DNA methylation and histone posttranslational modifications are epigenetics processes that contribute to neurophenotype of Down Syndrome (DS). Previous reports present strong evidence that nonhistone high-mobility-group N proteins (HMGN) are epigenetic regulators. They play important functions in various process to maintain homeostasis in the brain. We aimed to analyze the differential expression of five human HMGN genes in some brain structures and age ranks from DS postmortem brain samples. Methodology: We performed a computational analysis of the expression of human HMGN from the data of a DNA microarray experiment (GEO database ID GSE59630). Using the transformed log2 data, we analyzed the differential expression of five HMGN genes in several brain areas associated with cognition in patients with DS. Moreover, using information from different genome databases, we explored the co-expression and protein interactions of HMNGs with the histones of nucleosome core particle and linker H1 histone. Results: We registered that HMGN1 and HMGN5 were significantly overexpressed in the hippocampus and areas of prefrontal cortex including DFC, OFC, and VFC of DS patients. Age-rank comparisons between euploid control and DS individuals showed that HMGN2 and HMGN4 were overexpressed in the DS brain at 16 to 22 gestation weeks. From the BioGRID database, we registered high interaction scores of HMGN2 and HMGN4 with Hist1H1A and Hist1H3A. Conclusions: Overall, our results give strong evidence to propose that DS would be an epigenetics-based aneuploidy. Remodeling brain chromatin by HMGN1 and HMGN5 would be an essential pathway in the modification of brain homeostasis in DS.

Background: Although Down syndrome (DS) is the most frequent human chromosomal disorder and it causes mainly intellectual disability, its clinical presentation is complex and variable. Objective: We aimed to analyze and compare the transcriptome disruption in several brain areas from individuals with DS and euploid controls as a new approach to consider a global systemic differential disruption of gene expression beyond chromosome 21. Methods: We used data from a DNA microarray experiment with ID GSE59630 previously deposited in the GEO DataSet of NCBI database. The array contained log2 values of 17,537 human genes expressed in several aeras of the human brain. We calculated the differential gene expression (Z-ratio) of all genes. Results: We found several differences in gene expression along the DS brain transcriptome, not only in the genes located at chromosome 21 but in other chromosomes. Moreover, we registered the lowest Z-ratio correlation between the age ranks of 16–22 weeks of gestation and 39–42 years (R² = 0.06) and the highest Z-ratio correlation between the age ranks of 30–39 years and 40–42 years (R² = 0.89). The analysis per brain areas showed that the hippocampus and the cerebellar cortex had the most different gene expression pattern when compared to the brain as a whole. Conclusions: Our results support the hypothesis of a systemic imbalance of brain protein homeostasis, or proteostasis network of cognitive and neuroplasticity process, as new model to explain the important effect on the neurophenotype of trisomy that occur not only in the loci of chromosome 21 but also in genes located in other chromosomes.

Introduction: Skeletal muscle plasticity in exercise can be modulated by epigenomic events such as gene silencing, histone modifications and DNA methylation. In this context, our objective was to analyze the expression of genes associated with chromatin modifications in human muscle biopsies of vastus lateralis after a 20 week training program. Methods: Using data from DNA microarray experiments registered in the NCBI GEO DataSet database GSE117070, we calculated the Z ratio values as the criterion to evaluate the differential expression of genes associated with chromatin modification during aerobic training in skeletal muscle. Using the web interface GENEMANIA, we built a co-expression interaction network with the overexpressed genes. We compared Z-score values obtained from pre-trained and post-trained samples through nonparametric tests. Results: We found 10 overexpressed genes after the 20 week training program, namely, EZH1, KMT2A, KMT2D, KDM4C, KDM6A, CREBBP, HDAC10, HDAC4, DNMT3L, and H2AX. The most relevant biological processes obtained from the network included chromatin organization (FDR 9.04 × 10⁻⁹) and histone modification (FDR 9.04 × 10⁻⁹). Conclusions: In skeletal muscle, after aerobic training, there is overexpression of genes associated with the modification of the chromatin through alterations in histones and DNA, resulting in epigenetic transcriptional changes.

The starting point of our central argument is based on a general understanding of singularity as a point in time at which control is lost as processes break down due to an excessive rate of change. In this scenario, evolutionary singularity may be defined as the point at which ‘artificial evolution’ outpaces natural evolution to keep up. In such an evolutionary singularity, the editing of our genome, artificial intelligence, and technological and ecological changes on our planet are generating a new culture and ethics. According to this projection, post-humans will appear given the premise that the human species in its current form does not represent the end of their evolution. To understand the interaction of convergent technologies towards a singularity that will transform us into post-humans, it is important to redefine the concept of human evolution to face the advances in the editing of our genome, artificial intelligence, man-computer interfaces, as well as the changes in our physical, cultural, political, and creative environments. The extended evolutionary synthesis (EES) postulates that, in addition to natural selection, other dynamic forces converge, which change in time and space. The transformations in our biosphere, the use of technologies for editing our genome, and the improvement of brain-computer interfaces will condition new biological, social, and political adaptations. This stage of humankind will be that of the post-humans.

Introduction: Alzheimer's Disease (AD) is the most common cause of dementia worldwide and a chronic neurodegenerative disorder with well-established pathophysiological mechanisms. In Colombia, its prevalence is increasing, but in the southwestern region, information on its clinical course is scarce, limiting adequate care and public health strategies. This study aimed to describe the frequency and characteristics of genetic variants in AD candidate genes in a population in southwestern Colombia without a clinical diagnosis of the disease. Methods: A descriptive observational analysis was conducted on 320 whole exomes from patients without a clinical diagnosis of AD. Reported genomic variants in the APOE, ABCA7, APP, PSEN1, PSEN2, and CLU genes were examined for allele frequency, clinical significance, and interaction network predictions to assess their genetic impact on the population. Results: We identified 294 genetic variants, including 267 previously unreported. Among the 27 variants reported in ClinVar, most lacked a definitive clinical interpretation and were classified as Variants of Uncertain Significance (VUS) or as variants without a defined clinical significance in accordance with the guidelines of the American College of Medical Genetics and Genomics (ACMG). ABCA7 gene had the highest frequency of variants (n=164), and the PSEN1 gene had the lowest (n=14). While most variants lacked clinical significance, the APOE c.487C>T (p.Arg163Cys) variant was identified as likely pathogenic. Discussion: The genetics of AD are complex and contribute to a predisposition to developing the disease; hence, the importance of conducting studies in our Colombian population, which is characterized by great genetic variability. In our study, we identified 267 unreported variants associated with the genes APOE, ABCA7, APP, PSEN1, PSEN2, and CLU. The lack of updated data in our population underscores the need for further research to determine their clinical impact. conclusion: The present study identified germline variants associated with AD in a population from southwestern Colombia, many of which have not been previously studied. It suggests a unique genetic profile is circulating in this region. It highlights a likely pathogenic variant in the APOE gene (c.487C>T, p.Arg163Cys) linked to familial hyperlipoproteinemia type 3. These findings may facilitate early genetic diagnosis, risk prediction, more rigorous clinical monitoring, and advances in personalized medicine, biomarkers, and targeted therapies. It is important to conduct periodic reviews to reevaluate variants of uncertain significance as scientific knowledge advances. Conclusion: This research contributes to characterizing AD genetic variability in the Colombian population and identifies several previously unreported variants. According to our results, we recommend studying their potential functional and clinical impact to improve early diagnosis and support the development of targeted therapies, thereby contributing to a better understanding of the disease in southwestern Colombia.