Éditeur(s) : HAL CCSD American Society of Hematology
Résumé : International audience
Polycythemia vera (PV) is characterized by an increased RBC mass, spontaneous erythroid colony formation, and the JAK2V617F mutation. PV is associated with a high risk of mesenteric and cerebral thrombosis. PV RBC adhesion to endothelial laminin is increased and mediated by phosphorylated erythroid Lu/BCAM. In the present work, we investigated the mechanism responsible for Lu/BCAM phosphorylation in the presence of JAK2V617F using HEL and BaF3 cell lines as well as RBCs from patients with PV. High levels of Rap1-GTP were found in HEL and BaF3 cells expressing JAK2V617F compared with BaF3 cells with wild-type JAK2. This finding was associated with increased Akt activity, Lu/BCAM phosphorylation, and cell adhesion to laminin that were inhibited by the dominant-negative Rap1S17N or by the specific Rap1 inhibitor GGTI-298. Surprisingly, knocking-down EpoR in HEL cells did not alter Akt activity or cell adhesion to laminin. Our findings reveal a novel EpoR-independent Rap1/Akt signaling pathway that is activated by JAK2V617F in circulating PV RBCs and responsible for Lu/BCAM activation. This new characteristic of JAK2V617F could play a critical role in initiating abnormal interactions among circulating and endothelial cells in patients with PV.
ISSN: 0006-4971

inserm-00821109
http://www.hal.inserm.fr/inserm-00821109
http://www.hal.inserm.fr/inserm-00821109/document
http://www.hal.inserm.fr/inserm-00821109/file/De_Grandis_Blood_2013.pdf
DOI : 10.1182/blood-2012-07-440487

Éditeur(s) : HAL CCSD Elsevier
Résumé : Grain-size analyses, coupled with end-member modelling, have been performed on the terrigenous fraction of two Leg 184 Ocean Drilling Program sites (1144 and 1146) from the South China Sea. The grain-size distributions over the last 1.8 Ma enable a new interpretation of their connections to sea-level variations and East Asian monsoon strength. Previous investigations in this area have associated grain-size variability with enhanced eolian input during glacial stages. End-member modelling downgrades the importance of this eolian contribution and indicates that the sediments can be described as a mixture of three end-members: fluvial mud inputs, shelf reworking and river mouth migration. Grain-size variations in the Pleistocene section of the cores indicate a multiple-stage evolution: (i) from 1.8 to 1.25 Ma, the downcore grain-size variations are low but show a correspondence between monsoon rainfall intensity and the fine grain-sized fluvial inputs; no link with sea-level variations is noticeable; (ii) from 1.25 to 0.9 Ma, there is an increase (decrease) in the intermediate (fine) end-member (not, vert, similar 100 kyr cycle) that is associated with the onset of a stronger summer monsoon and modest shelf reworking; (iii) from 0.9 to 0 Ma the grain-size record is dominated by global sea-level variations; each glacial stage is associated with extensive shelf reworking and conveyance of coarse particles to the basin.
ISSN: 0033-5894

hal-00404671
https://hal.archives-ouvertes.fr/hal-00404671
DOI : 10.1016/j.yqres.2007.03.004

Éditeur(s) : Gauthier-Villars
Résumé : Moored current measurements carried out from 31 March 1990 to 15 September 1991 in two stages at a point (near 6 degrees N) located over the mid-continental slope off French Guiana are presented. Six current meters were positioned between 200 and 2700 m depth. Upper level mean current data showed a northwestward flowing North Brazil Current (NBC) with mean velocity values decreasing from 10 cm/s in the range 200-250 m to almost zero at 800 m depth, the level of the Antarctic Intermediate Waters. In the range 500-800 m, the current reversed in spring in the presence of the southeastward Western Boundary Under Current (WBUC); the mean velocity from February to June 1991 is around 2 cm/s. Deep currents over the continental rise show a strong southeastward Deep Western Boundary Current extending from around 1000 m depth to the bottom (3000 m depth in this case) with mean core speeds of 20 cm/s at 2000-2070 m depth. Transport estimates based on these data and a few Pegasus sections for the mean vertical and lateral extensions of the DWBC yield a value of 21 x 10(6) m(3)/s at that location. Low-frequency current fluctuations were dominated by a well-defined 50- to 70-day period oscillation with peak-to-peak northwestward velocity amplitude of around 90 cm/s at the upper level. The mean vertical eddy kinetic energy distribution showed an abrupt decrease of the energy down to 800 m depth and a slight decrease below and down to the bottom.
Oceanologica Acta (0399-1784) (Gauthier-Villars), 1994 , Vol. 17 , N. 4 , P. 345-354

