CART peptides are modulators of mesolimbic dopamine and psychostimulants

CART peptide produces behavioral effects when injected into the VTA or nucleus accumbens. In the VTA, the peptide behaves like an endogenous psychostimulant and produces increased locomotor activity and conditioned place preference. Since this is blocked by dopamine receptor blockers, it presumably involves release of dopamine. But in the nucleus accumbens, CART peptide reduces the locomotor-increasing effects of cocaine. This suggests that the peptide is an interesting target for medications development.     

Experimental stress in inflammatory rheumatic diseases: a review of psychophysiological stress responses

Introduction  

Stressful events are thought to contribute to the aetiology, maintenance and exacerbation of rheumatic diseases. Given the growing interest in acute stress responses and disease, this review investigates the impact of real-life experimental psychosocial, cognitive, exercise and sensory stressors on autonomic, neuroendocrine and immune function in patients with inflammatory rheumatic diseases.     

Identifying putative candidate genes and pathways involved in immune responses to porcine reproductive and respiratory syndrome virus (PRRSV) infection

Differences in gene expression were compared between RNAs from lungs of high (HR) and low (LR) porcine reproductive and respiratory syndrome virus (PRRSV) burden pigs using the swine protein-annotated long oligonucleotide microarray, the Pigoligoarray. Pathway analyses were carried out to determine biological processes, pathways and networks that differ between the LR and HR responses. Differences existed between HR and LR pigs for 16 signalling pathways [P < 0.01/-log (P-value) >1.96]. Top canonical pathways included acute phase response signalling, crosstalk between dendritic cells and natural killer cells and tight junction signalling, with numerous immune response genes that were upregulated (SOCS1, SOD2, RBP4, HLA-B, HLA-G, PPP2R1A and TAP1) or downregulated (IL18, TF, C4BPA, C1QA, C1QB and TYROBP). One mechanism, regulation of complement activation, may have been blocked in HR (PRRSV-susceptible) pigs and could account for the poor clearance of PRRSV by infected macrophages. Multiple inhibiting signals may have prevented effective immune responses in susceptible HR pigs, although some protective genes were upregulated in these pigs. It is likely that in HR pigs, expression of genes associated with protection was delayed, so that the immune response was not stimulated early; thus, PRRSV infection prevented protective immune responses.     

A Survey of Husbandry Practices for Lorisid Primates in North American Zoos and Related Facilities

Zoos and related facilities in North America currently manage five species in the primate family Lorisidae: the greater (Nycticebus coucang), Bengal (N. bengalensis) and pygmy (N. pygmaeus) slow lorises, red slender loris (Loris tardigradus), and potto (Perodicticus potto). We used an online survey to describe institutional housing and husbandry practices for these species and assess the extent to which practices are consistent with established guidelines. Our results show that most captive lorisids are housed solitarily or in pairs. Most individuals occupy a single exhibit space in a building dedicated to nocturnal animals. Facilities are commonly meeting recommendations for abiotic exhibit design and are providing animals with an enriched environment. However, pottos and slender lorises currently occupy exhibit spaces smaller than the recommended minimum, and the impact of cleaning protocols on olfactory communication should be critically evaluated. Few facilities are taking advantage of the benefits of positive reinforcement training for promoting animal welfare. Research is greatly needed on the effects of exhibit lighting on behavior, health, and reproduction; and to determine how best to manage the social needs of lorisids with naturally dispersed social structures. Although captive populations of slender lorises, pottos, and slow lorises are declining, we suggest that improved husbandry knowledge has the potential to positively influence population sustainability and to enhance future efforts to manage the growing pygmy loris population. Zoo Biol. 32:88‐100, 2013. © 2012 Wiley Periodicals, Inc.     

Evaluating risks of biological control introductions: A probabilistic risk-assessment approach

We address the need to develop improved quantitative procedures for estimating potential non-target impacts of biological control agents in this paper, and propose a probabilistic risk-assessment approach. This approach employs risk-assessment procedures commonly used in many disciplines. The procedure described here uses precision trees to estimate risk based on probabilities that biological control agents will demonstrate predictable behavior under specific conditions, based on their ecological characteristics. We use Trichogramma ostriniae, an egg parasitoid deployed augmentatively against Ostrina nubilalis in the US as case study to conceptually demonstrate the proposed procedure. We propose that this new approach has potential for widespread use in quantifying non-target risk of biological control introductions prior to introductions being made.     

CART knock out mice have impaired insulin secretion and glucose intolerance, altered beta cell morphology and increased body weight

CART peptides are anorexigenic and are widely expressed in the central and peripheral nervous systems, as well as in endocrine cells in the pituitary, adrenal medulla and the pancreatic islets. To study the role of CART in islet function, we used CART null mutant mice (CART KO mice) and examined insulin secretion in vivo and in vitro, and expression of islet hormones and markers of beta-cell function using immunocytochemistry. We also studied CART expression in the normal pancreas. In addition, body weight development and food intake were documented. We found that in the normal mouse pancreas, CART was expressed in numerous pancreatic nerve fibers, both in the exocrine and endocrine portion of the gland. CART was also expressed in nerve cell bodies in the ganglia. Double immunostaining revealed expression in parasympathetic (vasoactive intestinal polypeptide (VIP)-containing) and in fewer sensory fibers (calcitonin gene-related peptide (CGRP)-containing). Although the expression of islet hormones appeared normal, CART KO islets displayed age dependent reduction of pancreatic duodenal homeobox 1 (PDX-1) and glucose transporter-2 (GLUT-2) immunoreactivity, indicating beta-cell dysfunction. Consistent with this, CART KO mice displayed impaired glucose-stimulated insulin secretion both in vivo after an intravenous glucose challenge and in vitro following incubation of isolated islets in the presence of glucose. The impaired insulin secretion in vivo was associated with impaired glucose elimination, and was apparent already in young mice with no difference in body weight. In addition, CART KO mice displayed increased body weight at the age of 40 weeks, without any difference in food intake. We conclude that CART is required for maintaining normal islet function in mice.     

Synthesis and transporter binding properties of (R)-2β,3β- and (R)-2α,3α-diaryltropanes

(R)-2-Aryl-2-tropinone (9) was synthesized from (R)-2-carbomethoxy-3-tropinone (5) and was used as the key intermediate for the synthesis of (R)-2β,3β- and (R)-2α,3α-diaryltropanes. Inhibition of radioligand binding studies at the dopamine, serotonin, and norepinephrine transporters showed that the (R)-3β-(4-methylphenyl)-2β-phenyltropane (3b, RTI-422) possessed an IC₅₀ value of 1.96 nM at the dopamine transporter and was highly selective for this transporter relative to the serotonin and norepinephrine transporters.