Inflammatory bowel disease (IBD) is a complex genetic disease that is instigated and amplified by the confluence of multiple genetic and environmental variables that perturb the immune-microbiome ...axis. The challenge of dissecting pathological mechanisms underlying IBD has led to the development of transformative approaches in human genetics and functional genomics. Here we describe IBD as a model disease in the context of leveraging human genetics to dissect interactions in cellular and molecular pathways that regulate homeostasis of the mucosal immune system. Finally, we synthesize emerging insights from multiple experimental approaches into pathway paradigms and discuss future prospects for disease-subtype classification and therapeutic intervention.
Massive disk galaxies like the Milky Way are expected to form at late times in traditional models of galaxy formation
, but recent numerical simulations suggest that such galaxies could form as early ...as a billion years after the Big Bang through the accretion of cold material and mergers
. Observationally, it has been difficult to identify disk galaxies in emission at high redshift
in order to discern between competing models of galaxy formation. Here we report imaging, with a resolution of about 1.3 kiloparsecs, of the 158-micrometre emission line from singly ionized carbon, the far-infrared dust continuum and the near-ultraviolet continuum emission from a galaxy at a redshift of 4.2603, identified by detecting its absorption of quasar light. These observations show that the emission arises from gas inside a cold, dusty, rotating disk with a rotational velocity of about 272 kilometres per second. The detection of emission from carbon monoxide in the galaxy yields a molecular mass that is consistent with the estimate from the ionized carbon emission of about 72 billion solar masses. The existence of such a massive, rotationally supported, cold disk galaxy when the Universe was only 1.5 billion years old favours formation through either cold-mode accretion or mergers, although its large rotational velocity and large content of cold gas remain challenging to reproduce with most numerical simulations
.
The inflammatory bowel diseases (IBDs) are among the most closely studied chronic inflammatory disorders that involve environmental, host genetic, and commensal microbial factors. This combination of ...features has made IBD both an appropriate and a high-priority platform for translatable research in host-microbiome interactions. Decades of epidemiology have identified environmental risk factors, although most mechanisms of action remain unexplained. The genetic architecture of IBD has been carefully dissected in multiple large populations, identifying several responsible host epithelial and immune pathways but without yet a complete systems-level explanation. Most recently, the commensal gut microbiota have been found to be both ecologically and functionally perturbed during the disease, but with as-yet-unexplained heterogeneity among IBD subtypes and individual patients. IBD thus represents perhaps the most comprehensive current model for understanding the human microbiome’s role in complex inflammatory disease. Here, we review the influences of the microbiota on IBD and its potential for translational medicine.
Inflammatory bowel diseases (IBDs) involve environmental, host genetic, and commensal microbial factors, thereby allowing interrogation of interactions between the microbiome and immune system. Here Huttenhower et al. review the role of microbiota in IBD and its potential for translational medicine.
Perturbations in the intestinal microbiome are implicated in inflammatory bowel disease (IBD). Studies of treatment-naive patients have identified microbial taxa associated with disease course and ...treatment efficacy. To gain a mechanistic understanding of how the microbiome affects gastrointestinal health, we need to move from census to function. Bacteria, including those that adhere to epithelial cells as well as several Clostridium species, can alter differentiation of T helper 17 cells and regulatory T cells. Similarly, microbial products such as short-chain fatty acids and sphingolipids also influence immune responses. Metagenomics and culturomics have identified strains of Ruminococcus gnavus and adherent invasive Escherichia coli that are linked to IBD and gut inflammation. Integrated analysis of multiomics data, including metagenomics, metatranscriptomics and metabolomics, with measurements of host response and culturomics, have great potential in understanding the role of the microbiome in IBD. In this Review, we highlight current knowledge of gut microbial factors linked to IBD pathogenesis and discuss how multiomics data from large-scale population studies in health and disease have been used to identify specific microbial strains, transcriptional changes and metabolic alterations associated with IBD.
We present Keck NIRSPEC and Keck NIRES spectroscopy of sixteen metal-poor galaxies that have pre-existing optical observations. The near-infrared (NIR) spectroscopy specifically targets the He i ...λ10830 emission line, due to its sensitivity to the physical conditions of the gas in H ii regions. We use these NIR observations, combined with optical spectroscopy, to determine the helium abundance of sixteen galaxies across a metallicity range = 7.13-8.00. This data set is combined with two other samples where metallicity and helium abundance measurements can be secured: star-forming galaxies selected from the Sloan Digital Sky Survey spectroscopic database, and existing low-metallicity systems in the literature. We calculate a linear fit to these measurements, accounting for intrinsic scatter, and report a new determination of the primordial helium number abundance, , which corresponds to a primordial helium mass fraction . Using our determination of the primordial helium abundance in combination with the latest primordial deuterium measurement, , we place a bound on the baryon density and the effective number of neutrino species . These values are in 1.3 agreement with those deduced from the Planck satellite observations of the temperature fluctuations imprinted on the cosmic microwave background.
