Background: Liquid biopsies are emerging as an important source of minimally invasive biomarkers, especially in metastatic castration resistant prostate cancer (mCRPC), where tumors are often inaccessible for biopsy based strategies. In particular, circulating cell free nucleic acids, such as cfDNA, can harbor tumor specific genomic and epigenomic changes. Tumor related DNA methylation markers are detectable in circulation of mCRPC patients; however, genome wide changes in the cfDNA methylome of mCPRC patients undergoing current androgen targeting therapies have not been extensively investigated. Methods/Results: In collaboration with the University Health Network Genitourinary Biobank (Toronto, Canada), we prospectively collected a cohort of mCRPC patients that received treatment with either enzalutamide or abiraterone acetate. Plasma cfDNA was isolated at baseline (prior to starting treatment), week-12 and clinical progression. As cfDNA methylation detection can be challenging due to low yield and quality, we optimized a protocol that involves methylated DNA immuno precipitation (MeDIP) followed by next generation sequencing (NGS). Overall, we are able to obtain good quality NGS data with high mappability to the genome as well as >5x coverage of 46-51% CpGs in the genome. We applied this MeDIP-seq protocol to cfDNA samples from 11 enzalutamide treated and 5 abiraterone treated patients that completed all study visits. We performed within patient analysis to identify differentially methylated regions (DMRs) associated with treatment and clinical progression. Overall, there were a number of DMRs identified through our established pipeline, with known mCRPC genes implicated, such as members of the HOX family of transcription factors and Wnt pathway members. Conclusions: Overall, we are able to detect methylation signals from low yields of cfDNA and potentially tumor specific methylation markers. We are currently performing pathway analysis and correlation with clinical parameters. Validation of these methylation markers in mCRPC could further shed light on underlying disease mechanisms and novel biomarkers. Biography Madonna R Peter is currently a PhD student at the University of Toronto, Department of Laboratory Medicine & Pathobiology and under the Supervision of Dr. Bharati Bapat (Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada). Previously, she completed her MSc in the Department of Immunology (University of Toronto)
Background: The evaluation of active hexose correlated compound (AHCC) on hepatic metabolism mediateddrug interaction is critical in current clinical setting as there is little published information on the potential effect on drug efficacy and safety. The primary objective of this study was to evaluate the potential phase II hepatic metabolism pathways associated with the metabolism of AHCC and to determine potential drug/AHCC interactions. Methods: Four primary hepatic metabolism phase II pathways were evaluated: glutathione S-transferase (GST), quinone oxidoreductase (QOR), catechol-O-methyltransferases (COMT) and uridine diphosphate (UDP)- glucuronosyltransferase (UGT). Pooled human liver microsomes and human liver S9 fractions were utilized to evaluate QOR and UGT metabolism inhibition assays. The pool human liver S9 fractions were used to assess GST activity. Cryopreserved inducible human liver hepatocytes were used to evaluate potential induction of UGT and COMT metabolism. All experiments were carried out in triplicate. Results: Data demonstrated that AHCC is not an inhibitor of GST or UGT pathways, but may be a potential inhibitor of QOR pathway. Evaluation of induction of the phase II pathways demonstrated that AHCC showed potential induction of the UGT 1A3 and 1A6 pathways. There was no induction of the COMT pathway. Conclusion: Historically, drug interaction studies have only focused on Phase I metabolism pathways, so currently there is very limited information regarding the phase II metabolism of most commonly used medications. In conclusion, additional studies are warranted to determine potential of any phase II hepatic interactions with AHCC when administered with other medications or supplement that are substrates of these pathways.
The initial clinical diagnosis was hereditary optic neuropathy, after next-generation sequencing the final diagnosis are changed on 2 patients with retinal diseases. A 19 years old male visit my clinic for the evaluation of low vision. His cycloplegic refration was – sph 5.50 + cyl 0.25 Ax 105 on right eye, and –sph 5.00 + cyl 0.50 Ax 80. His best corrected vision was 20/100 on both eyes at initail visit. He has the maculo-papillary bundle defect on both eyes. And visual field test showed central scotoma on bothy eyes. The first case was identified the ABCA4 mutant variant carried compound heterozygous variant. A 19 years old male visit my clinic for the evaluation of low vision and color blindness. His cycloplegic refration was – sph 9.25 + cyl 0.75 Ax 105 on right eye, and –sph 9.75 + cyl 1.00 Ax 75. His best corrected vision was 20/100 on right eye and 20/70 on left eye at initail visit. He had temporal disc pallor and large cupping on both optic discs. And visual field defect showed superotemporal defect on right eye and central scotoma at left eye. The second case was identified the heterozygous R838C mutation in the GUCY2D gene. Next-generation sequencing (NGS) technology allowed more patients to obtain a accurate molecular diagnosis. Although in small proportion of patients precision care can be provided, these findings are significant as individualized management can be achieved through genetic testing.
