Search Results (24)

Tetrahelical DNA structures, such as G-quadruplexes (G4s) or i-motifs (iMs), are adopted by sequences comprising several G/C tracts, exist in equilibria with respective duplexes, and may contribute to genomic instability upon helicase deficiency. To understand genomic rearrangements resulting from the juxtaposition of G/C-rich DNA duplexes, models of possible intermediate structures are needed. In this study, a general strategy for creating and verifying in silico 3D models of tetrahelical DNA was proposed. This strategy was used to investigate contacts of two or more duplexes with n G₃/C₃ tracts (n = 2–6) separated by T/A nucleotides. The revealed viable structures of DNA–DNA contacts include stacks of right-handed and left-handed G-quadruplexes (G4s), Holliday structure-resembling assemblies with the G4 and iM opposite each other on the borders of the central “hole”, etc. Based on molecular dynamic simulations, the most probable variants were determined by estimating the contributions to the free energy. The results may be used to clarify the mechanisms of strand exchange and other rearrangements upon DNA breaks near prolonged G/C-rich sites in living systems. Additionally, they provide a balanced view on the polymorphic versus programmed DNA assemblies in artificial systems. Full article

In the past, the Silk Road was a vital trade route that spanned Eurasia, connecting East Asia to the Mediterranean Sea. The genus Prunus, belonging to the Rosaceae family and encompassing plums, peaches, apricots, cherries, and almonds, thrived as human travel along the Silk Road increased. The majority of fruits within this genus, whether wild or cultivated, are naturally sweet and easily preserved by drying for storage and transport. The interaction along the Silk Road between wild populations and diverse varieties of Prunus fruits led to the development of various hybrids. This article provides a summary of archaeological findings related to prominent Prunus fruits such as peaches, apricots, plums, cherries, and almonds, shedding light on their evolutionary history, genetic diversity, population structure, and historical dynamics crucial for species conservation. The origins of biodiversity may involve factors like migration of pre-adapted lineages, in situ variation, or the persistence of ancestral lineages. Furthermore, climate change is affecting spatial genetic patterns and potentially further threatening rare Prunus species. Evaluating the scope and composition of genetic diversity within germplasm collections is essential for enhancing plant breeding initiatives and preserving genetic resources in this changing context. From a molecular point of view, techniques such as genome-wide association studies (GWASs) and the identification of quantitative trait loci (QTLs) and genes responsible for phenotypic changes in cultivars and germplasm collections should be of great interest in these breeding programs, while genomic estimated breeding values (GEBVs) derived from genome-wide DNA polymorphism information can facilitate the selection of superior genotypes. Full article

The analysis of metabolite mediators has allowed a broader understanding of disease mechanisms. Experimental evidence indicates that metabolic rewiring is a key feature of inflammatory cells to restore tissue homeostasis upon damage. Over the last two decades, next-generation sequencing techniques have offered the possibility of looking at the genome-wide effect of the exposure of inflammatory cells to external stimuli. During gout flares, monosodium urate crystals activate a distinct metabolic profile and inflammatory transcriptional program in inflammatory cells. The extracellular signals are transduced through distinct signalling pathways, which are regulated by non-coding RNA and DNA sequences, and modification of histones. During response to inflammatory stimuli, changes in the abundance of metabolic mediators can regulate the activation of histones and of chromatin remodellers. The interplay between metabolic changes by MSUc, the regulation of epigenetic changes and the activation of transcription factor networks in inflammatory cells remains unknown. A better understanding of the interplay between metabolites and how it alters inflammatory response may provide novel insights into disease mechanisms during gout. In this review, we aim to provide a deeper understanding of the current view of how metabolic deregulation could alter the epigenetic landscape of inflammatory cells during gout. Full article

In the last decade, it has been suggested that epigenetics may enhance the adaptive possibilities of animals and plants to novel environments and/or habitats and that such epigenetic changes may be inherited from parents to offspring, favoring their adaptation. As a consequence, several Authors called for a shift in the Darwinian paradigm, asking for a neo-Lamarckian view of evolution. Regardless of what will be discovered about the mechanisms of rapid adaptation to environmental changes, the description of epigenetic inheritance as a Lamarckian process is incorrect from a historical point of view and useless at a scientific level. At the same time, even if some examples support the presence of adaptation without the involvement of changes in DNA sequences, in the current scenario no revolution is actually occurring, so we are simply working on a stimulating research program that needs to be developed but that is, at present, completely Darwinian. Full article

