Genetics and Molecular Biology最新文献

Oral squamous cell carcinoma (OSCC) has a poor prognosis and the treatment employed generates significant physical deformity in patients. In recent years, an increase in the incidence of cases of OSCC has been observed in adult patients up to 45 years old in several genetic underrepresented and underserved countries. The increase in OSCC cases in young people is very relevant because it shows that OSCC does not make exceptions and hereditarily must play an important role. This fact has not been associated with an evident biological basis, and a large majority of these patients do not present the classic principal risk factors association. OSCC is the result of accumulation of genetic and epigenetic alterations and this information is still fragmented in the literature, mainly in the young group. Conducting studies with a comprehensive analysis of genetic and epigenetic data is crucial, to provide greater understanding of the underlying biology of OSCC, because this information can be decisive to determine targets for therapeutic treatment. We review the main germline and somatic aspects of genetic and genomic variation in OSCC considering the absence of genomic data from developing countries such as Chile and the rest of Hispano-America.

Genetic, epigenetic and environmental factors play an important role in the genesis of Type 2 Diabetes Mellitus (T2D). In the genetic context, one of the strategies used to investigate possible associations with diabetes is the search for Single Nucleotide Polymorphisms (SNPs), involving the comparison of alelle frequencies, the phenotypic variations and other relevant factors, such as environmental influences and lifestyle choices, Thus, the aim of this study was to find the relationship of risk variants for T2D in SNPs (rs4994) in the ADRB3 gene; (rs1799854) in the ABCC8 gene; (rs7901695 and rs12255372) in the TCF7L2 gene; and (rs8050136) in the FTO gene in a sample of the population of the municipality of Santarém (PA), Brazilian Amazon, in the northern region of Brazil. ABCC8 (rs1799854 C>T) showed a statistically significant association with T2D. Each chosen gene and SNP has been previously implicated in T2D risk according to existing scientific literature, owing to their roles in glucose regulation and body fat.

The globally widespread genus Sulfurimonas are playing important roles in different habitats, including the deep-sea hydrothermal vents. However, phages infecting Sulfurimonas have never been isolated and characterized to date. In the present study, a novel prophage SNW-1 was identified from Sulfurimonas indica NW79. Whole genome sequencing resulted in a circular, double-stranded DNA molecule of 37,096 bp with a mol% G+C content of 37. The genome includes 64 putative open reading frames, 33 of which code for proteins with predicted functions. Presence of hallmark genes associated with Caudoviricetes and genes involved in lysis and lysogeny indicated that SNW-1 should be a temperate, tailed phage. Phylogenetic and comparative proteomic analyses suggested that Sulfurimonas phage SNW-1 was distinct from other double stranded DNA phages and might represent a new viral genus.

Transplantation of stem cells derived from donors with CCR5Δ32 homozygous genotype is a potential strategy to achieve both the control of malignant hematological disease as well as sustained remission of the HIV infection, and researchers in different countries are looking for CCR5Δ32 homozygous donors to replicate such a 'double-target' strategy. We determined the frequency of the CCR5Δ32 variant in a sample of 1,398 bone marrow donors from Rio Grande do Sul State, Brazil. This study also evaluated whether HLA-A, HLA-B and HLA-DRB1 genotypes are homogeneously distributed between CCR5Δ32 carriers and non-carriers in a population characterized by a significant genetic admixture. The CCR5Δ32 allele frequency was 7.4% (CI0.95 6.4-8.4%), and the frequency of the Δ32/Δ32 homozygous genotype was 0.72% (CI0.95 0.34-1.31%). In general, HLA genotypes are homogeneously distributed between CCR5Δ32 carriers and non-carriers. Considering the large number of bone marrow donors in Brazil and the high CCR5Δ32 allele frequency observed in our study, our results clearly indicate the existence of a considerable amount of potential CCR5Δ32 homozygous bone marrow donors in southern Brazil, suggesting that an active search for these donors is not only feasible but an attractive and promising strategy towards effective HIV infection control and treatment.

Free-living amoebas are natural predators of fungi, including human pathogens of the Cryptococcus genus. To survive and proliferate inside phagocytes, cryptococcal cells must acquire several nutrients. Zinc is fundamental for all life forms and develops a crucial role in the virulence of fungal pathogens, phagocytes reduce the availability of this metal to reduce the development of infection. The Acanthamoeba castellanii ACA1_271600 gene codes a metal transporter that is possibly associated with such antifungal strategy. Here, we evaluated the impact of A. castellanii metal homeostasis on C. gattii survival. Gene silencing of ACA1_271600 was performed and the interaction outcome of amoeba cells with both WT and zinc homeostasis-impaired mutant cryptococcal cells was evaluated. Decreased levels of ACA1_271600 in silenced amoeba cells led to higher proliferation of such cryptococcal strains. This effect was more pronounced in the zip1 mutant of C. gattii, suggesting that ACA1_271600 gene product modulates metal availability in Cryptococcus-infected amoebae. In addition, a systems biology analysis allowed us to infer that ACA1_271600 may also be involved in other biological processes that could compromise amoebae activity over cryptococcal cells. These results support the hypothesis that A. castellanii can apply nutritional immunity to hamper cryptococcal survival.

