Wednesday, 29 October 2014

What's new for 'JKB_daily1' in PubMed

This message contains My NCBI what's new results from the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).
Do not reply directly to this message.

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

Sent on Wednesday, 2014 October 29
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]))

View complete results in PubMed (results may change over time).

Edit saved search settings, or unsubscribe from these e-mail updates.


PubMed Results
Item 1 of 1

1. N Engl J Med. 2014 Oct 16;371(16):1496-506. doi: 10.1056/NEJMoa1404380. Epub 2014 Oct 1.

Goal-directed resuscitation for patients with early septic shock.

ARISE Investigators; ANZICS Clinical Trials Group, Peake SL, Delaney A, Bailey M, Bellomo R, Cameron PA, Cooper DJ, Higgins AM, Holdgate A, Howe BD, Webb SA, Williams P.

Collaborators: Peake S, Delaney A, Bellomo R, Cameron P, Higgins A, Holdgate A, Howe BD, Webb SA, Williams P, Peake S, Delaney A, Bellomo R, Cameron P, Cooper D, Cross A, Gomersall C, Graham C, Higgins AM, Holdgate A, Howe BD, Jacobs I, Johanson S, Jones P, Kruger P, McArthur C, Myburgh J, Nichol A, Pettilä V, Rajbhandari D, Webb SA, Williams A, Williams J, Williams P, Baigent C, Cuthbertson B, Benger J, Emberson J, Bailey M, Bellomo R, Bives G, Cooper D, Higgins A, Howe BD, Jovanovska A, Lam L, Little L, Newby L, Bennett V, Board J, McCracken P, McGloughlin S, Nanjayya V, Teo A, Hill E, Jones P, O'Brien E, Sawtell F, Schimanski K, Wilson D, Bellomo R, Bolch S, Eastwood G, Kerr F, Peak L, Young H, Edington J, Fletcher J, Smith J, Ghelani D, Nand K, Sara T, Cross A, Flemming D, Grummisch M, Purdue A, Fulton E, Grove K, Harney A, Milburn K, Millar R, Mitchell I, Rodgers H, Scanlon S, Coles T, Connor H, Dennett J, Van Berkel A, Barrington-Onslow S, Henderson S, Mehrtens J, Dryburgh J, Tankel A, Braitberg G, O'Bree B, Shepherd K, Vij S, Allsop S, Haji D, Haji K, Vuat J, Bone A, Elderkin T, Orford N, Ragg M, Kelly S, Stewart D, Woodward N, Harjola VP, Okkonen M, Pettilä V, Sutinen S, Wilkman E, Fratzia J, Halkhoree J, Treloar S, Ryan K, Sandford T, Walsham J, Jenkins C, Williamson D, Burrows J, Hawkins D, Tang C, Dimakis A, Holdgate A, Micallef S, Parr M, White H, Morrison L, Sosnowski K, Ramadoss R, Soar N, Wood J, Franks M, Williams A, Hogan C, Song R, Tilsley A, Rainsford D, Soar N, Wells R, Wood J, Dowling J, Galt P, Lamac T, Lightfoot D, Walker C, Braid K, DeVillecourt T, Tan HS, Seppelt I, Chang LF, Cheung WS, Fok SK, Lam PK, Lam SM, So HM, Yan WW, Altea A , Lancashire B, Gomersall CD, Graham CA, Leung P, Arora S, Bass F, Shehabi Y, Isoardi J, Isoardi K, Powrie D, Lawrence S, Ankor A, Chester L, Davies M, O'Connor S, Poole A, Soulsby T, Sundararajan K, Williams J, Greenslade JH, MacIsaac C, Gorman K, Jordan A, Moore L, Ankers S, Bird S, Delaney A, Dowling J, Fogg T, Hickson E, Jewell T, Kyneur K, O'Connor A, Townsend J , Yarad E, Brown S, Chamberlain J, Cooper J, Jenkinson E, McDonald E, Webb S, Buhr H, Coakley J, Cowell J, Hutch D, Gattas D, Keir M, Rajbhandari D, Rees C, Baker S, Roberts B, Farone E, Holmes J, Santamaria J, Winter C, Finckh A, Knowles S, McCabe J, Nair P, Reynolds C, Ahmed B, Barton D, Meaney E, Nichol A, Harris R, Shields L, Thomas K, Karlsson S, Kuitunen A, Kukkurainen A, Tenhunen J, Varila S, Burrows J, Ryan N, Trethewy C, Crosdale J, Smith J, Vellaichamy M, Furyk J, Gordon G, Jones L, Senthuran S, Bates S, Butler J, French C, Tippett A, Kelly J, Kwans J, Murphy M, O'Flynn D, Kurenda C, Otto T, Peake S, Raniga V, Williams P, Ho H, Leung A, Wu H.

