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Sender's message: Sepsis or genomics or altitude: JKB_daily1

Sent on Friday, 2014 May 16
Search: (sepsis[MeSH Terms] OR septic shock[MeSH Terms] OR altitude[MeSH Terms] OR genomics[MeSH Terms] OR genetics[MeSH Terms] OR retrotransposons[MeSH Terms] OR macrophage[MeSH Terms]) AND ("2009/8/8"[Publication Date] : "3000"[Publication Date]) AND (("Science"[Journal] OR "Nature"[Journal] OR "The New England journal of medicine"[Journal] OR "Lancet"[Journal] OR "Nature genetics"[Journal] OR "Nature medicine"[Journal]) OR (Hume DA[Author] OR Baillie JK[Author] OR Faulkner, Geoffrey J[Author]))

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PubMed Results

Items 1 - 3 of 3

1.	Science. 2014 Apr 25;344(6182):416-20. doi: 10.1126/science.1248575. Single-cell genomics reveals hundreds of coexisting subpopulations in wild Prochlorococcus. Kashtan N1, Roggensack SE, Rodrigue S, Thompson JW, Biller SJ, Coe A, Ding H, Marttinen P, Malmstrom RR, Stocker R, Follows MJ, Stepanauskas R, Chisholm SW. Author information: 1Department of Civil and Environmental Engineering, Massachusetts Institute of Technology (MIT), 77 Massachusetts Avenue, Cambridge, MA 02139, USA. Comment in Genetics. Being selective in the Prochlorococcus collective. [Science. 2014] Genetics. Being selective in the Prochlorococcus collective.Bowler C, Scanlan DJ. Science. 2014 Apr 25; 344(6182):366-7. Abstract Extensive genomic diversity within coexisting members of a microbial species has been revealed through selected cultured isolates and metagenomic assemblies. Yet, the cell-by-cell genomic composition of wild uncultured populations of co-occurring cells is largely unknown. In this work, we applied large-scale single-cell genomics to study populations of the globally abundant marine cyanobacterium Prochlorococcus. We show that they are composed of hundreds of subpopulations with distinct "genomic backbones," each backbone consisting of a different set of core gene alleles linked to a small distinctive set of flexible genes. These subpopulations are estimated to have diverged at least a few million years ago, suggesting ancient, stable niche partitioning. Such a large set of coexisting subpopulations may be a general feature of free-living bacterial species with huge populations in highly mixed habitats.
	PMID: 24763590 [PubMed - indexed for MEDLINE]
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2.	Nature. 2014 Apr 10;508(7495):222-7. doi: 10.1038/nature13194. Epub 2014 Apr 2. Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer strategy. Huber KV1, Salah E2, Radic B1, Gridling M1, Elkins JM2, Stukalov A1, Jemth AS3, Göktürk C3, Sanjiv K3, Strömberg K3, Pham T3, Berglund UW3, Colinge J1, Bennett KL1, Loizou JI1, Helleday T3, Knapp S2, Superti-Furga G1. Author information: 1CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria. 2Nuffield Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK. 3Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17121 Stockholm, Sweden. Comment in Cancer: Damage prevention targeted. [Nature. 2014] Cancer: Damage prevention targeted.Dominissini D, He C. Nature. 2014 Apr 10; 508(7495):191-2. Epub 2014 Apr 2. Abstract Activated RAS GTPase signalling is a critical driver of oncogenic transformation and malignant disease. Cellular models of RAS-dependent cancers have been used to identify experimental small molecules, such as SCH51344, but their molecular mechanism of action remains generally unknown. Here, using a chemical proteomic approach, we identify the target of SCH51344 as the human mutT homologue MTH1 (also known as NUDT1), a nucleotide pool sanitizing enzyme. Loss-of-function of MTH1 impaired growth of KRAS tumour cells, whereas MTH1 overexpression mitigated sensitivity towards SCH51344. Searching for more drug-like inhibitors, we identified the kinase inhibitor crizotinib as a nanomolar suppressor of MTH1 activity. Surprisingly, the clinically used (R)-enantiomer of the drug was inactive, whereas the (S)-enantiomer selectively inhibited MTH1 catalytic activity. Enzymatic assays, chemical proteomic profiling, kinome-wide activity surveys and MTH1 co-crystal structures of both enantiomers provide a rationale for this remarkable stereospecificity. Disruption of nucleotide pool homeostasis via MTH1 inhibition by (S)-crizotinib induced an increase in DNA single-strand breaks, activated DNA repair in human colon carcinoma cells, and effectively suppressed tumour growth in animal models. Our results propose (S)-crizotinib as an attractive chemical entity for further pre-clinical evaluation, and small-molecule inhibitors of MTH1 in general as a promising novel class of anticancer agents.
	PMID: 24695225 [PubMed - indexed for MEDLINE]
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3.	PLoS Genet. 2013 Nov;9(11):e1003944. doi: 10.1371/journal.pgen.1003944. Epub 2013 Nov 7. Retrotransposon silencing during embryogenesis: dicer cuts in LINE. Faulkner GJ. Author information: Cancer Biology Program, Mater Medical Research Institute, South Brisbane, Australia ; School of Biomedical Sciences, University of Queensland, Brisbane, Australia. Comment on RNAi-dependent and independent control of LINE1 accumulation and mobility in mouse embryonic stem cells. [PLoS Genet. 2013] RNAi-dependent and independent control of LINE1 accumulation and mobility in mouse embryonic stem cells.Ciaudo C, Jay F, Okamoto I, Chen CJ, Sarazin A, Servant N, Barillot E, Heard E, Voinnet O. PLoS Genet. 2013 Nov; 9(11):e1003791. Epub 2013 Nov 7. PMCID: PMC3820789 Free PMC Article
	PMID: 24244199 [PubMed - indexed for MEDLINE]
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