Multisite phosphorylation dictates selective E2-E3 pairing as revealed by Ubc8/UBE2H-GID/CTLH assemblies.

Ubiquitylation is catalyzed by coordinated actions of E3 and E2 enzymes. Molecular principles governing many important E3-E2 partnerships remain unknown, including those for RING-family GID/CTLH E3 ubiquitin ligases and their dedicated E2, Ubc8/UBE2H (yeast/human nomenclature). GID/CTLH-Ubc8/UBE2H-mediated ubiquitylation regulates biological processes ranging from yeast metabolic signaling to human development.

Vaping and Health Service Use: A Canadian Health Survey and Health Administrative Data Study.

Emerging research suggests that e-cigarette (EC) use may have detrimental health effects, increasing the burden on healthcare systems. To determine whether young EC users had increased asthma, asthma attacks, and health services use (HSU). This cohort study used the linked Canadian Community Health Survey (cycles 2015-16 and 2017-18) and health administrative data (January 2015-March 2018).

An Exploration of the Occupational Adaptation of Older Adults Living in Low-Income Housing During the Pandemic.

Health restrictions enacted during the COVID-19 pandemic made it difficult for older adults living in low-income housing (hereinafter referred to as residents) to maintain a routine. The study aimed to explore the ways in which residents carried on, experienced and adapted their activities during the pandemic. An action research study, conducted in cooperation with a community partner, involved nineteen residents who participated in semi-structured interviews inspired by health promotion model.

Serum biomarkers correlated with liver stiffness assessed in a multicenter study of pediatric cholestatic liver disease.

Background And Aims: Detailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis.

Approach And Results: A targeted enzyme-linked immunosorbent assay-based panel of nine biomarkers (lysyl oxidase, tissue inhibitor matrix metalloproteinase (MMP) 1, connective tissue growth factor [CTGF], IL-8, endoglin, periostin, Mac-2-binding protein, MMP-3, and MMP-7) was examined in children with biliary atresia (BA; n = 187), alpha-1 antitrypsin deficiency (A1AT; n = 78), and Alagille syndrome (ALGS; n = 65) and correlated with liver stiffness (LSM) and biochemical measures of liver disease. Median age and LSM were 9 years and 9.

Body mass index trajectories and their predictors in undergraduate students from Canada: Results from the GENEiUS study.

To explore the patterns and predictors of body mass index (BMI) change among undergraduate students from Ontario (Canada). 68 undergraduate students were followed longitudinally for 3 years with anthropometric data collected bi-annually. BMI measurements were plotted to generate individual BMI trajectory curves, which were categorized, based on the observed trajectory pattern.

Performance of 22 Rapid Lateral Flow Tests for SARS-CoV-2 Antigen Detection and Influence of "Variants of Concern": Implications for Clinical Use.

Large-scale head-to-head assessment of the performance of lateral-flow tests (LFTs) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen is required in the context of the continuous emergence of new viral variants. The aim of this study was to evaluate the performance of 22 rapid LFTs for the detection of SARS-CoV-2 antigens. The clinical performance of 22 LFTs was evaluated in 1,157 samples collected in the Greater Paris area.

A GID E3 ligase assembly ubiquitinates an Rsp5 E3 adaptor and regulates plasma membrane transporters.

Cells rapidly remodel their proteomes to align their cellular metabolism to environmental conditions. Ubiquitin E3 ligases enable this response, by facilitating rapid and reversible changes to protein stability, localization, or interaction partners. In Saccharomyces cerevisiae, the GID E3 ligase regulates the switch from gluconeogenic to glycolytic conditions through induction and incorporation of the substrate receptor subunit Gid4, which promotes the degradation of gluconeogenic enzymes.

Performance of a high-throughput, automated enzyme immunoassay for the detection of SARS-CoV-2 antigen, including in viral "variants of concern": Implications for clinical use.

Unlabelled: Direct detection of SARS-CoV-2 viral antigens could replace RT-PCR, provided that its clinical performance is validated in different epidemiological settings. Here, we evaluated the performance of the VITROS Antigen test, an enzyme immunoassay detecting a SARS-CoV-2 antigen, in NPSs from 3 cohorts of patients.

Methods: Three cohorts including SARS-CoV-2 RNA-positive samples collected during the first and second wave of the French epidemic between March 2020 and February 2021 (including variant B.

Down and High: Reflections Regarding Depression and Cannabis.

In light of the recent changes in the legal status of cannabis in Canada, the understanding of the potential impact of the use of cannabis by individuals suffering from depression is increasingly considered as being important. It is fundamental that we look into the existing literature to examine the influence of cannabis on psychiatric conditions, including mood disorders. In this article, we will explore the relationship that exists between depression and cannabis.

GID E3 ligase supramolecular chelate assembly configures multipronged ubiquitin targeting of an oligomeric metabolic enzyme.

How are E3 ubiquitin ligases configured to match substrate quaternary structures? Here, by studying the yeast GID complex (mutation of which causes deficiency in glucose-induced degradation of gluconeogenic enzymes), we discover supramolecular chelate assembly as an E3 ligase strategy for targeting an oligomeric substrate. Cryoelectron microscopy (cryo-EM) structures show that, to bind the tetrameric substrate fructose-1,6-bisphosphatase (Fbp1), two minimally functional GID E3s assemble into the 20-protein Chelator-GID, which resembles an organometallic supramolecular chelate. The Chelator-GID assembly avidly binds multiple Fbp1 degrons so that multiple Fbp1 protomers are simultaneously ubiquitylated at lysines near the allosteric and substrate binding sites.

