Nuclear DNA sequences from late Pleistocene megafauna

We report the retrieval and characterization of multi- and single-copy nuclear DNA sequences from Alaskan and Siberian mammoths (Mammuthus primigenius). In addition, a nuclear copy of a mitochondrial gene was recovered. Furthermore, a 13,000-year-old ground sloth and a 33,000- year-old cave bear yielded multicopy nuclear DNA sequences. Thus, multicopy and single-copy genes can be analyzed from Pleistocene faunal remains. The results also show that under some circumstances, nucleotide sequence differences between alleles found within one individual can be distinguished from DNA sequence variation caused by postmortem DNA damage. The nuclear sequences retrieved from the mammoths suggest that mammoths were more similar to Asian elephants than to African elephants.      

Influence of inorganic phosphate on the production of free radicals in UV-irradiated frozen tyrosine solutions

The role of inorganic phosphate as a catalyzer of the production of tyrosyl radical in frozen tyrosine solutions irradiated with near UV light at 77 K has been demonstrated by the EPR method. It was shown that the increase in the yield of tyrosyl radicals at pH < 7 correlates with the production of H^• atoms and can be explained by the fact that phosphate acts as an acceptor of photoejected electrons. At pH > 7, the increase in the yield of tyrosyl radicals is accompanied by the production of phosphate radicals and OH^• and is caused, presumably, by the catalysis of the formation of triplet states of tyrosine molecules by the HP form of phosphate, the fact shown by a number of authors. A quantitative estimation of relative concentrations of photosensitized paramagnetic products was carried out on the basis of computer analysis of resultant EPR signals.     

Nebulized Delivery of the MAPKAP Kinase 2 Peptide Inhibitor MMI-0100 Protects Against Ischemia-Induced Systolic Dysfunction

Acute myocardial infarction (AMI) results in systolic dysfunction, myocarditis and fibrotic remodeling, which causes irreversible pathological remodeling of the heart. Associated cell death and inflammation cause cytokine release, which activates the p38 MAPK signaling pathway to propagate damaging signals via MAPKAP kinase 2 (MK2). Previously we showed that intraperitoneal injection of a cell permeable peptide inhibitor of MK2, MMI-0100, protects against fibrosis, apoptosis and systolic dysfunction in a mouse model of AMI induced by left-anterior descending coronary artery (LAD) ligation. Here we tested a new route of administration of MMI-0100: inhalation of nebulized peptide. When given within 30 min of AMI and daily for 2 weeks thereafter, both inhaled and injected MMI-0100 improved cardiac function as measured by conscious echocardiography. Limited fibrosis was observed after 2 weeks by Massons trichrome staining, suggesting that MMI-0100 protects the heart prior to the formation of significant fibrosis. These results support a nebulized route of administration of MMI-0100 can protect the myocardium from ischemic damage.     

A regulatory variant at 3q21.1 confers an increased pleiotropic risk for hyperglycemia and altered bone mineral density

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