Auditory tasks for assessment of sensory function and affective prosody in schizophrenia

Schizophrenia patients exhibit impairments in auditory-based social cognition, indicated by deficits in detection of prosody, such as affective prosody and basic pitch perception. However, little is known about the psychometric properties of behavioral tests used to assess these functions. The goal of this paper is to characterize the properties of prosody and pitch perception tasks and to investigate whether they can be shortened. The pitch perception test evaluated is a tone-matching task developed by Javitt and colleagues (J-TMT). The prosody test evaluated is the auditory emotion recognition task developed by Juslin and Laukka (JL-AER). The sample includes 124 schizophrenia patients (SZ) and 131 healthy controls (HC). Properties, including facility and discrimination, of each item were assessed. Effects of item characteristics (e.g., emotion) were also evaluated. Shortened versions of the tests are proposed based on facility, discrimination, and/or ability of item characteristics to discriminate between patients and controls. Test–retest reliability is high for patients and controls for both the original and short forms of the J-TMT and JL-AER. Thus, the original as well as short forms of the J-TMT and JL-AER are suggested for inclusion in clinical trials of social cognitive and perceptual treatments. The development of short forms further increases the utility of these auditory tasks in clinical trials and clinical practice. The large SZ vs. HC differences reported here also highlight the profound nature of auditory deficits and a need for remediation.     

Factor Structure of Autistic Traits in Children with ADHD

Attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) often co-occur. Factor analyses of ASD traits in children with and without ASD indicate the presence of social and restrictive–repetitive behaviour (RRB) factors. This study used exploratory factor analyses to determine the structure of ASD traits (assessed using the Social Communication Questionnaire) in children with ADHD. Distinct factors were observed for ‘social’ and ‘rigidity’ traits, corresponding to previous factor analyses in clinical ASD and population samples. This indicates that the split between social-communicative and RRB dimensions is unaffected by ADHD in children. Moreover, the study also finds that there is some overlap across hyperactive-impulsive symptoms and RRB traits in children with ADHD, which merits further investigation.     

Emotional Control,Styles of Coping with Stress and Acceptance of Illness among Patients Suffering from Chronic Somatic Diseases

The purpose of this study was to analyse the associations of emotional control with sociodemographic and clinical variables in a sample of patients with a range of chronic somatic diseases. The relationships between emotional control, coping styles and adjustment to the disease were investigated. The sample consisted of 300 patients with the mean age of 54.60 ± 17.57 years. Courtauld Emotional Control Scale was used to measure the patients' tendency to suppress negative emotions, Coping Inventory for Stressful Situations was used to measure coping styles and Acceptance of Illness Scale was applied to determine adjustment to the disease. Patients with neurological conditions showed significantly lower suppression of anger. Levels of emotional control were found to be related to gender, age and educational level but not to the place of residence. Task‐oriented style of coping with stress correlated positively with suppression of depression and anxiety, whereas acceptance of illness correlated negatively with suppression of anger. Levels of emotional control are only weakly related to the type of diagnosis; however, some clinical samples may show lower suppression of anger. Suppression of negative emotions is weakly related to adjustment indicators such as certain coping styles and acceptance of illness. Copyright © 2013 John Wiley & Sons, Ltd.     

Identification of the 11-cis-specific retinyl-ester synthase in retinal Müller cells as multifunctional O-acyltransferase (MFAT)

