68 research outputs found
Genetic polymorphisms and expression of Rhesus blood group RHCE are associated with 2,3-bisphosphoglycerate in humans at high altitude
Red blood cell (RBC) metabolic reprogramming upon exposure to high altitude contributes to physiological human adaptations to hypoxia, a multifaceted process critical to health and disease. To delve into the molecular underpinnings of this phenomenon, first, we performed a multi-omics analysis of RBCs from six lowlanders after exposure to high-altitude hypoxia, with longitudinal sampling at baseline, upon ascent to 5,100 m and descent to sea level. Results highlighted an association between erythrocyte levels of 2,3-bisphosphoglycerate (BPG), an allosteric regulator of hemoglobin that favors oxygen off-loading in the face of hypoxia, and expression levels of the Rhesus blood group RHCE protein. We then expanded on these findings by measuring BPG in RBCs from 13,091 blood donors from the Recipient Epidemiology and Donor Evaluation Study. These data informed a genome-wide association study using BPG levels as a quantitative trait, which identified genetic polymorphisms in the region coding for the Rhesus blood group RHCE as critical determinants of BPG levels in erythrocytes from healthy human volunteers. Mechanistically, we suggest that the Rh group complex, which participates in the exchange of ammonium with the extracellular compartment, may contribute to intracellular alkalinization, thus favoring BPG mutase activity
Crossover From Individual to Collective Magnetism in Dense Nanoparticle Systems: Local Anisotropy Versus Dipolar Interactions
Dense systems of magnetic nanoparticles may exhibit dipolar collective
behavior. However, two fundamental questions remain unsolved: i) whether the
transition temperature may be affected by the particle anisotropy or it is
essentially determined by the intensity of the interparticle dipolar
interactions, and ii) what is the minimum ratio of dipole-dipole interaction
() to nanoparticle anisotropy (, anisotropy
volume) energies necessary to crossover from individual to collective
behavior. A series of particle assemblies with similarly intense dipolar
interactions but widely varying anisotropy is studied. The is
tuned through different degrees of cobalt-doping in maghemite nanoparticles,
resulting in a variation of nearly an order of magnitude. All the bare particle
compacts display collective behavior, except the one made with the highest
anisotropy particles, which presents ``marginal'' features. Thus, a threshold
of to suppress collective behavior
is derived, in good agreement with Monte Carlo simulations. This translates
into a crossover value of for the easily accessible parameter
(interacting)(non-interacting) (ratio of the peak
temperatures of the zero-field-cooled magnetization curves of interacting and
dilute particle systems), which is successfully tested against the literature
to predict the individual-likecollective behavior of any given interacting
particle assembly comprising relatively uniform particles.Comment: 24 pages (proof version), 6 figure
Design of Fe3–xO4 raspberry decorated graphene nanocomposites with high performances in lithium-ion battery
Fe3–xO4 raspberry shaped nanostructures/graphene nanocomposites were synthesized by a one-step polyol-solvothermal method to be tested as electrode materials for Li-ion battery (LIB). Indeed, Fe3–xO4 raspberry shaped nanostructures consist of original oriented aggregates of Fe3–xO4 magnetite nanocrystals, ensuring a low oxidation state of magnetite and a hollow and porous structure, which has been easily combined with graphene sheets. The resulting nanocomposite powder displays a very homogeneous spatial distribution of Fe3–xO4 nanostructures at the surface of the graphene sheets. These original nanostructures and their strong interaction with the graphene sheets resulted in very small capacity fading upon Li+ ion intercalation. Reversible capacity, as high as 660 mAh/g, makes this material promising for anode in Li-ion batteries application
Two dimensional dipolar coupling in monolayers of silver and gold nanoparticles on a dielectric substrate
The dimensionality of assembled nanoparticles plays an important role in their optical and magnetic properties, via dipolar effects and the interaction with their environment. In this work we develop a methodology for distinguishing between two (2D) and three (3D) dimensional collective interactions on the surface plasmon resonance of assembled metal nanoparticles. Towards that goal, we elaborate different sets of Au and Ag nanoparticles as suspensions, random 3D arrangements and well organized 2D arrays. Then we model their scattering cross-section using effective field methods in dimension n, including interparticle as well as particle-substrate dipolar interactions. For this modelling, two effective field medium approaches are employed, taking into account the filling factors of the assemblies. Our results are important for realizing photonic amplifier devices
Organised Genome Dynamics in the Escherichia coli Species Results in Highly Diverse Adaptive Paths
