139 research outputs found
\u3ci\u3eHelicobacter pylori\u3c/i\u3e: Genomic Insight into the Host-Pathogen Interaction
The advent of genomic analyses has revolutionized the study of human health. Infectious disease research in particular has experienced an explosion of bacterial genomic, transcriptomic, and proteomic data complementing the phenotypic methods employed in traditional bacteriology. Together, these techniques have revealed novel virulence determinants in numerous pathogens and have provided information for potential chemotherapeutics. The bacterial pathogen, Helicobacter pylori, has been recognized as a class 1 carcinogen and contributes to chronic inflammation within the gastric niche. Genomic analyses have uncovered remarkable coevolution between the human host and H. pylori. Perturbation of this coevolution results in dysregulation of the host-pathogen interaction, leading to oncogenic effects. This review discusses the relationship of H. pylori with the human host and environment and the contribution of each of these factors to disease progression, with an emphasis on features that have been illuminated by genomic tools
Nutrition and \u3ci\u3eHelicobacter pylori\u3c/i\u3e: Host Diet and Nutritional Immunity Influence Bacterial Virulence and Disease Outcome
Helicobacter pylori colonizes the stomachs of greater than 50% of the worldâs human population making it arguably one of the most successful bacterial pathogens. Chronic H. pylori colonization results in gastritis in nearly all patients; however in a subset of people, persistent infection with H. pylori is associated with an increased risk for more severe disease outcomes including B-cell lymphoma of mucosal-associated lymphoid tissue (MALT lymphoma) and invasive adenocarcinoma. Research aimed at elucidating determinants that mediate disease progression has revealed genetic differences in both humans and H. pylori which increase the risk for developing gastric cancer. Furthermore, host diet and nutrition status have been shown to influence H. pylori-associated disease outcomes. In this review we will discuss how H. pylori is able to create a replicative niche within the hostile host environment by subverting and modifying the host-generated immune response as well as successfully competing for limited nutrients such as transition metals by deploying an arsenal of metal acquisition proteins and virulence factors. Lastly, we will discuss how micronutrient availability or alterations in the gastric microbiome may exacerbate negative disease outcomes associated with H. pylori colonization
Nutrition and Helicobacter pylori
Helicobacter pylori colonizes the stomachs of greater than 50% of the worldâs human population making it arguably one of the most successful bacterial pathogens. Chronic H. pylori colonization results in gastritis in nearly all patients; however in a subset of people, persistent infection with H. pylori is associated with an increased risk for more severe disease outcomes including B-cell lymphoma of mucosal-associated lymphoid tissue (MALT lymphoma) and invasive adenocarcinoma. Research aimed at elucidating determinants that mediate disease progression has revealed genetic differences in both humans and H. pylori which increase the risk for developing gastric cancer. Furthermore, host diet and nutrition status have been shown to influence H. pylori-associated disease outcomes. In this review we will discuss how H. pylori is able to create a replicative niche within the hostile host environment by subverting and modifying the host-generated immune response as well as successfully competing for limited nutrients such as transition metals by deploying an arsenal of metal acquisition proteins and virulence factors. Lastly, we will discuss how micronutrient availability or alterations in the gastric microbiome may exacerbate negative disease outcomes associated with H. pylori colonization
S100A12 in Digestive Diseases and Health: A Scoping Review
Calgranulin proteins are an important class of molecules involved in innate immunity. These members of the S100 class of the EF-hand family of calcium-binding proteins have numerous cellular and antimicrobial functions. One protein in particular, S100A12 (also called EN-RAGE or calgranulin C), is highly abundant in neutrophils during acute inflammation and has been implicated in immune regulation. Structure-function analyses reveal that S100A12 has the capacity to bind calcium, zinc, and copper, processes that contribute to nutritional immunity against invading microbial pathogens. S100A12 is a ligand for the receptor for advanced glycation end products (RAGE), toll-like receptor 4 (TLR4), and CD36, which promote cellular and immunological pathways to alter inflammation. We conducted a scoping review of the existing literature to define what is known about the association of S100A12 with digestive disease and health. Results suggest that S100A12 is implicated in gastroenteritis, necrotizing enterocolitis, gastritis, gastric cancer, Crohnâs disease, irritable bowel syndrome, inflammatory bowel disease, and digestive tract cancers. Together, these results reveal S100A12 is an important molecule broadly associated with the pathogenesis of digestive diseases
