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The safety and efficacy of pharmacotherapy in children, particularly preterms, neonates and infants, is limited by a paucity of good‐quality data from prospective clinical drug trials. A specific challenge is the establishment of valid biomarkers. OMICs technologies may support these efforts by complementary information about targeted and nontargeted molecules through systematic characterization and quantitation of biological samples. OMICs technologies comprise at least genomics, epigenomics, transcriptomics, proteomics, metabolomics and microbiomics in addition to the patient's phenotype. OMICs technologies are in part hypothesis‐generating, allowing an in depth understanding of disease pathophysiology and pharmacological mechanisms. Application of OMICs technologies in paediatrics faces major challenges before routine adoption. First, developmental processes need to be considered, including a subdivision into specific age groups as developmental changes clearly impact OMICs data. Second, compared to the adult population, the number of patients is limited as are the type and amount of necessary biomaterial, especially in neonates and preterms. Thus, advanced trial designs and biostatistical methods, noninvasive biomarkers, innovative biobanking concepts including data and samples from healthy children, as well as analytical approaches (eg liquid biopsies) should be addressed to overcome these obstacles. The ultimate goal is to link OMICs technologies with innovative analysis tools, such as artificial intelligence at an early stage. The use of OMICs data based on a feasible approach will contribute to the identification complex phenotypes and subpopulations of patients to improve the development of medicines for children with potential economic advantages. [ABSTRACT FROM AUTHOR]

With the increasing availability of biomedical data from multiple platforms of the same patients in clinical research, such as epigenomics, gene expression, and clinical features, there is a growing need for statistical methods that can jointly analyze data from different platforms to provide complementary information for clinical studies. In this paper, we propose a two‐stage hierarchical Bayesian model that integrates high‐dimensional biomedical data from diverse platforms to select biomarkers associated with clinical outcomes of interest. In the first stage, we use Expectation Maximization‐based approach to learn the regulating mechanism between epigenomics (e.g., gene methylation) and gene expression while considering functional gene annotations. In the second stage, we group genes based on the regulating mechanism learned in the first stage. Then, we apply a group‐wise penalty to select genes significantly associated with clinical outcomes while incorporating clinical features. Simulation studies suggest that our model‐based data integration method shows lower false positives in selecting predictive variables compared with existing method. Moreover, real data analysis based on a glioblastoma (GBM) dataset reveals our method's potential to detect genes associated with GBM survival with higher accuracy than the existing method. Moreover, most of the selected biomarkers are crucial in GBM prognosis as confirmed by existing literature. [ABSTRACT FROM AUTHOR]

Alcohol use disorder (AUD) is a major contributor to morbidity and mortality worldwide. Although there is a heritable component, the etiology of AUD is complex and can involve environmental exposures like trauma and can be associated with many different patterns of alcohol consumption. Epigenetic modifications, which can mediate the influence of genetic variants and environmental variables on gene expression, have emerged as an important area of AUD research. Over the past decade, the number of studies investigating AUD and DNA methylation, a form of epigenetic modification, has grown rapidly. Yet we are still far from understanding how DNA methylation contributes to or reflects aspects of AUD. In this paper, we reviewed studies of DNA methylation and AUD and discussed how the field has evolved. We found that global DNA and candidate DNA methylation studies did not produce replicable results. To assess whether findings of epigenome‐wide association studies (EWAS) were replicated, we aggregated significant findings across studies and identified 184 genes and 15 gene ontological pathways that were differentially methylated in at least two studies and four genes and three gene ontological pathways that were differentially methylated in three studies. These genes and pathways repeatedly found enrichment of immune processes, which is in line with recent developments suggesting that the immune system may be altered in AUD. Finally, we assess the current limitations of studies of DNA methylation and AUD and make recommendations on how to design future studies to resolve outstanding questions. [ABSTRACT FROM AUTHOR]

Diagnosing bone and soft tissue neoplasms remains challenging because of the large number of subtypes, many of which lack diagnostic biomarkers. DNA methylation profiles have proven to be a reliable basis for the classification of brain tumours and, following this success, a DNA methylation‐based sarcoma classification tool from the Deutsches Krebsforschungszentrum (DKFZ) in Heidelberg has been developed. In this study, we assessed the performance of their classifier on DNA methylation profiles of an independent data set of 986 bone and soft tissue tumours and controls. We found that the 'DKFZ Sarcoma Classifier' was able to produce a diagnostic prediction for 55% of the 986 samples, with 83% of these predictions concordant with the histological diagnosis. On limiting the validation to the 820 cases with histological diagnoses for which the DKFZ Classifier was trained, 61% of cases received a prediction, and the histological diagnosis was concordant with the predicted methylation class in 88% of these cases, findings comparable to those reported in the DKFZ Classifier paper. The classifier performed best when diagnosing mesenchymal chondrosarcomas (CHSs, 88% sensitivity), chordomas (85% sensitivity), and fibrous dysplasia (83% sensitivity). Amongst the subtypes least often classified correctly were clear cell CHSs (14% sensitivity), malignant peripheral nerve sheath tumours (27% sensitivity), and pleomorphic liposarcomas (29% sensitivity). The classifier predictions resulted in revision of the histological diagnosis in six of our cases. We observed that, although a higher tumour purity resulted in a greater likelihood of a prediction being made, it did not correlate with classifier accuracy. Our results show that the DKFZ Classifier represents a powerful research tool for exploring the pathogenesis of sarcoma; with refinement, it has the potential to be a valuable diagnostic tool. [ABSTRACT FROM AUTHOR]

Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disease which mainly affects the spine, sacroiliac joint and peripheral joints. To date, the exact causes and pathogenesis of AS still remain unknown. It is considered that the pathogenesis of AS is associated with genetic, infection, environment, immunity and other factors. Among them, the role of genetic factors in the pathogenesis of AS has been studied most deeply. However, over the past few years, the function of environmental predisposition and epigenetic modification in the pathogenesis of AS has received extensive attention. This paper summarizes the recent progress in the epigenetics of AS, including abnormal epigenetic modifications at AS‐associated genomic loci, such as DNA methylation, histone modification, microRNA, and so on. In summary, the findings of this review attempt to explain the role of epigenetic modification in the occurrence and development of AS. Nevertheless, there are still unknown and complicated aspects worth exploring to deepen our understanding of the pathogenesis of AS. [ABSTRACT FROM AUTHOR]

Impaired regulation of immune function characterised by chronic inflammation together with a declining protective immune response is a major challenge to healthy ageing. It is therefore important to understand the mechanisms that regulate immune function and the impact of ageing upon such processes. Appropriate induction and resolution of the immune response require adequate availability of polyunsaturated fatty acids (PUFAs) for incorporation into cell membranes. However, humans are unable to synthesise PUFAs de novo and are dependent upon dietary intake for pre‐formed PUFAs or synthesis by the liver from the essential fatty acids, linoleic acid (LA, 18:2n‐6) and alpha‐linolenic acid (aLNA, 18:3n‐3). We have shown that activation of peripheral blood mononuclear cells increases PUFA biosynthesis from essential fatty acids via a mechanism that involves altered epigenetic regulation of a key gene in the pathway. Moreover, induction of PUFA synthesis is directly involved in the regulation of lymphocyte activation and proliferation. The aim of the Biotechnology and Biological Sciences Research Council responsive mode award described in this paper, 'How does polyunsaturated fatty acid biosynthesis regulate T‐lymphocyte function?', is to determine how PUFA biosynthesis regulates T‐cell function and the effect of ageing on this process. The project will identify points of regulation in the biosynthetic pathway and how these might influence the capacity for up‐regulation of PUFA synthesis in older individuals. We will use stable isotope tracers of LA and aLNA to determine whether newly synthesised PUFAs are preferential substrates for synthesis of lipid mediators and whether they are involved in formation of membrane microdomains that mediate cell signalling. [ABSTRACT FROM AUTHOR]

