1,252 research outputs found

    The Role of MMP9 in Satellite Cell Activation After Increased Activity

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    The unique adaptive ability of skeletal muscle to meet functional demands is exemplified in its response to exercise. Though little is known about the molecular mechanisms that regulate this plasticity, the extracellular matrix (ECM) is believed to play a large role. The basal lamina is a specialized layer of ECM that lies in direct contact with the cell membrane of muscle fibers and facilitates environment-to-cell interactions. Matrix metalloproteinase-9 (MMP-9) is an enzyme in the basal lamina that regulates much of these adaptive processes. During exercise, the regenerative process of damaged tissue requires the activation of muscle-specific stem cells known as satellite cells. Satellite cell activity has been proposed to be activated by MMP-9; However, there are no studies that look at this interaction. Thus the overall goal of the present proposal is to 1) determine the effects of MMP-9 on muscle hypertrophy via satellite cell activation and 2) assess whether hypertrophy of the plantaris muscle observed after functional overload (FO) is due to the increased size of existing muscle fibers or the addition of new muscle fibers. FO of the plantaris muscle, a calf muscle responsible for ankle extension, was performed in WT and MMP-9 knockout (MMP-9 KO) mice (~4 mos of age) by removing the soleus and gastrocnemius muscles and randomly placed into the following groups: 1) 2-day FO (n=5/group) and 14-day FO (n=5/group). A 0-day time point for each group was added as a baseline control (n=5/group). Fluorescence immunohistochemistry was performed using anti-Pax7 and anti-laminin antibodies to label satellite cells and the basal lamina, respectively. There was a general increase in satellite cells after 14-days FO compared to 0- and 2-days in both the WT and MMP-9 KO mice. There also was no observable trend or pattern in fiber count between time points for both WT and MMP-9 KO mice. However as the sample size is based on n=1 for each group at each time point no inference to statistical significance can be made. At this juncture, more samples are being analyzed to determine these relationships

    Dolomite study for in situ CO2 capture for chemical looping reforming

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    The non-isothermal kinetic and thermal behaviour of a naturally formed dolomite in conditions that approach in situ CO2 capture in chemical looping reforming, were investigated. The performance of this dolomite was studied at micro-scale in 'dry' conditions, as well as at macro-scale in 'dry' and 'wet' conditions to investigate the effects of scale (3 mg, 2.5 g), partial pressures of CO2 (<15 kPa) and steam, and deactivation upon limited cycling. The carbonation and calcination kinetics were modelled using an improved iterative Coats-Redfern method. Increasing CO2 partial pressures on the 'dry' macro-scale exacerbated the experimental carbonation conversions in an inversely proportional trend when compared with those at micro-scale. The presence of steam had a positive effect on CO2 chemisorption. Steam had a negligible influence on the calcination activation energies. The activation energies of carbonation were increased for the experiments at the highest CO2 partial pressures under wet conditions

    Using the Community Readiness Model to Select Communities for a Community-Wide Obesity Prevention Intervention

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    To build on a growing interest in community-based obesity prevention programs, methods are needed for matching intervention strategies to local needs and assets. We used the Community Readiness Model (CRM), a structured interview guide and scoring system, to assess community readiness to act on childhood obesity prevention, furthering a replication study of a successful intervention

    An archaeology of borders: qualitative political theory as a tool in addressing moral distance

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    Interviews, field observations and other qualitative methods increasingly are being used to inform the construction of arguments in normative political theory. This article works to demonstrate the strong salience of some kinds of qualitative material for cosmopolitan arguments to extend distributive boundaries. The incorporation of interviews and related qualitative material can make the moral claims of excluded others more vivid and possibly more difficult to dismiss by advocates of strong priority to compatriots in distributions. Further, it may help to promote the kind of perspective taking that has been associated with actually motivating a willingness to aid by individuals. Illustrative findings are presented from field work conducted for a normative project on global citizenship, including interviews with unauthorized immigrants and the analysis of artifacts left behind on heavily used migrant trails

    Decarboxylative and dehydrative coupling of dienoic acids and pentadienyl alcohols to form 1,3,6,8-tetraenes

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    Dienoic acids and pentadienyl alcohols are coupled in a decarboxylative and dehydrative manner at ambient temperature using Pd(0) catalysis to generate 1,3,6,8-tetraenes. Contrary to related decarboxylative coupling reactions, an anion-stabilizing group is not required adjacent to the carboxyl group. Of mechanistic importance, it appears that both the diene of the acid and the diene of the alcohol are required for this reaction. To further understand this reaction, substitutions at every unique position of both cou- pling partners was examined and two potential mechanisms are presented

