Saturday, 31 May 2014

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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 - 2 of 2

1. Nature. 2014 Apr 17;508(7496):287-8.

Cancer crossroads.

[No authors listed]
PMID: 24745068 [PubMed - indexed for MEDLINE]
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2. Nature. 2014 Apr 17;508(7496):411-5. doi: 10.1038/nature13069. Epub 2014 Mar 16.

miRNAs trigger widespread epigenetically activated siRNAs from transposons in Arabidopsis.

Creasey KM1, Zhai J2, Borges F1, Van Ex F1, Regulski M1, Meyers BC2, Martienssen RA3.

Author information:
1Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
2Delaware Biotechnology Institute and Department of Plant & Soil Sciences, 15 Innovation Way, University of Delaware, Newark, Delaware 19711, USA.
31] Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA [2] Howard Hughes Medical Institute-Gordon and Betty Moore Foundation, Cold Spring Harbor Laboratory, New York 11724, USA [3] Chaire Blaise Pascal, Institut de Biologie de l'Ecole Normale Supérieure (IBENS), 75230 Paris, France.

Comment in

Abstract

In plants, post-transcriptional gene silencing (PTGS) is mediated by DICER-LIKE 1 (DCL1)-dependent microRNAs (miRNAs), which also trigger 21-nucleotide secondary short interfering RNAs (siRNAs) via RNA-DEPENDENT RNA POLYMERASE 6 (RDR6), DCL4 and ARGONAUTE 1 (AGO1), whereas transcriptional gene silencing (TGS) of transposons is mediated by 24-nucleotide heterochromatic (het)siRNAs, RDR2, DCL3 and AGO4 (ref. 4). Transposons can also give rise to abundant 21-nucleotide 'epigenetically activated' small interfering RNAs (easiRNAs) in DECREASED DNA METHYLATION 1 (ddm1) and DNA METHYLTRANSFERASE 1 (met1) mutants, as well as in the vegetative nucleus of pollen grains and in dedifferentiated plant cell cultures. Here we show that easiRNAs in Arabidopsis thaliana resemble secondary siRNAs, in that thousands of transposon transcripts are specifically targeted by more than 50 miRNAs for cleavage and processing by RDR6. Loss of RDR6, DCL4 or DCL1 in a ddm1 background results in loss of 21-nucleotide easiRNAs and severe infertility, but 24-nucleotide hetsiRNAs are partially restored, supporting an antagonistic relationship between PTGS and TGS. Thus miRNA-directed easiRNA biogenesis is a latent mechanism that specifically targets transposon transcripts, but only when they are epigenetically reactivated during reprogramming of the germ line. This ancient recognition mechanism may have been retained both by transposons to evade long-term heterochromatic silencing and by their hosts for genome defence.

PMID: 24670663 [PubMed - indexed for MEDLINE]
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Friday, 30 May 2014

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PubMed Results
Items 1 - 3 of 3

1. Nat Med. 2014 Apr;20(4):335-7. doi: 10.1038/nm.3526.

Hypoferremia of infection: a double-edged sword?

Lokken KL, Tsolis RM, Bäumler AJ.

Author information:
Department of Medical Microbiology and Immunology, School of Medicine, University of California-Davis, Davis, California, USA.

PMID: 24710374 [PubMed - indexed for MEDLINE]
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2. Nat Med. 2014 Apr;20(4):419-24. doi: 10.1038/nm.3483. Epub 2014 Mar 23.

Inverse agonist of estrogen-related receptor γ controls Salmonella typhimurium infection by modulating host iron homeostasis.

Kim DK1, Jeong JH2, Lee JM3, Kim KS4, Park SH5, Kim YD3, Koh M6, Shin M3, Jung YS3, Kim HS7, Lee TH8, Oh BC9, Kim JI10, Park HT11, Jeong WI12, Lee CH13, Park SB14, Min JJ15, Jung SI16, Choi SY17, Choy HE4, Choi HS3.

