Les dépôts quaternaires de la région de Chibougamau, Québec

Cette étude des dépôts quaternaires dans la région de Chibougamau a deux objectifs: 1) décrire les principaux traits de la géomorphologie et les caractères des unités lithostratigraphiques; 2) discuter quelques concepts de la paléogéographie tardiglaciaire. Deux directions majeures d'écoulement glaciaire sont identifiées : l'une, ancienne, vers le SE (125°) attribuée à un centre de dispersion localisé vers la baie d'Hudson, mais d'âge inconnu; l'autre vers le SSO causée par la dernière glaciation du Wisconsinien. Ce dernier mouvement est identifié par des formes fuselées (045-225°), des stries (035-215°) et par des débris erratiques provenant du bassin du lac Misstassini, au NE. Lors du retrait de l'inlandsis, dans le secteur ouest de la région, la bordure du glacier s'écoulait vers le SO et l'OSO, influencée par la présence du lac Ojibway : le mode dominant des orientations des segments d'eskers (055-235°) est interprété comme une preuve complémentaire de cet écoulement tardif; dans le secteur E, par contre, près de la ligne de partage des eaux, les marques d'écoulement vers le S sont abondantes. Une seule nappe de till de fond est identifiée. Une séquence de faciès de fusion (till stratifié et d'ablation) lui succède. Des déformations glaciotectoniques démontrent que la glace est active lors du dépôt des faciès stratifiés. Les contraintes exercées sur le front glaciaire par les reliefs et les eaux du lac Ojibway commandent un réseau de crevasses conjuguées à 25°: des moraines « mineures » (de De Geer?) de dimensions et d'espacements très variables y sont mises en place. Leur espacement ne peut être utilisé qu'avec prudence pour évaluer le taux de retrait glaciaire de cette région. Le niveau relatif supérieur du lac Ojibway est réévalué à environ 445 m. Une tourbe datée à 7600 BP (à 420 m) indique une afforestation rapide après l'exondation.This Quaternary deposits study has two purposes: 1) a description of the main géomorphologie features and the lithostratigraphic units; 2) a discussion of some concepts regarding the paleogeography during the late stage of the déglaciation. Two main glacial flow directions are identified : an early movement, of unknown age, towards the SE is assigned to a centre of dispersion located in the area of Hudson Bay; another movement, towards the SSW is attributed to the latest Wisconsinian pleniglacial. Evidence for the latter include fluting (045-225°), striae (035°-215°) and the numerous erratics derived from the Mistassini Basin to the NE. During the retreat of the last ice sheet on the west side of the area, the ice-margin was spreading to the SW and WSW, towards Lake Ojibway: the predominant mode of the esker segments trends (055°-235°) is interpreted as additional evidence of this late flow; on the other hand, near the water divide in the eastern area abundant flow marks are in a southerly direction. Only one lodgement till sheet is recognized. A melt-out till sequence (stratified and ablation tills) overlaps the former. GIaciotectonic deformations demonstrate that the ice was active during the deposition of the stratified faciès. The stress exerted on the glacial front by the bottom topography and waters of the Lake Ojibway induced a conjugate system of crevasses at 25°, where minor (or De Geer?) moraines were emplaced. These moraines are of variable sizes and spacings. The spacing must be used with caution when evaluating the rate of glacial retreat in this area. An altitude of 445 m is proposed for the upper relative level of Lake Ojibway. Organic deposits started to accumulate as early as 7,600 BP (at + 420 m) a short time after exundation.Diese Studie der Quartâr-Ablagerungen in der Gegend von Chibougamau hat zwei Ziele: (1) eine Beschreibung der wichtigsten Merkmale der Géomorphologie und der Eigenschaften der Gesteinsschichtungs-Einheiten und (2) die Erôrterung einiger Kronzepte der Palâogeographie der Spàteiszeit. Zwei glaziale Hauptstrômungs-Richtungen werden identifiziert: eine friihe Bewegung nach SO (125°), die einem Streuugszentrum im Gebiet der Hudson Bay zugeschrieben wird, deren Alter aber nicht bekannt ist; die andere nach SSW, verursacht durch die letzte Eiszeit des Wisconsin. Diese letzte Bewegung ist durch geriefelte Formen (045'-225°), Kritzen (035°-215°) und durch erratisches Gerôll gekennzeichnet, das vom Becken des Mistassini-Sees im NO stammt. Wàhrend des Rùckgangs des lnlandeises auf der Westseite des Gebiets ergofS sich der Rand des Gletschers nach SW und WSW, unterdem Einflufi des Ojibway-Sees: die dominierende Weise der Orientierung der Esker-Segmente (055°-235°) wird als ein zusàtzlicher Beweis dieses spâten Flie[5ens interpretiert ; auf der Ost-Seite dagegen nahe der Wasserscheide, gibt es zahlreiche Zeichen fur ein Fliejien nach Suden. Eine einzige Till-Ablagerungsschicht wird festgestellt. Ihr folgt eine Sequenz von Fusions-Faszies (Schicht- und Ablations-Till). Glaziotektonische Deformierungen zeigen, dap das Eis wàhrend der Ablagerung der Schicht-Fazies aktiv war. Der Druck, der durch die Reliefs und durch das Wasser des Ojibways-Sees auf die Eisfront ausgeubt wird, fiihrte zu einem Netz von Spalten, die miteinanderverbundensind, bei 250: "kleinere" (De Geer?) Morànen von sehr unterschiedlicher GroBe und Verteilung finden sich dort. Ihre Verteilung dart nur mit Vorsicht benutzt werden, urn den Grad des Eisrùckgangs in diesern Gebiet zu bestimmen.Das relative Hôchst-Niveau des Ojibways-Sees wird auf etwa 445 m veranschlagt. Torf, der auf 7600 v.u.Z. datiert wird (in 420m Hôhe), weist auf eine schnelle Bewaldung nach der Trockenlegung

