Abstract We investigate here the potential of single step production of genetically engineered magnetosomes, bacterial biogenic iron-oxide nanoparticles embedded in a lipid vesicle, as a new ...tailorable magnetic resonance molecular imaging probe. We demonstrate in vitro the specific binding and the significant internalization into U87 cells of magnetosomes decorated with RGD peptide. After injection at the tail vein of glioblastoma-bearing mice, we evidence in the first 2 h the rapid accumulation of both unlabeled and functionalized magnetosomes inside the tumor by Enhanced Permeability and Retention effects. 24 h after the injection, a specific enhancement of the tumor contrast is observed on MR images only for RGD-labeled magnetosomes. Post mortem acquisition of histological data confirms MRI results with more magnetosomes found into the tumor treated with functionalized magnetosomes. This work establishes the first proof-of-concept of a successful bio-integrated production of molecular imaging probe for MRI.
Magnetosomes of magnetotactic bacteria (MTB) consist of structurally perfect, nano-sized magnetic crystals enclosed within vesicles of a proteo-lipid membrane. In species of
biosynthesis of their ...cubo-octahedral-shaped magnetosomes was recently demonstrated to be a complex process, governed by about 30 specific genes that are comprised within compact magnetosome gene clusters (MGCs). Similar, yet distinct gene clusters were also identified in diverse MTB that biomineralize magnetosome crystals with different, genetically encoded morphologies. However, since most representatives of these groups are inaccessible by genetic and biochemical approaches, their analysis will require the functional expression of magnetosome genes in foreign hosts. Here, we studied whether conserved essential magnetosome genes from closely and remotely related MTB can be functionally expressed by rescue of their respective mutants in the tractable model
of the
. Upon chromosomal integration, single orthologues from other magnetotactic
restored magnetosome biosynthesis to different degrees, while orthologues from distantly related
and
were found to be expressed but failed to re-induce magnetosome biosynthesis, possibly due to poor interaction with their cognate partners within multiprotein magnetosome organelle of the host. Indeed, co-expression of the known interactors MamB and MamM from the alphaproteobacterium
increased functional complementation. Furthermore, a compact and portable version of the entire MGCs of
was assembled by transformation-associated recombination cloning, and it restored the ability to biomineralize magnetite both in deletion mutants of the native donor and
, while co-expression of gene clusters from both
and
resulted in overproduction of magnetosomes. IMPORTANCE We provide proof of principle that
is a suitable surrogate host for the functional expression of foreign magnetosome genes and extended the transformation-associated recombination cloning platform for the assembly of entire large magnetosome gene cluster, which could then be transplanted to different magnetotactic bacteria. The reconstruction, transfer, and analysis of gene sets or entire magnetosome clusters will be also promising for engineering the biomineralization of magnetite crystals with different morphologies that would be valuable for biotechnical applications.
Magnetotactic bacteria are a diverse group of microorganisms that use intracellular chains of ferrimagnetic nanocrystals, produced within magnetosome organelles, to align and navigate along the ...geomagnetic field. Several conserved genes for magnetosome formation have been described, but the mechanisms leading to distinct species-specific magnetosome chain configurations remain unclear. Here, we show that the fragmented nature of magnetosome chains in Magnetospirillum magneticum AMB-1 is controlled by genes mcaA and mcaB. McaA recognizes the positive curvature of the inner cell membrane, while McaB localizes to magnetosomes. Along with the MamK actin-like cytoskeleton, McaA and McaB create space for addition of new magnetosomes in between pre-existing magnetosomes. Phylogenetic analyses suggest that McaA and McaB homologs are widespread among magnetotactic bacteria and may represent an ancient strategy for magnetosome positioning.
Under the same selection pressures, two genetically divergent populations may evolve in parallel toward the same adaptive solutions. Here, we hypothesized that magnetotaxis (i.e., magnetically guided ...chemotaxis) represents a key adaptation to micro-oxic habitats in aquatic sediments and that its parallel evolution homogenized the phenotypes of two evolutionary divergent clusters of freshwater spirilla. All magnetotactic bacteria affiliated to the Magnetospirillum genus (Alphaproteobacteria class) biomineralize the same magnetic particle chains and share highly similar physiological and ultrastructural features. We looked for the processes that could have contributed at shaping such an evolutionary pattern by reconciling species and gene trees using newly sequenced genomes of Magnetospirillum related bacteria. We showed that repeated horizontal gene transfers and homologous recombination of entire operons contributed to the parallel evolution of magnetotaxis. We propose that such processes could represent a more parsimonious and rapid solution for adaptation compared with independent and repeated de novo mutations, especially in the case of traits as complex as magnetotaxis involving tens of interacting proteins. Besides strengthening the idea about the importance of such a function in micro-oxic habitats, these results reinforce previous observations in experimental evolution suggesting that gene flow could alleviate clonal interference and speed up adaptation under some circumstances.
The historical evolution of incidence and outcome of cardiogenic shock (CS) in acute myocardial infarction (AMI) patients is debated. This study compared outcomes in AMI patients from 1995 to 2005, ...according to the presence of CS.
