Functional characterization of E- and P-cadherin in invasive breast cancer cells

BACKGROUND Alterations in the cadherin-catenin adhesion complexes are involved in tumor initiation, progression and metastasis. However, the functional implication of distinct cadherin types in breast cancer biology is still poorly understood. METHODS To compare the functional role of E-cadherin and P-cadherin in invasive breast cancer, we stably transfected these molecules into the MDA-MB-231 cell line, and investigated their effects on motility, invasion and gene expression regulation. RESULTS Expression of either E- and P-cadherin significantly increased cell aggregation and induced a switch from fibroblastic to epithelial morphology. Although expression of these cadherins did not completely reverse the mesenchymal phenotype of MDA-MB-231 cells, both E- and P-cadherin decreased fibroblast-like migration and invasion through extracellular matrix in a similar way. Moreover, microarray gene expression analysis of MDA-MB-231 cells after expression of E- and P-cadherins revealed that these molecules can activate signaling pathways leading to significant changes in gene expression. Although the expression patterns induced by E- and P-cadherin showed more similarities than differences, 40 genes were differentially modified by the expression of either cadherin type. CONCLUSION E- and P-cadherin have similar functional consequences on the phenotype and invasive behavior of MDA-MB-231 cells. Moreover, we demonstrate for the first time that these cadherins can induce both common and specific gene expression programs on invasive breast cancer cells. Importantly, these identified genes are potential targets for future studies on the functional consequences of altered cadherin expression in human breast cancer.

Thy-1-mediated cell-cell contact induces astrocyte migration through the engagement of αVβ3 integrin and syndecan-4.

Cell adhesion to the extracellular matrix proteins occurs through interactions with integrins that bind to Arg-Gly-Asp (RGD) tripeptides, and syndecan-4, which recognizes the heparin-binding domain of other proteins. Both receptors trigger signaling pathways, including those that activate RhoGTPases such as RhoA and Rac1. This sequence of events modulates cell adhesion to the ECM and cell migration. Using a neuron-astrocyte model, we have reported that the neuronal protein Thy-1 engages αVβ3 integrin and syndecan-4 to induce RhoA activation and strong astrocyte adhesion to their underlying substrate. Thus, because cell-cell interactions and strong cell attachment to the matrix are considered antagonistic to cell migration, we hypothesized that Thy-1 stimulation of astrocytes should preclude cell migration. Here, we studied the effect of Thy-1 expressing neurons on astrocyte polarization and migration using a wound-healing assay and immunofluorescence analysis. Signaling molecules involved were studied by affinity precipitation, western blotting and the usage of specific antibodies. Intriguingly, Thy-1 interaction with its two receptors was found to increase astrocyte polarization and migration. The latter events required interactions of these receptors with both the RGD-like sequence and the heparin-binding domain of Thy-1. Additionally, prolonged Thy-1-receptor interactions inhibited RhoA activation while activating FAK, PI3K and Rac1. Therefore, sustained engagement of integrin and syndecan-4 with the neuronal surface protein Thy-1 induces astrocyte migration. Interestingly we identify here, a cell-cell interaction that despite initially inducing strong cell attachment, favors cell migration upon persistent stimulation by engaging the same signaling receptors and molecules as those utilized by the extracellular matrix proteins to stimulate cell movement.

mTORC2 regulates PGE2-mediated endothelial cell survival and migration.

Prostaglandin E(2) (PGE(2)) promotes angiogenesis by in part inducing endothelial cell survival and migration. The present study examined the role of mTOR and its two complexes, mTORC1 and mTORC2, in PGE(2)-mediated endothelial cell responses. We used small interfering RNA (siRNA) to raptor or rictor to block mTORC1 or mTORC2, respectively. We observed that down-regulation of mTORC2 but not mTORC1 reduced baseline and PGE(2)-induced endothelial cell survival and migration. At the molecular level, we found that knockdown of mTORC2 inhibited PGE(2)-mediated Rac and Akt activation two important signaling intermediaries in endothelial cell migration and survival, respectively. In addition, inhibition of mTORC2 by prolonged exposure of endothelial cells to rapamycin also prevented PGE(2)-mediated endothelial cell survival and migration confirming the results obtained with the siRNA approach. Taken together these results show that mTORC2 but not mTORC1 is an important signaling intermediary in PGE(2)-mediated endothelial cell responses.

