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Personalized epigenetics

Robert John Aitken
This article is a personal perspective on male infertility, a condition that is not only extremely prevalent but also a major reason for couples to resort to assisted reproductive technology. The introduction of intra-cytoplasmic sperm injection (ICSI) as a form of facilitated fertilization had a revolutionary impact on our capacity to treat cases of male infertility associated with severely-compromised semen quality. However, the widespread use of this technique is also thought to pose risks in terms of the incidence of miscarriage, the health and wellbeing of the offspring and perpetuation of the infertile phenotype into future generations...
March 13, 2018: Molecular Human Reproduction
Jessica Tulloch, Lesley Leong, Sunny Chen, C Dirk Keene, Steven P Millard, Andrew Shutes-David, Oscar L Lopez, Julia Kofler, Jeffrey A Kaye, Randy Woltjer, Peter T Nelson, Janna H Neltner, Gregory A Jicha, Douglas Galasko, Eliezer Masliah, James B Leverenz, Chang-En Yu, Debby Tsuang
INTRODUCTION: Inheritance of the ε4 allele of apolipoprotein E (APOE) increases a person's risk of developing both Alzheimer's disease (AD) and Lewy body dementia (LBD), yet the underlying mechanisms behind this risk are incompletely understood. The recent identification of reduced APOE DNA methylation in AD postmortem brains prompted this study to investigate APOE methylation in LBD. METHODS: Genomic DNA from postmortem brain tissues (frontal lobe and cerebellum) of neuropathological pure (np) controls and npAD, LBD + AD, and npLBD subjects were bisulfite pyrosequenced...
March 12, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Gregory A Babbitt, Jamie S Mortensen, Erin E Coppola, Lily E Adams, Justin K Liao
Traditional informatics in comparative genomics work only with static representations of biomolecules (i.e., sequence and structure), thereby ignoring the molecular dynamics (MD) of proteins that define function in the cell. A comparative approach applied to MD would connect this very short timescale process, defined in femtoseconds, to one of the longest in the universe: molecular evolution measured in millions of years. Here, we leverage advances in graphics-processing-unit-accelerated MD simulation software to develop a comparative method of MD analysis and visualization that can be applied to any two homologous Protein Data Bank structures...
March 13, 2018: Biophysical Journal
Mariarosaria Conte, Raffaele De Palma, Lucia Altucci
In recent years, anti-tumor immunotherapy has shown promising results, and immune-oncology is now emerging as the fourth major wave in the treatment of tumors after radiotherapy, chemotherapy and molecular targeted therapy. Understanding the impact of the immune system on neoplastic cells is crucial to improve its effectiveness against cancer. The stratification of patients who might benefit from immunotherapy as well as the personalization of medicine have contributed to the discovery of new immunotherapeutic targets and molecules...
March 10, 2018: International Journal of Biochemistry & Cell Biology
Peng Wu, Jia-Li Liu, Shi-Mei Pei, Chang-Peng Wu, Kai Yang, Shu-Peng Wang, Song Wu
BACKGROUND: Renal cell carcinoma (RCC) account for over 80% of renal malignancies. The most common type of RCC can be classified into three subtypes including clear cell, papillary and chromophobe. ccRCC (the Clear Cell Renal Cell Carcinoma) is the most frequent form and shows variations in genetics and behavior. To improve accuracy and personalized care and increase the cure rate of cancer, molecular typing for individuals is necessary. METHODS: We adopted the genome, transcriptome and methylation HMK450 data of ccRCC in The Cancer Genome Atlas Network in this research...
March 13, 2018: BMC Cancer
Tsachi Ein-Dor, Willem J M I Verbeke, Michal Mokry, Pascal Vrtička
Attachment in the context of intimate pair bonds is most frequently studied in terms of the universal strategy to draw near, or away, from significant others at moments of personal distress. However, important interindividual differences in the quality of attachment exist, usually captured through secure versus insecure - anxious and/or avoidant - attachment orientations. Since Bowlby's pioneering writings on the theory of attachment, it has been assumed that attachment orientations are influenced by both genetic and social factors - what we would today describe and measure as gene by environment interaction mediated by epigenetic DNA modification - but research in humans on this topic remains extremely limited...
