323 research outputs found
HadA is an atypical new multifunctional trimeric coiled-coil adhesin of Haemophilus influenzae biogroup aegyptius, which promotes entry into host cells.
Summary The Oca (Oligomeric coiled-coil adhesin) family is a subgroup of the bacterial trimeric autotrans- porter adhesins, which includes structurally related proteins, such as YadA of Yersinia entero- colitica and NadA of Neisseria meningitidis. In this study, we searched in silico for novel members of this family in bacterial genomes and identified HadA (Haemophilus adhesin A), a trimeric autotransporter expressed only by Haemophilus influenzae biogroup aegyptius causing Brazilian purpuric fever (BPF), a fulminant septicemic disease of children. By comparative genomics and sequence analysis we predicted that the hadA gene is harboured on a mobile genetic element unique to BPF isolates. Biological analysis of HadA in the native background was limited because this organism is not amenable to genetic manipulation. Alternatively, we demonstrated that expression of HadA confers to a non-invasive Escherichia coli strain the ability to adhere to human cells and to extracellular matrix proteins and to induce in vitro bacterial aggregation and microcolony formation. Intriguingly, HadA is pre- dicted to lack the typical N-terminal head domain of Oca proteins generally associated with cellular receptor binding. We propose here a structural model of the HadA coiled-coil stalk and show that the N-terminal region is still responsible of the binding activity and a KGD motif plays a role. Interestingly, HadA promotes bacterial entry into mammalian cells. Our results show a cytoskeleton re-arrangement and an involvement of clathrin in the HadA-mediated internalization. These data give new insights on the structure-function relationship of oligomeric coiled-coil adhesins and suggest a potential role of this protein in the pathogenesis of BPF
Mutations in TGM6 induce the unfolded protein response in SCA35
Spinocerebellar ataxia type 35 (SCA35) is a rare autosomal-dominant neurodegenerative disease caused by mutations in the TGM6 gene, which codes for transglutaminase 6 (TG6). Mutations in TG6 induce cerebellar degeneration by an unknown mechanism. We identified seven patients bearing new mutations in TGM6. To gain insights into the molecular basis of mutant TG6-induced neurotoxicity, we analyzed all of the seven new TG6 mutants and the five TG6 mutants previously linked to SCA35. We found that wild-type (TG6-WT) mainly localized to the nucleus and perinuclear area, whereas five TG6 mutations showed nuclear depletion, increased accumulation in the perinuclear area, insolubility and loss of enzymatic function. Aberrant accumulation of these TG6 mutants in the perinuclear area led to activation of the unfolded protein response (UPR), suggesting that specific TG6 mutants elicit an endoplasmic reticulum (ER) stress response. Mutations associated with activation of the UPR caused death of primary neurons and reduced the survival of novel D. melanogaster models of SCA35. These results indicate that mutations differently impacting on TG6 function cause neuronal dysfunction and death through diverse mechanisms and highlight the UPR as a potential therapeutic target for patient treatment
An Observational Study to Develop a Predictive Model for Bacterial Pneumonia Diagnosis in Severe COVID-19 Patients-C19-PNEUMOSCORE
In COVID-19 patients, antibiotics overuse is still an issue. A predictive scoring model for the diagnosis of bacterial pneumonia at intensive care unit (ICU) admission would be a useful stewardship tool. We performed a multicenter observational study including 331 COVID-19 patients requiring invasive mechanical ventilation at ICU admission; 179 patients with bacterial pneumonia; and 152 displaying negative lower-respiratory samplings. A multivariable logistic regression model was built to identify predictors of pulmonary co-infections, and a composite risk score was developed using β-coefficients. We identified seven variables as predictors of bacterial pneumonia: vaccination status (OR 7.01; 95% CI, 1.73-28.39); chronic kidney disease (OR 3.16; 95% CI, 1.15-8.71); pre-ICU hospital length of stay ≥ 5 days (OR 1.94; 95% CI, 1.11-3.4); neutrophils ≥ 9.41 × 1
Relationship between immune response to SARS-CoV2 vaccines and development of breakthrough infection in solid organ transplant recipients: the CONTRAST cohort
Background: SARS-CoV-2 vaccination in solid organ transplant (SOT) is associated with poorer antibody response (AbR) compared to non-SOT recipients. However, its impact on the risk of breakthrough infection (BI) should yet be assessed. Methods: Single-center prospective longitudinal cohort study enrolling adult SOT recipients who received SARS-CoV2 vaccination during 1-year period from February 2021, and followed-up to April 30th 2022. Patients were tested for AbR at multiple timepoints. Primary endpoint was BI (laboratory confirmed SARS-CoV2 infection ≥14 days after 2nd dose). Immunization (positive AbR) was considered an intermediate state between vaccination and BI. Probabilities of being in vaccination, immunization and BI states were obtained for each type of graft and vaccination sequence with multistate survival analysis, then multivariable logistic regression was performed to analyse the risk of BI in AbR levels. Results: 614 SOT (275 kidney, 163 liver, 137 heart, 39 lung) recipients were included. Most patients (84.7%) received three vaccine doses, the first two consisted of BNT162b2 and mRNA-1273 in 73.5% and 26.5% of cases, respectively; while at the third dose mRNA-1273 was administered in 59.8% of patients. Overall, 75.4% of patients reached immunization and 18.4% developed BI. Heart transplant recipients showed lowest probability of immunization (0.418) and highest of BI (0.323), all-mRNA-1273 vaccine-sequence showed higher probability of immunization (0.732) and lowest of BI (0.098). Risk of BI was higher for non-high-level AbR, younger age and shorter time from transplant. Conclusions: SOT patients with non-high-level AbR, shorter time from transplantation, and heart recipients are at highest risk of BI