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Abstract: Our paper explores the value‐laden and epistemic resources that scientists working in epigenetics and developmental programming of health and disease (DOHaD) mobilise to produce scientific representations of pregnancy and parenthood, which in turn imagine norms, values, and responsibilities for the protection of future generations. In order to do so, we first describe the place of questions regarding the relative weight of paternal and maternal influences on the health of the offspring in the discursive formalisation of this research in scientific publications. This enables us to identify the mutual constitution of ‘prototypes’ (i.e. experimental designs, settings, techniques) and ‘stereotypes’ (i.e. social meanings, beliefs, norms and values) of parental roles in DOHaD and epigenetic biomedical sciences, by means of a specific gendered figuration of paternal influences: the ‘father‐as‐sperm’. Second, and drawing from a set of interviews (N = 15), we describe a tension between this dominant, objectifying molecular discourse and the perspective of individual scientists. The situated perspective of individual researchers provides in fact evidence for a conflictual (moral and epistemic) economy of gendered engagements with parental figurations in DOHaD and epigenetic research, and consequently suggests a more fine‐grained, as well as conflictual web of socio‐political positioning of this ‘knowledge’ in its societal circulation. [ABSTRACT FROM AUTHOR]

Histones serve as a major carrier of epigenetic information in the form of post‐translational modifications which are vital for controlling gene expression, maintaining cell identity, and ensuring proper cellular function. Loss of histones in the aging genome can drastically impact the epigenetic landscape of the cell leading to altered chromatin structure and changes in gene expression profiles. In this study, we investigated the impact of age‐related changes on histone levels and histone acetylation in the retinal pigment epithelium (RPE) and retina of mice. We observed a global reduction of histones H1, H2A, H2B, H3, and H4 in aged RPE/choroid but not in the neural retina. Transcriptomic analyses revealed significant downregulation of histones in aged RPE/choroid including crucial elements of the histone locus body (HLB) complex involved in histone pre‐mRNA processing. Knockdown of HINFP, a key HLB component, in human RPE cells induced histone loss, senescence, and the upregulation of senescence‐associated secretory phenotype (SASP) markers. Replicative senescence and chronological aging in human RPE cells similarly resulted in progressive histone loss and acquisition of the SASP. Immunostaining of human retina sections revealed histone loss in RPE with age. Acetyl‐histone profiling in aged mouse RPE/choroid revealed a specific molecular signature with loss of global acetyl‐histone levels, including H3K14ac, H3K56ac, and H4K16ac marks. These findings strongly demonstrate histone loss as a unique feature of RPE aging and provide critical insights into the potential mechanisms linking histone dynamics, cellular senescence, and aging. [ABSTRACT FROM AUTHOR]

DNA methylation is critical to the regulation of transposable elements and gene expression and can play an important role in the adaptation of stress response mechanisms in plants. Traditional methods of methylation quantification rely on bisulfite conversion that can compromise accuracy. Recent advances in long‐read sequencing technologies allow for methylation detection in real time. The associated algorithms that interpret these modifications have evolved from strictly statistical approaches to Hidden Markov Models and, recently, deep learning approaches. Much of the existing software focuses on methylation in the CG context, but methylation in other contexts is important to quantify, as it is extensively leveraged in plants. Here, we present methylation profiles for two maple species across the full range of 5mC sequence contexts using Oxford Nanopore Technologies (ONT) long‐reads. Hybrid and reference‐guided assemblies were generated for two new Acer accessions: Acer negundo (box elder; 65x ONT and 111X Illumina) and Acer saccharum (sugar maple; 93x ONT and 148X Illumina). The ONT reads generated for these assemblies were re‐basecalled, and methylation detection was conducted in a custom pipeline with the published Acer references (PacBio assemblies) and hybrid assemblies reported herein to generate four epigenomes. Examination of the transposable element landscape revealed the dominance of LTR Copia elements and patterns of methylation associated with different classes of TEs. Methylation distributions were examined at high resolution across gene and repeat density and described within the broader angiosperm context, and more narrowly in the context of gene family dynamics and candidate nutrient stress genes. [ABSTRACT FROM AUTHOR]

Background: Brain tumors are one of the leading causes of epilepsy, and brain tumor‐related epilepsy (BTRE) is recognized as the major cause of intractable epilepsy, resulting in huge treatment cost and burden to patients, their families, and society. Although optimal treatment regimens are available, the majority of patients with BTRE show poor resolution of symptoms. BTRE has a very complex and multifactorial etiology, which includes several influencing factors such as genetic and molecular biomarkers. Advances in multi‐omics technologies have enabled to elucidate the pathophysiological mechanisms and related biomarkers of BTRE. Here, we reviewed multi‐omics technology‐based research studies on BTRE published in the last few decades and discussed the present status, development, opportunities, challenges, and prospects in treating BTRE. Methods: First, we provided a general review of epilepsy, BTRE, and multi‐omics techniques. Next, we described the specific multi‐omics (including genomics, transcriptomics, epigenomics, proteomics, and metabolomics) techniques and related molecular biomarkers for BTRE. We then presented the associated pathogenetic mechanisms of BTRE. Finally, we discussed the development and application of novel omics techniques for diagnosing and treating BTRE. Results: Genomics studies have shown that the BRAF gene plays a role in BTRE development. Furthermore, the BRAF V600E variant was found to induce epileptogenesis in the neuronal cell lineage and tumorigenesis in the glial cell lineage. Several genomics studies have linked IDH variants with glioma‐related epilepsy, and the overproduction of D2HG is considered to play a role in neuronal excitation that leads to seizure occurrence. The high expression level of Forkhead Box O4 (FOXO4) was associated with a reduced risk of epilepsy occurrence. In transcriptomics studies, VLGR1 was noted as a biomarker of epileptic onset in patients. Several miRNAs such as miR‐128 and miRNA‐196b participate in BTRE development. miR‐128 might be negatively associated with the possibility of tumor‐related epilepsy development. The lncRNA UBE2R2‐AS1 inhibits the growth and invasion of glioma cells and promotes apoptosis. Quantitative proteomics has been used to determine dynamic changes of protein acetylation in epileptic and non‐epileptic gliomas. In another proteomics study, a high expression of AQP‐4 was detected in the brain of GBM patients with seizures. By using quantitative RT‐PCR and immunohistochemistry assay, a study revealed that patients with astrocytomas and oligoastrocytomas showed high BCL2A1 expression and poor seizure control. By performing immunohistochemistry, several studies have reported the relationship between D2HG overproduction and seizure occurrence. Ki‐67 overexpression in WHO grade II gliomas was found to be associated with poor postoperative seizure control. According to metabolomics research, the PI3K/AKT/mTOR pathway is associated with the development of glioma‐related epileptogenesis. Another metabolomics study found that SV2A, P‐gb, and CAD65/67 have the potential to function as biomarkers for BTRE. Conclusions: Based on the synthesized information, this review provided new research perspectives and insights into the early diagnosis, etiological factors, and personalized treatment of BTRE. [ABSTRACT FROM AUTHOR]