Abstract

BACKGROUND:

Early goal-directed therapy (EGDT) has been endorsed in the guidelines of the Surviving Sepsis Campaign as a key strategy to decrease mortality among patients presenting to the emergency department with septic shock. However, its effectiveness is uncertain.

METHODS:

In this trial conducted at 51 centers (mostly in Australia or New Zealand), we randomly assigned patients presenting to the emergency department with early septic shock to receive either EGDT or usual care. The primary outcome was all-cause mortality within 90 days after randomization.

RESULTS:

Of the 1600 enrolled patients, 796 were assigned to the EGDT group and 804 to the usual-care group. Primary outcome data were available for more than 99% of the patients. Patients in the EGDT group received a larger mean (±SD) volume of intravenous fluids in the first 6 hours after randomization than did those in the usual-care group (1964±1415 ml vs. 1713±1401 ml) and were more likely to receive vasopressor infusions (66.6% vs. 57.8%), red-cell transfusions (13.6% vs. 7.0%), and dobutamine (15.4% vs. 2.6%) (P<0.001 for all comparisons). At 90 days after randomization, 147 deaths had occurred in the EGDT group and 150 had occurred in the usual-care group, for rates of death of 18.6% and 18.8%, respectively (absolute risk difference with EGDT vs. usual care, -0.3 percentage points; 95% confidence interval, -4.1 to 3.6; P=0.90). There was no significant difference in survival time, in-hospital mortality, duration of organ support, or length of hospital stay.

CONCLUSIONS:

In critically ill patients presenting to the emergency department with early septic shock, EGDT did not reduce all-cause mortality at 90 days. (Funded by the National Health and Medical Research Council of Australia and the Alfred Foundation; ARISE ClinicalTrials.gov number, NCT00975793 .).

PMID: 25272316 [PubMed - indexed for MEDLINE]
Icon for Atypon

posted by JKB @ 03:20   0 Comments

Saturday, 25 October 2014

What's new for 'JKB_daily1' in PubMed

This message contains My NCBI what's new results from the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).
Do not reply directly to this message.

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

Sent on Saturday, 2014 October 25
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]))

View complete results in PubMed (results may change over time).

Edit saved search settings, or unsubscribe from these e-mail updates.


PubMed Results
Items 1 - 3 of 3

1. Nature. 2014 Aug 28;512(7515):400-5. doi: 10.1038/nature13497.

Regulatory analysis of the C. elegans genome with spatiotemporal resolution.

Araya CL1, Kawli T1, Kundaje A2, Jiang L1, Wu B1, Vafeados D3, Terrell R3, Weissdepp P3, Gevirtzman L3, Mace D3, Niu W4, Boyle AP1, Xie D1, Ma L5, Murray JI6, Reinke V4, Waterston RH3, Snyder M1.

