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Molecular and Microbial Microenvironments in Chronically Diseased Lungs Associated with Cystic Fibrosis.
To visualize the personalized distributions of pathogens and chemical environments, including microbial metabolites, pharmaceuticals, and their metabolic products, within and between human lungs afflicted with cystic fibrosis (CF), we generated three-dimensional (3D) microbiome and metabolome maps of six explanted lungs from three cystic fibrosis patients. These 3D spatial maps revealed that the chemical environments differ between patients and within the lungs of each patient. Although the microbial ecosystems of the patients were defined by the dominant pathogen, their chemical diversity was not. Additionally, the chemical diversity between locales in the lungs of the same individual sometimes exceeded interindividual variation. Thus, the chemistry and microbiome of the explanted lungs appear to be not only personalized but also regiospecific. Previously undescribed analogs of microbial quinolones and antibiotic metabolites were also detected. Furthermore, mapping the chemical and microbial distributions allowed visualization of microbial community interactions, such as increased production of quorum sensing quinolones in locations where Pseudomonas was in contact with Staphylococcus and Granulicatella, consistent with in vitro observations of bacteria isolated from these patients. Visualization of microbe-metabolite associations within a host organ in early-stage CF disease in animal models will help elucidate the complex interplay between the presence of a given microbial structure, antibiotics, metabolism of antibiotics, microbial virulence factors, and host responses.IMPORTANCE Microbial infections are now recognized to be polymicrobial and personalized in nature. Comprehensive analysis and understanding of the factors underlying the polymicrobial and personalized nature of infections remain limited, especially in the context of the host. By visualizing microbiomes and metabolomes of diseased human lungs, we reveal how different the chemical environments are between hosts that are dominated by the same pathogen and how community interactions shape the chemical environment or vice versa. We highlight that three-dimensional organ mapping methods represent hypothesis-building tools that allow us to design mechanistic studies aimed at addressing microbial responses to other microbes, the host, and pharmaceutical drugs
American Gut: An Open Platform For Citizen Science Microbiome Research
Copyright © 2018 McDonald et al. Although much work has linked the human microbiome to specific phenotypes and lifestyle variables, data from different projects have been challenging to integrate and the extent of microbial and molecular diversity in human stool remains unknown. Using standardized protocols from the Earth Microbiome Project and sample contributions from over 10,000 citizen-scientists, together with an open research network, we compare human microbiome specimens primarily from the United States, United Kingdom, and Australia to one another and to environmental samples. Our results show an unexpected range of beta-diversity in human stool microbiomes compared to environmental samples; demonstrate the utility of procedures for removing the effects of overgrowth during room-temperature shipping for revealing phenotype correlations; uncover new molecules and kinds of molecular communities in the human stool metabolome; and examine emergent associations among the microbiome, metabolome, and the diversity of plants that are consumed (rather than relying on reductive categorical variables such as veganism, which have little or no explanatory power). We also demonstrate the utility of the living data resource and cross-cohort comparison to confirm existing associations between the microbiome and psychiatric illness and to reveal the extent of microbiome change within one individual during surgery, providing a paradigm for open microbiome research and education. IMPORTANCE We show that a citizen science, self-selected cohort shipping samples through the mail at room temperature recaptures many known microbiome results from clinically collected cohorts and reveals new ones. Of particular interest is integrating n = 1 study data with the population data, showing that the extent of microbiome change after events such as surgery can exceed differences between distinct environmental biomes, and the effect of diverse plants in the diet, which we confirm with untargeted metabolomics on hundreds of samples
Advanced Technology Large-Aperture Space Telescope (ATLAST): A Technology Roadmap for the Next Decade
The Advanced Technology Large-Aperture Space Telescope (ATLAST) is a set of
mission concepts for the next generation of UVOIR space observatory with a
primary aperture diameter in the 8-m to 16-m range that will allow us to
perform some of the most challenging observations to answer some of our most
compelling questions, including "Is there life elsewhere in the Galaxy?" We
have identified two different telescope architectures, but with similar optical
designs, that span the range in viable technologies. The architectures are a
telescope with a monolithic primary mirror and two variations of a telescope
with a large segmented primary mirror. This approach provides us with several
pathways to realizing the mission, which will be narrowed to one as our
technology development progresses. The concepts invoke heritage from HST and
JWST design, but also take significant departures from these designs to
minimize complexity, mass, or both.
Our report provides details on the mission concepts, shows the extraordinary
scientific progress they would enable, and describes the most important
technology development items. These are the mirrors, the detectors, and the
high-contrast imaging technologies, whether internal to the observatory, or
using an external occulter. Experience with JWST has shown that determined
competitors, motivated by the development contracts and flight opportunities of
the new observatory, are capable of achieving huge advances in technical and
operational performance while keeping construction costs on the same scale as
prior great observatories.Comment: 22 pages, RFI submitted to Astro2010 Decadal Committe
American Gut: an Open Platform for Citizen Science Microbiome Research
McDonald D, Hyde E, Debelius JW, et al. American Gut: an Open Platform for Citizen Science Microbiome Research. mSystems. 2018;3(3):e00031-18
Finishing the euchromatic sequence of the human genome
The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead
1. Maisons de Rosette
Greg Robert Hyde. 1. Maisons de Rosette. In: Comité de Conservation des Monuments de l'Art Arabe. Fascicule 40, exercice 1946-1953, 1961. pp. 9-10
Sommaire
Greg Robert Hyde. Sommaire. In: Comité de Conservation des Monuments de l'Art Arabe. Fascicule 39, exercice 1941-1945, 1951. p. 322
7° Maison d'As-Suḥaymi
Greg Robert Hyde. 7° Maison d'As-Suḥaymi. In: Comité de Conservation des Monuments de l'Art Arabe. Fascicule 39, exercice 1941-1945, 1951. p. 295
8. Maison d'ar-Razzāz et de Ḳāytbāy
Greg Robert Hyde. 8. Maison d'ar-Razzāz et de Ḳāytbāy. In: Comité de Conservation des Monuments de l'Art Arabe. Fascicule 40, exercice 1946-1953, 1961. p. 187
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