Constraining ligand-binding site stoichiometry suggests that a cyclic nucleotide-gated channel is composed of two functional dimers

Cyclic nucleotide-gated ion channels are composed of four pore-forming subunits. Binding of cyclic nucleotide to a site in the intracellular carboxyl terminus of each subunit leads to channel activation. Since there are four subunits, four binding events are possible. In this study, we investigate the effects of individual binding events on activation by studying channels containing one, two, three, or four functional binding sites. The binding of a single ligand significantly increases opening, although four ligands are required for full activation. The data are inconsistent with models in which the four subunits activate in a single concerted step (Monod-Wyman-Changeux model) or in four independent steps (Hodgkin-Huxley model). Instead, the four subunits may associate and activate as two independent dimers.     

Behavioral lateralization in rats and dopaminergic system: Individual and population laterality.

Recently, we reported that practice facilitates the expression of the behavioral asymmetry in rats at individual and population levels. In the present study we investigated the side preference in the performance of four different tasks during 10 successive days. The practice increased individual laterality and internal consistency in all tasks. In addition, practice facilitated the expression of marked population laterality in two tasks (78.1% and 63.3% for right bias). The influence of dopaminergic systems on these behaviors was evaluated with apomorphine and with 6-hydroxydopamine lesions ipsi- and contralateral to the side preference. Results suggest that there is a presynaptic dominance contralateral to the side preference in the four tests. However, as influences of dopaminergic systems were different in each task and because the tests were unrelated, the results suggest that the behavioral laterality in rats, as in humans, is a phenomenon caused by different and relatively independent systems. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Clonal hematopoiesis and acquired thalassemia in common variable immunodeficiency

The Drosophila hairy gene encodes a basic helix-loop-helix protein that functions in at least two steps during Drosophila development: (1) during embryogenesis, when it partakes in the establishment of segments, and (2) during the larval stage, when it functions negatively in determining the pattern of sensory bristles on the adult fly. In the rat, a structurally homologous gene (RHL) behaves as an immediate-early gene in its response to growth factors and can, like that in Drosophila, suppress neuronal differentiation events. Here, we report the genomic cloning of the human hairy gene homolog (HRY). The coding region of the gene is contained within four exons. The predicted amino acid sequence reveals only four amino acid differences between the human and rat genes. Analysis of the DNA sequence 5' to the coding region reveals a putative untranslated exon. To increase the value of the HRY gene as a genetic marker and to assess its potential involvement in genetic disorders, we sublocalized the locus to chromosome 3q28-q29 by fluorescence in situ hybridization.     

Neuroimages as evidence in a mens rea defense: No impact.

Recent developments in the neuropsychology of criminal behavior have given rise to concerns that neuroimaging evidence (such as MRI and functional MRI [fMRI] images) could unduly influence jurors. Across four experiments, a nationally representative sample of 1,476 jury-eligible participants evaluated written summaries of criminal cases in which expert testimony was presented in support of a mental disorder as exculpatory. The evidence varied in the extent to which it presented neuroscientific explanations and neuroimages in support of the expert's conclusion. Despite suggestive findings from previous research, we found no evidence that neuroimagery affected jurors' judgments (verdicts, sentence recommendations, judgments of the defendant's culpability) over and above verbal neuroscience-based testimony. A meta-analysis of our four experiments confirmed these findings. In addition, we found that neuroscientific evidence was more effective than clinical psychological evidence in persuading jurors that the defendant's disorder reduced his capacity to control his actions, although this effect did not translate into differences in verdicts. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Thoughts about journeys to integrative psychotherapy.

What a humbling experience to be invited to offer commentary on the papers of such distinguished contributors to the field of integrative psychotherapy. Even the most junior member of the panel has a record of achievement impressive enough to place him in a competitive position for a tenured faculty position. As we read their stories, we have a wonderful opportunity to get glimpses into two decades of change in the field of psychotherapy as seen through the eyes of four colleagues who have been tremendously influential. In my effort to tie together these moving pieces I have looked for the "common factors" that have played out in the stories of these four clinician-scholars. In the pages that follow, I will review these commonalities, which include the following: (a) the role of personal life experiences on the development of an integrative approach; (b) the critical role of a mentor; (c) the challenge of defining one's approach; (d) views about the essential factors in effective psychotherapy; (e) an appreciation for the relationship between research and clinical practice; (f) a commitment to teaching and supervision; and (g) the significance of SEPI in the past, present, and future. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Components of hair bleaches as triggers of bronchial hypersensitivity--studies using a model for occupationally-induced lung damage