Absorption of a photon by a rhodopsin or cone-opsin pigment isomerizes its 11-cis-retinaldehyde (11-cis-RAL) chromophore to all-trans-retinaldehyde (all-trans-RAL), which dissociates after a brief period of activation. Light sensitivity is restored to the resulting apo-opsin when it recombines with another 11-cis-RAL. Conversion of all-trans-RAL to 11-cis-RAL is carried out by an enzyme pathway called the visual cycle in cells of the retinal pigment epithelium. A second visual cycle is present in Müller cells of the retina. The retinol isomerase for this noncanonical pathway is dihydroceramide desaturase (DES1), which catalyzes equilibrium isomerization of retinol. Because 11-cis-retinol (11-cis-ROL) constitutes only a small fraction of total retinols in an equilibrium mixture, a subsequent step involving selective removal of 11-cis-ROL is required to drive synthesis of 11-cis-retinoids for production of visual chromophore. Selective esterification of 11-cis-ROL is one possibility. Crude homogenates of chicken retinas rapidly convert all-trans-ROL to 11-cis-retinyl esters (11-cis-REs) with minimal formation of other retinyl-ester isomers. This enzymatic activity implies the existence of an 11-cis-specific retinyl-ester synthase in Müller cells. Here, we evaluated multifunctional O-acyltransferase (MFAT) as a candidate for this 11-cis-RE-synthase. MFAT exhibited much higher catalytic efficiency as a synthase of 11-cis-REs versus other retinyl-ester isomers. Further, we show that MFAT is expressed in Müller cells. Finally, homogenates of cells coexpressing DES1 and MFAT catalyzed the conversion of all-trans-ROL to 11-cis-RP, similar to what we observed with chicken-retina homogenates. MFAT is therefore an excellent candidate for the retinyl-ester synthase that cooperates with DES1 to drive synthesis of 11-cis-retinoids by mass action.Light perception begins with the absorption of a photon by an opsin pigment in the membranous outer segment (OS) of a rod or cone photoreceptor cell. The light-absorbing chromophore in most vertebrate opsins is 11-cis-retinaldehyde (11-cis-RAL). Photon capture isomerizes the 11-cis-RAL to all-trans-retinaldehyde (all-trans-RAL), inducing conformational changes in the protein that lead to its active meta-II state. After a brief period of signaling through the transduction cascade, meta II decays to yield apo-opsin and free all-trans-RAL. Light sensitivity is restored to the apo-opsin when it combines with 11-cis-RAL to regenerate the pigment. Conversion of all-trans-RAL to 11-cis-RAL is carried out by a multistep enzyme pathway called the visual cycle, located in cells of the retinal pigment epithelium (RPE) (1, 2). The retinoid isomerase in this pathway is Rpe65, which converts an all-trans-retinyl ester (all-trans-RE), such as all-trans-retinyl palmitate (all-trans-RP), to 11-cis-retinol (11-cis-ROL) and a free fatty acid (3–5). Retinyl esters are synthesized in RPE cells by lecithin:retinol acyl transferase (LRAT), which transfers a fatty acid from phosphatidylcholine to retinol (6, 7). LRAT converts both all-trans-ROL and 11-cis-ROL to their cognate esters with similar catalytic efficiency (8).A second visual cycle is present in Müller cells of the retina, providing 11-cis-ROL to cones (9–11). Cones, but not rods, can use 11-cis-ROL as a chromophore precursor to regenerate bleached opsin pigments (10, 12, 13). The isomerase in the noncanonical pathway is dihydroceramide desaturase (DES1) (11). DES1 catalyzes rapid equilibrium isomerization of retinol (11). At equilibrium, 11-cis-ROL is much less abundant than all-trans-ROL, due to the 4.1 kcal/mole difference in free energy between these isomers (14). Accordingly, a secondary source of energy is required to drive the conversion of all-trans-ROL to 11-cis-ROL by DES1. Retinas from cone-dominant species contain 11-cis-retinyl esters (11-cis-REs), whereas retinyl esters are much less abundant in retinas from rod-dominant species (11, 13, 15). Homogenates from cone-dominant chicken and ground-squirrel retinas convert all-trans-ROL predominantly to 11-cis-REs in the presence of palmitoyl CoA (palm CoA) (13, 16, 17). These observations suggest that selective esterification of 11-cis-ROL may be the driving force for 11-cis-retinoid formation. In the current work, we sought to identify the protein responsible for the 11-cis-RE-synthase activity in Müller cells. We evaluated multifunctional O-acyltransferase (MFAT) as a candidate for this synthase. MFAT, also called acyl-CoA wax-alcohol acyltransferase-2 (AWAT2), catalyzes palm CoA-dependent synthesis of triglycerides, wax monoesters, and retinyl esters (18). It is present in the endoplasmic reticulum and predominantly expressed in skin (18). The retinol-isomer specificity of MFAT, and its expression in ocular tissues, has not been studied.     

