Population-based risk assessment of APOL1 on renal disease

Case-control studies suggest that African Americans with genetic variants in both copies of APOL1 have increased risk for hypertension-attributable ESRD and focal segmental glomerulosclerosis. Here, we tested these risk variants in the Dallas Heart Study to ascertain the prevalence of APOL1-associated renal disease in a large population-based study and to estimate the contribution of APOL1 risk variants to disparities in renal disease. We determined the genotype of 1825 African Americans and 1042 European Americans. Among participants without diabetes, we identified microalbuminuria in 2.3% of European Americans, 6.0% of African Americans with no or one APOL1 risk allele, and 16.5% of African Americans with two risk alleles. In addition, the proportions of participants with estimated GFR < 60 ml/min per 1.73 m(2) was 1.5% for nondiabetic European Americans, 1.7% for African Americans with no or one APOL1 risk allele, and 6.7% for African Americans with two risk alleles. The APOL1 genotype did not associate with any differences in rates of CKD for study participants with diabetes. Our data suggest that more than 3 million African Americans likely have the high-risk genotype and are at markedly increased risk for nondiabetic CKD. In contrast, African Americans without the risk genotype and European Americans appear to have similar risk for developing nondiabetic CKD.     

A set of miniSTRs for population genetic analyses of tigers (Panthera tigris) with cross-species amplification for seven other Felidae

With ~3500 wild individuals restricted to 7% of their historical range, tigers are now a global conservation symbol. Here we describe eight miniSTR loci for the Indian tiger (Panthera tigris tigris). These loci were polymorphic (average number of alleles 6.75 (SD 1.39)) with high mean observed heterozygosity (0.43 (SD 0.1)). At least six of these loci could be successfully amplified from seven other feline species present in the Indian subcontinent. These miniSTRs could potentially help population genetic analyses of other elusive and endangered felids.     

NAD(+)-dependent DNA ligase: a novel target waiting for the right inhibitor

DNA ligases (EC.6.5.1.1) are key enzymes that catalyze the formation of phosphodiester bonds at single stranded or double stranded breaks between adjacent 5' phosphoryl and 3' hydroxyl groups of DNA. These enzymes are important for survival because they are involved in major cellular processes like DNA replication/repair and recombination. DNA ligases can be classified into two groups on the basis of their cofactor specificities. NAD(+)-dependent DNA ligases are present in bacteria, some entomopox viruses and mimi virus while ATP-dependent DNA ligases are ubiquitous. The former have recently been drawing a lot of attention as novel targets for antibiotics to overcome current drug resistance issues. Currently a diverse range of inhibitors have been identified. There are several issues to be addressed in the quest for optimized inhibitors of the enzyme. In the first part of the review we summarize current structural work on these enzymes. Subsequently we describe the currently available classes of inhibitors. We also address modalities to improve the specificity and potencies of new inhibitors identified using protein structure based rational approaches. In conclusion, NAD(+)-dependent ligases show great promise and represent a novel drug target whose time has come.     

Spontaneous intercostal artery bleeding in a patient with alcohol‐induced liver cirrhosis

Spontaneous intercostal artery bleeding is a rare disease seen in cirrhosis and can present with hemodynamically significant blood loss anemia, hypotension, and shock. Transcatheter arterial embolization is an effective treatment for severe cases.