen bonds, paving the way for detailed studies into their prevalence and potentially unique physical and chemical properties

    Glucagon-like peptide-1 enhances cardiac L-type Ca2+ currents via activation of the cAMP-dependent protein kinase A pathway

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    <p>Abstract</p> <p>Background</p> <p>Glucagon-like peptide-1 (GLP-1) is a hormone predominately synthesized and secreted by intestinal L-cells. GLP-1 modulates multiple cellular functions and its receptor agonists are now used clinically for diabetic treatment. Interestingly, preclinical and clinical evidence suggests that GLP-1 agonists produce beneficial effects on dysfunctional hearts via acting on myocardial GLP-1 receptors. As the effects of GLP-1 on myocyte electrophysiology are largely unknown, this study was to assess if GLP-1 could affect the cardiac voltage-gated L-type Ca<sup>2+ </sup>current (I<sub>Ca</sub>).</p> <p>Methods</p> <p>The whole-cell patch clamp method was used to record I<sub>Ca </sub>and action potentials in enzymatically isolated cardiomyocytes from adult canine left ventricles.</p> <p>Results</p> <p>Extracellular perfusion of GLP-1 (7-36 amide) at 5 nM increased I<sub>Ca </sub>by 23 ± 8% (<it>p </it>< 0.05, n = 7). Simultaneous bath perfusion of 5 nM GLP-1 plus 100 nM Exendin (9-39), a GLP-1 receptor antagonist, was unable to block the GLP-1-induced increase in I<sub>Ca</sub>; however, the increase in I<sub>Ca </sub>was abolished if Exendin (9-39) was pre-applied 5 min prior to GLP-1 administration. Intracellular dialysis with a protein kinase A inhibitor also blocked the GLP-1-enhanced I<sub>Ca</sub>. In addition, GLP-1 at 5 nM prolonged the durations of the action potentials by 128 ± 36 ms (<it>p </it>< 0.01) and 199 ± 76 ms (<it>p </it>< 0.05) at 50% and 90% repolarization (n = 6), respectively.</p> <p>Conclusions</p> <p>Our data demonstrate that GLP-1 enhances I<sub>Ca </sub>in canine cardiomyocytes. The enhancement of I<sub>Ca </sub>is likely via the cAMP-dependent protein kinase A mechanism and may contribute, at least partially, to the prolongation of the action potential duration.</p

    A Subgroup Analysis of Legal Needs Among Older Adults in Rural Communities

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    A legal needs assessment of older adults in Maine was conducted by surveying key populations of older adults who are often hard to reach through traditional outreach and service provision methods. The focus of this assessment was on basic demographics, use of LSE services, legal issues, preferred methods for receiving legal information, and the utility of various legal service options. Surveys were distributed via area agencies on aging, and concluded that the ley legal issues included financial scams, home repair problems, obtaining or retaining government benefits, debt collection, and accessing medical services. Sixty-seven percent of individuals aged 70 or older reported having legal issues in the previous year. Providing resources to local area agencies on aging is a critical component to allowing for information about resources to be distributed

    Prestrain relaxation in non-covalently modified ethylene-vinyl acetate | PyChol | multiwall carbon nanotube nanocomposites

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    Effects of aging on chemical structure and molecular dynamic behaviour of strained thermally active ethylene-vinyl acetate | multiwall carbon nanotube (EVA|MWCNT) composites were investigated by spectroscopy and microscopy techniques. Aged composites showed spatial inhomogeneity due to system relaxation. Inhomogeneity is attributed to segregation of non-covalently linked cholestryl 1-pyrenecarboxylate, acting as MWCNT dispersant and polymer compatibilizer. Analysis of molecular interplay between filler and matrix upon in situ temperature variation showed a lack of synchronicity, which had been observed in fresh composites. Reduced synchronous interplay allowed quantification of degraded π-π interactions, promoting PyChol unlatching as a result of both sonication and strained-derived π-π degradation

