Evidence That Interspecies Polymorphism in the Human and Rat Cholecystokinin Receptor-2 Affects Structure of the Binding Site for the Endogenous Agonist Cholecystokinin

The cholecystokinin (CCK) receptor-2 exerts very important central and peripheral functions by binding the neuropeptides cholecystokinin or gastrin. Because this receptor is a potential therapeutic target, great interest has been devoted to the identification of efficient antagonists. However, interspecies genetic polymorphism that does not alter cholecystokinin-induced signaling was shown to markedly affect activity of synthetic ligands. In this context, precise structural study of the agonist binding site on the human cholecystokinin receptor-2 is a prerequisite to elucidating the molecular basis for its activation and to optimizing properties of synthetic ligands. In this study, using site-directed mutagenesis and molecular modeling, we delineated the binding site for CCK on the human cholecystokinin receptor-2 by mutating amino acids corresponding to that of the rat homolog. By doing so, we demonstrated that, although resembling that of rat homolog, the human cholecystokinin receptor-2 binding site also displays important distinct structural features that were demonstrated by susceptibility to several point mutations (F120A, Y189A, H207A). Furthermore, docking of CCK in the human and rat cholecystokinin receptor-2, followed by dynamic simulations, allowed us to propose a plausible structural explanation of the experimentally observed difference between rat and human cholecystokinin-2 receptors.

Science for sale in a free market economy: But at what price? ABA and the treatment of autism in Europe.

Educating the public accurately about Applied Behavior Analysis (ABA) is an important undertaking, not least because misconceptions and myths about ABA abound. In this paper we argue that, unfortunately, the efforts of many dedicated professionals and parents to disseminate accurate information about the benefits of ABA for children diagnosed with autism spectrum disorder (ASD) are damaged by a few behavior analysts whose focus seems to be more on monetary gains than social responsibility. We cite examples of the resulting harm to the public image of behavior analysis from a number of European countries. We conclude by calling upon fellow scientists to unite in their opposition to unscrupulous abuses of free market forces for short-term monetary gains that damage the dissemination of the science of behavior analysis and thereby ultimately disadvantage those who should benefit primarily from our science, i.e., some of the most vulnerable citizens of society.

ABA-Based Programs for Children Diagnosed With Autism Spectrum Disorder: Parental and Professional Experiences at School and at Home

Having a child diagnosed with Autism Spectrum Disorder (ASD) poses a range of challenges to families, many of which can be addressed through appropriate intervention. A study of parental (n = 95) and professional (n = 67) experiences was carried out in relation to two settings: (a) schools that provided intensive interventions based on the science of Applied Behavior Analysis (ABA), and (b) non-intensive ABA-based home programs. Results show that parents whose children attend ABA-based schools were generally more satisfied with their child's educational provision, monitoring procedures, and level of staff training, than parents who were not offered ABA-based education in schools. © 2012 Copyright Taylor and Francis Group, LLC.

Endogenous Two-Sided Markets with Repeated Transactions

We consider homogeneous two-sided markets, in which connected buyer-seller pairs bargain and trade repeatedly. In this infinite market game with exogenous matching probabilities and a common discount factor, we prove the existence of equilibria in stationary strategies. The equilibrium payoffs are given implicitly as a solution to a system of linear equations. Then, we endogenize the matching mechanism in a link formation stage that precedes the market game. When agents are sufficiently patient and link costs are low, we provide an algorithm to construct minimally connected networks that are pairwise stable with respect to the expected payoffs in the trading stage. The constructed networks are essentially efficient and consist of components with a constant buyer-seller ratio. The latter ratio increases (decreases) for a buyer (seller) that deletes one of her links in a pairwise stable component.

ADP ribose is an endogenous ligand for the purinergic P2Y1 receptor

The mechanism by which extracellular ADP ribose (ADPr) increases intracellular free Ca2+ concentration ([Ca2+](i)) remains unknown. We measured [Ca2+](i) changes in fura-2 loaded rat insulinoma INS-1E cells, and in primary beta-cells from rat and human. A phosphonate analogue of ADPr (PADPr) and 8-Bromo-ADPr (8Br-ADPr) were synthesized. ADPr increased [Ca2+](i) in the form of a peak followed by a plateau dependent on extracellular Ca2+. NAD(+), cADPr, PADPr, 8Br-ADPr or breakdown products of ADPr did not increase [Ca2+](i). The ADPr-induced [Ca2+](i) increase was not affected by inhibitors of TRPM2, but was abolished by thapsigargin and inhibited when phospholipase C and IP3 receptors were inhibited. MRS 2179 and MRS 2279, specific inhibitors of the purinergic receptor P2Y1, completely blocked the ADPrinduced [Ca2+](i) increase. ADPr increased [Ca2+](i) in transfected human astrocytoma cells (1321N1) that express human P2Y1 receptors, but not in untransfected astrocytoma cells. We conclude that ADPr is a specific agonist of P2Y1 receptors. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Understanding applied behaviour analysis: An introduction to ABA for parents, teachers, and other professionals

book review

Diagnosis and treatment of endogenous fungal endophthalmitis

Endogenous infectious endophthalmitis is rare, and a primary source is usually identified. A case of primary fungal endophthalmitis successfully treated with vitrectomy and systemic antifungal therapy is presented. The aetiology and treatment of the condition are discussed.

Reasons for the variability in growth hormone (GH) responses to GHRH challenge:the endogenous hypothalamic-somatotroph rhythm (HSR)

The aims of this study were: (1) to test the possibility that pre-GHRH plasma GH values could reflect the functional status of the hypothalamic-somatotroph rhythm (HSR) at testing, and thus explain if it is responsible for the marked variability in GH responsiveness to GHRH challenge and (2) to see if exogenous somatostatin (SS) could disrupt this endogenous HSR and thus make the GH responses homogeneous. (1) Two to 14 GHRH acute tests (GRF-29, 1 µg/kg, i.v. bolus) were performed in 12 normal men and 10 normal women at the same time (0830 h) at random intervals (2 to 60 days). Blood samples to measure plasma GH were drawn at 15 min intervals before and after GHRH challenge. Given that the increments in pre-GHRH plasma GH values (I = value at 0 min minus value at -15 min) were highly correlated with either GHRH-elicited peaks of GH (men, r = 0.81; women, r = 0.69; P