    Branch Mode Selection during Early Lung Development

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    Many organs of higher organisms, such as the vascular system, lung, kidney, pancreas, liver and glands, are heavily branched structures. The branching process during lung development has been studied in great detail and is remarkably stereotyped. The branched tree is generated by the sequential, non-random use of three geometrically simple modes of branching (domain branching, planar and orthogonal bifurcation). While many regulatory components and local interactions have been defined an integrated understanding of the regulatory network that controls the branching process is lacking. We have developed a deterministic, spatio-temporal differential-equation based model of the core signaling network that governs lung branching morphogenesis. The model focuses on the two key signaling factors that have been identified in experiments, fibroblast growth factor (FGF10) and sonic hedgehog (SHH) as well as the SHH receptor patched (Ptc). We show that the reported biochemical interactions give rise to a Schnakenberg-type Turing patterning mechanisms that allows us to reproduce experimental observations in wildtype and mutant mice. The kinetic parameters as well as the domain shape are based on experimental data where available. The developed model is robust to small absolute and large relative changes in the parameter values. At the same time there is a strong regulatory potential in that the switching between branching modes can be achieved by targeted changes in the parameter values. We note that the sequence of different branching events may also be the result of different growth speeds: fast growth triggers lateral branching while slow growth favours bifurcations in our model. We conclude that the FGF10-SHH-Ptc1 module is sufficient to generate pattern that correspond to the observed branching modesComment: Initially published at PLoS Comput Bio

    Structural Elucidation of Cisoid and Transoid Cyclization Pathways of a Sesquiterpene Synthase Using 2-Fluorofarnesyl Diphosphates

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    Sesquiterpene skeletal complexity in nature originates from the enzyme-catalyzed ionization of (trans,trans)-farnesyl diphosphate (FPP) (1a) and subsequent cyclization along either 2,3-transoid or 2,3-cisoid farnesyl cation pathways. Tobacco 5-epi-aristolochene synthase (TEAS), a transoid synthase, produces cisoid products as a component of its minor product spectrum. To investigate the cryptic cisoid cyclization pathway in TEAS, we employed (cis,trans)-FPP (1b) as an alternative substrate. Strikingly, TEAS was catalytically robust in the enzymatic conversion of (cis,trans)-FPP (1b) to exclusively (≥99.5%) cisoid products. Further, crystallographic characterization of wild-type TEAS and a catalytically promiscuous mutant (M4 TEAS) with 2-fluoro analogues of both all-trans FPP (1a) and (cis,trans)-FPP (1b) revealed binding modes consistent with preorganization of the farnesyl chain. These results provide a structural glimpse into both cisoid and transoid cyclization pathways efficiently templated by a single enzyme active site, consistent with the recently elucidated stereochemistry of the cisoid products. Further, computational studies using density functional theory calculations reveal concerted, highly asynchronous cyclization pathways leading to the major cisoid cyclization products. The implications of these discoveries for expanded sesquiterpene diversity in nature are discussed

    Measurements of the Ratios B(Ds+η+ν)/B(Ds+ϕ+ν){\cal B}(D_s^+\to \eta\ell^+\nu)/{\cal B}(D_s^+\to \phi\ell^+\nu) and B(Ds+η+ν)/B(Ds+ϕ+ν){\cal B}(D_s^+\to \eta'\ell^+\nu)/{\cal B}(D_s^+\to \phi\ell^+\nu)

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    Using the CLEO~II detector we measure B(Ds+ηe+ν)/B(Ds+ϕe+ν)=1.24±0.12±0.15{\cal B}(D_s^+\to \eta e^+\nu)/{\cal B}(D_s^+\to \phi e^+\nu) =1.24\pm0.12\pm0.15, B(Ds+ηe+ν)/B(Ds+ϕe+ν)=0.43±0.11±0.07{\cal B}(D_s^+\to \eta' e^+\nu)/{\cal B}(D_s^+\to \phi e^+\nu) =0.43\pm0.11\pm0.07 and B(Ds+ηe+ν)/B(Ds+ηe+ν)=0.35±0.09±0.07{\cal B}(D_s^+\to \eta' e^+\nu)/{\cal B}(D_s^+\to \eta e^+\nu) =0.35\pm0.09\pm0.07. We find the vector to pseudoscalar ratio, B(Ds+ϕe+ν)/B(Ds+(η+η)e+ν)=0.60±0.06±0.06{\cal B}(D_s^+\to \phi e^+\nu)/{\cal B}(D_s^+\to (\eta+\eta') e^+\nu) =0.60\pm0.06\pm0.06, which is similar to the ratio found in non strange DD decays.Comment: 11 page uuencoded postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN
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