Spin-Exchange optical pumping in a van

International audienceThe advent of spin-hyperpolarization techniques designed to overcome the sensitivity issue of nuclear magnetic resonance owing to polarization transfer from more ordered systems has recently raised great enthusiasm. However, the out-of-equilibrium character of the polarization requires a close proximity between the area of production and the site of use. We present here a mobile spin-exchange optical pumping setup that enables production of laser-polarized noble gases in a standalone mode, in close proximity to hospitals or research laboratories. Only compressed air and mains power need to be supplied by the host laborator

Host cell transcriptional profiling during malaria liver stage infection reveals a coordinated and sequential set of biological events

<p>Abstract</p> <p>Background</p> <p><it>Plasmodium </it>sporozoites migrate to the liver where they traverse several hepatocytes before invading the one inside which they will develop and multiply into thousands of merozoites. Although this constitutes an essential step of malaria infection, the requirements of <it>Plasmodium </it>parasites in liver cells and how they use the host cell for their own survival and development are poorly understood.</p> <p>Results</p> <p>To gain new insights into the molecular host-parasite interactions that take place during malaria liver infection, we have used high-throughput microarray technology to determine the transcriptional profile of <it>P. berghei</it>-infected hepatoma cells. The data analysis shows differential expression patterns for 1064 host genes starting at 6 h and up to 24 h post infection, with the largest proportion correlating specifically with the early stages of the infection process. A considerable proportion of those genes were also found to be modulated in liver cells collected from <it>P. yoelii-</it>infected mice 24 and 40 h after infection, strengthening the data obtained with the <it>in vitro </it>model and highlighting genes and pathways involved in the host response to rodent <it>Plasmodium </it>parasites.</p> <p>Conclusion</p> <p>Our data reveal that host cell infection by <it>Plasmodium </it>sporozoites leads to a coordinated and sequential set of biological events, ranging from the initial stage of stress response up to the engagement of host metabolic processes and the maintenance of cell viability throughout infection.</p

Transition of plasmodium sporozoites into liver stage-like forms is regulated by the RNA binding protein pumilio

Many eukaryotic developmental and cell fate decisions that are effected post-transcriptionally involve RNA binding proteins as regulators of translation of key mRNAs. In malaria parasites (Plasmodium spp.), the development of round, non-motile and replicating exo-erythrocytic liver stage forms from slender, motile and cell-cycle arrested sporozoites is believed to depend on environmental changes experienced during the transmission of the parasite from the mosquito vector to the vertebrate host. Here we identify a Plasmodium member of the RNA binding protein family PUF as a key regulator of this transformation. In the absence of Pumilio-2 (Puf2) sporozoites initiate EEF development inside mosquito salivary glands independently of the normal transmission-associated environmental cues. Puf2- sporozoites exhibit genome-wide transcriptional changes that result in loss of gliding motility, cell traversal ability and reduction in infectivity, and, moreover, trigger metamorphosis typical of early Plasmodium intra-hepatic development. These data demonstrate that Puf2 is a key player in regulating sporozoite developmental control, and imply that transformation of salivary gland-resident sporozoites into liver stage-like parasites is regulated by a post-transcriptional mechanism

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

EMBO molecular medicine : fast forward

These are exciting times for translational medicine as the convergence between fundamental and clinical research comes of age. The new EMBO Press publishing platform reinforces the standing of EMBO Molecular Medicine as the journal that matches high quality, novel research with rigorous editorial and ethical standards. It will also cement the journal's global reach and relevance - whether in highly active fields or explorative forays into emerging areas

Following the growth of Saccharomyces Cerevisiae in standard culture conditions using hyperpolarized 129^{129}Xe NMR

International audienceXenon has several interesting properties for the NMR study of biological cells: 1) its nuclear polarization can beboosted via optical pumping, which increases the detection sensitivity by several orders of magnitude. 2) It is nontoxicand soluble in biologic medium and crosses the plasma membrane while keeping its polarization. 3) It has a wide rangeof chemical shift which makes its NMR signature sensitive to fine cell changes. In particular with cell suspensions twodistinct signals are observed on the $^{129}$Xe NMR spectrum, corresponding to xenon in the bulk and xenon inside thecells. This has led to promising applications, such as the discrimination of cells sensitive and resistant to chemotherapy.In this work, we studied Saccharomyces Cerevisiae cells at different times of a culture via hyperpolarized $^{129}$Xe NMR(xenon was hyperpolarized using our home made optical pumping setup) and controlled the number of cells by themeasure of the optical density at 600 nm. For each time stage of the yeast culture, a sample was withdrawn and afterhyperpolarized xenon addition, the corresponding $^{129}$Xe spectra were analyzed in a 11.7 Tesla spectrometer: thechemical shift splitting, the in-out exchange rate and the proportion of xenon inside the cells were extracted andcompared with classical analyses using optical density. The evolution of the spectral signature of $^{129}$Xe in S. Cerevisae isdependent of the culture time as presented in the figure. Hypotheses of explanations will be presented.In parallel, new methodologies, compatible with narrow-bore NMR spectrometers, were developed to allow the in situ follow-up of cell cultures by NMR, using microfluidic system and micro-NMR detection. Surface treatment such as parylene coating was shown to increase biocompatibilit

Inductively-Coupled Microcoils and Solution Flow for Increased NMR Sensitivity

International audienceInductively-Coupled Microcoils and Solution Flow for Increased NMR SensitivityGuillaume Carret, Thomas Berthelot, Céline Boutin, Patrick BerthaultNIMBE, CEA, CNRS, Paris-Saclay University, CEA Saclay, 91191 Gif-sur-Yvette, FranceTo circumvent the sensitivity problems inherent to slow return of magnetization to equilibrium in liquid-state NMR we present a 3D-printed NMR device based on a mini bubble-pump associated with fluidics and micro-detection that can be installed in every commercial liquid-state NMR probehead.It is based on the use of a closed-loop circuit ofthe solution near the NMR magnetic center, which presents two main advantages: i) pre-polarization is achieved for the whole solution volume, ii) this volume can be reduced to tens of microliters