We predicted miRNAs with regulatory impact on NFKB1 and TRAF6 gene expression and selected the miR-194-5p, miR-124-3p, miR-9-5p, and miR-340-5p and their target genes for expression analyses on CD14+ monocytes from rheumatoid arthritis (RA) patients and healthy controls. Additionally, we evaluated the influence of genes and miRNA expression on RA patients' cytokine levels. No difference was observed in genes or miRNAs expression when compared to healthy controls and RA patients or clinical parameters. However, we found a significant difference between miR-194-5p and miR-9-5p levels (FC=-2.31; p=0.031; FC=-3.05;p=0.031, respectively) and non-prednisone users as compared to prednisone using patients. We conducted correlation analyses to identify the strength of the relationship between expression data and cytokine plasma levels. We observed a moderate positive correlation between miR-124-3p expression and IL-6 plasma levels (r=0.46; p=0.033). In addition, overexpression of miRNAs was concomitant to TRAF6 and NFKB1 genes as indicated by correlation analyses: TRAF6 and miR-194-5p (r=0.60;p<0.001) and miR-9-5p (r=0.63;p<0.001) and NFKB1 and miR-194-5p (r=0.72;p<0.001), miR-9-5p (r=0.72;p<0.001) and miR-340-5p (r=0.61;p<0.001). NFKB1 and TRAF6 genes and miRNAs monocyte expression do not appear to be related to RA but showed a significant difference in different groups of RA therapy. In addition, increased levels of miRNAs can be linked to concomitant overexpression of TRAF6 and NFKB1 in monocytes and act as its regulators.

Animals adapt to the daily changes in their environmental conditions by means of genetically encoded circadian clocks. These clocks, found throughout the tree of life, regulate diverse biological functions, and allow periodical changes in physiology and behaviour. The molecular underpinnings of these clocks have been extensively studied across taxa, revealing a brain-based system that coordinates rhythmic activities through neuronal networks and signalling pathways. Entrainment, the alignment of internal rhythms with external cues or zeitgebers, is crucial for the adaptive value of these internal clocks. While the solar light-dark cycle is a primary zeitgeber for most animals, other relevant cues such as temperature, meal timing, predators, anxiety, fear, physical activity, and social interactions also play roles in entraining circadian clocks. The search of a detailed description of the circadian clocks is a goal for neurobiology and an area of growing societal interests. Moreover, as disruptions in circadian rhythms are implicated in various diseases, understanding the entrainment pathways contributes to developing interventions for improved wellbeing and health outcomes. This review focuses on socially relevant cues, examining their impact on animal physiology and behaviour, and explores the sensory pathways transmitting information to the central clock.

The breast microbiome presents a diverse microbial community that could affects health and disease states, in the context of breast cancer. Sequencing technologies have allowed describing the diversity and abundance of microbial communities among individuals. The complex tumoral microenvironment that includes the microbial composition could influence tumor growth. The imbalance of diversity and abundance inside the microbial community, known as dysbiosis plays a crucial role in this context. One the most prevalent bacterial genera described in breast invasive carcinoma are Bacillus, Pseudomonas, Brevibacillus, Mycobacterium, Thermoviga, Acinetobacter, Corynebacterium, Paenibacillus, Ensifer, and Bacteroides. Paenibacills genus shows a relation with patient survival. When the Paenibacills genus increases its abundance in patients with breast cancer, the survival probability decreases. Within this dysbiotic environment, various bacterial metabolites could play a pivotal role in the progression and modulation of breast cancer. Key bacterial metabolites, such as cadaverine, lipopolysaccharides (LPS), and trimethylamine N-oxide (TMAO), have been found to exhibit potential interactions within breast tissue microenvironments. Understanding the intricate relationships between dysbiosis and these metabolites in breast cancer may open new avenues for diagnostic biomarkers and therapeutic targets. Further research is essential to unravel the specific roles and mechanisms of these microbial metabolites in breast cancer progression.

Distinguishing between environmental adaptations and neutral processes poses a challenge in population genetics and evolutionary studies, particularly when phenomena can be explained by both processes. Clines are genotypic or phenotypic characters correlated with environmental variables, because of that correlation, they are used as examples of spatially varying selection. At the same time, many genotypic clines can be explained by demographic history, like isolation by distance or secondary contact zones. Clines have been extensively studied in Drosophila melanogaster, especially in North America and Australia, where they are attributed to both differential selection and various demographic processes. This review explores existing literature supporting this conclusion and suggests new approaches to better understand the influence of these processes on clines. These innovative approaches aim to shed light on the longstanding debate regarding the importance of natural selection versus neutral processes in maintaining variation in natural populations.

Growth differentiation factor 11 (GDF11) and myostatin (MSTN/GDF8) are closely related members of the transforming growth factor β (TGFβ) superfamily, sharing structural homology. Despite these structural similarities, recent research has shed light on the distinct roles these ligands play within muscle tissue. This study aims to uncover both the differences and similarities in gene expression at the transcriptome level by utilizing RNA sequencing. We conducted experiments involving five distinct groups, each with three biological replicates, using C2C12 cell cultures. The cells were subjected to high-throughput profiling to investigate disparities in gene expression patterns following preconditioning with either GDF11 or MSTN at concentrations of 1 nM and 10 nM, respectively. In addition, control groups were established. Our research revealed concentration-dependent gene expression patterns, with 38 genes showing significant differences when compared to the control groups. Notably, GADD45, SMAD7, EGR-1, and HOXA3 exhibited significant differential expression. We also conducted an over-representation analysis, highlighting the activation of MAPK and JNK signaling pathways, along with GO-terms related to genes that negatively regulate metabolic processes, biosynthesis, and protein phosphorylation. This study unveiled the activation of several genes not previously discussed in existing literature whose full biological implications are yet to be determined in future research.