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/00098/20897/18510.pdf
http://archimer.ifremer.fr/doc/00098/20897/

Éditeur(s) : HAL CCSD Ferrata Storti Foundation
Résumé : International audience
BACKGROUND: Abnormal interactions between red blood cells, leukocytes and endothelial cells play a critical role in the occurrence of the painful vaso-occlusive crises associated with sickle cell disease. We investigated the interaction between circulating leukocytes and red blood cells which could lead to aggregate formation, enhancing the incidence of vaso-occlusive crises. DESIGN AND METHODS: Blood samples from patients with sickle cell disease (n=25) and healthy subjects (n=5) were analyzed by imaging and classical flow cytometry after density gradient separation. The identity of the cells in the peripheral blood mononuclear cell layer was determined using antibodies directed specifically against white (anti-CD45) or red (anti-glycophorin A) blood cells. RESULTS: Aggregates between red blood cells and peripheral blood mononuclear cells were visualized in whole blood from patients with sickle cell disease. The aggregation rate was 10-fold higher in these patients than in control subjects. Both mature red blood cells and reticulocytes were involved in these aggregates through their interaction with mononuclear cells, mainly with monocytes. The size of the aggregates was variable, with one mononuclear cell binding to one, two or several red blood cells. Erythroid Lu/basal cell adhesion molecule and α(4)β(1) integrin were involved in aggregate formation. The aggregation rate was lower in patients treated with hydroxycarbamide than in untreated patients. CONCLUSIONS: Our study gives visual evidence of the existence of circulating red blood cell-peripheral blood mononuclear cell aggregates in patients with sickle cell disease and shows that these aggregates are decreased during hydroxycarbamide treatment. Our results strongly suggest that erythroid Lu/basal cell adhesion molecule proteins are implicated in these aggregates through their interaction with α(4)β(1) integrin on peripheral blood mononuclear cells.
ISSN: 0390-6078

inserm-00821120
http://www.hal.inserm.fr/inserm-00821120
http://www.hal.inserm.fr/inserm-00821120/document
http://www.hal.inserm.fr/inserm-00821120/file/1841.full.pdf
DOI : 10.3324/haematol.2010.026294

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : Reconstruction of Northern African monsoon between 6.2 and 4.9 Ma and possible relationships with Late Miocene events. Mineralogical and geochemical investigations have been realized on ODP Site 659 in order to better understand the detrital sedimentation of the Cap Verde plateau and to reconstruct African monsoon intensity variations between 6.2 and 4.9 Ma. Time intervals corresponding to an intensification of the summer African monsoon rainfall are associated to a reduction of eolian input from the Sahara and an intensification of the African river input. The reflooding of the Mediterranean Sea at the end of the Messinian salinity crisis (MSC) (5.33 Ma) is correlated to a greater aridity in the Sahara.
ISSN: 1631-0713

hal-00412151
https://hal.archives-ouvertes.fr/hal-00412151
DOI : 10.1016/j.crte.2008.07.005