The classical view of gene regulation draws from prokaryotic models, where responses to environmental changes involve operons regulated by sequence-specific protein interactions with DNA, although it is now known that operons are also modulated by small RNAs. In eukaryotes, pathways based on microRNAs (miR) regulate the readout of genomic information from transcripts, while alternative nucleic acid structures encoded by flipons influence the readout of genetic programs from DNA. Here, we provide evidence that miR- and flipon-based mechanisms are deeply connected. We analyze the connection between flipon conformation and the 211 highly conserved human miR that are shared with other placental and other bilateral species. The direct interaction between conserved miR (c-miR) and flipons is supported by sequence alignments and the engagement of argonaute proteins by experimentally validated flipons as well as their enrichment in promoters of coding transcripts important in multicellular development, cell surface glycosylation and glutamatergic synapse specification with significant enrichments at false discovery rates as low as 10⁻¹¹⁶. We also identify a second subset of c-miR that targets flipons essential for retrotransposon replication, exploiting that vulnerability to limit their spread. We propose that miR can act in a combinatorial manner to regulate the readout of genetic information by specifying when and where flipons form non-B DNA (NoB) conformations, providing the interactions of the conserved hsa-miR-324-3p with RELA and the conserved hsa-miR-744 with ARHGAP5 genes as examples. Full article

Cancer is a global epidemic that has affected millions of lives. Discovering novel cancer targets is widely viewed as a key step in developing more effective therapies for cancer and other fatal illnesses. More recently, potassium (K⁺) channels have been studied as a potential biological target for the creation of cancer treatments. Potassium Inwardly Rectifying Channel Subfamily J Member 14 (KCNJ14) is one of the cancer genome’s least investigated genes. This study conducted a comprehensive examination of the relationships between KCNJ14 gene expression analysis, survival, RNA modification, immunotherapy participation, and cancer stemness using several databases. KCNJ14 was shown to be dysregulated in a variety of cancers, including lung, intestinal, head and neck, oesophageal, and stomach. Additionally, KCNJ14 was shown to be linked to RNA and DNA stemness in 18 and 15 different tumour types, respectively. Moreover, KCNJ14 was discovered to be positively linked with immunological checkpoints and suppressor cells and to have a negative immunophenoscore (IPS). KCNJ14 was linked to tumour mutation burden (TMB), microsatellite instability (MSI), neoantigen (NEO), and programmed death ligand 1 (PD-L1); all four are potential targets for immunotherapies. In addition, a favourable relationship between genomic-instability markers such as heterozygosity (LOH), homologous recombination deficiency (HRD), and mutant-allele tumour heterogeneity (MATH) was demonstrated with KCNJ14. Based on these novel findings, KCNJ14 may be a useful independent prognostic biomarker for a range of cancers. Full article

Cervical cancer is the second most common cancer in low-income countries and the third most common cancer in Malaysia among women aged 15 to 44. This is a huge concern because of the high mortality rate compared to other countries. Cervical cancer is caused by a common sexually transmitted human papillomavirus (HPV). Of cervical cancer cases, 80% are attributed to serotypes 16 and 18; therefore, early detection of premalignant lesions and infections from these viruses is important. Diagnosis can be carried out by polymerase chain reaction (PCR)-based HPV DNA analysis and Pap smear, which act as a viable preventive strategy. (1) Background: This study determined the adoption of the human papillomavirus (HPV) vaccine and the willingness to get vaccinated in Malaysian women. (2) Methods: An online survey was conducted with women from across Malaysia to gather their views on the barriers that prevent them from accessing HPV services. Sentiment analysis was performed to detect and classify the comments into three groups (positive, neutral, and negative). (3) Results: A total of 449 opinions were received, and the findings revealed that 41.3% were not afraid to be diagnosed early, and were prepared to accept positive or negative screening results. In addition, 18.6% of those surveyed indicated that they feared a Pap smear and were very concerned that they would not get good results. Of the respondents, 36% believed in vaccination and preferred to know more about it; 43.24% claimed that their family members were very supportive towards screening and vaccination; and 21.3% felt embarrassed and were afraid to undergo the screening procedure, as they had no prior experience and were unsure of how the procedure was conducted. In addition, 40.5% indicated that they had no concerns about HPV testing and related procedures, as this information is widely available. Only a few respondents (8.1%) talked about the time constraints and busy work schedules that prevented them from going to medical appointments. The survey also revealed that women are prevented from participating in cervical cancer screening and vaccination programs due to a lack of knowledge, shyness, personal rumors, privacy issues, financial issues, a lack of access to medical services, and ignorance and beliefs about rumors spreading online. (4) Conclusion: Results indicate that awareness of HPV and related prevention measures among women is vague and that negative perceptions continue to exist. It is strongly advised to develop a well-designed and knowledge-based application on the efficacy of screening and vaccination among Malaysian women. Full article

