The Role of Erythrocyte Membrane Proteins in Haemolytic Anaemias in South African Populations

Faculty of Science School of Pathology(Molecular Medicine and Haematology). 9707563v [email protected] erythrocyte carries gases between the cells and the lungs, and has to distort to negotiate narrow splenic sinuses and capillaries. This distortion necessitates a high surface area to volume ratio that is maintained by the erythrocyte membrane skeleton, a network of proteins including spectrin and protein 4.1. The skeleton anchors the lipid bilayer through attachment to integral membrane proteins, notably the anion exchange protein, band 3. Abnormalities of the erythrocyte membrane proteins cause loss of cell elasticity and ultimately the erythrocytes become prematurely trapped in the spleen where they are phagocytosed, resulting in haemolytic anaemia. Three mutations causing band 3-deficient hereditary spherocytosis (HS), a haemolytic anaemia characterised by spherical erythrocytes, were located using restriction enzyme analysis and DNA sequencing. Proband A (Black) is heterozygous for band 3 Pinhal (R490H) and has mild clinical symptoms. Proband B and his mother (Caucasian) are heterozygous for band 3 Bicetre (R490C) and have severe anaemia requiring transfusions and splenectomy, respectively. These results confirm codon 490 as a hotspot for mutations and indicate the effect of different amino acid substitutions in the same position on clinical severity. Proband C (Black) is homozygous for a novel mutation (E508K) for which her parents are heterozygous. The proband is severely affected and transfusion- dependent whereas her father has moderate anaemia and her mother is asymptomatic. It is speculated that a secondary factor modulates their clinical symptoms. All of these mutations occur in a CpG dinucleotide, a common source of DNA mutations, and are located within the highly conserved exon 13, which encodes the third to fifth α-helices and the second extracellular loop of the transmembrane region of band 3. The mutations are likely to alter the conformation of band 3, impairing its insertion into the erythrocyte membrane. No causative mutations were located in another 12 band 3-deficient HS kindred using restriction enzymes and single strand conformation polymorphism analysis. Ten protein 4.1-deficient patients with hereditary elliptocytosis, a haemolytic anaemia characterised by elliptical erythrocytes, were also studied. Immunoblot analyses ruled out abnormally sized protein 4.1 and three known DNA mutations were excluded using restriction enzyme analysis. Further studies are required to elucidate the cause of the haemolytic anaemia in these kindred. This study advanced our knowledge of the molecular basis of HS in South African kindred and highlighted the susceptibility of CpG dinucleotides to mutations

Proposal of an Eco-design Framework based on a Design Education Perspective

AbstractIn order to overspread a successful sustainable design of products and services, it is necessary to educate engineering designers at university and along life. Although literature already provides eco-design processes, frameworks, methods and tools, it does not seem to take into consideration the need for a progressive education to eco-design practice. This research proposes a framework based on six fundamental dimensions fractioned into multiple levels: Choice and management of criteria; Modeling of life cycles; Management of the eco-design process; Levels of calling into question of products and services; Integration of industrial stakeholders; Integration of civil stakeholders. The eco-design framework is finally illustrated through its usefulness in describing tools and supporting eco-design education trajectories

Use of DBD plasma, photocatalysis, and combined DBD plasma/photocatalysis in a continuous annular reactor for isovaleraldehyde elimination - Synergetic effect and byproducts identification

International audienceRemoval of isovaleraldehyde from air was investigated experimentally by three processes: dielectric barrier discharge (DBD) plasma, photocatalysis and a DBD plasma/photocatalysis combination. The latter led to a synergetic effect. Many operating parameters were investigated in this study such as the specific energy of discharge, the inlet concentration of isovaleraldehyde and the relative humidity. The UV light generated by the DBD plasma reactor did not activate the photocatalytic medium. Thus, its contribution to the removal of isovaleraldehyde by photocatalysis could be ignored. On the other hand, the use of external UV light significantly improved the removal efficiency. Using a photocatalytic reactor in the presence of water vapor, in small amounts, had a promoting effect on the degradation due to the formation of OHradical dot radicals. The same phenomenon has been observed in other processes for small amounts of water in air. The identified and analyzed byproducts were classified into four groups: intermediate products (propionic acid, acetic acid and acetone), carbon monoxide, carbon dioxide and ozone. The carbon balance on carbon products was achieved at about 90%

Low genetic diversity contrasts with high phenotypic variability in heptaploid Spartina densiflora populations invading the Pacific coast of North America

