A membrane permeability database for nonpeptidic macrocycles.

The process of developing new drugs is arduous and costly, particularly for targets classified as "difficult-to-drug." Macrocycles show a particular ability to modulate difficult-to-drug targets, including protein-protein interactions, while still allowing oral administration. However, the determination of membrane permeability, critical for reaching intracellular targets and for oral bioavailability, is laborious and expensive.

Molecular profiles of blood from numerous species that differ in sensitivity to acute inflammation.

Vertebrates differ over 100,000-fold in responses to pro-inflammatory agonists such as bacterial lipopolysaccharide (LPS), complicating use of animal models to study human sepsis or inflammatory disorders. We compared transcriptomes of resting and LPS-exposed blood from six LPS-sensitive species (rabbit, pig, sheep, cow, chimpanzee, human) and four LPS-resilient species (mice, rats, baboon, rhesus), as well as plasma proteomes and lipidomes. Unexpectedly, at baseline, sensitive species already had enhanced expression of LPS-responsive genes relative to resilient species.

Greater and Earlier Exposure of Mother's Own Milk Compared to Donor Human Milk Moderates Risk and Severity of Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is a common complication of preterm very low birth weight (VLBW) infants. Mother's own milk (MOM) may mitigate the severity of BPD. Pasteurized donor human milk (PDHM) is often used as an alternative when MOM is unavailable with limited information on the influence of PDHM on BPD risk and severity.

A genetically encoded actuator boosts L-type calcium channel function in diverse physiological settings.

L-type Ca channels (Ca1.2/1.3) convey influx of calcium ions that orchestrate a bevy of biological responses including muscle contraction, neuronal function, and gene transcription.