80 research outputs found
A Prospective Study of Periodontal Disease and Risk of Gastric and Duodenal Ulcer in Male Health Professionals
OBJECTIVES: Periodontal disease has been associated with higher circulating levels of inflammatory markers and conditions associated with chronic inflammation, including vascular disease, diabetes mellitus, and cancer. Limited data exist on the relationship between periodontal disease and gastric and duodenal ulcer. METHODS: We conducted a prospective cohort study of 49,120 men in the Health Professionals Follow-up Study, aged 40–75 years at enrollment in 1986. Biennially, we assessed periodontal disease, tooth loss, and other risk factors for gastric and duodenal ulcer. We validated diagnoses of gastric and duodenal ulcer through medical record review. We used Cox proportional hazards modeling, adjusting for potential confounders, to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We documented 138 cases of gastric ulcer and 124 cases of duodenal ulcer with available information on Helicobacter pylori status over 24 years of follow-up. After adjustment for risk factors, including smoking and regular use of aspirin and non-steroidal anti-inflammatory drugs, men with periodontal disease with bone loss had a multivariate HR of ulcer of 1.62 (95% CI, 1.24–2.12). Periodontal disease appeared to be associated with a similar risk of developing ulcers that were H. pylori negative (HR 1.75; 95% CI, 1.26–2.43) than H. pylori positive (HR 1.40; 95% CI, 0.87-2.24), as well as ulcers in the stomach (HR 1.75; 95% CI, 1.21–2.53) than ulcers in the duodenum (HR 1.47; 95% CI, 0.98–2.19). CONCLUSIONS: Periodontal disease is associated with an increased risk of incident gastric and duodenal ulcer. This relationship may be mediated by alterations in the oral and gastrointestinal microbiome and/or systemic inflammatory factors
Relating the metatranscriptome and metagenome of the human gut
Although the composition of the human microbiome is now wellstudied, the microbiota’s \u3e8 million genes and their regulation remain largely uncharacterized. This knowledge gap is in part because of the difficulty of acquiring large numbers of samples amenable to functional studies of the microbiota. We conducted what is, to our knowledge, one of the first human microbiome studies in a well-phenotyped prospective cohort incorporating taxonomic, metagenomic, and metatranscriptomic profiling at multiple body sites using self-collected samples. Stool and saliva were provided by eight healthy subjects, with the former preserved by three different methods (freezing, ethanol, and RNAlater) to validate self-collection. Within-subject microbial species, gene, and transcript abundances were highly concordant across sampling methods, with only a small fraction of transcripts (\u3c5%) displaying between-method variation. Next, we investigated relationships between the oral and gut microbial communities, identifying a subset of abundant oral microbes that routinely survive transit to the gut, but with minimal transcriptional activity there. Finally, systematic comparison of the gut metagenome and metatranscriptome revealed that a substantial fraction (41%) of microbial transcripts were not differentially regulated relative to their genomic abundances. Of the remainder, consistently underexpressed pathways included sporulation and amino acid biosynthesis, whereas up-regulated pathways included ribosome biogenesis and methanogenesis. Across subjects, metatranscriptional profiles were significantly more individualized than DNA-level functional profiles, but less variable than microbial composition, indicative of subject-specific whole-community regulation. The results thus detail relationships between community genomic potential and gene expression in the gut, and establish the feasibility of metatranscriptomic investigations in subject-collected and shipped samples
Living longer, but with more care needs: late-life dependency and the social care crisis
Solving the crisis in social care provision for older people is not just a matter of building more care homes, argues Carol Jagger. She explains the various ways in which dependency has changed compared to 20 years ago, and suggests some of the solutions the government should consider
What Causes The Formation of Disks and End of Bursty Star Formation?
As they grow, galaxies can transition from irregular/spheroidal with 'bursty'
star formation histories (SFHs), to disky with smooth SFHs. But even in
simulations, the direct physical cause of such transitions remains unclear. We
therefore explore this in a large suite of numerical experiments re-running
portions of cosmological simulations with widely varied physics, further
validated with existing FIRE simulations. We show that gas supply,
cooling/thermodynamics, star formation model, Toomre scale, galaxy dynamical
times, and feedback properties do not have a direct causal effect on these
transitions. Rather, both the formation of disks and cessation of bursty star
formation are driven by the gravitational potential, but in different ways.