Differential migration of in vivo primed B and T lymphocytes to lymphoid and non-lymphoid organs.

Our study describes tissue-specific migration of T and B cells during a localized anti-viral immune response. After mouse mammary tumor virus (MMTV) injection, B lymphocytes of the draining lymph node become infected and present a retroviral superantigen to CD4(+) T lymphocytes. Infected B cells receive superantigen-mediated help in a fashion comparable to classical immune responses. To investigate the fate of T and B lymphocytes that had interacted via cognate help in the same peripheral lymph node microenvironment we adoptively transferred them into naive recipients. Here we show that MMTV-infected B cells and superantigen-stimulated T cells were programmed to migrate to distinct sites of the body. Plasmablasts but not T cells migrated to the mammary gland and activated alpha4beta1 integrins were found to have a crucial role in the migration to the mammary gland. In contrast, T cells had a much higher affinity for secondary lymphoid organs and large intestine. This demonstrates that upon antigen-driven B and T lymphocyte interaction in the local draining lymph node a subset-specific homing program for B and T lymphocytes is induced.

Induction of transendothelial migration in normal and malignant human T lymphocytes.

Activated CD 3+ enriched human peripheral blood T cells exhibited potent capacity for transendothelial migration through HUVEC layers in the absence of T cell ***. In contrast, malignant human T cell lines *** no or negligible ability of transendothelial migration in the absence of chemoattractants. Time lapse studies of transendothelial migration of activated CD 3+ enriched peripheral blood T cells through a HUVEC layer showed that the first T cells were detected in the lower compartment of a tissue culture insert after 1 hour and that migration increased to reach a maximum of 25 x 10(4) T cells/hr after 24 hours. Adhesion assays of human T cell lines demonstrated that all T cell lines were capable of adhesion to HUVEC and that adhesion of T cells to HUVECs was primarily mediated by CD11a/CD18 and ICAM-1 interactions. Furthermore, transendothelial migration of CD 3+ enriched human peripheral blood T cells was inhibited by pretreating the T cells with anti-CD 18 monoclonal antibodies. The inability of malignant T cells to migrate through HUVEC layers in the absence of chemoattractants was not due to poor motility per se, since both normal and malignant T cells migrated well on extracellular matrix components as determined by using Boyden chambers. Crosslinking of alpha 1 beta 2 and alpha 4 beta 1 with immobilized monoclonal antibodies induced motile behaviour in activated CD 3 enriched human peripheral blood T cells but not in malignant T cell lines. In conclusion, the differences in the ability of transendothelial migration between normal and malignant human T cells in the absence of chemoattractants is primarily due to the differences in the capacity of alpha 1 beta 2 and alpha 4 beta 1 to trigger motile behaviour in the separate cell types.

Movement, impacts and management of plant distributions in response to climate change: insights from invasions

A major challenge in this era of rapid climate change is to predict changes in species distributions and their impacts on ecosystems, and, if necessary, to recommend management strategies for maintenance of biodiversity or ecosystem services. Biological invasions, studied in most biomes of the world, can provide useful analogs for some of the ecological consequences of species distribution shifts in response to climate change. Invasions illustrate the adaptive and interactive responses that can occur when species are confronted with new environmental conditions. Invasion ecology complements climate change research and provides insights into the following questions: i) how will species distributions respond to climate change? ii) how will species movement affect recipient ecosystems? and iii) should we, and if so how can we, manage species and ecosystems in the face of climate change? Invasion ecology demonstrates that a trait-based approach can help to predict spread speeds and impacts on ecosystems, and has the potential to predict climate change impacts on species ranges and recipient ecosystems. However, there is a need to analyse traits in the context of life-history and demography, the stage in the colonisation process (e.g., spread, establishment or impact), the distribution of suitable habitats in the landscape, and the novel abiotic and biotic conditions under which those traits are expressed. As is the case with climate change, invasion ecology is embedded within complex societal goals. Both disciplines converge on similar questions of "when to intervene?" and "what to do?" which call for a better understanding of the ecological processes and social values associated with changing ecosystems.

