Advancing the defensive explanation for anxiety disorders: lorazepam effects on human defense are systematically modulated by personality and threat-type

Clinically effective drugs against human anxiety and fear systematically alter the innate defensive behavior of rodents, suggesting that in humans these emotions reflect defensive adaptations. Compelling experimental human evidence for this theory is yet to be obtained. We report the clearest test to date by investigating the effects of 1 and 2mg of the anti-anxiety drug lorazepam on the intensity of threat-avoidance behavior in 40 healthy adult volunteers (20 females). We found lorazepam modulated the intensity of participants’ threat-avoidance behavior in a dose-dependent manner. However, the pattern of effects depended upon two factors: type of threat-avoidance behavior and theoretically relevant measures of personality. In the case of flight behavior (one-way active avoidance), lorazepam increased intensity in low scorers on the Fear Survey Schedule tissuedamage fear but reduced it in high scorers. Conversely, in the case of risk-assessment behavior (two-way active avoidance), lorazepam reduced intensity in low scorers on the Spielberger trait anxiety but increased it in high scorers. Anti-anxiety drugs do not systematically affect rodent flight behavior; therefore, we interpret this new finding as suggesting that lorazepam has a broader effect on defense in humans than in rodents, perhaps by modulating general perceptions of threat intensity. The different patterning of lorazepam effects on the two behaviors implies that human perceptions of threat intensity are nevertheless distributed across two different neural streams, which influence effects observed on one-way or two-way active avoidance demanded by the situation

Grassmannian flows and applications to nonlinear partial differential equations

We show how solutions to a large class of partial differential equations with nonlocal Riccati-type nonlinearities can be generated from the corresponding linearized equations, from arbitrary initial data. It is well known that evolutionary matrix Riccati equations can be generated by projecting linear evolutionary flows on a Stiefel manifold onto a coordinate chart of the underlying Grassmann manifold. Our method relies on extending this idea to the infinite dimensional case. The key is an integral equation analogous to the Marchenko equation in integrable systems, that represents the coodinate chart map. We show explicitly how to generate such solutions to scalar partial differential equations of arbitrary order with nonlocal quadratic nonlinearities using our approach. We provide numerical simulations that demonstrate the generation of solutions to Fisher--Kolmogorov--Petrovskii--Piskunov equations with nonlocal nonlinearities. We also indicate how the method might extend to more general classes of nonlinear partial differential systems.Comment: 26 pages, 2 figure

Diversity and Seasonal Dynamics of an Assemblage of Sarcophagid Diptera in a Gradient of Urbanization

Sarcophagid species inhabiting different locations in a rural-urban gradient were surveyed in the east central Argentine district of the Almirante Brown, Buenos Aires province. The main objectives of this research were to identify the most prevalent sarcophagid species and to describe community richness and diversity according to the degree of urbanization and the environmental variables measured in three locations within a rural-urban gradient sampled during two years from May 2005 to April 2007. Spatial and seasonal variations were the main factors involved in structuring the sarcophagid communities. Diversity was lower in urbanized areas than in rural ones. Bait and microhabitat preferences (sunny or shady places) and seasonal fluctuations were described for 17 sarcophagid species

Desenvolvimento de instrumento para medida dos fatores psicossociais determinantes do comportamento de atividade física em coronariopatas

