Antigenic variation in Plasmodium falciparum : understanding the RIFIN protein family

RIFIN proteins are variable surface antigens, which have a central role in the survival and virulence of the malaria parasite Plasmodium falciparum. Antigenic variation is a mean for these parasites to avoid clearance by the host s immune system. However, this is often a secondary function to the main role of these proteins. In the case of RIFIN, P. falciparum s largest multicopy protein family, the main functions remain unknown. In order to elucidate a protein s function, it is crucial to understand its basic properties, including the structure of the protein family, their localization and the protein s topology. Through different methods, we have strived to simplify the RIFIN protein family into manageable entities. We have started with a simple classification of RIFIN proteins into meaningful sub-groups. We have predicted that these sub-groups are functionally distinct, although they probably share a related function. We then designed RSPred, an automatic method, based on hidden Markov models and a sorting program, to detect and classify RIFIN and STEVOR sequences according to their sub-group. Finally, using an in vitro method to determine protein topology, we have analyzed both A-RIFIN and B-RIFIN proteins for their number of transmembrane segments and their topologies. We show that both protein groups have a signal sequence targeting them to lipid bilayers and only one transmembrane domain. They both share a common topology where the bulk of the protein is exposed to the extracellular environment. With the current knowledge of RIFIN protein localizations, as well as the loss of expression of A-RIFIN but not B-RIFIN proteins in a splenectomized patient, it seems increasingly clear that B-RIFIN proteins are good targets for future studies, to decipher the functions of these variable proteins

Les pratiques corporelles des filles et des garçons : socialisations sexuées et variations interindividuelles

L'étude de la socialisation enfantine et des contraintes relatives à la construction du genre au sein d'un même groupe de sexe permet d'apprécier la pluralité de modèles de genre souvent présentés de manière binaire. Dans cette perspective, ce travail de thèse analyse la socialisation corporelle de filles et de garçons âgés de 9 à 12 ans (CM1-CM2). Les pratiques corporelles des enquêtés constituent un " terrain d'observation " du processus de socialisation dont ils et elles sont l'objet. Les rapports à l'activité physique et au travail de l'apparence se situent au centre de l'analyse, permettant ainsi d'étudier le rôle central de l'incorporation dans la construction du genre. La démonstration s'appuie sur des données qualitatives issues d'une enquête ethnographique en milieu scolaire, d'observations dans les contextes sportifs fréquentés et d'une série d'entretiens avec les enfants, les familles et les adultes encadrants (institutrices et éducateurs sportifs). Les résultats mettent en évidence différents " régimes de genre " (Connell, 1987) dans les contextes sportifs et plusieurs groupes d'affinités en milieu scolaire. L'articulation des effets de trois instances de socialisation (la pratique sportive associative, l'école (et notamment les réseaux relationnels enfantins) et la famille permet d'étudier la variabilité et la hiérarchie des modèles de masculinités et de féminités repérésThe analysis of child socialization and constraints relating to the construction of gender within groups of boys and girls offers a new perspective on the plurality of gender patterns, often presented in a binary way. This thesis analyses the body socialization of girls and boys aged between 9 and 12. We analyse their bodily practices as "field observation" of the socialization process and we have focused more specifically on the role of physical activity and the role of "work of the appearance" on gender construction, and the process of incorporation. The demonstration is based on qualitative ethnographic data from a school survey, observations in sport contexts and a series of interviews with children, families and adults (teachers, sports instructors). The study has identified different "gender regimes" (Connell, 1987) in sports contexts and a several affinity groups in school. The joint effects of three instances of socialization (associative sport, school and family) are taken into account to explain the variability and the hierarchy of the identified models of masculinities and femininitie

