846 research outputs found
Comparative host specificity of human- and pig- associated Staphylococcus aureus clonal lineages.
Bacterial adhesion is a crucial step in colonization of the skin. In this study, we investigated the differential adherence to human and pig corneocytes of six Staphylococcus aureus strains belonging to three human-associated [ST8 (CC8), ST22 (CC22) and ST36(CC30)] and two pig-associated [ST398 (CC398) and ST433(CC30)] clonal lineages, and their colonization potential in the pig host was assessed by in vivo competition experiments. Corneocytes were collected from 11 humans and 21 pigs using D-squameĀ® adhesive discs, and bacterial adherence to corneocytes was quantified by a standardized light microscopy assay. A previously described porcine colonization model was used to assess the potential of the six strains to colonize the pig host. Three pregnant, S. aureus-free sows were inoculated intravaginally shortly before farrowing with different strain mixes [mix 1) human and porcine ST398; mix 2) human ST36 and porcine ST433; and mix 3) human ST8, ST22, ST36 and porcine ST398] and the ability of individual strains to colonize the nasal cavity of newborn piglets was evaluated for 28 days after birth by strain-specific antibiotic selective culture. In the corneocyte assay, the pig-associated ST433 strain and the human-associated ST22 and ST36 strains showed significantly greater adhesion to porcine and human corneocytes, respectively (p<0.0001). In contrast, ST8 and ST398 did not display preferential host binding patterns. In the in vivo competition experiment, ST8 was a better colonizer compared to ST22, ST36, and ST433 prevailed over ST36 in colonizing the newborn piglets. These results are partly in agreement with previous genetic and epidemiological studies indicating the host specificity of ST22, ST36 and ST433 and the broad-host range of ST398. However, our in vitro and in vivo experiments revealed an unexpected ability of ST8 to adhere to porcine corneocytes and persist in the nasal cavity of pigs
Dual origin of enteric neurons in vagal Schwann cell precursors and the sympathetic neural crest
Most of the enteric nervous system derives from the āvagalā neural crest, lying at the level of somites 1ā7, which invades the digestive tract rostro-caudally from the foregut to the hindgut. Little is known about the initial phase of this colonization, which brings enteric precursors into the foregut. Here we show that the āvagal crestā subsumes two populations of enteric precursors with contrasted origins, initial modes of migration, and destinations. Crest cells adjacent to somites 1 and 2 produce Schwann cell precursors that colonize the vagus nerve, which in turn guides them into the esophagus and stomach. Crest cells adjacent to somites 3ā7 belong to the crest streams contributing to sympathetic chains: they migrate ventrally, seed the sympathetic chains, and colonize the entire digestive tract thence. Accordingly, enteric ganglia, like sympathetic ones, are atrophic when deprived of signaling through the tyrosine kinase receptor ErbB3, while half of the esophageal ganglia require, like parasympathetic ones, the nerve-associated form of the ErbB3 ligand, Neuregulin-1. These dependencies might bear relevance to Hirschsprung disease, with which alleles of Neuregulin-1 are associated
Are Dutch dental students and dental-care providers competent prescribers of drugs?
Dental students and dental-care providers should be able to prescribe drugs safely and effectively. As it is unknown whether this is the case, we assessed and compared the prescribing competence of dental students and dental-care providers in the Netherlands. In 2017, all Dutch final-year dental students and a random sample of all qualified general dental practitioners and dental specialists (oral and maxillofacial surgeons and orthodontists) were invited to complete validated prescribing knowledge-assessment and skills-assessment instruments. The knowledge assessment comprised 40 multiple-choice questions covering important drug topics. The skills assessment comprised three common clinical case scenarios. For the knowledge assessment, the response rates were 26 (20%) dental students, 28 (8%) general dental practitioners, and 19 (19%) dental specialists, and for the skills assessment the response rates were 14 (11%) dental students, eight (2%) general dental practitioners, and eight (8%) dental specialists. Dental specialists had higher knowledge scores (78% correct answers) than either dental practitioners (69% correct answers) or dental students (69% correct answers). A substantial proportion of all three groups made inappropriate treatment choices (35%-49%) and prescribing errors (47%-70%). Although there were some differences, dental students and dental-care providers in the Netherlands lack prescribing competence, which is probably because of poor prescribing education during under- and postgraduate dental training. Educational interventions are urgently needed
Annotation and query of tissue microarray data using the NCI Thesaurus