Inherited thrombophilia (i.e. venous thromboembolism, VTE) is due to rare genetic loss-of-function mutations, common genetic risk factors and acquired risk conditions, modulating onset age, severity, recurrence and penetrance of the main gene defect also within the same kindred. GWAS recently recognized about 1000 genes associated to VTE thought some gene defects may unpredictably remain asymptomatic, so calculating the individual genetic predisposition is a challenging task. Uncommon loss-of-function mutations in SERPINC1, PROC or PROS1 genes and common gain-of-function mutations in F5 (rs6025) or F2 (rs1799963) genes, are the key genetic risk factors. By multilocus genetic approach, we investigated a large family (68 members) characterized by severe VTE despite of life-long anticoagulant treatment. The main defects found were a common missense mutation (c.G1691A) in the exon_10 of F5 gene (p.R506Q, i.e. FV Leiden) and a type 1 antithrombin (AT) deficiency caused by a nonsense mutation (CGA>TGA) responsible for a premature stop codon (c.1171C>T; p.R391X) in the exon_6 of SERPINC1 gene. Cosegregation of both mutations was found in the propositus and in 18 (26.4%) family members, and the mutations never appeared as single-defect. SERPINC1 (1q25.1) and F5 (1q24.2) genes are very close in the long arm of chromosome 1, and the hypothesized cis-segregation was confirmed in all the carriers by linkage analysis of STR-(ATT)5-18 in the SERPINC1 IVS_5. Detailed studies in a branch of this family, revealed that the proposita had VTE after surgery (20y); one of her brothers had spontaneous VTE (21y) as well one of his sons after surgery (14y). Both his daughters had early VTE episodes and complicated pregnancies: i. the older had bilateral VTE (29y) and perinatal renal thrombosis in the newborn characterized by in-utero origin; ii. the younger had massive VTE and cerebral ictus (23y) requiring premature life-saving pregnancy-interruption. Molecular analyses performed in the newborn of the first daughter and in the aborted tissues from the second daughter confirmed the SERPINC1-F5 combined defect in both progenies. A multilocus-genetic approach performed in this branch of the family also included: F5 (rs1800595); F12 rs1801020; F13A1 rs5985; SERPINC1 rs121909548; SERPINA10 rs2232698; ABO rs8176719; F11 rs2036914; FGG rs2066865; KNG1 rs710446; F11 rs2289252. We found early VTE onset and recurrence being associated to FGG rs2066865 and F5 rs4524; whilst F5 (rs1800595) was fond in trans with F5 (rs6025) in the post-mortem analysis of the in-utero thrombosis material. The common F5 rs1800595 strongly synergizes with F5 rs6025 becoming a life-threatening condition when combined with SERPINC1 mutations. Merging classic and newly GWAS-identified genetic markers is mandatory for a complete and accurate VTE risk estimation and patient management in the clinical practice to avoid partial risk score estimation in unrecognized at risk patients.
A new systems approach to diseased states and wellness result in a new branch in the healthcare services, namely, personalized and precision medicine (PPM). To achieve the implementation of PPM concept, it is necessary to create a fundamentally new strategy based upon the recognition of biomarkers and thus the targets to secure the grand future of drug design and drug discovery. Each decision-maker values the impact of their decision to use PPM on their own budget and well-being, which may not necessarily be optimal for society as a whole. It would be extremely useful to integrate data harvesting from different databanks for applications such as prediction and personalization of further treatment to thus provide more tailored measures for the patients resulting in improved patient outcomes, reduced adverse events, and more cost effective use of the latest health care resources including diagnostic (companion ones), preventive and therapeutic (targeted molecular and cellular) etc. PPM, genomics and AI are those of the most rapidly emerging areas of biomedical research and the most promising technologies for improving health care and health outcomes. Examples include the use of AI for improved DNA sequencing and SNP analysis to target specific cell and tissue types, biosensors for specific molecules in vivo, and point-of-care molecular diagnostic devices enabled by genomics- and AI tools. The enormous development of genomics research has raised great expectations concerning its impact on PPM aiming to customize medical practice with a focus on the individual, based on the use of genetic tests, identification of genomic biomarkers, and development of targeted drugs. Personal genomics is an area of genomics focusing specifically on the sequencing and analysis of one person’s genome, and then giving them their genomic information. The emphasis on individuals and genomic knowledge needs to be counterbalanced with the subjects’ understanding in their sociocultural, political, and economic contexts and with the equivalent investment in actions on the social determinants of health. The above-mentioned areas being an integral part of PPM is really an interdisciplinary research field that results from the application of the innovative genomic and AI tools to medicine and has the potential to significantly improve some canonical treatments, prevention, prophylaxis and rehabilitation. Specifically, in the field of PPM, it is expected to have a great impact in the near future due to its multiple advantages, namely its versatility to adapt a drug to cohorts of patients and/or persons-at-risk. For instance, multimodal genomic and AI-driven approaches may indeed become a key driver in harmonizing the needs of the various stakeholders by allowing cost-effective delivery and monitoring of drug efficiency and safety, and close-meshed high-quality data collection. Personal genomics can be used to advise couples wanting to have children. By knowing the risk of passing on a genetic disorder to their child, they may decide to investigate other ways of having a baby, such as in vitro fertilisation (IVF). Meanwhile, personalized genomic medicine and surgery (PGMS) represents a new approach to health care that customizes patients’ medical treatment according to their own genetic information. This new approach is the result of increased knowledge of the human genome and ways this information can be applied by physicians in the medical and surgical management of their patients. Currently, personal genome sequencing and testing is a relatively niche market with a number of services available over the internet. However, the commercialization of personal genome sequencing is set to grow and, in future, it could become a routine part of clinical practice. Genomic research and thus the market offer clinicians new techniques for risk assessment and disease classification. However, the scope of this new testing paradigm remains to be determined. Genetic tests should be seen as the latest set of tools to assist clinicians and patients in the decision-making process. Some genetic tests will undoubtedly play an important role in identifying individuals with high risks for preventable disease, or in refining clinical diagnoses. Irrespective of the number of genetic tests that prove clinically useful, genomic research will continue to provide essential new information about how and why diseases occur. The promise of PPM is well understood and exists at the convergence of genomic sequencing, biomarker research, and big data analysis. One of the big challenges to bringing more lifesaving PPM-based treat treatments to patients is that the vast networks of hospitals, foundations, and other organizations working toward new treatments and cures lack consensus on how to pursue their common goal. As a consequence, duplicative efforts and inefficiencies proliferate in this network. It will take a business mindset to overcome these obstacles. By virtue of treating each person's condition as unique, personal genomics and PPM require health professionals to understand the nature of the data, its health implications, and its limitations. But the public understanding of the scope and impact of genetic variation has not kept up with the pace of the science or technology. We examine several venues for information, including print and online guides for both lay and health-oriented audiences, and summarize selected resources in multiple formats. We also stress that implementation of PPM thus requires a lot before the current model “physician-patient” could be gradually displaced by a new model “medical advisor-healthy person-at-risk”. This is the reason for developing global scientific, clinical, social, and educational projects in the area of PPM to elicit the content of the new branch. In short, PPM will transform the way doctor’s practice and will shake up the entire pharmaceutical value chain.
