Making Sense Of Blood-based Proteomics And Metabolomics In Psychiatric Research.

This manuscript describes the basics of proteomic and metabolic profiling of blood serum and plasma from patients with psychiatric disorders. It will also explain the rationale behind the use of these body fluids due to need for user friendly and rapid tests in the clinic with simple sampling procedures. It has emerged over the last 15 years or so that psychiatric disorders are whole body diseases and the bloodstream is a means of molecular transport and therefore provides a conduit for two way communication with the brain. Here we also describe some of the basic biomarker findings from studies of serum or plasma from patients with psychiatric disorders like schizophrenia, major depression and bipolar disorder. Finally, we will discuss potential future advancements in this area which includes the development of held devices containing miniature proteomic and metabolic assays which can be used for facilitating diagnosis in a point-of-care setting and yield results in less than 15 minutes from a single drop of blood

The L^2 geometry of spaces of harmonic maps S^2 -> S^2 and RP^2 -> RP^2

Harmonic maps from S^2 to S^2 are all weakly conformal, and so are represented by rational maps. This paper presents a study of the L^2 metric gamma on M_n, the space of degree n harmonic maps S^2 -> S^2, or equivalently, the space of rational maps of degree n. It is proved that gamma is Kaehler with respect to a certain natural complex structure on M_n. The case n=1 is considered in detail: explicit formulae for gamma and its holomorphic sectional, Ricci and scalar curvatures are obtained, it is shown that the space has finite volume and diameter and codimension 2 boundary at infinity, and a certain class of Hamiltonian flows on M_1 is analyzed. It is proved that \tilde{M}_n, the space of absolute degree n (an odd positive integer) harmonic maps RP^2 -> RP^2, is a totally geodesic Lagrangian submanifold of M_n, and that for all n>1, \tilde{M}_n is geodesically incomplete. Possible generalizations and the relevance of these results to theoretical physics are briefly discussed.Comment: 27 pages, 2 figure

The quantum brachistochrone problem for non-Hermitian Hamiltonians

Recently Bender, Brody, Jones and Meister found that in the quantum brachistochrone problem the passage time needed for the evolution of certain initial states into specified final states can be made arbitrarily small, when the time-evolution operator is taken to be non-Hermitian but PT-symmetric. Here we demonstrate that such phenomena can also be obtained for non-Hermitian Hamiltonians for which PT-symmetry is completely broken, i.e. dissipative systems. We observe that the effect of a tunable passage time can be achieved by projecting between orthogonal eigenstates by means of a time-evolution operator associated with a non-Hermitian Hamiltonian. It is not essential that this Hamiltonian is PT-symmetric

A scan for genes associated with cancer mortality and longevity in pedigree dog breeds.

Selective breeding of the domestic dog (Canis lupus familiaris) rigidly retains desirable features, and could inadvertently fix disease-causing variants within a breed. We combine phenotypic data from > 72,000 dogs with a large genotypic dataset to search for genes associated with cancer mortality and longevity in pedigree dog breeds. We validated previous findings that breeds with higher average body weight have higher cancer mortality rates and lower life expectancy. We identified a significant positive correlation between life span and cancer mortality residuals corrected for body weight, implying that long-lived breeds die more frequently from cancer compared to short-lived breeds. We replicated a number of known genetic associations with body weight (IGF1, GHR, CD36, SMAD2 and IGF2BP2). Subsequently, we identified five genetic variants in known cancer-related genes (located within SIPA1, ADCY7 and ARNT2) that could be associated with cancer mortality residuals corrected for confounding factors. One putative genetic variant was marginally significantly associated with longevity residuals that had been corrected for the effects of body weight; this genetic variant is located within PRDX1, a peroxiredoxin that belongs to an emerging class of pro-longevity associated genes. This research should be considered as an exploratory analysis to uncover associations between genes and longevity/cancer mortality

Identification of proteomic signatures associated with depression and psychotic depression in post-mortem brains from major depression patients

Major depressive disorder (MDD) is a leading cause of disability worldwide and results tragically in the loss of almost one million lives in Western societies every year. This is due to poor understanding of the disease pathophysiology and lack of empirical medical tests for accurate diagnosis or for guiding antidepressant treatment strategies. Here, we have used shotgun proteomics in the analysis of post-mortem dorsolateral prefrontal cortex brain tissue from 24 MDD patients and 12 matched controls. Brain proteomes were pre-fractionated by gel electrophoresis and further analyzed by shotgun data-independent label-free liquid chromatography-mass spectrometry. This led to identification of distinct proteome fingerprints between MDD and control subjects. Some of these differences were validated by Western blot or selected reaction monitoring mass spectrometry. This included proteins associated with energy metabolism and synaptic function and we also found changes in the histidine triad nucleotide-binding protein 1 (HINT1), which has been implicated recently in regulation of mood and behavior. We also found differential proteome profiles in MDD with (n=11) and without (n=12) psychosis. Interestingly, the psychosis fingerprint showed a marked overlap to changes seen in the brain proteome of schizophrenia patients. These findings suggest that it may be possible to contribute to the disease understanding by distinguishing different subtypes of MDD based on distinct brain proteomic profiles

