CONCLUSION Our findings indicate that the intestinal microbiota can control Trp availability and provide a link between the AhR pathway and host-microbiota interaction in acute infection with T. gondii. This article is protected by copyright. All rights reserved.Powdery mildew is a fungal disease that affects a wide range of plants and reduces crop yield worldwide. As obligate biotrophs, powdery mildew fungi manipulate living host cells to suppress defence responses and to obtain nutrients. Members of the plant order Brassicales produce indole glucosinolates that effectively protect them from attack by non-adapted fungi. Indol-3-ylmethyl glucosinolate is constitutively produced in the phloem and transported to epidermal cells for storage. Upon attack, indol-3-ylmethyl glucosinolate is activated by CYP81F2 to provide broad-spectrum defence against fungi. How de novo biosynthesis and transport contribute to defence of powdery mildew-attacked epidermal cells is unknown. Bioassays and glucosinolate analysis demonstrate that GTR glucosinolate transporters are not involved in antifungal defence. Using quantitative live-cell imaging of fluorophore-tagged markers, we show that accumulation of the glucosinolate biosynthetic enzymes CYP83B1 and SUR1 is induced in epidermal cells attacked by the non-adapted barley powdery mildew Blumeria graminis f.sp. hordei. By contrast, glucosinolate biosynthesis is attenuated during interaction with the virulent powdery mildew Golovinomyces orontii. Interestingly, SUR1 induction is delayed during the Golovinomyces orontii interaction. We conclude that epidermal de novo synthesis of indol-3-ylmethyl glucosinolate contributes to CYP81F2-mediated broad-spectrum antifungal resistance and that adapted powdery mildews may target this process.  https://www.selleckchem.com/products/jtc-801.html  This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Since the seminal work of Prentice and Pyke (1979), the prospective logistic likelihood has become the standard method of analysis for retrospectively collected case-control data, in particular for testing the association between a single genetic marker and a disease outcome in genetic case-control studies. In the study of multiple genetic markers with relatively small effects, especially those with rare variants, various aggregated approaches based on the same prospective likelihood have been developed to integrate subtle association evidence among all the markers considered. Many of the commonly used tests are derived from the prospective likelihood under a common-random-effect assumption, which assumes a common random effect for all subjects. We develop the locally most powerful aggregation test based on the retrospective likelihood under an independent-random-effect assumption, which allows the genetic effect to vary among subjects. In contrast to the fact that disease prevalence information cannot be used to improve efficiency for the estimation of odds ratio parameters in logistic regression models, we show that it can be utilized to enhance the testing power in genetic association studies. Extensive simulations demonstrate the advantages of the proposed method over the existing ones. A real genome-wide association study is analyzed for illustration. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Community-based projects that serve vulnerable families have the opportunity to identify and respond to interpersonal violence (IPV). We developed a readiness assessment tool to support selection of projects to participate in an initiative that involved implementing a community-based IPV intervention for mothers. The overarching aim of the current study was to describe the development of this tool and examine the reliability of coding, validity, and utility of the tool. After developing and refining the tool, 41 community-based projects completed the tool. Responses were coded and scored; scores were used to select projects for the initiative. Preliminary validation for the tool included (a) expert opinion, (b) uptake/implementation of the intervention, and (c) feedback and responses from service providers in terms of the usefulness and importance of the tool. This tool can be used by both researchers and service providers to assess community project readiness and capacity to provide trauma-informed services for vulnerable families. © 2020 Wiley Periodicals, Inc.Missense mutations of the RET gene have been identified in both multiple endocrine neoplasia (MEN) type 2A/B and Hirschsprung disease (HSCR congenital absence of the enteric nervous system, ENS). Current consensus holds that MEN2A/B and HSCR are respectively caused by activating and inactivating RET mutations. However, the biological significance of RET missense mutations in vivo has not been fully elucidated. In the present study, we introduced one MEN2B-associated (M918T) and two HSCR-associated (N394K and Y791F) RET missense mutations into the corresponding regions of the mouse Ret gene by genome editing (RetM919T , RetN396K and RetY792F ) and performed histological examinations of Ret-expressing tissues to understand the pathogenetic impact of each mutant in vivo. RetM919T/+ mice displayed MEN2B-related phenotypes, including C cell hyperplasia and abnormal enlargement of the primary sympathetic ganglia. Similar sympathetic phenotype was observed in RetM919T/- mice, demonstrating a strong pathogenetic effect of the Ret M918T by a single allele expression. In contrast, no abnormality was found in the ENS of mice harboring the Ret N394K or Y791F mutation. Most surprisingly, single allele expression of RET N394K or Y791F was sufficient for normal ENS development, indicating that these RET mutants exert largely physiological function in vivo. This study reveals contrasting pathogenetic effects between MEN2B- and HSCR-associated RET missense mutations, and suggests that some of HSCR-associated RET missense mutations are by themselves neither inactivating nor pathogenetic and require involvement of other gene mutations for disease expressivity. This article is protected by copyright. All rights reserved.