689 research outputs found
Production of the soluble pattern recognition receptor PTX3 by myeloid, but not plasmacytoid, dendritic cells
PTX3 is a prototypic of long pentraxin consisting of an N-terminal portion coupled to a C-terminal pentraxin domain, the latter related to short pentraxins (C-reactive protein and serum amyloid P component). PTX3 is a soluble pattern recognition receptor, which plays a non-redundant role in resistance against selected pathogens and in female fertility. The present study was designed to analyze the production of PTX3 by human dendritic cells (DC) and to define the role of different innate immunity receptors in its induction. Human monocyte-derived DC produced copious amounts of PTX3 in response to microbial ligands engaging different members of the Toll-like receptor (TLR) family (TLR1 through TLR6), whereas engagement of the mannose receptor had no substantial effect. DC were better producers of PTX3 than monocytes and macrophages. Freshly isolated peripheral blood myeloid DC produced PTX3 in response to diverse microbial stimuli. In contrast, plasmacytoid DC exposed to influenza virus or to CpG oligodeoxynucleotides engaging TLR9, did not produce PTX3. PTX3-expressing DC were present in inflammatory lymph nodes from HIV-infected patients. These results suggest that DC of myelomonocytic origin are a major source of PTX3, a molecule which facilitates pathogen recognition and subsequent activation of innate and adaptive immunity
Per una storia economica della Sanità. Finanziare e gestire la Ca’ Granda di Milano nei primi decenni post-unitari
La ricerca pone in analisi l\u2019amministrazione e la gestione finanziaria dell\u2019Ospedale Maggiore di Milano, la Ca\u2019 Granda, dall\u2019Unit\ue0 d\u2019Italia fino al volgere del secolo. La formidabile base documentaria - costituita dalla serie di bilanci e di altri documenti contabili, in larga parte inediti, conservati presso l\u2019Archivio dell\u2019istituzione assistenziale - ha consentito di mettere in luce l\u2019evoluzione delle modalit\ue0 di finanziamento, delle pratiche gestionali, della partecipazione dei privati e della citt\ue0, e dei rapporti con lo Stato centrale di una delle principali realt\ue0 ospedaliere europee dell\u2019epoca
Direct comparison of B-Type Natriuretic Peptide (BNP) and amino-terminal proBNP in a large population of patients with chronic and symptomatic heart failure: the Valsartan Heart Failure (Val-HeFT) data
Background: The B-type or brain natriuretic peptides
(BNP) and the amino-terminal probrain natriuretic peptide
(NT-proBNP) are good markers of prognosis and
diagnosis in chronic heart failure (HF). It is unclear,
however, whether differences in their biological characteristics
modify their clinical correlates and prognostic
performance in HF. This work aimed to provide a direct
comparison of the prognostic value of BNP and NTproBNP
in patients with chronic and stable HF.
Methods: We measured BNP and NT-proBNP at baseline
in 3916 patients enrolled in the Valsartan Heart
Failure Trial. To identify the variables associated with
both peptides, we conducted simple and multivariable
linear regression analyses. We used Cox multivariable
regression models to evaluate the independent prognostic
value for all-cause mortality, mortality and morbidity,
and hospitalization for HF. Prognostic performance
was assessed by pairwise comparisons of the area under
the curve of receiver-operator characteristic curves.
Results: NT-proBNP and BNP had similar relationships
with age, left ventrical ejection fraction, and internal
diameter and creatinine clearance. Either peptide
ranked as the first independent predictor of outcome
after adjustment for major confounding clinical characteristics.
ROC curves were almost superimposable for
all-cause mortality (area under the curve (SE): BNP
0.665 (0.011) vs NT-proBNP 0.679 (0.011); P 0.0734), but
NT-proBNP was superior to BNP for predicting mortality
and morbidity (P 0.032) or hospitalization for HF
(P 0.0143). Overall sensitivity and specificity ranged
from 0.590 to 0.696.
Conclusions: The natriuretic peptides BNP and NTproBNP
showed subtle differences in their relation to
clinical characteristics and prognostic performance in a
large population of patients with chronic and stable HF.
They were the most powerful independent markers of
outcome in HF
Clinical application of tumour-in-normal contamination assessment from whole genome sequencing
The unexpected contamination of normal samples with tumour cells reduces variant detection sensitivity, compromising downstream analyses in canonical tumour-normal analyses. Leveraging whole-genome sequencing data available at Genomics England, we develop a tool for normal sample contamination assessment, which we validate in silico and against minimal residual disease testing. From a systematic review of 771 patients with haematological malignancies and sarcomas, we find contamination across a range of cancer clinical indications and DNA sources, with highest prevalence in saliva samples from acute myeloid leukaemia patients, and sorted CD3+ T-cells from myeloproliferative neoplasms. Further exploration reveals 108 hotspot mutations in genes associated with haematological cancers at risk of being subtracted by standard variant calling pipelines. Our work highlights the importance of contamination assessment for accurate somatic variants detection in research and clinical settings, especially with large-scale sequencing projects being utilised to deliver accurate data from which to make clinical decisions for patient care
Membrane-binding peptides for extracellular vesicles on-chip analysis
Small extracellular vesicles (sEVs) present fairly distinctive lipid membrane features in the extracellular environment. These include high curvature, lipid-packing defects and a relative abundance in lipids such as phosphatidylserine and ceramide. sEV membrane could be then considered as a "universal" marker, alternative or complementary to traditional, characteristic, surface-associated proteins. Here, we introduce the use of membrane-sensing peptides as new, highly efficient ligands to directly integrate sEV capturing and analysis on a microarray platform. Samples were analysed by label-free, single-particle counting and sizing, and by fluorescence co-localisation immune staining with fluorescent anti-CD9/anti-CD63/anti-CD81 antibodies. Peptides performed as selective yet general sEV baits and showed a binding capacity higher than anti-tetraspanins antibodies. Insights into surface chemistry for optimal peptide performances are also discussed, as capturing efficiency is strictly bound to probes surface orientation effects. We anticipate that this new class of ligands, also due to the versatility and limited costs of synthetic peptides, may greatly enrich the molecular toolbox for EV analysis
2018 MAX-C/ExoMars Mission: The Orleans Mars-Analogue Rock Collection for Instrument Testing
International audienceIn order to reply to the exobiological goals of the 2018 MAX-C/ExoMars mission, the Orléans-OSUC analogue rock collection and database contains well characterised Mars analogue rocks and minerals for use in instrument testing and in situ missions
Trivial centralizers for Axiom A diffeomorphisms
We show there is a residual set of non-Anosov Axiom A
diffeomorphisms with the no cycles property whose elements have trivial
centralizer. If is a surface and , then we will show
there exists an open and dense set of of Axiom A diffeomorphisms with the
no cycles property whose elements have trivial centralizer. Additionally, we
examine commuting diffeomorphisms preserving a compact invariant set
where is a hyperbolic chain recurrent class for one of the
diffeomorphisms.Comment: 18 page
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