• Hjelm Irwin posted an update 6 months ago

    In selective autophagy, cargo selectivity is determined by autophagy receptors. However, it remains scarcely understood how autophagy receptors recognize specific protein cargos. In the fission yeast Schizosaccharomyces pombe, a selective autophagy pathway termed Nbr1-mediated vacuolar targeting (NVT) employs Nbr1, an autophagy receptor conserved across eukaryotes including humans, to target cytosolic hydrolases into the vacuole. Here, we identify two new NVT cargos, the mannosidase Ams1 and the aminopeptidase Ape4, that bind competitively to the first ZZ domain of Nbr1 (Nbr1-ZZ1). High-resolution cryo-EM analyses reveal how a single ZZ domain recognizes two distinct protein cargos. Nbr1-ZZ1 not only recognizes the N-termini of cargos via a conserved acidic pocket, similar to other characterized ZZ domains, but also engages additional parts of cargos in a cargo-specific manner. Our findings unveil a single-domain bispecific mechanism of autophagy cargo recognition, elucidate its underlying structural basis, and expand the understanding of ZZ domain-mediated protein-protein interactions.

    Malnutrition is associated with poorer outcomes in hospitalized patients. However, in hip fracture patients, the associations between malnutrition and poorer outcomes are unclear because of the use of nonestablished nutrition assessment tools in previous studies that may have some degree of misclassification bias. Therefore, this review aims to determine (1) the prevalence of malnutrition diagnosed in hospitalized hip fracture patients using established nutrition assessment tools and (2) the outcomes associated with malnutrition given some of the nonestablished nutrition assessment tools used in previous studies.

    Four electronic databases were used. Studies that used established nutrition assessment tools to diagnose malnutrition in hip fracture patients within 48 h of hospital admission were included.

    Nine studies were included (n = 1665). Patients’ mean age ranged from 79.9 to 86.1 years. Eight studies reported the frequencies of each sex, and for females, it ranged from 70% to 81.8%. The prevalence ocreening and intervention.

    Longitudinal studies assessing the association of profiles of allergen-specific IgE (sIgE) sensitization to a large range of allergen molecules and respiratory health are rare. We aimed to assess trajectories of molecular sIgE sensitization profiles from childhood to adulthood and their associations with respiratory health.

    IgE reactivity to microarrayed allergen molecules were measured in childhood (EGEA1) and 12years later in adult life (EGEA2) among 291 EGEA participants (152 with asthma). At each time point, sIgE sensitization profiles were identified by latent class analysis (LCA) by considering IgE-reactivity to the 38most prevalent respiratory allergens. The LCA-defined profiles were then studied in association with respiratory health.

    At baseline, the mean (min-max) age of the population was 11 (4.5-16) years. The LCA identified four sIgE sensitization profiles which were very similar at both time points (% at EGEA1 and EGEA2); A “no/few allergen(s)” (48%, 39%), B “pollen/animal allergens” (18%, 21%), C “most prevalent house dust mite allergens” (22%, 27%) and D “many allergens” (12%, 13%). Overall, 73% of the participants remained in the same profile from childhood to adulthood. The profiles were associated with asthma and rhinitis phenotypes. Participants of profiles C and D had lower FEV

    % and FEF

    % as compared to profile A. Similar patterns of associations were observed for participants with asthma. There was no association with change in lung function.

    Using high-resolution sIgE longitudinal data, the LCA identified four molecular sensitization profiles, mainly stable from childhood to adulthood, that were associated with respiratory health.

    Using high-resolution sIgE longitudinal data, the LCA identified four molecular sensitization profiles, mainly stable from childhood to adulthood, that were associated with respiratory health.Micronutrient powder (MNP) can reduce iron deficiency in young children, which has been well established in efficacy trials. However, the cost of different delivery platforms has not been determined. PHA665752 We calculated the cost and cost-efficiency of distributed MNP through community-based mechanisms and in health facilities in a primarily rural district in Uganda. An endline survey (n = 1072) identified reach and adherence. During the 9-month pilot, 37,458 (community platform) and 12,390 (facility platform) packets of MNP were distributed. Each packet consisted of 30 MNP sachets. In 2016, total costs were $277,082 (community platform, $0.24/sachet) and $221,568 (facility platform, $0.59/sachet). The cost per child reached was lower in the community platform ($53.24) than the facility platform ($65.97). The cost per child adhering to a protocol was $58.08 (community platform) and $72.69 (facility platform). The estimated cost of scaling up the community platform pilot to the district level over 3 years to cover approximately 17,890 children was $1.23 million (scale-up integrated into a partner agency program) to $1.62 million (government scale-up scenario). Unlike previous estimates, these included opportunity costs. Community-based MNP delivery costs were greater, yet more cost-efficient per child reached and adhering to protocol than facility-based delivery. However, total costs for untargeted MNP delivery under program settings are potentially prohibitive.Hericium erinaceus (Bull.) Persoon, a popular medicinal edible mushroom, owns a long history of usage in traditional Chinese medicine and also in other oriental countries. Along with this, its several bioactive compounds have been evolved into food supplements. Meanwhile, this present investigation aimed at extracting bioactive components from fruiting bodies of H. erinaceus using two different solvents and evaluating its in vitro antioxidant, antimicrobial, and antiproliferative efficacy. Chemical analysis showed extracts were rich in phenol, flavonoids, and ascorbic acids while lesser amount of carotenoids were also detected in these extracts. Both extracts were able to scavenge 1,1-diphenyl-2-picrylhydrazyl (~76%) and 2,2′-azinobis-(3-ethylbenzthiazoline-6-sulphonate) radicals (~81%) and also showed chelating activity (~73.05%). The ethanolic extract exhibited the highest antioxidant activity (total antioxidant capacity 2.17 µg ascorbic acid equivalent/mg of extract) whereas methanolic extract showed moderate capacity (total antioxidant capacity 1.

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