Thermal Adaptation of Cytosolic Malate Dehydrogenase Revealed by Deep Learning and Coevolutionary Analysis.

Protein evolution has shaped enzymes that maintain stability and function across diverse thermal environments. While sequence variation, thermal stability and conformational dynamics are known to influence an enzyme's thermal adaptation, how these factors collectively govern stability and function across diverse temperatures remains unresolved. Cytosolic malate dehydrogenase (cMDH), a citric acid cycle enzyme, is an ideal model for studying these mechanisms due to its temperature-sensitive flexibility and broad presence in species from diverse thermal environments.

Clinical significance of sleepiness: an American Academy of Sleep Medicine position statement.

Alertness is a necessity for well-being and performance, and sleepiness is associated with cognitive and functional impairments that can have a negative impact on performance, health, mood, safety, and quality of life. In severe cases, sleepiness can lead to debilitation, injury, or death. Sleepiness is a marker of insufficient sleep and is the major patient-reported symptom associated with disorders of sleep and wakefulness such as narcolepsy and obstructive sleep apnea.

Activity Protects Spinal Premotor Interneurons from Microglial Phagocytosis and Transneuronal Degeneration After Corticospinal Injury.

Spinal premotor circuits play a fundamental role in motor control. The corticospinal tract (CST) provides control signals to premotor circuits in the spinal cord, guiding voluntary skilled movements. Unilateral selective lesion of the CST in the medullary pyramidal tract (PTX) produces transneuronal degeneration, whereby Choline Acetyltransferase-positive (ChAT) premotor interneurons contralesionally undergo non-apoptotic degeneration by microglial phagocytosis.

Circulating neutralizing antibodies and SARS-CoV-2 variant replication following postvaccination infections.

The effect of preexisting neutralizing antibodies (NAb) on SARS-CoV-2 shedding in postvaccination infection (PVI) is not well understood. We characterized viral shedding longitudinally in nasal specimens in relation to baseline (pre/periinfection) serum NAb titers in 125 participants infected with SARS-CoV-2 variants. Among 68 vaccinated participants, we quantified the effect of baseline NAb titers on maximum viral RNA titers and infectivity duration.

Beltraniella portoricensis strain MRH42, a saprophytic fungus from Mexico, produces antimicrobial and cytotoxic hymenopsins.

Antimicrobial bioassay-guided isolation of metabolites from fermented rice cultures of Beltraniella portoricensis strain MRH42 yielded known metabolites hymenopsin A (1) and B (2). Their chemical structures were identified by comparison of their nuclear magnetic resonance and high-resolution mass spectra data reported in the literature. Both metabolites were cytotoxic to human tumour cell lines liver (HepG2), colon (HT29), breast (MCF-7), pancreatic (MiaPaca-2), and human epithelial liver cells transformed (THLE2), with ED50 ranging from 45.