Abstract in English:

ABSTRACT The literature shows a correlation between ethnicity and pathogenic variants of the thyroid stimulating hormone receptor (TSHR) gene. Some of these polymorphisms may be risk factors for the development of primary congenital hypothyroidism (PCH). In this study, we investigated the relationship between the frequency of TSHR gene polymorphisms and the genetic influence of African, Amerindian, and European ancestry-informative markers in patients from an Amazonian population in Brazil who were diagnosed with PCH. The study was conducted on samples from 106 patients who were diagnosed with PCH. Genomic DNA was isolated from peripheral blood samples, and 10 exons from the TSHR gene were automatically sequenced. Ancestry-informative marker identification was performed using a panel of 48 markers, and the results were compared with parental Amerindian, Western European, and Sub-Saharan African populations using Structure v2.3.4 software. Four nucleotide alterations were identified among 49 patients. The distribution of tested ancestry markers among the 106 patients indicated a significant difference in the percentages of Amerindian (25.90 %), European (41.80 %), and African (32.20 %) ancestry. Logistic regression analysis revealed no significant association between the rs2075179 and rs1991517 polymorphisms and genetic ancestry. This study revealed no evidence of a relationship between polymorphic TSHR gene variants and genetic ancestry markers in patients with PCH.

Abstract in English:

Abstract Circulating neutrophils and ferroptosis are vital for the development of intracranial atherosclerotic stenosis (ICAS). This study aimed to explore that whether neutrophil ferroptosis participate in ICAS. Sixteen patients with ICAS and 14 healthy controls were enrolled. We collected peripheral blood and separated neutrophils. LncRNA, mRNA, and miRNA sequencing were performed. The differently expressed (DE) lncRNAs, mRNAs, and miRNAs were selected. The protein-protein interaction (PPI) network was constructed, top 30 hubgenes were selected, and intersected with DE ferroptosis genes to obtain the core genes. Combined with DE lncRNAs and miRNAs, the ceRNA network and TF-miRNA-mRNA network were constructed. Finally, the expression levels of the core genes were verified by Quantitative Reverse Transcription PCR (qRT-PCR) in other 11 patients and 9 healthy controls. The five core ferroptosis hubgenes were preliminarily identified, and ceRNA network and TF-miRNA-mRNA network were constructed. We identified several pairs of interactions. Finally, verification of qRT-PCR results revealed that CTSB (P=0.001) and HNRNPL (P=0.002) were upregulated, KRAS (P=0.003) and MAP1LC3A (P=0.004) were downregulated in ICAS group, compared with healthy controls. Our results identified four core genes (CTSB, HNRNPL, KRAS and MAP1LC3A) and constructed potential regulatory network, providing the potential therapeutic targets for ICAS.

Abstract in English:

Abstract Crossovers (COs) generate genetic diversity and proper homologous chromosome segregation during meiosis. Mus musculus domesticus, with a diploid number of 2n=40, has 19 autosomal pairs plus one sex chromosome pair all of which are telocentric chromosomes. Frequently exhibits Robertsonian fusions (Rb), which create natural populations with reduced chromosome numbers according to the Rb chromosomes. We examined the number and distribution of COs in spermatocytes from standard homozygous 2n=40 individuals, compared to homozygous Rb 2n=24 and heterozygous Rb 2n=32 individuals carrying 8 trivalents. Spermatocyte nuclear spreads from homozygous and heterozygous were prepared, and immunocytochemistry was used to detect the MLH1 protein for crossover (CO) and the SYCP3 protein for synaptonemal complexes in bivalents or trivalents. We observed an average of 26 ± 2.1 COs in 2n=40, 20.1 ± 1.6 COs in 2n=24, and an intermediate value of 22.4 ± 2.0 COs in 2n=32 spermatocytes. The lower frequency of COs in 2n=24 and 2n=32 spermatocytes compared to 2n=40 may be due to interference from the pericentromeric heterochromatin present in the Rb bivalent or trivalent chromosomes. Additionally, we suggest that the spatial positioning and interactions of these derivative chromosomes in the nucleus could help explain the differences in COs between 2n=24, 2n=32, and 2n=40 spermatocytes.

