Optimized metrics for orthogonal combinatorial CRISPR screens.

CRISPR-based gene perturbation enables unbiased investigations of single and combinatorial genotype-to-phenotype associations. In light of efforts to map combinatorial gene dependencies at scale, choosing an efficient and robust CRISPR-associated (Cas) nuclease is of utmost importance. Even though SpCas9 and AsCas12a are widely used for single, combinatorial, and orthogonal screenings, side-by-side comparisons remain sparse.

Hepatitis C virus genotype 1 and 2 recombinant genomes and the phylogeographic history of the 2k/1b lineage.

Recombination is an important driver of genetic diversity, though it is relatively uncommon in hepatitis C virus (HCV). Recent investigation of sequence data acquired from HCV clinical trials produced twenty-one full-genome recombinant viruses belonging to three putative inter-subtype forms 2b/1a, 2b/1b, and 2k/1b. The 2k/1b chimera is the only known HCV circulating recombinant form (CRF), provoking interest in its genetic structure and origin.

Resveratrol prevents palmitic-acid-induced cardiomyocyte contractile impairment.

Long-chain saturated fatty acids, especially palmitic acid (PA), contribute to cardiomyocyte lipotoxicity. This study tests the effects of PA on adult rat cardiomyocyte contractile function and proteins associated with calcium regulating cardiomyocyte contraction and relaxation. Adult rat cardiomyocytes were pretreated with resveratrol (Resv) and then treated with PA.

Exercise-induced increases in the expression and activity of cardiac sarcoplasmic reticulum calcium ATPase 2 is attenuated in AMPKα kinase-dead mice.

Exercise enhances cardiac sarcoplasmic reticulum Ca-ATPase 2a (SERCA2a) function through unknown mechanisms. The present study tested the hypothesis that the positive effects of exercise on SERCA2a expression and function in the left ventricle is dependent on adenosine-monophosphate-activated protein kinase (AMPK) α2 function. AMPKα kinase-dead (KD) transgenic mice, which overexpress inactivated AMPKα subunit, and wild-type C57Bl/6 (WT) mice were randomized into sedentary groups or groups with access to running wheels.