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Tomasetti, C.; Vogelstein, B. |
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Title |
Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions |
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Journal Article |
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Year  |
2015 |
Publication |
Science (New York, N.Y.) |
Abbreviated Journal |
Science |
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Volume |
347 |
Issue |
6217 |
Pages |
78-81 |
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Abstract |
Some tissue types give rise to human cancers millions of times more often than other tissue types. Although this has been recognized for more than a century, it has never been explained. Here, we show that the lifetime risk of cancers of many different types is strongly correlated (0.81) 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. This is important not only for understanding the disease but also for designing strategies to limit the mortality it causes. |
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Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, 1650 Orleans Street, Baltimore, MD 21205, USA. ctomasetti@jhu.edu vogelbe@jhmi.edu |
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0036-8075 |
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PMID:25554788 |
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CBM.UAM @ ccobaleda @ |
Serial |
538 |
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Author |
Bateman, C.M.; Alpar, D.; Ford, A.M.; Colman, S.M.; Wren, D.; Morgan, M.; Kearney, L.; Greaves, M. |
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Title |
Evolutionary trajectories of hyperdiploid ALL in monozygotic twins |
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Journal Article |
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Year |
2015 |
Publication |
Leukemia |
Abbreviated Journal |
Leukemia |
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Volume |
29 |
Issue |
1 |
Pages |
58-65 |
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Abstract |
Identical twins have provided unique insights on timing or sequence of genetic events in acute lymphoblastic leukaemia (ALL). To date, this has mainly focused on ALL with MLL or ETV6-RUNX1 fusions, with hyperdiploid ALL remaining less well characterised. We examined three pairs of monozygotic twins, two concordant and one discordant for hyperdiploid ALL, for single-nucleotide polymorphism (SNP)-defined copy number alterations (CNAs), IGH/L plus TCR gene rearrangements and mutations in NRAS, KRAS, FLT3 and PTPN11 genes. We performed whole exome sequencing in one concordant twin pair. Potential 'driver' CNAs were low, 0-3 per case, and all were different within a pair. One patient had an NRAS mutation that was lacking from leukaemic cells of the twin sibling. By exome sequencing, there were 12 nonsynonymous mutations found in one twin and 5 in the other, one of which in SCL44A2 was shared or identical. Concordant pairs had some identical IGH/L and TCR rearrangements. In the twin pair with discordant hyperdiploid ALL, the healthy co-twin had persistent low level hyperdiploid CD19+ cells that lacked a CNA present in the ALL cells of her sibling. From these data, we propose that hyperdiploid ALL arises in a pre-B cell in utero and mutational changes necessary for clinical ALL accumulate subclonally and postnatally. |
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Centre for Evolution and Cancer, The Institute of Cancer Research, Sutton, UK |
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0887-6924 |
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PMID:24897505 |
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CBM.UAM @ ccobaleda @ |
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544 |
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Li, C.; Chen, Z.; Yang, L.; Lv, B.; Liu, J.; Varsier, N.; Hadjem, A.; Wiart, J.; Xie, Y.; Ma, L.; Wu, T. |
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Title |
Generation of infant anatomical models for evaluating electromagnetic field exposures |
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Journal Article |
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Year |
2015 |
Publication |
Bioelectromagnetics |
Abbreviated Journal |
Bioelectromagnetics |
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36 |
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1 |
Pages |
10-26 |
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Keywords |
electromagnetic fields exposure; finite-difference time-domain; magnetic resonance; reconstruction; segmentation |
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Realistic anatomical modeling is essential in analyzing human exposure to electromagnetic fields. Infants have significant physical and anatomical differences compared with other age groups. However, few realistic infant models are available. In this work, we developed one 12-month-old male whole body model and one 17-month-old male head model from magnetic resonance images. The whole body and head models contained 28 and 30 tissues, respectively, at spatial resolution of 1 mm x 1 mm x 1 mm. Fewer identified tissues in the whole body model were a result of the low original image quality induced by the fast imaging sequence. The anatomical and physical parameters of the models were validated against findings in published literature (e.g., a maximum deviation as 18% in tissue mass was observed compared with the data from International Commission on Radiological Protection). Several typical exposure scenarios were realized for numerical simulation. Dosimetric comparison with various adult and child anatomical models was conducted. Significant differences in the physical and anatomical features between adult and child models demonstrated the importance of creating realistic infant models. Current safety guidelines for infant exposure to radiofrequency electromagnetic fields may not be conservative. Bioelectromagnetics. 35:10-26, 2015. (c) 2014 Wiley Periodicals, Inc. |
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China Academy of Telecommunication Research of Ministry of Industry and Information Technology, Beijing, China; College of Computer and Communication Engineering, University of Science and Technology Beijing, Beijing, China |
