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

Sent on Saturday, 2013 March 30
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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1.	Nature. 2013 Mar 21;495(7441):293. doi: 10.1038/495293a. Gene-analysis firms reach for the cloud. Hayden EC.
	PMID: 23518540 [PubMed - indexed for MEDLINE]

What's new for 'JKB_daily1' in PubMed

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

Sent on Thursday, 2013 March 28
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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1.	Science. 2013 Mar 15;339(6125):1328-31. doi: 10.1126/science.1230593. Epub 2013 Jan 31. Proteomic mapping of mitochondria in living cells via spatially restricted enzymatic tagging. Rhee HW, Zou P, Udeshi ND, Martell JD, Mootha VK, Carr SA, Ting AY. Department of Chemistry, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. Abstract Microscopy and mass spectrometry (MS) are complementary techniques: The former provides spatiotemporal information in living cells, but only for a handful of recombinant proteins at a time, whereas the latter can detect thousands of endogenous proteins simultaneously, but only in lysed samples. Here, we introduce technology that combines these strengths by offering spatially and temporally resolved proteomic maps of endogenous proteins within living cells. Our method relies on a genetically targetable peroxidase enzyme that biotinylates nearby proteins, which are subsequently purified and identified by MS. We used this approach to identify 495 proteins within the human mitochondrial matrix, including 31 not previously linked to mitochondria. The labeling was exceptionally specific and distinguished between inner membrane proteins facing the matrix versus the intermembrane space (IMS). Several proteins previously thought to reside in the IMS or outer membrane, including protoporphyrinogen oxidase, were reassigned to the matrix by our proteomic data and confirmed by electron microscopy. The specificity of peroxidase-mediated proteomic mapping in live cells, combined with its ease of use, offers biologists a powerful tool for understanding the molecular composition of living cells.
	PMID: 23371551 [PubMed - indexed for MEDLINE]