Author information:
11] National Creative Research Initiatives Center for Nuclear Receptor Signals and Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea. [2].
21] Department of Microbiology, Chonnam National University Medical School, Gwangju, Republic of Korea. [2] Department of Molecular Medicine(BK21plus), Chonnam National University Graduate School, Gwangju, Republic of Korea. [3].
3National Creative Research Initiatives Center for Nuclear Receptor Signals and Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea.
41] Department of Microbiology, Chonnam National University Medical School, Gwangju, Republic of Korea. [2] Department of Molecular Medicine(BK21plus), Chonnam National University Graduate School, Gwangju, Republic of Korea.
5Department of Nuclear Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
6Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul, Republic of Korea.
7Department of Forensic Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
81] Department of Molecular Medicine(BK21plus), Chonnam National University Graduate School, Gwangju, Republic of Korea. [2] Department of Oral Biochemistry, Dental Science Research Institute, Chonnam National University, Gwangju, Republic of Korea.
9Lee Gil Ya Cancer and Diabetes Institute, Gachon University Graduate School of Medicine, Incheon, Republic of Korea.
101] School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea. [2] AnyGen, Jeonnam NanoBioResearch Center, Jangseong-gun, Republic of Korea.
11Department of Physiology, Mitochondria Hub Regulation Center, College of Medicine, Dong-A University, Busan, Republic of Korea.
12Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
13Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
141] Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul, Republic of Korea. [2] Department of Biophysics and Chemical Biology, College of Natural Sciences, Seoul National University, Seoul, Republic of Korea.
151] Department of Molecular Medicine(BK21plus), Chonnam National University Graduate School, Gwangju, Republic of Korea. [2] Department of Nuclear Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
161] Department of Molecular Medicine(BK21plus), Chonnam National University Graduate School, Gwangju, Republic of Korea. [2] Department of Infectious Diseases, Chonnam National University Medical School, Gwangju, Republic of Korea.
17Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, Republic of Korea.

Abstract

In response to microbial infection, expression of the defensin-like peptide hepcidin (encoded by Hamp) is induced in hepatocytes to decrease iron release from macrophages. To elucidate the mechanism by which Salmonella enterica var. Typhimurium (S. typhimurium), an intramacrophage bacterium, alters host iron metabolism for its own survival, we examined the role of nuclear receptor family members belonging to the NR3B subfamily in mouse hepatocytes. Here, we report that estrogen-related receptor γ (ERRγ, encoded by Esrrg) modulates the intramacrophage proliferation of S. typhimurium by altering host iron homeostasis, and we demonstrate an antimicrobial effect of an ERRγ inverse agonist. Hepatic ERRγ expression was induced by S. typhimurium-stimulated interleukin-6 signaling, resulting in an induction of hepcidin and eventual hypoferremia in mice. Conversely, ablation of ERRγ mRNA expression in liver attenuated the S. typhimurium-mediated induction of hepcidin and normalized the hypoferremia caused by S. typhimurium infection. An inverse agonist of ERRγ ameliorated S. typhimurium-mediated hypoferremia through reduction of ERRγ-mediated hepcidin mRNA expression and exerted a potent antimicrobial effect on the S. typhimurium infection, thereby improving host survival. Taken together, these findings suggest an alternative approach to control multidrug-resistant intracellular bacteria by modulating host iron homeostasis.

PMID: 24658075 [PubMed - indexed for MEDLINE]
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3. Nat Med. 2014 Apr;20(4):377-84. doi: 10.1038/nm.3467. Epub 2014 Mar 2.

Netrin-1 promotes adipose tissue macrophage retention and insulin resistance in obesity.

Ramkhelawon B1, Hennessy EJ1, Ménager M2, Ray TD1, Sheedy FJ1, Hutchison S1, Wanschel A1, Oldebeken S1, Geoffrion M3, Spiro W1, Miller G4, McPherson R4, Rayner KJ4, Moore KJ1.

Author information:
1Department of Medicine, Marc and Ruti Bell Program for Vascular Biology and Disease, The Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, New York, USA.
2Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York, USA.
3University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
4Department of Surgery, New York University School of Medicine, New York, New York, USA.

