Desipramine attenuates working memory impairments induced by partial loss of catecholamines in the rat medial prefrontal cortex

The density of tyrosine hydroxylase-immunoreactive (TH-IR) axons in the prefrontal cortex of schizophrenic subjects may be reduced by as much as 50% in the deep cortical layers (Am J Psychiatry 156:1580–1589, 1999). Previously, we demonstrated that ~60% loss of TH-IR axons in the rat medial prefrontal cortex (mPFC) decreases local basal and stress-evoked extracellular dopamine (DA) concentrations, suggesting that moderate loss of DA axons in the mPFC is sufficient to alter the neurochemical activity of the remaining DA neurons (Neuroscience 93:497–505, 1999).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46372/1/213_2005_Article_221.pd

Effects of a selectively bred novelty-seeking phenotype on the motivation to take cocaine in male and female rats

<p>Abstract</p> <p>Background</p> <p>Gender and enhanced novelty reactivity can predispose certain individuals to drug abuse. Previous research in male and female rats selectively bred for high or low locomotor reactivity to novelty found that bred High Responders (bHRs) acquire cocaine self-administration more rapidly than bred Low Responders (bLRs) and that bHR females in particular self-administered more cocaine than the other groups. The experiments presented here aimed to determine whether an individual's sex and behavioral phenotype interact to affect motivation to take cocaine.</p> <p>Methods</p> <p>We examined motivation for taking cocaine in two experiments using a range of doses on a progressive ratio (PR) schedule of responding in bHR or bLR males and females. Additionally, we included a measure of continuing to respond in the absence of reinforcement, a feature of addiction that has been recently incorporated into tests of animal models on the basis of the criteria for substance use disorder in the <it>Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition</it>. Statistical analyses were performed using PASW Statistics 18.0 software. Data were analyzed using repeated-measures analysis of variance followed by a Bonferroni correction <it>post hoc </it>test when applicable.</p> <p>Results</p> <p>We found sex differences as well as effects of novelty reactivity on the motivation to self-administer cocaine. Specifically, females demonstrated higher breaking points on the PR schedule compared with males, regardless of phenotype, and bHR males and females exhibited higher motivation than bLR animals at a number of the doses studied.</p> <p>Conclusions</p> <p>An individual's sex continues to be a predisposing factor with respect to drug abuse liability and can be compounded by additional individual differences such as reactivity to novelty.</p

Third-Party Effects in Stakeholder Interviews

This paper examines the effect of having a third-party scientific expert present in stakeholder interviews. The study was conducted as part of a larger project on stakeholder engagement for natural resource management in the Verde Valley region of Arizona. We employed an experimental design, conducting stakeholder interviews both with and without an identified scientific expert present. Our sample consisted of 12 pairs of interviewees (24 total participants) who we matched based on their occupation, sex, and spatial proximity. For each pair, the scientific expert was present as a third party in one interview and absent in the other. We used a word-based coding strategy to code all interview responses for three known areas of sensitivity among the study population (risk, gatekeeping, and competence). We then performed both quantitative and qualitative analyses to compare responses across the two interview groups. We found that the presence of a scientific expert did not have a statistically significant effect on the mention of sensitive topics among stakeholders. However, our qualitative results show that the presence of a scientific expert had subtle influences on the ways that stakeholders discussed sensitive topics, particularly in placing emphasis on their own credibility and knowledge. Our findings indicate that researchers may be able to pursue collaborative, interdisciplinary research designs with multiple researchers present during interviews without concerns of strongly influencing data elicitation on sensitive topics. However, researchers should be cognizant of the subtle ways in which the presence of a third-party expert may influence the credibility claims and knowledge assertions made by respondents when a third-party expert is present during stakeholder interviews

Individuals With Scleroderma May Have Increased Risk of Sleep-Disordered Breathing.