Author information:
1Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA.
2Department of Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
3Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
4Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
5Institute for Genomics and Systems Biology, University of Chicago, Chicago, Illinois 60637, USA.
6 Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

Comment in

Abstract

Discovering the structure and dynamics of transcriptional regulatory events in the genome with cellular and temporal resolution is crucial to understanding the regulatory underpinnings of development and disease. We determined the genomic distribution of binding sites for 92 transcription factors and regulatory proteins across multiple stages of Caenorhabditis elegans development by performing 241 ChIP-seq (chromatin immunoprecipitation followed by sequencing) experiments. Integration of regulatory binding and cellular-resolution expression data produced a spatiotemporally resolved metazoan transcription factor binding map. Using this map, we explore developmental regulatory circuits that encode combinatorial logic at the levels of co-binding and co-expression of transcription factors, characterizing the genomic coverage and clustering of regulatory binding, the binding preferences of, and biological processes regulated by, transcription factors, the global transcription factor co-associations and genomic subdomains that suggest shared patterns of regulation, and identifying key transcription factors and transcription factor co-associations for fate specification of individual lineages and cell types.

PMID: 25164749 [PubMed - indexed for MEDLINE]
Related citations
Icon for Nature Publishing Group

2. Nature. 2014 Aug 28;512(7515):359. doi: 10.1038/512359a.

Himalayan plants seek cooler climes.

Padma TV.
PMID: 25164731 [PubMed - indexed for MEDLINE]
Related citations
Icon for Nature Publishing Group

3. Nature. 2014 Aug 28;512(7515):431-5. doi: 10.1038/nature13375. Epub 2014 Jun 25.

miR-34a blocks osteoporosis and bone metastasis by inhibiting osteoclastogenesis and Tgif2.

Krzeszinski JY1, Wei W1, Huynh H1, Jin Z1, Wang X1, Chang TC2, Xie XJ3, He L4, Mangala LS5, Lopez-Berestein G6, Sood AK7, Mendell JT8, Wan Y9.

Author information:
1Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
2Department of Molecular Biology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
31] Simmons Cancer Center, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA [2] Department of Clinical Sciences, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
4Division of Cellular and Developmental Biology, Molecular and Cell Biology Department, University of California at Berkeley, Berkeley, California 94705, USA.
51] Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [2] Center for RNA Interference and Non-coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
61] Center for RNA Interference and Non-coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [2] Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
71] Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [2] Center for RNA Interference and Non-coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [3] Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
81] Department of Molecular Biology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA [2] Simmons Cancer Center, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
91] Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA [2] Simmons Cancer Center, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.

Comment in

Abstract

Bone-resorbing osteoclasts significantly contribute to osteoporosis and bone metastases of cancer. MicroRNAs play important roles in physiology and disease, and present tremendous therapeutic potential. Nonetheless, how microRNAs regulate skeletal biology is underexplored. Here we identify miR-34a as a novel and critical suppressor of osteoclastogenesis, bone resorption and the bone metastatic niche. miR-34a is downregulated during osteoclast differentiation. Osteoclastic miR-34a-overexpressing transgenic mice exhibit lower bone resorption and higher bone mass. Conversely, miR-34a knockout and heterozygous mice exhibit elevated bone resorption and reduced bone mass. Consequently, ovariectomy-induced osteoporosis, as well as bone metastasis of breast and skin cancers, are diminished in osteoclastic miR-34a transgenic mice, and can be effectively attenuated by miR-34a nanoparticle treatment. Mechanistically, we identify transforming growth factor-β-induced factor 2 (Tgif2) as an essential direct miR-34a target that is pro-osteoclastogenic. Tgif2 deletion reduces bone resorption and abolishes miR-34a regulation. Together, using mouse genetic, pharmacological and disease models, we reveal miR-34a as a key osteoclast suppressor and a potential therapeutic strategy to confer skeletal protection and ameliorate bone metastasis of cancers.

PMCID: PMC4149606 [Available on 2015/2/28]
PMID: 25043055 [PubMed - indexed for MEDLINE]
Related citations
Icon for Nature Publishing Group

posted by JKB @ 03:35   0 Comments

Friday, 24 October 2014

What's new for 'JKB_daily1' in PubMed

This message contains My NCBI what's new results from the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).
Do not reply directly to this message.

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

Sent on Friday, 2014 October 24
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]))

View complete results in PubMed (results may change over time).

Edit saved search settings, or unsubscribe from these e-mail updates.