Press Release Conferences Series LLC International Summit on 8th World Congress on Epigenetics and Chromosome Annual Meeting to Promote Research Worldwide-Reason behind the Confident Smile Conferences Series LLC has successfully concluded on 7th World Congress on Epigenetics and Chromosome from July 17-18, 2020 Helsinki, Finland. More than 55 distinguished scientists, researcher, academician participated for sharing research advance, knowledge and expertise related to the Epigenetic worldwide. The 2 days conference, held on July 17th through July 18th provides the leading academic scientists, researchers and scholars to share their experiences and research results about all aspects of Epigenetic Conference. 7th World Congress on Epigenetics and Chromosome, 2020 was inaugurated followed by the key note session Saleem Ali Banihani, Jordan University of Science and Technology, Jordan with the title Title: “Effect of urate, an end product of purine nucleosides catabolism, on sperm function”. The session was Chair by Ihsan Soytemiz, Turkish Biologist Association, Turkey and Co-Chair by Indraneel Mittra Tata Memorial Centre, India. Supported through the organizing committee network of renowned scientific and professional expert such as Bitsoev Vladimit Dodtievich, Medical and Technical Sciences Academy, Russia, Inna Mincheva Ivanova, Medical University of Sofia, Bulgaria, Ines Llamas-Ramos University Hospital of Salamanca, Spain, Elena Ziakova, Slovak Medical University in Bratislava, Slovak Republic, it provided a platform for collaboration among colleagues, vendors, and academia to reveal new innovations, solutions, ideas, and emerging technologies in Epigenetic in Treatment and Care. Forthcoming Conferences is on 8th World Congress on Epigenetics and Chromosome Annual Meeting during May 27-28, 2021 Dubai, UAE. Conferences Series LLC take great pleasure in inviting the scientific community across the globe to the 8th World Congress on Epigenetics and Chromosome Annual Meeting during May 27-28, 2021 at Dubai, UAE. Dubai is the largest city of UAE. Dubai is considered as one of the best venue for conducting conferences due its favourite tourist destinations. This meeting will explore advances in the GENETICS & MOLECULAR BIOLOGY. The upcoming Epigenetic Conference 2021 focuses on genetics & molecular biology, diagnosis, prevention and study of Oncology diseases. This conference will also present the advanced research, advanced techniques for treatment of health conditions and lifestyle related to the Epigenetic too. The participants can exchange and share their research results covering the scientific aspect of genetics & molecular biology Techniques Genetics, Genomics and Proteomics, Bioinformatics, Molecular Biology, Medicine, Organic Chemistry, Natural Science field, Stem cell biology, Cancer, Oncolog in the Epigenetics Conference 2021 Conference will encourage Young Researcher’s Forum, scientists and the researchers in their early stage of career graph to widely discuss their outcome so as to enrich and develop the idea. The ‘Best Poster Award’ is meant to encourage students in taking active part in the International Science platform to sharpen their skills and knowledgebase. The Sponsor in the Epigenetic Conference 2021 can reach and get exposure to new clients, customer, business, brand awareness and media exposure. The sponsorship has different levels Premium Sponsorship Packages: Elite Sponsor, Silver Sponsor, Gold Sponsor, Exhibition, Additional Sponsorship Packages and Advertisements. The 8th International Conference & Exhibition on GENETICS & MOLECULAR BIOLOGY will consist of organizing committee network of renowned scientific and professional expert such as EsraKinaci, Duzce University, Turkey, Shailendra Kumar Mehta, JanardanRai Nagar Rajasthan Vidyapeeth, India, Dario Furnari, Director Human Lab, United Kingdom.
Efficient and controlled delivery of nucleic acids by viral and synthetic carriers with low toxicity is one of the most important challenges facing the gene therapy. Nonviral vectors are perfect candidates for this goal because the use of viral vectors have a high risk of inducing unwanted immune responses. For medical applications, a use of nanostructured polymers every year brings more and more possibilities. The creation of new polymers and the study of their biocompatibility is very important to find better and safer vectors for gene therapy. In this work we compared conventional transfection and deposition transfection performed with the use of cationic star polymer. Obtained polyplexes were tested for cytotoxicity and luciferase activity using HT-1080 cells as a model. One of the solutions to increase transfection efficiency seems to be the deposition of the nucleic acid itself or its polyplex on solid support. The support used for the purpose is functioning as a substrate supporting the organization and differentiation of cells, while immobilized DNA or RNA delivers significant genetic information into the cells. The major advantages of the immobilization of nucleic acid/polyplexes include the direct contact of polymer layer loaded with the nucleic acid with the cells during the proliferation.The performed studies demonstrated that we obtained the novel effective system, based upon star polymer architecture, which is potentially useful for gene delivery. This work was supported by the Polish National Science Center contract no. UMO-2015/17/B/ST5/01095.
