ERα dysfunction caused by ESR1 mutations and therapeutic pressure promotes lineage plasticity in ER breast cancer.

Multiple next-generation molecules targeting estrogen receptor α (ERα) are being investigated in breast cancer clinical trials, encompassing thousands of women globally. Development of these molecules was partly motivated by the discovery of resistance-associated mutations in ESR1 (encodes ERα). Here, we studied the impact of ERα antagonist/degraders against Esr1 mutations expressed in mouse mammary glands.

The ATP-dependent DEAD-box RNA Helicase Dbp2 regulates the glucose/nitrogen stress response in baker's yeast by modulating reversible nuclear retention and decay of SKS1 mRNA.

In Saccharomyces cerevisiae, SKS1 mRNA encoding a glucose-sensing serine/threonine kinase belongs to "nucleus-retained" (NR) mRNAs representing a subset of otherwise normal transcripts, which exhibits slow nuclear export and excessively long nuclear dwell time. Nuclear retention of the SKS1 mRNA triggered by a 202 nt "export-retarding" nuclear zip code (NZ) element promotes its rapid degradation in the nucleus by the nuclear exosome/CTEXT. In this investigation, we demonstrate that Dbp2p, an ATP-dependent DEAD-box RNA helicase binds to SKS1 and other NR-mRNAs and thereby inhibits their export by antagonizing with the binding of the export factors Mex67p/Yra1p.

Cell Type Differentiation Using Network Clustering Algorithms.

Single cell RNA-seq (scRNA-seq) technologies provide unprecedented resolution representing transcriptomics at the level of single cell. One of the biggest challenges in scRNA-seq data analysis is the cell type annotation, which is usually inferred by cell separation approaches. In-silico algorithms that accurately identify individual cell types in ongoing single-cell sequencing studies are crucial for unlocking cellular heterogeneity and understanding the biological basis of diseases.

Navigating from cellular phenotypic screen to clinical candidate: selective targeting of the NLRP3 inflammasome.

The NLRP3 inflammasome plays a pivotal role in host defense and drives inflammation against microbial threats, crystals, and danger-associated molecular patterns (DAMPs). Dysregulation of NLRP3 activity is associated with various human diseases, making it an attractive therapeutic target. Patients with NLRP3 mutations suffer from Cryopyrin-Associated Periodic Syndrome (CAPS) emphasizing the clinical significance of modulating NLRP3.