127 research outputs found
Osmotic properties of polyethyleneglycols: quantitative features of brush and bulk scaling laws
From glycosylated cell surfaces to sterically stabilized liposomes, polymers
attached to membranes attract biological and therapeutic interest. Can the
scaling laws of polymer "brushes" describe the physical properties of these
coats? We delineate conditions where the Alexander - de Gennes theory of
polymer brushes successfully describes the intermembrane distance vs. applied
osmotic stress data of Kenworthy et al. for PEG-grafted multilamellar liposomes
[Biophys. J. (1995) 68:1921]. We establish that the polymer density and size in
the brush must be high enough that, in a bulk solution of equivalent density,
the polymer osmotic pressure is independent of polymer molecular weight (the
des Cloizeaux semi-dilute regime of bulk polymer solutions). The condition that
attached polymers behave as semi-dilute bulk solutions offers a rigorous
criterion for brush scaling-law behavior. There is a deep connection between
the behaviors of polymer solutions in bulk and polymers grafted to a surface at
a density such that neighbors pack to form a uniform brush. In this regime,
two-parameter unconstrained fits of the Alexander - de Gennes brush scaling
laws yield effective monomer lengths of 3.3 to 3.5 AA, which agree with
structural predictions. The fitted distances between grafting sites are larger
than expected from the nominal content of PEG-lipids; the chains apparently
saturate the surface. Osmotic stress measurements can be used to estimate the
actual densities of membrane-grafted polymers.Comment: 26 pages with figure
Heme oxygenase 1 polymorphism, occupational vapor, gas, dust, and fume exposure and chronic obstructive pulmonary disease in a Danish population-based study
Spawning manipulation, broodfish diet feeding and egg production in farmed Atlantic salmon
Atlantic salmon aquaculture relies on continuous supply of high quality eggs. Broodfish nutrition and manipulation of ovulation time (photoperiod and temperature) are key factors. The optimum feeding period with broodfish diet has not been investigated before. The present study examined how feeding period with broodfish diet (9 vs. 17 months) interacted with manipulation of ovulation time (early (Nov), normal (Dec), late (Feb)) on broodstock egg production capacity and egg quality in two-sea-winter female Atlantic salmon (∼12 kg). All groups were fed until June 2021 when they were transferred to tanks and starved until ovulation.publishedVersio
Night shift work, long working hours and dementia::a longitudinal study of the Danish Work Environment Cohort
Social Relations at Work and Incident Dementia:29-Years' Follow-Up of the Copenhagen Male Study
GLP-1 stimulates insulin secretion by PKC-dependent TRPM4 and TRPM5 activation.
Strategies aimed at mimicking or enhancing the action of the incretin hormone glucagon-like peptide 1 (GLP-1) therapeutically improve glucose-stimulated insulin secretion (GSIS); however, it is not clear whether GLP-1 directly drives insulin secretion in pancreatic islets. Here, we examined the mechanisms by which GLP-1 stimulates insulin secretion in mouse and human islets. We found that GLP-1 enhances GSIS at a half-maximal effective concentration of 0.4 pM. Moreover, we determined that GLP-1 activates PLC, which increases submembrane diacylglycerol and thereby activates PKC, resulting in membrane depolarization and increased action potential firing and subsequent stimulation of insulin secretion. The depolarizing effect of GLP-1 on electrical activity was mimicked by the PKC activator PMA, occurred without activation of PKA, and persisted in the presence of PKA inhibitors, the KATP channel blocker tolbutamide, and the L-type Ca(2+) channel blocker isradipine; however, depolarization was abolished by lowering extracellular Na(+). The PKC-dependent effect of GLP-1 on membrane potential and electrical activity was mediated by activation of Na(+)-permeable TRPM4 and TRPM5 channels by mobilization of intracellular Ca(2+) from thapsigargin-sensitive Ca(2+) stores. Concordantly, GLP-1 effects were negligible in Trpm4 or Trpm5 KO islets. These data provide important insight into the therapeutic action of GLP-1 and suggest that circulating levels of this hormone directly stimulate insulin secretion by β cells.We thank David Wiggins for excellent technical assistance. This work was supported by the Medical Research Council, Diabetes UK (to R. Ramracheya ), Oxford Biomedical Research Centre (to A. Tarasov), the Wellcome Trust (Senior Investigator Awards to A. Galione and P. Rorsman), the Warwick Impact Fund (to C. Weston and G. Ladds), the Biotechnology and Biological Sciences Research Council (to G. Ladds), the Knut and Alice Wallenberg Foundation (to P. Rorsman), and the Swedish Research Council (to P. Rorsman). The initial stages of M. Shigeto’s stay in Oxford were supported by a fellowship from Kawasaki Medical School.This is the final version of the article. It was first available from the American Society for Clinical Investigation via http://dx.doi.org/10.1172/JCI8197
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