Este estudo teve como objetivo apresentar o desenvolvimento, a análise de conteúdo e da confiabilidade do Questionário para identificação dos fatores psicossociais determinantes do comportamento de atividade física em coronariopatas, baseado na extensão da Teoria do Comportamento Planejado. O instrumento foi submetido à validade de conteúdo, com realização de sua avaliação por três juízes e pré-teste com cinco sujeitos, até mostrar-se conceitualmente adequado e compreensível aos sujeitos entrevistados. Foi aplicado em 51 sujeitos para a avaliação preliminar da consistência interna, por meio da determinação do coeficiente alfa de Crombach. Foram observados coeficientes alfa de Crombach >0,75 para os constructos Intenção, Atitude, Norma Subjetiva, Autoeficácia e Hábito. O instrumento desenvolvido mostrou evidências de validade de conteúdo e de confiabilidade.Este estudio tuvo como objetivo presentar el desarrollo, el análisis de contenido y de confiabilidad del Cuestionario para la identificación de los factores psicosociales determinantes del comportamiento de actividad física en pacientes afectados de coronariopatías, basado en la extensión de la Teoría del Comportamiento Planificado. Se sometió la validez del contenido del instrumento a la evaluación por parte de tres jueces y pre test con cinco sujetos, hasta mostrarse conceptualmente adecuado y comprensible para los sujetos entrevistados. Fue aplicado en 51 sujetos para la evaluación preliminar de consistencia interna, a través de la determinación del coeficiente Alfa de Cronbach. Fueron observados coeficientes Alfa de Cronbach >0,75 para los constructos Intención, Actitud, Norma Subjetiva, Autoeficacia y Hábito. El instrumento desarrollado evidenció la validez de su contenido, así como su confiabilidad.The aim of this study was to report the development and the analysis of content validity and reliability of the Psychosocial Determinants of Physical Activity among Coronary Heart Disease Patients Questionnaire, based on an extension of the Theory of Planned Behavior. In the content validity step, three experts evaluated the instrument which was, afterwards, pre-tested with five subjects in order to obtain a conceptually appropriate and easily understood instrument. Fifty-one patients participated in the evaluation of internal consistency of the reviewed instrument. Cronbach's alpha coefficients above 0.75 were observed for the constructs: Intention, Attitude, Subjective Norm, Self-efficacy and Habit. The new instrument demonstrated acceptable evidence of content validity and reliability

Regional Grey Matter Structure Differences between Transsexuals and Healthy Controls-A Voxel Based Morphometry Study.

Gender identity disorder (GID) refers to transsexual individuals who feel that their assigned biological gender is incongruent with their gender identity and this cannot be explained by any physical intersex condition. There is growing scientific interest in the last decades in studying the neuroanatomy and brain functions of transsexual individuals to better understand both the neuroanatomical features of transsexualism and the background of gender identity. So far, results are inconclusive but in general, transsexualism has been associated with a distinct neuroanatomical pattern. Studies mainly focused on male to female (MTF) transsexuals and there is scarcity of data acquired on female to male (FTM) transsexuals. Thus, our aim was to analyze structural MRI data with voxel based morphometry (VBM) obtained from both FTM and MTF transsexuals (n = 17) and compare them to the data of 18 age matched healthy control subjects (both males and females). We found differences in the regional grey matter (GM) structure of transsexual compared with control subjects, independent from their biological gender, in the cerebellum, the left angular gyrus and in the left inferior parietal lobule. Additionally, our findings showed that in several brain areas, regarding their GM volume, transsexual subjects did not differ significantly from controls sharing their gender identity but were different from those sharing their biological gender (areas in the left and right precentral gyri, the left postcentral gyrus, the left posterior cingulate, precuneus and calcarinus, the right cuneus, the right fusiform, lingual, middle and inferior occipital, and inferior temporal gyri). These results support the notion that structural brain differences exist between transsexual and healthy control subjects and that majority of these structural differences are dependent on the biological gender

Vitamin D supplementation decreases Aspergillus fumigatus specific Th2 responses in CF patients with aspergillus sensitization: A phase one open-label study