(1) Background: It has been recognized that the origin of fat-tailed sheep occurred within coarse wool breeds and that this character was introgressed several times into thin-tailed populations. However, no study has investigated this idea for Egyptian breeds using mtDNA analyses. (2) Methods: Using new sequences of the control region, we constructed a database of 467 sequences representing 37 breeds including fat- and thin-tailed ones with 80 Egyptian individuals belonging to six local breeds (Barki, Fallahi, Ossimi, Rahmani, Saidi, Sohagi). The phylogenetic tree obtained with the maximum likelihood method was submitted to the Newick Extra program to count the direct and indirect links between the individuals of each breed. (3) Results: Several Egyptian breeds were strongly connected to “primitive” thin-tailed breeds from Europe, indicating a clear genetic background of the “thin tail” breed type that supports the view of archeologists. In several cases, we suspected Western Asian breeds to be involved in the introgression of the fat tail character. In contrast, the Ossimi breed showed a high affinity to a fat-tailed breed of Western Asia, suggesting a direct migration and no thin tail ancestors. The Saidi is unique as our analyses revealed its strong connection with thin-tailed Sudanese breeds. Full article

The Tonle Sap Lake in Cambodia supports several species of threatened megafish and contains one of the largest networks of freshwater fish reserves in the world. Despite these traits, this system remains understudied in terms of its utility for endangered fish conservation and restoration. This study was the first of a series of planned fish releases designed to test the effectiveness of conservation supplementation programs in the Tonle Sap Lake. In March 2022 (during the dry season), 1582 captive-reared fishes, including 1538 striped catfish Pangasianodon hypopthalmus, 42 giant barb Catlocarpio siamensis, and two Mekong giant catfish Pangasianodon gigas, were tagged and released into a 986-hectare fish reserve to assess post-release dispersal and survival. Brightly colored external tags with unique identification numbers were used to facilitate tag returns. A high-profile release event was held to raise awareness about the activity, bringing attention to the importance of fish reserves and endangered species conservation, and disseminating information about the research and tag return and reward program. This, in concert with other efforts, served to be an important education and outreach tool and increased tag return rates. We found that mortality from fishing was rapid and very high. Nineteen percent of released fishes were recaptured in the first 2 days after the fish release, and 46% were recaptured by day 83 after the release, indicating intense fishing pressure on the Tonle Sap Lake fisheries. Eighty percent of recaptured fishes were caught in stationary gill nets, most within 10 km of the release site. Fishing mortality rates were independent of fish size or source (pond-reared or cage-reared). Environmental DNA (eDNA) was found to be capable of detecting each of these species’ presence in the water at the release site and could prove to be a useful tool for endangered species monitoring and restoration. Future research should explore alternative release timing, release location, and other methods of increasing post-release survival. Ultimately, underlying sources of mortality, especially fishing, will need to be addressed for conservation supplementation programs to succeed in the Tonle Sap Lake. Conservation supplementation should not be viewed as a substitute for more fundamental conservation measures, such as maintenance of environmental flows, preservation of ecological connectivity, and science-based fisheries management. Full article

