Associations between SNPs and immune-related circulating proteins in schizophrenia

Genome-wide association studies (GWAS) and proteomic studies have provided convincing evidence implicating alterations in immune/inflammatory processes in schizophrenia. However, despite the convergence of evidence, direct links between the genetic and proteomic findings are still lacking for schizophrenia. We investigated associations between single nucleotide polymorphisms (SNPs) from the custom-made PsychArray and the expression levels of 190 multiplex immunoassay profiled serum proteins in 149 schizophrenia patients and 198 matched controls. We identified associations between 81 SNPs and 29 proteins, primarily involved in immune/inflammation responses. Significant SNPxDiagnosis interactions were identified for eight serum proteins including Factor-VII[rs555212], Alpha-1-Antitrypsin[rs11846959], Interferon-Gamma Induced Protein 10[rs4256246] and von-Willebrand-Factor[rs12829220] in the control group; Chromogranin-A[rs9658644], Cystatin-C[rs2424577] and Vitamin K-Dependent Protein S[rs6123] in the schizophrenia group; Interleukin-6 receptor[rs7553796] in both the control and schizophrenia groups. These results suggested that the effect of these SNPs on expression of the respective proteins varies with diagnosis. The combination of patient-specific genetic information with blood biomarker data opens a novel approach to investigate disease mechanisms in schizophrenia and other psychiatric disorders. Our findings not only suggest that blood protein expression is influenced by polymorphisms in the corresponding gene, but also that the effect of certain SNPs on expression of proteins can vary with diagnosis

Inspiratory muscle training reduces blood lactate concentration during volitional hyperpnoea

Although reduced blood lactate concentrations ([lac−]B) have been observed during whole-body exercise following inspiratory muscle training (IMT), it remains unknown whether the inspiratory muscles are the source of at least part of this reduction. To investigate this, we tested the hypothesis that IMT would attenuate the increase in [lac−]B caused by mimicking, at rest, the breathing pattern observed during high-intensity exercise. Twenty-two physically active males were matched for 85% maximal exercise minute ventilation (V˙Emax) and divided equally into an IMT or a control group. Prior to and following a 6 week intervention, participants performed 10 min of volitional hyperpnoea at the breathing pattern commensurate with 85% V˙Emax

Gender differences in the associations between age trends of social media interaction and well-being among 10-15 year olds in the UK

Background Adolescents are among the highest consumers of social media while research has shown that their well-being decreases with age. The temporal relationship between social media interaction and well-being is not well established. The aim of this study was to examine whether the changes in social media interaction and two well-being measures are related across ages using parallel growth models. Methods Data come from five waves of the youth questionnaire, 10-15 years, of the Understanding Society, the UK Household Longitudinal Study (pooled n =9859). Social media interaction was assessed through daily frequency of chatting on social websites. Well-being was measured by happiness with six domains of life and the Strengths and Difficulties Questionnaire. Results Findings suggest gender differences in the relationship between interacting on social media and well-being. There were significant correlations between interacting on social media and well-being intercepts and between social media interaction and well-being slopes among females. Additionally higher social media interaction at age 10 was associated with declines in well-being thereafter for females, but not for males. Results were similar for both measures of well-being. Conclusions High levels of social media interaction in early adolescence have implications for well-being in later adolescence, particularly for females. The lack of an association among males suggests other factors might be associated with their reduction in well-being with age. These findings contribute to the debate on causality and may inform future policy and interventions

Theorems on existence and global dynamics for the Einstein equations

This article is a guide to theorems on existence and global dynamics of solutions of the Einstein equations. It draws attention to open questions in the field. The local-in-time Cauchy problem, which is relatively well understood, is surveyed. Global results for solutions with various types of symmetry are discussed. A selection of results from Newtonian theory and special relativity that offer useful comparisons is presented. Treatments of global results in the case of small data and results on constructing spacetimes with prescribed singularity structure or late-time asymptotics are given. A conjectural picture of the asymptotic behaviour of general cosmological solutions of the Einstein equations is built up. Some miscellaneous topics connected with the main theme are collected in a separate section.Comment: Submitted to Living Reviews in Relativity, major update of Living Rev. Rel. 5 (2002)

Protein disulphide isomerase-assisted functionalization of proteinaceous substrates

Protein disulphide isomerase (PDI) is an enzyme that catalyzes thiol-disulphide exchange reactions among a broad spectrum of substrates, including proteins and low-molecular thiols and disulphides. As the first protein-folding catalyst reported, the study of PDI has mainly involved the correct folding of several cysteine-containing proteins. Its application on the functionalization of protein-based materials has not been extensively reported. Herein, we review the applications of PDI on the modification of proteinaceous substrates and discuss its future potential. The mechanism involved in PDI functionalization of fibrous protein substrates is discussed in detail. These approaches allow innovative applications in textile dyeing and finishing, medical textiles, controlled drug delivery systems and hair or skin care products.We thank to FCT 'Fundacao para a Ciencia e Tecnologia' (scholarship SFRH/BD/38363/2007) for providing Margarida Fernandes the grant for PhD studies

