Intermolecular Vibrations in Liquid Secondary Chlorides

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69573/2/JCPSA6-52-8-4316-1.pd

A facile one pot synthetic approach for C3N4-ZnS composite interfaces as heterojunctions for sunlight-induced multifunctional photocatalytic applications

Herein, we report a facile one pot synthetic protocol for the creation of C3N4-ZnS composite interfaces by the co-pyrolysis of a precursor mix containing zinc nitrate, melamine, and thiourea at 550°C in air. The organic-inorganic semiconductor heterojunctions thus formed displayed increased absorbance in the longer wavelength region and facilitated broad absorption of visible light compared to pure ZnS, C3N4 and conventionally synthesized hybrid samples. The decreased emission intensity, increased photocurrent generation and decreased fluorescence lifetime revealed reduced exciton recombinations in the co-pyrolysed sample containing C3N4-ZnS heterostructures. The samples displayed sunlight driven photocatalytic reduction of nitrophenol as well as hydrogen generation (4 mmol g-1 h-1) by water splitting. © The Royal Society of Chemistry 2016

Assignment of torsion and low frequency bending vibrations of secondary chlorides

Far infrared and Raman spectra of 2-chloropropane, 2-chlorobutane and dl- and meso-2,4-dichloropentane have been analyzed in order to assign the torsional force constants in the valence force field for secondary chlorides. Band assignments have been based on experimental data as well as preliminary normal vibration calculations. With incorporation of torsional force constants, and a global refinement of the force field, the observed low frequency bands of the above molecules, as well as those of 3-chloropentane, are very well accounted for.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33808/1/0000064.pd

Optical determination of flexoelectric coefficients and surface polarization in a hybrid aligned nematic cell

A. Mazzulla, F. Ciuchi, and J. Roy Sambles, Physical Review E, Vol. 64, article 021708 (2001). "Copyright © 2001 by the American Physical Society."We present an optical study of the influence of both the flexoelectric effect and surface polarization on a hybrid-aligned nematic cell using the half-leaky guided mode technique. Tilt angle profiles, obtained from fits of experimental data (reflectivity curves) taken under applied voltages, are compared with the ones derived by a complete theoretical model. Measurements with an applied alternating voltage allow the evaluation of the anchoring energy by solving the torque balance equation at the planar surface. From measurements with static fields, the sum of flexoelectric coefficients and the surface polarization are determined by numerical solution of Euler-Lagrange equations

Gene-environment correlations and causal effects of childhood maltreatment on physical and mental health: a genetically informed approach.

BACKGROUND: Childhood maltreatment is associated with poor mental and physical health. However, the mechanisms of gene-environment correlations and the potential causal effects of childhood maltreatment on health are unknown. Using genetics, we aimed to delineate the sources of gene-environment correlation for childhood maltreatment and the causal relationship between childhood maltreatment and health. METHODS: We did a genome-wide association study meta-analysis of childhood maltreatment using data from the UK Biobank (n=143 473), Psychiatric Genomics Consortium (n=26 290), Avon Longitudinal Study of Parents and Children (n=8346), Adolescent Brain Cognitive Development Study (n=5400), and Generation R (n=1905). We included individuals who had phenotypic and genetic data available. We investigated single nucleotide polymorphism heritability and genetic correlations among different subtypes, operationalisations, and reports of childhood maltreatment. Family-based and population-based polygenic score analyses were done to elucidate gene-environment correlation mechanisms. We used genetic correlation and Mendelian randomisation analyses to identify shared genetics and test causal relationships between childhood maltreatment and mental and physical health conditions. FINDINGS: Our meta-analysis of genome-wide association studies (N=185 414) identified 14 independent loci associated with childhood maltreatment (13 novel). We identified high genetic overlap (genetic correlations 0·24-1·00) among different maltreatment operationalisations, subtypes, and reporting methods. Within-family analyses provided some support for active and reactive gene-environment correlation but did not show the absence of passive gene-environment correlation. Robust Mendelian randomisation suggested a potential causal role of childhood maltreatment in depression (unidirectional), as well as both schizophrenia and ADHD (bidirectional), but not in physical health conditions (coronary artery disease, type 2 diabetes) or inflammation (C-reactive protein concentration). INTERPRETATION: Childhood maltreatment has a heritable component, with substantial genetic correlations among different operationalisations, subtypes, and retrospective and prospective reports of childhood maltreatment. Family-based analyses point to a role of active and reactive gene-environment correlation, with equivocal support for passive correlation. Mendelian randomisation supports a (primarily bidirectional) causal role of childhood maltreatment on mental health, but not on physical health conditions. Our study identifies research avenues to inform the prevention of childhood maltreatment and its long-term effects. FUNDING: Wellcome Trust, UK Medical Research Council, Horizon 2020, National Institute of Mental Health, and National Institute for Health Research Biomedical Research Centre

