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Serine phosphorylation facilitates protein degradation by the human mitochondrial ClpXP protease.
Proc Natl Acad Sci U S A
February 2025
Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
ClpXP is a two-component mitochondrial matrix protease. The caseinolytic mitochondrial matrix peptidase chaperone subunit X (ClpX) recognizes and translocates protein substrates into the degradation chamber of the caseinolytic protease P (ClpP) for proteolysis. ClpXP degrades damaged respiratory chain proteins and is necessary for cancer cell survival.
View Article and Find Full Text PDFDiscovery and clinical translation of ceperognastat, an O-GlcNAcase (OGA) inhibitor, for the treatment of Alzheimer's disease.
Alzheimers Dement (N Y)
December 2024
Eli Lilly and Company Indianapolis Indiana USA.
Introduction: The aggregation and spread of hyperphosphorylated, pathological tau in the human brain is hypothesized to play a key role in Alzheimer's disease (AD) as well as other neurogenerative tauopathies. O-GlcNAcylation, an important post-translational modification of tau and many other proteins, is significantly decreased in brain tissue of AD patients relative to healthy controls. Increased tau O-GlcNAcylation has been shown to reduce tau pathology in mouse in vivo tauopathy models.
View Article and Find Full Text PDFDynamics of Mucosal Integration of Machined versus Anodized Titanium Implants.
J Dent Res
December 2024
Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Article Synopsis
- The success of dental implants relies on the formation of soft tissues that create a protective barrier against pathogens.
- Researchers studied how anodized surface modifications affect the integration of mucosal tissues in miniaturized implants placed in mice.
- Findings revealed that while soft tissue around implants matures slowly compared to bone, anodized surfaces show some temporary benefits, highlighting the need for strategies to enhance the speed of soft-tissue maturation for better clinical outcomes.
Single spike mutation differentiating XBB.1 and XBB.1.5 enhances SARS-CoV-2 cell-to-cell transmission and facilitates serum-mediated enhancement.
Front Immunol
December 2024
Laboratory of Microbiology and Virology, Vita-Salute San Raffaele University, Milan, Italy.
Introduction: The ongoing emergence of SARS-CoV-2 variants poses significant challenges to existing therapeutics. The spike (S) glycoprotein is central to both viral entry and cell-to-cell transmission via syncytia formation, a process that confers resistance to neutralizing antibodies. The mechanisms underlying this resistance, particularly in relation to spike-mediated fusion, remain poorly understood.
View Article and Find Full Text PDFAI tool for predicting MGMT methylation in glioblastoma for clinical decision support in resource limited settings.
Sci Rep
November 2024
Department of Radiation Oncology, Hospital Sírio-Libanês, São Paulo, Brazil.
Glioblastoma is an aggressive brain cancer with a poor prognosis. The O6-methylguanine-DNA methyltransferase (MGMT) gene methylation status is crucial for treatment stratification, yet economic constraints often limit access. This study aims to develop an artificial intelligence (AI) framework for predicting MGMT methylation.
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