Zoledronate inhibits endothelial cell adhesion, migration and survival through the suppression of multiple, prenylation-dependent signaling pathways.

BACKGROUND: Recent evidence indicates that zoledronate, a nitrogen-containing bisphosphonate used to treat conditions of increased bone resorption, may have anti-angiogenic activity. The endothelial cells signaling events modulated by zoledronate remain largely elusive. OBJECTIVES: The aim of this work was to identify signaling events suppressed by zoledronate in endothelial cells and responsible for some of its biological effects. METHODS: Human umbilical vein endothelial cells (HUVEC) were exposed to zoledronate, isoprenoid analogs (i.e. farnesol and geranylgeraniol) and various inhibitors of signaling, and the effect on adhesion, survival, migration, actin cytoskeleton and signaling events characterized. RESULTS: Zoledronate reduced Ras prenylation, Ras and RhoA translocation to the membrane, and sustained ERK1/2 phosphorylation and tumor necrosis factor (TNF) induced JNK phosphorylation. Isoprenoid analogs attenuated zoledronate effects on HUVEC adhesion, actin stress fibers and focal adhesions, migration and survival. Isoprenoid analogs also restored Ras prenylation, RhoA translocation to the membrane, sustained FAK and ERK1/2 phosphorylation and prevented suppression of protein kinase B (PKB) and JNK phosphorylation in HUVEC exposed to TNF in the presence of zoledronate. Pharmacological inhibition of Rock, a RhoA target mediating actin fiber formation, phosphatidylinositol 3-kinase, an activator of PKB, MEK1/2, an activator of ERK1/2, and JNK, recapitulated individual zoledronate effects, consistent with the involvement of these molecules and pathways and their inhibition in the zoledronate effects. CONCLUSIONS: This work has demonstrated that zoledronate inhibits HUVEC adhesion, survival, migration and actin stress fiber formation by interfering with protein prenylation and has identified ERK1/2, JNK, Rock, FAK and PKB as kinases affected by zoledronate in a prenylation-dependent manner.

The dexamethasone-induced inhibition of proliferation, migration, and invasion in glioma cell lines is antagonized by macrophage migration inhibitory factor (MIF) and can be enhanced by specific MIF inhibitors.

Glioblastomas (GBMs) are the most frequent and malignant brain tumors in adults. Glucocorticoids (GCs) are routinely used in the treatment of GBMs for their capacity to reduce the tumor-associated edema. Few in vitro studies have suggested that GCs inhibit the migration and invasion of GBM cells through the induction of MAPK phosphatase 1 (MKP-1). Macrophage migration inhibitory factor (MIF), an endogenous GC antagonist is up-regulated in GBMs. Recently, MIF has been involved in tumor growth and migration/invasion and specific MIF inhibitors have been developed on their capacity to block its enzymatic tautomerase activity site. In this study, we characterized several glioma cell lines for their MIF production. U373 MG cells were selected for their very low endogenous levels of MIF. We showed that dexamethasone inhibits the migration and invasion of U373 MG cells, through a glucocorticoid receptor (GR)- dependent inhibition of the ERK1/2 MAPK pathway. Oppositely, we found that exogenous MIF increases U373 MG migration and invasion through the stimulation of the ERK1/2 MAP kinase pathway and that this activation is CD74 independent. Finally, we used the Hs 683 glioma cells that are resistant to GCs and produce high levels of endogenous MIF, and showed that the specific MIF inhibitor ISO-1 could restore dexamethasone sensitivity in these cells. Collectively, our results indicate an intricate pathway between MIF expression and GC resistance. They suggest that MIF inhibitors could increase the response of GBMs to corticotherapy.

Targeting the PI3K p110alpha isoform inhibits medulloblastoma proliferation, chemoresistance, and migration.

