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https://www.readbyqxmd.com/read/29458203/precision-pharmacology-for-alzheimer-s-disease
#1
REVIEW
Harald Hampel, Andrea Vergallo, Lisi Flores Aguilar, Norbert Benda, Karl Broich, A Claudio Cuello, Jeffrey Cummings, Bruno Dubois, Howard J Federoff, Massimo Fiandaca, Remy Genthon, Marion Haberkamp, Eric Karran, Mark Mapstone, George Perry, Lon S Schneider, Lindsay A Welikovitch, Janet Woodcock, Filippo Baldacci, Simone Lista
The complex multifactorial nature of polygenic Alzheimer's disease (AD) presents significant challenges for drug development. AD pathophysiology is progressing in a non-linear dynamic fashion across multiple systems levels - from molecules to organ systems - and through adaptation, to compensation, and decompensation to systems failure. Adaptation and compensation maintain homeostasis: a dynamic equilibrium resulting from the dynamic non-linear interaction between genome, epigenome, and environment. An individual vulnerability to stressors exists on the basis of individual triggers, drivers, and thresholds accounting for the initiation and failure of adaptive and compensatory responses...
February 16, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29457866/epigenetic-effects-of-metformin-from-molecular-mechanisms-to-clinical-implications
#2
REVIEW
S C Bridgeman, G C Ellison, P E Melton, P Newsholme, Cds Mamotte
There is a growing body of evidence that links epigenetic modifications to type 2 diabetes. Researchers have more recently investigated effects of commonly used medications, including those prescribed for diabetes, on epigenetic processes. This work reviews the influence of the widely used antidiabetic drug metformin on epigenomics, microRNA levels and subsequent gene expression and potential clinical implications. Metformin may influence the activity of numerous epigenetic modifying enzymes, mostly via modulating the activation of AMP-activated protein kinase (AMPK)...
February 19, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29456765/peripheral-blood-epi-signature-of-claes-jensen-syndrome-enables-sensitive-and-specific-identification-of-patients-and-healthy-carriers-with-pathogenic-mutations-in-kdm5c
#3
Laila C Schenkel, Erfan Aref-Eshghi, Cindy Skinner, Peter Ainsworth, Hanxin Lin, Guillaume Paré, David I Rodenhiser, Charles Schwartz, Bekim Sadikovic
Background: Claes-Jensen syndrome is an X-linked inherited intellectual disability caused by mutations in the KDM5C gene. Kdm5c is a histone lysine demethylase involved in histone modifications and chromatin remodeling. Males with hemizygous mutations in KDM5C present with intellectual disability and facial dysmorphism, while most heterozygous female carriers are asymptomatic. We hypothesized that loss of Kdm5c function may influence other components of the epigenomic machinery including DNA methylation in affected patients...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29456242/bacterial-pathogenesis-channelling-the-host-epigenome
#4
Andrea Du Toit
No abstract text is available yet for this article.
February 19, 2018: Nature Reviews. Microbiology
https://www.readbyqxmd.com/read/29452938/harnessing-natural-dna-modifying-activities-for-editing-of-the-genome-and-epigenome
#5
REVIEW
Jamie E DeNizio, Emily K Schutsky, Kiara N Berrios, Monica Yun Liu, Rahul M Kohli
The introduction of site-specific DNA modifications to the genome or epigenome presents great opportunities for manipulating biological systems. Such changes are now possible through the combination of DNA-modifying enzymes with targeting modules, including dCas9, that can localize the enzymes to specific sites. In this review, we take a DNA modifying enzyme-centric view of recent advances. We highlight the variety of natural DNA-modifying enzymes-including DNA methyltransferases, oxygenases, deaminases, and glycosylases-that can be used for targeted editing and discuss how insights into the structure and function of these enzymes has further expanded editing potential by introducing enzyme variants with altered activities or by improving spatiotemporal control of modifications...
February 13, 2018: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/29452662/pathogenesis-of-follicular-lymphoma
#6
REVIEW
Tracy Lackraj, Rashmi Goswami, Robert Kridel
Follicular lymphoma (FL) is presented as a germinal centre B cell lymphoma that is characterized by an indolent clinical course, but remains - paradoxically - largely incurable to date. The last years have seen significant progress in our understanding of FL lymphomagenesis, which is a multi-step process beginning in the bone marrow with the hallmark t(14;18)(q32;q21) translocation. The pathobiology of FL is complex and combines broad somatic changes at the level of both the genome and the epigenome, the latter evidenced by highly recurrent mutations in chromatin-modifying genes such as KMT2D and CREBBP...