"Rocking your Nation" : le pow-wow de Kanhesatà:ke et les identités autochtones

Ce mémoire porte sur les pow-wow du sud-ouest du Québec, région circonscrite entre et autour de Montréal et de Québec, et les identités autochtones. Ici analysé en tant que fête, le pow-wow est un évènement ayant gagné en popularité chez les peuples autochtones, au Québec, au cours des dernières années. Le tambour, les chants et les danses sont au coeur de la célébration, mais elle est également constituée d’une variété d’autres pratiques. Elle est considérée comme un lieu privilégié d’expression des cultures autochtones. Cette étude met plus spécifiquement en lumière le pow-wow de Kanehsatà:ke, une communauté kanien'kehá:ka située dans les Basses-Laurentides. Y est approfondi le lien entre celui-ci et la construction, la négociation et l’affirmation des identités autochtones, tant d’un point de vue individuel que d’un point de vue collectif (communauté, pan-autochtonie). Afin d’inscrire la fête dans un contexte plus large, des observations participantes ont été réalisées lors de cinq rassemblements différents. Des observations participantes lors des préparatifs de la fête à Kanehsatà:ke et des entretiens semi-directifs avec dix personnes ont également été effectués. Ceux-ci ont permis de mieux comprendre la place de la célébration au sein de la collectivité et le sens de celle-ci. L’analyse démontre que le pow-wow est un évènement auquel la communauté semble être attachée. Il contribue à la construction, la négociation et l’affirmation des identités autochtones de par ses fonctions de guérison et de ressourcement (individuelle et collective), de transmission et d’apprentissage, de même que ses fonctions sociales, touristiques et économiques.This master’s thesis examines Southwestern Quebec’s powwows — a region circumscribed around and between Montreal and Quebec — and Indigenous identities. Here analyzed as a celebration, powwow is an event that gained popularity among Indigenous peoples in Quebec in the past years. Drum, songs and dances are at the heart of the celebration, but it is also composed of various other practices. It is considered as a privileged space to express Indigenous cultures. More specifically, this study brings up to light the powwow of Kanehsatà:ke, a kanien'kehá:ka community located in the Basses-Laurentides area. The link between this event and the building, negotiation and assertion of Indigenous identities, individual and collective (community, pan-aboriginality), is detailed. To situate the celebration in a broader context, participant observations of five gatherings were made. Participant observations of Kanehsatà:ke’s celebration’s preparations and semi-structured interviews with ten people were also conducted. They enabled a better understanding of the place of the powwow in the community and of the gathering’s meaning. The analysis demonstrates that the community seems attached to its celebration. The powwow contributes to build, negotiate and assert Indigenous identities because of its healing (individual and collective), transmission and learning, social, touristic and economic functions

Sub-grouping and sub-functionalization of the RIFIN multi-copy protein family

<p>Abstract</p> <p>Background</p> <p>Parasitic protozoans possess many multicopy gene families which have central roles in parasite survival and virulence. The number and variability of members of these gene families often make it difficult to predict possible functions of the encoded proteins. The families of extra-cellular proteins that are exposed to a host immune response have been driven via immune selection to become antigenically variant, and thereby avoid immune recognition while maintaining protein function to establish a chronic infection.</p> <p>Results</p> <p>We have combined phylogenetic and function shift analyses to study the evolution of the RIFIN proteins, which are antigenically variant and are encoded by the largest multicopy gene family in <it>Plasmodium falciparum</it>. We show that this family can be subdivided into two major groups that we named A- and B-RIFIN proteins. This suggested sub-grouping is supported by a recently published study that showed that, despite the presence of the <it>Plasmodium </it>export (PEXEL) motif in all RIFIN variants, proteins from each group have different cellular localizations during the intraerythrocytic life cycle of the parasite. In the present study we show that function shift analysis, a novel technique to predict functional divergence between sub-groups of a protein family, indicates that RIFINs have undergone neo- or sub-functionalization.</p> <p>Conclusion</p> <p>These results question the general trend of clustering large antigenically variant protein groups into homogenous families. Assigning functions to protein families requires their subdivision into meaningful groups such as we have shown for the RIFIN protein family. Using phylogenetic and function shift analysis methods, we identify new directions for the investigation of this broad and complex group of proteins.</p

A NEW DYNAMIC SUBSTRUCTURING METHOD FOR NONLINEAR AND DISSIPATIVE SYSTEMS

International audienceThis work is devoted to the development of a new dynamic substructuring method inspired by classic fixed-interface component mode synthesis, in order to compute the steady-state vibrations of dissipative, nonlinear structures. For each substructure, the displacement field is sought as a multiharmonic oscillation made of standard static mode shapes, supplemented by the eigenvectors of the nonlinear complex modes of the substructure computed with fixed-boundary conditions. The method eventually leads to a strongly reduced nonlinear algebraic system, easily solved by iterative solvers. The procedure is tested on a lumped parameter model of bladed disk subjected to dry friction nonlinearities, with or without structural mis-tuning, and proves very efficient in terms of computational cost. These results emphasize the promising capabilities of this new reduced-order modeling technique to tackle such nonlinear systems exhibiting high modal density