Abstract

During obesity, macrophage accumulation in adipose tissue propagates the chronic inflammation and insulin resistance associated with type 2 diabetes. The factors, however, that regulate the accrual of macrophages in adipose tissue are not well understood. Here we show that the neuroimmune guidance cue netrin-1 is highly expressed in obese but not lean adipose tissue of humans and mice, where it directs the retention of macrophages. Netrin-1, whose expression is induced in macrophages by the saturated fatty acid palmitate, acts via its receptor Unc5b to block their migration. In a mouse model of diet-induced obesity, we show that adipose tissue macrophages exhibit reduced migratory capacity, which can be restored by blocking netrin-1. Furthermore, hematopoietic deletion of Ntn1 facilitates adipose tissue macrophage emigration, reduces inflammation and improves insulin sensitivity. Collectively, these findings identify netrin-1 as a macrophage retention signal in adipose tissue during obesity that promotes chronic inflammation and insulin resistance.

PMCID: PMC3981930 [Available on 2014/10/1]
PMID: 24584118 [PubMed - indexed for MEDLINE]
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Friday, 23 May 2014

What's new for 'JKB_daily1' in PubMed

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PubMed Results
Items 1 - 2 of 2

1. N Engl J Med. 2014 May 8;370(19):1799-808. doi: 10.1056/NEJMoa1303944.

Parasite burden and severity of malaria in Tanzanian children.

Gonçalves BP1, Huang CY, Morrison R, Holte S, Kabyemela E, Prevots DR, Fried M, Duffy PE.

Author information:
1From the Laboratory of Malaria Immunology and Vaccinology (B.P.G., M.F., P.E.D.), Laboratory of Clinical Infectious Diseases-Epidemiology Unit (B.P.G., D.R.P.), and Biostatistics Research Branch (C.-Y.H.), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Rockville, MD; the Seattle Biomedical Research Institute (R.M., M.F., P.E.D.) and the Fred Hutchinson Cancer Research Center (S.H.) - both in Seattle; and the Mother-Offspring Malaria Studies Project, Muheza Designated District Hospital, Muheza, Tanzania (E.K., M.F., P.E.D.).

Abstract

BACKGROUND:

Severe Plasmodium falciparum malaria is a major cause of death in children. The contribution of the parasite burden to the pathogenesis of severe malaria has been controversial.

METHODS:

We documented P. falciparum infection and disease in Tanzanian children followed from birth for an average of 2 years and for as long as 4 years.

RESULTS:

Of the 882 children in our study, 102 had severe malaria, but only 3 had more than two episodes. More than half of first episodes of severe malaria occurred after a second infection. Although parasite levels were higher on average when children had severe rather than mild disease, most children (67 of 102) had high-density infection (>2500 parasites per 200 white cells) with only mild symptoms before severe malaria, after severe malaria, or both. The incidence of severe malaria decreased considerably after infancy, whereas the incidence of high-density infection was similar among all age groups. Infections before and after episodes of severe malaria were associated with similar parasite densities. Nonuse of bed nets, placental malaria at the time of a woman's second or subsequent delivery, high-transmission season, and absence of the sickle cell trait increased severe-malaria risk and parasite density during infections.

CONCLUSIONS:

Resistance to severe malaria was not acquired after one or two mild infections. Although the parasite burden was higher on average during episodes of severe malaria, a high parasite burden was often insufficient to cause severe malaria even in children who later were susceptible. The diverging rates of severe disease and high-density infection after infancy, as well as the similar parasite burdens before and after severe malaria, indicate that naturally acquired resistance to severe malaria is not explained by improved control of parasite density. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

Free Article
PMID: 24806160 [PubMed - indexed for MEDLINE]
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2. Science. 2014 May 9;344(6184):645-8. doi: 10.1126/science.1251414. Epub 2014 Apr 24.

The transcription factor Gata6 links tissue macrophage phenotype and proliferative renewal.

Rosas M1, Davies LC, Giles PJ, Liao CT, Kharfan B, Stone TC, O'Donnell VB, Fraser DJ, Jones SA, Taylor PR.

Author information:
1Cardiff Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.

