Caspersen Daly (gripsphynx7)

It can be used to individualize the treatment of bladder cancer. TRIB3 is a potential prognostic marker and therapeutic target. It can be used to individualize the treatment of bladder cancer. To describe the clinical and molecular spectrum of Stargardt disease (STGD) in a cohort of Argentinean patients. This retrospective study included 132 subjects comprising 95 probands clinically diagnosed with STGD and relatives from 16 of them. Targeted next-generation sequencing of the coding and splicing regions of and other phenocopying genes ( , , and ) was performed in 97 STGD patients. We found two or more disease-causing variants in the gene in 69/95 (73%) probands, a single A4 variant in 9/95 (9.5%) probands, and no variants in 17/95 (18%) probands. The final analysis identified 173 variants in . Seventy-nine variants were unique, of which nine were novel. Ziprasidone No significant findings were seen in the other evaluated genes. This study describes the phenotypic and genetic features of STGD1 in an Argentinean cohort. The mutations p.(Gly1961Glu) and p.(Arg1129Leu) were the most frequent, representing almost 20% of the mutated alleles. We also expanded the mutational spectrum with nine novel disease-causing variants, of which eight might be associated with South American natives. This study describes the phenotypic and genetic features of STGD1 in an Argentinean cohort. The mutations p.(Gly1961Glu) and p.(Arg1129Leu) were the most frequent, representing almost 20% of the mutated alleles. We also expanded the ABCA4 mutational spectrum with nine novel disease-causing variants, of which eight might be associated with South American natives.Telomeres, repetitive nucleoprotein complexes that protect chromosomal termini and prevent them from activating inappropriate DNA damage responses (DDRs), shorten with cell division and thus with aging. Here, we characterized the human cellular response to targeted telomeric double-strand breaks (DSBs) in telomerase-positive and telomerase-independent alternative lengthening of telomere (ALT) cells, specifically in G1 phase. Telomeric DSBs in human G1 cells elicited early signatures of a DDR; however, localization of 53BP1, an important regulator of resection at broken ends, was not observed at telomeric break sites. Consistent with this finding and previously reported repression of classical non-homologous end-joining (c-NHEJ) at telomeres, evidence for c-NHEJ was also lacking. Likewise, no evidence of homologous recombination (HR)-dependent repair of telomeric DSBs in G1 was observed. Rather, and supportive of rapid truncation events, telomeric DSBs in G1 human cells facilitated formation of extensive tracks of resected 5' C-rich telomeric single-stranded (ss)DNA, a previously proposed marker of the recombination-dependent ALT pathway. Indeed, induction of telomeric DSBs in human ALT cells resulted in significant increases in 5' C-rich (ss)telomeric DNA in G1, which rather than RPA, was bound by the complementary telomeric RNA, TERRA, presumably to protect these exposed ends so that they persist into S/G2 for telomerase-mediated or HR-dependent elongation, while also circumventing conventional repair pathways. Results demonstrate the remarkable adaptability of telomeres, and thus they have important implications for persistent telomeric DNA damage in normal human G1/G0 cells (e.g., lymphocytes), as well as for therapeutically relevant targets to improve treatment of ALT-positive tumors.Genetic information on species can inform decision making regarding conservation of biodiversity since the response of organisms to changing environments depend, in part, on their genetic makeup. Territories of central-southern Chile and Argentina have undergone a varying degree of impact during the Quaternary, where the response of local fauna and flora was rather species-specific. Here,