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

Sent on Thursday, 2012 July 19
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 - 5 of 5

1.	Nature. 2012 Jun 13;486(7402):271-5. doi: 10.1038/nature11090. Control of a Salmonella virulence locus by an ATP-sensing leader messenger RNA. Lee EJ, Groisman EA. Source Howard Hughes Medical Institute, Yale School of Medicine, Section of Microbial Pathogenesis, New Haven, Connecticut 06536-0812, USA. Abstract The facultative intracellular pathogen Salmonella enterica resides within a membrane-bound compartment inside macrophages. This compartment must be acidified for Salmonella to survive within macrophages, possibly because acidic pH promotes expression of Salmonella virulence proteins. We reasoned that Salmonella might sense its surroundings have turned acidic not only upon protonation of the extracytoplasmic domain of a protein sensor but also by an increase in cytosolic ATP levels, because conditions that enhance the proton gradient across the bacterial inner membrane stimulate ATP synthesis. Here we report that an increase in cytosolic ATP promotes transcription of the coding region for the virulence gene mgtC, which is the most highly induced horizontally acquired gene when Salmonella is inside macrophages. This transcript is induced both upon media acidification and by physiological conditions that increase ATP levels independently of acidification. ATP is sensed by the coupling/uncoupling of transcription of the unusually long mgtC leader messenger RNA and translation of a short open reading frame located in this region. A mutation in the mgtC leader messenger RNA that eliminates the response to ATP hinders mgtC expression inside macrophages and attenuates Salmonella virulence in mice. Our results define a singular example of an ATP-sensing leader messenger RNA. Moreover, they indicate that pathogens can interpret extracellular cues by the impact they have on cellular metabolites.
	PMID: 22699622 [PubMed - indexed for MEDLINE]
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2.	Nature. 2012 Apr 29;486(7402):266-70. doi: 10.1038/nature11114. The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma. Pérez-Mancera PA, Rust AG, van der Weyden L, Kristiansen G, Li A, Sarver AL, Silverstein KA, Grützmann R, Aust D, Rümmele P, Knösel T, Herd C, Stemple DL, Kettleborough R, Brosnan JA, Li A, Morgan R, Knight S, Yu J, Stegeman S, Collier LS, ten Hoeve JJ, de Ridder J, Klein AP, Goggins M, Hruban RH, Chang DK, Biankin AV, Grimmond SM; Australian Pancreatic Cancer Genome Initiative, Wessels LF, Wood SA, Iacobuzio-Donahue CA, Pilarsky C, Largaespada DA, Adams DJ, Tuveson DA. Collaborators: Biankin AV, Johns AL, Mawson A, Chang DK, Brancato MA, Rowe SJ, Simpson SL, Martyn-Smith M, Chantrill LA, Chin VT, Chou A, Cowley MJ, Humphris JL, Jones MD, Mead R, Nagrial AM, Pajic M, Pettit J, Pinese M, Rooman I, Wu J, Daly RJ, Musgrove EA, Sutherland RL, Grimmond SM, Waddell N, Kassahn KS, Miller DK, Wilson PJ, Patch AM, Song S, Harliwong I, Idrisoglu S, Nourse C, Nourbakhsh E, Manning S, Wani S, Gongora M, Anderson M, Holmes O, Leonard C, Taylor D, Wood S, Xu C, Nones K, Fink J, Christ A, Bruxner T, Cloonan N, Newell F, Pearson JV, Samra JS, Gill AJ, Pavlakis N, Guminski A, Toon C, Blankin AV, Asghari R, Merrett ND, Chang DK, Pavey DA, Das A, Cosman PH, Ismail K, O'Connor C, Lam VW, McLeod D, Pleass HC, James V, Kench JG, Cooper CL, Joseph D, Sandroussi C, Crawford L, Texler M, Forrest C, Laycock A, Epari KP, Ballal M, Fletcher DR, Mukhedkar S, Spry