Functional traits explain variation in plant life history strategies

Ecologists seek general explanations for the dramatic variation in species abundances in space and time. An increasingly popular solution is to predict species distributions, dynamics, and responses to environmental change based on easily measured anatomical and morphological traits. Trait-based approaches assume that simple functional traits influence fitness and life history evolution, but rigorous tests of this assumption are lacking, because they require quantitative information about the full lifecycles of many species representing different life histories. Here, we link a global traits database with empirical matrix population models for 222 species and report strong relationships between functional traits and plant life histories. Species with large seeds, long-lived leaves, or dense wood have slow life histories, with mean fitness (i.e., population growth rates) more strongly influenced by survival than by growth or fecundity, compared with fast life history species with small seeds, short-lived leaves, or soft wood. In contrast to measures of demographic contributions to fitness based on whole lifecycles, analyses focused on raw demographic rates may underestimate the strength of association between traits and mean fitness. Our results help establish the physiological basis for plant life history evolution and show the potential for trait-based approaches in population dynamics.Recent evidence for global patterns of functional variation in plants, such as the leaf economics spectrum (1, 2), the wood economics spectrum (3), and the seed size–seed number tradeoff (4, 5), has convinced many ecologists that functional traits offer the best available approach for achieving a general predictive understanding of communities and ecosystems (6, 7). Trait-based approaches are now being used to predict the outcome of community assembly (8–10), global vegetation dynamics (11), and the rate of ecosystem processes (6, 12–14). A central assumption of trait-based ecology is that morphological traits determine physiological performance, which influences vital rates and determines individual fitness and life history evolution (15, 16). However, because of the challenge of quantifying the contribution of traits to fitness, the assumed links between functional traits and life history have not been fully tested.Research in tropical and Mediterranean forests has revealed cross-species relationships between functional traits and the survival and growth rates of individuals (3, 17–24). Although these relationships provide evidence that functional traits influence vital rates, they offer only limited insight into associations between those traits and individual fitness and life history. Vital rates (e.g., survival and fecundity) represent fitness components, but their influence on mean fitness, defined as the population growth rate (λ), is best understood in the context of the full lifecycle of a species (25, 26). A significant negative correlation between wood density and individual growth (18) might not translate into a significant effect on mean fitness if individual growth has little influence on λ. Conversely, a weak relationship between a functional trait and another vital rate could have a significant effect on mean fitness if that vital rate has a strong influence on λ. Perturbation analyses, such as the sensitivities and elasticities frequently applied to matrix projection models (27), address this problem by quantifying the contribution of vital rates to λ (28), making it possible to characterize a species'' overall life history in terms of the relative importance of survival, individual growth, and fecundity to mean fitness. Species with slow life histories have population growth rates with high elasticities to survival, whereas species with fast life histories have relatively higher elasticities to individual growth or fecundity (29, 30).Armed with vital rate elasticities, we can test quantitative hypotheses about whether functional tradeoffs scale up to generate life history tradeoffs. For example, plants can allocate their reproductive effort to provision a few large seeds, which tolerate low light and resource availability and have a high survival probability, or they can spread their reproductive effort among many small seeds, maximizing fitness under high resource availability (31, 32). If this functional tradeoff at the seedling stage translates into a life history tradeoff, seed mass should be positively related to the elasticity of the population growth rate to survival and negatively related to elasticities to individual growth and fecundity. The leaf economics spectrum represents another allocation tradeoff. Species can construct long-lived, well-defended leaves that are often favored in low resource environments or build leaves that assimilate carbon quickly under conditions of high resource availability but are prone to rapid tissue loss (1, 33). Species with slow leaf economics traits, such as long leaf lifespans, low specific leaf area (SLA), and low leaf N, might also lead slow lives, characterized by high elasticities to survival and low elasticities to individual growth and recruitment. A wood economics spectrum also exists: species with dense wood tend to have higher survival but lower relative growth rates than species with soft wood (3, 34). Elasticities to survival should increase with wood density, whereas elasticities to individual growth and fecundity should decrease.The main obstacle in testing these hypotheses is availability of the detailed demographic data necessary to describe a species’ full lifecycle and estimate vital rate elasticities. We overcame this limitation by crossing the TRY Global Plant Traits Database (35) with the COMPADRE Plant Matrix Database (www.compadre-db.org/), a collection of published matrix population models. This approach produced a dataset of 222 plant species spanning a global range of biomes and perennial growth forms (Table S1), for which we have at least one functional trait measurement as well as a matrix population model that we used to calculate the elasticity of the population growth rate to each of the three vital rates: survival, growth, and fecundity (30).Our primary objective was to evaluate the ability of functional traits to explain variation across species in life history, which we quantified with vital rate elasticities. Our secondary objective was to evaluate whether inferences about life history can be drawn directly from the raw vital rates, which would save researchers the considerable time and effort required to parameterize population models and calculate elasticities. We used two statistical approaches to quantify relationships between vital rate elasticities and seed mass, wood density, and leaf economics traits (leaf lifespan, SLA, and leaf N). Dirichlet regression is a multivariate approach that accounts for the fact that the survival, growth, and fecundity elasticities for each species sum to one but does not account for phylogenetic relationships. Phylogenetic generalized least squares (PGLS) regression ignores the nonindependence of the elasticities but accounts for phylogenetic relationships. We repeated both types of regressions with plant growth form and then biome included as covariates to confirm that trait effects did not simply represent differences between trees and herbaceous species or plants adapted to different environments.     

Lnk controls mouse hematopoietic stem cell self-renewal and quiescence through direct interactions with JAK2

In addition to its role in megakaryocyte production, signaling initiated by thrombopoietin (TPO) activation of its receptor, myeloproliferative leukemia virus protooncogene (c-Mpl, or Mpl), controls HSC homeostasis and self-renewal. Under steady-state conditions, mice lacking the inhibitory adaptor protein Lnk harbor an expanded HSC pool with enhanced self-renewal. We found that HSCs from Lnk-/- mice have an increased quiescent fraction, decelerated cell cycle kinetics, and enhanced resistance to repeat treatments with cytoablative 5-fluorouracil in vivo compared with WT HSCs. We further provide genetic evidence demonstrating that Lnk controls HSC quiescence and self-renewal, predominantly through Mpl. Consistent with this observation, Lnk-/- HSCs displayed potentiated activation of JAK2 specifically in response to TPO. Biochemical experiments revealed that Lnk directly binds to phosphorylated tyrosine residues in JAK2 following TPO stimulation. Of note, the JAK2 V617F mutant, found at high frequencies in myeloproliferative diseases, retains the ability to bind Lnk. Therefore, we identified Lnk as a physiological negative regulator of JAK2 in stem cells and TPO/Mpl/JAK2/Lnk as a major regulatory pathway in controlling stem cell self-renewal and quiescence.