<p>Abstract</p> <p>Background</p> <p>The Stanford Tissue Microarray Database (TMAD) is a repository of data serving a consortium of pathologists and biomedical researchers. The tissue samples in TMAD are annotated with multiple free-text fields, specifying the pathological diagnoses for each sample. These text annotations are not structured according to any ontology, making future integration of this resource with other biological and clinical data difficult.</p> <p>Results</p> <p>We developed methods to map these annotations to the NCI thesaurus. Using the NCI-T we can effectively represent annotations for about 86% of the samples. We demonstrate how this mapping enables ontology driven integration and querying of tissue microarray data. We have deployed the mapping and ontology driven querying tools at the TMAD site for general use.</p> <p>Conclusion</p> <p>We have demonstrated that we can effectively map the diagnosis-related terms describing a sample in TMAD to the NCI-T. The NCI thesaurus terms have a wide coverage and provide terms for about 86% of the samples. In our opinion the NCI thesaurus can facilitate integration of this resource with other biological data.</p
Flavor Violating Higgs Decays
We study a class of nonstandard interactions of the newly discovered 125 GeV
Higgs-like resonance that are especially interesting probes of new physics:
flavor violating Higgs couplings to leptons and quarks. These interaction can
arise in many frameworks of new physics at the electroweak scale such as two
Higgs doublet models, extra dimensions, or models of compositeness. We rederive
constraints on flavor violating Higgs couplings using data on rare decays,
electric and magnetic dipole moments, and meson oscillations. We confirm that
flavor violating Higgs boson decays to leptons can be sizeable with, e.g., h ->
tau mu and h -> tau e branching ratios of order 10% perfectly allowed by low
energy constraints. We estimate the current LHC limits on h -> tau mu and h ->
tau e decays by recasting existing searches for the SM Higgs in the tau-tau
channel and find that these bounds are already stronger than those from rare
tau decays. We also show that these limits can be improved significantly with
dedicated searches and we outline a possible search strategy. Flavor violating
Higgs decays therefore present an opportunity for discovery of new physics
which in some cases may be easier to access experimentally than flavor
conserving deviations from the Standard Model Higgs framework.Comment: 39 pages, 12 figures, 3 tables; v2: Improved referencing, updated mu
-> 3e bounds to include large loop contributions, corrected single top
constraints; conclusions unchanged; matches version to be published in JHEP;
v3: included 2-loop contributions in mu -> e conversion, improved discussion
of tau -> 3 mu and of EDM constraints on FV top-Higgs couplings; conclusions
unchange
Network model of immune responses reveals key effectors to single and co-infection dynamics by a respiratory bacterium and a gastrointestinal helminth
Co-infections alter the host immune response but how the systemic and local processes at the site of infection interact is still unclear. The majority of studies on co-infections concentrate on one of the infecting species, an immune function or group of cells and often focus on the initial phase of the infection. Here, we used a combination of experiments and mathematical modelling to investigate the network of immune responses against single and co-infections with the respiratory bacterium Bordetella bronchiseptica and the gastrointestinal helminth Trichostrongylus retortaeformis. Our goal was to identify representative mediators and functions that could capture the essence of the host immune response as a whole, and to assess how their relative contribution dynamically changed over time and between single and co-infected individuals. Network-based discrete dynamic models of single infections were built using current knowledge of bacterial and helminth immunology; the two single infection models were combined into a co-infection model that was then verified by our empirical findings. Simulations showed that a T helper cell mediated antibody and neutrophil response led to phagocytosis and clearance of B. bronchiseptica from the lungs. This was consistent in single and co-infection with no significant delay induced by the helminth. In contrast, T. retortaeformis intensity decreased faster when co-infected with the bacterium. Simulations suggested that the robust recruitment of neutrophils in the co-infection, added to the activation of IgG and eosinophil driven reduction of larvae, which also played an important role in single infection, contributed to this fast clearance. Perturbation analysis of the models, through the knockout of individual nodes (immune cells), identified the cells critical to parasite persistence and clearance both in single and co-infections. Our integrated approach captured the within-host immuno-dynamics of bacteria-helminth infection and identified key components that can be crucial for explaining individual variability between single and co-infections in natural populations
Deriving a mutation index of carcinogenicity using protein structure and protein interfaces
