Exploring HLA-C methylation patterns and nutritional status in Kichwa mothers and infants from Tena, Ecuador.

Environment and lifestyle can affect the epigenome passed down from generation to generation. A mother's nutrition can impact the methylation levels of her offspring's epigenome, but it's unclear which genes may be affected by malnutrition during gestation or early development. In this study, we examined the levels of methylated GC in the promoter region of HLA-C in mothers and infants from the Kichwa community in Ecuador. To do this, we analyzed saliva samples using bisulfite DNA sequencing. While we did not observe any significant differences in the mean methylation percentages in exon 1 of HLA-C between mothers and their infants after the first two years of lactation and life, respectively, we did find that infants tended to increase their methylation level during the first two years of life, while mothers tended to decrease it after the first two years of breastfeeding. When we compared methylation levels between mothers and infants using an ANOVA/posthoc Tukey test, we found that the average methylation for the entire population was less than 3% at T1 and T2. Although there was a tendency for infants to have higher methylation levels during their first two years of life and for mothers to have lower methylation levels after the first two years of breastfeeding, the mean values were not significantly different. However, we found a significant difference when we contrasted the data using a Kruskal-Wallis test at 0.05 for T1 AND T2 (p-value: 0.0148). Specifically, mothers had an average of X̅ = 2.06% and sons had X̅ = 1.57% at T2 (p-value: 0.7227), while the average for mothers was X̅ = 1.83% and for sons X̅ =1.77%. Finally, we identified three CpG motif nucleotide positions (32-33, 43-44, and 96-97) along the 122 bp analysis of HLA-C exon one, which was found to retain methylation patterns over time and is inherited from mother to offspring. Finally, our small pilot study did not reveal significant correlations between maternal and offspring nutritional status and DNA methylation levels of HLA-C exon one.

"HLA-C: evolution, epigenetics, and pathological implications in the major histocompatibility complex".

HLA-C, a gene located within the major histocompatibility complex, has emerged as a prominent target in biomedical research due to its involvement in various diseases, including cancer and autoimmune disorders; even though its recent addition to the MHC, the interaction between HLA-C and KIR is crucial for immune responses, particularly in viral infections. This review provides an overview of the structure, origin, function, and pathological implications of HLA-C in the major histocompatibility complex. In the last decade, we systematically reviewed original publications from Pubmed, ScienceDirect, Scopus, and Google Scholar. Our findings reveal that genetic variations in HLA-C can determine susceptibility or resistance to certain diseases. However, the first four exons of HLA-C are particularly susceptible to epigenetic modifications, which can lead to gene silencing and alterations in immune function. These alterations can manifest in diseases such as alopecia areata and psoriasis and can also impact susceptibility to cancer and the effectiveness of cancer treatments. By comprehending the intricate interplay between genetic and epigenetic factors that regulate HLA-C expression, researchers may develop novel strategies for preventing and treating diseases associated with HLA-C dysregulation.

The role of auxin during early berry development in grapevine as revealed by transcript profiling from pollination to fruit set.

Auxin is a key phytohormone that modulates fruit formation in many fleshy fruits through the regulation of cell division and expansion. Auxin content rapidly increases after pollination and the manipulation in its levels may lead to the parthenocarpic development. ln Vitis vinifera L., little is known about the early fruit development that encompasses from pollination to fruit set. Pollination/fertilization events trigger fruit formation, and auxin treatment mimics their effect in grape berry set. However, the role of auxin in this process at the molecular level is not well understood. To elucidate the participation of auxin in grapevine fruit formation, morphological, reproductive, and molecular events from anthesis to fruit set were described in sequential days after pollination. Exploratory RNA-seq analysis at four time points from anthesis to fruit set revealed that the highest percentage of genes induced/repressed within the hormone-related gene category were auxin-related genes. Transcript profiling showed significant transcript variations in auxin signaling and homeostasis-related genes during the early fruit development. Indole acetic acid and several auxin metabolites were present during this period. Finally, application of an inhibitor of auxin action reduced cell number and the mesocarp diameter, similarly to unpollinated berries, further confirming the key role of auxin during early berry development. This work sheds light into the molecular features of the initial fruit development and highlights the auxin participation during this stage in grapevine.

Root transcriptomic responses of grafted grapevines to heterogeneous nitrogen availability depend on rootstock genotype.

In many fruit species, including grapevine, grafting is used to improve scion productivity and quality and to adapt the plant to environmental conditions. However, the mechanisms underlying the rootstock control of scion development are still poorly understood. The ability of rootstocks to regulate nitrogen uptake and assimilation may contribute to this control. A split-root system was used to grow heterografted grapevines and to investigate the molecular responses to changes in nitrate availability of two rootstocks known to affect scion growth differently. Transcriptome profiling by RNA sequencing was performed on root samples collected 3 and 24 h after nitrogen supply. The results demonstrated a common response involving nitrogen-related genes, as well as a more pronounced transcriptomic reprogramming in the genotype conferring the lower scion growth. A weighted gene co-expression network analysis allowed the identification of co-regulated gene modules, suggesting a role for nitrate transporter 2 family genes and some transcription factors as main actors controlling this genotype-dependent response to heterogeneous nitrogen supply. The relationship between nitrate, ethylene, and strigolactone hormonal pathways was found to differ between the two genotypes. These findings indicated that the genotypes responded differently to heterogeneous nitrogen availability, and this may contribute to their contrasting effect on scion growth.

Antimicrobial peptide LL-37 participates in the transcriptional regulation of melanoma cells.

Antimicrobial peptides are an ancient family of molecules that emerged millions of years ago and have been strongly conserved during the evolutionary process of living organisms. Recently, our group described that the human antimicrobial peptide LL-37 migrates to the nucleus, raising the possibility that LL-37 could directly modulate transcription under certain conditions. Here, we showed evidence that LL-37 binds to gene promoter regions, and LL-37 gene silencing changed the transcriptional program of melanoma A375 cells genes associated with histone, metabolism, cellular stress, ubiquitination and mitochondria.

Helicobacter pylori Infection Is Associated with Decreased Expression of SLC5A8, a Cancer Suppressor Gene, in Young Children.

Background:Helicobacter pylori infects half of the world's population and causes gastric cancer in a subset of infected adults. Previous blood microarray findings showed that apparently healthy children, persistently infected with H. pylori have differential gene expression compared to age-matched, non-infected children. SLC5A8, a cancer suppressor gene with decreased expression among infected children, was chosen for further study based on bioinformatics analysis. Methods: A pilot study was conducted using specific qRT-PCR amplification of SLC5A8 in blood samples from H. pylori infected and non-infected children, followed by a larger, blinded, case-control study. We then analyzed gastric tissue from H. pylori infected and non-infected children undergoing endoscopy for clinical purposes. Results: Demographics, clinical findings, and family history were similar between groups. SLC5A8 expression was decreased in infected vs. non-infected children in blood, 0.12 (IQR: 0-0.89) vs. 1.86 (IQR: 0-8.94, P = 0.002), and in gastric tissue, 0.08 (IQR: 0.04-0.15) vs. 1.88 (IQR: 0.55-2.56; P = 0.001). Children who were both stool positive and seropositive for H. pylori had the lowest SLC5A8 expression levels. Conclusions:H. pylori infection is associated with suppression of SCL5A8, a cancer suppressor gene, in both blood and tissue samples from young children. Key Points: Young children, persistently infected with Helicobacter pylori show decreased expression of SLC5A8 mRNA in both blood and tissue samples as compared to non-infected children.