Social brain activation during mentalizing in a large autism cohort: the Longitudinal European Autism Project

Abstract: Background: Autism spectrum disorder (ASD) is a neurodevelopmental condition with key deficits in social functioning. It is widely assumed that the biological underpinnings of social impairment are neurofunctional alterations in the “social brain,” a neural circuitry involved in inferring the mental state of a social partner. However, previous evidence comes from small-scale studies and findings have been mixed. We therefore carried out the to-date largest study on neural correlates of mentalizing in ASD. Methods: As part of the Longitudinal European Autism Project, we performed functional magnetic resonance imaging at six European sites in a large, well-powered, and deeply phenotyped sample of individuals with ASD (N = 205) and typically developing (TD) individuals (N = 189) aged 6 to 30 years. We presented an animated shapes task to assess and comprehensively characterize social brain activation during mentalizing. We tested for effects of age, diagnosis, and their association with symptom measures, including a continuous measure of autistic traits. Results: We observed robust effects of task. Within the ASD sample, autistic traits were moderately associated with functional activation in one of the key regions of the social brain, the dorsomedial prefrontal cortex. However, there were no significant effects of diagnosis on task performance and no effects of age and diagnosis on social brain responses. Besides a lack of mean group differences, our data provide no evidence for meaningful differences in the distribution of brain response measures. Extensive control analyses suggest that the lack of case-control differences was not due to a variety of potential confounders. Conclusions: Contrary to prior reports, this large-scale study does not support the assumption that altered social brain activation during mentalizing forms a common neural marker of ASD, at least with the paradigm we employed. Yet, autistic individuals show socio-behavioral deficits. Our work therefore highlights the need to interrogate social brain function with other brain measures, such as connectivity and network-based approaches, using other paradigms, or applying complementary analysis approaches to assess individual differences in this heterogeneous condition

Discovery of enzymes for toluene synthesis from anoxic microbial communities

Microbial toluene biosynthesis was reported in anoxic lake sediments more than three decades ago, but the enzyme catalyzing this biochemically challenging reaction has never been identified. Here we report the toluene-producing enzyme PhdB, a glycyl radical enzyme of bacterial origin that catalyzes phenylacetate decarboxylation, and its cognate activating enzyme PhdA, a radical S-adenosylmethionine enzyme, discovered in two distinct anoxic microbial communities that produce toluene. The unconventional process of enzyme discovery from a complex microbial community (>300,000 genes), rather than from a microbial isolate, involved metagenomics- and metaproteomics-enabled biochemistry, as well as in vitro confirmation of activity with recombinant enzymes. This work expands the known catalytic range of glycyl radical enzymes (only seven reaction types had been characterized previously) and aromatic-hydrocarbon-producing enzymes, and will enable first-time biochemical synthesis of an aromatic fuel hydrocarbon from renewable resources, such as lignocellulosic biomass, rather than from petroleum

9. Steinfurter Bioenergiefachtagung - Wärmewende im ländlichen Raum

Die Hälfte des Endenergiebedarfs in Deutschland wird zur Deckung des Wärmebedarfs der Wirtschaft und der privaten Haushalte benötigt; überwiegend erzeugt durch Erdgas und Heizöl. Gerade die energetisch nur unzureichend sanierten Einfamilienhausbestände des ländlichen Raumes bergen ein hohes Potenzial für Energieeinsparungs- und Effizienzsstrategien, um zum einen den Klimaschutz zu fördern und zum anderen eine nachhaltige wirtschaftliche Entwicklung des ländlichen Raumes anzustoßen. Die 9. Steinfurter Bioenergiefachtagung zeigt Strategien und Maßnahmen auf, die zeigen, wie eine "Wärmewende im ländlichen Raum" aussehen kann, welche Chancen und Möglichkeiten sie bietet und warum eine "Wärmewende" strategisch unabdingbar für das Gelingen des Generationenprojektes "Energiewende" insgesamt ist. Die Veranstaltung zeichnet den Pfad von konzeptionellen Ideen über Beispiele aus der Praxis bis hin zu zukunftsweisenden technologischen Ansätzen: Wärmekataster Kreis Steinfurt KWK-Modellkommune Saerbeck Wege zum Bioenergiedorf - Praxisbeispiele Technische Voraussetzungen und Möglichkeiten für effiziente Wärmenetze im ländlichen Raum Finanzierungs- und Fördermodelle für eine gelungene Wärmewend

Ezetimibe inhibits expression of acid sphingomyelinase in liver and intestine

Ezetimibe inhibits cholesterol absorption in the intestine. Sphingomyelin has strong interactions with cholesterol. We investigated the effects of ezetimibe on Sphingomyelinase (SMase) expression in intestine and liver. After feeding rats with ezetimibe (5 mg/kg per day) for 14 days, acid SMase activities in the liver and in the proximal part of small intestine were reduced by 34 and 25%, respectively. Alkaline SMase (alk-SMase) was increased in the proximal part of the small intestine. Administration of lower doses of ezetimibe reduced acid SMase only in the liver by 14% (P < 0.05). In cell culture studies, ezetimibe decreased acid SMase activity in Hep G2 and Caco-2 cells dose-dependently. The reductions were more rapid for Hep G2 cells than for Caco-2 cells. Western blot showed that acid SMase protein was decreased in both Hep G2 and Caco-2 cells by 100 muM ezetimibe. The SM content was increased in Hep G2 cells but not Caco-2 cells, and total cholesterol content was increased in both cell lines 24 h after stimulation with 100 muM ezetimibe. Mevastatin, the inhibitor of cholesterol synthesis, induced a mild increase in acid SMase activity in Hep G2 cells but not Caco-2 cells. Following the reduction of acid SMase, ezetimibe at high dose slightly increased alk-SMase activity. In conclusion, the study demonstrates an inhibitory effect of ezetimibe on acid SMase activity and expression in both liver and intestine