Inconsistent analytic strategies reduce robustness in fear extinction via skin conductance response

Robustness of fear conditioning and extinction paradigms has become increasingly important for many researchers interested in improving the study of anxiety and trauma disorders. We recently illustrated the wide variability in data analysis techniques in this paradigm, which we argued may result in lack of robustness. In the current study, we resampled data from six of our own fear acquisition and extinction datasets, with skin conductance as the outcome. In the resampled and original datasets, we found that effect sizes that were calculated using discrepant statistical strategies, sourced from a non-exhaustive search of high-impact articles, were often poorly correlated. The main contributors to poor correlations were selection of trials from different stages of each experimental phase and use of averaged compared to trial-by-trial analysis. These findings reinforce the importance of focusing on robustness in psychophysiological measurement of fear acquisition and extinction in the laboratory and may guide prospective researchers in which decisions may most impact the robustness of their results

Assessment of resolution and intercenter reproducibility of results of genotyping Staphylococcus aureus by pulsed-field gel electrophoresis of SmaI macrorestriction fragments: a multicenter study

Twenty well-characterized isolates of methicillin-resistant Staphylococcus aureus were used to study the optimal resolution and interlaboratory reproducibility of pulsed-field gel electrophoresis (PFGE) of DNA macrorestriction fragments. Five identical isolates (one PFGE type), 5 isolates that produced related PFGE subtypes, and 10 isolates with unique PFGE patterns were analyzed blindly in 12 different laboratories by in-house protocols. In several laboratories a standardized PFGE protocol with a commercial kit was applied successfully as well. Eight of the centers correctly identified the genetic homogeneity of the identical isolates by both the in-house and standard protocols. Four of 12 laboratories failed to produce interpretable data by the standardized protocol, due to technical problems (primarily plug preparation). With the five rel

Transcriptional programs regulating neuronal differentiation are disrupted in DLG2 knockout human embryonic stem cells and enriched for schizophrenia and related disorders risk variants

Coordinated programs of gene expression drive brain development. It is unclear which transcriptional programs, in which cell-types, are affected in neuropsychiatric disorders such as schizophrenia. Here we integrate human genetics with transcriptomic data from differentiation of human embryonic stem cells into cortical excitatory neurons. We identify transcriptional programs expressed during early neurogenesis in vitro and in human foetal cortex that are down-regulated in DLG2−/− lines. Down-regulation impacted neuronal differentiation and maturation, impairing migration, morphology and action potential generation. Genetic variation in these programs is associated with neuropsychiatric disorders and cognitive function, with associated variants predominantly concentrated in loss-of-function intolerant genes. Neurogenic programs also overlap schizophrenia GWAS enrichment previously identified in mature excitatory neurons, suggesting that pathways active during prenatal cortical development may also be associated with mature neuronal dysfunction. Our data from human embryonic stem cells, when combined with analysis of available foetal cortical gene expression data, de novo rare variants and GWAS statistics for neuropsychiatric disorders and cognition, reveal a convergence on transcriptional programs regulating excitatory cortical neurogenesis

Synaptic protein DLG2 controls neurogenic transcriptional programs disrupted in schizophrenia and related disorders

Genetic studies robustly implicate perturbation of DLG2-scaffolded mature postsynaptic signalling complexes in schizophrenia. Here we study in vitro cortical differentiation of DLG2-/- human embryonic stem cells via integrated phenotypic, gene expression and disease genetic analyses. This uncovers a developmental role for DLG2 in the regulation of neural stem cell proliferation and adhesion, and the activation of transcriptional programs during early excitatory corticoneurogenesis. Down-regulation of these programs in DLG2-/- lines delays expression of cell-type identity and causes marked deficits in neuronal migration, morphology and active properties. Genetic risk factors for neuropsychiatric and neurodevelopmental disorders converge on these neurogenic programs, each disorder displaying a distinct pattern of enrichment. These data unveil an intimate link between neurodevelopmental and mature signalling deficits contributing to disease - suggesting a dual role for known synaptic risk genes - and reveal a common pathophysiological framework for studying the neurodevelopmental origins of Mendelian and genetically complex mental disorders

Efeito anti-helmíntico dos extratos aquosos e etanólicos da Annona squamosa L. (fruta-do-conde) sobre o nematóide Ascaridia galli Anthelmintic effect of aqueous and ethanolic extracts from Annona squamosa L. (sweetsop) on the nematode Ascaridia galli

As plantas são fontes importantes de produtos naturais biologicamente ativos. Dentre as plantas usadas na medicina popular a Anonna squamosa conhecida como fruta-do-conde é citada como tendo várias ações medicinais, dentre elas a atividade inseticida e anti-helmíntica. Dentro desta perspectiva, objetivou-se determinar a atividade anti-helmíntica dos extratos aquosos (EA) e etanólicos (EE) das folhas da fruta-do-conde sobre o nematóide de aves Ascaridia galli, in vitro e in vivo. No primeiro, os nematóides foram colocados em placa de Petri contendo diferentes concentrações dos extratos e no segundo foram utilizadas seis galinhas poedeiras por grupo, as quais foram administrados10 mL Kg-1 dos extratos. No teste in vitro o EA da A. squamosa nas concentrações 2,4 e 9,6 mg mL-1 foi capaz de matar 63,33% e 53,33% dos nematóides, respectivamente. O EE não produziu efeito significativo. No teste in vivo, o percentual de eliminação do EA foi de 39% e do EE de 20%. Estes dados sugerem que neste caso a substância responsável pela mortalidade dos parasitos esteja em maior concentração na fração aquosa. Desta maneira, acredita-se que o EA de A. squamosa apresenta uma atividade anti-helmíntica potencial sobre o A. galli.<br>Plants are important sources of biologically active natural products. Among the plants used in popular medicine, Annona squamosa, known as sweetsop, is reported to have several medicinal actions such as insecticidal and anthelmintic activity. Therefore, this study aimed to assess the anthelmintic activity of aqueous (AE) and ethanolic (EE) extracts from sweetsop leaves on the chicken roundworm Ascaridia galli, both in vitro and in vivo. In the former, nematodes were placed on a Petri plate containing different concentrations of the extracts; in the in vivo test, six egg-laying chickens per group received 10 mL Kg-1 of the extracts. In vitro results indicated that A. squamosa AE at the concentrations 2.4 and 9.6 mg mL-1 could kill 63.33% and 53.33% nematodes, respectively. However, EE did not have any significant effect. According to the in vivo test, the elimination percentage for AE was 39% and for EE, 20%. These data suggest that the substance responsible for parasite mortality was present at a higher concentration in the aqueous fraction. Thus, A. squamosa AE is believed to have a potential anthelmintic activity on A. galli