A global assessment of cancer genomic alterations in epigenetic mechanisms

Muhammad A Shah, Emily L Denton, Cheryl H Arrowsmith, Mathieu Lupien and Matthieu Schapira Abstract Background The notion that epigenetic mechanisms may be central to cancer initiation and progression is supported by recent next-generation sequencing efforts revealing that genes involved in chromatin-mediated signaling are recurrently mutated in cancer patients. Results Here, we analyze mutational and transcriptional profiles from TCGA and the ICGC across a collection 441 chromatin factors and histones. Chromatin factors essential for rapid replication are frequently overexpressed, and those that maintain genome stability frequently mutated. We identify novel mutation hotspots such as K36M in histone H3.1, and uncover…

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A Mitochondrial Paradigm of Metabolic and Degenerative Diseases, Aging, and Cancer: A Dawn for Evolutionary Medicine

Progressive increase in mtDNA 3243A>G heteroplasmy causes abrupt transcriptional reprogramming Wallace hypothesized mitochondrial dysfunction as a central role in a wide range of age-related disorders and various forms of cancer. Steadily rising increases in mitochondrial DNA mutations cause abrupt shifts in diseases. Discrete changes in nuclear gene expression in response to small increases in DNA mutant level are analogous to the phase shifts that is well known in physics: As heat is added, the ice abruptly turns to water or with more heat abruptly to steam. Therefore, a quantitative change that is an increasing proportion of mitochondrial DNA mutation results…

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Variation in cancer risk among tissues can be explained by the number of stem cell divisions

Tomasetti and Vogelstein show that the lifetime risk of cancers of many different types is strongly correlated with the total number of divisions of the normal self-renewing cells maintaining that tissue’s homeostasis. These results suggest that only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions. The majority is due to bad luck, that is, random mutations arising during DNA replication in normal, noncancerous stem cells. Tomasetti C, Vogelstein B (2015): Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science 2 January 2015:…

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Quantum entanglement between the electron clouds of nucleic acids in DNA

Rieper, Anders and Vedral modelled the electron clouds of nucleic acids in a single strand of DNA as a chain of coupled quantum harmonic oscillators with dipole-dipole interaction between nearest neighbours. As a main result, the entanglement contained in the chain coincides with the binding energy of the molecule. Derived in the limit of long distances and periodic potentials analytic expressions linking the entanglement witnesses to the energy reduction due to the quantum entanglement in the electron clouds. Rieper E, Anders J, Vedral V (2011) Quantum entanglement between the electron clouds of nucleic acids in DNA. arxiv.org/abs/1006.4053  

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Three-dimensional super-resolution microscopy of the inactive X chromosome territory reveals a collapse of its active nuclear compartment harboring distinct Xist RNA foci

Daniel Smeets, Yolanda Markaki, Volker J Schmid, Felix Kraus, Anna Tattermusch, Andrea Cerase, Michael Sterr, Susanne Fiedler, Justin Demmerle, Jens Popken, Heinrich Leonhardt, Neil Brockdorff, Thomas Cremer1, Lothar Schermelleh and Marion Cremer Abstract Background A Xist RNA decorated Barr body is the structural hallmark of the compacted inactive X territory in female mammals. Using super-resolution three-dimensional structured illumination microscopy (3D-SIM) and quantitative image analysis, we compared its ultrastructure with active chromosome territories (CTs) in human and mouse somatic cells, and explored the spatio-temporal process of Barr body formation at onset of inactivation in early differentiating mouse embryonic stem cells (ESCs)….

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Forscher des HIPS und des HZI finden neues Antibiotikum gegen gram-negative Bakterien

Die Erreger von Infektionserkrankungen Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumanii und Pseudomonas aeruginosa haben zwei große Gemeinsamkeiten: Sie gehören zu den sogenannten gram-negativen Bakterien und sind in Krankenhäusern besonders gefürchtet. Wissenschaftler des Helmholtz-Instituts für Pharmazeutische Forschung Saarland (HIPS) und des Helmholtz-Zentrums für Infektionsforschung (HZI) in Braunschweig haben nun ein potenzielles neues Antibiotikum entdeckt, das gegen diese schwer zu bekämpfenden Bakterien wirkt. Ihre Ergebnisse veröffentlichten die Forscher im renommierten Journal Angewandte Chemie International Edition. Immer mehr Keime entwickeln Resistenzen gegen Antibiotika, sodass diese einstigen Wunderwaffen ihre Wirkungskraft verlieren. Vor allem in Krankenhäusern stellt die steigende Anzahl resistenter Keime das Personal vor…

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