Mutant huntingtin protein decreases with CAG repeat expansion: implications for therapeutics and bioassays.

Huntington's disease is an inherited neurodegenerative disorder caused by a CAG repeat expansion that encodes a polyglutamine tract in the huntingtin (HTT) protein. The mutant CAG repeat is unstable and expands in specific brain cells and peripheral tissues throughout life. Genes involved in the DNA mismatch repair pathways, known to act on expansion, have been identified as genetic modifiers; therefore, it is the rate of somatic CAG repeat expansion that drives the age of onset and rate of disease progression.

Treatment Strategies' Impact on Progression-Free Survival According to RMST Function in Metastatic Colorectal Cancer Patients: A Retrospective Study from Romania.

This retrospective study investigates the impact of various treatment strategies on progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC), a significant global health issue. We employed the restricted mean survival time (RMST) to evaluate how different treatments affect PFS over a defined period. The study included 225 patients with mCRC who were treated between 2015 and 2023 at the Oncology Department of Colțea Clinical Hospital in Bucharest.

A unifying modelling of multiple land degradation pathways in Europe.

Land degradation is a complex socio-environmental threat, which generally occurs as multiple concurrent pathways that remain largely unexplored in Europe. Here we present an unprecedented analysis of land multi-degradation in 40 continental countries, using twelve dataset-based processes that were modelled as land degradation convergence and combination pathways in Europe's agricultural (and arable) environments. Using a Land Multi-degradation Index, we find that up to 27%, 35% and 22% of continental agricultural (~2 million km) and arable (~1.

SecMet-FISH: labeling, visualization, and enumeration of secondary metabolite producing microorganisms.

Our understanding of the role of secondary metabolites in microbial communities is challenged by intrinsic limitations of culturing bacteria under laboratory conditions and hence cultivation independent approaches are needed. Here, we present a protocol termed Secondary Metabolite FISH (SecMet-FISH), combining advantages of gene-targeted fluorescence in situ hybridization (geneFISH) with in-solution methods (in-solution FISH) to detect and quantify cells based on their genetic capacity to produce secondary metabolites. The approach capitalizes on the conserved nature of biosynthetic gene clusters (BGCs) encoding adenylation (AD) and ketosynthase (KS) domains, and thus selectively targets the genetic basis of non-ribosomal peptide and polyketide biosynthesis.

A CAG repeat threshold for therapeutics targeting somatic instability in Huntington's disease.

The Huntington's disease mutation is a CAG repeat expansion in the huntingtin gene that results in an expanded polyglutamine tract in the huntingtin protein. The CAG repeat is unstable and expansions of hundreds of CAGs have been detected in Huntington's disease post-mortem brains. The age of disease onset can be predicted partially from the length of the CAG repeat as measured in blood.