Design of three dimensional isotropic microstructures for maximized stiffness and conductivity

The level-set method of topology optimization is used to design isotropic two-phase periodic multifunctional composites in three dimensions. One phase is stiff and insulating whereas the other is conductive and mechanically compliant. The optimization objective is to maximize a linear combination of the effective bulk modulus and conductivity of the composite. Composites with the Schwartz primitive and diamond minimal surfaces as the phase interface have been shown to have maximal bulk modulus and conductivity. Since these composites are not elastically isotropic their stiffness under uniaxial loading varies with the direction of the load. An isotropic composite is presented with similar conductivity which is at least 23% stiffer under uniaxial loading than the Schwartz structures when loaded uniaxially along their weakest direction. Other new near-optimal isotropic composites are presented, proving the capablities of the level-set method for microstructure design.Comment: 25 pages, 11 figures, to be submitted to International Journal of Solids and Structure

Targeting the Poor in Rural Java

Summaries This article examines the regional and household characteristics of poverty in rural Java to assess the efficacy of targeted anti?poverty programmes. Analysis of household data shows important geographic and spatial features to rural poverty in Java. However, it also highlights the limitations of geographic targeting; 43 per cent of remaining poor in rural Java live in non?poor regions. The article suggests that an effective anti?poverty strategy for rural Java would focus on continued broad?based growth, judicious use of geographic targeting, and special efforts to enhance the poor's access to productive assets, regardless of where they live

The effects of stress on hypothalamic-pituitary-adrenal (HPA) axis function in subjects with schizophrenia

Nas últimas décadas, têm surgido evidências sugerindo que a patogênese de desordens psiquiátricas, tais como a esquizofrenia, pode envolver perturbações no eixo hipotalâmico-pituitário-adrenal (HPA). Variações na manifestação desses efeitos poderiam estar relacionadas a diferenças em sintomas clínicos entre os indivíduos afetados, assim como a diferenças na resposta ao tratamento. Tais efeitos podem também ser originados de complexas interações entre genes e fatores ambientais. Aqui, revisamos os efeitos do estresse maternal em anormalidades na regulação do eixo HPA e desenvolvimento de desordens psiquiátricas, incluindo a esquizofrenia. Estudos nessa área podem gerar o aumento do nosso entendimento da natureza multidimensional da esquizofrenia. Posterior pesquisa nesse campo poderia, em última instância, levar ao desenvolvimento de melhores diagnósticos e novas abordagens terapêuticas para essa debilitante condição psiquiátrica.Over the last few decades, evidence has been emerging that the pathogenesis of psychiatric disorders such as schizophrenia can involve perturbations of the hypothalamic-pituitary-adrenal (HPA) axis. Variations in the manifestation of these effects could be related to the differences in clinical symptoms between affected individuals as well as to differences in treatment response. Such effects can also arise from the complex interaction between genes and environmental factors. Here, we review the effects of maternal stress on abnormalities in HPA axis regulation and the development of psychiatric disorders including schizophrenia. Studies in this area may prove critical for increasing our understanding of the multi-dimensional nature of schizophrenia. Further research in this area could ultimately lead to the development of improved diagnostics and novel therapeutic approaches for treating this debilitating psychiatric condition

Knowledge acquisition and effective socialization: the role of the psychological contract

Although studies reveal that acquiring knowledge about a new workplace during organizational socialization leads to better integration, the pathway through which this occurs is not well understood. Previous research has explored the psychological contract as an outcome of socialization. This study explores its role within the socialization process. A total of 161 organizational newcomers undertook surveys at months one and three of tenure, with data used to test a model within which four psychological contract dimensions mediate the relationship between knowledge acquisition and employee outcomes. At month one, organizational and employee promise strength mediated the relationship between knowledge and outcomes. At month three, organizational and employee promise fulfilment mediated this relationship. Findings confirm the role of the psychological contract in the socialization process and suggest that effective integration requires extensive knowledge provision and active employee knowledge acquisition. Practitioner points Acquisition of knowledge about a new work environment during the very early stages of tenure can positively affect newcomers’ attitudes and perceived employment relationships. Learning leads to mutual promises that are perceived to be stronger and more likely to be fulfilled, as well as reduced stress, greater commitment, and greater service quality behaviour. Employers should provide newcomers with information about their role, team, and organization, whilst newcomers should be encouraged to ask questions

On the shopfloor: exploring the impact of teacher trade unions on school-based industrial relations

Teachers are highly unionised workers and their trade unions exert an important influence on the shaping and implementation of educational policy. Despite this importance there is relatively little analysis of the impact of teacher trade unions in educational management literature. Very little empirical research has sought to establish the impact of teacher unions at school level. In an era of devolved management and quasi-markets this omission is significant. New personnel issues continue to emerge at school level and this may well generate increased trade union activity at the workplace. This article explores the extent to which devolved management is drawing school-based union representation into a more prominent role. It argues that whilst there can be significant differences between individual schools, increased school autonomy is raising the profile of trade union activity in the workplace, and this needs to be better reflected in educational management research