Nuclear receptors in vascular biology

Nuclear receptors sense a wide range of steroids and hormones (estrogens, progesterone, androgens, glucocorticoid, and mineralocorticoid), vitamins (A and D), lipid metabolites, carbohydrates, and xenobiotics. In response to these diverse but critically important mediators, nuclear receptors regulate the homeostatic control of lipids, carbohydrate, cholesterol, and xenobiotic drug metabolism, inflammation, cell differentiation and development, including vascular development. The nuclear receptor family is one of the most important groups of signaling molecules in the body and as such represent some of the most important established and emerging clinical and therapeutic targets. This review will highlight some of the recent trends in nuclear receptor biology related to vascular biology

Towards Customary Legal Empowerment

Rule of Law and Development: Formation, Implementation and Improvement of Law and Governance in Developing Countrie

P2 receptors are involved in the mediation of motivation-related behavior

The importance of purinergic signaling in the intact mesolimbic–mesocortical circuit of the brain of freely moving rats is reviewed. In the rat, an endogenous ADP/ATPergic tone reinforces the release of dopamine from the axon terminals in the nucleus accumbens as well as from the somatodendritic region of these neurons in the ventral tegmental area, as well as the release of glutamate, probably via P2Y1 receptor stimulation. Similar mechanisms may regulate the release of glutamate in both areas of the brain. Dopamine and glutamate determine in concert the activity of the accumbal GABAergic, medium-size spiny neurons thought to act as an interface between the limbic cortex and the extrapyramidal motor system. These neurons project to the pallidal and mesencephalic areas, thereby mediating the behavioral reaction of the animal in response to a motivation-related stimulus. There is evidence that extracellular ADP/ATP promotes goal-directed behavior, e.g., intention and feeding, via dopamine, probably via P2Y1 receptor stimulation. Accumbal P2 receptor-mediated glutamatergic mechanisms seem to counteract the dopaminergic effects on behavior. Furthermore, adaptive changes of motivation-related behavior, e.g., by chronic succession of starvation and feeding or by repeated amphetamine administration, are accompanied by changes in the expression of the P2Y1 receptor, thought to modulate the sensitivity of the animal to respond to certain stimuli

Effort-related functions of nucleus accumbens dopamine and associated forebrain circuits

Background Over the last several years, it has become apparent that there are critical problems with the hypothesis that brain dopamine (DA) systems, particularly in the nucleus accumbens, directly mediate the rewarding or primary motivational characteristics of natural stimuli such as food. Hypotheses related to DA function are undergoing a substantial restructuring, such that the classic emphasis on hedonia and primary reward is giving way to diverse lines of research that focus on aspects of instrumental learning, reward prediction, incentive motivation, and behavioral activation. Objective The present review discusses dopaminergic involvement in behavioral activation and, in particular, emphasizes the effort-related functions of nucleus accumbens DA and associated forebrain circuitry. Results The effects of accumbens DA depletions on food-seeking behavior are critically dependent upon the work requirements of the task. Lever pressing schedules that have minimal work requirements are largely unaffected by accumbens DA depletions, whereas reinforcement schedules that have high work (e.g., ratio) requirements are substantially impaired by accumbens DA depletions. Moreover, interference with accumbens DA transmission exerts a powerful influence over effort-related decision making. Rats with accumbens DA depletions reallocate their instrumental behavior away from food-reinforced tasks that have high response requirements, and instead, these rats select a less-effortful type of food-seeking behavior. Conclusions Along with prefrontal cortex and the amygdala, nucleus accumbens is a component of the brain circuitry regulating effort-related functions. Studies of the brain systems regulating effort-based processes may have implications for understanding drug abuse, as well as energy-related disorders such as psychomotor slowing, fatigue, or anergia in depression

The risk of metabolic syndrome as a result of lifestyle among Ellisras rural young adults

The study aimed to investigate the association between metabolic syndrome (MetS) and lifestyle risk factors among Ellisras adults. A cross-sectional study was conducted on 624 adults (306 males and 318 females). MetS was defined according to the criteria of the International Diabetes Federation. The prevalence of MetS was 23.1% (8.6% males and 36.8 % females). Females appeared to have higher mean values for waist circumference (WC), fasting blood glucose (FBG), total cholesterol (TCHOL) and low-density lipoprotein cholesterol (LDL-C), while males had high mean values for high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), systolic blood pressure (SBP) and diastolic blood pressure (DBP). No significant age and gender differences were observed for dietary intake. Significantly more females (51.9%) presented with increased WC than males (4.6%). Participants who had a high dietary energy intake were significantly less likely to present with larger WC (OR: 0.250 95% CI [0.161; 0.389]), low HDL-C (OR: 0.306 95% CI [0.220; 0.425]) and high LDL-C (OR: 0.583 95% CI [0.418; 0.812]) but more likely to present with elevated FBG (OR: 1.01 95% CI [0.735; 1.386]), high TCHOL (OR: 1.039 95% CI [0.575; 1.337]), high TG (OR: 1.186 95% CI [0.695; 2.023]) and hypertension (OR: 5.205 95% CI [3.156; 8.585]). After adjusting for age, gender, smoking, and alcohol status, high energy intake was more than two times likely to predict MetS in adults with a large WC (OR: 2.766 95% CI [0.863; 3.477] and elevated FBG (OR: 2.227 95% CI [1.051; 3.328]). Therefore, identifying groups that are at an increased risk and those that are in their early stages of MetS will help improve and prevent the increase of the MetS in the future

The CLAS12 Forward Tagger

This document presents the technical layout and the performance of the CLAS12 Forward Tagger (FT). The FT, composed of an electromagnetic calorimeter based on PbWO4 crystals (FT-Cal), a scintillation hodoscope (FT-Hodo), and several layers of Micromegas trackers (FT-Trk), has been designed to detect electrons and photons scattered at polar angles from 2∘ to 5∘ and to meet the physics goals of the hadron spectroscopy program and other experiments running with the CLAS12 spectrometer in Hall B