The Exclusivity Principle Determines the Correlation Monogamy

Adopting the graph-theoretic approach to the correlation experiments, we analyze the origin of monogamy and prove that it can be recognised as a consequence of exclusivity principle(EP). We provide an operational criterion for monogamy: if the fractional packing number of the graph corresponding to the union of event sets of several physical experiments does not exceed the sum of independence numbers of each individual experiment graph, then these experiments are monogamous. As applications of this observation, several examples are provided, including the monogamy for experiments of Clauser-Horne-Shimony-Holt (CHSH) type, Klyachko-Can-Binicio\u{g}lu-Shumovsky (KCBS) type, and for the first time we give some monogamy relations of Swetlichny's genuine nonlocality. We also give the necessary and sufficient condition for several experiments to be monogamous: several experiments are monogamous if and only if the Lov\'asz number the union exclusive graph is less than or equal to the sum of independence numbers of each exclusive graph

Hardy's Paradox for High-Dimensional Systems: Beyond Hardy's Limit

Hardy's proof is considered the simplest proof of nonlocality. Here we introduce an equally simple proof that (i) has Hardy's as a particular case, (ii) shows that the probability of nonlocal events grows with the dimension of the local systems, and (iii) is always equivalent to the violation of a tight Bell inequality.Comment: REVTeX4, 5 pages, 1 figure. Typo in Eq. (17) corrected. Ref. [5] complete

In Search of a Common European Approach to a Healthy Indoor Environment

Increasingly, policymakers in Europe and around the world are realizing the importance of healthy indoor environments for public health. Certain member states of the European Union (EU) have already achieved successes in improving indoor environmental quality, such as controlling certain contaminants (e.g., environmental tobacco smoke) or developing nationwide policies that address indoor air generally. However, a common European approach to achieving healthy indoor environments is desirable for several reasons including providing a broader recognition of the problem of unhealthy indoor air, setting a policy example for all 27 EU member states, and achieving greater public health equity across the different European nations. In this article we address the question “Why is it so difficult in the EU to develop a coherent approach on indoor environment?” We identify and describe four main barriers: a) the subsidiarity principle in EU policymaking, introducing decentralization of decision making to the member states; b) fragmentation of the topic of the indoor environment; c) the differences in climate and governance among different member states that make a common policy difficult; and d) economic issues. We discuss potential lessons and recommendations from EU and U.S. successes in achieving healthier indoor environments through various policy mechanisms

A weighted blanket increases pre-sleep salivary concentrations of melatonin in young, healthy adults

Weighted blankets have emerged as a potential non-pharmacological intervention to ease conditions such as insomnia and anxiety. Despite a lack of experimental evidence, these alleged effects are frequently attributed to a reduced activity of the endogenous stress systems and an increased release of hormones such as oxytocin and melatonin. Thus, the aim of the present in-laboratory crossover study (26 young and healthy participants, including 15 men and 11 women) was to investigate if using a weighted blanket (similar to 12% of body weight) at bedtime resulted in higher salivary concentrations of melatonin and oxytocin compared with a light blanket (similar to 2.4% of body weight). We also examined possible differences in salivary concentrations of the stress hormone cortisol, salivary alpha-amylase activity (as an indicative metric of sympathetic nervous system activity), subjective sleepiness, and sleep duration. When using a weighted blanket, the 1 hour increase of salivary melatonin from baseline (i.e., 22:00) to lights off (i.e., 23:00) was about 32% higher (p = 0.011). No other significant differences were found between the blanket conditions, including subjective sleepiness and total sleep duration. Our study is the first to suggest that using a weighted blanket may result in a more significant release of melatonin at bedtime. Future studies should investigate whether the stimulatory effect on melatonin secretion is observed on a nightly basis when frequently using a weighted blanket over weeks to months. It remains to be determined whether the observed increase in melatonin may be therapeutically relevant for the previously described effects of the weighted blanket on insomnia and anxiety

Corticotropin (ACTH) acts directly on amygdala neurons to down-regulate corticotropin-releasing hormone gene expression.

The hormone corticotropin (ACTH) is employed as therapy for diverse neurological disorders, but the mechanisms for its efficacy remain unknown. ACTH promotes the release of adrenal steroids (glucocorticoids), and most ACTH effects on the central nervous system (CNS) have been attributed to activation of glucocorticoid receptors. However, in several human disorders, ACTH has therapeutic actions that differ qualitatively or quantitatively from those of steroids. This study tested the hypothesis that ACTH directly influences limbic neurons via the recently characterized melanocortin receptors and focused on the effects of ACTH on the expression of corticotropin-releasing hormone (CRH), a neuropeptide involved in neuroimmune functions and in certain developmental seizures. The results demonstrated that ACTH potently reduced CRH expression in amygdala neurons. This down-regulation was not abolished by experimental elimination of steroids or by blocking their receptors and was reproduced by a centrally administered ACTH fragment that does not promote steroid release. Importantly, selective blocking of melanocortin receptors prevented ACTH-induced down-regulation of CRH expression. Taken together, these data indicate that ACTH activates central melanocortin receptors to modulate CRH gene expression in amygdala, supporting the notion that direct, steroid-independent actions of ACTH may account for some of its established clinical effects on the CNS