    An Analysis of Current and Projected Rural Older Adult Legal Services Needs

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    Maine is now the oldest state in the nation, and is one of the most rural states. A legal needs assessment of older adults in Maine was conducted by analyzing the findings from recent research conducted in six other states and service data from Maine Legal Services for the Elderly over a one-year time period. The six states analyzed were Kentucky, Michigan, Nevada, North Dakota, Ohio, and Utah. There were a total of over 7,300 older adults that responded to the legal needs surveys. The assessment concluded that the high-level service needs included the following: health insurance, government benefits, estate planning, and personal finances and consumer issues. Other needs included help with housing, abuse, employment, and family matters. This assessment was a crucial project in establishing means to plan to distribute a legal needs survey in Maine

    NEXAFS and XPS of p-Aminobenzoic Acid Polymorphs: The Influence of Local Environment

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    Nitrogen K-edge XPS and NEXAFS of the two polymorphic forms of para- aminobenzoic acid (PABA) are significantly different reflecting variation in hydrogen bonding. Alteration in hydrogen bonding at the amino group leads to a shift to high energy for both the XPS N 1s core level and the 3π* NEXAFS resonance with β-PABA. Participation of the amine group in the aromatic system causes the 1π* resonance to be sensitive to the nature of the intermolecular bonding at the para-carboxylic acid group, and a shift to low energy for α- PABA is observed due to hydrogen-bonded carboxylic acid dimer formation. FEFF calculations also successfully reproduce both the energy and intensity variations observed for the σ* shape resonance associated with the C-N bond, with the majority of the decrease in energy observed for b-PABA arising from the longer C-N bond

    Immune Reconstitution Inflammatory Syndrome and the Influence of T Regulatory Cells: A Cohort Study in the Gambia

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    The factors associated with the development of immune reconstitution inflammatory syndrome in HIV patients commencing antiretroviral therapy have not been fully elucidated. Using a longitudinal study design, this study addressed whether alteration in the levels of T regulatory cells contributed to the development of IRIS in a West African cohort of HIV-1 and HIV-2 patients. Seventy-one HIV infected patients were prospectively recruited to the study and followed up for six months. The patients were categorized as IRIS or non-IRIS cases following published clinical guidelines. The levels of T regulatory cells were measured using flow cytometry at baseline and all follow-up visits. Baseline cytokine levels of IL-2, IL-6, IFN-(Gamma), TNF-(Alpha), MIP-1(Beta), IL-1, IL-12, IL-13, and IL-10 were measured in all patients

    CD4 intragenic SNPs associate with HIV-2 plasma viral load and CD4 count in a community-based study from Guinea-Bissau, West Africa.

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    OBJECTIVES: The human genetics of HIV-2 infection and disease progression is understudied. Therefore, we studied the effect of variation in 2 genes that encode products critical to HIV pathogenesis and disease progression: CD4 and CD209. DESIGN: This cross-sectional study consisted of 143 HIV-2, 30 HIV-1 + HIV-2 and 29 HIV-1-infected subjects and 194 uninfected controls recruited from rural Guinea-Bissau. METHODS: We genotyped 14 CD4 and 4 CD209 single nucleotide polymorphisms (SNPs) that were tested for association with HIV infection, HIV-2 plasma viral load (high vs. low), and CD4 T-cell count (high vs. low). RESULTS: The most significant association was between a CD4 haplotype rs11575097-rs10849523 and high viral load [odds ratio (OR): = 2.37, 95% confidence interval (CI): 1.35 to 4.19, P = 0.001, corrected for multiple testing], suggesting increased genetic susceptibility to HIV-2 disease progression for individuals carrying the high-risk haplotype. Significant associations were also observed at a CD4 SNP (rs2255301) with HIV-2 infection (OR: = 2.36, 95% CI: 1.19 to 4.65, P = 0.01) and any HIV infection (OR: = 2.50, 95% CI: 1.34 to 4.69, P = 0.004). CONCLUSIONS: Our results support a role of CD4 polymorphisms in HIV-2 infection, in agreement with recent data showing that CD4 gene variants increase risk to HIV-1 in Kenyan female sex workers. These findings indicate at least some commonality in HIV-1 and HIV-2 susceptibility
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