STUDY OBJECTIVES:Scleroderma is associated with abnormal skin thickening, interstitial lung disease, pulmonary hypertension, and abnormalities of the upper airway. These changes can cause cardiopulmonary complications, potentially including sleep-disordered breathing. The objective of this study is to examine the risk of sleep-disordered breathing in patients with scleroderma. METHODS:We retrospectively identified patients with documented scleroderma. We abstracted data from their electronic health records, including findings from antibody tests, serial pulmonary function tests, transthoracic echocardiography, high-resolution computed tomography, and overnight forehead oximetry. RESULTS:We identified 171 patients with scleroderma. Mean age at the time of initial consult was 56.5 years (range, 18-96 years), and 150 (86.7%) were women. Scleroderma was categorized as limited disease for 108 (62.4%), diffuse disease for 59 (34.1%), and mixed connective tissue disease for 6 (3.5%). Fifty-four patients (31.2%) had abnormal overnight forehead oximetry results, defined as an oxygen desaturation index greater than 5 or a baseline mean arterial oxygen saturation level less than 90%. CONCLUSIONS:Cardiopulmonary complications are common in patients with scleroderma, one of which may be sleep-disordered breathing. In our cohort, approximately one-third of individuals with scleroderma had evidence of sleep-disordered breathing. Moreover, the rate of sleep-disordered breathing in our population of scleroderma patients was twice the rate of pulmonary hypertension and was approximately the same as the rate of interstitial lung disease. Future prospective studies are needed to further assess the role of sleep-disordered breathing in scleroderma clinical outcomes

Selective Breeding for Divergence in Novelty-seeking Traits: Heritability and Enrichment in Spontaneous Anxiety-related Behaviors

Outbred Sprague–Dawley rats can be classified as high responders (HR) or low responders (LR) based on their levels of exploratory locomotion in a novel environment. While this novelty-seeking dimension was originally related to differential vulnerability to substance abuse, behavioral, neuroendocrine and gene expression studies suggest a fundamental difference in emotional reactivity between these animals. Here, we report the first study to selectively breed rats based on this novelty-seeking dimension. Response to novelty was clearly heritable, with a >2-fold difference in behavior seen after eight generations of selection. Three tests of anxiety-like behavior consistently showed significantly greater anxiety in LR-bred rats compared to HR-bred animals, and this difference was diminished in the open field test by administration of the anxiolytic benzodiazepine drug, chlordiazepoxide. Cross-fostering revealed that responses to novelty were largely unaffected by maternal interactions, though there was an effect on anxiety-like behavior. These selected lines will enable future research on the interplay of genetic, environmental and developmental variables in controlling drug seeking behavior, stress and emotional reactivity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42783/1/10519_2006_Article_9058.pd

Strategies and methods to study sex differences in cardiovascular structure and function: a guide for basic scientists

<p>Abstract</p> <p>Background</p> <p>Cardiovascular disease remains the primary cause of death worldwide. In the US, deaths due to cardiovascular disease for women exceed those of men. While cultural and psychosocial factors such as education, economic status, marital status and access to healthcare contribute to sex differences in adverse outcomes, physiological and molecular bases of differences between women and men that contribute to development of cardiovascular disease and response to therapy remain underexplored.</p> <p>Methods</p> <p>This article describes concepts, methods and procedures to assist in the design of animal and tissue/cell based studies of sex differences in cardiovascular structure, function and models of disease.</p> <p>Results</p> <p>To address knowledge gaps, study designs must incorporate appropriate experimental material including species/strain characteristics, sex and hormonal status. Determining whether a sex difference exists in a trait must take into account the reproductive status and history of the animal including those used for tissue (cell) harvest, such as the presence of gonadal steroids at the time of testing, during development or number of pregnancies. When selecting the type of experimental animal, additional consideration should be given to diet requirements (soy or plant based influencing consumption of phytoestrogen), lifespan, frequency of estrous cycle in females, and ability to investigate developmental or environmental components of disease modulation. Stress imposed by disruption of sleep/wake cycles, patterns of social interaction (or degree of social isolation), or handling may influence adrenal hormones that interact with pathways activated by the sex steroid hormones. Care must be given to selection of hormonal treatment and route of administration.</p> <p>Conclusions</p> <p>Accounting for sex in the design and interpretation of studies including pharmacological effects of drugs is essential to increase the foundation of basic knowledge upon which to build translational approaches to prevent, diagnose and treat cardiovascular diseases in humans.</p

Maternal Style Selectively Shapes Amygdalar Development and Social Behavior in Rats Genetically Prone to High Anxiety