PubMed Results
Items 1 - 9 of 9

1. Nature. 2014 Oct 2;514(7520):E2. doi: 10.1038/nature13689.

Kruidenier et al. reply.

Kruidenier L1, Chung CW2, Cheng Z3, Liddle J1, Che K4, Joberty G5, Bantscheff M5, Bountra C6, Bridges A2, Diallo H1, Eberhard D5, Hutchinson S2, Jones E2, Katso R2, Leveridge M2, Mander PK1, Mosley J2, Ramirez-Molina C1, Rowland P2, Schofield CJ6, Sheppard RJ1, Smith JE1, Swales C7, Tanner R2, Thomas P2, Tumber A6, Drewes G5, Oppermann U4, Patel DJ3, Lee K8, Wilson DM1.

Author information:
1Epinova DPU, Immuno-Inflammation Therapy Area, GlaxoSmithKline R&D, Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, UK.
2Platform Technology and Science, GlaxoSmithKline R&D, Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, UK.
3Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.
41] Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Headington OX3 7DQ, UK [2] Botnar Research Centre, NIHR Biomedical Research Unit, University of Oxford OX3 7LD, UK.
5Cellzome AG, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
6Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Headington OX3 7DQ, UK.
7Botnar Research Centre, NIHR Biomedical Research Unit, University of Oxford OX3 7LD, UK.
81] Epinova DPU, Immuno-Inflammation Therapy Area, GlaxoSmithKline R&D, Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, UK [2] Pfizer, Biotherapeutics R&D, 200 Cambridgepark Drive, Cambridge, Massachusetts 02140, USA.

Comment on

PMID: 25279927 [PubMed - indexed for MEDLINE]
Related citations
Icon for Nature Publishing Group

2. Nature. 2014 Oct 2;514(7520):E1-2. doi: 10.1038/nature13688.

Inhibition of demethylases by GSK-J1/J4.

Heinemann B1, Nielsen JM1, Hudlebusch HR1, Lees MJ2, Larsen DV1, Boesen T1, Labelle M1, Gerlach LO1, Birk P1, Helin K3.

Author information:
1EpiTherapeutics Aps, Ole Maaløes Vej 3, 2200 Copenhagen, Denmark.
2Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark.
31] Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark [2] Centre for Epigenetics, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark [3] The Danish Stem Cell Center (DanStem), University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark.

Comment in

  • Kruidenier et al. reply. [Nature. 2014]

Comment on

PMID: 25279926 [PubMed - indexed for MEDLINE]
Related citations
Icon for Nature Publishing Group

3. Nature. 2014 Oct 2;514(7520):59-64. doi: 10.1038/nature13786.

Biogeography and individuality shape function in the human skin metagenome.

Oh J1, Byrd AL1, Deming C1, Conlan S1; NISC Comparative Sequencing Program, Kong HH2, Segre JA3.

Collaborators: Barnabas B, Blakesley R, Bouffard G, Brooks S, Coleman H, Dekhtyar M, Gregory M, Guan X, Gupta J, Han J, Ho SL, Legaspi R, Maduro Q, Masiello C, Maskeri B, McDowell J, Montemayor C, Mullikin J, Park M, Riebow N, Schandler K, Schmidt B, Sison C, Stantripop M, Thomas J, Thomas P, Vemulapalli M, Young A.

Author information:
1Translational and Functional Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland 20892, USA.
21] Dermatology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA [2].
31] Translational and Functional Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland 20892, USA [2].

Comment in

Abstract

The varied topography of human skin offers a unique opportunity to study how the body's microenvironments influence the functional and taxonomic composition of microbial communities. Phylogenetic marker gene-based studies have identified many bacteria and fungi that colonize distinct skin niches. Here metagenomic analyses of diverse body sites in healthy humans demonstrate that local biogeography and strong individuality define the skin microbiome. We developed a relational analysis of bacterial, fungal and viral communities, which showed not only site specificity but also individual signatures. We further identified strain-level variation of dominant species as heterogeneous and multiphyletic. Reference-free analyses captured the uncharacterized metagenome through the development of a multi-kingdom gene catalogue, which was used to uncover genetic signatures of species lacking reference genomes. This work is foundational for human disease studies investigating inter-kingdom interactions, metabolic changes and strain tracking, and defines the dual influence of biogeography and individuality on microbial composition and function.