The genetics of cortical organisation and development: A study of 2,347 neuroimaging phenotypes

Our understanding of the genetic architecture of the human cerebral cortex is limited both in terms of the diversity of brain structural phenotypes and the anatomical granularity of their associations with genetic variants. Here, we conducted genome-wide association meta-analysis of 13 structural and diffusion magnetic resonance imaging derived cortical phenotypes, measured globally and at 180 bilaterally averaged regions in 36,843 individuals from the UK Biobank and the ABCD cohorts. These phenotypes include cortical thickness, surface area, grey matter volume, and measures of folding, neurite density, and water diffusion. We identified 4,349 experiment-wide significant loci associated with global and regional phenotypes. Multiple lines of analyses identified four genetic latent structures and causal relationships between surface area and some measures of cortical folding. These latent structures partly relate to different underlying gene expression trajectories during development and are enriched for different cell types. We also identified differential enrichment for neurodevelopmental and constrained genes and demonstrate that common genetic variants associated with surface area and volume specifically are associated with cephalic disorders. Finally, we identified complex inter-phenotype and inter-regional genetic relationships among the 13 phenotypes which reflect developmental differences among them. These analyses help refine the role of common genetic variants in human cortical development and organisation

Sebomic identification of sex- and ethnicity-specific variations in residual skin surface components (RSSC) for bio-monitoring or forensic applications

Background: “Residual skin surface components” (RSSC) is the collective term used for the superficial layer of sebum, residue of sweat, small quantities of intercellular lipids and components of natural moisturising factor present on the skin surface. Potential applications of RSSC include use as a sampling matrix for identifying biomarkers of disease, environmental exposure monitoring, and forensics (retrospective identification of exposure to toxic chemicals). However, it is essential to first define the composition of “normal” RSSC. Therefore, the aim of the current study was to characterise RSSC to determine commonalities and differences in RSSC composition in relation to sex and ethnicity. Methods: Samples of RSSC were acquired from volunteers using a previously validated method and analysed by high-pressure liquid chromatography–atmospheric pressure chemical ionisation–mass spectrometry (HPLC-APCI-MS). The resulting data underwent sebomic analysis. Results: The composition and abundance of RSSC components varied according to sex and ethnicity. The normalised abundance of free fatty acids, wax esters, diglycerides and triglycerides was significantly higher in males than females. Ethnicity-specific differences were observed in free fatty acids and a diglyceride. Conclusions: The HPLC-APCI-MS method developed in this study was successfully used to analyse the normal composition of RSSC. Compositional differences in the RSSC can be attributed to sex and ethnicity and may reflect underlying factors such as diet, hormonal levels and enzyme expression.Peer reviewedFinal Published versio

Neurodegeneration and Epilepsy in a Zebrafish Model of CLN3 Disease (Batten Disease)

