Fluctuation spectrum of fluid membranes coupled to an elastic meshwork: jump of the effective surface tension at the mesh size

We identify a class of composite membranes: fluid bilayers coupled to an elastic meshwork, that are such that the meshwork's energy is a function $F_\mathrm{el}[A_\xi]$ \textit{not} of the real microscopic membrane area $A$, but of a \textit{smoothed} membrane's area $A_\xi$, which corresponds to the area of the membrane coarse-grained at the mesh size $\xi$. We show that the meshwork modifies the membrane tension $\sigma$ both below and above the scale $\xi$, inducing a tension-jump $\Delta\sigma=dF_\mathrm{el}/dA_\xi$. The predictions of our model account for the fluctuation spectrum of red blood cells membranes coupled to their cytoskeleton. Our results indicate that the cytoskeleton might be under extensional stress, which would provide a means to regulate available membrane area. We also predict an observable tension jump for membranes decorated with polymer "brushes"

Phase transition of triangulated spherical surfaces with elastic skeletons

A first-order transition is numerically found in a spherical surface model with skeletons, which are linked to each other at junctions. The shape of the triangulated surfaces is maintained by skeletons, which have a one-dimensional bending elasticity characterized by the bending rigidity $b$, and the surfaces have no two-dimensional bending elasticity except at the junctions. The surfaces swell and become spherical at large $b$ and collapse and crumple at small $b$. These two phases are separated from each other by the first-order transition. Although both of the surfaces and the skeleton are allowed to self-intersect and, hence, phantom, our results indicate a possible phase transition in biological or artificial membranes whose shape is maintained by cytoskeletons.Comment: 15 pages with 10 figure

Inhibition of Y1 receptor signaling improves islet transplant outcome

Failure to secrete sufficient quantities of insulin is a pathological feature of type-1 and type-2 diabetes, and also reduces the success of islet cell transplantation. Here we demonstrate that Y1 receptor signaling inhibits insulin release in β-cells, and show that this can be pharmacologically exploited to boost insulin secretion. Transplanting islets with Y1 receptor deficiency accelerates the normalization of hyperglycemia in chemically induced diabetic recipient mice, which can also be achieved by short-term pharmacological blockade of Y1 receptors in transplanted mouse and human islets. Furthermore, treatment of non-obese diabetic mice with a Y1 receptor antagonist delays the onset of diabetes. Mechanistically, Y1 receptor signaling inhibits the production of cAMP in islets, which via CREB mediated pathways results in the down-regulation of several key enzymes in glycolysis and ATP production. Thus, manipulating Y1 receptor signaling in β-cells offers a unique therapeutic opportunity for correcting insulin deficiency as it occurs in the pathological state of type-1 diabetes as well as during islet transplantation.Islet transplantation is considered one of the potential treatments for T1DM but limited islet survival and their impaired function pose limitations to this approach. Here Loh et al. show that the Y1 receptor is expressed in β- cells and inhibition of its signalling, both genetic and pharmacological, improves mouse and human islet function.info:eu-repo/semantics/publishe

Dynorphin knockout reduces fat mass and increases weight loss during fasting in mice

Endogenous opioids, particularly dynorphins, have been implicated in regulation of energy balance, but it is not known how they mediate this in vivo. We investigated energy homeostasis in dynorphin knockout mice (Dyn -/- mice) and probed the interactions between dynorphins and the neuropeptide Y (NPY) system. Dyn-/- mice were no different from wild types with regards to body weight and basal and fasting-induced food intake, but fecal output was increased, suggesting decreased nutrient absorption, and they had significantly less white fat and lost more weight during a 24-h fast. The neuroendocrine and thermal responses to fasting were at least as pronounced in Dyn-/- as in wild types, and there was no stimulatory effect of dynorphin knockout on 24-h energy expenditure (kilocalories of heat produced) or physical activity. However, Dyn-/- mice showed increased circulating concentrations of 3,4-dihydroxyphenlacetic acid and 3,4-dihydroxyphenylglycol, suggesting increased activity of the sympathetic nervous system. The respiratory exchange ratio of male but not female Dyn-/- mice was reduced, demonstrating increased fat oxidation. Interestingly, expression of the orexigenic acting NPY in the hypothalamic arcuate nucleus was reduced in Dyn-/- mice. However, fasting-induced increases in pre-prodynorphin expression in the arcuate nucleus, the paraventricular nucleus, and the ventromedial hypothalamus but not the lateral hypothalamus were abolished by deletion of Y1 but not Y2 receptors. Therefore, ablation of dynorphins results in increases in fatty acid oxidation in male mice, reductions in adiposity, and increased weight loss during fasting, possibly via increases in sympathetic activity, decreases in intestinal nutrient absorption, and interactions with the NPYergic system

Effects Of Length, Complexity, And Grammatical Correctness On Stuttering In Spanish-Speaking Preschool Children

Purpose: To explore the effects of utterance length, syntactic complexity, and grammatical correctness on stuttering in the spontaneous speech of young, monolingual Spanish-speaking children. Method: Spontaneous speech samples of 11 monolingual Spanish-speaking children who stuttered, ages 35 to 70 months, were examined. Mean number of syllables, total number of clauses, utterance complexity (i.e., containing no clauses, simple clauses, or subordinate and/or conjoined clauses), and grammatical correctness (i.e., the presence or absence of morphological and syntactical errors) in stuttered and fluent utterances were compared. Results: Findings revealed that stuttered utterances in Spanish tended to be longer and more often grammatically incorrect, and contain more clauses, including more subordinate and/or conjoined clauses. However, when controlling for the interrelatedness of syllable number and clause number and complexity, only utterance length and grammatical incorrectness were significant predictors of stuttering in the spontaneous speech of these Spanish-speaking children. Use of complex utterances did not appear to contribute to the prediction of stuttering when controlling for utterance length. Conclusions: Results from the present study were consistent with many earlier reports of English-speaking children. Both length and grammatical factors appear to affect stuttering in Spanish-speaking children. Grammatical errors, however, served as the greatest predictor of stuttering.Communication Sciences and Disorder

Phase transition of meshwork models for spherical membranes

We have studied two types of meshwork models by using the canonical Monte Carlo simulation technique. The first meshwork model has elastic junctions, which are composed of vertices, bonds, and triangles, while the second model has rigid junctions, which are hexagonal (or pentagonal) rigid plates. Two-dimensional elasticity is assumed only at the elastic junctions in the first model, and no two-dimensional bending elasticity is assumed in the second model. Both of the meshworks are of spherical topology. We find that both models undergo a first-order collapsing transition between the smooth spherical phase and the collapsed phase. The Hausdorff dimension of the smooth phase is H\simeq 2 in both models as expected. It is also found that H\simeq 2 in the collapsed phase of the second model, and that H is relatively larger than 2 in the collapsed phase of the first model, but it remains in the physical bound, i.e., H<3. Moreover, the first model undergoes a discontinuous surface fluctuation transition at the same transition point as that of the collapsing transition, while the second model undergoes a continuous transition of surface fluctuation. This indicates that the phase structure of the meshwork model is weakly dependent on the elasticity at the junctions.Comment: 21 pages, 12 figure