Brisures de symétrie dans des superespaces cristallographiques : aspects structuraux et dynamiques

Aperiodic crystals have the property to possess long range order without translational symmetry. These crystals are described within the formalism of superspace crystallography. In this manuscript, we will focus on symmetry breakings which take place in such crystallographic superspace groups, considering the prototype family of n-alkane/urea. Studies performed by X-ray diffraction using synchrotron sources reveal multiple structural solutions implying or not changes of the dimension of the superspace. Once the characterization of the order parameter and of the symmetry breaking is done, we present the critical pretransitionnal phenomena associated to phase transitions of group/subgroup types. Coherent neutron scattering and X-ray scattering allow a dynamical analysis of different kind of excitations in these materials (phonons, phasons). The inclusion compounds with short guest molecules (alkane CnH2n+2, n varying from 7 to 13) show at room temperature unidimensional “liquid-like” phases. The dynamical disorder along the incommensurate direction of these materials generates new structural solutions at low temperature (intermodulated monoclinic composite, commensurate lock-in).Les cristaux apériodiques possèdent la propriété d’avoir un ordre à grande distance mais sans la symétrie de translation. Ces cristaux se décrivent dans des superespaces cristallographiques de dimension supérieure à trois. Dans ce mémoire, nous nous intéressons plus particulièrement aux brisures de symétrie présentes dans de tels espaces cristallographiques en considérant la famille prototype de n-alcane/urée. Des études par diffraction de rayons X sur sources synchrotron révèlent de multiples solutions structurales impliquant des changements ou non de la dimension du groupe de superespace. Une fois la caractérisation du paramètre d’ordre et de la brisure de symétrie faite nous présentons les phénomènes prétransitionnels critiques associés à ces transitions de phase de type groupe/sous-groupe. La diffusion cohérente de neutrons et la diffusion de rayons X inélastiques permettent une analyse dynamique des différentes excitations dans ces matériaux (phonons, phasons). Les composés d’inclusion avec des molécules invitées courtes (alcane CnH2n+2 avec n variant de 7 à 13) révèlent à température ambiante des phases « quasi-liquides » uni-dimensionnelles. Ce désordre dynamique le long de la direction d'incommensurabilité de ces matériaux génère à basse température des solutions structurales nouvelles (composite monoclinique intermodulé, ancrages commensurables)

Assessment of replicate bias in 454 pyrosequencing and a multi-purpose read-filtering tool

<p>Abstract</p> <p>Background</p> <p>Roche 454 pyrosequencing platform is often considered the most versatile of the Next Generation Sequencing technology platforms, permitting the sequencing of large genomes, the analysis of variations or the study of transcriptomes. A recent reported bias leads to the production of multiple reads for a unique DNA fragment in a random manner within a run. This bias has a direct impact on the quality of the measurement of the representation of the fragments using the reads. Other cleaning steps are usually performed on the reads before assembly or alignment.</p> <p>Findings</p> <p>PyroCleaner is a software module intended to clean 454 pyrosequencing reads in order to ease the assembly process. This program is a free software and is distributed under the terms of the GNU General Public License as published by the Free Software Foundation. It implements several filters using criteria such as read duplication, length, complexity, base-pair quality and number of undetermined bases. It also permits to clean flowgram files (.sff) of paired-end sequences generating on one hand validated paired-ends file and the other hand single read file.</p> <p>Conclusions</p> <p>Read cleaning has always been an important step in sequence analysis. The pyrocleaner python module is a Swiss knife dedicated to 454 reads cleaning. It includes commonly used filters as well as specialised ones such as duplicated read removal and paired-end read verification.</p

Country-wide assessment of the genetic polymorphism in Plasmodium falciparum and Plasmodium vivax antigens detected with rapid diagnostic tests for malaria