PURPOSE: The phosphoinositide 3-kinase (PI3K)/Akt pathway is frequently activated in human cancer and plays a crucial role in medulloblastoma biology. We were interested in gaining further insight into the potential of targeting PI3K/Akt signaling as a novel antiproliferative approach in medulloblastoma. EXPERIMENTAL DESIGN: The expression pattern and functions of class I(A) PI3K isoforms were investigated in medulloblastoma tumour samples and cell lines. Effects on cell survival and downstream signaling were analyzed following down-regulation of p110alpha, p110beta, or p110delta by means of RNA interference or inhibition with isoform-specific PI3K inhibitors. RESULTS: Overexpression of the catalytic p110alpha isoform was detected in a panel of primary medulloblastoma samples and cell lines compared with normal brain tissue. Down-regulation of p110alpha expression by RNA interference impaired the growth of medulloblastoma cells, induced apoptosis, and led to decreased migratory capacity of the cells. This effect was selective, because RNA interference targeting of p110beta or p110delta did not result in a comparable impairment of DAOY cell survival. Isoform-specific p110alpha inhibitors also impaired medulloblastoma cell proliferation and sensitized the cells to chemotherapy. Medulloblastoma cells treated with p110alpha inhibitors further displayed reduced activation of Akt and the ribosomal protein S6 kinase in response to stimulation with hepatocyte growth factor and insulin-like growth factor-I. CONCLUSIONS: Together, our data reveal a novel function of p110alpha in medulloblastoma growth and survival.

NSAIDs inhibit alpha V beta 3 integrin-mediated and Cdc42/Rac-dependent endothelial-cell spreading, migration and angiogenesis.

Cyclooxygenase-2 (COX-2), a key enzyme in arachidonic acid metabolism, is overexpressed in many cancers. Inhibition of COX-2 by nonsteroidal anti-inflammatory drugs (NSAIDs) reduces the risk of cancer development in humans and suppresses tumor growth in animal models. The anti-cancer effect of NSAIDs seems to involve suppression of tumor angiogenesis, but the underlying mechanism is not completely understood. Integrin alpha V beta 3 is an adhesion receptor critically involved in mediating tumor angiogenesis. Here we show that inhibition of endothelial-cell COX-2 by NSAIDs suppresses alpha V beta 3-dependent activation of the small GTPases Cdc42 and Rac, resulting in inhibition of endothelial-cell spreading and migration in vitro and suppression of fibroblast growth factor-2-induced angiogenesis in vivo. These results establish a novel functional link between COX-2, integrin alpha V beta 3 and Cdc42-/Rac-dependent endothelial-cell migration. Moreover, they provide a rationale to the understanding of the anti-angiogenic activity of NSAIDs.

The overexpression of SOX2 affects the migration of human teratocarcinoma cell line NT2/D1.

The altered expression of the SOX2 transcription factor is associated with oncogenic or tumor suppressor functions in human cancers. This factor regulates the migration and invasion of different cancer cells. In this study we investigated the effect of constitutive SOX2 overexpression on the migration and adhesion capacity of embryonal teratocarcinoma NT2/D1 cells derived from a metastasis of a human testicular germ cell tumor. We detected that increased SOX2 expression changed the speed, mode and path of cell migration, but not the adhesion ability of NT2/D1 cells. Additionally, we demonstrated that SOX2 overexpression increased the expression of the tumor suppressor protein p53 and the HDM2 oncogene. Our results contribute to the better understanding of the effect of SOX2 on the behavior of tumor cells originating from a human testicular germ cell tumor. Considering that NT2/D1 cells resemble cancer stem cells in many features, our results could contribute to the elucidation of the role of SOX2 in cancer stem cells behavior and the process of metastasis.

The nuclear hormone receptor peroxisome proliferator-activated receptor beta/delta potentiates cell chemotactism, polarization, and migration.