March 7, 2018: Attachment & Human Development
Fritz Trillmich, Thorben Müller, Caroline Müller
Research on animal personality explains the coexistence of distinct behavioural phenotypes within a species and demonstrates limits to individual plasticity. However, the mechanisms guiding the lifelong development of personality should receive more attention, because many elements of personality are emergent properties of interactions between the environment and an individual's genetic background. In these interactions, mechanisms (e.g. genetic regulatory networks, epigenetic processes and neuroendocrine regulation) influencing personality may be modified...
February 2018: Biology Letters
Layla T Ghaffari, Alexander Starr, Andrew T Nelson, Rita Sattler
Neurological diseases, including dementias such as Alzheimer's disease (AD) and fronto-temporal dementia (FTD) and degenerative motor neuron diseases such as amyotrophic lateral sclerosis (ALS), are responsible for an increasing fraction of worldwide fatalities. Researching these heterogeneous diseases requires models that endogenously express the full array of genetic and epigenetic factors which may influence disease development in both familial and sporadic patients. Here, we discuss the two primary methods of developing patient-derived neurons and glia to model neurodegenerative disease: reprogramming somatic cells into induced pluripotent stem cells (iPSCs), which are differentiated into neurons or glial cells, or directly converting (DC) somatic cells into neurons (iNeurons) or glial cells...
2018: Frontiers in Neuroscience
Giacomo Sgalla, Bruno Iovene, Mariarosaria Calvello, Margherita Ori, Francesco Varone, Luca Richeldi
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disease characterized by the aberrant accumulation of fibrotic tissue in the lungs parenchyma, associated with significant morbidity and poor prognosis. This review will present the substantial advances achieved in the understanding of IPF pathogenesis and in the therapeutic options that can be offered to patients, and will address the issues regarding diagnosis and management that are still open. MAIN BODY: Over the last two decades much has been clarified about the pathogenic pathways underlying the development and progression of the lung scarring in IPF...
February 22, 2018: Respiratory Research
Annely M Richardson, Ann M Moyer, Linda Hasadsri, Roshini S Abraham
PURPOSE OF REVIEW: The purpose of this review is to provide an overview of diagnostic testing in primary immunodeficiency and immune dysregulatory disorders (PIDDs), particularly focusing on flow cytometry and genetic techniques, utilizing specific examples of PIDDs. RECENT FINDINGS: Flow cytometry remains a vital tool in the diagnosis and monitoring of immunological diseases. Its utility ranges from cellular analysis and specific protein quantitation to functional assays and signaling pathway analysis...
February 22, 2018: Current Allergy and Asthma Reports
M May, S D Brookman-May, T H Ecke, M Burger
Squamous cell carcinoma of the penis (SCCP) is a rare cancer type in Western industrialized nations; nevertheless, it shows an aggressive course of disease in advanced tumor stages with accordantly high recurrence and progression rates. While molecular biomarkers are not established in clinical routine for the management of SCCP patients yet, the accordant unmet need is enormous, as adequate biomarkers would be meaningful for prognostic determination, planning of modality and extent of primary therapy, indication for inguinal lymph node resection, adjuvant treatment, and as potential targets for specific systemic treatment...
February 22, 2018: Der Urologe. Ausg. A
Gianluca Colella, Flavio Fazioli, Michele Gallo, Annarosaria De Chiara, Gaetano Apice, Carlo Ruosi, Amelia Cimmino, Filomena de Nigris
Cancer treatment is rapidly evolving toward personalized medicine, which takes into account the individual molecular and genetic variability of tumors. Sophisticated new in vitro disease models, such as three-dimensional cell cultures, may provide a tool for genetic, epigenetic, biomedical, and pharmacological research, and help determine the most promising individual treatment. Sarcomas, malignant neoplasms originating from mesenchymal cells, may have a multitude of genomic aberrations that give rise to more than 70 different histopathological subtypes...
February 21, 2018: International Journal of Molecular Sciences
Monika Toma, Tomasz Skorski, Tomasz Sliwinski
Cancer is a heterogeneous disease with a high degree of diversity between and within tumors. Our limited knowledge of their biology results in ineffective treatment. However, personalized approach may represent a milestone in the field of anticancer therapy. It can increase specificity of treatment against tumor initiating cancer stem cells (CSCs) and cancer progenitor cells (CPCs) with minimal effect on normal cells and tissues. Cancerous cells carry multiple genetic and epigenetic aberrations which may disrupt pathways essential for cell survival...
