Down-Regulation of TRPM5s During the Development of the Rat Neocortex and Hippocampus

The transient receptor potential (TRP) superfamily of cation membrane channels includes a large number of recently identified protein molecules that share the sequence homology with the Drosophila protein named after a phototransduction mutant of this insect called trp. Believing that one or more TRP channels might be involved in the process of neural development, we examined the possibility by searching the full profile of TRPC1­7, TRPV1­6, TRPM1­8, and TRPA1 channels during the development of the neocortex and hippocampus of rats (from the embryonic state to adults). The RT­PCR experiment was performed with mRNA isolated from the above­mentioned cerebral structures. Developmental changes were identified in transcripts for the profiles of TRPC1­7, TRPV1­6, TRPM1­8, and TRPA1. Down­regulation of exclusively TRPM5, whose mRNA expression level gradually decreased in the course of pre­ and post­natal development of both neocortex and hippocampus, was the most striking finding. Our results suggest that TRPM5s might have some important function in neural development. There is a possibility that TRPM5s are key components of the physiological function for sensing the environmental temperature in the developmental period of rats.Суперсімейство мембранних катіонних каналів транзієнтного рецепторного потенціалу (TRP) включає в себе велику кількість нещодавно ідентифікованих канальних протеїнів, у котрих первинні послідовності є гомологічними такій у протеїну мутанта дрозофіли, отриманого в результаті фототрансдукції та названого trp. Вважаючи, що один або більше типів TRP­каналів можуть бути задіяними в процес розвитку нервової системи, ми намагалися дослідити повні часові профілі представленості каналів TRPC1­7, TRPV1­6, TRPM1­8 та TRPA1 у перебігу розвитку неокортексу та гіпокампа у щурів (від ембріонального стану до дорослого віку). Зворотна рескриптаза – полімеразні ланцюгові реакції (ЗР­ПЛР) були проведені зі зразками мРНК, виділеними зі згаданих структур. Пов’язані з розвитком зміни були ідентифіковані в транскриптах для профілів TRPC1­7, TRPV1­ 6, TRPM1­8 та TRPA1. Найбільш вражаючим випадком була негативна регуляція (down­regulation) тільки кількості TRPM5; рівень експресії їх мРНК поступово зменшувався в перебігу пре­ та постнатального розвитку як неокортексу, так і гіпокампа. Наші результати дають досить переконливі підстави вважати, що TRPM5 можуть виконувати якусь важливу функцію в онтогенетичного розвитку нервової системи. Розглядається можливість того, що TRPM5 є ключовими компонентами в системі сприйняття температури середовища в початковий період онтогенезу щурів

Simulations of the Static Friction Due to Adsorbed Molecules

The static friction between crystalline surfaces separated by a molecularly thin layer of adsorbed molecules is calculated using molecular dynamics simulations. These molecules naturally lead to a finite static friction that is consistent with macroscopic friction laws. Crystalline alignment, sliding direction, and the number of adsorbed molecules are not controlled in most experiments and are shown to have little effect on the friction. Temperature, molecular geometry and interaction potentials can have larger effects on friction. The observed trends in friction can be understood in terms of a simple hard sphere model.Comment: 13 pages, 13 figure

Supervised selective kernel fusion for membrane protein prediction

Membrane protein prediction is a significant classification problem, requiring the integration of data derived from different sources such as protein sequences, gene expression, protein interactions etc. A generalized probabilistic approach for combining different data sources via supervised selective kernel fusion was proposed in our previous papers. It includes, as particular cases, SVM, Lasso SVM, Elastic Net SVM and others. In this paper we apply a further instantiation of this approach, the Supervised Selective Support Kernel SVM and demonstrate that the proposed approach achieves the top-rank position among the selective kernel fusion variants on benchmark data for membrane protein prediction. The method differs from the previous approaches in that it naturally derives a subset of “support kernels” (analogous to support objects within SVMs), thereby allowing the memory-efficient exclusion of significant numbers of irrelevant kernel matrixes from a decision rule in a manner particularly suited to membrane protein prediction

Persistent Spin Currents in Helimagnets

We demonstrate that weak external magnetic fields generate dissipationless spin currents in the ground state of systems with spiral magnetic order. Our conclusions are based on phenomenological considerations and on microscopic mean-field theory calculations for an illustrative toy model. We speculate on possible applications of this effect in spintronic devices.Comment: 9 pages, 6 figures, updated version as published, Journal referenc

Process Simulation and Control Optimization of a Blast Furnace Using Classical Thermodynamics Combined to a Direct Search Algorithm

Several numerical approaches have been proposed in the literature to simulate the behavior of modern blast furnaces: finite volume methods, data-mining models, heat and mass balance models, and classical thermodynamic simulations. Despite this, there is actually no efficient method for evaluating quickly optimal operating parameters of a blast furnace as a function of the iron ore composition, which takes into account all potential chemical reactions that could occur in the system. In the current study, we propose a global simulation strategy of a blast furnace, the 5-unit process simulation. It is based on classical thermodynamic calculations coupled to a direct search algorithm to optimize process parameters. These parameters include the minimum required metallurgical coke consumption as well as the optimal blast chemical composition and the total charge that simultaneously satisfy the overall heat and mass balances of the system. Moreover, a Gibbs free energy function for metallurgical coke is parameterized in the current study and used to fine-tune the simulation of the blast furnace. Optimal operating conditions and predicted output stream properties calculated by the proposed thermodynamic simulation strategy are compared with reference data found in the literature and have proven the validity and high precision of this simulation

Carotid Intima-Media Thickness Progression as Surrogate Marker for Cardiovascular Risk Meta-Analysis of 119 Clinical Trials Involving 100 667 Patients

Background: To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk. Methods: We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. The primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach. Results: We analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 μm/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87–0.94), with an additional relative risk for CVD of 0.92 (0.87–0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 μm/y would yield relative risks of 0.84 (0.75–0.93), 0.76 (0.67–0.85), 0.69 (0.59–0.79), or 0.63 (0.52–0.74), respectively. Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary versus secondary prevention trials, type of cIMT measurement, and proportion of female patients. Conclusions: The extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials

Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of l

Virtual Ontogeny of Cortical Growth Preceding Mental Illness

Background: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. Methods: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. Results: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. Conclusions: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy