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Anabolic steroid hormonal influence on melanomagenesis.
Similar eating was induced by stimulation of LH GABA terminals or GABA cell bodies in this peri-LC region. Lesion of peri-LC GABA neurons blocked LH stimulation-induced eating, establishing them as a critical downstream circuit element for LH neurons. Surprisingly, lesions did not alter body weight, suggesting that this system is not involved in the hunger or satiety mechanisms that govern normal feeding. Thus, we present a characterization of brain circuitry that may promote overeating and contribute to obesity. Copyright © 2020 the Author(s). Published by PNAS.Working memory (WM) plays an important role in action planning and decision making; however, both the informational content of memory and how that information is used in decisions remain poorly understood. To investigate this, we used a color WM task in which subjects viewed colored stimuli and reported both an estimate of a stimulus color and a measure of memory uncertainty, obtained through a rewarded decision. Reported memory uncertainty is correlated with memory error, showing that people incorporate their trial-to-trial memory quality into rewarded decisions. Moreover, memory uncertainty can be combined with other sources of information; after inducing expectations (prior beliefs) about stimuli probabilities, we found that estimates became shifted toward expected colors, with the shift increasing with reported uncertainty. The data are best fit by models in which people incorporate their trial-to-trial memory uncertainty with potential rewards and prior beliefs. Our results suggest that WM represents uncertainty information, and that this can be combined with prior beliefs. This highlights the potential complexity of WM representations and shows that rewarded decision can be a powerful tool for examining WM and informing and constraining theoretical, computational, and neurobiological models of memory. DMXAA ic50 Copyright © 2020 the Author(s). Published by PNAS.In the adult brain, vascular endothelial growth factor D (VEGFD) is required for structural integrity of dendrites and cognitive abilities. Alterations of dendritic architectures are hallmarks of many neurologic disorders, including stroke-induced damage caused by toxic extrasynaptic NMDA receptor (eNMDAR) signaling. Here we show that stimulation of eNMDARs causes a rapid shutoff of VEGFD expression, leading to a dramatic loss of dendritic structures. Using the mouse middle cerebral artery occlusion (MCAO) stroke model, we have established the therapeutic potential of recombinant mouse VEGFD delivered intraventricularly to preserve dendritic architecture, reduce stroke-induced brain damage, and facilitate functional recovery. An easy-to-use therapeutic intervention for stroke was developed that uses a new class of VEGFD-derived peptide mimetics and postinjury nose-to-brain delivery.Human tuberculosis is caused by members of the Mycobacterium tuberculosis complex (MTBC) that vary in virulence and transmissibility. While genome-wide association studies have uncovered several mutations conferring drug resistance, much less is known about the factors underlying other bacterial phenotypes. Variation in the outcome of tuberculosis infection and diseases has been attributed primarily to patient and environmental factors, but recent evidence indicates an additional role for the genetic diversity among MTBC clinical strains. Here, we used metabolomics to unravel the effect of genetic variation on the strain-specific metabolic adaptive capacity and vulnerability. To define the functionality of single-nucleotide polymorphisms (SNPs) systematically, we developed a constraint-based approach that integrates metabolomic and genomic data. Our model-based predictions correctly classify SNP effects in pyruvate kinase and suggest a genetic basis for strain-specific inherent baseline susceptibility to the antibiotic para-aminosalicylic acid. Our method is broadly applicable across microbial life, opening possibilities for the development of more selective treatment strategies.In the 16th century, the Calusa, a fisher-gatherer-hunter society, were the most politically complex polity in Florida, and the archaeological site of Mound Key was their capital. Based on historic documents, the ruling elite at Mound Key controlled surplus production and distribution. The question remains exactly how such surplus pooling occurred and when such traditions were elaborated on and reflected in the built environment. Our work focuses on the "watercourts" and associated areas at Mound Key. These subrectangular constructions of shell and other sediments around centralized inundated areas have been variously interpreted. Here, we detail when these enclosures were constructed and their engineering and function. We argue that these structures were for large surplus capture and storage of aquatic resources that were controlled and managed by corporate groups.Nearly 20% of tropical forests are within 100 m of a nonforest edge, a consequence of rapid deforestation for agriculture. Despite widespread conversion, roughly 1.2 billion ha of tropical forest remain, constituting the largest terrestrial component of the global carbon budget. Effects of deforestation on carbon dynamics in remnant forests, and spatial variation in underlying changes in structure and function at the plant scale, remain highly uncertain. Using airborne imaging spectroscopy and light detection and ranging (LiDAR) data, we mapped and quantified changes in forest structure and foliar characteristics along forest/oil palm boundaries in Malaysian Borneo to understand spatial and temporal variation in the influence of edges on aboveground carbon and associated changes in ecosystem structure and function. We uncovered declines in aboveground carbon averaging 22% along edges that extended over 100 m into the forest. Aboveground carbon losses were correlated with significant reductions in canopy height and leaf mass per area and increased foliar phosphorus, three plant traits related to light capture and growth. Carbon declines amplified with edge age. Our results indicate that carbon losses along forest edges can arise from multiple, distinct effects on canopy structure and function that vary with edge age and environmental conditions, pointing to a need for consideration of differences in ecosystem sensitivity when developing land-use and conservation strategies. Our findings reveal that, although edge effects on ecosystem structure and function vary, forests neighboring agricultural plantations are consistently vulnerable to long-lasting negative effects on fundamental ecosystem characteristics controlling primary productivity and carbon storage.
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