Foot-and-Mouth Disease: Optimization, Reproducibility, and Scalability of High-Yield Production of Virus-Like Particles for a Next-Generation Vaccine

Inactivated Foot-and-Mouth Disease (FMD) vaccine has proven to be effective in the control of the disease. However, its production has some disadvantages, including the costly biosafety facilities required for the production of huge amounts of growing live virus, the need of an exhaustive purification process to eliminate non-structural proteins of the virus in the final formulations in order to differentiate infected from vaccinated animals and variable local regulatory restrictions to produce and commercialize the vaccine. Thus, a novel vaccine against FMD that overcome these restrictions is desirable. Although many developments have been made in this regard, most of them failed in terms of efficacy or when considering their transferability to the industry. We have previously reported the use of transient gene expression in mammalian cells to produce FMD virus-like particles (VLPs) as a novel vaccine for FMD and demonstrated the immunogenicity of the recombinant structures in animal models. Here, we report the optimization of the production system by assaying different DNA:polyethylenimine concentrations, cell densities, and direct and indirect protocols of transfection. Also, we evaluated the reproducibility and scalability of the technology to produce high yields of recombinant VLPs in a cost-effective and scalable system compatible with industrial tech-transfer of an effective and safe vaccine.Estación Experimental Agropecuaria BarilocheFil: Mignaqui, Ana Clara. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto de Investigaciones Forestales y Agropecuarias Bariloche; ArgentinaFil: Ferella, Alejandra. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Cass, Brian. Human Health Therapeutics Research Center, National Research Council Canada; CanadáFil Mukankurayija, Larissa. Human Health Therapeutics Research Center, National Research Council Canada; CanadáFil: L’Abbé, Denis. Human Health Therapeutics Research Center, National Research Council Canada; CanadáFil: Bisson, Louis. Human Health Therapeutics Research Center, National Research Council Canada; CanadaFil: Sánchez, Cintia. Biogénesis-Bagó; ArgentinaFil: Scian, Romina. Biogénesis-Bagó; ArgentinaFil: Cardillo, Sabrina Beatriz. Biogénesis-Bagó; ArgentinaFil: Durocher, Yves. Human Health Therapeutics Research Center, National Research Council Canada; CanadáFil: Wigdorovitz, Andres. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; Argentin

Use of stable CHO pools and CHO TGE to accelerate SARS-CoV-2 vaccine development

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Stable high volumetric production of glycosylated human recombinant IFNalpha2b in HEK293 cells