Ammonium persulfate (APS) is used as an oxidant in many industrial branches and is contained in bleaching substances used in hair cosmetic industry. In addition to skin diseases, respiratory disorders have been frequently reported. We examined whether APS can induce bronchial hyperresponsiveness (BHR) which has to be regarded as a first step in the development of obstructive respiratory disorders. In a rabbit model we tested the influence of aerosolized APS-solutions in concentrations of 0.1, 0.01 and 0.001 M (50, 5, 0,5 ppm in air) for about four hours on the contractile bronchial reaction. Exposure to APS-aerosols does not alter basal airway Resistance (RI), dynamic Elastance (Edyn), slope of inspiratory pressure generation (delta Poes/tI), arterial blood pressure and blood gases (PaO2, PaCO2). Before, after two and after four hours the influence of APS application on the bronchial reactivity to 0.2%- and 2% acetylcholine-aerosols (ACH) was tested. Exposure to an aerosol from 0.1 M APS solution, which is equivalent to a concentration of 50 ppm APS in air for two hours induces a significant increase in bronchoconstrictory responses to ACH. A nebulized 0.01 M APS solution causes an increased ACH response after four hours of exposure. However, inhalation of 0.001 M APS (0.5 ppm in air) does not alter sensitivity to ACH within four hours of exposure. In bronchoalveolar lavage an increased number of inflammatory cells was found. Our results demonstrate, aerolized APS-solutions to cause bronchial hyper-responsiveness after few hours of exposure presumably under the participation of inflammatory cells.     

Oral 17 beta-estradiol continuously combined with dydrogesterone lowers serum lipoprotein(a) concentrations in healthy postmenopausal women

Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerosis. Serum Lp(a) concentrations increase after menopause, and postmenopausal estrogen replacement appears to decrease Lp(a) levels. In a randomized, double blind study, we examined the effects of 6-month treatment with daily 17 beta-estradiol (E2; 2 mg, orally) continuously combined with one of four dosages [2.5 mg (n = 41), 5 mg (n = 38), 10 mg (n = 38), and 15 mg (n = 20)] of dydrogesterone on fasting serum Lp(a) concentrations in 137 healthy postmenopausal women. At baseline, no significant differences were noted among the four treatment groups. During the study period of 6 months the median serum Lp(a) concentration decreased significantly from 128 mg/L (range, 5-1660) to 110 mg/L (range, 1-1530) in the total population, corresponding to a reduction of 13% (P < 0.001). The percent changes in serum Lp(a) correlated positively with the percent changes in serum E2 at 3 as well as 6 months of therapy (r = 0.38; P < 0.001 and r = 0.35; P < 0.001, respectively). A dose response of dydrogesterone on serum Lp(a) was not found. In addition, serum lipids and (apo)lipoproteins improved significantly in all four treatment groups. In conclusion, oral E2 continuously combined with dydrogesterone has beneficial effects on the lipid and lipoprotein profile and is effective in lowering Lp(a) concentrations in postmenopausal women.     

Effect of changing the unconditioned stimulus on appetitive blocking.

In four experiments we examined the effects of the unconditioned stimulus (US) on appetitive blocking. In Experiments 1{a}, 1{b}, and 2 we established that substituting food for water, or water for food, in the compound stage did not attenuate blocking relative to groups that received the same US throughout conditioning. Experiment 3 showed that satiation with the US used prior to compound conditioning with a different US does not affect blocking. Experiment 4 revealed that changing the location of US delivery, as well as the quality of the US, also leaves blocking unaffected. It is suggested that these results demonstrate that blocking occurs, provided that there is no change in the affective properties of the US. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A polymorphism in exon b2 of the major breakpoint cluster region (M-bcr) identified in chronic myeloid leukaemia patients

The BCR/ABL junctional region and the b3 exon from chronic myeloid leukaemia (CML) patients were sequenced. In all 21 samples analysed the junctional region, as well as the b3 exon of 8 b3a2 mRNA molecules, presented no differences to the already described sequences. However, we identified a polymorphic base in the b2 exon in two out of seven b3a2 samples, four out of 10 b2a2 samples and all four b3a2/b2a2 samples analysed. In the eighth position before the junctional region of BCR/ABL cDNA, a cytosine replaces thymine in these cases. The polymorphism described here could be a useful marker for the differentiation of normal and rearranged BCR alleles in heterozygotes.     

