2,164 research outputs found

    Metabolic effects of overnight continuous infusion of unacylated ghrelin in humans

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    Objective: To clarify the metabolic effects of an overnight i.v. infusion of unacylated ghrelin (UAG) in humans. UAG exerts relevant metabolic actions, likely mediated by a still unknown ghrelin receptor subtype, including effects on Ī²-cell viability and function, insulin secretion and sensitivity, and glucose and lipid metabolism. Design: We studied the effects of a 16-h infusion (from 2100 to 1300 h) of UAG (1.0 Ī¼g/kg per h) or saline in eight normal subjects (age (meanĀ±S.E.M.), 29.6Ā±2.4 years; body mass index (BMI), 22.4Ā±1.7 kg/m2), who were served, at 2100 and 0800 h respectively, with isocaloric balanced dinner and breakfast. Glucose, insulin, and free fatty acid (FFA) levels were measured every 20 min. Results: In comparison with saline, UAG induced significant (P<0.05) changes in glucose, insulin, and FFA profiles. UAG infusion decreased glucose area under the curve (AUC) values by 10% (UAG0-960 min: 79.0Ā±1.7Ɨ10 3 mg/dl per min vs saline0-960 min: 87.5Ā±3. 8Ɨ103 mg/dl per min) and the AUC at night by 14% (UAG 180-660 min: 28.4Ā±0.5Ɨ103 mg/dl per min vs saline180-660 min: 33.2Ā±1.1Ɨ103 mg/dl per min). The overall insulin AUC was not significantly modified by UAG infusion; however, insulin AUC observed after meals was significantly increased under the exposure to UAG with respect to saline at either dinner or breakfast. The FFA AUC values were decreased by 52% under the exposure to UAG in comparison with saline (UAG0-960 min: 0.3Ā±0.02Ɨ103 mEq/l per min vs saline0-960 min: 0.6Ā±0.05Ɨ103 mEq/l per min). Conclusions: Exposure to the i.v. administration of UAG improves glucose metabolism and inhibits lipolysis in healthy volunteers. Thus, in contrast to the diabetogenic action of AG, UAG displays hypoglycemic properties

    A Quasi-Classical Model of Intermediate Velocity Particle Production in Asymmetric Heavy Ion Reactions

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    The particle emission at intermediate velocities in mass asymmetric reactions is studied within the framework of classical molecular dynamics. Two reactions in the Fermi energy domain were modelized, 58^{58}Ni+C and 58^{58}Ni+Au at 34.5 MeV/nucleon. The availability of microscopic correlations at all times allowed a detailed study of the fragment formation process. Special attention was paid to the physical origin of fragments and emission timescales, which allowed us to disentangle the different processes involved in the mid-rapidity particle production. Consequently, a clear distinction between a prompt pre- equilibrium emission and a delayed aligned asymmetric breakup of the heavier partner of the reaction was achieved.Comment: 8 pages, 7 figures. Final version: figures were redesigned, and a new section discussing the role of Coulomb in IMF production was include

    Identification of pannexin 1-regulated genes, interactome, and pathways in rhabdomyosarcoma and its tumor inhibitory interaction with AHNAK

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    Rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children, is an aggressive cancer with a poor prognosis. Despite current management, the 5-year survival rate for patients with metastatic RMS is āˆ¼30%; underscoring the need to develop better treatment strategies. We have recently reported that pannexin 1 (PANX1) levels are downregulated in RMS and that restoring its expression inhibits RMS progression. Here, we have surveyed and characterized the molecular changes induced by PANX1 re-expression in RMS. We cataloged transcriptomic changes in this context by RNA sequencing. At the protein level, we unveiled PANX1 interactors using BioID, complemented by co-immunoprecipitation coupled to high-performance liquid chromatography/electrospray ionization tandem mass spectrometry performed in PANX1-enriched fractions. Using these data, we generated searchable public databases for the PANX1 interactome and changes to the RMS transcriptome occurring when PANX1 expression is restored. STRING network analyses revealed a PANX1 interactome involving plasma membrane and cytoskeleton-associated proteins including the previously undescribed interactor AHNAK. Indeed, AHNAK knockdown abrogated the PANX1-mediated reduction in RMS cell viability and migration. Using these unbiased approaches, we bring insight to the mechanisms by which PANX1 inhibits RMS progression, identifying the cell migration protein AHNAK as a key modifier of PANX1-mediated changes in RMS malignant properties