Corrigendum to “Pollen-based paleoenvironmental and paleoclimatic change at Lake Ohrid (south-eastern Europe) during the past 500 ka” published in Biogeosciences, 13, 1423–1437, 2016

In this corrigendum we report an updated pollen record from the Lake Ohrid DEEP site spanning the past 500 ka whereby we have reprocessed and re-analyzed 104 samples affected by chemical procedure problems that occurred in one palynological laboratory. Firstly, these samples were affected by the use of wrong containers, causing in- adequate settling of particles at the set centrifuging speed. Secondly, HCl and HF treatments were combined without the prescribed intermediate centrifuging and decanting steps. The inaccuracy in the protocol resulted in the loss of smaller pollen grains and in the overrepresentation of bisaccate ones in most of the re-analyzed samples. We therefore provide an updated set of figures with the new data and have revised the description of the results, discussion and conclusions re- ported in Sadori et al. (2016) where necessary. We stress that the majority of the original results and conclusions remain valid, while the records’ reliability and resolution have improved as 12 samples that had been omitted in the original study because of low count sums are now included in the revised dataset (Sadori et al., 2018)

Environmental Drivers of Holocene Forest Development in the Middle Atlas, Morocco

In semi-arid regions subject to rising temperatures and drought, palaeoecological insights into past vegetation dynamics under a range of boundary conditions are needed to develop our understanding of environmental responses to climatic changes. Here, we present a new high-resolution record of vegetation history and fire activity spanning the last 12,000 years from Lake Sidi Ali in the southern Middle Atlas Mountains, Morocco. The record is underpinned by a robust AMS radiocarbon and 210Pb/137Cs chronology and multi-proxy approach allowing direct comparison of vegetation, hydroclimate, and catchment tracers. The record reveals the persistence of steppic landscapes until 10,340 cal yr BP, prevailing sclerophyll woodland with evergreen Quercus until 6,300 cal yr BP, predominance of montane conifers (Cedrus and Cupressaceae) until 1,300 cal yr BP with matorralization and increased fire activity from 4,320 cal yr BP, and major reduction of forest cover after 1,300 cal yr BP. Detailed comparisons between the pollen record of Lake Sidi Ali (2,080m a.s.l.) and previously published data from nearby Tigalmamine (1,626m a.s.l.) highlight common patterns of vegetation change in response to Holocene climatic and anthropogenic drivers, as well as local differences relating to elevation and bioclimate contrasts between the sites. Variability in evergreen Quercus and Cedrus at both sites supports a Holocene summer temperature maximum between 9,000 and 7,000 cal yr BP in contrast with previous large-scale pollen-based climate reconstructions, and furthermore indicates pervasive millennial temperature variability. Millennial-scale cooling episodes are inferred from Cedrus expansion around 10,200, 8,200, 6,100, 4,500, 3,000, and 1,700 cal yr BP, and during the Little Ice Age (400 cal yr BP). A two-part trajectory of Late Holocene forest decline is evident, with gradual decline from 4,320 cal yr BP linked to synergism between pastoralism, increased fire and low winter rainfall, and a marked reduction from 1,300 cal yr BP, attributed to intensification of human activity around the Early Muslim conquest of Morocco. This trajectory, however, does not mask vegetation responses to millennial climate variability. The findings reveal the sensitive response ofMiddle Atlas forests to rapid climate changes and underscore the exposure of the montane forest ecosystems to future warming

A Sequence in Subdomain 2 of DBL1a of Plasmodium falciparum Erythrocyte Membrane Protein 1 Induces Strain Transcending Antibodies

Immunity to severe malaria is the first level of immunity acquired to Plasmodium falciparum. Antibodies to the variant antigen PfEMP1 (P. falciparum erythrocyte membrane protein 1) present at the surface of the parasitized red blood cell (pRBC) confer protection by blocking microvascular sequestration. Here we have generated antibodies to peptide sequences of subdomain 2 of PfEMP1-DBL1a previously identified to be associated with severe or mild malaria. A set of sera generated to the amino acid sequence KLQTLTLHQVREYWWALNRKEVWKA, containing the motif ALNRKE, stained the live pRBC. 50% of parasites tested (7/14) were positive both in flow cytometry and immunofluorescence assays with live pRBCs including both laboratory strains and in vitro adapted clinical isolates. Antibodies that reacted selectively with the sequence REYWWALNRKEVWKA in a 15-mer peptide array of DBL1a-domains were also found to react with the pRBC surface. By utilizing a peptide array to map the binding properties of the elicited anti-DBL1a antibodies, the amino acids WxxNRx were found essential for antibody binding. Complementary experiments using 135 degenerate RDSM peptide sequences obtained from 93 Ugandan patient-isolates showed that antibody binding occurred when the amino acids WxLNRKE/D were present in the peptide. The data suggests that the ALNRKE sequence motif, associated with severe malaria, induces strain-transcending antibodies that react with the pRBC surfac