Spinal Locomotor Circuits Develop Using Hierarchical Rules Based on Motorneuron Position and Identity
SummaryThe coordination of multi-muscle movements originates in the circuitry that regulates the firing patterns of spinal motorneurons. Sensory neurons rely on the musculotopic organization of motorneurons to establish orderly connections, prompting us to examine whether the intraspinal circuitry that coordinates motor activity likewise uses cell position as an internal wiring reference. We generated a motorneuron-specific GCaMP6f mouse line and employed two-photon imaging to monitor the activity of lumbar motorneurons. We show that the central pattern generator neural network coordinately drives rhythmic columnar-specific motorneuron bursts at distinct phases of the locomotor cycle. Using multiple genetic strategies to perturb the subtype identity and orderly position of motorneurons, we found that neurons retained their rhythmic activityâbut cell position was decoupled from the normal phasing pattern underlying flexion and extension. These findings suggest a hierarchical basis of motor circuit formation that relies on increasingly stringent matching of neuronal identity and position
Haplotype-based association analysis of general cognitive ability in Generation Scotland, the English Longitudinal Study of Ageing, and UK Biobank
Background: Cognitive ability is a heritable trait with a polygenic architecture, for which several associated variants have been identified using genotype-based and candidate gene approaches. Haplotype-based analyses are a complementary technique that take phased genotype data into account, and potentially provide greater statistical power to detect lower frequency variants.
Methods: In the present analysis, three cohort studies (ntotal = 48,002) were utilised: Generation Scotland: Scottish Family Health Study (GS:SFHS), the English Longitudinal Study of Ageing (ELSA), and the UK Biobank. A genome-wide haplotype-based meta-analysis of cognitive ability was performed, as well as a targeted meta-analysis of several gene coding regions.
Results: None of the assessed haplotypes provided evidence of a statistically significant association with cognitive ability in either the individual cohorts or the meta-analysis. Within the meta-analysis, the haplotype with the lowest observed P-value overlapped with the D-amino acid oxidase activator (DAOA) gene coding region. This coding region has previously been associated with bipolar disorder, schizophrenia and Alzheimerâs disease, which have all been shown to impact upon cognitive ability. Another potentially interesting region highlighted within the current genome-wide association analysis (GS:SFHS: P = 4.09 x 10-7), was the butyrylcholinesterase (BCHE) gene coding region. The protein encoded by BCHE has been shown to influence the progression of Alzheimerâs disease and its role in cognitive ability merits further investigation.
Conclusions: Although no evidence was found for any haplotypes with a statistically significant association with cognitive ability, our results did provide further evidence that the genetic variants contributing to the variance of cognitive ability are likely to be of small effect
Volume 02
Introduction from Dean Dr. Charles Ross
Mike\u27s Nite: New Jazz for an Old Instrument by Joseph A. Mann
Investigation of the use of Cucumis Sativus for Remediation Of Chromium from Contaminated Environmental Matrices: An Interdisciplinary Instrumental Analysis Project by Kathryn J. Greenly, Scott E. Jenkins, and Andrew E. Puckette
Development of GC-MS and Chemometric Methods for the Analysis of Accelerants in Arson Cases by Scott Jenkins
Building and Measuring Scalable Computing Systems by Daniel M. Honey and Jeffery P. Ravenhorst
Nomini Hall: A Case Study in the Use of Archival Resources as Guides for Excavation at An Archaeological Site by Jamie Elizabeth Mesrobian
Two Stories: In Ohio and How to Stay Out of the Brazilian Army by Thomas Scott
Forgerson des Hommes/Stealing the Steel in Zola\u27s Men by Jay Crowell
Paul Gauguin\u27s Escape into Primitivism by Sarah Spangenberg
Lee Krasner, Abstract Expressionist by Amy S. Eason
Artist Book âParisâ by Kenny Wolfe
Artist Book âSequence of Every Dayâ by Liz Hale
Artist Book âApple Treeâ by Rachel Bouchard
Artist Book âNot so Pretty in Pinkâ by Will Semonco
Artist Book âLook into the Moonâ by Carley York
Artist Books âExtraâ and âGreenâ by Ryan Higgenbothom
Artist Book âRe-growing Appalachiaâ by Adrienne Heinbaugh
Artist Books âCheeziestâ, âUh-ohâ and âThe Girl with the Glassesâ by Melissa Dorton
âSelf-Reflectionâ by Madeline Hunter
Artist Book âThe Princess and the Frogâ by June Ashmore