Recent findings in epigenetics have been attracting much attention from social scientists and bioethicists because they reveal the molecular mechanisms by which exposure to socioenvironmental factors, such as pollutants and social adversity, can influence the expression of genes throughout life. Most surprisingly, some epigenetic modifications may also be heritable via germ cells across generations. Epigenetics may be the missing molecular evidence of the importance of using preventive strategies at the policy level to reduce the incidence and prevalence of common diseases. But while this "policy translation" of epigenetics introduces new arguments in favor of public health strategies and policy-making, a more "clinical translation" of epigenetics is also emerging. It focuses on the biochemical mechanisms and epigenetic variants at the origin of disease, leading to novel biomedical means of assessing epigenetic susceptibility and reversing detrimental epigenetic variants. In this paper, we argue that the impetus to create new biomedical interventions to manipulate and reverse epigenetic variants is likely to garner more attention than effective social and public health interventions and therefore also to garner a greater share of limited public resources. This is likely to happen because of the current biopolitical context in which scientific findings are translated. This contemporary neoliberal "regime of truth," to use a term from Michel Foucault, greatly influences the ways in which knowledge is being interpreted and implemented. Building on sociologist Thomas Lemke's Foucauldian "analytics of biopolitics" and on literature from the field of science and technology studies, we present two sociological trends that may impede the policy translation of epigenetics: molecularization and biomedicalization. These trends, we argue, are likely to favor the clinical translation of epigenetics-in other words, the development of new clinical tools fostering what has been called "personalized" or "precision" medicine. In addition, we argue that an overemphasized clinical translation of epigenetics may further reinforce this biopolitical landscape through four processes closely related to neoliberal pathways of thinking: the internalization and isolation (aspects of liberal individualism) of socioenvironmental determinants of health and increased opportunities for commodification and technologicalization (aspects of economic liberalism) of health care interventions., (© 2015 The Hastings Center.)

Aging is a significant risk factor for various human disorders, and DNA methylation clocks have emerged as powerful tools for estimating biological age and predicting health‐related outcomes. Methylation data from blood DNA has been a focus of more recently developed DNA methylation clocks. However, the impact of immune cell composition on epigenetic age acceleration (EAA) remains unclear as only some clocks incorporate partial cell type composition information when analyzing EAA. We investigated associations of 12 immune cell types measured by cell‐type deconvolution with EAA predicted by six widely‐used DNA methylation clocks in data from >10,000 blood samples. We observed significant associations of immune cell composition with EAA for all six clocks tested. Across the clocks, nine or more of the 12 cell types tested exhibited significant associations with EAA. Higher memory lymphocyte subtype proportions were associated with increased EAA, and naïve lymphocyte subtypes were associated with decreased EAA. To demonstrate the potential confounding of EAA by immune cell composition, we applied EAA in rheumatoid arthritis. Our research maps immune cell type contributions to EAA in human blood and offers opportunities to adjust for immune cell composition in EAA studies to a significantly more granular level. Understanding associations of EAA with immune profiles has implications for the interpretation of epigenetic age and its relevance in aging and disease research. Our detailed map of immune cell type contributions serves as a resource for studies utilizing epigenetic clocks across diverse research fields, including aging‐related diseases, precision medicine, and therapeutic interventions. [ABSTRACT FROM AUTHOR]

Epigenetics is the study of changes in gene expression patterns that occur without any modification of the underlying nucleotide sequence of the DNA. Modifications of the so-called epigenome include complex transient or permanent chemical changes of the DNA or histone proteins resulting in the suppression or enhancement of gene expression, together with an array of post-translational events that modify the translational products. Epigenomic programming ( EP) of the genome is an essential component of embryonic development in animals from the totipotent fertilized egg to the pluripotent stem cells, stem cell differentiation and final tissue and organ formation. Many of these EP processes are influenced transiently and some permanently by environmental influences. In eutherian mammals, environmentally related EP of embryos is linked to permanent changes in the phenotype of the progeny, some of which have been associated with adult onset metabolic disorders. Moreover, because some of the epigenetic remodelling occurs in both the soma and germ line, the resultant phenotypic characteristics (some of which are linked to disease states) may be heritable. Although far less is known about the effects of environmentally linked EP on the ontogeny of fishes, the available information suggests that the EP processes are similar amongst all vertebrates, and there are clear parallels between fish and mammals that are discussed in this paper. Our perspective takes the well-established findings in mammals and uses them to proactively extrapolate to the as yet under-recognized implications of EP for fish biology and for fish production in intensive aquaculture. [ABSTRACT FROM AUTHOR]

Background: Canine hepatocellular tumours (HCTs) are common primary liver tumours. However, the exact mechanisms of tumourigenesis remain unclear. Although some genetic mutations have been reported, DNA methylation alterations in canine HCT have not been well studied. Objectives: In this study, we aimed to analyse the DNA methylation status of canine HCT. Methods: Tissues from 33 hepatocellular carcinomas, 3 hepatocellular adenomas, 1 nodular hyperplasia, 21 non‐tumour livers from the patients and normal livers from 5 healthy dogs were used. We analysed the DNA methylation levels of 72,367 cytosine–guanine dinucleotides (CpG sites) in all 63 samples. Results and conclusions: Although a large fraction of CpG sites that were highly methylated in the normal liver became hypomethylated in tumours from most patients, we also found some patients with less remarkable change or no change in DNA methylation. Hierarchical clustering analysis revealed that 32 of 37 tumour samples differed from normal livers, although the remaining 5 tumour livers fell into the same cluster as normal livers. In addition, the number of hypermethylated genes in tumour livers varied among tumour cases, suggesting various DNA methylation patterns in different tumour groups. However, patient and clinical parameters, such as age, were not associated with DNA methylation status. In conclusion, we found that HCTs undergo aberrant and diverse patterns of genome‐wide DNA methylation compared with normal liver tissue, suggesting a complex epigenetic mechanism in canine HCT. [ABSTRACT FROM AUTHOR]

Objectives: The significant role of epigenetics has been revealed in normal enamel formation process and occurrence of developmental defects. This presented literature is aiming at summarizing the regulatory function of epigenetics in physiological amelogenesis process and reviewing the epigenetic mechanisms in occurrence of developmental defects of enamel (DDE), so as to provide biological foundation evidence to support early predication and clinical management of DDE. Method: An extensive literature review was conducted using electronic databases MEDLINE (through PubMed), Web of Science and EMBASE up to November 30, 2022. Studies about epigenetic effects on enamel tissue or cells associated with amelogenesis, including in vivo studies using human or animal models, and in vitro studies, are selected. Results: A total of 22 studies were included. Epigenetic factors or effects specifically activate or silence certain genes, which may regulate related biological activities including cell proliferation, cell differentiation, enamel secretion, and mineralization during the process of amelogenesis. Once the status of epigenetic modification is altered, the quantity and quality of enamel may both be disturbed, which can finally result in DDE. Conclusion: Epigenetics plays a noteworthy role of regulating the amelogenesis process and DDE potentially by altering the expression levels of genes related to enamel formation, providing a new perspective of early predication and clinical management of DDE. [ABSTRACT FROM AUTHOR]