Abstract

Tissue-resident macrophages are heterogeneous as a consequence of anatomical niche-specific functions. Many populations self-renew independently of bone marrow in the adult, but the molecular mechanisms of this are poorly understood. We determined a transcriptional profile for the major self-renewing population of peritoneal macrophages in mice. These cells specifically expressed the transcription factor Gata6. Selective deficiency of Gata6 in myeloid cells caused substantial alterations in the transcriptome of peritoneal macrophages. Gata6 deficiency also resulted in dysregulated peritoneal macrophage proliferative renewal during homeostasis and in response to inflammation, which was associated with delays in the resolution of inflammation. Our investigations reveal that the tissue macrophage phenotype is under discrete tissue-selective transcriptional control and that this is fundamentally linked to the regulation of their proliferation renewal.

PMID: 24762537 [PubMed - indexed for MEDLINE]
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Wednesday, 21 May 2014

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PubMed Results
Items 1 - 2 of 2

1. Nat Genet. 2014 Apr;46(4):409-15. doi: 10.1038/ng.2924. Epub 2014 Mar 16.

Ancestry estimation and control of population stratification for sequence-based association studies.

Wang C1, Zhan X2, Bragg-Gresham J3, Kang HM3, Stambolian D4, Chew EY5, Branham KE6, Heckenlively J6; FUSION Study, Fulton R7, Wilson RK7, Mardis ER7, Lin X8, Swaroop A9, Zöllner S10, Abecasis GR3.

Author information:
1 1] Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA. [2] Department of Biostatistics, Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA. [3].
21] Department of Biostatistics, Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA. [2].
3Department of Biostatistics, Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.
4Department of Ophthalmology, University of Pennsylvania Medical School, Philadelphia, Pennsylvania, USA.
5Division of Epidemiology and Clinical Research, National Eye Institute, Bethesda, Maryland, USA.
6Department of Ophthalmology, University of Michigan Kellogg Eye Center, Ann Arbor, Michigan, USA.
7Genome Institute, Washington University School of Medicine, St. Louis, Missouri, USA.
8Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA.
9Neurobiology-Neurodegeneration & Repair Laboratory, National Eye Institute, Bethesda, Maryland, USA.
101] Department of Biostatistics, Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA. [2] Department of Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan, USA.

Abstract

Estimating individual ancestry is important in genetic association studies where population structure leads to false positive signals, although assigning ancestry remains challenging with targeted sequence data. We propose a new method for the accurate estimation of individual genetic ancestry, based on direct analysis of off-target sequence reads, and implement our method in the publicly available LASER software. We validate the method using simulated and empirical data and show that the method can accurately infer worldwide continental ancestry when used with sequencing data sets with whole-genome shotgun coverage as low as 0.001×. For estimates of fine-scale ancestry within Europe, the method performs well with coverage of 0.1×. On an even finer scale, the method improves discrimination between exome-sequenced study participants originating from different provinces within Finland. Finally, we show that our method can be used to improve case-control matching in genetic association studies and to reduce the risk of spurious findings due to population structure.

PMID: 24633160 [PubMed - indexed for MEDLINE]
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2. Nat Genet. 2014 Apr;46(4):329-35. doi: 10.1038/ng.2900. Epub 2014 Feb 16.

Recurrent somatic mutations of PTPN1 in primary mediastinal B cell lymphoma and Hodgkin lymphoma.

Gunawardana J1, Chan FC2, Telenius A3, Woolcock B3, Kridel R1, Tan KL3, Ben-Neriah S3, Mottok A3, Lim RS3, Boyle M3, Rogic S4, Rimsza LM5, Guiter C6, Leroy K7, Gaulard P7, Haioun C8, Marra MA9, Savage KJ3, Connors JM3, Shah SP10, Gascoyne RD1, Steidl C1.