PMCID: PMC4185404 [Available on 2015/4/1]
PMID: 25279917 [PubMed - indexed for MEDLINE]
Related citations
Icon for Nature Publishing Group

4. Nature. 2014 Oct 2;514(7520):24-6. doi: 10.1038/514024a.

The first South Americans: Extreme living.

Fraser B.
PMID: 25279901 [PubMed - indexed for MEDLINE]
Related citations
Icon for Nature Publishing Group

5. Nature. 2014 Oct 2;514(7520):16-7. doi: 10.1038/514016a.

Tibetan plateau gets wired up for monsoon prediction.

Qiu J.
PMID: 25279896 [PubMed - indexed for MEDLINE]
Related citations
Icon for Nature Publishing Group

6. Nature. 2014 Oct 2;514(7520):13-4. doi: 10.1038/514013a.

Fast genetic sequencing saves newborn lives.

Reardon S.
PMID: 25279893 [PubMed - indexed for MEDLINE]
Related citations
Icon for Nature Publishing Group

7. Science. 2014 Sep 26;345(6204):1251086. doi: 10.1126/science.1251086.

Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity.

Saeed S1, Quintin J2, Kerstens HH1, Rao NA1, Aghajanirefah A1, Matarese F1, Cheng SC2, Ratter J2, Berentsen K1, van der Ent MA1, Sharifi N1, Janssen-Megens EM1, Ter Huurne M1, Mandoli A1, van Schaik T1, Ng A3, Burden F4, Downes K4, Frontini M4, Kumar V5, Giamarellos-Bourboulis EJ6, Ouwehand WH4, van der Meer JW2, Joosten LA2, Wijmenga C5, Martens JH1, Xavier RJ3, Logie C7, Netea MG8, Stunnenberg HG7.

Author information:
1Department of Molecular Biology, Faculties of Science and Medicine, Radboud Institute for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, Netherlands.
2Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands.
3Center for Computational and Integrative Biology and Gastrointestinal Unit, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA 02114, USA. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
4Department of Haematology, University of Cambridge, Cambridge, UK. National Health Service, Blood and Transplant Cambridge Centre, Cambridge Biomedical Campus, Cambridge CB0 2PT, UK.
5University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands.
6Fourth Department of Internal Medicine, University of Athens, Medical School, 1 Rimini Street, 12462 Athens, Greece.
7Department of Molecular Biology, Faculties of Science and Medicine, Radboud Institute for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, Netherlands. h.stunnenberg@ncmls.ru.nl mihai.netea@radboudumc.nl c.logie@ncmls.ru.nl.
8Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands. h.stunnenberg@ncmls.ru.nl mihai.netea@radboudumc.nl c.logie@ncmls.ru.nl.

Abstract

Monocyte differentiation into macrophages represents a cornerstone process for host defense. Concomitantly, immunological imprinting of either tolerance or trained immunity determines the functional fate of macrophages and susceptibility to secondary infections. We characterized the transcriptomes and epigenomes in four primary cell types: monocytes and in vitro-differentiated naïve, tolerized, and trained macrophages. Inflammatory and metabolic pathways were modulated in macrophages, including decreased inflammasome activation, and we identified pathways functionally implicated in trained immunity. β-glucan training elicits an exclusive epigenetic signature, revealing a complex network of enhancers and promoters. Analysis of transcription factor motifs in deoxyribonuclease I hypersensitive sites at cell-type-specific epigenetic loci unveiled differentiation and treatment-specific repertoires. Altogether, we provide a resource to understand the epigenetic changes that underlie innate immunity in humans.

Copyright © 2014, American Association for the Advancement of Science.

PMID: 25258085 [PubMed - indexed for MEDLINE]
Related citations
Icon for HighWire

8. Science. 2014 Sep 26;345(6204):1250684. doi: 10.1126/science.1250684.

mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity.