Background: Patients with cystic fibrosis (CF) complicated by allergic bronchopulmonary aspergillosis (ABPA) are vitamin D deficient and in vitro treatment with 1,25 (OH) vitamin D of CD4+ cells from CF patients with ABPA decreases Aspergillus fumigatus(Af)-induced Th2 responses. This Phase I clinical trial investigated the safety and effectiveness of daily vitamin D supplementation in CF patients with ABPA to reduce allergic responses and ABPA symptoms, and increase serum vitamin D levels. Methods: Seven patients ages 12 years and older with a clinical diagnosis of CF and ABPA with current evidence of Af sensitization received 4000 IU vitamin D (cholecalciferol) daily for 24 weeks. The primary outcome of the study was safety followed by the Aspergillus induced IL-13 response in CD4+ T cells to test the hypothesis that vitamin D supplementation is safe and reduces Aspergillus induced IL-13 responses in CD4+ T cells. Secondary outcomes included total IgE, Aspergillus- specific IgE, vitamin D levels, FEV , urinary calcium/creatinine ratio, and cytokine production by Aspergillus-stimulated peripheral blood T cells. Results: Six months of vitamin D supplementation resulted in significant increases in serum 25-(OH) vitamin D level, and the treatment was well tolerated without evidence of vitamin D toxicity or hypercalcemia. There were no serious adverse events. Daily vitamin D supplementation led to significantly decreased Aspergillus induced IL-13 responses between the baseline visit and that at 24 weeks (p = 0.04). Aspergillus-specific IgE level was also significantly decreased after 8 (p = 0.035) and 24 weeks of daily vitamin D supplementation (p = 0.04). Conclusions: 4000 IU vitamin D daily over a 24-week period is well tolerated in CF patients with a history ABPA and current evidence of Th2 immunity to Af. Daily vitamin D supplementation was associated with reduced Aspergillus induced IL-13 responses from peripheral. CD4+ T cells and Aspergillus-specific IgE levels, as well as increased serum vitamin D levels. This treatment was well tolerated and the study supports further investigation of the use of vitamin D supplementation in Th2 mediated diseases. 2 3 3 3 1 3

Alteration of Sequence Specificity of the Type IIS Restriction Endonuclease BtsI

The Type IIS restriction endonuclease BtsI recognizes and digests at GCAGTG(2/0). It comprises two subunits: BtsIA and BtsIB. The BtsIB subunit contains the recognition domain, one catalytic domain for bottom strand nicking and part of the catalytic domain for the top strand nicking. BtsIA has the rest of the catalytic domain that is responsible for the DNA top strand nicking. BtsIA alone has no activity unless it mixes with BtsIB to reconstitute the BtsI activity. During characterization of the enzyme, we identified a BtsIB mutant R119A found to have a different digestion pattern from the wild type BtsI. After characterization, we found that BtsIB(R119A) is a novel restriction enzyme with a previously unreported recognition sequence CAGTG(2/0), which is named as BtsI-1. Compared with wild type BtsI, BtsI-1 showed different relative activities in NEB restriction enzyme reaction buffers NEB1, NEB2, NEB3 and NEB4 and less star activity. Similar to the wild type BtsIB subunit, the BtsI-1 B subunit alone can act as a bottom nicking enzyme recognizing CAGTG(-/0). This is the first successful case of a specificity change among this restriction endonuclease type

Growth factor stimulation of cardiomyocytes induces changes in the transcriptional contents of secreted exosomes

Exosomes are nano-sized extracellular vesicles, released from various cells, which can stimulate or repress responses in targets cells. We recently reported that cultured cardiomyocytes are able to release exosomes and that they, in turn, are involved in facilitating events in target cells by alteration of gene expression. We investigated whether external stimuli of the cardiomyocyte might influence the transcriptional content of the released exosomes.Exosomes were isolated from media collected from cultured cardiomyocytes (HL-1) with or without growth factor treatment (TGF-β2 and PDGF-BB), with a series of differential centrifugations, including preparative ultracentrifugation and separation with a sucrose gradient. The exosomes were characterized with dynamic light scattering (DLS), electron microscopy (EM) and Western blot and analyzed with Illumina whole genome microarray gene expression.The exosomes were rounded in shape and had an average size of 50–90 nm in diameter with no difference between treatment groups. Analysis of the mRNA content in repeated experiments conclusively revealed 505 transcripts in the control group, 562 in the TGF-β2-treated group and 300 in the PDGF-BB-treated group. Common transcripts (217) were found in all 3 groups.We show that the mode of stimulation of parental cells affects the characteristics of exosomes released. Hence, there is a difference in mRNA content between exosomes derived from cultured cardiomyocytes stimulated, or not stimulated, with growth factors. We also conclude that all exosomes contain a basic package consisting of ribosomal transcripts and mRNAs coding for proteins with functions within the energy supply system. To access the supplementary material to this article, please see Supplementary files under Article Tools online