The intestinal microbiota, which is composed of bacteria, viruses, and micro-eukaryotes, acts as an accessory organ system with distinct functions along the intestinal tract that are critical for ...health. This review focuses on how the microbiota drives intestinal disease through alterations in microbial community architecture, disruption of the mucosal barrier, modulation of innate and adaptive immunity, and dysfunction of the enteric nervous system. Inflammatory bowel disease is used as a model system to understand these microbial-driven pathologies, but the knowledge gained in this space is extended to less-well-studied intestinal diseases that may also have an important microbial component, including environmental enteropathy and chronic colitis-associated colorectal cancer.
The human gut microbiota plays an important role in maintaining a healthy gastrointestinal tract. In this review, Wlodarska et al. discuss the current knowledge of host-microbiota interactions in gut health, and how microbial dysbiosis contributes to the development and pathology of inflammatory diseases of the intestine, including inflammatory bowel disease.
Recent advances have provided substantial insight into the maintenance of mucosal immunity and the pathogenesis of inflammatory bowel disease. Cellular programs responsible for intestinal homeostasis ...use diverse intracellular and intercellular networks to promote immune tolerance, inflammation or epithelial restitution. Complex interfaces integrate local host and microbial signals to activate appropriate effector programs selectively and even drive plasticity between these programs. In addition, genetic studies and mouse models have emphasized the role of genetic predispositions and how they affect interactions with microbial and environmental factors, leading to pro-colitogenic perturbations of the host-commensal relationship.
Taxonomic and functional changes to the composition of the gut microbiome have been implicated in multiple human diseases. Recent microbiome genome-wide association studies reveal that variants in ...many human genes involved in immunity and gut architecture are associated with an altered composition of the gut microbiome. Although many factors can affect the microbial organisms residing in the gut, a number of recent findings support the hypothesis that certain host genetic variants predispose an individual towards microbiome dysbiosis. This condition, in which the normal microbiome population structure is disturbed, is a key feature in disorders of metabolism and immunity.
Studies of the roles of microbial communities in the development of inflammatory bowel disease (IBD) have reached an important milestone. A decade of genome-wide association studies and other genetic ...analyses have linked IBD with loci that implicate an aberrant immune response to the intestinal microbiota. More recently, profiling studies of the intestinal microbiome have associated the pathogenesis of IBD with characteristic shifts in the composition of the intestinal microbiota, reinforcing the view that IBD results from altered interactions between intestinal microbes and the mucosal immune system. Enhanced technologies can increase our understanding of the interactions between the host and its resident microbiota and their respective roles in IBD from both a large-scale pathway view and at the metabolic level. We review important microbiome studies of patients with IBD and describe what we have learned about the mechanisms of intestinal microbiota dysfunction. We describe the recent progress in microbiome research from exploratory 16S-based studies, reporting associations of specific organisms with a disease, to more recent studies that have taken a more nuanced view, addressing the function of the microbiota by metagenomic and metabolomic methods. Finally, we propose study designs and methodologies for future investigations of the microbiome in patients with inflammatory gut and autoimmune diseases in general.
Correcting C iv-based virial black hole masses Coatman, Liam; Hewett, Paul C; Banerji, Manda ...
Monthly notices of the Royal Astronomical Society,
02/2017, Letnik:
465, Številka:
2
Journal Article
Recenzirano
Odprti dostop
The C IV...1498,1501 broad emission line is visible in optical spectra to redshifts exceeding z ~ 5. C IV has long been known to exhibit significant displacements to the blue and these 'blueshifts' ...almost certainly signal the presence of strong outflows. As a consequence, single-epoch virial black hole (BH) mass estimates derived from C IV velocity widths are known to be systematically biased compared to masses from the hydrogen Balmer lines. Using a large sample of 230 high-luminosity (LBol = 10...-10... erg s...), redshift 1.5 < z < 4.0 quasars with both C IV and Balmer line spectra, we have quantified the bias in C IV BH masses as a function of the C IV blueshift. C IV BH masses are shown to be a factor of 5 larger than the corresponding Balmer-line masses at C IV blueshifts of 3000 km s... and are overestimated by almost an order of magnitude at the most extreme blueshifts, ...5000 km s... Using the monotonically increasing relationship between the C IV blueshift and the mass ratio BH(C IV)/BH(Ha), we derive an empirical correction to all C IV BH masses. The scatter between the corrected C IV masses and the Balmer masses is 0.24 dex at low C IV blueshifts (~0 km s...) and just 0.10 dex at high blueshifts (~3000 km s...), compared to 0.40 dex before the correction. The correction depends only on the C IV line properties -- i.e. full width at half-maximum and blueshift -- and can therefore be applied to all quasars where C IV emission line properties have been measured, enabling the derivation of unbiased virial BH-mass estimates for the majority of high-luminosity, high-redshift, spectroscopically confirmed quasars in the literature. (ProQuest: ... denotes formulae/symbols omitted.)
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