The neuronal ceroid lipofuscinoses are a group of lysosomal storage disorders that comprise the most common, genetically heterogeneous, fatal neurodegenerative disorders of children. They are characterised by childhood onset, visual failure, epileptic seizures, psychomotor retardation and dementia. CLN3 disease, also known as Batten disease, is caused by autosomal recessive mutations in the CLN3 gene, 80–85% of which are a ~1 kb deletion. Currently no treatments exist, and after much suffering, the disease inevitably results in premature death. The aim of this study was to generate a zebrafish model of CLN3 disease using antisense morpholino injection, and characterise the pathological and functional consequences of Cln3 deficiency, thereby providing a tool for future drug discovery. The model was shown to faithfully recapitulate the pathological signs of CLN3 disease, including reduced survival, neuronal loss, retinopathy, axonopathy, loss of motor function, lysosomal storage of subunit c of mitochondrial ATP synthase, and epileptic seizures, albeit with an earlier onset and faster progression than the human disease. Our study provides proof of principle that the advantages of the zebrafish over other model systems can be utilised to further our understanding of the pathogenesis of CLN3 disease and accelerate drug discovery

Childhood abuse v. neglect and risk for major psychiatric disorders

Background. Childhood maltreatment (CM) is a strong risk factor for psychiatric disorders but serves in its current definitions as an umbrella for various fundamentally different childhood experiences. As first step toward a more refined analysis of the impact of CM, our objective is to revisit the relation of abuse and neglect, major subtypes of CM, with symptoms across disorders.Methods. Three longitudinal studies of major depressive disorder (MDD, N = 1240), bipolar disorder (BD, N = 1339), and schizophrenia (SCZ, N = 577), each including controls (N = 881), were analyzed. Multivariate regression models were used to examine the relation between exposure to abuse, neglect, or their combination to the odds for MDD, BD, SCZ, and symptoms across disorders. Bidirectional Mendelian randomization (MR) was used to probe causality, using genetic instruments of abuse and neglect derived from UK Biobank data (N = 143 473).Results. Abuse was the stronger risk factor for SCZ (OR 3.51, 95% CI 2.17-5.67) and neglect for BD (OR 2.69, 95% CI 2.09-3.46). Combined CM was related to increased risk exceeding additive effects of abuse and neglect for MDD (RERI = 1.4) and BD (RERI = 1.1). Across disorders, abuse was associated with hallucinations (OR 2.16, 95% CI 1.55-3.01) and suicide attempts (OR 2.16, 95% CI 1.55-3.01) whereas neglect was associated with agitation (OR 1.24, 95% CI 1.02-1.51) and reduced need for sleep (OR 1.64, 95% CI 1.08-2.48). MR analyses were consistent with a bidirectional causal effect of abuse with SCZ (IVWforward = 0.13, 95% CI 0.01-0.24).Conclusions. Childhood abuse and neglect are associated with different risks to psychiatric symptoms and disorders. Unraveling the origin of these differences may advance understanding of disease etiology and ultimately facilitate development of improved personalized treatment strategies

Large-scale associations between the leukocyte transcriptome and BOLD responses to speech differ in autism early language outcome subtypes.

Heterogeneity in early language development in autism spectrum disorder (ASD) is clinically important and may reflect neurobiologically distinct subtypes. Here, we identified a large-scale association between multiple coordinated blood leukocyte gene coexpression modules and the multivariate functional neuroimaging (fMRI) response to speech. Gene coexpression modules associated with the multivariate fMRI response to speech were different for all pairwise comparisons between typically developing toddlers and toddlers with ASD and poor versus good early language outcome. Associated coexpression modules were enriched in genes that are broadly expressed in the brain and many other tissues. These coexpression modules were also enriched in ASD-associated, prenatal, human-specific, and language-relevant genes. This work highlights distinctive neurobiology in ASD subtypes with different early language outcomes that is present well before such outcomes are known. Associations between neuroimaging measures and gene expression levels in blood leukocytes may offer a unique in vivo window into identifying brain-relevant molecular mechanisms in ASD