Characterization of interleukin-8 receptors in non-human primates

Interleukin-8 is a chemokine with a potent neutrophil chemoattractant activity. In humans, two different cDNAs encoding human IL8 receptors designated IL8RA and IL8RB have been cloned. IL8RA binds IL8, while IL8RB binds IL8 as well as other alpha-chemokines. Both human IL8Rs are encoded by two genes physically linked on chromosome 2. The IL8RA and IL8RB genes have open reading frames (ORF) lacking introns. By direct sequencing of the polymerase chain reaction products, we sequenced the IL8R genes of cell lines from four non-human primates: chimpanzee, gorilla, orangutan, and macaca. The IL8RB encodes an ORF in the four non-human primates, showing 95% - 99% similarity to the human IL8RB sequence. The IL8RA homologue in gorilla and chimpanzee consisted of two ORF 98% - 99% identical to the human sequence. The macaca and orangutan IL8RA homologues are pseudogenes: a 2 base pair insertion generated a sequence with several stop codons. In addition, we describe the physical linkage of these genes in the four non-human primates and discuss the evolutionary implications of these findings.     

The role of judgment calls in meta-analysis.

The use of meta-analysis in literature reviews is increasing at a geometric rate, even though many researchers are still not familiar with the technique. Although most of the criticism of meta-analysis has focused on the formulas used, we believe there should be concern with the many judgment calls that must be made and how they affect the results of a meta-analysis. In recent years four topics have each been independently meta-analyzed twice. These four pairs are reexamined, and the differences in results between each of the pairs are diagnosed as resulting from judgment calls. Future users of meta-analysis are advised to be explicit about the judgments they make, and a summary of judgment calls is offered as a guide for reporting them. In addition to reporting judgment calls, their effects on the estimates of the population mean effect size and standard deviation should be tested. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

重视理化检验技术,提高产品实物质量

本文从以下四个方面叙述了应当重视理化检验技术提高产品实物质量:(1)以标准化为中心,为钢铁工业生产提供适用的理化分析检验技术;(2)以在线分析为目标,使理化分析检验技术积极参与质量控制过程;(3)以研究开发为对象,不断提高理化分析检验技术水平;(4)以学科发展为基础,逐步使理化分析检验技术完善化和系统化。     

Confidentiality, ethics, and informed consent.

Comments on the article Protecting confidentiality rights: The need for an ethical practice model by Mary Alice Fisher (see record 2007-19520-001). In Fisher's excellent and much-needed article, she rightly implied that when discussing ethical dilemmas, psychologists may find themselves saying "consult an attorney" almost as often as they find themselves saying, "consult a fellow psychologist." Fisher's article was meant to turn the ship so to speak, by providing psychologists with a foundation for thinking clearly about confidentiality issues--a foundation that does not use legal arguments as primary building blocks. The above being said, we offer comments about four issues that we hope will add to the fine ideas expressed by Fisher. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Early and late selection in unconscious information processing.

In four experiments, we investigated whether masked stimuli in priming experiments are subjected to early or to late selection. In Experiment 1, participants classified four target-pictures as being small or large. In line with early selection accounts, prime-pictures with a different perceptual appearance as the experienced targets did not elicit congruency effect. In Experiment 2, 40 targets all depicting animals were presented. Results were in line with late selections assumptions because novel animal primes but not novel primes from different semantic categories yielded congruency effects. In Experiment 3, the targets were chosen such that there is a second semantic feature that covaried with the required response. Here, novel primes picturing small animals did not influence target responses with regard to the instructed size classification, but with regard to their affiliation to the category animal. In Experiment 4, small and large pictures from two categories were presented. Category match did not influence priming, ruling out that feature overlap contaminated the former results. The results indicate that participants’ prestimulus expectations determine in which stage in the processing-stream masked stimuli are selected. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The relation between event processing and the duration of emotional experience.

An emotional experience can last for only a couple of seconds up to several hours or even longer. In the present study, we examine to which extent covert intrapersonal actions (cognitions both related and unrelated to the emotion-eliciting stimulus) as well as overt interpersonal actions (social sharing) account for this variability in emotion duration. Participants were asked to report the duration of their anger, sadness, joy, and gratitude episodes on a daily basis during five days. Furthermore, information was collected with regard to their cognitions during the episodes and their social sharing behavior. Discrete-time survival analyses revealed that for three of the four emotions under study, stimulus-related cognitions with the same valence as the emotion lead to a prolongation of the episode; in contrast, both stimulus-related and stimulus-unrelated cognitions with a valence opposite to the emotion lead to a shortening. Finally, for the four emotions under study, social sharing was associated with a prolongation. The findings are discussed in terms of a possible process basis underlying the time dynamics of negative as well as positive emotions. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Learning to learn during visual discrimination in group housed dwarf goats (Capra hircus).