NA, DeBoer B, Chai M, Feeney K, Zeps N, Beilin M, Nguyen NQ, Ruszkiewicz AR, Worthley C, Tan CP, Debrencini T, Chen J, Brooke-Smith ME, Papangelis V, Tang H, Barbour AP, Clouston AD, Martin P, O'Rourke TJ, Chiang A, Fawcet JW, Slater K, Yeung S, Hatzifotis M, Hodgkinson P, Christophi C, Nikfarjam M, Eshleman JR, Hruban RH, Maitra A, Iacobuzio-Donahue CA, Schulick RD, Wolfgang CL, Morgan RA, Lawlor RT, Beghelli S, Corbo V, Scardoni M, Bassi C, Tempero MA. Source Li Ka Shing Centre, Cambridge Research Institute, Cancer Research UK, Cambridge CB2 0RE, UK. Abstract Pancreatic ductal adenocarcinoma (PDA) remains a lethal malignancy despite much progress concerning its molecular characterization. PDA tumours harbour four signature somatic mutations in addition to numerous lower frequency genetic events of uncertain significance. Here we use Sleeping Beauty (SB) transposon-mediated insertional mutagenesis in a mouse model of pancreatic ductal preneoplasia to identify genes that cooperate with oncogenic Kras(G12D) to accelerate tumorigenesis and promote progression. Our screen revealed new candidate genes for PDA and confirmed the importance of many genes and pathways previously implicated in human PDA. The most commonly mutated gene was the X-linked deubiquitinase Usp9x, which was inactivated in over 50% of the tumours. Although previous work had attributed a pro-survival role to USP9X in human neoplasia, we found instead that loss of Usp9x enhances transformation and protects pancreatic cancer cells from anoikis. Clinically, low USP9X protein and messenger RNA expression in PDA correlates with poor survival after surgery, and USP9X levels are inversely associated with metastatic burden in advanced disease. Furthermore, chromatin modulation with trichostatin A or 5-aza-2'-deoxycytidine elevates USP9X expression in human PDA cell lines, indicating a clinical approach for certain patients. The conditional deletion of Usp9x cooperated with Kras(G12D) to accelerate pancreatic tumorigenesis in mice, validating their genetic interaction. We propose that USP9X is a major tumour suppressor gene with prognostic and therapeutic relevance in PDA. PMCID: PMC3376394 [Available on 2012/10/29]
	PMID: 22699621 [PubMed - indexed for MEDLINE]
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3.	Nature. 2012 Jun 13;486(7402):215-21. doi: 10.1038/nature11209. A framework for human microbiome research. Human Microbiome Project Consortium. Collaborators: Methé BA, Nelson KE, Pop M, Creasy HH, Giglio MG, Huttenhower C, Gevers D, Petrosino JF, Abubucker S, Badger JH, Chinwalla AT, Earl AM, FitzGerald MG, Fulton RS, Hallsworth-Pepin K, Lobos EA, Madupu R, Magrini V, Martin JC, Mitreva M, Muzny DM, Sodergren EJ, Versalovic J, Wollam AM, Worley KC, Wortman JR, Young SK, Zeng Q, Aagaard KM, Abolude OO, Allen-Vercoe E, Alm EJ, Alvarado L, Andersen GL, Anderson S, Appelbaum E, Arachchi HM, Armitage G, Arze CA, Ayvaz T, Baker CC, Begg L, Belachew T, Bhonagiri V, Bihan M, Blaser MJ, Bloom T, Bonazzi VR, Brooks P, Buck GA, Buhay CJ, Busam DA, Campbell JL, Canon SR, Cantarel BL, Chain PS, Chen IM, Chen L, Chhibba S, Chu K, Ciulla DM, Clemente JC, Clifton SW, Conlan S, Crabtree J, Cutting MA, Davidovics NJ, Davis CC, DeSantis TZ, Deal C, Delehaunty KD, Dewhirst FE, Deych E, Ding Y, Dooling DJ, Dugan SP, Dunne W Jr, Durkin A, Edgar RC, Erlich RL, Farmer CN, Farrell RM, Faust K, Feldgarden M, Felix VM, Fisher S, Fodor AA, Forney L, Foster L, Di Francesco V, Friedman J, Friedrich DC, Fronick CC, Fulton LL, Gao H, Garcia N, Giannoukos