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

Sent on Wednesday, 2013 March 27
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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1.	Nature. 2013 Feb 28;494(7438):416-9. doi: 10.1038/494416a. Big biology: The 'omes puzzle. Baker M.
	PMID: 23446398 [PubMed - indexed for MEDLINE]
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2.	Nat Genet. 2013 Feb;45(2):172-9. doi: 10.1038/ng.2517. Epub 2013 Jan 6. Genomic analysis of smooth tubercle bacilli provides insights into ancestry and pathoadaptation of Mycobacterium tuberculosis. Supply P, Marceau M, Mangenot S, Roche D, Rouanet C, Khanna V, Majlessi L, Criscuolo A, Tap J, Pawlik A, Fiette L, Orgeur M, Fabre M, Parmentier C, Frigui W, Simeone R, Boritsch EC, Debrie AS, Willery E, Walker D, Quail MA, Ma L, Bouchier C, Salvignol G, Sayes F, Cascioferro A, Seemann T, Barbe V, Locht C, Gutierrez MC, Leclerc C, Bentley SD, Stinear TP, Brisse S, Médigue C, Parkhill J, Cruveiller S, Brosch R. Institut National de la Santé et de la Recherche Médicale INSERM U1019, Center for Infection and Immunity of Lille, Lille, France. philip.supply@ibl.fr Abstract Global spread and limited genetic variation are hallmarks of M. tuberculosis, the agent of human tuberculosis. In contrast, Mycobacterium canettii and related tubercle bacilli that also cause human tuberculosis and exhibit unusual smooth colony morphology are restricted to East Africa. Here, we sequenced and analyzed the whole genomes of five representative strains of smooth tubercle bacilli (STB) using Sanger (4-5× coverage), 454/Roche (13-18× coverage) and/or Illumina DNA sequencing (45-105× coverage). We show that STB isolates are highly recombinogenic and evolutionarily early branching, with larger genome sizes, higher rates of genetic variation, fewer molecular scars and distinct CRISPR-Cas systems relative to M. tuberculosis. Despite the differences, all tuberculosis-causing mycobacteria share a highly conserved core genome. Mouse infection experiments showed that STB strains are less persistent and virulent than M. tuberculosis. We conclude that M. tuberculosis emerged from an ancestral STB-like pool of mycobacteria by gain of persistence and virulence mechanisms, and we provide insights into the molecular events involved.
	PMID: 23291586 [PubMed - indexed for MEDLINE]
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3.	Nat Genet. 2013 Feb;45(2):197-201. doi: 10.1038/ng.2507. Epub 2012 Dec 23. Exome array analysis identifies new loci and low-frequency variants influencing insulin processing and secretion. Huyghe JR, Jackson AU, Fogarty MP, Buchkovich ML, Stančáková A, Stringham HM, Sim X, Yang L, Fuchsberger C, Cederberg H, Chines PS, Teslovich TM, Romm JM, Ling H, McMullen I, Ingersoll R, Pugh EW, Doheny KF, Neale BM, Daly MJ, Kuusisto J, Scott LJ, Kang HM, Collins FS, Abecasis GR, Watanabe RM, Boehnke M, Laakso M, Mohlke KL. Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA. Abstract Insulin secretion has a crucial role in glucose homeostasis, and failure to secrete sufficient insulin is a hallmark of type 2 diabetes. Genome-wide association studies (GWAS) have identified loci contributing to insulin processing and secretion; however, a substantial fraction of the genetic contribution remains undefined. To examine low-frequency (minor allele frequency (MAF) 0.5-5%) and rare (MAF < 0.5%) nonsynonymous variants, we analyzed exome array data in 8,229 nondiabetic Finnish males using the Illumina HumanExome Beadchip. We identified low-frequency coding variants associated with fasting proinsulin concentrations at the SGSM2 and MADD GWAS loci and three new genes with low-frequency variants associated with fasting proinsulin or insulinogenic index: TBC1D30, KANK1 and PAM. We also show that the interpretation of single-variant and gene-based tests needs to consider the effects of noncoding SNPs both nearby and megabases away. This study demonstrates that exome array genotyping is a valuable approach to identify low-frequency variants that contribute to complex traits.
