Functional genomics of human skeletal development and the patterning of height heritability.

Underlying variation in height are regulatory changes to chondrocytes, cartilage cells comprising long-bone growth plates. Currently, we lack knowledge on epigenetic regulation and gene expression of chondrocytes sampled across the human skeleton, and therefore we cannot understand basic regulatory mechanisms controlling height biology. We first rectify this issue by generating extensive epigenetic and transcriptomic maps from chondrocytes sampled from different growth plates across developing human skeletons, discovering novel regulatory networks shaping human bone/joint development.

Cognitive performance at first episode of psychosis and the relationship with future treatment resistance: Evidence from an international prospective cohort study.

Background: Antipsychotic treatment resistance affects up to a third of individuals with schizophrenia, with recent research finding systematic biological differences between antipsychotic resistant and responsive patients. Our aim was to determine whether cognitive impairment at first episode significantly differs between future antipsychotic responders and resistant cases.

Methods: Analysis of data from seven international cohorts of first-episode psychosis (FEP) with cognitive data at baseline (N = 683) and follow-up data on antipsychotic treatment response: 605 treatment responsive and 78 treatment resistant cases.

Clinical predictors of antipsychotic treatment resistance: Development and internal validation of a prognostic prediction model by the STRATA-G consortium.

Introduction: Our aim was to, firstly, identify characteristics at first-episode of psychosis that are associated with later antipsychotic treatment resistance (TR) and, secondly, to develop a parsimonious prediction model for TR.

Methods: We combined data from ten prospective, first-episode psychosis cohorts from across Europe and categorised patients as TR or non-treatment resistant (NTR) after a mean follow up of 4.18 years (s.

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus.

Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries.

Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions.

Mercury (II) reduction and co-precipitation of metallic mercury on hydrous ferric oxide in contaminated groundwater.

Mercury (Hg) speciation and sorption analyses in contaminated aquifers are useful for understanding transformation, retention, and mobility of Hg in groundwater. In most aquifers hydrous ferric oxides (HFOs) are among the most important sorbents for trace metals; however, their role in sorption or mobilization of Hg in aquifers has been rarely analyzed. In this study, we investigated Hg chemistry and Hg sorption to HFO under changing redox conditions in a highly HgCl2-contaminated aquifer (up to 870μgL(-1) Hg).

Modeling depression in Parkinson disease: disease-specific and nonspecific risk factors.

Objective: To construct a model for depression in Parkinson disease (PD) and to study the relative contribution of PD-specific and nonspecific risk factors to this model.

Methods: Structural equation modeling of direct and indirect associations of risk factors with the latent depression outcome using a cross-sectional dataset of 342 patients with PD.

Results: A model with acceptable fit was generated that explained 41% of the variance in depression.

Distinguishing between roles for calcium in Limulus photoreceptor excitation.

The role for Ca2+ in the excitation process by which light opens membrane channels in Limulus photoreceptors is discussed. Light initiates a phospholipase C/IP3 pathway that results in a rapid elevation of intracellular Ca2+, but whether this elevation is causal in triggering the light response or merely synergistic to some other second messenger pathway has been unclear. We have developed a procedure using progressive injection of Ca2+ buffers that distinguishes between mediation and synergy models [Shin J-H.