G, Giblin C, Giovanni MY, Goldberg JM, Goll J, Gonzalez A, Griggs A, Gujja S, Haas BJ, Hamilton HA, Harris EL, Hepburn TA, Herter B, Hoffmann DE, Holder ME, Howarth C, Huang KH, Huse SM, Izard J, Jansson JK, Jiang H, Jordan C, Joshi V, Katancik JA, Keitel WA, Kelley ST, Kells C, Kinder-Haake S, King NB, Knight R, Knights D, Kong HH, Koren O, Koren S, Kota KC, Kovar CL, Kyrpides NC, La Rosa PS, Lee SL, Lemon KP, Lennon N, Lewis CM, Lewis L, Ley RE, Li K, Liolios K, Liu B, Liu Y, Lo CC, Lozupone CA, Lunsford R, Madden T, Mahurkar AA, Mannon PJ, Mardis ER, Markowitz VM, Mavrommatis K, McCorrison JM, McDonald D, McEwen J, McGuire AL, McInnes P, Mehta T, Mihindukulasuriya KA, Miller JR, Minx PJ, Newsham I, Nusbaum C, O'Laughlin M, Orvis J, Pagani I, Palaniappan K, Patel SM, Pearson M, Peterson J, Podar M, Pohl C, Pollard KS, Priest ME, Proctor LM, Qin X, Raes J, Ravel J, Reid JG, Rho M, Rhodes R, Riehle KP, Rivera MC, Rodriguez-Mueller B, Rogers YH, Ross MC, Russ C, Sanka RK, Sankar P, Sathirapongsasuti J, Schloss JA, Schloss PD, Schmidt TM, Scholz M, Schriml L, Schubert AM, Segata N, Segre JA, Shannon WD, Sharp RR, Sharpton TJ, Shenoy N, Sheth NU, Simone GA, Singh I, Smillie CS, Sobel JD, Sommer DD, Spicer P, Sutton GG, Sykes SM, Tabbaa DG, Thiagarajan M, Tomlinson CM, Torralba M, Treangen TJ, Truty RM, Vishnivetskaya TA, Walker J, Wang L, Wang Z, Ward DV, Warren W, Watson MA, Wellington C, Wetterstrand KA, White JR, Wilczek-Boney K, Wu YQ, Wylie KM, Wylie T, Yandava C, Ye L, Ye Y, Yooseph S, Youmans BP, Zhang L, Zhou Y, Zhu Y, Zoloth L, Zucker JD, Birren BW, Gibbs RA, Highlander SK, Weinstock GM, Wilson RK, White O. Comment in Microbiology: Learning about who we are. [Nature. 2012] Microbiology: Learning about who we are.Relman DA. Nature. 2012 Jun 13; 486(7402):194-5. Epub 2012 Jun 13. Abstract A variety of microbial communities and their genes (the microbiome) exist throughout the human body, with fundamental roles in human health and disease. The National Institutes of Health (NIH)-funded Human Microbiome Project Consortium has established a population-scale framework to develop metagenomic protocols, resulting in a broad range of quality-controlled resources and data including standardized methods for creating, processing and interpreting distinct types of high-throughput metagenomic data available to the scientific community. Here we present resources from a population of 242 healthy adults sampled at 15 or 18 body sites up to three times, which have generated 5,177 microbial taxonomic profiles from 16S ribosomal RNA genes and over 3.5 terabases of metagenomic sequence so far. In parallel, approximately 800 reference strains isolated from the human body have been sequenced. Collectively, these data represent the largest resource describing the abundance and variety of the human microbiome, while providing a framework for current and future studies. PMCID: PMC3377744 [Available on 2012/12/14]
	PMID: 22699610 [PubMed - indexed for MEDLINE]
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4.	Nature. 