Kandaswamy R India Extended Abstract What is epigenetics in practical terms, especially with respect to autism? The term Epigenetics means “control above genes”. This means that genes are not destiny. Therefore, genetic diseases and disorders are not necessarily “incurable” anymore because, by applying epigenetic tools, such as environmental changes [1-3], lifestyle modifications, dietary changes, stress reduction techniques, energy medicine based techniques, and now, shifting in the direction of a positive expectation of an outcome after aligning one’s energies to match that expectation, one can gain freedom from the limiting symptoms of the “genetic” condition. Not only that, this evolutionary advantage can then be passed onto future generations too. Genes can be switched “on” or “off” with these Epigenetic tools and the possibilities are endless. In order to understand the relevance of this in Autism, let's begin with the Human Genome Project that set out to map the entire genetic makeup of Human Beings with the premise that once the all the genes encoding the proteins would be discovered one gene would be ascribed for each protein. What the scientists were hoping for was to be able to this discovery, namely the gene map, to correct and treat any and all diseases and disorders. The unexpected outcome of this project was that it was found that the DNA coding for proteins were only around 3 % and the rest of it 97% was actually junk DNA. It’s Meaning, DNA that did not seemingly code for any protein, and therefore, of no particular use for humans [4]. The human Genome Project was thus abandoned as a failure. The unanswered question here is WHY would nature and evolution considers it Vital to have the presence of these “junk” DNA that constitutes the MAJOR part of the DNA in human being. Wouldn’t it be more scientific to actually explore the importance of this “junk” DNA instead of dismissing them as “useless”? What if the “junk” DNA held epigenetic Potential of freedom from diseases and hereditary conditions? What if this “junk” DNA is connected to and is directly impacted by dark matter and dark energy? And what if the Blueprint of the future evolution of Mankind on this planet lies in this “junk” DNA? The implications of this discovery is of particular significance in Autism as many scientists are still on the trail of discovering all the genes supposedly associated with causing autism, and these genes run into the thousands and rising by the day. This is being done under the “Autism Genome Project”. This has led to a situation where these scientists are caught up in the “autism genetic discovery quagmire” that is keeping them going round in circles still trying to understand the problem of autism, rather than investigating the Solution in autism that is already showing results on the ground. And this Solution that is already working in autism resulting in the complete recovery of children with autism from all their limiting symptoms is based on the principles of Applied Intentional Epigenetics in particular and Applied Energy Medicine. For the published evidence of these successfully healed cases and for the further understanding of the application of these cutting-edge sciences in healing the limiting symptoms in autism, one can peruse all the articles given under the reference section at the end of this article. The epigenetics of “thought pools and streams” and the power of holding expectations The understanding of morphic resonance and the 100th monkey principle has shown how genes do not play a major role in many of the diseases or disorders, as previously [5]. That brings us to the question-If it is not the genes, then what is it that is continuing to result in more and more diseases and disorders being discovered as humans continue to become more and more technologically advanced? The answer is-it is the habitual tuning-in to “thought pools and streams” due to Conditioning and the resultant expectations that set up the field for a person to manifest any of these conditions in one’s own life experience. Let’s understand this further. There are these habits of patterns and thought pools and streams that one is always downloading from. This “thought pool and stream” has been in existence since centuries and is growing with more and more thoughts being added to the stream with the thinking process in each human being contributing to this as well [6]. Autistic children are particularly tuned-in to these “Thought Pools and Thought Streams” as they are highly Energy Sensitive and invariably with poor “Energy Boundaries” [7]. To understand these terms and the mechanism in greater detail it is recommended to read through the articles under the ‘Reference” section below. Not only this, the same mechanism operates when they are downloading information and energy patterns in the form of thoughts “
Introduction: The metabolic syndrome (ms) constitutes a combination of underlying risk factors for an adverse outcome, cardiovascular disease. Thus, the medical behavior of the ms can be regarded as a whole. Nevertheless, from a pathogenic point of view, understanding of the underlying mechanisms of each ms intermediate phenotype, obesity, hypertension, type 2 diabetes and particularly insulin resistance is a difficult task. Systems biology brings a new concept for revealing the pathogenesis of human disorders and express the presence of common physiologic processes and molecular networks influencing the risk of a disease. It will be showed a model of this concept to explain the genetic determinants of ms associated phenotypes. Objective: Based on the hypothesis that common physiologic processes and molecular networks may increase the risk of “ms” disease components, we propose the systems biology approaches i.e. a gene enrichment analysis and the use of a protein-protein interaction network. Our results show that a network driven by many members of the nuclear receptor super family of proteins, including retinoid X receptor and farnesoid X receptor (FXR), in addition to Clock, SLC6A4, PGC1A, etc, may be implicated in the pathogenesis of the MS by their interactions at multiple levels of complexity with genes involved in metabolism, cell differentiation and oxidative stress. And, will be discussed alternative genetic mechanisms those are gaining acceptance in the physiopathology of the “ms” components, in particular fatty liver disease: the regulation of transcriptional and post-transcriptional gene expression by micro-RNAs and epigenetic modifications such as DNA methylation of not only nuclear but mitochondrial genes. Result: The obesity incidence has increased at an alarming rate in recent years, becoming a worldwide health problem. Due to the serious negative effects of available anti-obesity drugs and some success of identifying natural products for overcoming obesity, more researches have been focused on the identification of natural products with less unpleasant adverse effects. Orthosiphon stamineus Benth. or java tea, is traditionally used to treat multiple disorders. Therefore, this study investigated the anti-obesity and lipid lowering activity of O. stamineus (200 and 400 mg/kg) on high-fat diet induced obese mice. Conclusion: The oral administration of O. stamineus, for 8 weeks, concluded in a significant decrease in body weight gain in mice fed a high-fat diet. Subsequently, the food recess between the treatment and the “hfd” groups were similar which suggested that O. stamineus did not suppress appetite. Moreover, administration of O. STAMINEUS commonly reduced the serum triglycerides, total cholesterol, low-density lipoprotein cholesterol, and liver oxidative stress levels compared to the HFD control group. Besides, the O. STAMINEUS extract treatment elicited a important reduction of serum glucose, insulin, leptin and adiponectin levels compared to that of the HFD control. The present study thus concludes that O. STAMINEUS can express hypolipidemic and anti-obesity activity that protects the body against adverse effects of high fat diet-induced obesity, possibly through suppression of body weight gain, lipid lowering action, improvement in insulin and leptin sensitivity.
