Dorsal striatum does not mediate feedback-based, stimulus-response learning: An event-related fMRI study in patients with Parkinson\u27s disease tested on and off dopaminergic therapy

© 2018 Learning associations between stimuli and responses is essential to everyday life. Dorsal striatum (DS) has long been implicated in stimulus-response learning, though recent results challenge this contention. We have proposed that discrepant findings arise because stimulus-response learning methodology generally confounds learning and response selection processes. In 19 patients with Parkinson\u27s disease (PD) and 18 age-matched controls, we found that dopaminergic therapy decreased the efficiency of stimulus-response learning, with corresponding attenuation of ventral striatum (VS) activation. In contrast, exogenous dopamine improved response selection accuracy related to enhanced DS BOLD signal. Contrasts between PD patients and controls fully support these within-subject patterns. These double dissociations in terms of behaviour and neural activity related to VS and DS in PD and in response to dopaminergic therapy, strongly refute the view that DS mediates stimulus-response learning through feedback. Our findings integrate with a growing literature favouring a role for DS in decision making rather than learning, and unite two literature that have been evolving independently

HDAC3 is a molecular brake of the metabolic switch supporting white adipose tissue browning.

White adipose tissue (WAT) can undergo a phenotypic switch, known as browning, in response to environmental stimuli such as cold. Post-translational modifications of histones have been shown to regulate cellular energy metabolism, but their role in white adipose tissue physiology remains incompletely understood. Here we show that histone deacetylase 3 (HDAC3) regulates WAT metabolism and function. Selective ablation of Hdac3 in fat switches the metabolic signature of WAT by activating a futile cycle of de novo fatty acid synthesis and β-oxidation that potentiates WAT oxidative capacity and ultimately supports browning. Specific ablation of Hdac3 in adipose tissue increases acetylation of enhancers in Pparg and Ucp1 genes, and of putative regulatory regions of the Ppara gene. Our results unveil HDAC3 as a regulator of WAT physiology, which acts as a molecular brake that inhibits fatty acid metabolism and WAT browning.Histone deacetylases, such as HDAC3, have been shown to alter cellular metabolism in various tissues. Here the authors show that HDAC3 regulates WAT metabolism by activating a futile cycle of fatty acid synthesis and oxidation, which supports WAT browning

Fitness Correlates Of Song Repertoire Size In Free-Living Song Sparrows (Melospiza Melodia)

Models of sexual selection propose that exaggerated secondary sexual ornaments indicate a male\u27s own fitness and the fitness of his offspring. These hypotheses have rarely been thoroughly tested in free-living individuals because overall fitness, as opposed to fitness components, is difficult to measure. We used 20 years of data from song sparrows ( Melospiza melodia) inhabiting Mandarte Island, British Columbia, Canada, to test whether a male\u27s song repertoire size, a secondary sexual trait, predicted overall measures of male or offspring fitness. Males with larger song repertoires contributed more independent and recruited offspring, and independent and recruited grandoffspring, to Mandarte\u27s population. This was because these males lived longer and reared a greater proportion of hatched chicks to independence from parental care, not because females mated to males with larger repertoires laid or hatched more eggs. Furthermore, independent offspring of males with larger repertoires were more likely to recruit and then to leave more grandoffspring than were offspring of males with small repertoires. Although we cannot distinguish whether observed fitness variation reflected genetic or environmental effects on males or their offspring, these data suggest that female song sparrows would gain immediate and intergenerational fitness benefits by pairing with males with large song repertoires

Imaging the dephasing of spin wave modes in a square thin film magnetic element

Copyright © 2004 The American Physical SocietyWe have used time-resolved scanning Kerr effect microscopy to study dephasing of spin wave modes in a square Ni81Fe19 element of 10 μm width and 150 nm thickness. When a static magnetic field H was applied parallel to an edge of the square, demagnetized regions appeared at the edges orthogonal to the field. When H was applied along a diagonal, a demagnetized region appeared along the opposite diagonal. Time-resolved images of the out-of-plane magnetization component showed stripes that lie perpendicular to H and indicate the presence of spin wave modes with wave vector parallel to the static magnetization. The transient Kerr rotation was measured at different positions along an axis parallel to H, and the power spectra revealed a number of different modes. Micromagnetic simulations reproduce both the observed images and the mode frequencies. This study allows us to understand an anisotropic damping observed at the center of the square element in terms of dephasing of the resonant mode spectrum

Measurement of the Spin Correlation Parameters all and Asl for the Reaction Pp-]D-Pi+ in the Energy Region 500-800 Mev

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Early numerical competencies in 5- and 6-year-old children with autism spectrum disorder

Research Findings: To date, studies comparing the mathematical abilities of children with autism spectrum disorder (ASD) and typically developing children are scarce, and results remain inconclusive. In general, studies on this topic focus on mathematical abilities learned from elementary school onward, with little attention for possible precursors at younger ages. The current exploratory study focused on the important developmental period of preschool age, investigating 5 early numerical competencies in 30 high-functioning children with ASD and 30 age-matched control children: verbal subitizing, counting, magnitude comparison, estimation, and arithmetic operations. Children were examined at 5 or 6 years of age, attending the 3rd and final year of preschool. Overall, rather similar early number processing was found in children with and without ASD, although marginally significant results indicated a weaker performance of children with ASD on verbal subitizing and conceptual counting. Practice or Policy: Given the pervasiveness and impact of ASD on other domains of functioning, it is important to know that no general deficits in early numerical competencies were found in this study. However, some downward trends in mathematics performance were identified in children with ASD, which can serve as the basis for additional research in this field

MTG16 regulates colonic epithelial differentiation, colitis, and tumorigenesis by repressing E protein transcription factors

Aberrant epithelial differentiation and regeneration contribute to colon pathologies, including inflammatory bowel disease (iBD) and colitis-associated cancer (CAC). Myeloid translocation gene 16 (MTG16, also known as CBFA2T3) is a transcriptional corepressor expressed in the colonic epithelium. MTG16 deficiency in mice exacerbates colitis and increases tumor burden in CAC, though the underlying mechanisms remain unclear. Here, we identified MTG16 as a central mediator of epithelial differentiation, promoting goblet and restraining enteroendocrine cell development in homeostasis and enabling regeneration following dextran sulfate sodium-induced (DSS-induced) colitis. Transcriptomic analyses implicated increased Ephrussi box-binding transcription factor (E protein) activity in MTG16-deficient colon crypts. Using a mouse model with a point mutation that attenuates MTG16:E protein interactions (Mtg16(P20ST)), we showed that MTG16 exerts control over colonic epithelial differentiation and regeneration by repressing E protein-mediated transcription. Mimicking murine colitis, MTG16 expression was increased in biopsies from patients with active IBD compared with unaffected controls. Finally, uncoupling MTG16:E protein interactions partially phenocopied the enhanced tumorigenicity of Mtg16(-/)(-) colon in the azoxymethane/DSS-induced model of CAC, indicating that MTG16 protects from tumorigenesis through additional mechanisms. Collectively, our results demonstrate that MTG16, via its repression of E protein targets. is a key regulator of cell fate decisions during colon homeostasis, colitis, and cancer.Peer reviewe