Systemic and Intra-Habenular Activation of the Orphan G Protein-Coupled Receptor GPR139 Decreases Compulsive-Like Alcohol Drinking and Hyperalgesia in Alcohol-Dependent Rats.

GPR139 is an orphan G protein-coupled receptor (GPCR) that is expressed mainly in the brain, with the highest expression in the medial habenula. The modulation of GPR139 receptor function has been hypothesized to be beneficial in the treatment of some mental disorders, but behavioral studies have not yet provided causal evidence of the role of GPR139 in brain dysfunction. Because of the high expression of GPR139 in the habenula, a critical brain region in addiction, we hypothesized that GPR139 may play role in alcohol dependence. Thus, we tested the effect of GPR139 receptor activation using the selective, brain-penetrant receptor agonist JNJ-63533054 on addiction-like behaviors in alcohol-dependent male rats. Systemic administration of JNJ-63533054 (30 mg/kg but not 10 mg/kg, p.o.) reversed the escalation of alcohol self-administration in alcohol-dependent rats, without affecting water or saccharin intake in dependent rats or alcohol intake in nondependent rats. Moreover, systemic JNJ-63533054 administration decreased withdrawal-induced hyperalgesia, without affecting somatic signs of alcohol withdrawal. Further analysis demonstrated that JNJ-63533054 was effective only in a subgroup of dependent rats that exhibited compulsive-like alcohol drinking. Finally, site-specific microinjection of JNJ-63533054 in the habenula but not interpeduncular nucleus (IPN) reduced both alcohol self-administration and withdrawal-induced hyperalgesia in dependent rats. These results provide robust preclinical evidence that GPR139 receptor activation reverses key addiction-like behaviors in dependent animals, suggest that GPR139 may be a novel target for the treatment of alcohol use disorder, and demonstrate that GPR139 is functionally relevant in regulating mammalian behavior

Bid distributions of competing agents in simple models of auctions

Models of auctions or tendering processes are introduced. In every round of bidding the players select their bid from a probability distribution and whenever a bid is unsuccessful, it is discarded and replaced. For simple models, the probability distributions evolve to a stationary power law with the exponent dependent only on the number of players. For most situations, the system converges towards a state where all players are identical. A number of variations of this model are introduced and the application of these models to the dynamics of market makers is discussed. The effect of price uncertainty on bid distributions is presented. An underlying market structure generates heterogenous agents which do not have power law bid distribution in general

Cognitive constraints, contraction consistency, and the satisficing criterion

© 2007, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0

Consumption-Based Conservation Targeting: Linking Biodiversity Loss to Upstream Demand through a Global Wildlife Footprint.

Although most conservation efforts address the direct, local causes of biodiversity loss, effective long-term conservation will require complementary efforts to reduce the upstream economic pressures, such as demands for food and forest products, which ultimately drive these downstream losses. Here, we present a wildlife footprint analysis that links global losses of wild birds to consumer purchases across 57 economic sectors in 129 regions. The United States, India, China, and Brazil have the largest regional wildlife footprints, while per-person footprints are highest in Mongolia, Australia, Botswana, and the United Arab Emirates. A US$100 purchase of bovine meat or rice products occupies approximately 0.1 km2 of wild bird ranges, displacing 1-2 individual birds, for 1 year. Globally significant importer regions, including Japan, the United Kingdom, Germany, Italy, and France, have large footprints that drive wildlife losses elsewhere in the world and represent important targets for consumption-focused conservation attention

In-lab three-dimensional printing:an inexpensive tool for experimentation and visualization for the field of organogenesis

The development of the microscope in 1590 by Zacharias Janssenby and Hans Lippershey gave the world a new way of visualizing details of morphogenesis and development. More recent improvements in this technology including confocal microscopy, scanning electron microscopy (SEM) and optical projection tomography (OPT) have enhanced the quality of the resultant image. These technologies also allow a representation to be made of a developing tissue’s three-dimensional (3-D) form. With all these techniques however, the image is delivered on a flat two-dimensional (2-D) screen. 3-D printing represents an exciting potential to reproduce the image not simply on a flat screen, but in a physical, palpable three-dimensional structure. Here we explore the scope that this holds for exploring and interacting with the structure of a developing organ in an entirely novel way. As well as being useful for visualization, 3-D printers are capable of rapidly and cost-effectively producing custom-made structures for use within the laboratory. We here describe the advantages of producing hardware for a tissue culture system using an inexpensive in-lab printer

Quality of Life Before and After Cosmetic Surgery: Should Body Dysmorphic Disorder Be Considered an Absolute or Relative Contraindication for Cosmetic Surgery?

Body Dysmorphic Disorder (BDD) has historically been regarded as a strong contraindication for cosmetic plastic surgery. New research now suggests that the contraindications to cosmetic surgery in patients with BDD may not be so absolute. This paper reviews diagnostic criteria, diagnostic challenges, and current standard of treatment of BDD. It then presents the idea of insight analysis in the BDD patient as a significant factor in determining if patients with BDD may or may not benefit from cosmetic surgery or procedures