Disk formation is promoted when the mass profile becomes sufficiently
centrally-concentrated in shape (relative to circularization radii): we show
that this provides a well-defined dynamical center, ceases to support the
global 'breathing modes' which can persist indefinitely in less-concentrated
profiles and efficiently destroy disks, promotes orbit mixing to form a
coherent angular momentum, and stabilizes the disk. Smooth SF is promoted by
the potential or escape velocity (not circular velocity) becoming sufficiently
large at the radii of star formation that cool, mass-loaded
(momentum-conserving) outflows are trapped/confined near the galaxy, as opposed
to escaping after bursts. We discuss the detailed physics, how these conditions
arise in cosmological contexts, their relation to other correlated phenomena
(e.g. inner halo virialization, vertical disk 'settling'), and observations.Comment: Submitted to MNRAS. 44 pages, 32 figures. Comments welcome. (Minor
text corrections from previous version
Abnormal Expression Of Homeobox Genes And Transthyretin In C9Orf72 Expansion Carriers
Objective: We performed a genome-wide brain expression study to reveal the underpinnings of diseases linked to a repeat expansion in chromosome 9 open reading frame 72 (C9ORF72). Methods: The genome-wide expression profile was investigated in brain tissue obtained from C9ORF72 expansion carriers (n = 32), patients without this expansion (n = 30), and controls (n = 20). Using quantitative real-time PCR, findings were confirmed in our entire pathologic cohort of expansion carriers (n = 56) as well as nonexpansion carriers (n = 31) and controls (n = 20). Results: Our findings were most profound in the cerebellum, where we identified 40 differentially expressed genes, when comparing expansion carriers to patients without this expansion, including 22 genes that have a homeobox (e.g., HOX genes) and/or are located within the HOX gene cluster (top hit: homeobox A5 [HOXA5]). In addition to the upregulation of multiple homeobox genes that play a vital role in neuronal development, we noticed an upregulation of transthyretin (TTR), an extracellular protein that is thought to be involved in neuroprotection. Pathway analysis aligned with these findings and revealed enrichment for gene ontology processes involved in (anatomic) development (e.g., organ morphogenesis). Additional analyses uncovered that HOXA5 and TTR levels are associated with C9ORF72 variant 2 levels as well as with intron-containing transcript levels, and thus, disease-related changes in those transcripts may have triggered the upregulation of HOXA5 and TTR. Conclusions: In conclusion, our identification of genes involved in developmental processes and neuroprotection sheds light on potential compensatory mechanisms influencing the occurrence, presentation, and/or progression of C9ORF72-related diseases
Creation of an Open-Access, Mutation-Defined Fibroblast Resource for Neurological Disease Research
Our understanding of the molecular mechanisms of many neurological disorders has been greatly enhanced by the discovery of mutations in genes linked to familial forms of these diseases. These have facilitated the generation of cell and animal models that can be used to understand the underlying molecular pathology. Recently, there has been a surge of interest in the use of patient-derived cells, due to the development of induced pluripotent stem cells and their subsequent differentiation into neurons and glia. Access to patient cell lines carrying the relevant mutations is a limiting factor for many centres wishing to pursue this research. We have therefore generated an open-access collection of fibroblast lines from patients carrying mutations linked to neurological disease. These cell lines have been deposited in the National Institute for Neurological Disorders and Stroke (NINDS) Repository at the Coriell Institute for Medical Research and can be requested by any research group for use in in vitro disease modelling. There are currently 71 mutation-defined cell lines available for request from a wide range of neurological disorders and this collection will be continually expanded. This represents a significant resource that will advance the use of patient cells as disease models by the scientific community
Magellan/M2FS Spectroscopy of Tucana 2 and Grus 1
We present results from spectroscopic observations with the Michigan/Magellan
Fiber System (M2FS) of stellar targets along the line of sight to the
newly-discovered `ultrafaint' stellar systems Tucana 2 (Tuc 2) and Grus 1 (Gru
1). Based on simultaneous estimates of line-of-sight velocity and
stellar-atmospheric parameters, we identify 8 and 7 stars as probable members
of Tuc 2 and and Gru 1, respectively. Our sample for Tuc 2 is sufficient to
resolve an internal velocity dispersion of km s
about a mean of km s (solar rest frame), and to
estimate a mean metallicity of [Fe/H]= . These results
place Tuc 2 on chemodynamical scaling relations followed by dwarf galaxies,
suggesting a dominant dark matter component with dynamical mass
enclosed within the central
pc, and dynamical mass-to-light ratio
. For Gru 1 we estimate a mean velocity of
km s and a mean metallicity of
[Fe/H]=, but our sample does not resolve Gru 1's
velocity dispersion. The radial coordinates of Tuc 2 and Gru 1 in Galactic
phase space suggest that their orbits are among the most energetic within
distance kpc. Moreover, their proximity to each other in this space
arises naturally if both objects are trailing the Large Magellanic Cloud.Comment: replaced with ApJ-accepted version, all spectra and data products
(including samples from posterior PDFs) are available at
http://www.andrew.cmu.edu/user/mgwalker/tuc2gru1_dataproducts.tar.g
Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe
- …