Species can respond to environmental pressures through genetic and epigenetic changes and through phenotypic plasticity, but few studies have evaluated the relationships between genetic differentiation and phenotypic plasticity of plant species along changing environmental conditions throughout wide latitudinal ranges. We studied inter‐ and intrapopulation genetic diversity (using simple sequence repeats and chloroplast DNA sequencing) and inter‐ and intrapopulation phenotypic variability of 33 plant traits (using field and common‐garden measurements) for five populations of the invasive cordgrass Spartina densiflora Brongn. along the Pacific coast of North America from San Francisco Bay to Vancouver Island. Studied populations showed very low genetic diversity, high levels of phenotypic variability when growing in contrasted environments and high intrapopulation phenotypic variability for many plant traits. This intrapopulation phenotypic variability was especially high, irrespective of environmental conditions, for those traits showing also high phenotypic plasticity. Within‐population variation represented 84% of the total genetic variation coinciding with certain individual plants keeping consistent responses for three plant traits (chlorophyll b and carotenoid contents, and dead shoot biomass) in the field and in common‐garden conditions. These populations have most likely undergone genetic bottleneck since their introduction from South America; multiple introductions are unknown but possible as the population from Vancouver Island was the most recent and one of the most genetically diverse. S. densiflora appears as a species that would not be very affected itself by climate change and sea‐level rise as it can disperse, establish, and acclimate to contrasted environments along wide latitudinal ranges

How Ebola Impacts Genetics of Western Lowland Gorilla Populations

12 pagesInternational audienceBackground: Emerging infectious diseases in wildlife are major threats for both human health and biodiversity conservation. Infectious diseases can have serious consequences for the genetic diversity of populations, which could enhance the species' extinction probability. The Ebola epizootic in western and central Africa induced more than 90% mortality in Western lowland gorilla population. Although mortality rates are very high, the impacts of Ebola on genetic diversity of Western lowland gorilla have never been assessed. Methodology/Principal Findings: We carried out long term studies of three populations of Western lowland gorilla in the Republic of the Congo (Odzala-Kokoua National Park, Lossi gorilla sanctuary both affected by Ebola and Lossi's periphery not affected). Using 17 microsatellite loci, we compared genetic diversity and structure of the populations and estimate their effective size before and after Ebola outbreaks. Despite the effective size decline in both populations, we did not detect loss in genetic diversity after the epizootic. We revealed temporal changes in allele frequencies in the smallest population. Conclusions/Significance: Immigration and short time elapsed since outbreaks could explain the conservation of genetic diversity after the demographic crash. Temporal changes in allele frequencies could not be explained by genetic drift or random sampling. Immigration from genetically differentiated populations and a non random mortality induced by Ebola, i.e., selective pressure and cost of sociality, are alternative hypotheses. Understanding the influence of Ebola on gorilla genetic dynamics is of paramount importance for human health, primate evolution and conservation biology

Estudio técnico de las pinturas murales de Germolles: la contribución de las técnicas de imagen

[EN] The Château de Germolles is one of the rare palace in France dating from the 14th century. The noble floor is decorated with wall paintings that are a unique example of courtly love spirit that infused the princely courts of the time. After being concealed sometime in the 19th century, the paintings were rediscovered and uncovered in the middle of the 20th century and partly restored at the end of the 1990s. No scientific documentation accompanied these interventions and important questions, such as the level of authenticity of the mural decorations and the original painting technique(s) used in the medieval times remained unanswered. The combined scientific and financial supports of COSCH Cost Action and DRAC-Burgundy enabled to study Germolles’ wall paintings using some of the most innovative imaging and analytical techniques and to address some of the questions raised. The study provided significant information on the material used in the medieval times and on the conservation condition of the paintings. The data collected is vast and varied and exposed the owners of the property to the challenges of data management.[ES] El castillo de Germolles es uno de los raros palacios principescos en Francia que data del siglo XIV. La planta noble está decorada con pinturas murales que son un ejemplo único del amor cortés, ese espíritu que se divulgó en las cortes de la época.Ocultadas desde el fin del siglo XIX, las pinturas fueron descubiertas en la mitad del siglo XXy fueron parcialmente restauradas al finalde la década de 1990. No hay documentación científica queacompañelas intervenciones, y cuestiones importantesse quedaronsin repuesta, en particular el nivel de autenticidad de las decoraciones de las paredes, así como lastécnicaspictóricasutilizadasen laépoca medieval. El apoyo científico y económico de la Acción Cost COSCH y de la DRAC de Borgoña permitió elestudio delas pinturas murales de Germolles con algunas de las técnicas de imagen y analíticasmás innovadoras, con tal de responder a algunas de las cuestiones planteadas. El estudio proporcionó informaciónrelevante en lo que se refiere al material utilizado durante la Edad Mediay sobreel estado de conservación de las pinturas. La toma de datos es ampliay variada, y expuso a los dueños de la propiedad al desafío de la gestión de datos.This project would not have been possible without the financial support by DRAC-Burgundy and the COST Action TD1201: Colour and Space in Cultural Heritage (COSCH) (www.cosch.info) which the authors wish to sincerely thank.Degrigny, C.; Piqué, F.; Papiashvili, N.; Guery, J.; Mansouri, A.; Le Goïc, G.; Detalle, V.... (2016). Technical study of Germolles’ wall paintings: the input of imaging technique. Virtual Archaeology Review. 7(15):1-8. https://doi.org/10.4995/var.2016.5831SWORD18715Giovannoni, S., Matteini, M., & Moles, A. (1990). Studies and developments concerning the problem of altered lead pigments in wall painting. Studies in Conservation, 35(1), 21-25. doi:10.1179/sic.1990.35.1.21Manuel, A., Gattet, E., De Luca, L., & Veron, P. (2013). An approach for precise 2D/3D semantic annotation of spatially-oriented images for in situ visualization applications. 2013 Digital Heritage International Congress (DigitalHeritage). doi:10.1109/digitalheritage.2013.6743752Wefers, S., Reich, T., Tietz, B. and Boochs, F. 2016. SIVT – Processing, Viewing, and Analysis of 3D Scans of the Porthole Slab and Slab B2 of Züschen I. In: S. Campana, R. Sopigno, G. Carpentiero and M. Cirillo, eds, CAA2015. Keep the Revolution Going. Proceedings of the 43rd Annual Conference on Computer Applications and Quantitative Methods In Archaeology. Oxford : Archaeopress Publishing Ltd, pp. 1067-1080