The Escherichia coli species represents one of the best-studied model organisms, but also encompasses a variety of commensal and pathogenic strains that diversify by high rates of genetic change. We uniformly (re-) annotated the genomes of 20 commensal and pathogenic E. coli strains and one strain of E. fergusonii (the closest E. coli related species), including seven that we sequenced to completion. Within the ∼18,000 families of orthologous genes, we found ∼2,000 common to all strains. Although recombination rates are much higher than mutation rates, we show, both theoretically and using phylogenetic inference, that this does not obscure the phylogenetic signal, which places the B2 phylogenetic group and one group D strain at the basal position. Based on this phylogeny, we inferred past evolutionary events of gain and loss of genes, identifying functional classes under opposite selection pressures. We found an important adaptive role for metabolism diversification within group B2 and Shigella strains, but identified few or no extraintestinal virulence-specific genes, which could render difficult the development of a vaccine against extraintestinal infections. Genome flux in E. coli is confined to a small number of conserved positions in the chromosome, which most often are not associated with integrases or tRNA genes. Core genes flanking some of these regions show higher rates of recombination, suggesting that a gene, once acquired by a strain, spreads within the species by homologous recombination at the flanking genes. Finally, the genome's long-scale structure of recombination indicates lower recombination rates, but not higher mutation rates, at the terminus of replication. The ensuing effect of background selection and biased gene conversion may thus explain why this region is A+T-rich and shows high sequence divergence but low sequence polymorphism. Overall, despite a very high gene flow, genes co-exist in an organised genome
Difficult tracheal intubation in neonates and infants. NEonate and Children audiT of Anaesthesia pRactice IN Europe (NECTARINE): a prospective European multicentre observational study
Background: Neonates and infants are susceptible to hypoxaemia in the perioperative period. The aim of this study was to analyse interventions related to anaesthesia tracheal intubations in this European cohort and identify their clinical consequences. Methods: We performed a secondary analysis of tracheal intubations of the European multicentre observational trial (NEonate and Children audiT of Anaesthesia pRactice IN Europe [NECTARINE]) in neonates and small infants with difficult tracheal intubation. The primary endpoint was the incidence of difficult intubation and the related complications. The secondary endpoints were the risk factors for severe hypoxaemia attributed to difficult airway management, and 30 and 90 day outcomes. Results: Tracheal intubation was planned in 4683 procedures. Difficult tracheal intubation, defined as two failed attempts of direct laryngoscopy, occurred in 266 children (271 procedures) with an incidence (95% confidence interval [CI]) of 5.8% (95% CI, 5.1e6.5). Bradycardia occurred in 8% of the cases with difficult intubation, whereas a significant decrease in oxygen saturation (SpO2<90% for 60 s) was reported in 40%. No associated risk factors could be identified among comorbidities, surgical, or anaesthesia management. Using propensity scoring to adjust for confounders, difficult anaesthesia tracheal intubation did not lead to an increase in 30 and 90 day morbidity or mortality. Conclusions: The results of the present study demonstrate a high incidence of difficult tracheal intubation in children less than 60 weeks post-conceptual age commonly resulting in severe hypoxaemia. Reassuringly, the morbidity and mortality at 30 and 90 days was not increased by the occurrence of a difficult intubation event. Clinical trial registration: NCT02350348
Variation in Structure and Process of Care in Traumatic Brain Injury: Provider Profiles of European Neurotrauma Centers Participating in the CENTER-TBI Study.
INTRODUCTION: The strength of evidence underpinning care and treatment recommendations in traumatic brain injury (TBI) is low. Comparative effectiveness research (CER) has been proposed as a framework to provide evidence for optimal care for TBI patients. The first step in CER is to map the existing variation. The aim of current study is to quantify variation in general structural and process characteristics among centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. METHODS: We designed a set of 11 provider profiling questionnaires with 321 questions about various aspects of TBI care, chosen based on literature and expert opinion. After pilot testing, questionnaires were disseminated to 71 centers from 20 countries participating in the CENTER-TBI study. Reliability of questionnaires was estimated by calculating a concordance rate among 5% duplicate questions. RESULTS: All 71 centers completed the questionnaires. Median concordance rate among duplicate questions was 0.85. The majority of centers were academic hospitals (n = 65, 92%), designated as a level I trauma center (n = 48, 68%) and situated in an urban location (n = 70, 99%). The availability of facilities for neuro-trauma care varied across centers; e.g. 40 (57%) had a dedicated neuro-intensive care unit (ICU), 36 (51%) had an in-hospital rehabilitation unit and the organization of the ICU was closed in 64% (n = 45) of the centers. In addition, we found wide variation in processes of care, such as the ICU admission policy and intracranial pressure monitoring policy among centers. CONCLUSION: Even among high-volume, specialized neurotrauma centers there is substantial variation in structures and processes of TBI care. This variation provides an opportunity to study effectiveness of specific aspects of TBI care and to identify best practices with CER approaches
Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research
No abstract available
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