âHunterâs Nicheâ and âThe Wildâ by Clark Barkley
âTo Thine Own Self be Trueâ by Jay Haley
âNot Funnyâ Ten-Minute Play Festiva
The IMPROVE guidelines (Ischaemia Models: Procedural Refinements Of in Vivo Experiments)
Most in vivo models of ischaemic stroke target the middle cerebral artery and a spectrum of stroke severities, from mild to substantial, can be achieved. This review describes opportunities to improve the in vivo modelling of ischaemic stroke and animal welfare. It provides a number of recommendations to minimise the level of severity in the most common rodent models of middle cerebral artery occlusion, while sustaining or improving the scientific outcomes. The recommendations cover basic requirements pre-surgery, selecting the most appropriate anaesthetic and analgesic regimen, as well as intraoperative and post-operative care. The aim is to provide support for researchers and animal care staff to refine their procedures and practices, and implement small incremental changes to improve the welfare of the animals used and to answer the scientific question under investigation. All recommendations are recapitulated in a summary poster (see supplementary information)
The NANOGrav 15-year Data Set: Evidence for a Gravitational-Wave Background
We report multiple lines of evidence for a stochastic signal that is
correlated among 67 pulsars from the 15-year pulsar-timing data set collected
by the North American Nanohertz Observatory for Gravitational Waves. The
correlations follow the Hellings-Downs pattern expected for a stochastic
gravitational-wave background. The presence of such a gravitational-wave
background with a power-law-spectrum is favored over a model with only
independent pulsar noises with a Bayes factor in excess of , and this
same model is favored over an uncorrelated common power-law-spectrum model with
Bayes factors of 200-1000, depending on spectral modeling choices. We have
built a statistical background distribution for these latter Bayes factors
using a method that removes inter-pulsar correlations from our data set,
finding (approx. ) for the observed Bayes factors in the
null no-correlation scenario. A frequentist test statistic built directly as a
weighted sum of inter-pulsar correlations yields (approx. ). Assuming a fiducial
characteristic-strain spectrum, as appropriate for an ensemble of binary
supermassive black-hole inspirals, the strain amplitude is (median + 90% credible interval) at a reference frequency of
1/(1 yr). The inferred gravitational-wave background amplitude and spectrum are
consistent with astrophysical expectations for a signal from a population of
supermassive black-hole binaries, although more exotic cosmological and
astrophysical sources cannot be excluded. The observation of Hellings-Downs
correlations points to the gravitational-wave origin of this signal.Comment: 30 pages, 18 figures. Published in Astrophysical Journal Letters as
part of Focus on NANOGrav's 15-year Data Set and the Gravitational Wave
Background. For questions or comments, please email [email protected]
The NANOGrav 15-year data set: Search for Transverse Polarization Modes in the Gravitational-Wave Background
Recently we found compelling evidence for a gravitational wave background
with Hellings and Downs (HD) correlations in our 15-year data set. These
correlations describe gravitational waves as predicted by general relativity,
which has two transverse polarization modes. However, more general metric
theories of gravity can have additional polarization modes which produce
different interpulsar correlations. In this work we search the NANOGrav 15-year
data set for evidence of a gravitational wave background with quadrupolar
Hellings and Downs (HD) and Scalar Transverse (ST) correlations. We find that
HD correlations are the best fit to the data, and no significant evidence in
favor of ST correlations. While Bayes factors show strong evidence for a
correlated signal, the data does not strongly prefer either correlation
signature, with Bayes factors when comparing HD to ST correlations,
and for HD plus ST correlations to HD correlations alone. However,
when modeled alongside HD correlations, the amplitude and spectral index
posteriors for ST correlations are uninformative, with the HD process
accounting for the vast majority of the total signal. Using the optimal
statistic, a frequentist technique that focuses on the pulsar-pair
cross-correlations, we find median signal-to-noise-ratios of 5.0 for HD and 4.6
for ST correlations when fit for separately, and median signal-to-noise-ratios
of 3.5 for HD and 3.0 for ST correlations when fit for simultaneously. While
the signal-to-noise-ratios for each of the correlations are comparable, the
estimated amplitude and spectral index for HD are a significantly better fit to
the total signal, in agreement with our Bayesian analysis.Comment: 11 pages, 5 figure
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