Previous investigations mainly focused on the associations of dietary fatty acids with colorectal cancer (CRC) risk, which ignored gene‐environment interaction and mechanisms interpretation. We conducted a case‐control study (751 cases and 3058 controls) and a prospective cohort study (125 021 participants) to explore the associations between dietary fatty acids, genetic risks, and CRC. Results showed that high intake of saturated fatty acid (SFA) was associated with a higher risk of CRC than low SFA intake (HR =1.22, 95% CI:1.02‐1.46). Participants at high genetic risk had a greater risk of CRC with the HR of 2.48 (2.11‐2.91) than those at low genetic risk. A multiplicative interaction of genetic risk and SFA intake with incident CRC risk was found (PInteraction = 7.59 × 10−20), demonstrating that participants with high genetic risk and high SFA intake had a 3.75‐fold greater risk of CRC than those with low genetic risk and low SFA intake. Furthermore, incorporating PRS and SFA into traditional clinical risk factors improved the discriminatory accuracy for CRC risk stratification (AUC from 0.706 to 0.731). Multi‐omics data showed that exposure to SFA‐rich high‐fat dietary (HFD) can responsively induce epigenome reprogramming of some oncogenes and pathological activation of fatty acid metabolism pathway, which may contribute to CRC development through changes in gut microbiomes, metabolites, and tumor‐infiltrating immune cells. These findings suggest that individuals with high genetic risk of CRC may benefit from reducing SFA intake. The incorporation of SFA intake and PRS into traditional clinical risk factors will help improve high‐risk sub‐populations in individualized CRC prevention. [ABSTRACT FROM AUTHOR]

Chromatin has an extremely flexible structure that allows the fine regulation of gene expression. To orchestrate this process, small chemical modifications are dynamically added or removed on DNA, RNA and histone substrates. Epigenetic modifications govern a plethora of key cellular functions, whose dysregulation contributes to oncogenesis. The interrelationship between (irreversible) genetic mutations and (reversible) epigenetic alterations and how this crosstalk regulates gene expression has long been a major area of interest. Marks modulating the RNA code (epitranscriptome), such as the well‐studied N6‐methyladenosine (m6A), are known to influence stability, metabolism and life cycle of many mRNAs, including cancer‐associated transcripts. Together, epigenetic and epitranscriptomic pathways therefore control the entire cellular expression profile and, eventually, cell fate. Recently, previously undescribed crosstalk between these two pathways has started to be unrevealed. For example, m6A and its effectors cooperate with histone modifications to localize chromatin‐modifying complexes to their target regions. Epigenetic marks governing the expression of m6A factors can also be found at specific genetic loci. m6A itself can mark noncoding RNAs (including lncRNAs, circRNAs and miRNAs), influencing their structure, maturation and function. These interactions affect both cell physiology and pathology. Clear evidence that dysregulation of this network plays a role in cancer has emerged, suggesting a new layer of complexity in the landscape of gene expression. Here, we summarize current knowledge on the interplay between m6A epitranscriptome and epigenome, focusing on cancer processes. We also discuss strategies to target m6A machinery for future therapeutic intervention. [ABSTRACT FROM AUTHOR]

Introduction: We recently developed a non‐invasive sampling procedure for oral squamous cell carcinoma (OSCC) detection based on DNA methylation analysis of a panel of 13 genes. Oral cancer, as well as acute and chronic inflammatory diseases, may influence the methylation level of several genes in the oral cavity. In the present study, we evaluated the presence of periodontal disease (PD) and the methylation status using our 13‐gene panel. Methods: Oral brushing specimens were collected from three different patient groups: 23 gingival OSCC patients, 15 patients affected by PD, and 15 healthy volunteers lacking evidence of PD. DNA methylation analysis was performed and each sample was determined to be positive or negative based on a predefined cut‐off value. Results: Positive results were found for 23/23 OSCC patients, 3/15 PD patients, and 0/15 samples from healthy volunteers. The GP1BB and MIR193 genes in the PD group exhibited mean methylation levels similar to OSCC patients. ZAP70 showed different methylation levels among three groups. Conclusion: Preliminary data identified shared epigenetic alterations between PD and OSCC patients in two inflammatory genes (GP1BB and MIR193). This study may help to identify potential links between the two diseases and serve as a starting point for the future research focused on pathogenesis. [ABSTRACT FROM AUTHOR]

Age‐associated changes in the DNA methylation state can be used to assess the pace of aging. However, it is not understood what mechanisms drive these changes and whether these changes affect the development of aging phenotypes and the aging process in general. This study was aimed at gaining a more comprehensive understanding of aging‐related methylation changes across the whole genome, and relating these changes to biological functions. It has been shown that skeletal muscle and blood monocytes undergo typical changes with aging. Using whole‐genome bisulfite sequencing, we sought to characterize the genome‐wide changes in methylation of DNA derived from both skeletal muscle and blood monocytes, and link these changes to specific genes and pathways through enrichment analysis. We found that methylation changes occur with aging at the locations enriched for developmental and neuronal pathways regulated in these two peripheral tissues. These results contribute to our understanding of changes in epigenome in human aging. [ABSTRACT FROM AUTHOR]

Neurodegenerative illnesses refer to the gradual, cumulative loss of neural activity. Neurological conditions are considered to be the second leading cause of mortality in the modern world and the two most prevalent ones are Parkinson's disease and Alzheimer's disease. The negative side effects of pharmaceutical use are a major global concern, despite the availability of many different treatments for therapy. We concentrated on different types of neurological problems and their influence on targets, in vitro, in vivo, and in silico methods toward neurological disorders, as well as the molecular approaches influencing the same, in the first half of the review. The bulk of the second half of the review focuses on the many categories of treatment possibilities, including natural and artificial. Nevertheless, herbal treatment solutions are piquing scholarly attention due to their anti‐oxidative properties and accessibility. However, more quality investigations and innovations are undoubtedly needed to back up these conclusions. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to systematically review the evidence across studies that assessed DNA methylome variations in association with food allergy (FA). Design: A systematic review of the literature and meta‐analysis were carried out within several databases. However, the risk of bias in the included articles was not evaluated. Data sources PubMed, Cochrane Database of Systematic Reviews, and Web of Science were used to search up to July 2022. Eligibility criteria: We included targeted and epigenome‐wide association studies (EWASs) that assessed DNA methylome alterations in association with FA in adult or paediatric populations. Results: Among 366 publications, only 16 were retained, which were mainly focused on FA in children. Seven candidate gene‐targeted studies found associations in Th1/Th2 imbalance (IL4, IL5, IL10, INFG, IL2 and IL12B genes), regulatory T cell function (FOXP3 gene), Toll‐like receptors pathway (TLR2, CD14 genes) and digestive barrier integrity (FLG gene). Nine EWAS assessed the association with peanut allergy (n = 3), cow's milk allergy (n = 2) or various food allergens (n = 4). They highlighted 11 differentially methylated loci in at least two studies (RPS6KA2, CAMTA1, CTBP2, RYR2, TRAPPC9, DOCK1, GALNTL4, HDAC4, UMODL1, ZAK and TNS3 genes). Among them, CAMTA1 and RPS6KA2, and CTBP2 are involved in regulatory T cell function and Th2 cell differentiation, respectively. Gene‐functional analysis revealed two enriched gene clusters involved in immune responses and protein phosphorylation. ChIP‐X Enrichment Analysis 3 showed eight significant transcription factors (RXRA, ZBTB7A, ESR1, TCF3, MYOD1, CTCF, GATA3 and CBX2). Ingenuity Pathway Analysis identified canonical pathways involved, among other, in B cell development, pathogen‐induced cytokine storm signalling pathway and dendritic cell maturation. Conclusion: This review highlights the involvement of epigenomic alterations of loci in Th1/Th2 and regulatory T cell differentiation in both candidate gene studies and EWAS. These alterations provide a better insight into the mechanistic aspects in FA pathogenesis and may guide the development of epigenome‐based biomarkers for FA. [ABSTRACT FROM AUTHOR]