March 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29451304/distinct-methylation-profile-of-mucinous-ovarian-carcinoma-reveals-susceptibility-to-proteasome-inhibitors
#7
Phui-Ly Liew, Rui-Lan Huang, Yu-Chun Weng, Chia-Lang Fang, Tim Hui-Ming Huang, Hung-Cheng Lai
Mucinous type of epithelial ovarian cancer (MuOC) is a unique subtype with a poor survival outcome in recurrent and advanced stages. The role of type-specific epigenomics and its clinical significance remain uncertain. We analyzed the methylomic profiles of six benign mucinous adenomas, 24 MuOCs, 103 serous type of epithelial ovarian cancers (SeOCs), and 337 nonepithelial ovarian cancers. MuOC and SeOC exhibited distinct DNA methylation profiles comprising 101 genes, 81 of which exhibited low methylation in MuOC and were associated with the response to glucocorticoid, ATP hydrolysis-coupled proton transport, proteolysis involved in the cellular protein catabolic process, and ion transmembrane transport...
February 16, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29450572/plant-genetics-and-molecular-biology-an-introduction
#8
Rajeev K Varshney, Manish K Pandey, Annapurna Chitikineni
The rapidly evolving technologies can serve as a potential growth engine in agriculture as many of these technologies have revolutionized several industries in the recent past. The tremendous advancements in biotechnology methods, cost-effective sequencing technology, refinement of genomic tools, and standardization of modern genomics-assisted breeding methods hold great promise in taking the global agriculture to the next level through development of improved climate-smart seeds. These technologies can dramatically increase our capacity to understand the molecular basis of traits and utilize the available resources for accelerated development of stable high-yielding, nutritious, input-use efficient, and climate-smart crop varieties...
February 16, 2018: Advances in Biochemical Engineering/biotechnology
https://www.readbyqxmd.com/read/29449903/specific-or-not-specific-recruitment-of-dnmts-for-dna-methylation-an-epigenetic-dilemma
#9
REVIEW
Eric Hervouet, Paul Peixoto, Régis Delage-Mourroux, Michaël Boyer-Guittaut, Pierre-François Cartron
Our current view of DNA methylation processes is strongly moving: First, even if it was generally admitted that DNMT3A and DNMT3B are associated with de novo methylation and DNMT1 is associated with inheritance DNA methylation, these distinctions are now not so clear. Secondly, since one decade, many partners of DNMTs have been involved in both the regulation of DNA methylation activity and DNMT recruitment on DNA. The high diversity of interactions and the combination of these interactions let us to subclass the different DNMT-including complexes...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29449798/dna-methylation-master-or-slave-of-neural-fate-decisions
#10
REVIEW
Stefan H Stricker, Magdalena Götz
The pristine formation of complex organs depends on sharp temporal and spatial control of gene expression. Therefore, epigenetic mechanisms have been frequently attributed a central role in controlling cell fate determination. A prime example for this is the first discovered and still most studied epigenetic mark, DNA methylation, and the development of the most complex mammalian organ, the brain. Recently, the field of epigenetics has advanced significantly: new DNA modifications were discovered, epigenomic profiling became widely accessible, and methods for targeted epigenomic manipulation have been developed...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29448075/improving-mass-univariate-analysis-of-neuroimaging-data-by-modelling-important-unknown-covariates-application-to-epigenome-wide-association-studies
#11
Bryan Guillaume, Changqing Wang, Joann Poh, Mo Jun Shen, Mei Lyn Ong, Pei Fang Tan, Neerja Karnani, Michael Meaney, Anqi Qiu
Statistical inference on neuroimaging data is often conducted using a mass-univariate model, equivalent to fitting a linear model at every voxel with a known set of covariates. Due to the large number of linear models, it is challenging to check if the selection of covariates is appropriate and to modify this selection adequately. The use of standard diagnostics, such as residual plotting, is clearly not practical for neuroimaging data. However, the selection of covariates is crucial for linear regression to ensure valid statistical inference...
February 12, 2018: NeuroImage
https://www.readbyqxmd.com/read/29447015/optogenetics-in-cancer-drug-discovery
#12
Michał Kiełbus, Jakub Czapiński, Adrian Odrzywolski, Grażyna Stasiak, Kamila Szymańska, Joanna Kałafut, Michał Kos, Krzysztof Giannopoulos, Andrzej Stepulak, Adolfo Rivero-Müller
The discovery and domestication of biomolecules that respond to light has taken a light of its own, providing new molecular tools with incredible spatio-temporal resolution to manipulate cellular behavior. Areas covered: The authors herein analyze the current optogenetic tools in light of their current, and potential, uses in cancer drug discovery, biosafety and cancer biology. Expert opinion: The pipeline from drug discovery to the clinic is plagued with drawbacks, where most drugs fail in either efficacy or safety...
February 15, 2018: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/29445860/origin-and-initiation-mechanisms-of-neuroblastoma
#13
REVIEW
Shoma Tsubota, Kenji Kadomatsu
Neuroblastoma is an embryonal malignancy that affects normal development of the adrenal medulla and paravertebral sympathetic ganglia in early childhood. Extensive studies have revealed the molecular characteristics of human neuroblastomas, including abnormalities at genome, epigenome and transcriptome levels. However, neuroblastoma initiation mechanisms and even its origin are long-standing mysteries. In this review article, we summarize the current knowledge about normal development of putative neuroblastoma sources, namely sympathoadrenal lineage of neural crest cells and Schwann cell precursors that were recently identified as the source of adrenal chromaffin cells...
