Brodersenvestergaard8820

Overall, this overview ultimately provides a rationale for the use of small-molecule HDAC6 inhibitors as a therapeutic strategy for this devastating disease. A direct measure of spoken lexical processing based on neuroimaging technology would provide us useful information to understand the neural mechanisms underlying speech or auditory language processing. The neural mechanisms of spoken word segmentation for English as a second language (ESL) learners remain elusive. The present study, using functional near-infrared spectroscopy (fNIRS), addresses this issue by measuring hemodynamic responses in the temporo-parietal junction (TPJ) and the prefrontal cortex (PFC) in a word-spotting task, designed with two task conditions (easy vs. difficult). Thirty participants, divided into a high listening proficiency group (HLG) and a low listening proficiency group (LLG), were tested. Results revealed significantly less TPJ activation in the HLG than in the LLG. Further analyses supported this result by showing that activation in the TPJ was in a negative correlation with listening proficiency. This association appears to be related to the more efficient use of processing resources in a bottom-up fashion for accurate and efficient sensory representations in high proficient language learners. In contrast, cortical activation in the PFC increased with listening proficiency and was stronger in the difficult task condition than in the easy task condition, implying that recruitment of top-down cognitive control functions might play a role in word segmentation. Our results suggest that the combination of the functions mediated via bottom-up sensory input processing (demonstrated in the TPJ activation) and top-down cognitive processing (demonstrated in the PFC activation) are crucial for ESL listeners' spoken word segmentation. V.Neuroimaging research has shown that patients with obsessive-compulsive disorder (OCD) may present brain structural and functional alterations, but the results across imaging modalities and task paradigms are difficult to reconcile. Are the same brain systems that are structurally different in OCD patients also involved in executive function and emotional processing? To answer this, we conducted separate meta-analyses of voxel-based morphometry studies, executive function functional magnetic resonance imaging (fMRI) studies, and emotional processing fMRI studies. Next, with a multimodal approach (conjunction analysis), we identified the common alterations across meta-analyses. Patients presented increased gray matter volume and hyperactivation in the putamen, but the putamen subregions affected differed depending on the psychological process. Left posterior/dorsal putamen showed hyperactivation during executive processing tasks, while predominantly right anterior/ventral putamen showed hyperactivation during emotional processing tasks. Interestingly, age was significantly associated with increased right putamen volume. Finally, the left dorsolateral prefrontal cortex was hyperactive in both functional domains. Our findings highlight task-specific correlates of brain structure and function in OCD and help integrate a growing literature. Animal models in neuropsychiatric research need validation. One way to address external validity is systematic reviews and meta-analyses. The present study presents a meta-analysis of the effects of antidepressants in the mouse tail suspension test (TST). A PubMed search identified studies that examined imipramine and fluoxetine effects in the TST. Inclusion criteria were testing in the light phase; trial duration was six minutes; immobility time scored 6 or (last) 4 min; adult mice; acute intraperitoneal (IP) administration. Effect sizes (ES) were estimated using Cohen's d, heterogeneity of ES with Cochran's Q test, correlations between dose and ES with Pearson's correlation and differences between strains with Analysis of variance. Results show that antidepressants decrease immobility time in the TST and a correlation between drug dose and ES but no effects of strain. We suggest that the TST is a valid tool to quantitatively, consistently and reproducibly capture the immobility-reducing aspects of fluoxetine and imipramine and that the lack of strain effects is due to small number of experiments in many of the strains. FK506 binding proteins (FKBPs) participate in regulation of diverse biological processes. However, the role of these proteins in insect-pathogenic fungi is far from well understood. To investigate the functions of FKBPs in Beauveria bassiana, a widely used entomopathogenic fungus for control of insect pests, we identify three putative FKBP genes, Bbfkbp12, Bbfkbp15, and Bbfkbp50, in the fungus. Gene-disruption experiments show that loss of Bbfkbp12 results in a significant increase of resistance of B. bassiana against the immunosuppressive compounds FK506 and rapamycin, while loss of Bbfkbp50 leads to the resistance to the ergosterol synthesis inhibitor lovastatin. Transcription assays of calcineurin (CaN)- and mTOR (mammalian target of rapamycin)-downstream target genes confirm that BbFKBP12 is the target of both FK506 and rapamycin, associated with CaN- and mTOR-signal pathways in B. bassiana. Selleck TGFbeta inhibitor GFP-tagging of the proteins shows that BbFKBP12 and BbFKBP15 localize in cytoplasm while BbFKBP50 in nucleus. Our results provide useful information for the study of functions of CaN- and mTOR-mediated signaling, and ergosterol synthesis in the entomopathogenic fungi. Millions of people are infected with the liver fluke, Opisthorchis viverrini (OV), but only ~25% of those infected develop liver disease and even fewer develop cholangiocarcinoma. The reasons for these differential outcomes following infection are unknown but it has been proposed that differential immune responses to the parasite may play a role. We therefore measured granulocyte (neutrophil) function in OV-infected individuals, with and without advanced periductal fibrosis, to determine if these cells have a "pro-inflammatory" phenotype that may contribute to liver disease post-infection. A case-controlled study (n = 54 in each cohort) from endemic OV-infected areas of northeastern Thailand measured neutrophil functions in whole blood from non-infected (healthy controls) and OV-infected individuals with and without APF. We measured reactive oxygen species production, phagocytosis, receptor expression and apoptosis. Secreted products from OV cultures (obtained after in vitro culture of parasites) stimulated reactive oxygen species production in non-infected healthy controls, but levels were two-fold greater after OV infection (P  less then  0.