The holm oak (Quercus ilex L.) is the dominant tree species of the Mediterranean forest and the Spanish agrosilvopastoral ecosystem, “dehesa.” It has been, since the prehistoric period, an important part of the Iberian population from a social, cultural, and religious point of view, providing an ample variety of goods and services, and forming the basis of the economy in rural areas. Currently, there is renewed interest in its use for dietary diversification and sustainable food production. It is part of cultural richness, both economically (tangible) and environmentally (intangible), and must be preserved for future generations. However, a worrisome degradation of the species and associated ecosystems is occurring, observed in an increase in tree decline and mortality, which requires urgent action. Breeding programs based on the selection of elite genotypes by molecular markers is the only plausible biotechnological approach. To this end, the authors’ group started, in 2004, a research line aimed at characterizing the molecular biology of Q. ilex. It has been a challenging task due to its biological characteristics (long life cycle, allogamous, high phenotypic variability) and recalcitrant nature. The biology of this species has been characterized following the central dogma of molecular biology using the omics cascade. Molecular responses to biotic and abiotic stresses, as well as seed maturation and germination, are the two main objectives of our research. The contributions of the group to the knowledge of the species at the level of DNA-based markers, genomics, epigenomics, transcriptomics, proteomics, and metabolomics are discussed here. Moreover, data are compared with those reported for Quercus spp. All omics data generated, and the genome of Q. ilex available, will be integrated with morphological and physiological data in the systems biology direction. Thus, we will propose possible molecular markers related to resilient and productive genotypes to be used in reforestation programs. In addition, possible markers related to the nutritional value of acorn and derivate products, as well as bioactive compounds (peptides and phenolics) and allergens, will be suggested. Subsequently, the selected molecular markers will be validated by both genome-wide association and functional genomic analyses. Full article

Background and Objectives: Genomic information is increasingly relevant for disease prevention and risk management at the individual and population levels. Screening healthy adults for Tier 1 conditions of hereditary breast and ovarian cancer, Lynch syndrome, and familial hypercholesterolemia using a population-based approach can help identify the 1–2% of the US population at increased risk of developing diseases associated with these conditions and tailor prevention strategies. Our objective is to report findings from an implementation science study that evaluates multi-level facilitators and barriers to implementation of the In Our DNA SC population-wide genomic screening initiative. Methods: We established an IMPACTeam (IMPlementAtion sCience for In Our DNA SC Team) to evaluate the pilot phase using principles of implementation science. We used a parallel convergent mixed methods approach to assess the Reach, Implementation, and Effectiveness outcomes from the RE-AIM implementation science framework during the pilot phase of In Our DNA SC. Quantitative assessment included the examination of frequencies and response rates across demographic categories using chi-square tests. Qualitative data were audio-recorded and transcribed, with codes developed by the study team based on the semi-structured interview guide. Results: The pilot phase (8 November 2021, to 7 March 2022) included recruitment from ten clinics throughout South Carolina. Reach indicators included enrollment rate and representativeness. A total of 23,269 potential participants were contacted via Epic’s MyChart patient portal with 1976 (8.49%) enrolled. Black individuals were the least likely to view the program invitation (28.9%) and take study-related action. As a result, there were significantly higher enrollment rates among White (10.5%) participants than Asian (8.71%) and Black (3.46%) individuals (p < 0.0001). Common concerns limiting reach and participation included privacy and security of results and the impact participation would have on health or life insurance. Facilitators included family or personal history of a Tier 1 condition, prior involvement in genetic testing, self-interest, and altruism. Assessment of implementation (i.e., adherence to protocols/fidelity to protocols) included sample collection rate (n = 1104, 55.9%) and proportion of samples needing recollection (n = 19, 1.7%). There were no significant differences in sample collection based on demographic characteristics. Implementation facilitators included efficient collection processes and enthusiastic clinical staff. Finally, we assessed the effectiveness of the program, finding low dropout rates (n = 7, 0.35%), the identification of eight individuals with Tier 1 conditions (0.72% positive), and high rates of follow-up genetic counseling (87.5% completion). Conclusion: Overall, Asian and Black individuals were less engaged, with few taking any study-related actions. Strategies to identify barriers and promoters for the engagement of diverse populations are needed to support participation. Once enrolled, individuals had high rates of completing the study and follow-up engagement with genetic counselors. Findings from the pilot phase of In Our DNA SC offer opportunities for improvement as we expand the program and can provide guidance to organizations seeking to begin efforts to integrate population-wide genomic screening. Full article