<p>Abstract</p> <p>Background</p> <p>Rapid diagnostic tests (RDTs) are becoming increasingly indispensable in malaria management, as a means of increasing the accuracy of diagnosis. The WHO has issued recommendations, but the selection of the most suitable RDT remains difficult for users in endemic countries. The genetic variability of the antigens detected with RDTs has been little studied, but may affect the sensitivity of RDTs. This factor has been studied by comparisons between countries at continental level, but little information is available concerning antigen variability within a given country.</p> <p>Methods</p> <p>A country-wide assessment of polymorphism of the PfHRP2, PfHRP3, pLDH and aldolase antigens was carried out in 260 <it>Plasmodium falciparum </it>and 127 <it>Plasmodium vivax </it>isolates, by sequencing the genes encoding these antigens in parasites originating from the various epidemiological strata for malaria in Madagascar.</p> <p>Results</p> <p>Higher levels of polymorphism were observed for the <it>pfhrp2 </it>and <it>pfhrp3 </it>genes than for the <it>P. falciparum </it>and <it>P. vivax aldolase </it>and <it>pldh </it>genes. <it>Pfhrp2 </it>sequence analysis predicted that 9% of Malagasy isolates would not be detected at parasite densities ≤ 250 parasites/μl (ranging from 6% in the north to 14% in the south), although RDTs based on PfHRP2 detection are now recommended in Madagascar.</p> <p>Conclusion</p> <p>These findings highlight the importance of training of health workers and the end users of RDTs in the provision of information about the possibility of false-negative results for patients with clinical symptoms of malaria, particularly in the south of Madagascar.</p

More rapid blood interferon α2 decline in fatal versus surviving COVID-19 patients

BackgroundThe clinical outcome of COVID-19 pneumonia is highly variable. Few biological predictive factors have been identified. Genetic and immunological studies suggest that type 1 interferons (IFN) are essential to control SARS-CoV-2 infection.ObjectiveTo study the link between change in blood IFN-α2 level and plasma SARS-Cov2 viral load over time and subsequent death in patients with severe and critical COVID-19.MethodsOne hundred and forty patients from the CORIMUNO-19 cohort hospitalized with severe or critical COVID-19 pneumonia, all requiring oxygen or ventilation, were prospectively studied. Blood IFN-α2 was evaluated using the Single Molecule Array technology. Anti-IFN-α2 auto-Abs were determined with a reporter luciferase activity. Plasma SARS-Cov2 viral load was measured using droplet digital PCR targeting the Nucleocapsid gene of the SARS-CoV-2 positive-strand RNA genome.ResultsAlthough the percentage of plasmacytoid dendritic cells was low, the blood IFN-α2 level was higher in patients than in healthy controls and was correlated to SARS-CoV-2 plasma viral load at entry. Neutralizing anti-IFN-α2 auto-antibodies were detected in 5% of patients, associated with a lower baseline level of blood IFN-α2. A longitudinal analysis found that a more rapid decline of blood IFN-α2 was observed in fatal versus surviving patients: mortality HR=3.15 (95% CI 1.14–8.66) in rapid versus slow decliners. Likewise, a high level of plasma SARS-CoV-2 RNA was associated with death risk in patients with severe COVID-19.ConclusionThese findings could suggest an interest in evaluating type 1 IFN treatment in patients with severe COVID-19 and type 1 IFN decline, eventually combined with anti-inflammatory drugs.Clinical trial registrationhttps://clinicaltrials.gov, identifiers NCT04324073, NCT04331808, NCT04341584

The BioMart community portal: an innovative alternative to large, centralized data repositories.

The BioMart Community Portal (www.biomart.org) is a community-driven effort to provide a unified interface to biomedical databases that are distributed worldwide. The portal provides access to numerous database projects supported by 30 scientific organizations. It includes over 800 different biological datasets spanning genomics, proteomics, model organisms, cancer data, ontology information and more. All resources available through the portal are independently administered and funded by their host organizations. The BioMart data federation technology provides a unified interface to all the available data. The latest version of the portal comes with many new databases that have been created by our ever-growing community. It also comes with better support and extensibility for data analysis and visualization tools. A new addition to our toolbox, the enrichment analysis tool is now accessible through graphical and web service interface. The BioMart community portal averages over one million requests per day. Building on this level of service and the wealth of information that has become available, the BioMart Community Portal has introduced a new, more scalable and cheaper alternative to the large data stores maintained by specialized organizations

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Broken symmetry within crystallographic superspaces : structural and dynamical aspects