Cheng SC1, Quintin J1, Cramer RA2, Shepardson KM2, Saeed S3, Kumar V4, Giamarellos-Bourboulis EJ5, Martens JH3, Rao NA3, Aghajanirefah A3, Manjeri GR6, Li Y4, Ifrim DC1, Arts RJ1, van der Meer BM4, Deen PM7, Logie C3, O'Neill LA8, Willems P6, van de Veerdonk FL1, van der Meer JW1, Ng A9, Joosten LA1, Wijmenga C4, Stunnenberg HG4, Xavier RJ9, Netea MG10.

Author information:
1Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands.
2Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
3Department of Molecular Biology, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, Netherlands.
4Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
54th Department of Internal Medicine, University of Athens Medical School, 12462 Athens, Greece.
6Department of Biochemistry, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, Netherlands.
7Department of Physiology, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands.
8School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
9Center for Computational and Integrative Biology and Gastrointestinal Unit, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA 02114, USA. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
10Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands. mihai.netea@radboudumc.nl.

Abstract

Epigenetic reprogramming of myeloid cells, also known as trained immunity, confers nonspecific protection from secondary infections. Using histone modification profiles of human monocytes trained with the Candida albicans cell wall constituent β-glucan, together with a genome-wide transcriptome, we identified the induced expression of genes involved in glucose metabolism. Trained monocytes display high glucose consumption, high lactate production, and a high ratio of nicotinamide adenine dinucleotide (NAD(+)) to its reduced form (NADH), reflecting a shift in metabolism with an increase in glycolysis dependent on the activation of mammalian target of rapamycin (mTOR) through a dectin-1-Akt-HIF-1α (hypoxia-inducible factor-1α) pathway. Inhibition of Akt, mTOR, or HIF-1α blocked monocyte induction of trained immunity, whereas the adenosine monophosphate-activated protein kinase activator metformin inhibited the innate immune response to fungal infection. Mice with a myeloid cell-specific defect in HIF-1α were unable to mount trained immunity against bacterial sepsis. Our results indicate that induction of aerobic glycolysis through an Akt-mTOR-HIF-1α pathway represents the metabolic basis of trained immunity.

Copyright © 2014, American Association for the Advancement of Science.

PMID: 25258083 [PubMed - indexed for MEDLINE]
Related citations
Icon for HighWire

9. Nature. 2014 Oct 2;514(7520):47-53. doi: 10.1038/nature13777. Epub 2014 Aug 29.

Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp.

Qiu X1, Wong G2, Audet J2, Bello A2, Fernando L1, Alimonti JB1, Fausther-Bovendo H2, Wei H3, Aviles J1, Hiatt E4, Johnson A4, Morton J4, Swope K4, Bohorov O5, Bohorova N5, Goodman C5, Kim D5, Pauly MH5, Velasco J5, Pettitt J6, Olinger GG6, Whaley K5, Xu B7, Strong JE8, Zeitlin L5, Kobinger GP9.

Author information:
1National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.
21] National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada [2] Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada.
31] National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada [2] Institute of Infectious Disease, Henan Centre for Disease Control and Prevention, Zhengzhou, 450012 Henan, China.
4Kentucky BioProcessing, Owensboro, Kentucky 42301, USA.
5Mapp Biopharmaceutical Inc., San Diego, California 92121, USA.
61] United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland 21702, USA [2] Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland 21702, USA.
7Institute of Infectious Disease, Henan Centre for Disease Control and Prevention, Zhengzhou, 450012 Henan, China.
81] National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada [2] Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada [3] Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba R3A 1S1, Canada.
91] National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada [2] Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada [3] Department of Immunology, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada [4] Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.