    Exploratory Investigation on the Occurrence, Spatial Distribution, and Risk Factors of Selected Zoonotic Enteropathogens in Davao City Backyard Farms

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    The swine industry is the second largest economic contributor to Philippine agriculture and is dominated by backyard farms, which are plagued by outdated management practices and poor animal health support that promote the spread of pathogens. Zoonotic enteropathogens pose a public health threat, especially to backyard farmers who have daily close contact with the infected animals and their waste. Hence, there is a need to survey such pathogens. This exploratory study generated baseline information on enteropathogen occurrence in backyard farms of Davao City, Philippines; the spatial distribution of affected farms; and the risk factors for enteropathogen occurrence. Protozoans such as Blastocystis sp., Balantidium coli, Entamoeba sp., Iodamoeba sp., Giardia sp., and coccidia, while helminths such as hookworm and strongylids were identified by direct wet smear. Rotavirus A was detected by reverse transcription-nested polymerase chain reaction. Almost 73% of the farms harbored enteropathogens with mostly asymptomatic infections, and weaners and growers are major carriers. Geospatial analysis identified Barangay Bato in Toril District as a hotspot for the pathogens. Probit regression analysis revealed that use of treatments increased the likelihood of pathogen occurrence by 24%, possibly due to misapplication of medications such as anthelmintics. On the other hand, there was 40% reduced likelihood for farms that use traditional feeds, which can promote gut immunity. Therefore, high-fiber diet can be explored for broad-spectrum protection against enteropathogens. Promoting awareness on the benefits of traditional feeds and education on the proper use of medication are also recommended, especially for vulnerable farms in hotspot areas

    Mixed methods, materialism and the micropolitics of the research-assemblage

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    We assess the potential for mixing social research methods, based upon a materialist and micropolitical analysis of the research-assemblage and of what individual research techniques and methods do in practice. Applying a DeleuzoGuattarian toolkit of assemblages, affects and capacities, we document what happens when research methods and techniques interact with the events they wish to study. Micropolitically, many of these techniques and methods have unintended effects of specifying and aggregating events, with the consequently that the knowledge produced by social inquiry is invested with these specifications and aggregations. We argue that rather than abandoning these social research tools, we may use the micropolitical analysis to assess precisely how each method affects knowledge production, and engineer the research designs we use accordingly. This forms the justification for mixing methods that are highly aggregative or specifying with those that are less so, effectively rehabilitating methods that have often been rejected by social researchers, including surveys and experiments

    Functional characterization of a melon alcohol acyl-transferase gene family involved in the biosynthesis of ester volatiles. Identification of the crucial role of a threonine residue for enzyme activity

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    Volatile esters, a major class of compounds contributing to the aroma of many fruit, are synthesized by alcohol acyl-transferases (AAT). We demonstrate here that, in Charentais melon (Cucumis melo var. cantalupensis), AAT are encoded by a gene family of at least four members with amino acid identity ranging from 84% (Cm-AAT1/Cm-AAT2) and 58% (Cm-AAT1/Cm-AAT3) to only 22% (Cm-AAT1/Cm-AAT4). All encoded proteins, except Cm-AAT2, were enzymatically active upon expression in yeast and show differential substrate preferences. Cm-AAT1 protein produces a wide range of short and long-chain acyl esters but has strong preference for the formation of E-2-hexenyl acetate and hexyl hexanoate. Cm-AAT3 also accepts a wide range of substrates but with very strong preference for producing benzyl acetate. Cm-AAT4 is almost exclusively devoted to the formation of acetates, with strong preference for cinnamoyl acetate. Site directed mutagenesis demonstrated that the failure of Cm-AAT2 to produce volatile esters is related to the presence of a 268-alanine residue instead of threonine as in all active AAT proteins. Mutating 268-A into 268-T of Cm-AAT2 restored enzyme activity, while mutating 268-T into 268-A abolished activity of Cm-AAT1. Activities of all three proteins measured with the prefered substrates sharply increase during fruit ripening. The expression of all Cm-AAT genes is up-regulated during ripening and inhibited in antisense ACC oxidase melons and in fruit treated with the ethylene antagonist 1-methylcyclopropene (1-MCP), indicating a positive regulation by ethylene. The data presented in this work suggest that the multiplicity of AAT genes accounts for the great diversity of esters formed in melon
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