Spatial dysregulation of T follicular helper cells impairs vaccine responses in aging.

The magnitude and quality of the germinal center (GC) response decline with age, resulting in poor vaccine-induced immunity in older individuals. A functional GC requires the co-ordination of multiple cell types across time and space, in particular across its two functionally distinct compartments: the light and dark zones. In aged mice, there is CXCR4-mediated mislocalization of T follicular helper (TFH) cells to the dark zone and a compressed network of follicular dendritic cells (FDCs) in the light zone. Here we show that TFH cell localization is critical for the quality of the antibody response and for the expansion of the FDC network upon immunization. The smaller GC and compressed FDC network in aged mice were corrected by provision of TFH cells that colocalize with FDCs using CXCR5. This demonstrates that the age-dependent defects in the GC response are reversible and shows that TFH cells support stromal cell responses to vaccines

An analysis of the deinstitutionalization of inflation-adjusted accounting practices in Brazilian companies

This article aims to analyze the deinstitutionalization of the inflation-adjustment accounting practices used by large Brazilian companies. The theoretical assumptions used were based on institutional theory, which provides a sociological interpretation of human behavior that recognizes the phenomenon of limited rationality and the political character of social action. Analyses were based on the empirical approach that was proposed by Oliver (1992). The research strategy consisted of questionnaires and interviews conducted in a population of 118 large Brazilian companies from Exame Magazine's list of the 500 largest companies. The primary respondents were accountants and controllers. Factor analysis, one-way ANOVA and the Kruskal-Wallis test were conducted using the approach proposed by Oliver (1992), and the research included 22 variables comprising 12 constructs and 6 qualitative hypotheses regarding the pressures that motivate the deinstitutionalization of inflation-adjusted accounting practices. Therefore, with regard to the constructs assessed, emphasis was placed on identifying the political pressures (the environment) and the functional pressures in both the organizational and environmental dimensions. However, the social pressures did not prove to be significant. We conclude that the process of deinstitutionalization results from a distinct combination of institutional factors, and these results are consistent with the findings from research conducted in the US market and in the UK

Brain energy rescue:an emerging therapeutic concept for neurodegenerative disorders of ageing

The brain requires a continuous supply of energy in the form of ATP, most of which is produced from glucose by oxidative phosphorylation in mitochondria, complemented by aerobic glycolysis in the cytoplasm. When glucose levels are limited, ketone bodies generated in the liver and lactate derived from exercising skeletal muscle can also become important energy substrates for the brain. In neurodegenerative disorders of ageing, brain glucose metabolism deteriorates in a progressive, region-specific and disease-specific manner — a problem that is best characterized in Alzheimer disease, where it begins presymptomatically. This Review discusses the status and prospects of therapeutic strategies for countering neurodegenerative disorders of ageing by improving, preserving or rescuing brain energetics. The approaches described include restoring oxidative phosphorylation and glycolysis, increasing insulin sensitivity, correcting mitochondrial dysfunction, ketone-based interventions, acting via hormones that modulate cerebral energetics, RNA therapeutics and complementary multimodal lifestyle changes

dCas9-Based Scn1a Gene Activation Restores Inhibitory Interneuron Excitability and Attenuates Seizures in Dravet Syndrome Mice

Colasante et al. exploit an activatory CRISPR-targeting Scn1a gene promoter as a therapeutic strategy to rescue Scn1a haploinsufficiency in a mouse model of Dravet syndrome and restore physiological levels of its gene product, the Nav1.1 voltage-gated sodium channel