	PMID: 23263489 [PubMed - indexed for MEDLINE]
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4.	Nat Genet. 2013 Feb;45(2):191-6. doi: 10.1038/ng.2505. Epub 2012 Dec 23. Genome-wide association analyses in East Asians identify new susceptibility loci for colorectal cancer. Jia WH, Zhang B, Matsuo K, Shin A, Xiang YB, Jee SH, Kim DH, Ren Z, Cai Q, Long J, Shi J, Wen W, Yang G, Delahanty RJ; Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO); Colon Cancer Family Registry (CCFR), Ji BT, Pan ZZ, Matsuda F, Gao YT, Oh JH, Ahn YO, Park EJ, Li HL, Park JW, Jo J, Jeong JY, Hosono S, Casey G, Peters U, Shu XO, Zeng YX, Zheng W. State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China. Abstract To identify new genetic factors for colorectal cancer (CRC), we conducted a genome-wide association study in east Asians. By analyzing genome-wide data in 2,098 cases and 5,749 controls, we selected 64 promising SNPs for replication in an independent set of samples, including up to 5,358 cases and 5,922 controls. We identified four SNPs with association P values of 8.58 × 10(-7) to 3.77 × 10(-10) in the combined analysis of all east Asian samples. Three of the four were replicated in a study conducted in 26,060 individuals of European descent, with combined P values of 1.22 × 10(-10) for rs647161 (5q31.1), 6.64 × 10(-9) for rs2423279 (20p12.3) and 3.06 × 10(-8) for rs10774214 (12p13.32 near the CCND2 gene), derived from meta-analysis of data from both east Asian and European-ancestry populations. This study identified three new CRC susceptibility loci and provides additional insight into the genetics and biology of CRC.
	PMID: 23263487 [PubMed - indexed for MEDLINE]
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Sent on Friday, 2013 March 22
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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1.	Immunity. 2013 Jan 24;38(1):79-91. doi: 10.1016/j.immuni.2012.12.001. Epub 2012 Dec 27. Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Yona S, Kim KW, Wolf Y, Mildner A, Varol D, Breker M, Strauss-Ayali D, Viukov S, Guilliams M, Misharin A, Hume DA, Perlman H, Malissen B, Zelzer E, Jung S. Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel. Abstract Mononuclear phagocytes, including monocytes, macrophages, and dendritic cells, contribute to tissue integrity as well as to innate and adaptive immune defense. Emerging evidence for labor division indicates that manipulation of these cells could bear therapeutic potential. However, specific ontogenies of individual populations and the overall functional organization of this cellular network are not well defined. Here we report a fate-mapping study of the murine monocyte and macrophage compartment taking advantage of constitutive and conditional CX(3)CR1 promoter-driven Cre recombinase expression. We have demonstrated that major tissue-resident macrophage populations, including liver Kupffer cells and lung alveolar, splenic, and peritoneal macrophages, are established prior to birth and maintain themselves subsequently during adulthood independent of replenishment by blood monocytes. Furthermore, we have established that short-lived Ly6C(+) monocytes constitute obligatory steady-state precursors of blood-resident Ly6C(-) cells and that the abundance of Ly6C(+) blood monocytes dynamically controls the circulation lifespan of their progeny. Copyright © 2013 Elsevier Inc. All rights reserved.
	PMID: 23273845 [PubMed - indexed for MEDLINE]