Introduction: Epigenetic mechanisms play a fundamental role in controlled development and gene expression in different types of cells of an organism, carrying the same genomic DNA sequence. These mechanisms control differences in the gene expression that are mitotically heritable although not altering the primary DNA sequence [1]. A large number of proteins write, read or erase particular epigenetic modifications and thus define where and when the transcriptional machinery can access the primary DNA sequence to drive normal growth and differentiation in the developing embryo along with the fetus. Different type of epigenetic marks work in concert to drive appropriate gene expression. These are DNA methylation at CpG dinucleotides, covalent modifications of histone proteins, noncoding RNA’s (ncRNA) along with other complementary mechanisms contributing to higher order chromatin organization, within the cell nucleus. There are two special examples e.g., chromosome inactivation and genome imprinting, which explains how 2016 Vol. 2 No. 4: 20 Journal of Clinical Epigenetics ISSN 2472-1158 2 This article is available in: http://www.clinical-epigenetics.imedpub.com/ important are the epigenetic mechanisms in regulating correct patterns of gene expression during early development chromosome inactivation basically is an example of dosage compensation in females leading to monoallelic expression of a huge number of X linked genes in female. Genome imprinting is a process in which special genes carrying epigenetic marks from parents of origin have the capacity for getting monoallelic parent of origin specific cell types at specific times of development. In germ cells in development as well as in embryo, there is genome wide reprogramming which is responsible for erasure as well as reestablishing of the correct epigenetic patterns. In contrast to these naturally occurring processes, the processes used in induced pluripotent stem cells from somatic cells are quite different [2], reviewed by Huang et al[3]. Changes in epigenetics can occur by different mechanisms and lead to infertility and imprinting disorders. Genetic as well as environmental factors impact genetic marks, which develop phenotypic differences varying from normal variation to human disease [4]. Both environmental factors e.g., starvation as well as artificial reproductive technologies (ART) have been shown to affect the epigenome of the embryo e.g., of the epigenetic changes which are associated with maternal starvation in fetal life can remain throughout adulthood, contributing to late onset disorders e.g., CVS disorders and type 2 diabetes mellitus [5-9].
Background Human endogenous retroviruses (HERVs), suspected to be transposition-defective, may reshape the transcriptional network of the human genome by regulatory elements distributed in their long terminal repeats (LTRs). HERV-K (HML-2), the most preserved group with the least number of accumulated of mutations, has been associated with aberrant gene expression in tumorigenesis and autoimmune diseases. Because of the high sequence similarity between different HERV-Ks, current methods have limitations in providing genome-wide mapping specific for individual HERV-K (HML-2) members, a major barrier in delineating HERV-K (HML-2) function. Results In an attempt to obtain detailed distribution information of HERV-K (HML-2), we utilized a PCR-based target enrichment sequencing protocol for HERV-K (HML-2) (PTESHK) loci, which not only maps the presence of reference loci, but also identifies non-reference loci, enabling determination of the genome-wide distribution of HERV-K (HML-2) loci. Here we report on the genomic data obtained from three individuals. We identified a total of 978 loci using this method, including 30 new reference loci and 5 non-reference loci. Among the 3 individuals in our study, 14 polymorphic HERV-K (HML-2) loci were identified, and solo-LTR330 and N6p21.32 were identified as polymorphic for the first time. Conclusions Interestingly, PTESHK provides an approach for the identification of the genome-wide distribution of HERV-K (HML-2) and can be used for the identification of polymorphic loci. Since polymorphic HERV-K (HML-2) integrations are suspected to be related to various diseases, PTESHK can supplement other emerging techniques in accessing polymorphic HERV-K (HML-2) elements in cancer and autoimmune diseases.