Using an automated learning device, we investigated "learning to learn" by dwarf goats (Capra hircus) in what was for them a familiar environment and normal social settings. Nine problems, each consisting of four discriminable black symbols, each with one S+ and three different S-, were presented on a computer screen. Mean daily learning success improved over the course of the first four problems, and the improvement was maintained throughout the remaining five problems. The number of trials to reach the learning criterion decreased significantly beginning with problem four. Such results may be interpreted as evidence that the goats were developing a learning set. In the present case, the learning set appeared to have two components. One involved gaining familiarity and apparent understanding of the learning device and the basic requirements of the discrimination task. The second component involved learning potential error factors to be ignored, as well as learning commonalities that carried over from one problem to the next. Among the error factors, evidence of apparent preferences for specific symbols was seen, which had a predictable effect on performances. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neurohormonal functioning and sexual orientation: A theory of homosexuality–heterosexuality.

Following a historical sketch of attempts to explain homosexuality, we review evidence indicating that the process of determining human sexual orientation is fundamentally the same in all mammals. In this process, four phenotypic dimensions of sexuality develop from two more or less distinct sex genotypes. Studies are reviewed that indicate how phenotypic deviations from these two genotypes (called sexual inversions) can occur. The causes of sexual inversions are categorized as genetic-hormonal, pharmacological, maternal stress, immunological, and social experiential. From this evidence, we propose a theory of how the entire spectrum of human sexual orientation (vs. simply homosexuality) is determined. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Genome scan for human obesity and linkage to markers in 20q13

Obesity is a highly prevalent, multigenic trait that predicts increased morbidity and mortality. Here we report results from a genome scan based on 354 markers in 513 members of 92 nuclear families ascertained through extreme obesity and normal body weight. The average marker interval was approximately 10 cM. We examined four correlated obesity phenotypes, including the body-mass index (BMI) (both as a quantitative trait and as a discrete trait with a threshold of BMI > or /=30 kg/m2) and percentage of fat (both as a quantitative trait and as a discrete trait with a threshold of 40%) as assessed by bioelectrical impedance. In the initial stage of the genome scan, four markers in 20q gave positive evidence for linkage, which was consistent across most obesity phenotypes and analytic methods. After saturating 20q with additional markers (25 markers total) in an augmented sample of 713 members from 124 families, we found linkage to several markers in a region, 20q13, previously implicated in both human and animal studies. Three markers (D20S107, D20S211, and D20S149) in 20q13 had empirical P values (based on Monte Carlo simulations, which controlled for multiple testing) < or /=. 01 for single-point analysis. In addition, the parametric, affecteds-only analysis for D20S476 yielded a LOD score of 3.06 (P=. 00009), and the affected-sib-pair test yielded a LOD score of 3.17 (P=.000067). Multipoint analyses further strengthened and localized these findings. This region includes several plausible candidate genes for obesity. Our results suggest that one or more genes affecting obesity are located in 20q13.     

Motivational factors in nonincarcerated sexually aggressive men.

Research on convicted rapists has demonstrated the importance of several key motivational factors in male sexual aggression. In particular, anger at women and the need to dominate or control them have been repeatedly implicated. Although anger and power have also been shown to be important in understanding college men who report sexually aggressive behavior, there has been little research on what underlies these motives. This research combined questions assessing these underlying motivational factors, as well as questions dealing with underlying sexual motivation and disinhibition, with a slightly modified version of the Sexual Experiences Survey (Koss & Oros, 1982). In Study 1, subjects were 184 male undergraduates. Factor analysis of the questions composing the four scales yielded four slightly modified scales. Scales measuring underlying anger, underlying power, and disinhibition significantly differentiated sexually aggressive from nonaggressive men but did not distinguish between men who were coercive, manipulative, or nonaggressive. In a replication on a smaller sample (n?=?70), underlying anger, underlying power, and disinhibition again differentiated sexually aggressive from nonaggressive men. (PsycINFO Database Record (c) 2010 APA, all rights reserved)