Impairment of Auditory-Motor Timing and Compensatory Reorganization after Ventral Premotor Cortex Stimulation

Integrating auditory and motor information often requires precise timing as in speech and music. In humans, the position of the ventral premotor cortex (PMv) in the dorsal auditory stream renders this area a node for auditory-motor integration. Yet, it remains unknown whether the PMv is critical for auditory-motor timing and which activity increases help to preserve task performance following its disruption. 16 healthy volunteers participated in two sessions with fMRI measured at baseline and following rTMS (rTMS) of either the left PMv or a control region. Subjects synchronized left or right finger tapping to sub-second beat rates of auditory rhythms in the experimental task, and produced self-paced tapping during spectrally matched auditory stimuli in the control task. Left PMv rTMS impaired auditory-motor synchronization accuracy in the first sub-block following stimulation (p<0.01, Bonferroni corrected), but spared motor timing and attention to task. Task-related activity increased in the homologue right PMv, but did not predict the behavioral effect of rTMS. In contrast, anterior midline cerebellum revealed most pronounced activity increase in less impaired subjects. The present findings suggest a critical role of the left PMv in feed-forward computations enabling accurate auditory-motor timing, which can be compensated by activity modulations in the cerebellum, but not in the homologue region contralateral to stimulation

Consumption & class in evolutionary macroeconomics

This article contributes to the field of evolutionary macroeconomics by highlighting the dynamic interlinkages between micro-meso-macro with a Veblenian meso foundation in an agent-based macroeconomic model. Consumption is dependent on endogenously changing social class and signaling, such as bandwagon, Veblen and snob effects. In particular, we test the macroeconomic effects of this meso foundation in a generic agent-based model of a closed artificial economy. The model is stock-flow consistent and builds upon local decision heuristics of heterogeneous agents characterized by bounded rationality and satisficing behavior. These agents include a multitude of households (workers and capitalists), firms, banks as well as a capital goods firm, a government and a central bank. Simulation experiments indicate coevolutionary dynamics between signaling-by-consuming and firm specialization that eventually effect employment and consumer prices, as well as other macroeconomic aggregates

Recapitulation of tumor heterogeneity and molecular signatures in a 3D brain cancer model with decreased sensitivity to histone deacetylase inhibition

INTRODUCTION Physiologically relevant pre-clinical ex vivo models recapitulating CNS tumor micro-environmental complexity will aid development of biologically-targeted agents. We present comprehensive characterization of tumor aggregates generated using the 3D Rotary Cell Culture System (RCCS). METHODS CNS cancer cell lines were grown in conventional 2D cultures and the RCCS and comparison with a cohort of 53 pediatric high grade gliomas conducted by genome wide gene expression and microRNA arrays, coupled with immunohistochemistry, ex vivo magnetic resonance spectroscopy and drug sensitivity evaluation using the histone deacetylase inhibitor, Vorinostat. RESULTS Macroscopic RCCS aggregates recapitulated the heterogeneous morphology of brain tumors with a distinct proliferating rim, necrotic core and oxygen tension gradient. Gene expression and microRNA analyses revealed significant differences with 3D expression intermediate to 2D cultures and primary brain tumors. Metabolic profiling revealed differential profiles, with an increase in tumor specific metabolites in 3D. To evaluate the potential of the RCCS as a drug testing tool, we determined the efficacy of Vorinostat against aggregates of U87 and KNS42 glioblastoma cells. Both lines demonstrated markedly reduced sensitivity when assaying in 3D culture conditions compared to classical 2D drug screen approaches. CONCLUSIONS Our comprehensive characterization demonstrates that 3D RCCS culture of high grade brain tumor cells has profound effects on the genetic, epigenetic and metabolic profiles of cultured cells, with these cells residing as an intermediate phenotype between that of 2D cultures and primary tumors. There is a discrepancy between 2D culture and tumor molecular profiles, and RCCS partially re-capitulates tissue specific features, allowing drug testing in a more relevant ex vivo system

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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Національно-демократичні об'єднання та політичні партії в Україні кінця XIX - початку XX століття

Deep brain stimulation (DBS) has become increasingly important for the treatment and relief of neurological disorders such as Parkinson's disease, tremor, dystonia and psychiatric illness. As DBS implantations and any other stereotactic and functional surgical procedure require accurate, precise and safe targeting of the brain structure, the technical aids for preoperative planning, intervention and postoperative follow-up have become increasingly important. The aim of this paper was to give and overview, from a biomedical engineering perspective, of a typical implantation procedure and current supporting techniques. Furthermore, emerging technical aids not yet clinically established are presented. This includes the state-of-the-art of neuroimaging and navigation, patient-specific simulation of DBS electric field, optical methods for intracerebral guidance, movement pattern analysis, intraoperative data visualisation and trends related to new stimulation devices. As DBS surgery already today is an important technology intensive domain, an "intuitive visualisation" interface for improving management of these data in relation to surgery is suggested