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
The Nile delta sedimentation constitutes a continuous high resolution (1.6 mm/year) record of Ethiopian African monsoon regime intensity. Multiproxy analyses performed on core MS27PT recovered in hemipelagic Nile sediment margin (<90 km outward of the Rosetta mouth of the Nile) allow the quantification of the Saharan aeolian dust and the Blue/White Nile River suspended matter frequency fluctuations during the last 21 cal. ka BP. The radiogenic Sr and Nd isotopes, clay mineralogy, bulk elemental composition and palynological analyses reveal large changes in source components, oscillating between a dominant aeolian Saharan contribution during the LGM and the Late Holocene (~4 to 2 cal. ka BP), a dominant Blue/Atbara Nile River contribution during the early Holocene (15 to 8.4 cal. ka BP) and a probable White Nile River contribution during the Middle Holocene (8.4 to 4 cal. ka BP). The following main features are highlighted: 1. The rapid shift from the LGM arid conditions to the African Humid Period (AHP) started at about 15 cal. ka BP. AHP extends until 8.4 cal. ka BP, and we suggest that the Ethiopian African Monsoon maximum between 12 and 8 cal. ka BP is responsible for a larger Blue/Atbara Nile sediment load and freshwater input into the Eastern Mediterranean Sea. 2. The transition between the AHP and the arid Late Holocene is gradual and occurs in two main phases between 8.4 and 6.5 cal. ka BP and 6.5 to 3.2 cal. ka BP. We suggest that the main rain belt shifted southward from 8.4 to ~4 cal. ka BP and was responsible for progressively reduced sediment load and freshwater input into the eastern Mediterranean Sea. 3. The aridification along the Nile catchments occurred from ~4 to 2 cal. ka BP. A dry period, which culminates at 3.2 cal. ka BP, and seems to coincide with a re-establishment of increased oceanic primary productivity in the western Mediterranean Sea. We postulate that the decrease in thermo-haline water Mediterranean circulation could be part of a response to huge volumes of fresh-water delivered principally by the Nile River from 12 to 8.4 cal. ka BP in the eastern Mediterranean. We propose that the large hydrological change in Ethiopian latitude could be a trigger for the 8.2 ka cooling event recorded in high latitude. Revel R., Colin C., Bernasconi S., Combourieu-Nebout N., Ducassou E., Grousset F.E., Rolland Y., Migeon S., Brunet P., Zhaa Y., Bosch D., Mascle J.,. "21,000 years of Ethiopian African moonsoon variability recorded in sediments of the western Nile deep sea fan", Regional Environmental Change,
ISSN: 1436-3798

hal-00836300
https://hal.archives-ouvertes.fr/hal-00836300

Éditeur(s) : HAL CCSD Elsevier
Résumé : Rh (Rhesus) is a major blood group system in man, which is clinically significant in transfusion medicine. Rh antigens are carried by an oligomer of two major erythroid specific polypeptides, the Rh (D and CcEe) proteins and the RhAG glycoprotein, that shared a common predicted structure with 12 transmembrane a-helices (M0 to M11). Non erythroid homologues of these proteins have been identified (RhBG and RhCG), notably in diverse organs specialized in ammonia production and excretion, such as kidney, liver and intestine. Phylogenetic studies and experimental evidence have shown that these proteins belong to the Amt/Mep/Rh protein superfamily of ammonium/methylammonium permease, but another view suggests that Rh proteins might function as CO2 gas channels. Until recently no information on the structure of these proteins were available. However, in the last two years, new insight has been gained into the structural features of Rh proteins (through the determination of the crystal structures of bacterial AmtB and archeaebacterial Amt-1. Here, models of the subunit and oligomeric architecture of human Rh proteins are proposed, based on a refined alignment with and crystal structure of the bacterial ammonia transporter AmtB, a member of the Amt/ Mep/Rh superfamily. This alignment was performed considering invariant structural features, which were revealed through Hydrophobic Cluster Analysis, and led to propose alternative predictions for the less conserved regions, particularly in the N-terminal sequences. The Rh models, on which an additional Rh-specific, N-terminal helix M0 was tentatively positioned, were further assessed through the consideration of biochemical and immunochemical data, as well as of stereochemical and topological constraints. These models highlighted some Rh specific features that have not yet been reported. Among these, are the prediction of some critical residues, which may play a role in the channel function, but also in the stability of the subunit structure and oligomeric assembly. These results provide a basis to further understand the structure/function relationships of Rh proteins, and the alterations occurring in variant phenotypes.
ISSN: 1246-7820

