3,093 research outputs found
Pleiotropic Effects of Cell Wall Amidase LytA on Streptococcus pneumoniae Sensitivity to the Host Immune Response
The complement system is a key component of the host immune response for the recognition and clearance of Streptococcus pneumoniae. In this study, we demonstrate that the amidase LytA, the main pneumococcal autolysin, inhibits complement-mediated immunity independently of effects on pneumolysin by a complex process of impaired complement activation, increased binding of complement regulators, and direct degradation of complement C3. The use of human sera depleted of either C1q or factor B confirmed that LytA prevented activation of both the classical and alternative pathways, whereas pneumolysin inhibited only the classical pathway. LytA prevented binding of C1q and the acute-phase protein C-reactive protein to S. pneumoniae, thereby reducing activation of the classical pathway on the bacterial surface. In addition, LytA increased recruitment of the complement downregulators C4BP and factor H to the pneumococcal cell wall and directly cleaved C3b and iC3b to generate degradation products. As a consequence, C3b deposition and phagocytosis increased in the absence of LytA and were markedly enhanced for the lytA ply double mutant, confirming that a combination of LytA and Ply is essential for the establishment of pneumococcal pneumonia and sepsis in a murine model of infection. These data demonstrate that LytA has pleiotropic effects on complement activation, a finding which, in combination with the effects of pneumolysin on complement to assist with pneumococcal complement evasion, confirms a major role of both proteins for the full virulence of the microorganism during septicemia
Modular framework to assess the risk of African swine fever virus entry into the European Union
BACKGROUND
The recent occurrence and spread of African swine fever (ASF) in Eastern Europe is perceived as a serious risk for the pig industry in the European Union (EU). In order to estimate the potential risk of ASF virus (ASFV) entering the EU, several pathways of introduction were previously assessed separately. The present work aimed to integrate five of these assessments (legal imports of pigs, legal imports of products, illegal imports of products, fomites associated with transport and wild boar movements) into a modular tool that facilitates the visualization and comprehension of the relative risk of ASFV introduction into the EU by each analyzed pathway.
RESULTS
The framework's results indicate that 48% of EU countries are at relatively high risk (risk score 4 or 5 out of 5) for ASFV entry for at least one analyzed pathway. Four of these countries obtained the maximum risk score for one pathway: Bulgaria for legally imported products during the high risk period (HRP); Finland for wild boar; Slovenia and Sweden for legally imported pigs during the HRP. Distribution of risk considerably differed from one pathway to another; for some pathways, the risk was concentrated in a few countries (e.g., transport fomites), whereas other pathways incurred a high risk for 4 or 5 countries (legal pigs, illegal imports and wild boar).
CONCLUSIONS
The modular framework, developed to estimate the risk of ASFV entry into the EU, is available in a public domain, and is a transparent, easy-to-interpret tool that can be updated and adapted if required. The model's results determine the EU countries at higher risk for each ASFV introduction route, and provide a useful basis to develop a global coordinated program to improve ASFV prevention in the EU
Force and Compliance Measurements on Living Cells Using Atomic Force Microscopy (AFM)
We describe the use of atomic force microscopy (AFM) in studies of cell adhesion and cell compliance. Our studies use the interaction between leukocyte function associated antigen-1 (LFA-1)/intercellular adhesion molecule-1 (ICAM-1) as a model system. The forces required to unbind a single LFA-1/ICAM-1 bond were measured at different loading rates. This data was used to determine the dynamic strength of the LFA-1/ICAM-1 complex and characterize the activation potential that this complex overcomes during its breakage. Force measurements acquired at the multiple- bond level provided insight about the mechanism of cell adhesion. In addition, the AFM was used as a microindenter to determine the mechanical properties of cells. The applications of these methods are described using data from a previous study
Two Loop Scalar Self-Mass during Inflation
We work in the locally de Sitter background of an inflating universe and
consider a massless, minimally coupled scalar with a quartic self-interaction.