Comment in

Abstract

Without an approved vaccine or treatments, Ebola outbreak management has been limited to palliative care and barrier methods to prevent transmission. These approaches, however, have yet to end the 2014 outbreak of Ebola after its prolonged presence in West Africa. Here we show that a combination of monoclonal antibodies (ZMapp), optimized from two previous antibody cocktails, is able to rescue 100% of rhesus macaques when treatment is initiated up to 5 days post-challenge. High fever, viraemia and abnormalities in blood count and blood chemistry were evident in many animals before ZMapp intervention. Advanced disease, as indicated by elevated liver enzymes, mucosal haemorrhages and generalized petechia could be reversed, leading to full recovery. ELISA and neutralizing antibody assays indicate that ZMapp is cross-reactive with the Guinean variant of Ebola. ZMapp exceeds the efficacy of any other therapeutics described so far, and results warrant further development of this cocktail for clinical use.

PMID: 25171469 [PubMed - indexed for MEDLINE]
Related citations
Icon for Nature Publishing Group

posted by JKB @ 03:20   0 Comments

Thursday, 23 October 2014

What's new for 'JKB_daily1' in PubMed

This message contains My NCBI what's new results from the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).
Do not reply directly to this message.

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

Sent on Thursday, 2014 October 23
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]))

View complete results in PubMed (results may change over time).

Edit saved search settings, or unsubscribe from these e-mail updates.


PubMed Results
Items 1 - 2 of 2

1. N Engl J Med. 2014 Oct 9;371(15):1459-61. doi: 10.1056/NEJMe1408976. Epub 2014 Oct 1.

Transfusion threshold of 7 g per deciliter--the new normal.

Hébert PC1, Carson JL.

Author information:
1From the Canadian Critical Care Trials Group, Department of Medicine and Centre de Recherche, Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal (P.C.H.); and the Division of General Internal Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ (J.L.C.).

Comment on

PMID: 25270276 [PubMed - indexed for MEDLINE]
Related citations
Icon for Atypon

2. N Engl J Med. 2014 Oct 9;371(15):1381-91. doi: 10.1056/NEJMoa1406617. Epub 2014 Oct 1.

Lower versus higher hemoglobin threshold for transfusion in septic shock.

Holst LB1, Haase N, Wetterslev J, Wernerman J, Guttormsen AB, Karlsson S, Johansson PI, Aneman A, Vang ML, Winding R, Nebrich L, Nibro HL, Rasmussen BS, Lauridsen JR, Nielsen JS, Oldner A, Pettilä V, Cronhjort MB, Andersen LH, Pedersen UG, Reiter N, Wiis J, White JO, Russell L, Thornberg KJ, Hjortrup PB, Müller RG, Møller MH, Steensen M, Tjäder I, Kilsand K, Odeberg-Wernerman S, Sjøbø B, Bundgaard H, Thyø MA, Lodahl D, Mærkedahl R, Albeck C, Illum D, Kruse M, Winkel P, Perner A; TRISS Trial Group; Scandinavian Critical Care Trials Group.

Collaborators: Holst LB, Haase N, Wernerman J, Guttormsen AB, Karlsson S, Johansson PI, Åneman A, Wetterslev J, Perner A, Holst LB, Wetterslev J, Perner A, Walsh T, Lacroix J, Fergusson D, De Backer D, Rowan K, Petersen JH, Holst LB, Perner A, Andersen LH, Pedersen U, Reiter N, Wiis J, White JO, Russell L, Thornberg KJ, Quist L, Ibsen M, Hjortrup PB, Müller RG, Møller MH, Steensen M, Claudius C, Kjær MN, Uhre KR, Christiansen V, Nislev LH, Sjøvall F, Jarnvig IL, Nielsen J, Thorsen HC, Bredahl P, Vang M, Bundgaard H, Thyø MA, Villumsen M, Wernerman J, Kilsand K, Tjäder I, Wernerman S, Winding R, Lodahl D, Mærkedahl R, Dey N, Haubjerg S, Nebrich L, Albeck C, Christensen A, Nibro H, Keld D, Larsen K, Dyrskog SE, Illum D, Rasmussen B, Granum SN, Bülow H, Elkjær J, Lauridsen J, Nielsen J, Guttormsen A, Sjøbø B, Oldner A, Friman O, Pettilä V, Pettilä L, Sutinen S, Cronhjort M, Kristensen B, Kirkegaard P, Lindhardt A, Strange D, Krogh EH, Rian O, Kruse M, Aagaard S, Pawlowicz MB, Madsen J, Poulsen L, Berezowicz P, Chew M, Abdeen F, Müller W, Sternheden G, Holmstrøm S, Thormar K, Mtchedlishvili N, Strand K, Karlsson S, Varila S, Kukkurainen A, Bendtsen A, Reinikainen M, Iversen S, Leivdal S, Bådstøløkken P, Longva J, Johansen R, Nielsen N, Breider J.