BACKGROUND: Mammalian cells are becoming the prevailing expression system for the production of recombinant proteins because of their capacity for proper protein folding, assembly, and post-translational modifications. These systems currently allow high volumetric production of monoclonal recombinant antibodies in the range of grams per litre. However their use for large-scale expression of cytokines typically results in much lower volumetric productivity. RESULTS: We have engineered a HEK293 cell clone for high level production of human recombinant glycosylated IFNα2b and developed a rapid and efficient method for its purification. This clone steadily produces more than 200 mg (up to 333 mg) of human recombinant IFNα2b per liter of serum-free culture, which can be purified by a single-step cation-exchange chromatography following media acidification and clarification. This rapid procedure yields 98% pure IFNα2b with a recovery greater than 70%. Purified IFNα2b migrates on SDS-PAGE as two species, a major 21 kDa band and a minor 19 kDa band. N-terminal sequences of both forms are identical and correspond to the expected mature protein. Purified IFNα2b elutes at neutral pH as a single peak with an apparent molecular weight of 44,000 Da as determined by size-exclusion chromatography. The presence of intramolecular and absence of intermolecular disulfide bridges is evidenced by the fact that non-reduced IFNα2b has a greater electrophoretic mobility than the reduced form. Treatment of purified IFNα2b with neuraminidase followed by O-glycosidase both increases electrophoretic mobility, indicating the presence of sialylated O-linked glycan. A detailed analysis of glycosylation by mass spectroscopy identifies disialylated and monosialylated forms as the major constituents of purified IFNα2b. Electron transfer dissociation (ETD) shows that the glycans are linked to the expected threonine at position 106. Other minor glycosylated forms and non-sialylated species are also detected, similar to IFNα2b produced naturally by lymphocytes. Further, the HEK293-produced IFNα2b is biologically active as shown with reporter gene and antiviral assays. CONCLUSION: These results show that the HEK293 cell line is an efficient and valuable host for the production of biologically active and glycosylated human IFNα2b

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Atomistic simulations of dislocation mobility in Al, Ni and Al/Mg alloys

Dislocation velocities and mobilities are studied by Molecular Dynamics simulations for edge and screw dislocations in pure aluminum and nickel, and edge dislocations in Al-2.5%Mg and Al-5.0%Mg random substitutional alloys using EAM potentials. In the pure materials, the velocities of all dislocations are close to linear with the ratio of (applied stress)/(temperature) at low velocities, consistent with phonon drag models and quantitative agreement with experiment is obtained for the mobility in Al. At higher velocities, different behavior is observed. The edge dislocation velocity remains dependent solely on (applied stress)/(temperature) up to approximately 1.0 MPa/K, and approaches a plateau velocity that is lower than the smallest "forbidden" speed predicted by continuum models. In contrast, above a velocity around half of the smallest continuum wave speed, the screw dislocation damping has a contribution dependent solely on stress with a functional form close to that predicted by a radiation damping model of Eshelby. At the highest applied stresses, there are several regimes of nearly constant (transonic or supersonic) velocity separated by velocity gaps in the vicinity of forbidden velocities; various modes of dislocation disintegration and destabilization were also encountered in this regime. In the alloy systems, there is a temperature- and concentration-dependent pinning regime where the velocity drops sharply below the pure metal velocity. Above the pinning regime but at moderate stresses, the velocity is again linear in (applied stress)/(temperature) but with a lower mobility than in the pure metal.Comment: PDF, 30 pages including figures, submitted to Modelling Simul. Mater. Sci. En

Rare copy number variation in posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) is a heritable (h2 = 24-71%) psychiatric illness. Copy number variation (CNV) is a form of rare genetic variation that has been implicated in the etiology of psychiatric disorders, but no large-scale investigation of CNV in PTSD has been performed. We present an association study of CNV burden and PTSD symptoms in a sample of 114,383 participants (13,036 cases and 101,347 controls) of European ancestry. CNVs were called using two calling algorithms and intersected to a consensus set. Quality control was performed to remove strong outlier samples. CNVs were examined for association with PTSD within each cohort using linear or logistic regression analysis adjusted for population structure and CNV quality metrics, then inverse variance weighted meta-analyzed across cohorts. We examined the genome-wide total span of CNVs, enrichment of CNVs within specified gene-sets, and CNVs overlapping individual genes and implicated neurodevelopmental regions. The total distance covered by deletions crossing over known neurodevelopmental CNV regions was significant (beta = 0.029, SE = 0.005, P = 6.3 × 10-8). The genome-wide neurodevelopmental CNV burden identified explains 0.034% of the variation in PTSD symptoms. The 15q11.2 BP1-BP2 microdeletion region was significantly associated with PTSD (beta = 0.0206, SE = 0.0056, P = 0.0002). No individual significant genes interrupted by CNV were identified. 22 gene pathways related to the function of the nervous system and brain were significant in pathway analysis (FDR q < 0.05), but these associations were not significant once NDD regions were removed. A larger sample size, better detection methods, and annotated resources of CNV are needed to explore this relationship further

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/ mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology