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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. 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, we focus on the sigmodontine rodent Abrothrix hirta, distributed from 35° S in Chile and Argentina to northern Tierra del Fuego. Based on 119,226 transcriptome-derived SNP loci from 46 individuals of A. hirta, we described the geographic distribution of the genetic diversity of this species using a maximum likelihood tree, principal component and admixture analyses. We also addressed the demographic history of the main intraspecific lineages of A. hirta using GADMA. We found that A. hirta exhibited four allopatric intraspecific lineages. Three main genetic groups were identified by a Principal Component Analysis and by Ancestry analysis. The demographic history of A. hirta was characterized by recent population stability for populations at the northernmost part of the range, while southern populations experienced a recent population expansion.We recently reported a deviation of local ancestry on the chromosome (ch) 8p23.1, which led to positive selection signals in a Brazilian population sample. The deviation suggested that the genetic variability of candidate genes located on ch 8p23.1 may have been evolutionarily advantageous in the early stages of the admixture process. see more In the present work, we aim to extend the previous work by studying additional Brazilian admixed individuals and examining DNA sequencing data from the ch 8p23.1 candidate region. Thus, we inferred the local ancestry of 125 exomes from individuals born in five towns within the Southeast region of Brazil (São Paulo, Campinas, Barretos, and Ribeirão Preto located in the state of São Paulo and Belo Horizonte, the capital of the state of Minas Gerais), and compared to data from two public Brazilian reference genomic databases, BIPMed and ABraOM, and with information from the 1000 Genomes Project phase 3 and gnomAD databases. Our results revealed that ancestry is similar among indiviposition in admixed individuals of the Brazilian population. Furthermore, we present evidence that the exploration of local ancestry deviation in admixed individuals may provide information with the potential to be translated into health care improvement.Lipid species are known to have various biological functions owing to their structural differences, and each of them possesses a specific role to play depending upon their location and distribution in the cell. Some of these lipids interact with proteins on the cell membrane and acts as second messengers. The level of lipid mediators is generally maintained in the cell by feedback mechanisms; however, their improper degradation or enhanced production leads to their accumulation in the tumor microenvironment and disturbs the homeostasis of the cell. Platelet activating factor (PAF) is a known phospholipid mediator secreted upon immunological challenges by platelets, neutrophils, basophils, and macrophages. PAF, as a potent inflammatory molecule, is well studied, and its role in various cancers and cardiovascular diseases has also been investigated. Interestingly, increased levels of PAF have been found in the blood plasma of smokers, and breast cancer cells have shown the accumulation of PAF in presence of cigarette smoke extract.