26 research outputs found
Characterization of the murine macrophage response to infection with virulent and avirulent Burkholderia species
A framework for human microbiome research
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
Structure, function and diversity of the healthy human microbiome
Author Posting. © The Authors, 2012. This article is posted here by permission of Nature Publishing Group. The definitive version was published in Nature 486 (2012): 207-214, doi:10.1038/nature11234.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.This research was supported in
part by National Institutes of Health grants U54HG004969 to B.W.B.; U54HG003273
to R.A.G.; U54HG004973 to R.A.G., S.K.H. and J.F.P.; U54HG003067 to E.S.Lander;
U54AI084844 to K.E.N.; N01AI30071 to R.L.Strausberg; U54HG004968 to G.M.W.;
U01HG004866 to O.R.W.; U54HG003079 to R.K.W.; R01HG005969 to C.H.;
R01HG004872 to R.K.; R01HG004885 to M.P.; R01HG005975 to P.D.S.;
R01HG004908 to Y.Y.; R01HG004900 to M.K.Cho and P. Sankar; R01HG005171 to
D.E.H.; R01HG004853 to A.L.M.; R01HG004856 to R.R.; R01HG004877 to R.R.S. and
R.F.; R01HG005172 to P. Spicer.; R01HG004857 to M.P.; R01HG004906 to T.M.S.;
R21HG005811 to E.A.V.; M.J.B. was supported by UH2AR057506; G.A.B. was
supported by UH2AI083263 and UH3AI083263 (G.A.B., C. N. Cornelissen, L. K. Eaves
and J. F. Strauss); S.M.H. was supported by UH3DK083993 (V. B. Young, E. B. Chang,
F. Meyer, T. M. S., M. L. Sogin, J. M. Tiedje); K.P.R. was supported by UH2DK083990 (J.
V.); J.A.S. and H.H.K. were supported by UH2AR057504 and UH3AR057504 (J.A.S.);
DP2OD001500 to K.M.A.; N01HG62088 to the Coriell Institute for Medical Research;
U01DE016937 to F.E.D.; S.K.H. was supported by RC1DE0202098 and
R01DE021574 (S.K.H. and H. Li); J.I. was supported by R21CA139193 (J.I. and
D. S. Michaud); K.P.L. was supported by P30DE020751 (D. J. Smith); Army Research
Office grant W911NF-11-1-0473 to C.H.; National Science Foundation grants NSF
DBI-1053486 to C.H. and NSF IIS-0812111 to M.P.; The Office of Science of the US
Department of Energy under Contract No. DE-AC02-05CH11231 for P.S. C.; LANL
Laboratory-Directed Research and Development grant 20100034DR and the US
Defense Threat Reduction Agency grants B104153I and B084531I to P.S.C.; Research
Foundation - Flanders (FWO) grant to K.F. and J.Raes; R.K. is an HHMI Early Career
Scientist; Gordon&BettyMoore Foundation funding and institutional funding fromthe
J. David Gladstone Institutes to K.S.P.; A.M.S. was supported by fellowships provided by
the Rackham Graduate School and the NIH Molecular Mechanisms in Microbial
Pathogenesis Training Grant T32AI007528; a Crohn’s and Colitis Foundation of
Canada Grant in Aid of Research to E.A.V.; 2010 IBM Faculty Award to K.C.W.; analysis
of the HMPdata was performed using National Energy Research Scientific Computing
resources, the BluBioU Computational Resource at Rice University
Aberrant angiogenesis: The gateway to diabetic complications
Diabetes Mellitus is a metabolic cum vascular syndrome with resultant abnormalities in both micro- and macrovasculature. The adverse long-term effects of diabetes mellitus have been described to involve many organ systems. Apart from hyperglycemia, abnormalities of angiogenesis may cause or contribute toward many of the clinical manifestations of diabetes. These are implicated in the pathogenesis of vascular abnormalities of the retina, kidneys, and fetus, impaired wound healing, increased risk of rejection of transplanted organs, and impaired formation of coronary collaterals. A perplexing feature of the aberrant angiogenesis is that excessive and insufficient angiogenesis can occur in different organs in the same individual. The current article hereby reviews the molecular mechanisms including abnormalities in growth factors, cytokines, and metabolic derangements, clinical implications, and therapeutic options of dealing with abnormal angiogenesis in diabetes
Tuberous Sclerosis: An uncommon cause of hyperprolactinemia
Tuberous Sclerosis is a multi system genetic disorder affecting skin, central nervous system,kidney,heart and lungs. We present a case report of a 26 year old female with tuberous sclerosis who presented with galactorrhea and menstrual irregularities due to hyperprolactinemia
In situ nuclear organization of regulatory machinery
Regulatory machinery for gene expression, replication, and repair are architecturally organized in nuclear microenvironments. This compartmentalization provides threshold concentrations of macromolecules for the organization and assembly of regulatory complexes for combinatorial control. A mechanistic under standing of biological control requires the combined application of molecular, cellular, biochemical, and in vivo genetic approaches. This chapter provides methodologies to characterize nuclear organization of regulatory machinery by in situ immunofluorescence microscopy