The expression and organization of the phototransduction signaling proteins into a specialized light-sensing organelle, the rhabdomere, is required for photoreceptor cells to detect light. We report the characterization of the mutant Pph13 hazy . Pph13 is a homeodomain transcription factor expressed only in photoreceptor cells. Pph13 expression correlates with the differentiation and not specification of photoreceptor cells. In agreement with its expression profile, we find Pph13 is required for both rhabdomere morphogenesis and for the proper detection of light. In addition, we demonstrate that Pph13 exerts its effect by the regulation of photoreceptor specific gene expression.
Dopamine D 2 receptor antagonism contributes to the therapeutic action of antipsychotic drugs (APDs) but also produces undesirable side effects, including extrapyramidal motor deficits, cognitive dulling, and prolactinemia. The introduction of atypical APDs was a significant advancement in the treatment of schizophrenia. Whereas these agents are D 2 receptor antagonists, they are also potent 5-hydroxytryptamine (5-HT) 2A receptor inverse agonists, a feature that may explain their improved efficacy and tolerability. Recently, we reported that N-(4-fluorophenylmethyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2-methylpropyloxy)phenylmethyl) carbamide (2R,3R)-dihydroxybutanedioate (2:1) (ACP-103), a novel selective 5-HT 2A receptor inverse agonist that fails to bind D 2 receptors, is active in several models predictive of antipsychotic activity. Using ACP-103, we tested the hypothesis that combining high levels of 5-HT 2A inverse agonism with low levels of D 2 antagonism would result in a favorable interaction, such that antipsychotic efficacy could be achieved with reduced D 2 receptor-related adverse effects. Here we show that ACP-103 1) potently inhibited head-twitching produced by the 5-HT 2A/2C receptor agonist (Ϯ)-2,5-dimethoxy-4-iodoamphetamine, 2) increased the potency of haloperidol against amphetamine-induced hyperactivity, 3) interacted synergistically with haloperidol or risperidone to suppress hyperactivity induced by the N-methyl-D-aspartate receptor antagonist (5R,10S)-(ϩ)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801), and, by contrast, 4) attenuated haloperidol-or risperidone-induced prolactinemia. ACP-103 also attenuated catalepsy produced by haloperidol or risperidone. However, the doses that were required for this effect were higher than would be expected for a 5-HT 2A receptor-mediated mechanism. These data indicate that utilizing ACP-103 as an adjunctive therapy to currently used APDs may result in enhanced antipsychotic efficacy while reducing adverse effects including those attributable to D 2 receptor antagonism.
issues about where to obtain one's education, the accrediting of professional helping bodies, retirement, exercises, and vitality issues related to helping.The discussion on vitality issues, in many ways, reminded me of chapter 13 of Corey and Corey (1998), in which the authors extensively discuss ways helpers might be able to nurture themselves in an effort to regain their vitality and vigor.Nevertheless, what seems uniquely different in the Srebalus and Brown book is that the authors provide ideas about developing a healthy lifestyle and then move to an area not as heavily explored in helping, namely, spirituality.Although the discussion on spirituality, on one hand, is not a complete expository of elements of spirituality as Stump (1993) in Reasoned Faith would have it, on the other hand it does not extol or diminish beliefs of any kind. Readers, therefore, need to be cautioned about the danger of Srebalus' and Brown's book supposing a counseling religion (or speaking of replacing spirituality with religion) or inadvertently clamoring for a pantheistic conception of spirituality (which may be of a bit of a stretch here). In my mind, the book at this juncture seems to address the possibility that there are those clients for whom the concept of spirituality requires "establishing an intimate relationship with this higher power" (p. 297). The chapter ends with quizzes and suggested learning activities.I find the book quite interesting and would like to recommend it to both first-year graduate and undergraduate students in any helping profession.
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