We use dimensional regularization to compute the fully renormalized scalar
self-mass-squared at one and two loop order for a state which is released in
Bunch-Davies vacuum at t=0. Although the field strength and coupling constant
renormalizations are identical to those of lfat space, the geometry induces a
non-zero mass renormalization. The finite part also shows a sort of growing
mass that competes with the classical force in eventually turning off this
system's super-acceleration.Comment: 31 pages, 5 figures, revtex4, revised for publication with extended
list of reference
Increased serum levels of MRP-8/14 in type 1 diabetes induce an increased expression of CD11b and an enhanced adhesion of circulating monocytes to fibronectin
The recruitment of monocytes from the bloodstream is crucial in the
accumulation of macrophages and dendritic cells in type 1 diabetic
pancreases. Adhesion via integrins to endothelium and extracellular matrix
proteins, such as fibronectin (FN), and the production of myeloid-related
protein (MRP)-8, -14, and -8/14 by recently transmigrated monocytes are
thought to be instrumental in such recruitment. We determined the
FN-adhesive capacity and integrin expression of monocytes of type 1 and
type 2 diabetic patients and related them to the subjects' serum levels of
MRP-8, -14 and -8/14. Monocytes of type 1 diabetic patients displayed an
increased adhesion to fibronectin in comparison with type 2 patients and
healthy control subjects but had a normal expression of the FN binding
integrins CD29, CD49a, CD49d, and CD49e (although CD11b and CD18
expression was increased). MRP-8/14, which was increased in the sera of
type 1 diabetic patients, induced healthy donor monocytes to adhere to FN
and upregulate CD11b expression in a dosage-dependent manner. The observed
MRP-induced increased adhesion of monocytes to FN and upregulation of
CD11b most likely contributed to a facilitated accumulation of monocytes
and monocyte-derived cells at the site of inflammation, in this case the
pancreatic islets
An Overview of the 2014 ALMA Long Baseline Campaign
A major goal of the Atacama Large Millimeter/submillimeter Array (ALMA) is to
make accurate images with resolutions of tens of milliarcseconds, which at
submillimeter (submm) wavelengths requires baselines up to ~15 km. To develop
and test this capability, a Long Baseline Campaign (LBC) was carried out from
September to late November 2014, culminating in end-to-end observations,
calibrations, and imaging of selected Science Verification (SV) targets. This
paper presents an overview of the campaign and its main results, including an
investigation of the short-term coherence properties and systematic phase
errors over the long baselines at the ALMA site, a summary of the SV targets
and observations, and recommendations for science observing strategies at long
baselines. Deep ALMA images of the quasar 3C138 at 97 and 241 GHz are also
compared to VLA 43 GHz results, demonstrating an agreement at a level of a few
percent. As a result of the extensive program of LBC testing, the highly
successful SV imaging at long baselines achieved angular resolutions as fine as
19 mas at ~350 GHz. Observing with ALMA on baselines of up to 15 km is now
possible, and opens up new parameter space for submm astronomy.Comment: 11 pages, 7 figures, 2 tables; accepted for publication in the
Astrophysical Journal Letters; this version with small changes to
affiliation
Fragmentation and disk formation during high-mass star formation: The IRAM NOEMA (Northern Extended Millimeter Array) large program CORE
Aims: We aim to understand the fragmentation as well as the disk formation, outflow generation and chemical processes during high-mass star formation on spatial scales of individual cores. Methods: Using the IRAM Northern Extended Millimeter Array (NOEMA) in combination with the 30m telescope, we have observed in the IRAM large program CORE the 1.37mm continuum and spectral line emission at high angular resolution (~0.4'') for a sample of 20 well-known high-mass star-forming regions with distances below 5.5kpc and luminosities larger than 10^4Lsun. Results: We present the overall survey scope, the selected sample, the observational setup and the main goals of CORE. Scientifically, we concentrate on the mm continuum emission on scales on the order of 1000AU. We detect strong mm continuum emission from all regions, mostly due to the emission from cold dust. The fragmentation properties of the sample are diverse. We see extremes where some regions are dominated by a single high-mass core whereas others fragment into as many as 20 cores. A minimum-spanning-tree analysis finds fragmentation at scales on the order of the thermal Jeans length or smaller suggesting that turbulent fragmentation is less important than thermal gravitational fragmentation. The diversity of highly fragmented versus singular regions can be explained by varying initial density structures and/or different initial magnetic field strengths. Conclusions: The smallest observed separations between cores are found around the angular resolution limit which indicates that further fragmentation likely takes place on even smaller spatial scales. The CORE project with its numerous spectral line detections will address a diverse set of important physical and chemical questions in the field of high-mass star formation
Immunohistochemical, morphological and ultrastructural resemblance between dendritic cells and folliculo-stellate cells in normal human and rat anterior pituitaries
Immunolabeling of cryo-sections of human anterior pituitaries obtained at autopsy, and of cryo-sections of freshly prepared rat anterior pituitaries, with a panel of monoclonal antibodies against markers of the monocyte/dendritic cell/macrophage lineage, reveals in both species a characteristic pattern of immunopositive cells, among which many cells with dendritic phenotype are found. Cells characterized by marker expression of MHC-class II determinants and a dendritic morphology are present in both human and rat anterior pituitary. Markers characteristic of dendritic cells such as the L25 antigen and the OX62 antigen were present in anterior pituitaries from human and rat respectively. The population of MHC-class II expressing dendritic cells of the rat anterior pituitary is compared at the ultrastructural level with the folliculo-stellate cell population, which cell type has been previously characterized by its distinctive ultrastructure and immunopositivity for the S100 protein. Using immune-electron microscopy of rat anterior pituitaries fixed with periodate-lysine-paraformaldehyde, we were able to distinguish non-granulated cells expressing MHC-class II determinants, whereas no MHC-class II expression was found in the granulated endocrine cells. Using double immunolabeling of cryo-sections of these rat AP with 25 nm and 15 nm gold labels, we demonstrated an overlap between the populations of MHC-class II-expressing and S100 protein-expressing cells. Furthermore, MHC-class II-expressing and S100-positive cells showed ultrastructural characteristics that have been previously ascribed to folliculo-stellate cells. At the light microscopical level in the rat AP, a proportion of 10 to 20% of the S100-positive cells was found immunopositive for the MHC-class II marker OX6. In the hu
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