The early-life environment critically influences neurodevelopment and later psychological health. To elucidate neural and environmental elements that shape emotional behavior, we developed a rat model of individual differences in temperament and environmental reactivity. We selectively bred rats for high vs. low behavioral response to novelty and found that high reactive (bHR) rats display greater risk-taking, impulsivity, and aggression relative to low reactive (bLR) rats, which show high levels of anxiety/depression-like behavior and certain stress vulnerability. The bHR/bLR traits are heritable but prior work revealed bHR/bLR maternal style differences, with bLR dams showing more maternal attention than bHRs. The present study implemented a cross-fostering paradigm to examine the contribution of maternal behavior on bLR offspring’s brain development and emotional behavior. bLR offspring were reared by biological bLR mothers or fostered to a bLR or bHR mother and then evaluated to determine effects on: 1) developmental gene expression in the hippocampus and amygdala; and 2) adult anxiety/depression-like behavior. Genome-wide expression profiling showed that cross-fostering bLR rats to bHR mothers shifted developmental gene expression in the amygdala (but not hippocampus), reduced adult anxiety and enhanced social interaction. Our findings illustrate how an early-life manipulation such as cross-fostering changes the brain’s developmental trajectory and ultimately impacts adult behavior. Moreover, while earlier studies highlighted hippocampal differences contributing to the bHR/bLR phenotypes, our results point to a role of the amygdala as well. Future work will pursue genetic and cellular mechanisms within the amygdala that contribute to bHR/bLR behavior either at baseline or following environmental manipulations

Logically Inferred Tuberculosis Transmission (LITT): A Data Integration Algorithm to Rank Potential Source Cases

Understanding tuberculosis (TB) transmission chains can help public health staff target their resources to prevent further transmission, but currently there are few tools to automate this process. We have developed the Logically Inferred Tuberculosis Transmission (LITT) algorithm to systematize the integration and analysis of whole-genome sequencing, clinical, and epidemiological data. Based on the work typically performed by hand during a cluster investigation, LITT identifies and ranks potential source cases for each case in a TB cluster. We evaluated LITT using a diverse dataset of 534 cases in 56 clusters (size range: 2–69 cases), which were investigated locally in three different U.S. jurisdictions. Investigators and LITT agreed on the most likely source case for 145 (80%) of 181 cases. By reviewing discrepancies, we found that many of the remaining differences resulted from errors in the dataset used for the LITT algorithm. In addition, we developed a graphical user interface, user's manual, and training resources to improve LITT accessibility for frontline staff. While LITT cannot replace thorough field investigation, the algorithm can help investigators systematically analyze and interpret complex data over the course of a TB cluster investigation.Code available at:https://github.com/CDCgov/TB_molecular_epidemiology/tree/1.0; https://zenodo.org/badge/latestdoi/166261171

Building consensus around the assessment and interpretation of Symbiodiniaceae diversity

Within microeukaryotes, genetic variation and functional variation sometimes accumulate more quickly than morphological differences. To understand the evolutionary history and ecology of such lineages, it is key to examine diversity at multiple levels of organization. In the dinoflagellate family Symbiodiniaceae, which can form endosymbioses with cnidarians (e.g., corals, octocorals, sea anemones, jellyfish), other marine invertebrates (e.g., sponges, molluscs, flatworms), and protists (e.g., foraminifera), molecular data have been used extensively over the past three decades to describe phenotypes and to make evolutionary and ecological inferences. Despite advances in Symbiodiniaceae genomics, a lack of consensus among researchers with respect to interpreting genetic data has slowed progress in the field and acted as a barrier to reconciling observations. Here, we identify key challenges regarding the assessment and interpretation of Symbiodiniaceae genetic diversity across three levels: species, populations, and communities. We summarize areas of agreement and highlight techniques and approaches that are broadly accepted. In areas where debate remains, we identify unresolved issues and discuss technologies and approaches that can help to fill knowledge gaps related to genetic and phenotypic diversity. We also discuss ways to stimulate progress, in particular by fostering a more inclusive and collaborative research community. We hope that this perspective will inspire and accelerate coral reef science by serving as a resource to those designing experiments, publishing research, and applying for funding related to Symbiodiniaceae and their symbiotic partnerships.journal articl