180 research outputs found
Medawar’s post era: Galectins emerged as key players during fetal-maternal glycoimmune adaptation
Lectin-glycan interactions, in particular those mediated by the galectin family, regulate many processes required for a successful pregnancy. Over the past decades, increasing evidence gathered from in vitro and in vivo experiments indicate that members of the galectin family specifically bind to both intracellular and membrane bound carbohydrate ligands regulating angiogenesis, immune-cell adaptations required to tolerate the fetal semi-allograft and mammalian embryogenesis. Therefore, galectins play important roles in fetal development and placentation contributing to maternal and fetal health. This review discusses the expression and role of galectins during the course of pregnancy, with an emphasis on maternal immune adaptions and galectin-glycan interactions uncovered in the recent years. In addition, we summarize the galectin fingerprints associated with pathological gestation with particular focus on preeclampsia
Proving The Ergodic Hypothesis for Billiards With Disjoint Cylindric Scatterers
In this paper we study the ergodic properties of mathematical billiards
describing the uniform motion of a point in a flat torus from which finitely
many, pairwise disjoint, tubular neighborhoods of translated subtori (the so
called cylindric scatterers) have been removed. We prove that every such system
is ergodic (actually, a Bernoulli flow), unless a simple geometric obstacle for
the ergodicity is present.Comment: 24 pages, AMS-TeX fil
Resonant enhancements of high-order harmonic generation
Solving the one-dimensional time-dependent Schr\"odinger equation for simple
model potentials, we investigate resonance-enhanced high-order harmonic
generation, with emphasis on the physical mechanism of the enhancement. By
truncating a long-range potential, we investigate the significance of the
long-range tail, the Rydberg series, and the existence of highly excited states
for the enhancements in question. We conclude that the channel closings typical
of a short-range or zero-range potential are capable of generating essentially
the same effects.Comment: 7 pages revtex, 4 figures (ps files
Disruption of beta cell acetyl-CoA carboxylase-1 in mice impairs insulin secretion and beta cell mass
Aims/hypothesis
Pancreatic beta cells secrete insulin to maintain glucose homeostasis, and beta cell failure is a hallmark of type 2 diabetes. Glucose triggers insulin secretion in beta cells via oxidative mitochondrial pathways. However, it also feeds mitochondrial anaplerotic pathways, driving citrate export and cytosolic malonyl-CoA production by the acetyl-CoA carboxylase 1 (ACC1) enzyme. This pathway has been proposed as an alternative glucose-sensing mechanism, supported mainly by in vitro data. Here, we sought to address the role of the beta cell ACC1-coupled pathway in insulin secretion and glucose homeostasis in vivo.
Methods
Acaca, encoding ACC1 (the principal ACC isoform in islets), was deleted in beta cells of mice using the Cre/loxP system. Acaca floxed mice were crossed with Ins2cre mice (βACC1KO; life-long beta cell gene deletion) or Pdx1creER mice (tmx-βACC1KO; inducible gene deletion in adult beta cells). Beta cell function was assessed using in vivo metabolic physiology and ex vivo islet experiments. Beta cell mass was analysed using histological techniques.
Results
βACC1KO and tmx-βACC1KO mice were glucose intolerant and had defective insulin secretion in vivo. Isolated islet studies identified impaired insulin secretion from beta cells, independent of changes in the abundance of neutral lipids previously implicated as amplification signals. Pancreatic morphometry unexpectedly revealed reduced beta cell size in βACC1KO mice but not in tmx-βACC1KO mice, with decreased levels of proteins involved in the mechanistic target of rapamycin kinase (mTOR)-dependent protein translation pathway underpinning this effect.
Conclusions/interpretation
Our study demonstrates that the beta cell ACC1-coupled pathway is critical for insulin secretion in vivo and ex vivo and that it is indispensable for glucose homeostasis. We further reveal a role for ACC1 in controlling beta cell growth prior to adulthood
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