Author information:
11] Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada. [2] Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
21] Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada. [2] Bioinformatics Training Program, University of British Columbia, Vancouver, British Columbia, Canada.
3Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada.
4Centre for High-Throughput Biology, University of British Columbia, Vancouver, British Columbia, Canada.
5Department of Pathology, University of Arizona, Tucson, Arizona, USA.
6INSERM U955, Créteil, France.
71] INSERM U955, Créteil, France. [2] Université Paris Est, Créteil, France. [3] Département de Pathologie-Service d'Hématologie-Plateforme de Ressources Biologiques, Groupe Hospitalier Henri-MONDOR, Assistance Publique-Hôpitaux de Paris, Créteil, France.
81] Université Paris Est, Créteil, France. [2] Département de Pathologie-Service d'Hématologie-Plateforme de Ressources Biologiques, Groupe Hospitalier Henri-MONDOR, Assistance Publique-Hôpitaux de Paris, Créteil, France.
91] Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada. [2] Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
10Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

Abstract

Classical Hodgkin lymphoma and primary mediastinal B cell lymphoma (PMBCL) are related lymphomas sharing pathological, molecular and clinical characteristics. Here we discovered by whole-genome and whole-transcriptome sequencing recurrent somatic coding-sequence mutations in the PTPN1 gene. Mutations were found in 6 of 30 (20%) Hodgkin lymphoma cases, in 6 of 9 (67%) Hodgkin lymphoma-derived cell lines, in 17 of 77 (22%) PMBCL cases and in 1 of 3 (33%) PMBCL-derived cell lines, consisting of nonsense, missense and frameshift mutations. We demonstrate that PTPN1 mutations lead to reduced phosphatase activity and increased phosphorylation of JAK-STAT pathway members. Moreover, silencing of PTPN1 by RNA interference in Hodgkin lymphoma cell line KM-H2 resulted in hyperphosphorylation and overexpression of downstream oncogenic targets. Our data establish PTPN1 mutations as new drivers in lymphomagenesis.

PMID: 24531327 [PubMed - indexed for MEDLINE]
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Friday, 16 May 2014

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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

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

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

PMCID: PMC3820789 Free PMC Article
PMID: 24244199 [PubMed - indexed for MEDLINE]
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Sunday, 11 May 2014

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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. N Engl J Med. 2014 May 1;370(18):1673-6. doi: 10.1056/NEJMp1400276. Epub 2014 Apr 16.

Regulatory mandates for sepsis care--reasons for caution.

Rhee C1, Gohil S, Klompas M.

Author information:
1From the Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, and the Department of Medicine, Brigham and Women's Hospital - both in Boston (C.R., M.K.); and the Department of Medicine, University of California at Irvine, Irvine (S.G.).

Free Article
PMID: 24738642 [PubMed - indexed for MEDLINE]
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2. N Engl J Med. 2014 May 1;370(18):1750-1. doi: 10.1056/NEJMe1402564. Epub 2014 Mar 18.

The ProCESS trial--a new era of sepsis management.

Lilly CM.

Author information:
From the Division of Pulmonary, Allergy and Critical Care Medicine, University of Massachusetts Medical School, UMass Memorial Medical Center, Worcester.

Comment on

  • A randomized trial of protocol-based care for early septic shock. [N Engl J Med. 2014]
PMID: 24635774 [PubMed - indexed for MEDLINE]
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3. N Engl J Med. 2014 May 1;370(18):1683-93. doi: 10.1056/NEJMoa1401602. Epub 2014 Mar 18.

A randomized trial of protocol-based care for early septic shock.

ProCESS Investigators, Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, Pike F, Terndrup T, Wang HE, Hou PC, LoVecchio F, Filbin MR, Shapiro NI, Angus DC.

Collaborators: Angus DC, Barnato AE, Eaton TL, Gimbel E, Huang DT, Keener C, Kellum JA, Landis K , Pike F, Stapleton DK, Weissfeld LA, Willochell M, Wofford KA, Yealy DM, Kulstad E, Watts H, Venkat A, Hou PC, Massaro A, Parmar S, Limkakeng AT Jr, Brewer K, Delbridge TR, Mainhart A, Chawla LS, Miner JR, Allen TL, Grissom CK, Swadron S, Conrad SA, Carlson R, LoVecchio F, Bajwa EK, Filbin MR, Parry BA, Ellender TJ, Sama AE, Fine J, Nafeei S, Terndrup T, Wojnar M, Pearl RG, Wilber ST, Sinert R, Orban DJ, Wilson JW, Ufberg JW, Albertson T, Panacek EA, Parekh S, Gunn SR, Rittenberger JS, Wadas RJ, Edwards AR, Kelly M, Wang HE, Holmes TM, McCurdy MT, Weinert C, Harris ES, Self WH, Dubinski D, Phillips CA, Migues RM, Bernard GR, Berry DA, Brock DW, Cnaan A, Fost NC, Lewis RJ, Nathens AB, Rubenfeld GD.