Introduction: The knowledge of epigenetical mechanisms significantly enlightens the dilemma ‘nature or nurture’ and constitutes a very important component for the outcome of psychiatric treatment and psychotherapeutic relationship with patients or clients who report traumatic memories and had experienced negligence or maltreatment. The story starts from the beginning in the early 19th Century, when Lamarck argued that organisms can acquire characteristics and properties through their interaction and adaptation to the environment. Case Report These new ‘personality traits’ can become lifelong stable and can be heredited by the next generation. The term ‘epigenetics’ which derived from Greek, was given to this organismic property. It means “above genetics”. There are two main mechanisms involved in epigenetics: DNA methylation and histone modification. A third mechanism concerning non coding RNA (ncRNA) needs to be more elucidated. DNA methylation occurs when one methylgroup (CH3) is added on the aminoacid cytosine. This is completed through the action of a methyltransferase only when cytosine is followed by guanine, and results in long term silencing of the expression of the specific gene. It is important to note that gene methylation is a multi-step procedure, while demethylation is performed through one single step. These facts are highly important for the personality changes during psychotherapeutic interventions and psychiatry, since they show very high potential and flexibility on the multitude of lived experiences and they have a determining role in neuroplastic functions like learning, memorising and adaptive behaviour. The second mechanism concerns histone modification. Histones are proteins positively charged. Unused DNA which remains unneeded carries a negative charge and, through attraction, it is packaged around an octamer of histones. Histone molecules are subjected to methylation, acetylation or phosphorylation and can repress the genes expression by increasing the electrostatic load and tightening the coils, thus silencing DNA expression. Histone modification is transient resulting in less permanent changes than DNA methylation. The agouti mice example shows the epigenetic changes that can be observed through gene methylation without DNA modification. The mouse with a methylated gene for hair and weight has dark gray hair and is underweighted in comparison to the mouse with non-methylated gene which is yellow and normal weighted. As far as the research on Diabetes Mellitus type 2 is concerned, Dayeh et al. found about 17 genes that seem to be differentially methylated in the pancreatic islets, thus contributing to decreased insulin release after glucose stimulation. Two years later, the same research team reduced the number of implicated genes to four. Another brilliant example of epigenetic changes is the increased methylation of the gene which controls the production of the Brain Derived Neurotrophic Factor (BDNF) in stressful environments. BDNF has a crucial role in the creation of new synapses. The reduction of BDNF production results in a decreased number of new synapses and reduced symbolisation of experiences, thus diminishing the ability to memorise and learn. In mice, stressful early life results in higher responses of corticosterone, which is the equivalent of cortisol in mice, and reduced neurogenesis in hippocampus during their adulthood. This methylation marker remains stable during life and is inherited to the next generation. So silencing of the BDNF gene, combined with the down regulation on the BDNF transcription levels are a good indicator of early life stress and abusive childhood. BDNF levels reduction in traumatic chlidhood may also have a teleological meaning, i.e., like a natural protection, so as to reduce acurate symbolisation of painful memories and support emotional survival. Studied the brains of suicidal children and found hypermethylation of the ribosomal RNA in the region 5’ at the hippocampal area which controls the hypothalamo-pituitary-adrenal (HPA) axis. The outcome of this hypermethylation was abnormal regulation of the response to stress and suicidal tendency. In addition, Bustamante et al. found a direct relationship between the increased cytosine-phosphate-guanine DNA methylation, childhood maltreatment and Major Depressive Disorder (MDD). Oxytocin calms amygdala through reinforcement of the adducting fibers of GABA. In order to have this outcome the BDNF production needs to be increased through demethylation of the BDNF gene. Psychotherapy or relaxation or even an appropriate environment will result in this gene demethylation as will be described below. Result Empathic listening increases symbolization and reduces amygdala firing through activation of its middle and basolateral nucleus Uzefovsky et al. studied the neurogenetic path of empathy in participants and showed its close relationship with the oxytocin and arginin-vasopressin related genes. Schneiderman et al. found a direct relationship of oxytocin secretion with the reciprocity of the partners, their positive regard, their tender touch and their caring for the relationship. They concluded that this situation has many similarities with the mother-infant relationship and the primary attachment. Lutz et al. assert that empathy and compassion create an environment for a higher integration degree of our nervous system. Yoga-although it is not therapy-contributes to relaxation and insight. One controlled study showed a significant increase of oxytocin in fifteen schizophrenic patients after a month of yoga exercise It would be of interest to study the degrees of methylation of oxytocin and of BDNF gene and their relationship with empathic understanding, in order to understand the exact path to higher neurogenesis and synaptic activity. Studies examining demethylation of the oxytocin gene after couple therapy would be mostly interesting, for the neuroscience of romantic relationships. Concerning the pharmacology progress in this field, Lopez et al. Conclusion Cortex after an eight week therapy with citalopram. Clinical signs of depression were also improved. They proposed that the methylation demethylation procedure is a dynamic process which is included in the substrate of cognitive changes during therapy. Methyltransferase and histone deacetylase inhibitors are, at present, the main target for preparation of epigenetic drugs which will be used in mental disorders.
Three main evolutionary events in eukaryotic gene structures are intron gain, loss and sliding. The last one means the change of intron position over several nucleotides. Due to its ambiguous molecular mechanism and rarity of occurrence, the existence of intron sliding could still be debatable. Here we analyzed 36 genome pairwise alignments of vertabrates, including human, rat, chicken and zebrafish in search of intron sliding events. The thorough comparison of exon-intron boundaries in the pairwise genome alignments from UCSC Genome Browser showed that the sliding is indeed very rare - the maximum number of hits for each analyzed pair of organisms does not exceed 20. In addition, comparison of gene annotations from different databases called into question almost half of all cases. To confirm that the found sliding events are not being the result of gene annotation errors we used transcriptome data from UCSC Genome Browser. We found out that majority of sliding events predicted by alignments seemed to happen in the low frequency isoforms, as we were not able to confirm them by transcriptome data. Only several cases were partially supported by transcriptome (e.g. sliding in EIF1AX gene between human and sheep) which leaves the question open whether the sliding occurs at all. The study was funded by RFBR according to the research project â 18-34-00932.