Abstract in English:

Abstract Cancer, neurodegeneration and other chronic diseases have been a primary focus for researchers studying the effects of genotoxins on human populations. However, when the scope shifts to non-human animals in natural environments, the impact of genotoxins extends beyond aging-related diseases. In ecological studies, DNA damage biomarkers (e.g., fragmentation of genetic material, micronuclei) in animal populations are often used to indicate “environmental quality”, but usually with a focus on human health. For example, an increase in the micronuclei frequency in an animal (sentinel) population may indicate risks to the genomic stability of the human population living in the same environment. This human-oriented approach frequently overlooks the ecological impacts of genotoxins on animal populations as an end, limiting the benefits for nature conservation from geno-toxicological studies. Environmental genotoxins pose a significant threat to biodiversity by causing multiple classes of DNA damage and mutations that impair varied cellular functions and reproduction, ultimately jeopardizing species survival through non-carcinogenic processes. This phenomenon, termed “genotoxic syndrome”, will be revisited in this article with examples of its detrimental effects on non-human animal populations. Finally, challenges and opportunities in evaluating genotoxic syndrome and its importance for conservation strategies are also discussed.

Abstract in English:

Abstract Apurinic/apyrimidinic sites are one of the most frequent spontaneous lesions in DNA. Evolutionarily conserved AP endonucleases (ExoIII and EndoIV families) incise the DNA backbone 5′ to the AP site and the cleaved AP sites are subsequently repaired by the base excision repair machinery. AP endonucleases additionally exhibit 3′-5′ exonuclease activity. Novel AP endonucleases that are not member of AP endonuclease families keep being reported and exhibit 3′-5′ exonuclease activity and other important DNA processing. Interestingly, human and mouse WRN helicases contain a 3′-5′ exonuclease domain, but the precise functional roles of the exonuclease activity in vivo remain unclear. We searched for WRN-like exonuclease proteins in the Caenorhabditis elegans database and found a new gene, zk1098.3, which shows a high similarity to human EXD3. Here, we assigned zk1098.3 to exd3-1. We cloned exd3-1 from an ORF clone and purified the recombinant EXD3-1 protein. We found that EXD3-1 displays incision at AP sites and exonucleolytic digestion on the nicked AP site and that EXD3-1 is involved in recovery from replication stress-induced cell cycle arrest. This work suggests that EXD3-1 either plays a role in base excision repair, although the extent of this repair remains to be determined, or has a specialized DNA damage response function.

Abstract in English:

Abstract The Hogei’s side-necked turtle, Ranacephala hogei, an endemic species of the Southern Paraíba basin, is the most endangered species of chelonians in Brazil. Here, we sequenced, assembled and described the complete mitogenome for R. hogei. The circularized mitogenome of R. hogei was 16,513 bp in length, containing all the typical 13 protein-coding genes, 2 rRNAs, 22 tRNAs and the D-loop region, as expected for animal mitogenomes. The gene arrangement also met the expectation for vertebrates, though R. hogei NAD6 gene was shorter than observed in other closely related species. Additionally, we provided an assembly of the Podocnemis expansa mitochondrial genome based on public data in SRA database. Maximum likelihood and Bayesian phylogenomic trees were constructed using the concatenation of the alignments of all protein coding and ribosomal genes and compared to the data obtained from other 15 complete mitochondrial genomes available for the suborder Pleurodira plus five Cryptodira taxa as outgroups in the GenBank database. Our phylogenomic results placed the mitogenome of R. hogei in a monophyletic South American clade which is deeply within the family Chelidae, corroborating the evolutionary affinities of the sequence. The remaining phylogenomic results also agrees with previous phylogenetic studies in Pleurodira, namely the reciprocal monophyly of the Australasian and South American Chelidae clades, and the monophyly of all higher clades such as families and suborder.

Abstract in English:

Abstract The identification of novel functional biomarkers is crucial in recognizing high-risk colorectal cancer (CRC) patients. Despite this need, no prognostic biomarker has been implemented in clinical practice for CRC. To address this gap, we utilized integrated transcriptomic data from public databases alongside our original multi-omics data, including proteome and chromatin accessibility datasets. Bioinformatics studies on transcriptomic datasets from 487 CRC patients led us to identify three Golgi apparatus prognostic genes: NIPAL1, ZYG11B, and PARP10. We found that decreased expression of NIPAL1 and ZYG11B, as well as increased expression of PARP10, elevated the risk of CRC. These genes are potentially involved in cellular processes such as nucleotide excision repair and DNA replication. Additionally, our original multi-omics datasets, encompassing proteomic data and chromatin accessibility profiling from assay for transposase-accessible chromatin with sequencing (ATAC-Seq), identified alterations in protein levels of potential upstream transcription factors CDX2 and YY1 for three genes. Furthermore, chromatin accessibility at DNA binding regions corresponding to transcription factors such as SPI1 and JUND changed, potentially explaining the observed variations in mRNA levels for these genes. Our findings highlight the biological activities of these genes, including NIPAL1, PARP10, and ZYG11B, and their upstream regulators, offering a functional context for future in-depth mechanistic studies.