The effectiveness of state-of-the-art cross-linking strategies and mass spectrometry (MS) detection was explored in an important biological context, namely, the ubiquitin-proteasome system, which is responsible for most of the regulated protein degradation in eukaryotic cells. The locations of possible binding sites on the 19S proteasome regulatory particle for Lys linked polyubiquitin chains were examined using cross-linking strategies and MS based detection by comparing two types of cross-linkers: a (bis)-sulfosuccinimidyl suberate (BS) and diethyl suberothioimidate (DEST). The well-established BS-based strategy produced 328 cross-linked peptides; however, no ubiquitin-19S cross-links were observed.
View Article and Find Full Text PDFPathogenic heterozygous variants in CHD4 cause Sifrim-Hitz-Weiss syndrome, a neurodevelopmental disorder associated with brain anomalies, heart defects, macrocephaly, hypogonadism, and additional features with variable expressivity. Most individuals have non-recurrent missense variants, complicating variant interpretation. A few were reported with truncating variants, and their role in disease is unclear.
View Article and Find Full Text PDFBackground And Objectives: Assessment and care of substance use disorder within mental health services are essential due to the high prevalence and harms associated with comorbidity. Substance use disorder assessment and care are routinely recommended in clinical guidelines; however, processes are not agreed. This systematic review of routine clinical practice in relation to substance use disorders in adult mental health service aims to identify routine assessment and diagnosis processes, the proportion of patients and service episodes in which they occur and their outputs.
View Article and Find Full Text PDFNutritional epidemiology aims to link dietary exposures to chronic disease, but the instruments for evaluating dietary intake are inaccurate. One way to identify unreliable data and the sources of errors is to compare estimated intakes with the total energy expenditure (TEE). In this study, we used the International Atomic Energy Agency Doubly Labeled Water Database to derive a predictive equation for TEE using 6,497 measures of TEE in individuals aged 4 to 96 years.
View Article and Find Full Text PDFBackground: To determine if the positive outcomes from clinical trials regarding the safety and efficacy of metabolic bariatric surgery are reproducible at a national level.
Methods: A longitudinal registry-based observation study with data collected from all persons undergoing metabolic bariatric surgery in Australia from 28 February 2012-31 December 2021 including data from 122,567 index patients who underwent 134,625 completed bariatric procedures.
Main Outcomes And Measures: Defined adverse outcomes at 90-days (unplanned readmission, intensive care admission and re-operation; death), annual change in weight (percent total body weight loss (TBWL)), diabetes treatment and need for re-operation.