The identification of non-invasive cancer stem cells markers for predicting patients at high risk of Hepatocelular carcinoma (HCC) development to allow early intervention and consequently reducing mortality and disease burden. In HCC, liver Cancer stem sells (LCSCs), expressing molecular markers (e.g. CD133, CD90, CD44 and EpCAM), exhibited resistance to radiotherapy and chemotherapy in vitro and in vivo through up-regulating the expression of drug efflux-related proteins and activating anti-apoptotic pathways and stem cell-related pathways. In the present study we used Chronic HCV infection group (n= 40), HCV with liver cirrhosis group (n= 40), HCV-HCC group (n= 40) and Age- and sex-matched individuals (n=35) as controls. The results revealed a variation in CD133/EpCAM lymphocytes in compare to EpCAM lymphocytes or CD133 lymphocytes and so is CD133/EpCAM Granulocytes or EpCAM Granulocytes and CD133 Granulocytes and the percentage of total CD133, total CD133/EpCAM. Total EpCAM expression was associated with younger age, and. The prognostic role of CD133 was most significant in HCC, while the prognostic role of EpCAM was more apparent in more advanced stages. We are planing to evaluate mononuclear cells nuclic acid Single nucleotide polymorphisms (SNPs) in CD133 (rs2240688A>C and rs3130C>T) using taqMan genotyping. TaqMan miRNA Reverse Transcription and qPCR reactions will be performed using MicroRNA-1825 primer assay while miRNA-39 will utilized as an endogenous control to normalize the data.
Note I am pleased to introduce you with Journal of Clinical which is an open access, companion assessed journal l that includes all parts of epigenetic standards and instruments in connection to human illness, conclusion and treatment. Clinical trials and research in illness model living beings are especially welcome. We have been started in year 2015. Journal of Clinical (ISSN: 2472-1158) is growing continuously. It is our pleasure to announce that during year 2020, all issues of volume 6 were published online on time and the print issues were also brought out and dispatched within 30 days of publishing the issue online. All published articles of this journal are included in the indexing and abstracting coverage of CAS Source Index (CASSI), Index Copernicus, Google Scholar, Sherpa Romeo, Academic Journals Database, GenamicsJournalSeek, JournalTOCs, CiteFactor, Electronic Journals Library, RefSeek, Hamdard University, EBSCO A-Z, Directory of Abstract Indexing for Journals, World Catalogue of Scientific Journals, OCLC- WorldCat, Scholarsteer, SWB online catalog, Virtual Library of Biology (vifabio), Publons, Dtufindit, Geneva Foundation for Medical Education and Research. During the calendar year 2019, Journal of Clinical (ISSN: 2472-1158) received a total of 30 papers, out of which 6 articles were rejected in the preliminary screening due to plagiarism or being out of the format and peer review process. During 2019 around 16 articles were subjected for publication after they are accepted in the peer review process. In the 4 issues of Volume 5 published during the year 2019, a total of 16 articles were published (at an average of 3 articles per issue of which, articles were published from authors all around the world. A total of 30 research scientists from all over the world reviewed the 16 articles published in volume 12. Average publication period of an article was further reduced to 14-21 days. During the calendar year 2019, a total of three Editors, ten Reviewers joined the board of Journal of Clinical and contributed their valuable services towards contribution as well as publication of articles, and their valuable reviewer comments will beneficial to publish quality of article in the Journal. I take this opportunity to acknowledge the contribution of Editor-in-chief and Associate Editor during the final editing of articles published andbringing out issues of Journal of Clinical in time. I would also like to express my gratitude to all the authors, reviewers, the publisher, language editor, honorary editors,the scientific advisory and the editorial board of Journal of Clinical , the office bearers for their support in bringing out the new volume (Volume 6) of Journal of Clinical for the calendar year 2020 and look forward to their unrelenting support further to release more issues for Journal of Clinical in scheduled time. How to cite this article: Ihtisham Bukhari. Editorial Highlights for Journal of Clinical Epigenetics doi: 6.2472/imedipce.2020.6.006
In December 2019, a novel severe acute respiratory syndrome (SARS) from a new coronavirus (SARS-CoV-2) was recognized in the city of Wuhan, China. Rapidly, it became an epidemic in China and has now spread throughout the world reaching pandemic proportions. High mortality rates characterize SARS-CoV-2 disease (COVID-19), which mainly affects the elderly, causing unrestrained cytokines-storm and subsequent pulmonary shutdown, also suspected micro thromboembolism events. At the present time, no specific and dedicated treatments, nor approved vaccines, are available, though very promising data come from the use of anti-inflammatory, anti-malaria, and anti-coagulant drugs. In addition, it seems that males are more susceptible to SARS-CoV-2 than females, with males 65% more likely to die from the infection than females. Data from the World Health Organization (WHO) and Chinese scientists show that of all cases about 1.7% of women who contract the virus will die compared with 2.8% of men, and data from Hong Kong hospitals state that 32% of male and 15% of female COVID-19 patients required intensive care or died. On the other hand, the long-term fallout of coronavirus may be worse for women than for men due to social and psychosocial reasons. Regardless of sex- or gender-biased data obtained from WHO and those gathered from sometimes controversial scientific journals, some central points should be considered. Firstly, SARS-CoV-2 has a strong interaction with the human ACE2 receptor, which plays an essential role in cell entry together with transmembrane serine protease 2 (TMPRSS2); it is interesting to note that the ACE2 gene lays on the X-chromosome, thus allowing females to be potentially heterozygous and differently assorted compared to men who are definitely hemizygous. Secondly, the higher ACE2 expression rate in females, though controversial, might ascribe them the worst prognosis, in contrast with worldwide epidemiological data. Finally, several genes involved in inflammation are located on the X-chromosome, which also contains high number of immune-related genes responsible for innate and adaptive immune responses to infection. Other genes, out from the RAS-pathway, might directly or indirectly impact on the ACE1/ACE2 balance by influencing its main actors (e.g., ABO locus, SRY, SOX3, ADAM17). Unexpectedly, the higher levels of ACE2 or ACE1/ACE2 rebalancing might improve the outcome of COVID-19 in both sexes by reducing inflammation, thrombosis, and death. Moreover, X-heterozygous females might also activate a mosaic advantage and show more pronounced sex-related differences resulting in a sex dimorphism, further favoring them in counteracting the progression of the SARS-CoV-2 infection.
