The RNA-guided CRISPR-associated (Cas) enzyme Cas12a cleaves specific double-stranded (ds-) or single-stranded (ss-) DNA targets (in cis), unleashing non-specific ssDNA cleavage (in trans). Though this trans-activity is widely coopted for diagnostics, little is known about target determinants promoting optimal enzyme performance. Using quantitative kinetics, we show formation of activated nuclease proceeds via two steps whereby rapid binding of Cas12a ribonucleoprotein to target is followed by a slower allosteric transition.
View Article and Find Full Text PDFBackground & Objectives: Investment in mental health is quite meagre worldwide, including in India. The costs of new interventions must be clarified to ensure the appropriate utilization of available resources. The government of Gujarat implemented QualityRights intervention at six public mental health hospitals.
View Article and Find Full Text PDFThe single nucleotide polymorphisms rs35349669 and rs10933431 within Inositol Polyphosphate-5-Phosphatase D () are strongly associated with Alzheimer's Disease risk. To better understand expression in the brain, we investigated isoform expression as a function of rs35349669 and rs10933431, as well as Alzheimer's disease neuropathology, by qPCR and isoform-specific primers. In addition, allelic expression imbalance was evaluated relative to rs1141328 within exon 1.
View Article and Find Full Text PDFL-type transposition of the great vessels is a rare congenital heart disease in which both the great arteries and the ventricular chambers are reversed. Because this condition preserves a physiologic circulatory pathway, it can be challenging to diagnose in infants with no concurrent cardiac abnormalities. Early detection is essential, however, because these patients will eventually experience severe complications, as the structural right ventricle is unable to function long-term in the systemic position.
View Article and Find Full Text PDF