Involvement of the V2 Vasopressin Receptor in Adaptation to Limited Water Supply

Mammals adapted to a great variety of habitats with different accessibility to water. In addition to changes in kidney morphology, e.g. the length of the loops of Henle, several hormone systems are involved in adaptation to limited water supply, among them the renal-neurohypophysial vasopressin/vasopressin receptor system. Comparison of over 80 mammalian V2 vasopressin receptor (V2R) orthologs revealed high structural and functional conservation of this key component involved in renal water reabsorption. Although many mammalian species have unlimited access to water there is no evidence for complete loss of V2R function indicating an essential role of V2R activity for survival even of those species. In contrast, several marsupial V2R orthologs show a significant increase in basal receptor activity. An increased vasopressin-independent V2R activity can be interpreted as a shift in the set point of the renal-neurohypophysial hormone circuit to realize sufficient water reabsorption already at low hormone levels. As found in other desert mammals arid-adapted marsupials show high urine osmolalities. The gain of basal V2R function in several marsupials may contribute to the increased urine concentration abilities and, therefore, provide an advantage to maintain water and electrolyte homeostasis under limited water supply conditions

Elevated Non-Esterified Fatty Acid Concentrations during Bovine Oocyte Maturation Compromise Early Embryo Physiology

Elevated concentrations of serum non-esterified fatty acids (NEFA), associated with maternal disorders such as obesity and type II diabetes, alter the ovarian follicular micro-environment and have been associated with subfertility arising from reduced oocyte developmental competence. We have asked whether elevated NEFA concentrations during oocyte maturation affect the development and physiology of zygotes formed from such oocytes, using the cow as a model. The zygotes were grown to blastocysts, which were evaluated for their quality in terms of cell number, apoptosis, expression of key genes, amino acid turnover and oxidative metabolism. Oocyte maturation under elevated NEFA concentrations resulted in blastocysts with significantly lower cell number, increased apoptotic cell ratio and altered mRNA abundance of DNMT3A, IGF2R and SLC2A1. In addition, the blastocysts displayed reduced oxygen, pyruvate and glucose consumption, up-regulated lactate consumption and higher amino acid metabolism. These data indicate that exposure of maturing oocytes to elevated NEFA concentrations has a negative impact on fertility not only through a reduction in oocyte developmental capacity but through compromised early embryo quality, viability and metabolism

Current and Future Drug Targets in Weight Management

Obesity will continue to be one of the leading causes of chronic disease unless the ongoing rise in the prevalence of this condition is reversed. Accumulating morbidity figures and a shortage of effective drugs have generated substantial research activity with several molecular targets being investigated. However, pharmacological modulation of body weight is extremely complex, since it is essentially a battle against one of the strongest human instincts and highly efficient mechanisms of energy uptake and storage. This review provides an overview of the different molecular strategies intended to lower body weight or adipose tissue mass. Weight-loss drugs in development include molecules intended to reduce the absorption of lipids from the GI tract, various ways to limit food intake, and compounds that increase energy expenditure or reduce adipose tissue size. A number of new preparations, including combinations of the existing drugs topiramate plus phentermine, bupropion plus naltrexone, and the selective 5-HT2C agonist lorcaserin have recently been filed for approval. Behind these leading candidates are several other potentially promising compounds and combinations currently undergoing phase II and III testing. Some interesting targets further on the horizon are also discussed

Serotonin controlling feeding and satiety

Serotonin has been implicated in the control of satiety for almost four decades. Historically, the insight that the appetite suppressant effect of fenfluramine is linked to serotonin has stimulated interest in and research into the role of this neurotransmitter in satiety. Various rodent models, including transgenic models, have been developed to identify the involved 5-HT receptor subtypes. This approach also required the availability of receptor ligands of different selectivity, and behavioural techniques had to be developed simultaneously which allow differentiating between unspecific pharmacological effects of these ligands and ‘true’ satiation and satiety. Currently, 5-HT1B, 5-HT2C and 5-HT6 receptors have been identified to mediate serotonergic satiety in different ways. The recently approved anti-obesity drug lorcaserin is a 5-HT2C receptor agonist. In brain, both hypothalamic (arcuate nucleus, paraventricular nucleus) and extrahypothalamic sites (parabrachial nucleus, nucleus of the solitary tract) have been identified to mediate the serotonergic control of satiety. Serotonin interacts within the hypothalamus with endogenous orexigenic (Neuropeptide Y/Agouti related protein) and anorectic (α-melanocyte stimulating hormone) peptides. In the nucleus of the solitary tract serotonin integrates peripheral satiety signals. Here, the 5-HT3, but possibly also the 5-HT2C receptor play a role. It has been found that 5-HT acts in concert with such peripheral signals as cholecystokinin and leptin. Despite the recent advances of our knowledge, many of the complex interactions between 5-HT and other satiety factors are not fully understood yet. Further progress in research will also advance the development of new serotonergic anti-obesity drugs