Hurler disease (mucopolysaccharidosis type IH): clinical features and consanguinity in Tunisian population

Mucopolysaccharidosis type I (MPS I) was a group of rare autosomal recessive disorder caused by the deficiency of the lysosomal enzyme, alpha -L -iduronidase, and the resulting accumulation of undergraded dematan sulfate and heparan sulfate. MPS I patients have a wide range of clinical presentations, that makes it difficult to predict patient phenotype which is needed for genetic counseling and also impedes the selection and evaluation of patients undergoing therapy bone marrow transplantation

The role of recent admixture in forming the contemporary West Eurasian genomic landscape

Over the past few years, studies of DNA isolated from human fossils and archaeological remains have generated considerable novel insight into the history of our species. Several landmark papers have described the genomes of ancient humans across West Eurasia, demonstrating the presence of large-scale, dynamic population movements over the last 10,000 years, such that ancestry across present-day populations is likely to be a mixture of several ancient groups [1-7]. While these efforts are bringing the details of West Eurasian prehistory into increasing focus, studies aimed at understanding the processes behind the generation of the current West Eurasian genetic landscape have been limited by the number of populations sampled or have been either too regional or global in their outlook [8-11]. Here, using recently described haplotype-based techniques [11], we present the results of a systematic survey of recent admixture history across Western Eurasia and show that admixture is a universal property across almost all groups. Admixture in all regions except North Western Europe involved the influx of genetic material from outside of West Eurasia, which we date to specific time periods. Within Northern, Western, and Central Europe, admixture tended to occur between local groups during the period 300 to 1200 CE. Comparisons of the genetic profiles of West Eurasians before and after admixture show that population movements within the last 1,500 years are likely to have maintained differentiation among groups. Our analysis provides a timeline of the gene flow events that have generated the contemporary genetic landscape of West Eurasia

Alpha-1 antitrypsin gene polymorphism in Chronic Obstructive Pulmonary Disease (COPD)

Alpha-1-antitrypsin (AAT) plays an important role in the pathogenesis of emphysema, the pathological lesion underlying the majority of the manifestations of Chronic Obstructive Pulmonary Disease (COPD). In this study we tested the hypothesis that common AAT polymorphisms influence the risk of developing COPDs. We investigated PiM1 (Ala213Val), PiM2 (Arg101His), PiM3 (Glu376Asp), PiS (Glu264Val) and PiZ (Glu342Lys) SERPINA1 alleles in 100 COPD patients and 200 healthy controls. No significant differences were observed in allele frequencies between COPD patients and controls, neither did haplotype analysis show significant differences between the two groups. A cross-sectional study revealed no significant relationship between common SERPINA1 polymorphisms (PiM1, PiM2, PiM3) and the emphysematous type of COPD. In addition, FEV1 annual decline, determined during a two-year follow up period, revealed no difference among carriers of the tested polymorphisms

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Viscoelastic analysis of RFDA measurements applied to oxide glasses

International audienceThe Resonance Frequency and Damping Analysis (RFDA) is now a common experimental technique to measure the elastic moduli of materials vs. temperature. Nevertheless, the elastic moduli are calculated assuming that the frequency measured is the natural one, not impacted by any damping. In oxide glasses, a significant damping occurs below the glass transition temperature, and it may impact the frequency measured, the elastic moduli calculated, as well as the estimated glass transition temperature. We show here, using the equations of linear viscoelasticity, how we can know if the frequency measured is significantly lowered by damping, and how we can estimate the natural frequency to calculate the correct elastic moduli, only from the data provided by the RFDA the frequency measured and the damping. © 2020 Elsevier B.V

Caractérisation numérique de l'aéroacoustique de train d'atterrissage par application de méthodes avancées de simulation et d'analyse numériques

International audienceWith the objective of aircraft noise mitigation, we here address the numerical characterization of the aeroacoustics by a simplified nose landing gear (NLG), through the use of advanced simulation and signal processing techniques. To this end, the NLG noise physics is first simulated through an advanced hybrid approach, which relies on Computational Fluid Dynamics (CFD) and Computational AeroAcoustics (CAA) calculations. Compared to more traditional hybrid methods (e.g. those relying on the use of an Acoustic Analogy), and although it is used here with some approximations made (e.g. design of the CFD-CAA interface), the present approach does not rely on restrictive assumptions (e.g. equivalent noise source, homogeneous propagation medium), which allows to incorporate more realism into the prediction. In a second step, the outputs coming from such CFD-CAA hybrid calculations are processed through both traditional and advanced post-processing techniques, thus offering to further investigate the NLG's noise source mechanisms. Among other things, this work highlights how advanced computational methodologies are now mature enough to not only simulate realistic problems of airframe noise emission, but also to investigate their underlying physics.Relativement à la problématique générale de la réduction du bruit aéronautique, nous étudions numériquement l’aéroacoustique caractérisant un train d'atterrissage avant simplifié, ceci par l’emploi de techniques avancées de simulation et de traitement du signal. A cette fin, la physique du bruit de train d’atterrissage est tout d'abord simulé via une approche aéroacoustique hybride innovante, qui repose sur un couplage faible de calculs de mécanique des fluides et d’aéroacoustique numériques (CFD et CAA, respectivement). Par rapport aux méthodes hybrides traditionnelles (telles que celles reposant sur une analogie acoustique), et bien qu'utilisée ici avec sous approximations (e.g. design de l'interface de couplage CFD-CAA), l'approche présente n’inclut pas d’hypothèses restrictives (e.g. source de bruit équivalente, milieu de propagation homogène), ce qui permet d'incorporer plus de réalisme dans la prédiction. Dans un second temps, les données issues de ces calculs CFD-CAA hybrides sont exploitées via des techniques de post-traitement traditionnelles et avancées, permettant ainsi d’étudier plus précisément les mécanismes de génération acoustique caractérisant le train d’atterrissage. Entre autres choses, ce travail démontre comment les techniques avancées de calcul et d’analyse sont désormais suffisamment matures pour non seulement simuler des problèmes réalistes d'émission de bruit de cellule avion, mais également d’investiguer leur physique sous-jacente

Rapid genotyping of alpha 1 antitrypsin deletion mutation (PI*Mmalton) using Bi-directional PCR allele-specific amplification

Alpha 1 antitrypsin deficiency (AATD) is a well recognized genetic risk factor for pulmonary disease and less common liver disease. The two most common deficiency alleles worldwide PI*S and PI*Z can be easily detected using several molecular methods. However, there are at least 30 other AATD variants, which are only detectable by alpha 1 antitrypsin (AAT) gene sequencing and, therefore, seem to be more under-recognized than the PI*S and PI*Z alleles. PI*Mmalton is the most frequent AATD variant in different regions of the Southern Mediterranean basin countries, where its prevalence seems to prevail over PI*S and PI*Z. In this work, we report the development of a simple PCR-based analysis designed for the detection of the PI*Mmalton deficiency alleles using two specific primers. A one-tube reaction enables the distinction between the different genotypes. This reliable, easy, fast, and low-cost technique might be useful for laboratories involved in the study of AATD-related diseases, especially those of the Southern Mediterranean basin area with modest budget or where sophisticated equipment is not available. This will allow larger targeted screening for PI*Mmalton in order to better understand this mutation epidemiology and its origin. \ua9 Springer Science+Business Media, LLC 2010