Three nationwide French registries were conducted 5 years apart, using a similar methodology in consecutive patients admitted over a 1-month period. All 7531 AMI patients presenting ≤48 h of symptom onset were included. The evolution of mortality was compared in the 486 patients with CS vs. those without CS. The incidence of CS tended to decrease over time (6.9% in 1995; 5.7% in 2005, P = 0.07). Thirty-day mortality was considerably higher in CS patients (60.9 vs. 5.2%). Over the 10-year period, mortality decreased for both patients with (70-51%, P = 0.003) and without CS (9-4%, P < 0.001). In CS patients, the use of percutaneous coronary intervention (PCI) increased from 20 to 50% (P < 0.001). Time period was an independent predictor of early mortality in CS patients (OR for death, 2005 vs. 1995 = 0.45; 95% CI: 0.27-0.75, P = 0.005), along with age, diabetes, and smoking status. When added to the multivariate model, PCI was associated with decreased mortality (OR = 0.38; 95% CI: 0.24-0.58, P < 0.001). In propensity-score-matched cohorts, CS patients with PCI had a significantly higher survival.
Cardiogenic shock remains a clinical concern, although early mortality has decreased. Improved survival is concomitant with a broader use of PCI and recommended medications at the acute stage. Beyond the acute stage, however, 1-year survival has remained unchanged.
We measure the effects of transverse wakefields driven by a relativistic proton bunch in plasma with densities of 2.1×10^{14} and 7.7×10^{14} electrons/cm^{3}. We show that these wakefields ...periodically defocus the proton bunch itself, consistently with the development of the seeded self-modulation process. We show that the defocusing increases both along the bunch and along the plasma by using time resolved and time-integrated measurements of the proton bunch transverse distribution. We evaluate the transverse wakefield amplitudes and show that they exceed their seed value (<15 MV/m) and reach over 300 MV/m. All these results confirm the development of the seeded self-modulation process, a necessary condition for external injection of low energy and acceleration of electrons to multi-GeV energy levels.
Bunched-beam Schottky monitoring in the LHC Betz, M.; Jones, O.R.; Lefevre, T. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
12/2017, Letnik:
874
Journal Article
Recenzirano
Odprti dostop
The LHC Schottky beam diagnostic system has the potential to measure beam parameters such as tune, chromaticity and momentum spread in a non-invasive way. It does so by detecting beam induced signals ...at 4.8 GHz, and extracting the characteristic modulation caused by incoherent motion of particles within a bunch. The system was commissioned in 2011 and provided satisfactory beam-parameter measurements during LHC Run I for lead-ions. However, for protons its usability was substantially limited due to strong interfering common-mode signals. The system was upgraded with optimized traveling-wave pick-ups and an improved microwave signal path. Design and operational aspects for the complete system are shown, and the results from measurements with LHC beams in Run II are presented and discussed.
This work presents our contribution to a data challenge organized by the French Radiology Society during the Journées Francophones de Radiologie in October 2018. This challenge consisted in ...classifying MR images of the knee with respect to the presence of tears in the knee menisci, on meniscal tear location, and meniscal tear orientation.
We trained a mask region-based convolutional neural network (R-CNN) to explicitly localize normal and torn menisci, made it more robust with ensemble aggregation, and cascaded it into a shallow ConvNet to classify the orientation of the tear.
Our approach predicted accurately tears in the database provided for the challenge. This strategy yielded a weighted AUC score of 0.906 for all three tasks, ranking first in this challenge.
The extension of the database or the use of 3D data could contribute to further improve the performances especially for non-typical cases of extensively damaged menisci or multiple tears.
Transcatheter aortic valve implantation is a therapeutic alternative for high-surgical-risk patients with severe symptomatic aortic stenosis. Two models of prosthesis are currently commercialized in ...France, which can be implanted either via a transarterial or a transapical approach. The aim of the study was to evaluate in a national French registry the early safety and efficacy of transcatheter aortic valve replacement (AVR) using either the Edwards SAPIEN™ or CoreValve™ in high-surgical-risk patients with severe aortic stenosis.
The multicentre national registry was conducted in 16 centres between February 2009 and June 2009, under the authority of the French Societies of Cardiology and Thoracic and Cardio-Vascular Surgery. The primary endpoint was mortality at 1 month. Two hundred and forty-four high-surgical-risk patients (logistic EuroSCORE ≥20%, STS ≥10%, or contra-indication to AVR) were enrolled. Mean age was 82 ± 7 years and 43.9% were female. Edwards SAPIEN and CoreValve were implanted in 68 and 32% of patients, respectively. The approaches used were transarterial (transfemoral: 66%; subclavian: 5%) or transapical in 29%. Device success rate was 98.3% and 30-day mortality was 12.7%. Severe complications included stroke (3.6%), tamponade (2%), acute coronary occlusion (1.2%), and vascular complications (7.3%). Pacemaker was required in 11.8%. At 1 month, 88% of patients were in NYHA class II or less.
This prospective registry reflects the real-life experience of transcatheter aortic valve implantation in high-risk elderly patients in France. The early results are satisfactory in terms of feasibility, short-term haemodynamic and functional improvement, and safety. Longer term follow-up will be further assessed.
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