Author information:
1From the Department of Intensive Care (L.B.H., N.H., L.H.A., U.G.P., N.R., J. Wiis, J.O.W., L.R., K.J.T., P.B.H., R.G.M., M.H.M., M.S., A.P.), Copenhagen Trial Unit, Center for Clinical Intervention Research (J. Wetterslev, P.W.), and Section for Transfusion Medicine (P.I.J.), Rigshospitalet and University of Copenhagen, Copenhagen, Randers Hospital, Randers (M.L.V., H.B., M.A.T.), Herning Hospital, Herning (R.W., D.L., R.M.), Hvidovre Hospital, Hvidovre (L.N., C.A.), Aarhus University Hospital, Aarhus (H.L.N., D.I.), Aalborg University Hospital, Aalborg (B.S.R.), Holbæk Hospital, Holbæk (J.R.M.L.), Kolding Hospital, Kolding (J.S.N.), and Hjørring Hospital, Hjørring (M.K.) - all in Denmark; Karolinska University Hospital, Huddinge, Stockholm (J. Wernerman, I.T., K.K., S.O.-W.), Karolinska University Hospital, Solna (A.O.), and Södersjukhuset, Stockholm (M.B.C.) - all in Sweden; Haukeland University Hospital and University of Bergen, Bergen, Norway (A.B.G., B.S.); Tampere University Hospital, Tampere (S.K.), and Helsinki University Hospital and University of Helsinki, Helsinki (V.P.) - all in Finland; and Liverpool Hospital, Sydney (A.Å.).

Comment in

Abstract

BACKGROUND:

Blood transfusions are frequently given to patients with septic shock. However, the benefits and harms of different hemoglobin thresholds for transfusion have not been established.

METHODS:

In this multicenter, parallel-group trial, we randomly assigned patients in the intensive care unit (ICU) who had septic shock and a hemoglobin concentration of 9 g per deciliter or less to receive 1 unit of leukoreduced red cells when the hemoglobin level was 7 g per deciliter or less (lower threshold) or when the level was 9 g per deciliter or less (higher threshold) during the ICU stay. The primary outcome measure was death by 90 days after randomization.

RESULTS:

We analyzed data from 998 of 1005 patients (99.3%) who underwent randomization. The two intervention groups had similar baseline characteristics. In the ICU, the lower-threshold group received a median of 1 unit of blood (interquartile range, 0 to 3) and the higher-threshold group received a median of 4 units (interquartile range, 2 to 7). At 90 days after randomization, 216 of 502 patients (43.0%) assigned to the lower-threshold group, as compared with 223 of 496 (45.0%) assigned to the higher-threshold group, had died (relative risk, 0.94; 95% confidence interval, 0.78 to 1.09; P=0.44). The results were similar in analyses adjusted for risk factors at baseline and in analyses of the per-protocol populations. The numbers of patients who had ischemic events, who had severe adverse reactions, and who required life support were similar in the two intervention groups.

CONCLUSIONS:

Among patients with septic shock, mortality at 90 days and rates of ischemic events and use of life support were similar among those assigned to blood transfusion at a higher hemoglobin threshold and those assigned to blood transfusion at a lower threshold; the latter group received fewer transfusions. (Funded by the Danish Strategic Research Council and others; TRISS ClinicalTrials.gov number, NCT01485315.).

PMID: 25270275 [PubMed - indexed for MEDLINE]
Related citations
Icon for Atypon

posted by JKB @ 03:15   0 Comments