Pollen-based reconstruction of Holocene vegetation and climate in Southern Italy: the case of Lago di Trifoglietti

International audienceA high-resolution pollen record from Lago Trifoglietti in Calabria (southern Italy) provides new insights into the paleoenvironmental and palaeoclimatic changes which characterise the Holocene period in the southern Italy. The chronology is based on 11 AMS radiocarbon dates from terrestrial organic material. The Holocene history of the vegetation cover shows the persistence of an important and relatively stable Fagus forest present over that entire period, offering a rare example of a beech woodstand able to withstand climate changes for more than 11 000 yr. Probably in relation with early Holocene dry climate conditions which affected southern Italy, the Trifoglietti pollen record supports a southward delay in thermophyllous forest expansion dated to ca. 13 500 cal BP at Monticchio, ca. 11 000 cal BP at Trifoglietti, and finally ca. 9800 cal BP in Sicily. Regarding the human impact history, the Trifoglietti pollen record shows only poor imprints of agricultural activities and anthopogenic indicators, apart from those indicating pastoralism activities beneath forest cover. The selective exploitation of Abies appears to have been the strongest human impact on the Trifoglietti surroundings. On the basis of (1) a specific ratio between hygrophilous and terrestrial taxa, and (2) the Modern Analogue Technique, the pollen data collected at Lago Trifoglietti led to the establishment of two palaeoclimatic records tracing changes in (1) lake depth and (2) annual precipitation. On a millennial scale, these records give evidence of increasing moisture from ca. 11 000 to ca. 9400 cal BP and maximum humidity from ca. 9400 to ca. 6200 cal BP, prior to a general trend towards the drier climate conditions that have prevailed up to the present. In addition, several successive centennial-scale oscillations appear to have punctuated the entire Holocene. The identification of a cold dry event around 11 300 cal BP, responsible for a marked decline in timberline altitude and possibly equivalent to the PBO, remains to be confirmed by further investigations verifying both chronology and magnitude. Two cold and possibly drier Boreal oscillations developed at ca. 9800 and 9200 cal BP. At Trifoglietti, the 8.2 kyr event corresponds to the onset of cooler and drier climatic conditions which persisted until ca. 7500 cal BP. Finally, the second half of the Holocene was characterised by dry phases at ca. 6100–5200, 4400–3500, and 2500–1800 cal BP, alternating with more humid phases at ca. 5200–4400 and ca. 3500–2500 cal BP. Considered as a whole, these millennial-scale trends and centennial-scale climatic oscillations support contrasting patterns of palaeohydrological changes recognised between the north- and south-central Mediterranean

Mid Holocene vegetation reconstruction from Vanevan peat (south-eastern shore of Lake Sevan, Armenia)

International audienceA sediment core has been retrieved from Vanevan peat (south-eastern shore of Lake Sevan, Armenia), which is today disconnected from Lake Sevan thanks to an artificial shallowing of the lake. Based on 5 radiocarbon dates, Vanevan record covers the Mid Holocene (from ca. 7800 to ca. 5100 cal. BP). The Late Holocene is today absent in the peat stratigraphy due to modern peat exploitation by surface mining. This study focuses on a multi-proxy approach including pollen, charcoals, and pollen-inferred climate reconstruction. An open-land, steppic vegetation is recorded up to ca. 7700 cal. BP, followed by a more forested landscape during the Mid Holocene (up to ca. 5700 cal. BP), and ending again with an open-land vegetation (to the end of record, 5100 cal. BP). This vegetation dynamics responds to general climate changes documented in the Near East. Whether human activities are documented since ca. 7500 cal. BP (Late Neolithic) in Vanevan, they remain marginal and probably did not affect the area. Early Holocene dry climate, which caused the steppic environment to be widespread through the Near East, is strongly related to low late spring precipitation (PMay–Jun = 180 mm). Mid Holocene forested landscape and increasing lake-level seem related to late spring precipitation (+28%), which is the main change in estimated climate parameters. This has to be linked with reinforcement of the Westerlies and less active Siberian High, which are inversely involved in the following, dry phase starting at ca. 5700 cal. B