With the advent of Next Generation Sequencing the identification of mutations in the genomes of healthy and diseased tissues has become commonplace. While much progress has been made to elucidate the aetiology of disease processes in cancer, the contributions to disease that many individual mutations make remain to be characterised and their downstream consequences on cancer phenotypes remain to be understood. Missense mutations commonly occur in cancers and their consequences remain challenging to predict. However, this knowledge is becoming more vital, for both assessing disease progression and for stratifying drug treatment regimes. Coupled with structural data, comprehensive genomic databases of mutations such as the 1000 Genomes project and COSMIC give an opportunity to investigate general principles of how cancer mutations disrupt proteins and their interactions at the molecular and network level. We describe a comprehensive comparison of cancer and neutral missense mutations; by combining features derived from structural and interface properties we have developed a carcinogenicity predictor, InCa (Index of Carcinogenicity). Upon comparison with other methods, we observe that InCa can predict mutations that might not be detected by other methods. We also discuss general limitations shared by all predictors that attempt to predict driver mutations and discuss how this could impact high-throughput predictions. A web interface to a server implementation is publicly available at http://inca.icr.ac.uk/
Muon conversion to electron in nuclei in type-I seesaw models
We compute the muon to electron conversion in the type-I seesaw model, as a
function of the right-handed neutrino mixings and masses. The results are
compared with previous computations in the literature. We determine the
definite predictions resulting for the ratios between the muon to electron
conversion rate for a given nucleus and the rate of two other processes which
also involve a mu-e flavour transition: mu -> e gamma and mu -> eee. For a
quasi-degenerate mass spectrum of right-handed neutrino masses -which is the
most natural scenario leading to observable rates- those ratios depend only on
the seesaw mass scale, offering a quite interesting testing ground. In the case
of sterile neutrinos heavier than the electroweak scale, these ratios vanish
typically for a mass scale of order a few TeV. Furthermore, the analysis
performed here is also valid down to very light masses. It turns out that
planned mu -> e conversion experiments would be sensitive to masses as low as 2
MeV. Taking into account other experimental constraints, we show that future mu
-> e conversion experiments will be fully relevant to detect or constrain
sterile neutrino scenarios in the 2 GeV-1000 TeV mass range.Comment: 32 pages 14 figures, references added and some minor precisions;
results unchange
The Custodial Randall-Sundrum Model: From Precision Tests to Higgs Physics
We reexamine the Randall-Sundrum (RS) model with enlarged gauge symmetry
SU(2)_L x SU(2)_R x U(1)_X x P_LR in the presence of a brane-localized Higgs
sector. In contrast to the existing literature, we perform the Kaluza-Klein
(KK) decomposition within the mass basis, which avoids the truncation of the KK
towers. Expanding the low-energy spectrum as well as the gauge couplings in
powers of the Higgs vacuum expectation value, we obtain analytic formulas which
allow for a deep understanding of the model-specific protection mechanisms of
the T parameter and the left-handed Z-boson couplings. In particular, in the
latter case we explain which contributions escape protection and identify them
with the irreducible sources of P_LR symmetry breaking. We furthermore show
explicitly that no protection mechanism is present in the charged-current
sector confirming existing model-independent findings. The main focus of the
phenomenological part of our work is a detailed discussion of Higgs-boson
couplings and their impact on physics at the CERN Large Hadron Collider. For
the first time, a complete one-loop calculation of all relevant Higgs-boson
production and decay channels is presented, incorporating the effects stemming
from the extended electroweak gauge-boson and fermion sectors.Comment: 74 pages, 13 figures, 3 tables. v2: Matches version published in JHE
NSUSY fits
We perform a global fit to Higgs signal-strength data in the context of light
stops in Natural SUSY. In this case, the Wilson coefficients of the higher
dimensional operators mediating g g -> h and h -> \gamma \gamma, given by c_g,
c_\gamma, are related by c_g = 3 (1 + 3 \alpha_s/(2 \pi)) c_\gamma/8. We
examine this predictive scenario in detail, combining Higgs signal-strength
constraints with recent precision measurements of m_W, b-> s \gamma constraints
and direct collider bounds on weak scale SUSY, finding regions of parameter
space that are consistent with all of these constraints. However it is
challenging for the allowed parameter space to reproduce the observed Higgs
mass value with sub-TeV stops. We discuss some of the direct stop discovery
prospects and show how global Higgs fits can be used to exclude light stop
parameter space difficult to probe by direct collider searches. We determine
the current status of such indirect exclusions and estimate their reach by the
end of the 8 TeV LHC run.Comment: 41 pages, 13 figures. v3: final JHEP version, b to s gamma updated to
latest data and typos correcte
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