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Sent on Friday, 2013 March 15
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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1.	Science. 2013 Mar 8;339(6124):1155-6. doi: 10.1126/science.1234106. Medicine. (De)personalized medicine. Horwitz RI, Cullen MR, Abell J, Christian JB. Clinical Evaluation Sciences, GlaxoSmithKline, King of Prussia, PA 19406, USA.
	PMID: 23471391 [PubMed - indexed for MEDLINE]

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Sent on Wednesday, 2013 March 13
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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1.	Nature. 2013 Feb 21;494(7437):296-9. doi: 10.1038/494296a. Neuroscience: As the worm turns. Hall SS.
	PMID: 23426306 [PubMed - indexed for MEDLINE]
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2.	Nature. 2013 Feb 21;494(7437):290-1. doi: 10.1038/494290a. Gene sequencing leaves the laboratory. Hayden EC.
	PMID: 23426300 [PubMed - indexed for MEDLINE]
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3.	Nature. 2013 Feb 14;494(7436):201-6. doi: 10.1038/nature11866. Epub 2013 Jan 30. Identification of a candidate therapeutic autophagy-inducing peptide. Shoji-Kawata S, Sumpter R, Leveno M, Campbell GR, Zou Z, Kinch L, Wilkins AD, Sun Q, Pallauf K, MacDuff D, Huerta C, Virgin HW, Helms JB, Eerland R, Tooze SA, Xavier R, Lenschow DJ, Yamamoto A, King D, Lichtarge O, Grishin NV, Spector SA, Kaloyanova DV, Levine B. Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas 75390, USA. Comment in Cell biology: Beneficial lessons from viruses. [Nature. 2013] Cell biology: Beneficial lessons from viruses.García-Sastre A. Nature. 2013 Feb 14; 494(7436):181-2. Epub 2013 Jan 30. Abstract The lysosomal degradation pathway of autophagy has a crucial role in defence against infection, neurodegenerative disorders, cancer and ageing. Accordingly, agents that induce autophagy may have broad therapeutic applications. One approach to developing such agents is to exploit autophagy manipulation strategies used by microbial virulence factors. Here we show that a peptide, Tat-beclin 1-derived from a region of the autophagy protein, beclin 1, which binds human immunodeficiency virus (HIV)-1 Nef-is a potent inducer of autophagy, and interacts with a newly identified negative regulator of autophagy, GAPR-1 (also called GLIPR2). Tat-beclin 1 decreases the accumulation of polyglutamine expansion protein aggregates and the replication of several pathogens (including HIV-1) in vitro, and reduces mortality in mice infected with chikungunya or West Nile virus. Thus, through the characterization of a domain of beclin 1 that interacts with HIV-1 Nef, we have developed an autophagy-inducing peptide that has potential efficacy in the treatment of human diseases.
	PMID: 23364696 [PubMed - indexed for MEDLINE]
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4.	Nature. 2013 Feb 14;494(7436):266-70. doi: 10.1038/nature11835. Epub 2013 Jan 20. A complete mass-spectrometric map of the yeast proteome applied to quantitative trait analysis. Picotti P, Clément-Ziza M, Lam H, Campbell DS, Schmidt A, Deutsch EW, Röst H, Sun Z, Rinner O, Reiter L, Shen Q, Michaelson JJ, Frei A, Alberti S, Kusebauch U, Wollscheid B, Moritz RL, Beyer A, Aebersold R. Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich CH-8093, Switzerland. paola.picotti@bc.biol.ethz.ch Abstract Experience from different fields of life sciences suggests that accessible, complete reference maps of the components of the system under study are highly beneficial research tools. Examples of such maps include libraries of the spectroscopic properties of molecules, or databases of drug structures in analytical or forensic chemistry. Such maps, and methods to navigate them, constitute reliable assays to probe any sample for the presence and amount of molecules contained in the map. So far, attempts to generate such maps for any proteome have failed to reach complete proteome coverage. Here we use a strategy based on high-throughput peptide synthesis and mass spectrometry to generate an almost complete reference map (97% of the genome-predicted proteins) of the Saccharomyces cerevisiae proteome. We generated two versions of this mass-spectrometric map, one supporting discovery-driven (shotgun) and the other supporting hypothesis-driven (targeted) proteomic measurements. Together, the two versions of the map constitute a complete set of proteomic assays to support most studies performed with contemporary proteomic technologies. To show the utility of the maps, we applied them to a protein quantitative trait locus (QTL) analysis, which requires precise measurement of the same set of peptides over a large number of samples. Protein measurements over 78 S. cerevisiae strains revealed a complex relationship between independent genetic loci, influencing the levels of related proteins. Our results suggest that selective pressure favours the acquisition of sets of polymorphisms that adapt protein levels but also maintain the stoichiometry of functionally related pathway members.
	PMID: 23334424 [PubMed - indexed for MEDLINE]
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Sender's message: Sepsis or genomics or altitude: JKB_daily1