Les cristaux apériodiques possèdent la propriété d’avoir un ordre à grande distance mais sans la symétrie de translation. Ces cristaux se décrivent dans des superespaces cristallographiques de dimension supérieure à trois. Dans ce mémoire, nous nous intéressons plus particulièrement aux brisures de symétrie présentes dans de tels espaces cristallographiques en considérant la famille prototype de n-alcane/urée. Des études par diffraction de rayons X sur sources synchrotron révèlent de multiples solutions structurales impliquant des changements ou non de la dimension du groupe de superespace. Une fois la caractérisation du paramètre d’ordre et de la brisure de symétrie faite nous présentons les phénomènes prétransitionnels critiques associés à ces transitions de phase de type groupe/sous-groupe. La diffusion cohérente de neutrons et la diffusion de rayons X inélastiques permettent une analyse dynamique des différentes excitations dans ces matériaux (phonons, phasons). Les composés d’inclusion avec des molécules invitées courtes (alcane CnH2n+2 avec n variant de 7 à 13) révèlent à température ambiante des phases « quasi-liquides » uni-dimensionnelles. Ce désordre dynamique le long de la direction d'incommensurabilité de ces matériaux génère à basse température des solutions structurales nouvelles (composite monoclinique intermodulé, ancrages commensurables).Aperiodic crystals have the property to possess long range order without translational symmetry. These crystals are described within the formalism of superspace crystallography. In this manuscript, we will focus on symmetry breakings which take place in such crystallographic superspace groups, considering the prototype family of n-alkane/urea. Studies performed by X-ray diffraction using synchrotron sources reveal multiple structural solutions implying or not changes of the dimension of the superspace. Once the characterization of the order parameter and of the symmetry breaking is done, we present the critical pretransitionnal phenomena associated to phase transitions of group/subgroup types. Coherent neutron scattering and X-ray scattering allow a dynamical analysis of different kind of excitations in these materials (phonons, phasons). The inclusion compounds with short guest molecules (alkane CnH2n+2, n varying from 7 to 13) show at room temperature unidimensional “liquid-like” phases. The dynamical disorder along the incommensurate direction of these materials generates new structural solutions at low temperature (intermodulated monoclinic composite, commensurate lock-in)

Broken symmetry within crystallographic superspaces : structural and dynamical aspects

Les cristaux apériodiques possèdent la propriété d’avoir un ordre à grande distance mais sans la symétrie de translation. Ces cristaux se décrivent dans des superespaces cristallographiques de dimension supérieure à trois. Dans ce mémoire, nous nous intéressons plus particulièrement aux brisures de symétrie présentes dans de tels espaces cristallographiques en considérant la famille prototype de n-alcane/urée. Des études par diffraction de rayons X sur sources synchrotron révèlent de multiples solutions structurales impliquant des changements ou non de la dimension du groupe de superespace. Une fois la caractérisation du paramètre d’ordre et de la brisure de symétrie faite nous présentons les phénomènes prétransitionnels critiques associés à ces transitions de phase de type groupe/sous-groupe. La diffusion cohérente de neutrons et la diffusion de rayons X inélastiques permettent une analyse dynamique des différentes excitations dans ces matériaux (phonons, phasons). Les composés d’inclusion avec des molécules invitées courtes (alcane CnH2n+2 avec n variant de 7 à 13) révèlent à température ambiante des phases « quasi-liquides » uni-dimensionnelles. Ce désordre dynamique le long de la direction d'incommensurabilité de ces matériaux génère à basse température des solutions structurales nouvelles (composite monoclinique intermodulé, ancrages commensurables).Aperiodic crystals have the property to possess long range order without translational symmetry. These crystals are described within the formalism of superspace crystallography. In this manuscript, we will focus on symmetry breakings which take place in such crystallographic superspace groups, considering the prototype family of n-alkane/urea. Studies performed by X-ray diffraction using synchrotron sources reveal multiple structural solutions implying or not changes of the dimension of the superspace. Once the characterization of the order parameter and of the symmetry breaking is done, we present the critical pretransitionnal phenomena associated to phase transitions of group/subgroup types. Coherent neutron scattering and X-ray scattering allow a dynamical analysis of different kind of excitations in these materials (phonons, phasons). The inclusion compounds with short guest molecules (alkane CnH2n+2, n varying from 7 to 13) show at room temperature unidimensional “liquid-like” phases. The dynamical disorder along the incommensurate direction of these materials generates new structural solutions at low temperature (intermodulated monoclinic composite, commensurate lock-in)