Effect of sex/gender on obesity traits in Canadian first year university students: The GENEiUS study.

Background: While weight gain during first year of university has been well documented in North America, literature on sex-specific effects is scarce and inconsistent. The objective of this investigation was to explore sex-specific changes in obesity traits during first year of university at McMaster University (Ontario, Canada).

Methods: 245 first-year students (80.

DIA-based systems biology approach unveils E3 ubiquitin ligase-dependent responses to a metabolic shift.

The yeast is a powerful model system for systems-wide biology screens and large-scale proteomics methods. Nearly complete proteomics coverage has been achieved owing to advances in mass spectrometry. However, it remains challenging to scale this technology for rapid and high-throughput analysis of the yeast proteome to investigate biological pathways on a global scale.

Engaging patients as partners in a multicentre trial of spinal versus general anaesthesia for older adults.

Engaging patients-defined broadly as individuals with lived experience of a given condition, family members, caregivers, and the organisations that represent them-as partners in research is a priority for policymakers, funders, and the public. Nonetheless, formal efforts to engage patients are absent from most studies, and models to support meaningful patient engagement in clinical anaesthesia research have not been previously described. Here, we review our experience in developing and implementing a multifaceted patient engagement strategy within the Regional Versus General Anesthesia for Promoting Independence After Hip Fracture (REGAIN) surgery trial, an ongoing randomised trial comparing spinal vs general anaesthesia for hip fracture surgery in 1600 older adults across 45 hospitals in the USA and Canada.

The effect of race/ethnicity on obesity traits in first year university students from Canada: The GENEiUS study.

Background: Little is known about the impact of race/ethnicity on weight change at university. The objective of this study is to determine if ethnicity has an impact on obesity traits in a multiethnic cohort of first-year students at McMaster University in Ontario, Canada.

Methods: 183 first year students from the three most represented ethnic groups (South Asian, East Asian, and white-Caucasian) in our study sample were followed longitudinally with data collected early in the academic year and towards the end of the year.

Effect of living arrangement on anthropometric traits in first-year university students from Canada: The GENEiUS study.

Background: The transition to university often involves a change in living arrangement for many first-year students. While weight gain during first year of university has been well documented, Canadian literature on the impact of living arrangement within this context is limited. The objective of this investigation was to explore the effect of living arrangement on anthropometric traits in first-year university students from Ontario, Canada.

Effects of an intensive voice treatment on articulatory function and speech intelligibility in children with motor speech disorders: A phase one study.

Producing speech that is clear, audible, and intelligible to others is a challenge for many children with cerebral palsy (CP) and children with Down syndrome (DS). Previous studies have demonstrated the effectiveness of using the Lee Silverman Voice Treatment (LSVT LOUD®) to increase vocal loudness and improve speech intelligibility in individuals with dysarthria secondary to Parkinson's disease (PD), and some research suggests that it also may be effective for individuals with dysarthria secondary to other conditions, including CP and DS. Although LSVT LOUD targets healthy vocal loudness, there is some evidence of spreading effects to the articulatory system.

The Alzheimer's Prevention Initiative Composite Cognitive Test: a practical measure for tracking cognitive decline in preclinical Alzheimer's disease.

Background: There is growing interest in identifying sensitive composite cognitive tests to serve as primary endpoints in preclinical Alzheimer's disease (AD) treatment trials. We reported previously a composite cognitive test score sensitive to tracking preclinical AD decline up to 5 years prior to clinical diagnosis. Here we expand upon and refine this work, empirically deriving a composite cognitive test score sensitive to tracking preclinical AD decline up to 11 years prior to diagnosis and suitable for use as a primary endpoint in a preclinical AD trial.

Alzheimer's Prevention Initiative Generation Program: Development of an genetic counseling and disclosure process in the context of clinical trials.

Introduction: As the number of Alzheimer's disease (AD) prevention studies grows, many individuals will need to learn their genetic and/or biomarker risk for the disease to determine trial eligibility. An alternative to traditional models of genetic counseling and disclosure is needed to provide comprehensive standardized counseling and disclosure of apolipoprotein E () results efficiently, safely, and effectively in the context of AD prevention trials.

Methods: A multidisciplinary Genetic Testing, Counseling, and Disclosure Committee was established and charged with operationalizing the Alzheimer's Prevention Initiative (API) Genetic Counseling and Disclosure Process for use in the API Generation Program trials.

Interconversion between Anticipatory and Active GID E3 Ubiquitin Ligase Conformations via Metabolically Driven Substrate Receptor Assembly.

Cells respond to environmental changes by toggling metabolic pathways, preparing for homeostasis, and anticipating future stresses. For example, in Saccharomyces cerevisiae, carbon stress-induced gluconeogenesis is terminated upon glucose availability, a process that involves the multiprotein E3 ligase GID recruiting N termini and catalyzing ubiquitylation of gluconeogenic enzymes. Here, genetics, biochemistry, and cryoelectron microscopy define molecular underpinnings of glucose-induced degradation.

Towards large scale orientation mapping using the eCHORD method.

eCHORD is an alternative method for orientation mapping in Scanning Electron Microscopy that involves channeling contrast observed in BSE images. The sample tilt being small (10°), eCHORD could be a promising method for large scale maps as it limits the image deformation sometimes observed with EBSD maps. However, when the magnification is low, the scan deflection of the beam becomes important, which may modify the channeling conditions of analyzed grains, leading to orientation errors.