Sent on Friday, 2013 March 08
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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1.	Science. 2013 Mar 1;339(6123):1033. doi: 10.1126/science.339.6123.1033-a. Data re-identification: protect the children. Gurwitz D. Comment on Research ethics. The complexities of genomic identifiability. [Science. 2013] Research ethics. The complexities of genomic identifiability.Rodriguez LL, Brooks LD, Greenberg JH, Green ED. Science. 2013 Jan 18; 339(6117):275-6.
	PMID: 23449578 [PubMed - indexed for MEDLINE]
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2.	Science. 2013 Mar 1;339(6123):1032-3. doi: 10.1126/science.339.6123.1032-c. Data re-identification: societal safeguards. Altman RB, Clayton EW, Kohane IS, Malin BA, Roden DM. Comment on Identifying personal genomes by surname inference. [Science. 2013] Identifying personal genomes by surname inference.Gymrek M, McGuire AL, Golan D, Halperin E, Erlich Y. Science. 2013 Jan 18; 339(6117):321-4.
	PMID: 23449577 [PubMed - indexed for MEDLINE]
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3.	Science. 2013 Mar 1;339(6123):1030-1. doi: 10.1126/science.339.6123.1030. Environmental science. Pollutants capture the high ground in the Himalayas. Qiu J.
	PMID: 23449574 [PubMed - indexed for MEDLINE]
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4.	Science. 2013 Mar 1;339(6123):1077-80. doi: 10.1126/science.1233009. Epub 2013 Jan 24. Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO. Clark VE, Erson-Omay EZ, Serin A, Yin J, Cotney J, Ozduman K, Avşar T, Li J, Murray PB, Henegariu O, Yilmaz S, Günel JM, Carrión-Grant G, Yilmaz B, Grady C, Tanrikulu B, Bakircioğlu M, Kaymakçalan H, Caglayan AO, Sencar L, Ceyhun E, Atik AF, Bayri Y, Bai H, Kolb LE, Hebert RM, Omay SB, Mishra-Gorur K, Choi M, Overton JD, Holland EC, Mane S, State MW, Bilgüvar K, Baehring JM, Gutin PH, Piepmeier JM, Vortmeyer A, Brennan CW, Pamir MN, Kiliç T, Lifton RP, Noonan JP, Yasuno K, Günel M. Department of Neurosurgery, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, CT 06510, USA. Abstract We report genomic analysis of 300 meningiomas, the most common primary brain tumors, leading to the discovery of mutations in TRAF7, a proapoptotic E3 ubiquitin ligase, in nearly one-fourth of all meningiomas. Mutations in TRAF7 commonly occurred with a recurrent mutation (K409Q) in KLF4, a transcription factor known for its role in inducing pluripotency, or with AKT1, a mutation known to activate the PI3K pathway. SMO mutations, which activate Hedgehog signaling, were identified in ~5% of non-NF2 mutant meningiomas. These non-NF2 meningiomas were clinically distinctive-nearly always benign, with chromosomal stability, and originating from the medial skull base. In contrast, meningiomas with mutant NF2 and/or chromosome 22 loss were more likely to be atypical, showing genomic instability, and localizing to the cerebral and cerebellar hemispheres. Collectively, these findings identify distinct meningioma subtypes, suggesting avenues for targeted therapeutics.
	PMID: 23348505 [PubMed - indexed for MEDLINE]
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Sent on Thursday, 2013 March 07
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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1.	Nat Med. 2013 Jan;19(1):9. doi: 10.1038/nm0113-9. Straight talk with...Stephen O'Brien. Interviewed by Elie Dolgin. O'Brien S. Abstract Stephen O'Brien joined the US National Cancer Institute as a post doc in 1971 and climbed the ranks to become head of the institute's Laboratory of Genomic Diversity, a position he held for 25 years. But, after four decades at the government agency, O'Brien was ready for something new. In December 2011, he stepped down and took up a three-year, $5 million 'megagrant' in Russia through a program started a year earlier by the Russian Ministry of Education and Science to attract big-name researchers to work at least part-time in that country. O'Brien used his money to help launch the Theodosius Dobzhansky Center for Genome Bioinformatics at Saint Petersburg State University. Although O'Brien is a cancer researcher, he has diverse scientific interests. He led the team that discovered the CCR5-Δ32 mutation that confers resistance to HIV, and he has helped document the remarkable genetic uniformity of African cheetahs. Recently, he and two California scientists started the Genome 10K project, which aims to sequence the genetic blueprints of 10,000 vertebrate species. On a trip back to the US, O'Brien spoke with Elie Dolgin about how comparative genomics and his new Russian center will help advance the search for new therapeutics.
	PMID: 23295996 [PubMed - indexed for MEDLINE]
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2.	Nat Med. 2013 Jan;19(1):57-64. doi: 10.1038/nm.2999. Epub 2012 Dec 2. Chemotherapy-triggered cathepsin B release in myeloid-derived suppressor cells activates the Nlrp3 inflammasome and promotes tumor growth. Bruchard M, Mignot G, Derangère V, Chalmin F, Chevriaux A, Végran F, Boireau W, Simon B, Ryffel B, Connat JL, Kanellopoulos J, Martin F, Rébé C, Apetoh L, Ghiringhelli F. Institut National de Santé et de Recherche Médicale (INSERM) U866, Dijon, France. Comment in Dual role of immunomodulation by anticancer chemotherapy. [Nat Med. 2013] Dual role of immunomodulation by anticancer chemotherapy.Shurin MR. Nat Med. 2013 Jan; 19(1):20-2. Abstract Chemotherapeutic agents are widely used for cancer treatment. In addition to their direct cytotoxic effects, these agents harness the host's immune system, which contributes to their antitumor activity. Here we show that two clinically used chemotherapeutic agents, gemcitabine (Gem) and 5-fluorouracil (5FU), activate the NOD-like receptor family, pyrin domain containing-3 protein (Nlrp3)-dependent caspase-1 activation complex (termed the inflammasome) in myeloid-derived suppressor cells (MDSCs), leading to production of interleukin-1β (IL-1β), which curtails anticancer immunity. Chemotherapy-triggered IL-1β secretion relied on lysosomal permeabilization and the release of cathepsin B, which bound to Nlrp3 and drove caspase-1 activation. MDSC-derived IL-1β induced secretion of IL-17 by CD4(+) T cells, which blunted the anticancer efficacy of the chemotherapy. Accordingly, Gem and 5FU exerted higher antitumor effects when tumors were established in Nlrp3(-/-) or Casp1(-/-) mice or wild-type mice treated with interleukin-1 receptor antagonist (IL-1Ra). Altogether, these results identify how activation of the Nlrp3 inflammasome in MDSCs by 5FU and Gem limits the antitumor efficacy of these chemotherapeutic agents.
	PMID: 23202296 [PubMed - indexed for MEDLINE]
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Sent on Wednesday, 2013 March 06
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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1.	Science. 2013 Feb 22;339(6122):913-5. doi: 10.1126/science.1228565. Biochemistry. Integrative structural biology. Ward AB, Sali A, Wilson IA. Department of Integrative Structural and Computational Biology, International AIDS Vaccine Initiative Neutralizing Antibody Center, Scripps Research Institute, La Jolla, CA 92037, USA. abward@scripps.edu
	PMID: 23430643 [PubMed - indexed for MEDLINE]