February 14, 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/29442595/dietary-modulation-of-the-epigenome
#14
Folami Y Ideraabdullah, Steven H Zeisel
Epigenetics is the study of heritable mechanisms that can modify gene activity and phenotype without modifying the genetic code. The basis for the concept of epigenetics originated more than 2,000 yr ago as a theory to explain organismal development. However, the definition of epigenetics continues to evolve as we identify more of the components that make up the epigenome and dissect the complex manner by which they regulate and are regulated by cellular functions. A substantial and growing body of research shows that nutrition plays a significant role in regulating the epigenome...
April 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29440655/functional-variants-identified-efficiently-through-an-integrated-transcriptome-and-epigenome-analysis
#15
Fanlin Meng, Guohong Yuan, Xiurui Zhu, Yiming Zhou, Dong Wang, Yong Guo
Although genome-wide association studies (GWAS) have identified numerous genetic loci associated with complex diseases, the underlying molecular mechanisms of how these loci contribute to disease pathogenesis remain largely unknown, due to the lack of an efficient strategy to identify these risk variants. Here, we proposed a new strategy termed integrated transcriptome and epigenome analysis (iTEA) to identify functional genetic variants in non-coding elements. We considered type 2 diabetes mellitus as a model and identified a well-known diabetic risk variant rs35767 using iTEA...
February 13, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29439385/alv-integration-associated-hypomethylation-at-the-tert-promoter-locus
#16
Gary Lam, Karen Beemon
Avian leukosis virus (ALV) is a simple retrovirus that can induce B-cell lymphoma in chicken(s) and other birds by insertional mutagenesis. The promoter region of telomerase reverse transcriptase (TERT) has been identified as an important integration site for tumorigenesis. Tumors with TERT promoter integrations are associated with increased TERT expression. The mechanism of this activation is still under investigation. We asked whether insertion of proviral DNA perturbs the epigenome of the integration site and, subsequently, impacts the regulation of neighboring genes...
February 10, 2018: Viruses
https://www.readbyqxmd.com/read/29438498/chromswitch-a-flexible-method-to-detect-chromatin-state-switches
#17
Selin Jessa, Claudia L Kleinman, John Hancock
Summary: Chromatin state plays a major role in controlling gene expression, and comparative analysis of ChIP-seq data is key to understanding epigenetic regulation. We present chromswitch, an R/Bioconductor package to integrate epigenomic data in a defined window of interest to detect an overall switch in chromatin state. Chromswitch accurately classifies a benchmarking dataset, and when applied genome-wide, the tool successfully detects chromatin changes that result in brain-specific expression...
February 9, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29436575/identification-of-novel-hyper-%C3%A2-or-hypomethylated-cpg-sites-and-genes-associated-with-atherosclerotic-plaque-using-an-epigenome-wide-association-study
#18
Yoshiji Yamada, Hideki Horibe, Mitsutoshi Oguri, Jun Sakuma, Ichiro Takeuchi, Yoshiki Yasukochi, Kimihiko Kato, Motoji Sawabe
DNA methylation is an important epigenetic modification that has been implicated in the pathogenesis of atherosclerosis. Although previous studies have identified various CpG sites and genes whose methylation is associated with atherosclerosis in populations with European or Mexican ancestry, the genome‑wide pattern of DNA methylation in the atherosclerotic human aorta is yet to be elucidated in Japanese individuals. In the present study, a genome‑wide analysis of DNA methylation at ~853,000 CpG sites was performed using 128 postmortem aortic intima specimens obtained from 64 Japanese patients...
February 2, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29436261/an-epigenomic-approach-to-identifying-differential-overlapping-and-cis-acting-lncrnas-in-cisplatin-resistant-cancer-cells
#19
Olga Vera, Carlos Rodriguez-Antolin, Javier de Castro, Florian A Karreth, Thomas A Sellers, Inmaculada Ibañez de Caceres
Long noncoding RNAs (lncRNAs) are critical regulators of cell biology whose alteration can lead to the development of diseases such as cancer. The potential role of lncRNAs and their epigenetic regulation in response to platinum treatment are largely unknown. We analyzed four paired cisplatin-sensitive/resistant non-small cell lung cancer and ovarian cancer cell lines. The epigenetic landscape of overlapping and cis-acting lncRNAs was determined by combining human microarray data on 30,586 lncRNAs and 20,109 protein coding mRNAs with whole-genome bisulfite sequencing...
February 13, 2018: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29434619/from-bioengineering-to-crispr-cas9-a-personal-retrospective-of-20-years-of-research-in-programmable-genome-targeting
#20
Albert Jeltsch
Genome targeting of restriction enzymes and DNA methyltransferases has many important applications including genome and epigenome editing. 15-20 years ago, my group was involved in the development of approaches for programmable genome targeting, aiming to connect enzymes with an oligodeoxynucleotide (ODN), which could form a sequence-specific triple helix at the genomic target site. Importantly, the target site of such enzyme-ODN conjugate could be varied simply by altering the ODN sequence promising great applicative values...
2018: Frontiers in Genetics
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