The future of Genomics holds much promise and opportunities. These are briefly mentioned here and will be expanded in an oral presentation. Evaluating scientific evidence to support valid and useful genetic tests and counseling. Monitoring the use of genetic tests and family health history in populations, and evaluating the outcome in various families. Exploring the use of valid and useful genetic tests and family health history tools to plan clinical practice, policy, and design programs to detect people who are at risk for disease, make diagnoses, and suggest appropriate interventions. Inserting genomic information and clinical decisions in health records. Developing practical recommendations that evaluate the net health benefit of genetic tests and family health information. Evaluating the impact of genetic applications in individual families, local communities and populations. Develop efficient methods to interpret and translate recommendations into practice. Incorporating genomics education at all levels in schools. Maintaining the privacy and confidentiality of genomic information of all kinds. Coordination of Genomic data from all sectors of the academia, the industry, as well as all other sections of the society.
The worldwide epigenetics advertise is anticipated to reach USD 1.60 billion by 2022 from USD 0.85 billion of every 2016, at a CAGR of 13.3% from 2017 to 2022. The development in this market is principally credited to diminishing sequencing costs, expanding research action, financing for epigenetics inquire about, rising predominance of malignancy and developing utilizationsof epigenetics in non-oncology illnesses. Extending application regions of epigenetics in non-oncology ailments, customized drug, and target treatment are relied upon to give development chances to players working in the market in the coming years. The base year considered for the examination is 2016, and the figure has been accommodated the period somewhere in the range of 2017 and 2022.
Introduction: Despite having no mammary glands, Drosophila is a very useful model for conducting research on molecular mechanisms as well as the regulation of transcription including epigenetic changes associated with breast cancer development. Drosophila has been used as one of the model systems since it was first introduced by Thomas Morgan, a pioneer in genetics for the study of heredity, in the early 20th century [1]. The complete mapping of all Drosophila chromosomes was completed by Dr. Morgan and his colleagues. Drosophila has extremely large polytene chromosomes in the salivary glands. These polytene chromosomes have enabled us to directly observe chromosomal structures and band-patterns including euchromatin and heterochromatin since the early 1960s [2,3]. Most notably, the loci involved in gene activation can be visualized as chromosome puffing [3,4]. When chromosomes including puffs are immuno-stained using antibodies against factors associated with transcription and chromatin structures such as RNA polymerase II and histones, we can evaluate the state of transcription as well as modification of histone tails which are epigenetic markers on genes of interest [4,5]. In Drosophila, Position-effect variegation (PEV) which is observed when a gene normally in euchromatin is juxtaposed with heterochromatin, is also a very useful phenotype for analyzing factors which can convert chromatin structures from euchromatin to heterochromatin or vice versa [6].
Targeted sequencing data will never be better than the input material generated during the targeted enrichment process! While this may seem trivial, very few targeted enrichment technologies allow maintaining the integrity and quality of the DNA during enrichment. This results in both false positives and false negative results and can significantly impact conclusions. The Xdrop™ innovation, a novel robotized microfluidics-based focused on advancement framework, empowers quick focused on improvement while keeping up the nature of the DNA and subsequently makes it conceivable to dodge the ancient rarities presented with other enhancement advances. Here we show the Xdrop™ framework being utilized to succession incorporated infections and their encompassing obscure chromosomal grouping, long GC rehashes, and we show staging of malignant growth changes from sub-nanograms of DNA. Districts of 40-70 kb are enhanced and sequenced utilizing Illumina, PacBio, and Oxford Nanopore sequencing at high inclusion. Apart from the Xdrop™ reagents, just 0.2-10 ng of input DNA and two adjacent 20-25 bp primers are used for the enrichment of a chromosomal region and it is therefore fast and easy to set up for a new region. The primers are located in the central part of the enriched region which means that partially unknown regions can also be enriched using the system making it relevant for regions with structural variation, CRISPR gene editing, gap closing, variable viruses or bacteria, pseudogenes etc. We also show that the Xdrop™ system can be used for general, unbiased isothermal amplification of small amounts of samples of DNA for any type of downstream sequencing.
