Studying C9orf72 dipeptide repeat polypeptide aggregation using an analytical ultracentrifuge equipped with fluorescence detection.

Sedimentation velocity, using an analytical ultracentrifuge equipped with fluorescence detection, and electrophoresis methods are used to study aggregation of proteins in transgenic animal model systems. Our previous work validated the power of this approach in an analysis of mutant huntingtin aggregation. We demonstrate that this method can be applied to another neurodegenerative disease studying the aggregation of three dipeptide repeats (DPRs) produced by aberrant translation of mutant c9orf72 containing large GC hexanucleotide repeats.

The Effects of poly-GA and poly-PR Dipeptide Repeats on Sleep Patterns in .

is the most common familial gene associated with amyotrophic lateral sclerosis (ALS). Dipeptide repeats (DPRs) encoded by an expanded nucleotide repeat sequence in the gene were found in the sleep-related neurons of patients, indicating a role of DPRs in ALS-associated sleep disruptions. Poly-GA or poly-PR DPRs were expressed in male to study their effect on sleep Poly-PR expression caused sleep disruptions while poly-GA expression did not.

Support for nicotine reduction in cigarettes: findings from the 2016 and 2020 ITC Four Country Smoking and Vaping Surveys.

Introduction: The USA and New Zealand have sought to establish a product standard to set a maximum nicotine level for cigarettes to reduce their addictiveness. This study examined support for very low nicotine cigarettes (VLNCs) in Australia, Canada, England and the USA between 2016 and 2020.

Methods: Repeated cross-sectional data were analysed from participants who currently smoke, formerly smoked or vaped and/or currently vape in the 2016 (n=11 150) and/or 2020 (n=5432) International Tobacco Control (ITC) Four Country Smoking and Vaping Survey.

Technique and Outcomes of Concomitant Aortic and Caval Resection and Reconstruction for Retroperitoneal Tumors.

Background: Major vascular involvement is often considered a contraindication to resection of malignant tumors, but in highly selected patients, it can be performed safely, with results that are highly dependent upon the tumor biology. Resection of both the aorta and inferior vena cava (IVC) is a rare undertaking, requiring both favorable tumor biology and a patient fit for a substantial surgical insult; nevertheless, it provides the possibility of a cure.

Methods: Patients requiring resection and reconstruction of both the aorta and IVC from 2009 through 2019 at 2 university medical centers were included.

C9orf72 proline-arginine dipeptide repeats disrupt the proteasome and perturb proteolytic activities.

The hexanucleotide G4C2 repeat expansion in C9orf72 is the most frequent genetic cause of familial amyotrophic lateral sclerosis (ALS). Aberrant translation of this hexanucleotide sequence leads to production of 5 dipeptide repeats (DPRs). One of these DPRs is proline-arginine (polyPR), which is found in C9orf72-expanded ALS (C9ALS) patient brain tissue and is neurotoxic across multiple model systems.