2012 Jun 13;486(7402):207-14. doi: 10.1038/nature11234. Structure, function and diversity of the healthy human microbiome. Human Microbiome Project Consortium. Collaborators: Huttenhower C, Gevers D, Knight R, Abubucker S, Badger JH, Chinwalla AT, Creasy HH, Earl AM, FitzGerald MG, Fulton RS, Giglio MG, Hallsworth-Pepin K, Lobos EA, Madupu R, Magrini V, Martin JC, Mitreva M, Muzny DM, Sodergren EJ, Versalovic J, Wollam AM, Worley KC, Wortman JR, Young SK, Zeng Q, Aagaard KM, Abolude OO, Allen-Vercoe E, Alm EJ, Alvarado L, Andersen GL, Anderson S, Appelbaum E, Arachchi HM, Armitage G, Arze CA, Ayvaz T, Baker CC, Begg L, Belachew T, Bhonagiri V, Bihan M, Blaser MJ, Bloom T, Bonazzi V, Brooks J, Buck GA, Buhay CJ, Busam DA, Campbell JL, Canon SR, Cantarel BL, Chain PS, Chen IM, Chen L, Chhibba S, Chu K, Ciulla DM, Clemente JC, Clifton SW, Conlan S, Crabtree J, Cutting MA, Davidovics NJ, Davis CC, DeSantis TZ, Deal C, Delehaunty KD, Dewhirst FE, Deych E, Ding Y, Dooling DJ, Dugan SP, Dunne WM, Durkin A, Edgar RC, Erlich RL, Farmer CN, Farrell RM, Faust K, Feldgarden M, Felix VM, Fisher S, Fodor AA, Forney LJ, Foster L, Di Francesco V, Friedman J, Friedrich DC, Fronick CC, Fulton LL, Gao H, Garcia N, Giannoukos G, Giblin C, Giovanni MY, Goldberg JM, Goll J, Gonzalez A, Griggs A, Gujja S, Haake SK, Haas BJ, Hamilton HA, Harris EL, Hepburn TA, Herter B, Hoffmann DE, Holder ME, Howarth C, Huang KH, Huse SM, Izard J, Jansson JK, Jiang H, Jordan C, Joshi V, Katancik JA, Keitel WA, Kelley ST, Kells C, King NB, Knights D, Kong HH, Koren O, Koren S, Kota KC, Kovar CL, Kyrpides NC, La Rosa PS, Lee SL, Lemon KP, Lennon N, Lewis CM, Lewis L, Ley RE, Li K, Liolios K, Liu B, Liu Y, Lo CC, Lozupone CA, Lunsford R, Madden T, Mahurkar AA, Mannon PJ, Mardis ER, Markowitz VM, Mavromatis K, McCorrison JM, McDonald D, McEwen J, McGuire AL, McInnes P, Mehta T, Mihindukulasuriya KA, Miller JR, Minx PJ, Newsham I, Nusbaum C, O'Laughlin M, Orvis J, Pagani I, Palaniappan K, Patel SM, Pearson M, Peterson J, Podar M, Pohl C, Pollard KS, Pop M, Priest ME, Proctor LM, Qin X, Raes J, Ravel J, Reid JG, Rho M, Rhodes R, Riehle KP, Rivera MC, Rodriguez-Mueller B, Rogers YH, Ross MC, Russ C, Sanka RK, Sankar P, Sathirapongsasuti J, Schloss JA, Schloss PD, Schmidt TM, Scholz M, Schriml L, Schubert AM, Segata N, Segre JA, Shannon WD, Sharp RR, Sharpton TJ, Shenoy N, Sheth NU, Simone GA, Singh I, Smillie CS, Sobel JD, Sommer DD, Spicer P, Sutton GG, Sykes SM, Tabbaa DG, Thiagarajan M, Tomlinson CM, Torralba M, Treangen TJ, Truty RM, Vishnivetskaya TA, Walker J, Wang L, Wang Z, Ward DV, Warren W, Watson MA, Wellington C, Wetterstrand KA, White JR, Wilczek-Boney K, Wu Y, Wylie KM, Wylie T, Yandava C, Ye L, Ye Y, Yooseph S, Youmans BP, Zhang L, Zhou Y, Zhu Y, Zoloth L, Zucker JD, Birren BW, Gibbs RA, Highlander SK, Methé BA, Nelson KE, Petrosino JF, Weinstock GM, Wilson RK, White O. Comment in Microbiology: Learning about who we are. [Nature. 2012] Microbiology: Learning about who we are.Relman DA. Nature. 2012 Jun 13; 486(7402):194-5. Epub 2012 Jun 13. Abstract Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat's signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81-99% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology and translational applications of the human microbiome.
	PMID: 22699609 [PubMed - indexed for MEDLINE]
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5.	Nature. 2012 Jun 13;486(7402):194-5. doi: 10.1038/486194a. Microbiology: Learning about who we are. Relman DA. Comment on Structure, function and diversity of the healthy human microbiome. [Nature. 2012] Structure, function and diversity of the healthy human microbiome.Human Microbiome Project Consortium. Nature. 2012 Jun 13; 486(7402):207-14. Epub 2012 Jun 13. A framework for human microbiome research. [Nature. 2012] A framework for human microbiome research.Human Microbiome Project Consortium. Nature. 2012 Jun 13; 486(7402):215-21. Epub 2012 Jun 13.
	PMID: 22699602 [PubMed - indexed for MEDLINE]
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