Private, public, and bottled drinking water: Shared contaminant-mixture exposures and effects challenge.

Background: Humans are primary drivers of environmental-contaminant exposures worldwide, including in drinking-water (DW). In the United States, point-of-use DW (POU-DW) is supplied via private tapwater (TW), public-supply TW, and bottled water (BW). Differences in management, monitoring, and messaging and lack of directly-intercomparable exposure data influence the actual and perceived quality and safety of different DW supplies and directly impact consumer decision-making.

Catalytic inhibition of KAT6/KAT7 enhances the efficacy and overcomes primary and acquired resistance to Menin inhibitors in MLL leukaemia.

Understanding the molecular pathogenesis of MLL fusion oncoprotein (MLL-FP) leukaemia has spawned epigenetic therapies that have improved clinical outcomes in this often-incurable disease. Using genetic and pharmacological approaches, we define the individual and combined contribution of KAT6A, KAT6B and KAT7, in MLL-FP leukaemia. Whilst inhibition of KAT6A/B is efficacious in some pre-clinical models, simultaneous targeting of KAT7, with the novel inhibitor PF-9363, increases the therapeutic efficacy.

Early childhood respiratory morbidity according to gestational age at birth: A nationwide cohort study.

Background: Preterm birth survivors are at risk for short- and long-term respiratory morbidity. This includes increased rates of chronic obstructive pulmonary disease and infectious morbidity. Previous studies showed increased utilization of healthcare services throughout early childhood.

Ligand-coupled conformational changes in a cyclic nucleotide-gated ion channel revealed by time-resolved transition metal ion FRET.

Cyclic nucleotide-binding domain (CNBD) ion channels play crucial roles in cellular-signaling and excitability and are regulated by the direct binding of cyclic adenosine- or guanosine-monophosphate (cAMP, cGMP). However, the precise allosteric mechanism governing channel activation upon ligand binding, particularly the energetic changes within domains, remains poorly understood. The prokaryotic CNBD channel SthK offers a valuable model for investigating this allosteric mechanism.