Resumo em Inglês:

Abstract Single nucleotide polymorphisms (SNPs) in the HLA DR/DQ region have the greatest impact on susceptibility to type 1 diabetes mellitus (T1DM). Non-HLA SNPs interact with the HLA, influencing the risk for T1DM. The aim of this study was to develop a genetic risk score (GRS) based on HLA DR/DQ and non-HLA SNPs to discriminate patients with T1DM. The sample comprised 466 patients with T1DM and 469 controls. The rs689/INS, rs2476601/PTPN22, rs231775/CTLA-4, rs2304256/TYK2, rs2292239/ERBB3, and HLA DR/DQ SNPs were genotyped using real-time PCR. The unweighted GRS (uGRS) was calculated by summing the risk alleles of each SNP and the weighted GRS (wGRS) by multiplying the risk alleles by their odds ratios. The uGRS was higher in T1DM patients than in non-diabetic controls (0.34 ± 0.14 vs. 0.26 ± 0.13, P <0.0001), being positively correlated with HbA1c levels (P <0.0001). wGRSs exhibited higher AUCs than uGRSs. The wGRS containing only HLA DR/DQ SNPs showed an AUC of 0.75 (95% CI 0.72 - 0.78). The wGRS containing both HLA DR/DQ and non-HLA SNPs, adjusted for race, demonstrated the best discriminative power [AUC 0.91 (95% CI 0.89 - 0.93)]. The race adjusted-wGRS, including all SNPs, seems to be a useful genetic tool for assessing individual’s predisposition to T1DM.

Resumo em Inglês:

Abstract Research has highlighted the significant role of methylated genes associated with DNA damage repair in pathogenesis of Lung adenocarcinoma (LUAD). However, the potential of DNA damage repair-related gene (DDRG) methylation as a prognostic biomarker remains underexplored. This study aimed to assess the prognostic value of methylated DDRGs in LUAD. Analysis of the TCGA-LUAD dataset revealed differentially expressed genes (DEGs) and differentially methylated genes (DE-MGs), from which methylated DE-DDRGs were identified. An independent prognostic risk model was constructed based on these methylated DE-DDRGs by integrating risk scores with clinical features. Additionally, the study examined responses to immunotherapy. Results indicated that CLU exhibited hypermethylation and elevated expression in LUAD tissues, while eight other genes (BUB1B, SHCBP1, RRM2, RPL39L, TRIP13, GAPDH, ENO1, and CENPM) showed high expression and hypomethylation. Among these, RRM2 and GAPDH were significantly linked to poorer overall survival. Furthermore, single-sample gene set enrichment analysis (ssGSEA) revealed that patients with LUAD in the high-risk group had lower immune scores and less immune cell infiltration. TIDE analysis suggested that patients in the low-risk group may exhibit greater sensitivity to immune checkpoint inhibitor therapy. In conclusion, RRM2 and GAPDH represent promising prognostic and immunotherapeutic biomarkers, offering new avenues for LUAD treatment strategies.

Resumo em Inglês:

Abstract Acute lymphoblastic leukemia (ALL) stands out as the most prevalent neoplasm during childhood, characterized by the rapid production of abnormal lymphoid cells. Chemotherapy administered to these patients may induce a substantial imbalance in the oral microbiota. A prospective pediatric study encompassing a control group (without ALL) and ALL patients at two treatment stages (pre-induction and consolidation) was conducted. Clinical and laboratory data were meticulously collected. Moreover, DNA from saliva samples was extracted for 16S rRNA sequencing. Clinical data revealed a heightened incidence of oral mucositis during the consolidation phase. Analysis of alpha biodiversity (observed taxa) exhibited a significant reduction in bacterial richness among patients in the consolidation phase. Network analysis identified key taxa during this phase, namely Neisseria flavescens, Prevotella melaninogenica and Porphyromonas. The findings underscore the substantial impact of ALL treatment on the oral microbiota composition, indicating diminished bacterial diversity and an elevated prevalence of oral mucositis.

Resumo em Inglês:

Abstract The contemporary genetic diversity of the cheetah (Acinonyx jubatus) has been the focus of several studies, which have revealed very low levels of variation. Different hypotheses have been proposed to explain this pattern of low diversity, and require additional scrutiny. Here, we used published microsatellite data and coalescence-based analytical methods to explore the historical demography of the largest free-ranging cheetah population, aiming to assess whether present-day diversity may have been impacted by a historical demographic decline. Our results support the hypothesis of a historical (and most likely gradual) demographic decline over the past ~10,000 years, leading to a present-day N e ranging from 700 to 1,600 individuals. This decline was likely induced by climate-driven vegetational shifts affecting habitat suitability and possibly also interspecies interactions with prey and competitors. These results help clarify the demographic history of cheetahs in southern Africa and its impact on the current genetic diversity of this population.