2.	Science. 2013 Feb 22;339(6122):912-3. doi: 10.1126/science.1235639. Immunology. Bacterial escape artists set afire. Cemma M, Brumell JH. Cell Biology Program, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada. Comment on Caspase-11 protects against bacteria that escape the vacuole. [Science. 2013] Caspase-11 protects against bacteria that escape the vacuole.Aachoui Y, Leaf IA, Hagar JA, Fontana MF, Campos CG, Zak DE, Tan MH, Cotter PA, Vance RE, Aderem A, et al. Science. 2013 Feb 22; 339(6122):975-8. Epub 2013 Jan 24.
	PMID: 23430642 [PubMed - indexed for MEDLINE]

3.	Science. 2013 Feb 22;339(6122):975-8. doi: 10.1126/science.1230751. Epub 2013 Jan 24. Caspase-11 protects against bacteria that escape the vacuole. Aachoui Y, Leaf IA, Hagar JA, Fontana MF, Campos CG, Zak DE, Tan MH, Cotter PA, Vance RE, Aderem A, Miao EA. Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Comment in Immunology. Bacterial escape artists set afire. [Science. 2013] Immunology. Bacterial escape artists set afire.Cemma M, Brumell JH. Science. 2013 Feb 22; 339(6122):912-3. Abstract Caspases are either apoptotic or inflammatory. Among inflammatory caspases, caspase-1 and -11 trigger pyroptosis, a form of programmed cell death. Whereas both can be detrimental in inflammatory disease, only caspase-1 has an established protective role during infection. Here, we report that caspase-11 is required for innate immunity to cytosolic, but not vacuolar, bacteria. Although Salmonella typhimurium and Legionella pneumophila normally reside in the vacuole, specific mutants (sifA and sdhA, respectively) aberrantly enter the cytosol. These mutants triggered caspase-11, which enhanced clearance of S. typhimurium sifA in vivo. This response did not require NLRP3, NLRC4, or ASC inflammasome pathways. Burkholderia species that naturally invade the cytosol also triggered caspase-11, which protected mice from lethal challenge with B. thailandensis and B. pseudomallei. Thus, caspase-11 is critical for surviving exposure to ubiquitous environmental pathogens.
	PMID: 23348507 [PubMed - indexed for MEDLINE]
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Sender's message: Sepsis or genomics or altitude: JKB_daily1