January 31, 2018: Current Medicinal Chemistry
Imane Saif, Yassine Kasmi, Karam Allali, Moulay Mustapha Ennaji
The epigenetics methylation of cytosine is the most common epigenetic form in DNA sequences. It is highly concentrated in the promoter regions of the genes, leading to an inactivation of tumor suppressors regardless of their initial function. In this work, we aim to identify the highly methylated regions; the cytosine-phosphate-guanine (CpG) island located on the promoters and/or the first exon gene known for their key roles in the cell cycle, hence the need to study gene-gene interactions. The Frommer and hidden Markov model algorithms are used as computational methods to identify CpG islands with specificity and sensitivity up to 76% and 80%, respectively...
February 2, 2018: Gene
Adrian Raine
Although antisocial personality disorder (APD) is one of the most researched personality disorders, it is still surprisingly resistant to treatment. This lack of clinical progress may be partly due to the failure to view APD as a neurodevelopmental disorder and to consider early interventions. After first defining what constitutes a neurodevelopmental disorder, this review evaluates the extent to which APD meets neurodevelopmental criteria, covering structural and functional brain imaging, neurocognition, genetics and epigenetics, neurochemistry, and early health risk factors...
January 25, 2018: Annual Review of Clinical Psychology
(no author information available yet)
First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Magdalena Woloszynska is the first author on 'The Elongator complex regulates hypocotyl growth in darkness and during photomorphogenesis', published in Journal of Cell Science. While completing this work, Magdalena was a postdoctoral fellow in the Chromatin and Growth Control group at the VIB-UGent Center for Plant Systems Biology at Ghent University, Belgium...
January 29, 2018: Journal of Cell Science
José I López, Javier C Angulo
PURPOSE OF REVIEW: Intratumor heterogeneity is an inherent event in tumor development that is receiving much attention in the last years since it is responsible for most failures of current targeted therapies. The purpose of this review is to offer clinicians an updated insight of the multiple manifestations of a complex event that impacts significantly patient's life. RECENT FINDINGS: Clear cell renal cell carcinoma is the most common renal tumor and a paradigmatic example of a heterogeneous neoplasm...
January 27, 2018: Current Urology Reports
Qingzhong Wang, Bhaskar Roy, Gustavo Turecki, Richard C Shelton, Yogesh Dwivedi
OBJECTIVE: Proinflammatory cytokines have recently received considerable attention for their role in suicidal behavior; however, how the expression of cytokine genes is regulated is not clearly known. The authors examined underlying mechanisms of critical cytokine gene tumor necrosis factor-alpha (TNF-α) dysregulation in the brains of individuals who died by suicide. METHOD: TNF-α expression was examined in the dorsolateral prefrontal cortex of the postmortem brains of persons with and without major depressive disorder who died by suicide and of persons with major depressive disorder who died of causes other than suicide...
January 24, 2018: American Journal of Psychiatry
An-An Yin, Nan Lu, Amandine Etcheverry, Marc Aubry, Jill Barnholtz-Sloan, Lu-Hua Zhang, Jean Mosser, Wei Zhang, Xiang Zhang, Yu-He Liu, Ya-Long He
AIMS: We aimed to identify a clinically useful biomarker using DNA methylation-based information to optimize individual treatment of patients with glioblastoma (GBM). METHODS: A six-CpG panel was identified by incorporating genome-wide DNA methylation data and clinical information of three distinct discovery sets and was combined using a risk-score model. Different validation sets of GBMs and lower-grade gliomas and different statistical methods were implemented for prognostic evaluation...
January 19, 2018: CNS Neuroscience & Therapeutics
Ares Pasipoularides
Genomics designates the coordinated investigation of a large number of genes in the context of a biological process or disease. It may be long before we attain comprehensive understanding of the genomics of common complex cardiovascular diseases (CVDs) such as inherited cardiomyopathies, valvular diseases, primary arrhythmogenic conditions, congenital heart syndromes, hypercholesterolemia and atherosclerotic heart disease, hypertensive syndromes, and heart failure with preserved/reduced ejection fraction. Nonetheless, as genomics is evolving rapidly, it is constructive to survey now pertinent concepts and breakthroughs...
January 16, 2018: Journal of Molecular and Cellular Cardiology
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