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There is current awareness about the central role of mitochondrial dysfunction in the development of cardiac dysfunction in systemic inflammatory syndromes, especially in sepsis and endotoxemia. The aim of this work was to elucidate the mechanism that governs the link between the severity of the systemic inflammatory insult and mitochondrial function, analysing the consequences on heart function, particularly in cardiac contractile state. Female Sprague–Dawley rats were subjected to low-grade endotoxemia (i.p. injection LPS 0.5 mg kg−1 body weight) and severe endotoxemia (i.p. injection LPS 8 mg kg−1 body weight) for 6 h. Blood NO, as well as cardiac TNF-α and IL-1β mRNA, were found increased as the severity of the endotoxemia increases. Cardiac relaxation was altered only in severe endotoxemia, although contractile and lusitropic reserves were found impaired in both treatments in response to work-overload. Cardiac ultrastructure showed disorientation of myofibrillar structure in both endotoxemia degrees, but mitochondrial swelling and cristae disruption were only observed in severe endotoxemia. Mitochondrial ATP production, O2 consumption and mitochondrial inner membrane potential decreases were related to blood NO levels and mitochondrial protein nitration, leading to diminished ATP availability and impairment of contractile state. Co-treatment with the NOS inhibitor l-NAME or the administration of the NO scavenger c-PTIO leads to the observation that mitochondrial bioenergetics status depends on the degree of the inflammatory insult mainly determined by blood NO levels. Unravelling the mechanisms involved in the onset of sepsis and endotoxemia improves the interpretation of the pathology, and provides new horizons for novel therapeutic targets.

Obtaining informative short tandem repeat (STR) profiles from degraded DNA samples is a challenging task usually undermined by locus or allele dropouts and peak-high imbalances observed in capillary electrophoresis (CE) electropherograms, especially for those markers with large amplicon sizes. We hereby show that the current STR assays may be greatly improved for the detection of genetic markers in degraded DNA samples by using long single stranded DNA polynucleotides (ssDNA polynucleotides) as surrogates for PCR primers. These long primers allow a closer annealing to the repeat sequences, thereby reducing the length of the template required for the amplification in fragmented DNA samples, while at the same time rendering amplicons of larger sizes suitable for multiplex assays. We also demonstrate that the annealing of long ssDNA polynucleotides does not need to be fully complementary in the 5' region of the primers, thus allowing for the design of practically any long primer sequence for developing new multiplex assays. Furthermore, genotyping of intact DNA samples could also benefit from utilizing long primers since their close annealing to the target STR sequences may overcome wrong profiling generated by insertions/deletions present between the STR region and the annealing site of the primers. Additionally, long ssDNA polynucleotides might be utilized in multiplex PCR assays for other types of degraded or fragmented DNA, e.g. circulating, cell-free DNA (ccfDNA).

Historical records suggest that Chiriguano tribe is the result of a genetic admixture event. The process involved the arrival of Guaraní tribesmen descending from Amazonian region of Brazil along with groups of Arawak origin that inhabited the foothill plains of Bolivia. Later they arrived in Argentina at the beginning of the twentieth century. Aiming to test the historical records, we analysed a set of 46 samples collected at San Ramon de la Nueva Orán, Province of Salta, Argentina. A wide set of uni- and biparentally transmitted genetic markers were analysed, including 23 autosomal STRs; 46 AIM-DIPs and 24 AIM-SNPs all located at diverse autosomal chromosome locations; 23 Y-STRs and the entire mtDNA D-Loop sequence. Ancestry informative markers allowed for the detection of a strong Native American component in the genomes (> 94%), while all mtDNA haplotypes showed Native American characteristic motives, and 93% of Y-haplotypes belonged to the Q1a3a Y-haplogroup. The analysis of mitochondrial haplotypes and Y chromosome, although they did not match other populations, revealed a relationship between the Chiriguano and other groups of Guaraní and Arawak origin inhabiting Brazil and Bolivia, confirming, at least in part, the historical records describing the origins of Chiriguano tribal settlements in northwestern Argentina.