Polygenic overlap between schizophrenia risk and antipsychotic response: a genomic medicine approach

Therapeutic treatments for schizophrenia do not alleviate symptoms for all patients and efficacy is limited by common, often severe, side-effects. Genetic studies of disease can identify novel drug targets, and drugs for which the mechanism has direct genetic support have increased likelihood of clinical success. Large-scale genetic studies of schizophrenia have increased the number of genes and gene sets associated with risk. We aimed to examine the overlap between schizophrenia risk loci and gene targets of a comprehensive set of medications to potentially inform and improve treatment of schizophrenia

Water vapor and the dynamics of climate changes

Water vapor is not only Earth's dominant greenhouse gas. Through the release of latent heat when it condenses, it also plays an active role in dynamic processes that shape the global circulation of the atmosphere and thus climate. Here we present an overview of how latent heat release affects atmosphere dynamics in a broad range of climates, ranging from extremely cold to extremely warm. Contrary to widely held beliefs, atmospheric circulation statistics can change non-monotonically with global-mean surface temperature, in part because of dynamic effects of water vapor. For example, the strengths of the tropical Hadley circulation and of zonally asymmetric tropical circulations, as well as the kinetic energy of extratropical baroclinic eddies, can be lower than they presently are both in much warmer climates and in much colder climates. We discuss how latent heat release is implicated in such circulation changes, particularly through its effect on the atmospheric static stability, and we illustrate the circulation changes through simulations with an idealized general circulation model. This allows us to explore a continuum of climates, constrain macroscopic laws governing this climatic continuum, and place past and possible future climate changes in a broader context.Comment: 22 pages, 11 figure

Dopamine receptor alterations in female rats with diet-induced decreased brain docosahexaenoic acid (DHA): interactions with reproductive status

Decreased tissue levels of n-3 (omega-3) fatty acids, particularly docosahexaenoic acid (DHA), are implicated in the etiologies of non-puerperal and postpartum depression. This study examined the effects of a diet-induced loss of brain DHA content and concurrent reproductive status on dopaminergic parameters in adult female Long–Evans rats. An α-linolenic acid-deficient diet and breeding protocols were used to produce virgin and parous female rats with cortical phospholipid DHA levels 20–22% lower than those fed a control diet containing adequate α-linolenic acid. Decreased brain DHA produced a significant main effect of decreased density of ventral striatal D2-like receptors. Virgin females with decreased DHA also exhibited higher density of D1-like receptors in the caudate nucleus than virgin females with normal DHA. These receptor alterations are similar to those found in several rodent models of depression, and are consistent with the proposed hypodopaminergic basis for anhedonia and motivational deficits in depression

Systemic hormonal and physiological abnormalities in anxiety disorders

Among the studies of systemic hormonal and physiological abnormalities associated with anxiety disorders, the most consistent and extensive findings suggest (a) peripheral adrenergic hyperactivity (including increases in norepinephrine but not epinephrine) and functional dysregulation, (b) increased incidence of mitral valve prolapse in panic patients, and (c) normal suppressibility of the hypothalamic-pituitary-adrenal cortical endocrine system with dexamethasone in panic patients. Other less-certain findings include (a) increased circulating concentrations of plasma ACTH and/or cortisol, and prolactin, in panic patients, (b) increased platelet monoamine oxidase activity in generalized anxiety and/or panic patients, (c) decreased gonadal axis activity in some anxious individuals, (d) decreased nighttime melatonin plasma concentrations in panic patients, and (e) peripheral [alpha]2 and [beta]-adrenoreceptor down-regulation, with normal serotonin binding parameters. These findings, taken together, provide tentative support for dysfunction in adrenergic and GABAergic central nervous system mechanisms in people with anxiety disorders. Abnormal anxiety and normal stress both show evidence of adrenergic hyperactivity; however, there appear to be differences in hormonal profiles, especially the apparent lack of increase of epinephrine during panic attacks, as well as differences in the reactivity of the system, and in the "trigger" mechanisms which determine when the response occurs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27526/1/0000570.pd

Creativity and commerce: Michael Klinger and new film history

The crisis in film studies and history concerning their legitimacy and objectives has provoked a reinvigoration of scholarly energy in historical enquiry. 'New film history' attempts to address the concerns of historians and film scholars by working self-reflexively with an expanded range of sources and a wider conception of 'film' as a dynamic set of processes rather than a series of texts. The practice of new film history is here exemplified through a detailed case study of the independent British producer Michael Klinger (active 1961-87) with a specific focus on his unsuccessful attempt to produce a war film, Green Beach, based on a memoir of the Dieppe raid (August 1942). This case study demonstrates the importance of analysing the producer's role in understanding the complexities of film-making, the continual struggle to balance the competing demands of creativity and commerce. In addition, its subject matter - an undercover raid and a Jewish hero - disturbed the dominant myths concerning the Second World War, creating what turned out to be intractable ideological as well as financial problems. The paper concludes that the concerns of film historians need to engage with broader cultural and social histories. © 2010 Taylor & Francis

Multi vegetation model evaluation of the Green Sahara climate regime

During the Quaternary, the Sahara desert was periodically colonized by vegetation, likely because of orbitally induced rainfall increases. However, the estimated hydrological change is not reproduced in climate model simulations, undermining confidence in projections of future rainfall. We evaluated the relationship between the qualitative information on past vegetation coverage and climate for the mid-Holocene using three different dynamic vegetation models. Compared with two available vegetation reconstructions, the models require 500–800 mm of rainfall over 20°–25°N, which is significantly larger than inferred from pollen but largely in agreement with more recent leaf wax biomarker reconstructions. The magnitude of the response also suggests that required rainfall regime of the early to middle Holocene is far from being correctly represented in general circulation models. However, intermodel differences related to moisture stress parameterizations, biases in simulated present-day vegetation, and uncertainties about paleosoil distributions introduce uncertainties, and these are also relevant to Earth system model simulations of African humid periods

Urbanisation affects ecosystem functioning more than structure in tropical streams

Urbanisation poses a clear threat to tropical freshwater streams, yet fundamental knowledge gaps hinder our ability to effectively conserve stream biodiversity and preserve ecosystem functioning. Here, we studied the impact of urbanisation on structural and functional ecosystem responses in low-order streams in Singapore, a tropical city with a mosaic landscape of protected natural forests, managed buffer zones (between forest and open-country habitats), and built-up urban areas. We quantified an urbanisation gradient based on landscape, in-stream, and riparian conditions, and found an association between urbanisation and pollution-tolerant macroinvertebrates (e.g. freshwater snail and worm species) in litter bags. We also found greater macroinvertebrate abundance (mean individuals bag−1; forest: 30.3, buffer: 70.1, urban: 109.0) and richness (mean taxa bag−1; forest: 4.53, buffer: 4.75, urban: 7.50) in urban streams, but similar diversity across habitats. Higher levels of primary productivity (measured from algal accrual on ceramic tiles) and microbial decomposition (measured from litter-mass loss in mesh bags) at urban sites indicate rapid microbial activity at higher light, temperature, and nutrient levels. We found that urbanisation affected function 32% more than structure in the studied tropical streams, likely driven by greater algal growth in urban streams. These changes in ecological processes (i.e. ecosystem functioning) possibly lead to a loss of ecosystem services, which would negatively affect ecology, society, and economy. Our results point to possible management strategies (e.g. increasing vegetation density through buffer park creation) to reduce the impacts of urbanisation, restore vital ecosystem functions in tropical streams, and create habitat niches for native species