Background and Aim: Aberrant DNA methylation has been found in various cancer types including gastric cancer, yet the genome‐wide DNA methylation profile of gastric cardia cancer (GCC) remains unclear. Therefore, we aimed to profile the DNA methylation pattern of GCC and identify promising diagnostic epigenetic biomarkers. Methods: We investigated the genome‐wide DNA methylation pattern in eight pairs of GCC and adjacent normal tissues using Illumina 850K microarrays. Subsequently, bisulfite‐pyrosequencing and quantitative real‐time PCR were performed on eight pairs of GCC‐adjacent normal tissues for validation. Finally, we performed immunohistochemistry to examine ADHFE1 expression on 126 pairs of GCC‐adjacent normal samples. Results: DNA methylome analysis showed global hypomethylation and local hypermethylation of promoter cytosine‐phosphate‐guanine (CpG) islands (CGIs) in GCC tissues compared with gastric cardia normal mucosa (P < 2.2 × 10−16). Differential methylation analysis identified a total of 91 723 differentially‐methylated probes (DMPs), and the candidate gene with the largest average DNA methylation difference mapped to ADHFE1 (mean Δβ = 0.53). Subsequently, three DMPs in the ADHFE1 promoter were validated by pyrosequencing. Notably, the mean methylation level of the three candidate DMPs (ADHFE1_cg08090772, ADHFE1_cg19283840, and ADHFE1_cg20295442) was negatively associated with ADHFE1 mRNA expression level (Spearman rho = −0.64, P = 0.01). Moreover, both mRNA (P = 0.0213) and protein (P < 0.0001) expression of ADHFE1 were significantly decreased in GCCs compared with the adjacent normal tissues. Conclusions: Our results reveal DNA methylation aberrations in GCC and that ADHFE1 gene DNA methylation contributes to the risk of GCC, thus providing novel mechanistic insights into gastric cardia cancer carcinogenesis. [ABSTRACT FROM AUTHOR]

Summary: Chronic lymphocytic leukaemia (CLL) is not only characterised by driver genetic alterations but by extensive epigenetic changes. Over the last decade, epigenomic studies have described the DNA methylome, chromatin accessibility, histone modifications and the three‐dimensional (3D) genome architecture of CLL. Beyond its regulatory role, the DNA methylome contains imprints of the cellular origin and proliferative history of CLL cells. These two aspects are strong independent prognostic factors. Integrative analyses of chromatin marks have uncovered novel regulatory elements and altered transcription factor networks as non‐genetic means mediating gene deregulation in CLL. Additionally, CLL cells display a disease‐specific pattern of 3D genome interactions. From the technological perspective, we are currently witnessing a transition from bulk omics to single‐cell analyses. This review aims at summarising the major findings from the epigenomics field as well as providing a prospect of the present and future of single‐cell analyses in CLL. [ABSTRACT FROM AUTHOR]

All animals have evolved solutions to manage their genomes, enabling the efficient organization of meters of DNA strands in the nucleus and allowing for nuanced regulation of gene expression while keeping transposable elements suppressed. Epigenetic modifications are central to accomplishing all these. Recent advances in sequencing technologies and the development of techniques that profile epigenetic marks and chromatin accessibility using reagents that can be used in any species has catapulted epigenomic studies in diverse animal species, shedding light on the multitude of epigenomic mechanisms utilized across the evolutionary tree. Now, comparative epigenomics is a rapidly growing field that is uncovering mechanistic aspects of epigenetic modifications and chromatin organization in non‐model invertebrates, ranging from octopus to sponges. This review puts recent discoveries in the epigenetics of non‐model invertebrates in historical context, and describes new insight into the patterning and functions of DNA methylation and other highly conserved epigenetic modifications. [ABSTRACT FROM AUTHOR]

Background: Genome‐wide information on epigenetic modifications in mammalian preimplantation embryos was an unexplored sanctuary of valuable research insights protected by the difficulty of its analysis. However, that is no longer the case, and many epigenome maps are now available for sightseeing there. Methods: This review overviews the current status of genome‐wide epigenetic profiling in terms of DNA methylome and histone modifications in mammalian preimplantation embryos. Main findings: As the sensitivity of methods for analyzing epigenetic modifications increased, pioneering work began to explore the genome‐wide epigenetic landscape in the mid‐2010s, first for DNA methylation and then for histone modifications. Since then, a huge amount of data has accumulated, revealing typical epigenetic profiles in preimplantation development and, more recently, changes in response to environmental interventions. Conclusions: These accumulating data may be used to improve the quality of preimplantation embryos, both in terms of their short‐term developmental competence and their subsequent long‐term health implications. [ABSTRACT FROM AUTHOR]

Objective: Obesity is a significant public health concern across the globe. Research investigating epigenetic mechanisms related to obesity and obesity‐associated conditions has identified differences that may contribute to cellular dysregulation that accelerates the development of disease. However, few studies include Black women, who experience the highest incidence of obesity and early onset of cardiometabolic disorders. Methods: The association of BMI with epigenome‐wide DNA methylation (DNAm) was examined using the 850K Illumina EPIC BeadChip in two Black populations (Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure [InterGEN], n = 239; and The Genetic Epidemiology Network of Arteriopathy [GENOA] study, n = 961) using linear mixed‐effects regression models adjusted for batch effects, cell type heterogeneity, population stratification, and confounding factors. Results: Cross‐sectional analysis of the InterGEN discovery cohort identified 28 DNAm sites significantly associated with BMI, 24 of which had not been previously reported. Of these, 17 were replicated using the GENOA study. In addition, a meta‐analysis, including both the InterGEN and GENOA cohorts, identified 658 DNAm sites associated with BMI with false discovery rate < 0.05. In a meta‐analysis of Black women, we identified 628 DNAm sites significantly associated with BMI. Using a more stringent significance threshold of Bonferroni‐corrected p value 0.05, 65 and 61 DNAm sites associated with BMI were identified from the combined sex and female‐only meta‐analyses, respectively. Conclusions: This study suggests that BMI is associated with differences in DNAm among women that can be identified with DNA extracted from salivary (discovery) and peripheral blood (replication) samples among Black populations across two cohorts. [ABSTRACT FROM AUTHOR]

