Expanding the Landscape of Dual Action Antifolate Antibacterials through 2,4-Diamino-1,6-dihydro-1,3,5-triazines.

Antibiotics that operate multiple mechanisms of action are a promising strategy to combat growing resistance. Previous studies have shown that dual action antifolates formed from a pyrroloquinazolinediamine core can inhibit the growth of bacterial pathogens without developing resistance. In this work, we expand the scope of dual action antifolates by repurposing the 2,4-diamino-1,6-dihydro-1,3,5-triazine (DADHT) cycloguanil scaffold to a variety of derivatives designed to inhibit dihydrofolate reductase (DHFR) and disrupt bacterial membranes.

Single-point mutations in disordered proteins: Linking sequence, ensemble, and function.

Mutations in genomic DNA often result in single-point missense mutations in proteins. For folded proteins, the functional effect of these missense mutations can often be understood by their impact on structure. However, missense mutations in intrinsically disordered protein regions (IDRs) remain poorly understood.

Soil data from the Barbastro-Balaguer gypsum belt, NE Spain.

The dataset [1] hosts pedological info and images of the lands -locally known as - of the outcropping gypsiferous core of the Barbastro-Balaguer anticline (Fig. 1). It stands out in the landscape for the linear reliefs due to outcrops of dipping strata with differential resistance to erosion, and also because of its whitish color (Fig.

Protein quality control machinery: regulators of condensate architecture and functionality.

Protein quality control (PQC) mechanisms including the ubiquitin (Ub)-proteasome system (UPS), autophagy, and chaperone-mediated refolding are essential to maintain protein homeostasis in cells. Recent studies show that these PQC mechanisms are further modulated by biomolecular condensates that sequester PQC components and compartmentalize reactions. Accumulating evidence points towards the PQC machinery playing a pivotal role in regulating the assembly, disassembly, and viscoelastic properties of several condensates.

First-Line (1L) Treatment Decision Patterns and Survival of Hormone Receptor (HR)-Positive/HER2-Negative Advanced Breast Cancer (ABC) Patients in a Latin American (LATAM) Public Institution.

Advanced breast cancer is an incurable disease, with a median overall survival of 3 years, including in countries without access problems. Although chemotherapy is reserved in some cases, it is still used in many countries as a first-line therapy. The aim of our study is to evaluate the first-line treatment choices and the factors that influence therapeutic decisions.