hal-00068842
https://hal.archives-ouvertes.fr/hal-00068842

Éditeur(s) : HAL CCSD INRA/EDP Sciences
Résumé : 11 ref.
absent
ISSN: 0003-4312

hal-01032357
https://hal.archives-ouvertes.fr/hal-01032357

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Rh (Rhesus) is a major blood group system in man, which is clinically significant in transfusion medicine. Rh antigens are carried by an oligomer of two major erythroid specific polypeptides, the Rh (D and CcEe) proteins and the RhAG glycoprotein, that shared a common predicted structure with 12 transmembrane a-helices (M0 to M11). Non erythroid homologues of these proteins have been identified (RhBG and RhCG), notably in diverse organs specialized in ammonia production and excretion, such as kidney, liver and intestine. Phylogenetic studies and experimental evidence have shown that these proteins belong to the Amt/Mep/Rh protein superfamily of ammonium/methylammonium permease, but another view suggests that Rh proteins might function as CO2 gas channels. Until recently no information on the structure of these proteins were available. However, in the last two years, new insight has been gained into the structural features of Rh proteins (through the determination of the crystal structures of bacterial AmtB and archeaebacterial Amt-1. Here, models of the subunit and oligomeric architecture of human Rh proteins are proposed, based on a refined alignment with and crystal structure of the bacterial ammonia transporter AmtB, a member of the Amt/Mep/Rh superfamily. This alignment was performed considering invariant structural features, which were revealed through Hydrophobic Cluster Analysis, and led to propose alternative predictions for the less conserved regions, particularly in the N-terminal sequences. The Rh models, on which an additional Rh-specific, N-terminal helix M0 was tentatively positioned, were further assessed through the consideration of biochemical and immunochemical data, as well as of stereochemical and topological constraints. These models highlighted some Rh specific features that have not yet been reported. Among these, are the prediction of some critical residues, which may play a role in the channel function, but also in the stability of the subunit structure and oligomeric assembly. These results provide a basis to further understand the structure/function relationships of Rh proteins, and the alterations occurring in variant phenotypes.
ISSN: 1246-7820

hal-00112914
https://hal.archives-ouvertes.fr/hal-00112914
DOI : 10.1016/j.tracli.2006.02.001

Éditeur(s) : HAL CCSD American Society of Hematology
Résumé : International audience
Sickle cell disease is characterized by painful vaso-occlusive crises during which abnormal interactions between erythroid adhesion molecules and vessel-wall proteins are thought to play a critical role. Hydroxyurea, the only drug with proven benefit in sickle cell disease, diminishes these interactions, but its mechanism of action is not fully understood. We report that, under hydroxyurea, expression of the unique erythroid laminin receptor Lu/BCAM was increased, but red blood cell adhesion to laminin decreased. Because Lu/BCAM phosphorylation is known to activate cell adhesion to laminin, it was evaluated and found to be dramatically lower in hydroxyurea-treated patients. Analysis of the protein kinase A pathway showed decreased intracellular levels of the upstream effector cyclic adenosine monophosphate during hydroxyurea treatment. Using a cellular model expressing recombinant Lu/BCAM, we showed that hydroxyurea led to decreased intracellular cyclic adenosine monophosphate levels and diminished Lu/BCAM phosphorylation and cell adhesion. We provide evidence that hydroxyurea could reduce abnormal sickle red blood cell adhesion to the vascular wall by regulating the activation state of adhesion molecules independently of their expression level.
ISSN: 0006-4971

inserm-00821117
http://www.hal.inserm.fr/inserm-00821117
http://www.hal.inserm.fr/inserm-00821117/document
http://www.hal.inserm.fr/inserm-00821117/file/Bartolucci_Blood_2010.pdf
DOI : 10.1182/blood-2009-12-257444