Smoking is a serious public health issue linked to more than 8 million deaths per year worldwide and may lead to nicotine dependence (ND). Although the epigenomic literature on smoking is well established, studies evaluating the role of epigenetics in ND are limited. In this study, we examined the epigenomic signatures of ND and how these differ from smoking exposure to identify biomarkers specific to ND. We investigated the peripheral epigenetic profile of smoking status (SS) and ND in a US male veteran cohort. DNA from saliva was collected from 1135 European American (EA) male US military veterans. DNAm was assessed using the Illumina Infinium Human MethylationEPIC BeadChip array. SS was evaluated as current smokers (n = 137; 12.1%) and non‐current smokers (never and former; n = 998; 87.9%). NDFTND was assessed as a continuous variable using the Fagerström Test for ND (FTND; n = 1135; mean = 2.54 ± 2.29). Epigenome‐wide association studies (EWAS) and co‐methylation analyses were conducted for SS and NDFTND. A total of 450 and 22 genome‐wide significant differentially methylated sites (DMS) were associated with SS and NDFTND, respectively (15 overlapped DMS). We identified 97 DMS (43 genes) in SS‐EWAS previously reported in the literature, including AHRR and F2RL3 genes (p‐value: 1.95 × 10−83 to 4.55 × 10−33). NDFTND novel DMS mapped to NEUROG1, ANPEP, and SLC29A1. Co‐methylation analysis identified 386 modules (11 SS‐related and 19 NDFTND‐related). SS‐related modules showed enrichment for alcoholism, while NDFTND‐related modules were enriched for nicotine addiction. This study confirms previous findings associated with SS and identifies novel and—potentially specific—epigenetic biomarkers of ND that may inform prognosis and novel treatment strategies. [ABSTRACT FROM AUTHOR]

Inflammation and ageing‐related DNA methylation patterns in the blood have been linked to a variety of morbidities, including cognitive decline and neurodegenerative disease. However, it is unclear how these blood‐based patterns relate to patterns within the brain and how each associates with central cellular profiles. In this study, we profiled DNA methylation in both the blood and in five post mortem brain regions (BA17, BA20/21, BA24, BA46 and hippocampus) in 14 individuals from the Lothian Birth Cohort 1936. Microglial burdens were additionally quantified in the same brain regions. DNA methylation signatures of five epigenetic ageing biomarkers ('epigenetic clocks'), and two inflammatory biomarkers (methylation proxies for C‐reactive protein and interleukin‐6) were compared across tissues and regions. Divergent associations between the inflammation and ageing signatures in the blood and brain were identified, depending on region assessed. Four out of the five assessed epigenetic age acceleration measures were found to be highest in the hippocampus (β range = 0.83–1.14, p ≤ 0.02). The inflammation‐related DNA methylation signatures showed no clear variation across brain regions. Reactive microglial burdens were found to be highest in the hippocampus (β = 1.32, p = 5 × 10−4); however, the only association identified between the blood‐ and brain‐based methylation signatures and microglia was a significant positive association with acceleration of one epigenetic clock (termed DNAm PhenoAge) averaged over all five brain regions (β = 0.40, p = 0.002). This work highlights a potential vulnerability of the hippocampus to epigenetic ageing and provides preliminary evidence of a relationship between DNA methylation signatures in the brain and differences in microglial burdens. [ABSTRACT FROM AUTHOR]

Background: Longitudinal studies are needed to clarify whether early adversities are associated with advanced methylation age or if they actually accelerate methylation aging. This study test whether different dimensions of childhood adversity accelerate biological aging from childhood to adulthood, and, if so, via which mechanisms. Methods: 381 participants provided one blood sample in childhood (average age 15.0; SD = 2.3) and another in young adulthood (average age 23.1; SD = 2.8). Participants and their parents provided a median of 6 childhood assessments (total = 1,950 childhood observations), reporting exposures to different types of adversity dimensions (i.e. threat, material deprivation, loss, unpredictability). The blood samples were assayed to estimate DNA methylation age in both childhood and adulthood and also change in methylation age across this period. Results: Cross‐sectional associations between the childhood adversity dimensions and childhood measures of methylation age were non‐significant. In contrast, multiple adversity dimensions were associated with accelerated within‐person change in methylation age from adolescence to young adulthood. These associations attenuated in model testing all dimensions at the same time. Accelerated aging increased with increasing number of childhood adversities: Individuals with highest number of adversities experienced 2+ additional years of methylation aging compared to those with no exposure to childhood adversities. The association between total childhood adversity exposure and accelerated aging was partially explained by childhood depressive symptoms, but not anxiety or behavioral symptoms. Conclusions: Early adversities accelerate epigenetic aging long after they occur, in proportion to the total number of such experiences, and in a manner consistent with a shared effect that crosses multiple early dimensions of risk. [ABSTRACT FROM AUTHOR]

Comparative genomics of social insects has been intensely pursued in recent years with the goal of providing insights into the evolution of social behaviour and its underlying genomic and epigenomic basis. However, the comparative approach has been hampered by a paucity of data on some of the most informative social forms (e.g. incipiently and primitively social) and taxa (especially members of the wasp family Vespidae) for studying social evolution. Here, we provide a draft genome of the primitively eusocial model insect Polistes dominula, accompanied by analysis of caste-related transcriptome and methylome sequence data for adult queens and workers. Polistes dominula possesses a fairly typical hymenopteran genome, but shows very low genomewide GC content and some evidence of reduced genome size. We found numerous caste-related differences in gene expression, with evidence that both conserved and novel genes are related to caste differences. Most strikingly, these -omics data reveal a major reduction in one of the major epigenetic mechanisms that has been previously suggested to be important for caste differences in social insects: DNA methylation. Along with a conspicuous loss of a key gene associated with environmentally responsive DNA methylation (the de novo DNA methyltransferase Dnmt3), these wasps have greatly reduced genomewide methylation to almost zero. In addition to providing a valuable resource for comparative analysis of social insect evolution, our integrative -omics data for this important behavioural and evolutionary model system call into question the general importance of DNA methylation in caste differences and evolution in social insects. [ABSTRACT FROM AUTHOR]

Workflow scheduling is an important way to manage the execution of a workflow. It introduces the concept of providing suitable resources to workflow tasks in order to finish workflow execution and meet the user's objectives. However, the problem becomes more complex when scheduling must balance two conflicting objectives, such as minimizing execution cost and maximizing load across all computing resources. A workflow has many interdependent tasks, and the cloud datacenter has many computing resources to execute the workflow. There can be an asymptotically infinite number of mappings of tasks‐to‐computing resources. Every mapping produces different execution costs with different workloads on computing resources. The main challenge for the researcher is to develop an intelligent scheduling algorithm to identify an optimal mapping that produces minimal execution cost with fair workload distribution on resources. We developed a novel meta‐heuristic algorithm named Investment‐Based Optimization (IBO) to identify an optimal mapping. The IBO algorithm was first tested on optimization benchmark functions and then simulated in CloudSim to see its performance for scheduling workflows. Finally, IBO was tested over Montage, Epigenomics, Sipht, and a sample workflow, and it was found that IBO reduces execution costs by 33%, 16%, 16.36%, and 20% with a fair workload distribution. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the impact of the modified ketogenic diet on DNA methylation in adults with epilepsy. Methods: In this prospective study, we investigated the genome‐wide DNA methylation in whole blood in 58 adults with epilepsy treated with the modified ketogenic for 12 weeks. Patients were recruited from the National Center for Epilepsy, Norway, from March 1, 2011 to February 28, 2017. DNA methylation was analyzed using the Illumina Infinium MethylationEPIC BeadChip array. Analysis of variance and paired t‐test were used to identify differentially methylated loci after 4 and 12 weeks of dietary treatment. A false discovery rate approach with a significance threshold of <5% was used to adjust for multiple comparisons. Results: We observed a genome‐wide decrease in DNA methylation, both globally and at specific sites, after 4 and 12 weeks of dietary treatment. A substantial share of the differentially methylated positions (CpGs) were annotated to genes associated with epilepsy (n = 7), lipid metabolism (n = 8), and transcriptional regulation (n = 10). Furthermore, five of the identified genes were related to inositol phosphate metabolism, which may represent a possible mechanism by which the ketogenic diet attenuates seizures. Significance: A better understanding of the modified ketogenic diet's influence at the molecular level may be the key to unraveling the mechanisms by which the diet can ameliorate seizures and possibly to identifying novel therapeutic targets for epilepsy. [ABSTRACT FROM AUTHOR]