Comment in

Abstract

BACKGROUND:

In a single-center study published more than a decade ago involving patients presenting to the emergency department with severe sepsis and septic shock, mortality was markedly lower among those who were treated according to a 6-hour protocol of early goal-directed therapy (EGDT), in which intravenous fluids, vasopressors, inotropes, and blood transfusions were adjusted to reach central hemodynamic targets, than among those receiving usual care. We conducted a trial to determine whether these findings were generalizable and whether all aspects of the protocol were necessary.

METHODS:

In 31 emergency departments in the United States, we randomly assigned patients with septic shock to one of three groups for 6 hours of resuscitation: protocol-based EGDT; protocol-based standard therapy that did not require the placement of a central venous catheter, administration of inotropes, or blood transfusions; or usual care. The primary end point was 60-day in-hospital mortality. We tested sequentially whether protocol-based care (EGDT and standard-therapy groups combined) was superior to usual care and whether protocol-based EGDT was superior to protocol-based standard therapy. Secondary outcomes included longer-term mortality and the need for organ support.

RESULTS:

We enrolled 1341 patients, of whom 439 were randomly assigned to protocol-based EGDT, 446 to protocol-based standard therapy, and 456 to usual care. Resuscitation strategies differed significantly with respect to the monitoring of central venous pressure and oxygen and the use of intravenous fluids, vasopressors, inotropes, and blood transfusions. By 60 days, there were 92 deaths in the protocol-based EGDT group (21.0%), 81 in the protocol-based standard-therapy group (18.2%), and 86 in the usual-care group (18.9%) (relative risk with protocol-based therapy vs. usual care, 1.04; 95% confidence interval [CI], 0.82 to 1.31; P=0.83; relative risk with protocol-based EGDT vs. protocol-based standard therapy, 1.15; 95% CI, 0.88 to 1.51; P=0.31). There were no significant differences in 90-day mortality, 1-year mortality, or the need for organ support.

CONCLUSIONS:

In a multicenter trial conducted in the tertiary care setting, protocol-based resuscitation of patients in whom septic shock was diagnosed in the emergency department did not improve outcomes. (Funded by the National Institute of General Medical Sciences; ProCESS ClinicalTrials.gov number, NCT00510835.).

PMID: 24635773 [PubMed - indexed for MEDLINE]
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Thursday, 8 May 2014

What's new for 'JKB_daily1' in PubMed

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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. N Engl J Med. 2014 Apr 17;370(16):1524-31. doi: 10.1056/NEJMoa1303359.

Transferable vancomycin resistance in a community-associated MRSA lineage.

Rossi F1, Diaz L, Wollam A, Panesso D, Zhou Y, Rincon S, Narechania A, Xing G, Di Gioia TS, Doi A, Tran TT, Reyes J, Munita JM, Carvajal LP, Hernandez-Roldan A, Brandão D, van der Heijden IM, Murray BE, Planet PJ, Weinstock GM, Arias CA.

Author information:
1From the Department of Pathology, Division of Microbiology of the Central Laboratory (LIM 03) and Department of Infectious Disease (LIM 54), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo (F.R., T.S.R.D.G., A.D., D.B., I.M.H.); Molecular Genetics and Antimicrobial Resistance Unit, Universidad El Bosque, Bogota (L.D., D.P., S.R., J.R., L.P.C., C.A.A.), and Centro Internacional de Entrenamiento e Investigaciones Medicas (CIDEIM), Cali (A.H.-R.) - both in Colombia; Clinica Alemana de Santiago, Universidad del Desarrollo, Santiago, Chile (J.M.M.); the Department of Internal Medicine, Division of Infectious Diseases (L.D., D.P., T.T.T., J.R., J.M.M., A.H.-R., B.E.M, C.A.A.), and the Department of Microbiology and Molecular Genetics (B.E.M., C.A.A.), University of Texas Medical School at Houston, and the University of Houston College of Pharmacy (T.T.T.) - both in Houston; the Genome Institute, Washington University at St. Louis, St. Louis (A.W., Y.Z., G.M.W.); and Sackler Institute for Comparative Genomics, American Museum of Natural History (A.N., P.J.P.), and Division of Pediatric Infectious Diseases, Columbia University (G.X., P.J.P.) - both in New York.

