Rational Exploration of 2,4-Diaminopyrimidines as DHFR Inhibitors Active against and , Two Emerging Human Pathogens.

Nontuberculous mycobacteria (NTM) are emerging human pathogens linked to severe pulmonary diseases. Current treatments involve the prolonged use of multiple drugs and are often ineffective. Bacterial dihydrofolate reductase (DHFR) is a key enzyme targeted by antibiotics in Gram-negative bacterial infections.

Investigating microstructural changes between in vivo and perfused ex vivo marmoset brains using oscillating gradient and b-tensor encoded diffusion MRI at 9.4 T.

Purpose: To investigate microstructural alterations induced by perfusion fixation in brain tissues using advanced diffusion MRI techniques and estimate their potential impact on the application of ex vivo models to in vivo microstructure.

Methods: We used oscillating gradient spin echo (OGSE) and b-tensor encoding diffusion MRI to examine in vivo and ex vivo microstructural differences in the marmoset brain. OGSE was used to shorten effective diffusion times, whereas b-tensor encoding allowed for the differentiation of isotropic and anisotropic kurtosis.

Foam Rolling on the Whole Leg and Its Immediate Effects on Postural Control in Collegiate Female Athletes.

The maintenance of body posture relies on mechanoreceptors, suggesting myofascial release could assist postural control. The effects of this have not been well documented, providing room for this investigation. Twenty-one female athletes spent approximately 2.

Formamide denaturation of double-stranded DNA for fluorescence in situ hybridization (FISH) distorts nanoscale chromatin structure.

As imaging techniques rapidly evolve to probe nanoscale genome organization at higher resolution, it is critical to consider how the reagents and procedures involved in sample preparation affect chromatin at the relevant length scales. Here, we investigate the effects of fluorescent labeling of DNA sequences within chromatin using the gold standard technique of three-dimensional fluorescence in situ hybridization (3D FISH). The chemical reagents involved in the 3D FISH protocol, specifically formamide, cause significant alterations to the sub-200 nm (sub-Mbp) chromatin structure.

Mutations in the non-catalytic polyproline motif destabilize TREX1 and amplify cGAS-STING signaling.

The cGAS-STING pathway detects cytosolic DNA and activates a signaling cascade that results in a type I interferon (IFN) response. The endoplasmic reticulum (ER)-associated exonuclease TREX1 suppresses cGAS-STING by eliminating DNA from the cytosol. Mutations that compromise TREX1 function are linked to autoinflammatory disorders, including systemic lupus erythematosus (SLE) and Aicardi-Goutières syndrome (AGS).