TMEM106B C-terminal fragments aggregate and drive neurodegenerative proteinopathy in transgenic Caenorhabditis elegans.

Introduction: Genetic variation in the lysosomal and transmembrane protein 106B (TMEM106B) modifies risk for several neurodegenerative disorders, especially frontotemporal lobar degeneration (FTLD). The C-terminal (CT) domain of TMEM106B occurs as fibrillar protein deposits in the brains of dementia patients.

Methods: To determine the TMEM CT aggregation propensity and neurodegenerative potential, we generated transgenic Caenorhabditis elegans expressing the human TMEM CT fragment aggregating in FTLD cases.

Nutritionally physiological cell culture medium and 3D culture influence breast tumour proteomics and anti-cancer drug effectiveness.

Many drugs have been discontinued during phase II/III breast cancer clinical trials due to lack of clinical efficacy, indicating shortcomings in predictive value of preclinical data. Nutrient availability in the tumour cell microenvironment and the dimensionality of in vitro tumour cells likely impact on drug responsiveness. Global proteomics experiments were conducted to assess the impact of nutrient availability and dimensionality of culture.

Functional and Symptomatic Improvements Based on the Femoral Tunnel Drilling Technique in Anterior Cruciate Ligament (ACL) Reconstruction.

Background: The current literature comparing femoral tunnel techniques often reports on short-term outcomes after anterior cruciate ligament reconstruction (ACLR), but only a few studies have analyzed long-term outcomes. In addition, many studies have compared transtibial to anteromedial portal techniques without differentiating whether rigid or flexible reaming is used, making it difficult to infer how the techniques truly compare to one another.

Purpose: This study aimed to detect differences in patient-reported outcome scores in those treated with three different femoral tunnel drilling techniques.

Mechanisms of Gut-Related Viral Persistence in Long COVID.

Long COVID (post-acute sequelae of COVID-19-PASC) is a consequence of infection by SARS-CoV-2 that continues to disrupt the well-being of millions of affected individuals for many months beyond their first infection. While the exact mechanisms underlying PASC remain to be defined, hypotheses regarding the pathogenesis of long COVID are varied and include (but are not limited to) dysregulated local or systemic inflammatory responses, autoimmune mechanisms, viral-induced hormonal imbalances, skeletal muscle abnormalities, complement dysregulation, novel abzymes, and long-term persistence of virus and/or fragments of viral RNA or proteins. This review article is based on a comprehensive review of the wide range of symptoms most often observed in long COVID and an attempt to integrate that information into a plausible hypothesis for the pathogenesis of PASC.

Endoplasmic reticulum unfolded protein response transcriptional targets of XBP-1s mediate rescue from tauopathy.

Pathological tau disrupts protein homeostasis (proteostasis) within neurons in Alzheimer's disease (AD) and related disorders. We previously showed constitutive activation of the endoplasmic reticulum unfolded protein response (UPR) transcription factor XBP-1s rescues tauopathy-related proteostatic disruption in a tau transgenic Caenorhabditis elegans (C. elegans) model of human tauopathy.