Background: Low birthweight (LBW) and preterm birth (PTB) are more common among Black infants than white infants in the United States. Although multiple hypotheses have been proposed to explain elevated rates of PTB and LBW, the perspectives of Black midwives who serve Black communities are largely missing from the literature. Methods: Using semi‐structured interviews and focus groups with a purposive sample of midwives (n = 29), we elicited midwives' perceptions of PTB and LBW causation, as well as insights on culturally congruent strategies for prevention. We used consensus coding and reciprocal ethnography to increase the rigor of our analyses. Results: Midwives identified three intersecting and predisposing root causes: (1) systemic racism; (2) the epigenetic legacy of enslavement; and (3) ongoing cultural loss. In response to these stressors, midwives recommended variants of two additional themes—(4) community building; and (5) culturally centered care—as essential to reversing mortality trends among Black babies. Discussion: Midwives' perspectives, which are supported by relevant literature, provide critical insights that should inform both research and policy aimed at promoting birth justice in the United States and beyond. [ABSTRACT FROM AUTHOR]

As humans age multiple forms of biological decay ensue, and many aspects of human biology can be measured to determine how far biological machinery has drifted from homeostasis. Research has led to aging clocks being developed that claim to predict biological age as opposed to chronological age. Aging could be regarded as a measured loss of homeostatic biological equilibrium that augments biological decay in fully developed tissues. Measuring aspects of how far various elements of biology have drifted from a youthful state may allow us to make determinations on a subject's health but also make informed predictions on their biological age. As we see across human physiology, many facets that maintain human health taper off such as nicotinamide adenine dinucleotide, glutathione, catalase, super oxide dismutase, and more. Extracellular vesicle density also tapers off during age combined with epigenetic drift, telomere attrition, and stem cell exhaustion, whilst genomic instability and biological insults from environment and lifestyle factors increase. Measuring these types of biomarkers with aging clocks may allow subjects to understand their own health more accurately and enable subjects to better focus on their efforts in the pursuit of longevity and, in addition, allow healthcare practitioners to deliver better health advice. [ABSTRACT FROM AUTHOR]

DNA methylation is a common epigenetic signalling tool and an important biological process which is widely studied in a large array of species. The presence, level and function of DNA methylation vary greatly across species. In some insects, DNA methylation systems are minimal, and overall methylation rates tend to be low in all studied insect species. Low methylation levels probed by whole‐genome bisulphite sequencing require great care with respect to data quality control and interpretation. Here, we introduce BWASP/R, a complete workflow that allows efficient, scalable and entirely reproducible analyses of raw DNA methylation sequencing data. Consistent application of quality control filters and analysis parameters provides fair comparisons among different studies and an integrated view of all experiments on one species. We describe the capabilities of the BWASP/R workflow by re‐analysing several publicly available social insect WGBS data sets, comprising 70 samples and cumulatively 147 replicates from four different species. We show that the CpG methylome comprises only about 1.5% of CpG sites in the honeybee genome and that the cumulative data are consistent with genetic signatures of site accessibility and physiological control of methylation levels. [ABSTRACT FROM AUTHOR]

Summary: Meiotic recombination is a major evolutionary process generating genetic diversity at each generation in sexual organisms. However, this process is highly regulated, with the majority of crossovers lying in the distal chromosomal regions that harbor low DNA methylation levels. Even in these regions, some islands without recombination remain, for which we investigated the underlying causes.Genetic maps were established in two Brassica napus hybrids to detect the presence of such large nonrecombinant islands. The role played by DNA methylation and structural variations in this local absence of recombination was determined by performing bisulfite sequencing and whole genome comparisons. Inferred structural variations were validated using either optical mapping or oligo fluorescence in situ hybridization.Hypermethylated or inverted regions between Brassica genomes were associated with the absence of recombination. Pairwise comparisons of nine B. napus genome assemblies revealed that such inversions occur frequently and may contain key agronomic genes such as resistance to biotic stresses.We conclude that such islands without recombination can have different origins, such as DNA methylation or structural variations in B. napus. It is thus essential to take into account these features in breeding programs as they may hamper the efficient combination of favorable alleles in elite varieties. [ABSTRACT FROM AUTHOR]

Capicua (CIC)'s transcriptional repressor function is implicated in neurodevelopment and in oligodendroglioma (ODG) aetiology. However, CIC's role in these contexts remains obscure, primarily from our currently limited knowledge regarding its biological functions. Moreover, CIC mutations in ODG invariably co‐occur with a neomorphic IDH1/2 mutation, yet the functional relationship between these two genetic events is unknown. Here, we analysed models derived from an E6/E7/hTERT‐immortalized (i.e. p53‐ and RB‐deficient) normal human astrocyte cell line. To examine the consequences of CIC loss, we compared transcriptomic and epigenomic profiles between CIC wild‐type and knockout cell lines, with and without mutant IDH1 expression. Our analyses revealed dysregulation of neurodevelopmental genes in association with CIC loss. CIC ChIP‐seq was also performed to expand upon the currently limited ensemble of known CIC target genes. Among the newly identified direct CIC target genes were EPHA2 and ID1, whose functions are linked to neurodevelopment and the tumourigenicity of in vivo glioma tumour models. NFIA, a known mediator of gliogenesis, was discovered to be uniquely overexpressed in CIC‐knockout cells expressing mutant IDH1‐R132H protein. These results identify neurodevelopment and specific genes within this context as candidate targets through which CIC alterations may contribute to the progression of IDH‐mutant gliomas. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Summary: Gram‐negative bacteria (GNB) continue to develop resistance against important antibiotics including last‐resort ones such as carbapenems and polymyxins. An analysis of GNB with co‐resistance to carbapenems and polymyxins from a One Health perspective is presented. Data of species name, country, source of isolation, resistance genes (ARGs), plasmid type, clones and mobile genetic elements (MGEs) were deduced from 129 articles from January 2016 to March 2021. Available genomes and plasmids were obtained from PATRIC and NCBI. Resistomes and methylomes were analysed using BAcWGSTdb and REBASE whilst Kaptive was used to predict capsule typing. Plasmids and other MEGs were identified using MGE Finder and ResFinder. Phylogenetic analyses were done using RAxML and annotated with MEGA 7. A total of 877 isolates, 32 genomes and 44 plasmid sequences were analysed. Most of these isolates were reported in Asian countries and were isolated from clinical, animal and environmental sources. Colistin resistance was mostly mediated by mgrB inactivation (37%; n = 322) and mcr‐1 (36%; n = 312), while OXA‐48/181 was the most reported carbapenemase. IncX and IncI were the most common plasmids hosting carbapenemases and mcr genes. The isolates were co‐resistant to other antibiotics, with floR (chloramphenicol) and fosA3 (fosfomycin) being common; E. coli ST156 and K. pneumoniae ST258 strains were common globally. Virulence genes and capsular KL‐types were also detected. Type I, II, III and IV restriction modification systems were detected, comprising various MTases and restriction enzymes. The escalation of highly resistant isolates drains the economy due to untreatable bacterial infections, which leads to increasing global mortality rates and healthcare costs. [ABSTRACT FROM AUTHOR]

