Nanobiopsy investigation of the subcellular mtDNA heteroplasmy in human tissues.

Mitochondrial function is critical to continued cellular vitality and is an important contributor to a growing number of human diseases. Mitochondrial dysfunction is typically heterogeneous, mediated through the clonal expansion of mitochondrial DNA (mtDNA) variants in a subset of cells in a given tissue. To date, our understanding of the dynamics of clonal expansion of mtDNA variants has been technically limited to the single cell-level.

Insulin-Degrading Enzyme Efficiently Degrades polyQ Peptides but not Expanded polyQ Huntingtin Fragments.

Background: Huntington's disease is an inheritable autosomal dominant disorder caused by an expanded CAG trinucleotide repeat within the Huntingtin gene, leading to a polyglutamine (polyQ) expansion in the mutant protein.

Objective: A potential therapeutic approach for delaying or preventing the onset of the disease involves enhancing the degradation of the aggregation-prone polyQ-expanded N-terminal mutant huntingtin (mHTT) exon1 fragment. A few proteases and peptidases have been identified that are able to cleave polyQ fragments with low efficiency.

Identification of TRDV-TRAJ V domains in human and mouse T-cell receptor repertoires.

Here, we describe the identification of two T-cell receptors (TRs) containing TRDV genes in their TRA chains, the first one in human and the second one in mouse. First, using 5'RACE on a mixed lymphocyte-tumor cell culture (MLTC), we identified TRDV1 5'-untranslated region (UTR) and complete coding sequence rearranged productively to TRAJ24. Single-cell TR RNA sequencing (RNA-seq) of the MLTC, conducted to identify additional clonotypes, revealed that the analysis software detected the hybrid TRDV-TRAJ TRA (TRA) chain but excluded it from the final results.

Decreased vector magnitudes may help identify events in patients with Long QT syndrome.

Introduction: All Long QT syndrome (LQTS) patients are at elevated risk for channelopathy-induced delayed myocardial repolarization and consequently potentially life-threatening cardiac events with 90% of initial cardiac events occurring between preteen and 40 years old. Utilizing ECG and derived vectorcardiographic parameters, including T wave Vector Magnitude (TwVM) measurement data, this study attempts to determine whether TwVM from baseline ECGs is effectively predictive of future cardiac events for genotype-positive LQTS patients.

Methods: Verified carriers of established LQTS disease-causing genotypes were selected from University of Minnesota patient encounters between 2010 and 2020 for inclusion in this retrospective study.

Reduction in PA28αβ activation in HD mouse brain correlates to increased mHTT aggregation in cell models.

Huntington's disease is an autosomal dominant heritable disorder caused by an expanded CAG trinucleotide repeat at the N-terminus of the Huntingtin (HTT) gene. Lowering the levels of soluble mutant HTT protein prior to aggregation through increased degradation by the proteasome would be a therapeutic strategy to prevent or delay the onset of disease. Native PAGE experiments in HdhQ150 mice and R6/2 mice showed that PA28αβ disassembles from the 20S proteasome during disease progression in the affected cortex, striatum and hippocampus but not in cerebellum and brainstem.