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0197-8462 |
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PMID:25328088 |
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CBM.UAM @ ccobaleda @ |
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584 |
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Edelman, N.B.; Fritz, T.; Nimpf, S.; Pichler, P.; Lauwers, M.; Hickman, R.W.; Papadaki-Anastasopoulou, A.; Ushakova, L.; Heuser, T.; Resch, G.P.; Saunders, M.; Shaw, J.A.; Keays, D.A. |
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Title |
No evidence for intracellular magnetite in putative vertebrate magnetoreceptors identified by magnetic screening |
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Journal Article |
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Year |
2015 |
Publication |
Proceedings of the National Academy of Sciences of the United States of America |
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Proc Natl Acad Sci U S A |
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112 |
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1 |
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262-267 |
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magnetite; magnetoreception; pigeons |
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The cellular basis of the magnetic sense remains an unsolved scientific mystery. One theory that aims to explain how animals detect the magnetic field is the magnetite hypothesis. It argues that intracellular crystals of the iron oxide magnetite (Fe3O4) are coupled to mechanosensitive channels that elicit neuronal activity in specialized sensory cells. Attempts to find these primary sensors have largely relied on the Prussian Blue stain that labels cells rich in ferric iron. This method has proved problematic as it has led investigators to conflate iron-rich macrophages with magnetoreceptors. An alternative approach developed by Eder et al. [Eder SH, et al. (2012) Proc Natl Acad Sci USA 109(30):12022-12027] is to identify candidate magnetoreceptive cells based on their magnetic moment. Here, we explore the utility of this method by undertaking a screen for magnetic cells in the pigeon. We report the identification of a small number of cells (1 in 476,000) with large magnetic moments (8-106 fAm(2)) from various tissues. The development of single-cell correlative light and electron microscopy (CLEM) coupled with electron energy loss spectroscopy (EELS) and energy-filtered transmission electron microscopy (EFTEM) permitted subcellular analysis of magnetic cells. This revealed the presence of extracellular structures composed of iron, titanium, and chromium accounting for the magnetic properties of these cells. Application of single-cell CLEM to magnetic cells from the trout failed to identify any intracellular structures consistent with biogenically derived magnetite. Our work illustrates the need for new methods to test the magnetite hypothesis of magnetosensation. |
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Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), 1030 Vienna, Austria; keays@imp.ac.at |
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0027-8424 |
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PMID:25535350 |
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CBM.UAM @ ccobaleda @ |
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588 |
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Author |
Zhang, Y.; Liu, X.; Zhang, J.; Li, N. |
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Title |
Short-term effects of extremely low frequency electromagnetic fields exposure on Alzheimer's disease in rats |
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Journal Article |
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Year |
2015 |
Publication |
International Journal of Radiation Biology |
Abbreviated Journal |
Int J Radiat Biol |
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91 |
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1 |
Pages |
28-34 |
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Extremely low frequency; cognition and memory; electromagnetic fields; rat |
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Abstract Purpose: With the development and widespread use of electromagnetic field (EMF) technology, recent studies are focusing on the effects of EMF on human health. Recently, extremely low frequency electromagnetic fields (ELF-EMF) have been studied with great interest due to their possible effects on Alzheimer's disease (AD). The objective of the present study was to investigate the interaction between ELF-EMF exposure and memory impairment in rats. MATERIALS AND METHODS: Twenty healthy male Sprague Dawley (SD) rats were randomly divided into two groups (n = 10). Animals were exposed to 100 muT/50 Hz ELF-EMF or subjected to sham exposure when 12 weeks old. After 12 weeks, the Morris water maze (MWM) was used to test the changes in cognitive and memory ability. Amyloid-beta (Abeta) content in cortex, hippocampus and plasma were measured by ELISA assays. The morphology of neuron was detected by H&E staining. RESULTS: After exposure, the body weight of rats showed no difference compared with the control group. The application of ELF-EMF did not induce any cognitive and memory impairment compared with the sham-exposure group. The determination of Abeta showed no significant change between the two groups, and there was no histological change in ELF-EMF exposure group. CONCLUSION: The present study indicated that short-term exposure of 100 muT/50 Hz ELF-EMF had no effects on cognition and memory of rats, and did not alter the expression of Abeta and the neuron morphology. However, more comprehensive studies are still required to elucidate the possible effects and underlying mechanisms of ELF-EMF exposure on living organisms. |
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High Voltage Research Institute, China Electric Power Research Institute , Wuhan , P. R. China |
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0955-3002 |
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PMID:25118893 |
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CBM.UAM @ ccobaleda @ |
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602 |
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