In recent years, there has been significant progress toward understanding the transcriptional networks underlying mammalian immune responses, fueled by advances in regulatory genomic technologies. Epigenomic studies profiling immune cells have generated detailed genome‐wide maps of regulatory elements that will be key to deciphering the regulatory networks underlying cellular immune responses and autoimmune disorders. Unbiased analyses of these genomic maps have uncovered endogenous retroviruses as an unexpected ally in the regulation of human immune systems. Despite their parasitic origins, studies are finding an increasing number of examples of retroviral sequences having been co‐opted for beneficial immune function and regulation by the host cell. Here, we review how endogenous retroviruses have given rise to numerous regulatory elements that shape the epigenetic landscape of host immune responses. We will discuss the implications of these elements on the function, dysfunction, and evolution of innate immunity. [ABSTRACT FROM AUTHOR]

Different cellular and molecular mechanisms contribute to chondrocyte and osteocyte development. Although vital roles of the mothers against decapentaplegic homolog 4 (also called 'SMAD4') have been discussed in different cancers and stem cell‐related studies, there are a few reviews summarizing the roles of this protein in the skeletal development and bone homeostasis. In order to fill this gap, we discuss the critical roles of SMAD4 in the skeletal development. To this end, we review the different signalling pathways and also how SMAD4 defines stem cell features. We also elaborate how the epigenetic factors—ie DNA methylation, histone modifications and noncoding RNAs—make a contribution to the chondrocyte and osteocyte development. To better grasp the important roles of SMAD4 in the cartilage and bone development, we also review the genotype‐phenotype correlation in animal models. This review helps us to understand the importance of the SMAD4 in the chondrocyte and bone development and the potential applications for therapeutic goals. [ABSTRACT FROM AUTHOR]

In this editorial, I discuss findings and implications of a hypothesis‐generating study by Copeland and colleagues showing that early adverse events related to unpredictability as well as a cumulative score summarising environmental adversity in childhood and adolescence are linked to accelerated epigenetic ageing. The setting of this study is the longitudinal Great Smoky Mountains Study, a richly phenotyped longitudinal cohort with biological information. In my discussion, I focus on potential mechanisms behind the reported findings and opportunities for next steps, for example provided by the richness of data in the cohort used in this study. [ABSTRACT FROM AUTHOR]

Neurodegenerative movement disorders (NMDs) are age‐dependent disorders that are characterised by the degeneration and loss of neurons, typically accompanied by pathological accumulation of different protein aggregates in the brain, which lead to motor symptoms. NMDs include Parkinson's disease, multiple system atrophy, progressive supranuclear palsy, and Huntington's disease, among others. Epigenetic modifications are responsible for functional gene regulation during development, adult life and ageing and have progressively been implicated in complex diseases such as cancer and more recently in neurodegenerative diseases, such as NMDs. DNA methylation is by far the most widely studied epigenetic modification and consists of the reversible addition of a methyl group to the DNA without changing the DNA sequence. Although this research field is still in its infancy in relation to NMDs, an increasing number of studies point towards a role for DNA methylation in disease processes. This review addresses recent advances in epigenetic and epigenomic research in NMDs, with a focus on human brain DNA methylation studies. We discuss the current understanding of the DNA methylation changes underlying these disorders, the potential for use of these DNA modifications in peripheral tissues as biomarkers in early disease detection, classification and progression as well as a promising role in future disease management and therapy. [ABSTRACT FROM AUTHOR]

Characterizing the capacity of marine organisms to adapt to climate change related drivers (e.g., pCO2 and temperature), and the possible rate of this adaptation, is required to assess their resilience (or lack thereof) to these drivers. Several studies have hypothesized that epigenetic markers such as DNA methylation, histone modifications and noncoding RNAs, act as drivers of adaptation in marine organisms, especially corals. However, this hypothesis has not been tested in zooplankton, a keystone organism in marine food webs. The objective of this study is to test the hypothesis that acute ocean acidification (OA) exposure alters DNA methylation in two zooplanktonic species—copepods (Acartia clausii) and cladocerans (Evadne nordmanii). We exposed these two species to near‐future OA conditions (400 and 900 ppm pCO2) for 24 h and assessed transcriptional and DNA methylation patterns using RNA sequencing and Reduced Representation Bisulfite Sequencing (RRBS). OA exposure caused differential expression of genes associated with energy metabolism, cytoskeletal and extracellular matrix functions, hypoxia and one‐carbon metabolism. Similarly, OA exposure also caused altered DNA methylation patterns in both species but the effect of these changes on gene expression and physiological effects remains to be determined. The results from this study form the basis for studies investigating the potential role of epigenetic mechanisms in OA induced phenotypic plasticity and/or adaptive responses in zooplanktonic organisms. [ABSTRACT FROM AUTHOR]

Background: There has been increasing awareness that polycystic ovary syndrome (PCOS) phenotypes may represent a mismatch between ancient genetically programmed metabolic and reproductive survival mechanisms and modern lifestyle practices. In‐utero developmental programming of metabolic and endocrine pathways may play an important role in activating gene variants that predispose the offspring to develop PCOS when exposed to specific postnatal conditions. Postnatal exposure to lifestyle factors such as poor‐quality diet and endocrine disrupting chemicals may modulate epigenetically programmed pathways that result in the observed pathophysiological changes and clinical features seen in women with PCOS. Aim: To review the developmental origins and transgenerational transmission of PCOS and the impact of lifestyle, androgens and endocrine disrupting chemicals on fetal epigenetic programming. Materials and Methods: The literature was reviewed using Google, Google Scholar, Medline and PubMed databases. The results are presented as a narrative review. Results: Human observational and animal experimental data support the hypothesis that PCOS is an inherited condition that arises as a result of developmental programming of normal gene variants. It is likely that these genes can be amplified by in‐utero androgen exposure and activated by a range of postnatal lifestyle and environmental factors. Endocrine disrupting chemicals have the potential to influence developmental programming of PCOS susceptibility genes. Conclusions: The current evidence suggests that developmental epigenetic programming following exposure to an adverse maternal metabolic and endocrine environment contributes to the pathogenesis of PCOS. Lifestyle interventions, as recommended by the International Guidelines, have the potential to reduce both symptoms and transgenerational transmission of PCOS. [ABSTRACT FROM AUTHOR]