Approche archéologique et environnementale des premiers peuplements alpins autour du col du Petit-Saint-Bernard (Savoie, vallée d’Aoste) : un bilan d’étape

De 2003 à 2007, une étude archéologique et sédimentaire a été réalisée sur les versants du col du Petit-Saint-Bernard (2188 m, Alpes occidentales), par de grandes séries de sondages manuels effectués dans des contextes sélectionnés. Les avantages et les inconvénients de cette méthode sont exposés et discutés. Ce travail a permis d’identifier, interstratifiés dans les remplissages holocènes, des sols bruns fersiallitiques sur les versants et des sols hydromorphes en altitude. Les répartitions chronologique et altitudinale des découvertes archéologiques sont analysées, puis comparées à une compilation des connaissances préexistantes dans les vallées alpines du Beaufortin, de la Maurienne et de la Tarentaise. Les analyses paléo-environnementales et archéologiques en cours sont présentées.An archaeological and sedimentary study was realized on the hillsides of the Petit-Saint-Bernard pass (2188 m, western Alps), from 2003 to 2007. It consisted of great series of manual boreholes in selected contexts. The efficiency of this method is discussed. This work allowed identifying brown fersiallitics soils in hillsides and hyrdromorphic soils in the heights, interstratified in the Holocene fillings. The chronological and altitudinal distributions of the findings are analysed and compared to previous data from Beaufortin, Maurienne and Tarentaise. An additional project of palaeo-environmental and archaeological analyses is presented

USF-1 Is Critical for Maintaining Genome Integrity in Response to UV-Induced DNA Photolesions

An important function of all organisms is to ensure that their genetic material remains intact and unaltered through generations. This is an extremely challenging task since the cell's DNA is constantly under assault by endogenous and environmental agents. To protect against this, cells have evolved effective mechanisms to recognize DNA damage, signal its presence, and mediate its repair. While these responses are expected to be highly regulated because they are critical to avoid human diseases, very little is known about the regulation of the expression of genes involved in mediating their effects. The Nucleotide Excision Repair (NER) is the major DNA–repair process involved in the recognition and removal of UV-mediated DNA damage. Here we use a combination of in vitro and in vivo assays with an intermittent UV-irradiation protocol to investigate the regulation of key players in the DNA–damage recognition step of NER sub-pathways (TCR and GGR). We show an up-regulation in gene expression of CSA and HR23A, which are involved in TCR and GGR, respectively. Importantly, we show that this occurs through a p53 independent mechanism and that it is coordinated by the stress-responsive transcription factor USF-1. Furthermore, using a mouse model we show that the loss of USF-1 compromises DNA repair, which suggests that USF-1 plays an important role in maintaining genomic stability

L’émergence du sujet

L’entretien est orienté par une visée, qui consiste à faire émerger le sujet, dans une perspective psychodynamique orientée par la psychanalyse. Dans la place que la présentation occupe au sein d’un service de psychiatrie, le clinicien n’est pas le réceptacle neutre des associations libres du patient. Parfois, il est amené à relancer ce travail associatif, parfois aussi à le contenir