Skinnermackay3922

Context guides perception by influencing stimulus saliency. Accordingly, in visual cortex, responses to a stimulus are modulated by context, the visual scene surrounding the stimulus. Responses are suppressed when stimulus and surround are similar but not when they differ. The underlying mechanisms remain unclear. Here, we use optical recordings, manipulations, and computational modeling to show that disinhibitory circuits consisting of vasoactive intestinal peptide (VIP)-expressing and somatostatin (SOM)-expressing inhibitory neurons modulate responses in mouse visual cortex depending on similarity between stimulus and surround, primarily by modulating recurrent excitation. When stimulus and surround are similar, VIP neurons are inactive, and activity of SOM neurons leads to suppression of excitatory neurons. However, when stimulus and surround differ, VIP neurons are active, inhibiting SOM neurons, which leads to relief of excitatory neurons from suppression. We have identified a canonical cortical disinhibitory circuit that contributes to contextual modulation and may regulate perceptual saliency.Anti-oxidant and anti-inflammatory properties of caffeic acid (CA) have been reported recently. In this study, the therapeutic effects of CA on ethanol-induced ulcer and the roles of nitric oxide and cholinergic pathways in these effects were investigated. Ulcer was induced by ethanol via oral gavage. Ulcer induced rats were treated with either vehicle (ulcer group) or CA (100, 250 or 500 mg/kg, per oral gavage). Macroscopic evaluation showed that 250 mg/kg CA was the effective dose. To elucidate the action mechanism of CA, 10 mg/kg l-NAME or 1 mg/kg atropine sulfate was administered to 250 mg/kg CA treated groups. All rats were decapitated 1 h after ulcer induction and gastric samples were scored macroscopically and microscopically, and analyzed for myeloperoxidase (MPO), malondialdehyde (MDA), and glutathione (GSH) levels. ANOVA test was used for statistical analyses. Macroscopic and microscopic damage scores, MDA levels and MPO activity were increased while GSH levels were decreased in ulcer group. Treatment with 250 mg/kg and 500 mg/kg CA reduced macroscopic and microscopic damage scores, decreased MPO activity and MDA levels, and preserved the depleted glutathione significantly. l-NAME administration before CA treatment elevated MDA levels, MPO activity and depleted glutathione. However, atropine sulfate had no effect on biochemical parameters. We conclude that CA ameliorates ethanol-induced gastric mucosal damage, and NO pathway contributes to this effect. On the other hand, there is a lack of evidence for the contribution of the muscarinic cholinergic system.Production of leavened bread dates to the second millennium BCE. Since then, the art of bread making has developed, yet the evolution of bread-associated microbial species remains largely unknown. Nowadays, leavened bread is made either by using a pure commercial culture of the yeast Saccharomyces cerevisiae or by propagating a sourdough-a mix of flour and water spontaneously fermented by yeasts and bacteria. We studied the domestication of S. cerevisiae originating from industrial sources and artisanal sourdoughs and tested whether different bread-making processes led to population divergence. We found that S. cerevisiae bakery strains are polyphyletic with 67% of strains clustering into two main clades most industrial strains were tetraploid and clustered with strains having diverse origins, including beer. By contrast, most sourdough strains were diploid and grouped in a second clade of strains having mosaic genomes and diverse origins, including fruits and natural environments. They harbored a higher copy number of genes involved in maltose utilization, and a high level of gene flow from multiple contributors was detected. this website Bakery strains displayed higher CO2 production than do strains from other domesticated lineages (such as beer and wine), revealing a specific phenotypic signature of domestication. Interestingly, industrial strains had a shorter fermentation onset than sourdough strains, which were better adapted to a sourdough-like environment, suggesting divergent selection by industrial and artisanal processes. Our results reveal that the domestication of bakery yeast has been accompanied by dispersion, hybridization, and divergent selection through industrial and artisanal processes.Eastern equine encephalitis virus (EEEV) is one of the most virulent viruses endemic to North America. No licensed vaccines or antiviral therapeutics are available to combat this infection, which has recently shown an increase in human cases. Here, we characterize human monoclonal antibodies (mAbs) isolated from a survivor of natural EEEV infection with potent ( less then 20 pM) inhibitory activity of EEEV. Cryo-electron microscopy reconstructions of two highly neutralizing mAbs, EEEV-33 and EEEV-143, were solved in complex with chimeric Sindbis/EEEV virions to 7.2 Å and 8.3 Å, respectively. The mAbs recognize two distinct antigenic sites that are critical for inhibiting viral entry into cells. EEEV-33 and EEEV-143 protect against disease following stringent lethal aerosol challenge of mice with highly pathogenic EEEV. These studies provide insight into the molecular basis for the neutralizing human antibody response against EEEV and can facilitate development of vaccines and candidate antibody therapeutics.Obesity is a major cancer risk factor, but how differences in systemic metabolism change the tumor microenvironment (TME) and impact anti-tumor immunity is not understood. Here, we demonstrate that high-fat diet (HFD)-induced obesity impairs CD8+ T cell function in the murine TME, accelerating tumor growth. We generate a single-cell resolution atlas of cellular metabolism in the TME, detailing how it changes with diet-induced obesity. We find that tumor and CD8+ T cells display distinct metabolic adaptations to obesity. Tumor cells increase fat uptake with HFD, whereas tumor-infiltrating CD8+ T cells do not. These differential adaptations lead to altered fatty acid partitioning in HFD tumors, impairing CD8+ T cell infiltration and function. Blocking metabolic reprogramming by tumor cells in obese mice improves anti-tumor immunity. Analysis of human cancers reveals similar transcriptional changes in CD8+ T cell markers, suggesting interventions that exploit metabolism to improve cancer immunotherapy.