Resumo em Inglês:

Abstract Symphytum officinale is a perennial herb belonging to the Boraginaceae. Here, we sequenced the complete chloroplast (cp) genomes of S. officinale using Illumina sequencing technology. The results revealed that the cp genome is 148,149 bp in length and exhibits a typical quadripartite structure, with a pair of inverted repeat regions (IR) comprising 27,001 bp, a large single-copy (LSC) region comprising 77,366 bp, and a small single-copy (SSC) region comprising 16,781 bp. The sequence contained 133 unique genes, including 86 protein-coding genes, 37 transfer RNAs, eight ribosomal RNAs, and two pseudogenes. Six tandem, 42 dispersed, and 38 simple sequence repeats were identified. Sequence divergence analysis across 21 Boraginaceae species revealed that the most divergent regions, potentially serving as specific DNA barcodes, were found in non-coding spacers. A comparative analysis of the IR/SC boundary regions of the 21 Boraginaceae species revealed IR expansion events in S. officinale. Phylogenetic analysis based on 63 protein-coding genes demonstrated that S. officinale was closely related to Nonea vesicaria. This represents the first cp genome sequenced in Symphytum, and our results provide valuable genetic information for future population and phylogenetic studies of Boraginaceae.

Resumo em Inglês:

Abstract The genome of Corynebacterium pseudotuberculosis, etiologic agent of Caseous Lymphadenitis (CLA), was sequenced to comprehend its genetics, pathogenicity, and virulence mechanisms due to its economic importance. A focus was placed on the G/U mismatch-specific DNA glycosylase (Mug), an enzyme vital for base excision repair in DNA that can play an important role in uracil repair, since the high G+C content of C. pseudotuberculosis makes it prone to deamination events, accentuating the potential significance of Mug. Through in silico and in vitro analyses, the Corynebacterium pseudotuberculosis Mug protein (CpMug) was characterized to confirm its DNA glycosylase activity and lesion affinity. The mug gene was identified in both pathogenic and non-pathogenic Corynebacterium species, lacking a discernible ancestry pattern. Bioinformatics analyses revealed the preservation of essential uracil DNA glycosylase catalytic residues in CpMug. The 3D structure of CpMug was constructed, and molecular docking analysis demonstrated its interaction with DNA containing uracil and other lesions. Comparative analyses revealed a higher affinity of CpMug’s catalytic residues for uracil over other DNA lesions and enzymatic assays with purified CpMug affirmed its uracil DNA glycosylase activity, while it exhibited no activity on 8-oxoguanine, tetrahydrofuran, or thymine glycol, consistent with computational simulations.

Resumo em Inglês:

Abstract Different phthalate compounds, known as emerging contaminants, such as Di-n-butyl (DBP) and di-iso-pentyl (DiPeP) phthalates, have been found in aquatic environments and are widely used as additives to increase the flexibility of plastics. This study intended to evaluate the toxicity in zebrafish embryos and larvae of DBP and DiPeP, as well as the mixture of the two compounds. Fish embryo toxicity, neurotoxicity, oxidative stress, and genotoxicity studies were carried out in Danio rerio (zebrafish) embryos and larvae. Fish were exposed to DBP and DiPeP in concentrations ranging from 0.001 to 0.125 mg/L and also a combination of compounds DBP + DiPeP (1:1 MIX). DBP caused mortality and embryo malformations from 0.062 mg/L, DiPeP at 0.125 mg/L and the mixture at 0.031 mg/L, indicating the potential toxicity of these phthalates. Isolated phthalates and in mixture induced neurotoxicity and oxidative stress, at low concentrations in zebrafish larvae. No genotoxicity was found through comet assay in larvae. DBP was more toxic than DiPeP, and the mixture was more toxic than both phthalates when tested in isolation, showing some kind of interaction.

Resumo em Inglês:

Abstract We report a viral metagenomic analysis of fecal samples from Bradypus crinitus (Pilosa: Bradypodidae), a recently described sloth species that occurs in the Atlantic Forest of Espírito Santo and Rio de Janeiro states, Southeast Brazil. Through Illumina sequencing, we generated a total of 2,065,344 raw reads, of which 945,386 reads (45.77%) passed the quality and size filter. The highest proportion of them was assigned to Eukarya, followed by Bacteria and only a small proportion to Virus. However, we identified 24 viral families using distinct taxonomic assignment tools, including phages and vertebrate viruses, such as retroviruses and papillomaviruses. Also, we identified four bacterial genus already associated with disease in sloths. Our study sheds light on the microbiome of a previously unexplored species, further contributing to the comprehension of metagenomic global diversity.