A fundamental bimodal role for neuropeptide Y1 receptor in the immune system

Psychological conditions, including stress, compromise immune defenses. Although this concept is not novel, the molecular mechanism behind it remains unclear. Neuropeptide Y (NPY) in the central nervous system is a major regulator of numerous physiological functions, including stress. Postganglionic sympathetic nerves innervating lymphoid organs release NPY, which together with other peptides activate five Y receptors (Y1, Y2, Y4, Y5, and y6). Using Y1-deficient (Y1−/−) mice, we showed that Y1−/− T cells are hyperresponsive to activation and trigger severe colitis after transfer into lymphopenic mice. Thus, signaling through Y1 receptor on T cells inhibits T cell activation and controls the magnitude of T cell responses. Paradoxically, Y1−/− mice were resistant to T helper type 1 (Th1) cell–mediated inflammatory responses and showed reduced levels of the Th1 cell–promoting cytokine interleukin 12 and reduced interferon γ production. This defect was due to functionally impaired antigen-presenting cells (APCs), and consequently, Y1−/− mice had reduced numbers of effector T cells. These results demonstrate a fundamental bimodal role for the Y1 receptor in the immune system, serving as a strong negative regulator on T cells as well as a key activator of APC function. Our findings uncover a sophisticated molecular mechanism regulating immune cell functions that can lead to stress-induced immunosuppression

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 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

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

Combined Simulation and Experimental Study of Large Deformation of Red Blood Cells in Microfluidic Systems

Author manuscript; available in PMC 2012 March 1.We investigate the biophysical characteristics of healthy human red blood cells (RBCs) traversing microfluidic channels with cross-sectional areas as small as 2.7 × 3 μm. We combine single RBC optical tweezers and flow experiments with corresponding simulations based on dissipative particle dynamics (DPD), and upon validation of the DPD model, predictive simulations and companion experiments are performed in order to quantify cell deformation and pressure–velocity relationships for different channel sizes and physiologically relevant temperatures. We discuss conditions associated with the shape transitions of RBCs along with the relative effects of membrane and cytosol viscosity, plasma environments, and geometry on flow through microfluidic systems at physiological temperatures. In particular, we identify a cross-sectional area threshold below which the RBC membrane properties begin to dominate its flow behavior at room temperature; at physiological temperatures this effect is less profound.Singapore-MIT Alliance for Research and TechnologyUnited States. National Institutes of Health (National Heart, Lung, and Blood Institute Award R01HL094270

Tooling design and microwave curing technologies for the manufacturing of fiber-reinforced polymer composites in aerospace applications

The increasing demand for high-performance and quality polymer composite materials has led to international research effort on pursuing advanced tooling design and new processing technologies to satisfy the highly specialized requirements of composite components used in the aerospace industry. This paper reports the problems in the fabrication of advanced composite materials identified through literature survey, and an investigation carried out by the authors about the composite manufacturing status in China’s aerospace industry. Current tooling design technologies use tooling materials which cannot match the thermal expansion coefficient of composite parts, and hardly consider the calibration of tooling surface. Current autoclave curing technologies cannot ensure high accuracy of large composite materials because of the wide range of temperature gradients and long curing cycles. It has been identified that microwave curing has the potential to solve those problems. The proposed technologies for the manufacturing of fiber-reinforced polymer composite materials include the design of tooling using anisotropy composite materials with characteristics for compensating part deformation during forming process, and vacuum-pressure microwave curing technology. Those technologies are mainly for ensuring the high accuracy of anisotropic composite parts in aerospace applications with large size (both in length and thickness) and complex shapes. Experiments have been carried out in this on-going research project and the results have been verified with engineering applications in one of the project collaborating companies

Development and psychometric properties the Barriers to Access to Care Evaluation scale (BACE) related to people with mental ill health

Many people with mental illness do not seek or delay seeking care. This study aimed to develop, and provide an initial validation of, a comprehensive measure for assessing barriers to access to mental health care including a 'treatment stigma' subscale, and to present preliminary evidence about the prevalence of barriers experienced by adults currently or recently using secondary mental health services in the UK

Peptide YY ablation in mice leads to the development of hyperinsulinaemia and obesity

Aims/hypothesis. Obese people exhibit reduced circulating peptide YY (PYY) levels, but it is unclear whether this is a consequence or cause of obesity. We therefore investigated the effect of Pyy ablation on energy homeostasis. Methods. Body composition, i.p. glucose tolerance, food intake and hypothalamic neuropeptide expression were determined in Pyy knock-out and wild-type mice on a normal or high-fat diet. Results. Pyy knock-out significantly increased bodyweight and increased fat mass by 50% in aged females on a normal diet. Male chow-fed Pyy −/− mice were resistant to obesity but became significantly fatter and glucose-intolerant compared with wild-types when fed a high-fat diet. Pyy knock-out animals exhibited significantly elevated fasting or glucose-stimulated serum insulin concentrations vs wild-types, with no increase in basal or fasting-induced food intake. Pyy knock-out decreased or had no effect on neuropeptide Y expression in the arcuate nucleus of the hypothalamus, and significantly increased proopiomelanocortin expression in this region. Male but not female knock-outs exhibited significantly increased growth hormone-releasing hormone expression in the ventromedial hypothalamus and significantly elevated serum IGF-I and testosterone levels. This sex difference in activation of the hypothalamo–pituitary somatotrophic axis by Pyy ablation may contribute to the resistance of chow-fed male knock-outs to late-onset obesity. Conclusions/interpretation. PYY signalling is important in the regulation of energy balance and glucose homeostasis, possibly via regulation of insulin release. Therefore reduced PYY levels may predispose to the development of obesity, particularly with ageing or under conditions of high-fat feeding

Need for criteria for the diagnosis and severity assessment of acute cholangitis and cholecystitis: Tokyo Guidelines

The Tokyo Guidelines formulate clinical guidance for healthcare providers regarding the diagnosis, severity assessment, and treatment of acute cholangitis and acute cholecystitis. The Guidelines were developed through a comprehensive literature search and selection of evidence. Recommendations were based on the strength and quality of evidence. Expert consensus opinion was used to enhance or formulate important areas where data were insufficient. A working group, composed of gastroenterologists and surgeons with expertise in biliary tract surgery, supplemented with physicians in critical care medicine, epidemiology, and laboratory medicine, was selected to formulate draft guidelines. Several other groups (including members of the Japanese Society for Abdominal Emergency Medicine, the Japan Biliary Association, and the Japanese Society of Hepato-Biliary-Pancreatic Surgery) have reviewed and revised the draft guidelines. To build a global consensus on the management of acute biliary infection, an international expert panel, representing experts in this area, was established. Between April 1 and 2, 2006, an International Consensus Meeting on acute biliary infections was held in Tokyo. A consensus was determined based on best available scientific evidence and discussion by the panel of experts. This report describes the highlights of the Tokyo International Consensus Meeting in 2006. Some important areas focused on at the meeting include proposals for internationally accepted diagnostic criteria and severity assessment for both clinical and research purposes