Sent on Tuesday, 2013 March 05
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 - 4 of 4

1.	Nature. 2013 Jan 24;493(7433):451. Genetic privacy. [No authors listed] Comment in Parental consent: Guarding children's genetic privacy. [Nature. 2013] Parental consent: Guarding children's genetic privacy.Lunshof JE, Gurwitz D. Nature. 2013 Feb 28; 494(7438):430.
	PMID: 23350074 [PubMed - indexed for MEDLINE]
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2.	Nature. 2013 Jan 17;493(7432):346-55. doi: 10.1038/nature11862. Metabolism of inflammation limited by AMPK and pseudo-starvation. O'Neill LA, Hardie DG. School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland. laoneill@tcd.ie Abstract Metabolic changes in cells that participate in inflammation, such as activated macrophages and T-helper 17 cells, include a shift towards enhanced glucose uptake, glycolysis and increased activity of the pentose phosphate pathway. Opposing roles in these changes for hypoxia-inducible factor 1α and AMP-activated protein kinase have been proposed. By contrast, anti-inflammatory cells, such as M2 macrophages, regulatory T cells and quiescent memory T cells, have lower glycolytic rates and higher levels of oxidative metabolism. Some anti-inflammatory agents might act by inducing, through activation of AMP-activated protein kinase, a state akin to pseudo-starvation. Altered metabolism may thus participate in the signal-directed programs that promote or inhibit inflammation.
	PMID: 23325217 [PubMed - indexed for MEDLINE]
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3.	Nature. 2013 Jan 17;493(7432):284. doi: 10.1038/493284a. Behaviour genes unearthed. Callaway E. Comment in Natural history. [Nature. 2013] Natural history.[No authors listed]Nature. 2013 Jan 17; 493(7432):272.
	PMID: 23325188 [PubMed - indexed for MEDLINE]
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4.	Nature. 2013 Jan 24;493(7433):557-60. doi: 10.1038/nature11716. Epub 2012 Nov 14. RNAi triggered by specialized machinery silences developmental genes and retrotransposons. Yamanaka S, Mehta S, Reyes-Turcu FE, Zhuang F, Fuchs RT, Rong Y, Robb GB, Grewal SI. Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Abstract RNA interference (RNAi) is a conserved mechanism in which small interfering RNAs (siRNAs) guide the degradation of cognate RNAs, but also promote heterochromatin assembly at repetitive DNA elements such as centromeric repeats. However, the full extent of RNAi functions and its endogenous targets have not been explored. Here we show that, in the fission yeast Schizosaccharomyces pombe, RNAi and heterochromatin factors cooperate to silence diverse loci, including sexual differentiation genes, genes encoding transmembrane proteins, and retrotransposons that are also targeted by the exosome RNA degradation machinery. In the absence of the exosome, transcripts are processed preferentially by the RNAi machinery, revealing siRNA clusters and a corresponding increase in heterochromatin modifications across large domains containing genes and retrotransposons. We show that the generation of siRNAs and heterochromatin assembly by RNAi is triggered by a mechanism involving the canonical poly(A) polymerase Pla1 and an associated RNA surveillance factor Red1, which also activate the exosome. Notably, siRNA production and heterochromatin modifications at these target loci are regulated by environmental growth conditions, and by developmental signals that induce gene expression during sexual differentiation. Our analyses uncover an interaction between RNAi and the exosome that is conserved in Drosophila, and show that differentiation signals modulate RNAi silencing to regulate developmental genes. PMCID: PMC3554839 [Available on 2013/7/24]
	PMID: 23151475 [PubMed - indexed for MEDLINE]
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