Maintenance of neuronal TDP-43 expression requires axonal lysosome transport.

TDP-43 mislocalization and pathology occurs across a range of neurodegenerative diseases, but the pathways that modulate TDP-43 in neurons are not well understood. We generated a Halo-TDP-43 knock-in iPSC line and performed a genome-wide CRISPR interference FACS-based screen to identify modifiers of TDP-43 levels in neurons. A meta-analysis of our screen and publicly available screens identified both specific hits and pathways present across multiple screens, the latter likely responsible for generic protein level maintenance.

Substygophily in Dinaric Karst: A Model Case of Locally Endemic Minnows (Leuciscinae).

The Dinaric Karst extends along the Adriatic coast of the Western Balkan Peninsula and is home to a group of "karst minnows" of the genera , , and , which have adapted to the highly variable water conditions in the karst by spending up to several months underground, but require surface habitats for spawning, defining them as substygophiles. The three species of the genus , , , and , are defined by restricted ranges, making them vulnerable to pollution and extended draughts caused by the climate change. In this study, the phylogeny of Leusciscinae was reconstructed using 15 and one , one , and one complete mitochondrial genomes and the position of the genus within the subfamily as sister species to the clade was confirmed.

Exploring Toxicity of Per- and Polyfluoroalkyl Substances (PFAS) Mixture Through ADMET and Toxicogenomic In Silico Analysis: Molecular Insights.

This study aimed to explore the health impacts, mechanisms of toxicity, and key gene biomarkers of a mixture of the most prominent perfluoroalkyl/polyfluoroalkyl substances (PFAS) through in silico ADMET and toxicogenomic analysis. The following databases and tools were used: AdmetSAR (2.0), ADMETlab (2.

Targeting ZNF638 activates antiviral immune responses and potentiates immune checkpoint inhibition in glioblastoma.

Viral mimicry refers to the activation of innate anti-viral immune responses due to the induction of endogenous retroelement (RE) expression. Viral mimicry has been previously described to augment anti-tumor immune responses and sensitize solid tumors to immunotherapy including colorectal cancer, melanoma, and clear renal cell carcinoma. Here, we found that targeting a novel, master epigenetic regulator, Zinc Finger Protein 638 (ZNF638), induces viral mimicry in glioblastoma (GBM) preclinical models and potentiates immune checkpoint inhibition (ICI).