Abstract

We report the case of a patient from Brazil with a bloodstream infection caused by a strain of methicillin-resistant Staphylococcus aureus (MRSA) that was susceptible to vancomycin (designated BR-VSSA) but that acquired the vanA gene cluster during antibiotic therapy and became resistant to vancomycin (designated BR-VRSA). Both strains belong to the sequence type (ST) 8 community-associated genetic lineage that carries the staphylococcal chromosomal cassette mec (SCCmec) type IVa and the S. aureus protein A gene (spa) type t292 and are phylogenetically related to MRSA lineage USA300. A conjugative plasmid of 55,706 bp (pBRZ01) carrying the vanA cluster was identified and readily transferred to other staphylococci. The pBRZ01 plasmid harbors DNA sequences that are typical of the plasmid-associated replication genes rep24 or rep21 described in community-associated MRSA strains from Australia (pWBG745). The presence and dissemination of community-associated MRSA containing vanA could become a serious public health concern.

PMID: 24738669 [PubMed - indexed for MEDLINE]
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Saturday, 3 May 2014

What's new for 'JKB_daily1' in PubMed

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

Sent on Saturday, 2014 May 03
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
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1. Vet Immunol Immunopathol. 2013 Oct 1;155(4):219-28. doi: 10.1016/j.vetimm.2013.07.003. Epub 2013 Jul 20.

The equine alveolar macrophage: functional and phenotypic comparisons with peritoneal macrophages.

Karagianni AE1, Kapetanovic R, McGorum BC, Hume DA, Pirie SR.

Author information:
1The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9PS, UK. Electronic address: anna.karagianni@roslin.ed.ac.uk.

Abstract

Alveolar macrophages (AMs) constitute the first line of defence in the lung of all species, playing a crucial role in the regulation of immune responses to inhaled pathogens. A detailed understanding of the function and phenotype of AMs is a necessary pre-requisite to both elucidating their role in preventing opportunistic bacterial colonisation of the lower respiratory tract and developing appropriate preventative strategies. The purpose of the study was to characterise this important innate immune cell at the tissue level by making functional and phenotypic comparisons with peritoneal macrophages (PMs). We hypothesised that the tissue of origin determines a unique phenotype of AMs, which may constitute an appropriate therapeutic target for certain equine respiratory diseases. Macrophages isolated from the lung and the peritoneal cavity of 9 horses were stimulated with various toll like receptor (TLR) ligands and the production of nitrite, tumour necrosis factor alpha (TNFα), interleukin (IL) 10 and indoleamine 2,3-dioxygenase (IDO) were measured by the Griess reaction and enzyme linked immunosorbent assay (ELISA) and/or quantitative polymerase chain reaction, respectively. Cells were also compared on the basis of phagocytic-capacity and the expression of several cell surface markers. AMs, but not PMs, demonstrated increased TNFα release following stimulation with LPS, polyinosinic polycytidylic acid (Poly IC) and heat-killed Salmonella typhinurium and increased TNFα and IDO mRNA expression when stimulated with LPS. AMs showed high expression of the specific macrophage markers cluster of differentiation (CD) 14, CD163 and TLR4, whereas PMs showed high expression of TLR4 only. AMs, but not PMs, demonstrated efficient phagocytic activity. Our results demonstrate that AMs are more active than PMs when stimulated with various pro-inflammatory ligands, thus supporting the importance of the local microenvironment in the activation status of the macrophage. This information provides a valuable knowledge base on which to improve our understanding of the role of macrophages and their microenvironment in equine innate immunity.

Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

PMCID: PMC3795452 Free PMC Article
PMID: 23978307 [PubMed - indexed for MEDLINE]
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