The instrument control unit of the AIRS instrument on-board the ARIEL mission: design status after PDR
ARIEL (Atmospheric Remote-sensing InfraRed Large-survey) is the fourth medium-class mission (M4) of the European Space Agency, part of the Cosmic Vision program, whose launch is planned by late 2029. ARIEL aims to study the composition of exoplanet atmospheres, their formation and evolution. The ARIEL’s target will be a sample of about 1000 planets observed with one or more of the following methods: transit, eclipse and phase-curve spectroscopy, in both visible and infrared light. The scientific payload is composed by a reflective telescope having a 1m-class elliptical primary mirror, built in solid Aluminum, and two focal-plane instruments: FGS and AIRS. FGS (Fine Guidance System)3 has the double purpose of performing photometry (0.50-0.55 µm) and low resolution spectrometry over three bands (from 0.8 to 1.95 µm) and, simultaneously, to provide data to the spacecraft AOCS (Attitude and Orbit Control System). AIRS (ARIEL InfraRed Spectrometer) instrument will perform IR spectrometry in two wavelength ranges: between 1.95 and 3.9 µm (with a spectral resolution R > 100) and between 3.9 and 7.8 µm with a spectral resolution R > 30. This paper provides the status of the ICU (Instrument Control Unit), an electronic box whose purpose is to command and supply power to the AIRS warm front-end (as well as acquire science data from its two channels) and to command and control the TCU (Telescope Control Unit)
Impaired thromboxane receptor dimerization reduces signaling efficiency:A potential mechanism for reduced platelet function in vivo
SHARK-NIR, the coronagraphic camera for LBT, moving toward construction
SHARK-NIR is one of the two coronagraphic instruments proposed for the Large
Binocular Telescope. Together with SHARK-VIS (performing coronagraphic imaging
in the visible domain), it will offer the possibility to do binocular
observations combining direct imaging, coronagraphic imaging and coronagraphic
low resolution spectroscopy in a wide wavelength domain, going from 0.5{\mu}m
to 1.7{\mu}m. Additionally, the contemporary usage of LMIRCam, the
coronagraphic LBTI NIR camera, working from K to L band, will extend even more
the covered wavelength range. In January 2017 SHARK-NIR underwent a successful
final design review, which endorsed the instrument for construction and future
implementation at LBT. We report here the final design of the instrument, which
foresees two intermediate pupil planes and three focal planes to accomodate a
certain number of coronagraphic techniques, selected to maximize the instrument
contrast at various distances from the star. Exo-Planets search and
characterization has been the science case driving the instrument design, but
the SOUL upgrade of the LBT AO will increase the instrument performance in the
faint end regime, allowing to do galactic (jets and disks) and extra-galactic
(AGN and QSO) science on a relatively wide sample of targets, normally not
reachable in other similar facilities.Comment: 8 pages, 6 figures, AO4ELT5 conference proceeding
Silicon calorimeter for cosmic antimatter search
Abstract The silicon sampling calorimeter presented is conceived as a fine grained imaging device to carry out studies of the anti-matter component in the primary cosmic radiation; it will be used in balloon payload program starting in 1993. The first sampling layer (48Ă—48 cm2) of this silicon calorimeter has been completed and successfully tested. We report the first results form studies performed at the CERN PS t7 beam. The complete calorimeter contains 20 xy sampling layers (strip pitch 3.6 mm) interleaved with 19 showering material planes (tungsten 0.5 X0). This allows to picture the transverse distributions of the shower in both coordinates at each sampling. The outstanding imaging capabilities reflects in high particle identification power. Preliminary results from beam tests performed with antiprotons at 3.5 GeV on a tower prototype of the calorimeter are reported
A silicon imaging calorimeter prototype for antimatter search in space: experimental results
Abstract This report presents the results obtained with a prototype silicon-tungsten (Si-W) electromagnetic calorimeter, conceived as a fine-grained imaging device to carry out studies of the antimatter component in primary cosmic radiation. The calorimeter prototype contains 20 x , y sampling layers interleaved with 19 showering material planes. One sensitive layer is obtained with two silicon strip detectors (Si-D) (60 × 60) mm 2 , each divided into 16 strips, 3.6 mm wide; the two detectors are assembled back to back with perpendicular strips. This allows the transverse distributions of the shower in both coordinates at each sampling (0.5 X 0 ) to be pictured. The basic characteristics of the design and the experimental results obtained on a test beam at the CERN proton synchrotron (PS) for electrons and pions are reported. The main results presented are the response of the calorimeter to the electron at various energies (1–7 GeV), and the transverse shower profiles at different calorimeter depths as well as the patterns of the electromagnetic shower and those of the interacting and non-interacting pions. The capability of the calorimeter in measuring the direction of the incoming electromagnetic particle from the pattern of the shower has been evaluated at different energies. These results are encouraging in view of the possible use of this detector to search for high-energy γ sources in space
- …