Throughout the process of carcinogenesis, cancer cells develop intricate networks to adapt to a variety of stressful conditions including DNA damage, nutrient deprivation, and hypoxia. These molecular networks encounter genomic instability and mutations coupled with changes in the gene expression programs due to genetic and epigenetic alterations. Histone deacetylases (HDACs) are important modulators of the epigenetic constitution of cancer cells. It has become increasingly known that HDACs have the capacity to regulate various cellular systems through the deacetylation of histone and bounteous nonhistone proteins that are rooted in complex pathways in cancer cells to evade death pathways and immune surveillance. Elucidation of the signaling pathways involved in the adaptive responses to cellular stress and the role of HDACs may lead to the development of novel therapeutic agents. In this article, we overview the dominant stress types including metabolic, oxidative, genotoxic, and proteotoxic stress imposed on cancer cells in the context of HDACs, which guide stress adaptation responses. Next, we expose a closer view on the therapeutic interventions and clinical trials that involve HDACs inhibitors, in addition to highlighting the impact of using HDAC inhibitors in combination with stress-inducing agents for the management of cancer and to overcome the resistance to current cancer therapy. Full article

With more than 6200 fresh species, the Neotropical Water Fish Fauna (NFF) constitutes the most diverse continental vertebrate fauna on Earth. This diversity is quite impressive when we realize that it is concentrated in less than 0.5% of the total area of the Earth’s surface. The diversity of this ichthyofauna has been extensively explored through extensive morphological work by renowned ichthyologists who produced the basic knowledge available today. The use of tools for generating and interpreting morphological data has progressed considerably in recent decades, as has the number of researchers working in this field. Thus, only considering the families of the three main orders of NFF (Siluriformes, Gymnotiformes and Characiformes), 853 new species were described in the last 10 years. With the advancement of DNA sequencing techniques, a new class of data began to be incorporated into NFF biodiversity studies, allowing for a new and more complete view of the group. New phylogenies, such as the proposal for Charciformes, ordered the groups into monophyletic families, and, thus, we advanced in the description of species in these families. Furthermore, the development of data analysis methods for species identification, associated with large DNA barcode generation programs, allowed an unprecedented expansion in our knowledge of NFF. As an example, we can mention the genus Tetragonopterus, which just over 15 years ago contained only 2 species and today has 14 species, and the genus Neoplecostomus, which had only 3 species and now has 16 species. In both cases the combination of morphological and molecular data was fundamental for a better definition of species in these groups. Currently, with new generation sequencing techniques, our knowledge of fish groups is improving so that large monophyletic or polyphyletic groups are being redescribed as smaller units in order to make possible taxonomic revisions that can effectively better evaluate the diversity of these groups. Our results and experiences will be presented at this congress. Full article

Mutually linked expression and methylation dynamics in the brain govern genome regulation over the whole lifetime with an impact on cognition, psychological disorders, and cancer. We performed a joint study of gene expression and DNA methylation of brain tissue originating from the human prefrontal cortex of individuals across the lifespan to describe changes in cellular programs and their regulation by epigenetic mechanisms. The analysis considers previous knowledge in terms of functional gene signatures and chromatin states derived from independent studies, aging profiles of a battery of chromatin modifying enzymes, and data of gliomas and neuropsychological disorders for a holistic view on the development and aging of the brain. Expression and methylation changes from babies to elderly adults decompose into different modes associated with the serial activation of (brain) developmental, learning, metabolic and inflammatory functions, where methylation in gene promoters mostly represses transcription. Expression of genes encoding methylome modifying enzymes is very diverse reflecting complex regulations during lifetime which also associates with the marked remodeling of chromatin between permissive and restrictive states. Data of brain cancer and psychotic disorders reveal footprints of pathophysiologies related to brain development and aging. Comparison of aging brains with gliomas supports the view that glioblastoma-like and astrocytoma-like tumors exhibit higher cellular plasticity activated in the developing healthy brain while oligodendrogliomas have a more stable differentiation hierarchy more resembling the aged brain. The balance and specific shifts between volatile and stable and between more irreversible and more plastic epigenomic networks govern the development and aging of healthy and diseased brain. Full article

The present paper proposes a new level of regulation of programmed cell death (PCD) in developing systems based on epigenetics. We argue against the traditional view of PCD as an altruistic “cell suicide” activated by specific gene-encoded signals with the function of favoring the development of their neighboring progenitors to properly form embryonic organs. In contrast, we propose that signals and local tissue interactions responsible for growth and differentiation of the embryonic tissues generate domains where cells retain an epigenetic profile sensitive to DNA damage that results in its subsequent elimination in a fashion reminiscent of what happens with scaffolding at the end of the construction of a building. Canonical death genes, including Bcl-2 family members, caspases, and lysosomal proteases, would reflect the downstream molecular machinery that executes the dying process rather than being master cell death regulatory signals. Full article