After an injury, keratinocytes acquire the plasticity necessary for the reepithelialization of the wound. Here, we identify a novel pathway by which a nuclear hormone receptor, until now better known for its metabolic functions, potentiates cell migration. We show that peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) enhances two phosphatidylinositol 3-kinase-dependent pathways, namely, the Akt and the Rho-GTPase pathways. This PPARbeta/delta activity amplifies the response of keratinocytes to a chemotactic signal, promotes integrin recycling and remodeling of the actin cytoskeleton, and thereby favors cell migration. Using three-dimensional wound reconstructions, we demonstrate that these defects have a strong impact on in vivo skin healing, since PPARbeta/delta-/- mice show an unexpected and rare epithelialization phenotype. Our findings demonstrate that nuclear hormone receptors not only regulate intercellular communication at the organism level but also participate in cell responses to a chemotactic signal. The implications of our findings may be far-reaching, considering that the mechanisms described here are important in many physiological and pathological situations.

Post-Plutonic Magmatism: from the Source to the Emplacement of an Upper Crustal Dyke Swarm, Adamello Massif, Italy

Magmas of the arc-tholeiitic and calc-alkaline differentiation suites contribute substantially to the formation of continental crust in subduction zones. Different geochemical-petrological models have been put forward to achieve evolved magmas forming large volumes of tonalitic to granitic plutons, building an important part of the continental crust. Primary magmas produced in the mantle wedge overlying the subducted slab migrate through the mantle and the crust. During the transfer, magma can accumulate in intermediate reservoirs at different levels where crystallization leads to differentiation and the heat transfer from the magma, together with gained heat from solidification, lead to partial melting of the crust. Partial melts can be assimilated and mix with more primitive magma. Moreover, already formed crystal cumulates or crystal mushes can be recycled and reactivated to transfer to higher crustal levels. Magma transport in the crust involves fow through fractures within a brittle elastic rock. The solidified magma filled crack, a dyke, can crosscut previously formed geological structures and thus serves as a relative or absolute time marker. The study area is situated in the Adamello massif. The Adamello massif is a composite of plutons that were emplaced between 42 and 29 million years. A later dyke swarm intruded into the southern part of the Adamello Batholith. A fractionation model covering dyke compositions from picrobasalts to dacites results in the cummulative crystallization of 17% olivine, 2% Cr-rich spinel, 18% clinopyroxene, 41% amphibole, 4% plagioclase and 0.1% magnetite to achieve an andesitic composition out of a hydrous primitive picrobasalt. These rocks show a similar geochemical evolution as experimental data simulating fractional crystallization and associated magma differentiation at lower crustal depth (7-10 kbar). The peraluminous, corundum normative composition is one characteristic of more evolved dacitic magmas, which has been explained in a long lasting debate with two di_erent models. Melting of mafic crust or politic material provides one model, whereas an alternative is fractionation from primary mantle derived melts. Amphibole occurring in basaltic-andesitic and andesitic dyke rocks as fractionating cumulate phase extracted from lower crustal depth (6-7.5 kbar) is driving the magmas to peraluminous, corundum normative compositions, which are represented by tonalites forming most of the Adamello Batholith. Most primitive picrobasaltic dykes have a slightly steepened chondrite normalized rare earth elements (REE) pattern and the increased enrichment of light-REE (LREE) for andesites and dacites can be explained by the fractional crystallization model originating from a picrobasalt, taking the changing fractionating phase assemblage and temperature into account. The injection of hot basaltic magma (~1050°C) in a closely spaced dyke swarm increases the surface of the contact to the mainly tonalitic wallrock. Such a setting induces partial melting of the wall rock and selective assimilation. Partial melting of the tonalite host is further expressed through intrusion breccias from basaltic dykes. Heat conduction models with instantaneous magma injection for such a dyke swarm geometry can explain features of partial melting observed in the field. Geochemical data of minerals and bulk rock further underline the selective or bulk assimilation of the tonalite host rock at upper crustal levels (~2-3 kbar), in particular with regard to light ion lithophile elements (LILE) such as Sr, Ba and Rb. Primitive picrobasalts carry an immiscible felsic assimilant as enclaves that bring along refractory rutile and zircon with textures typically found in oceanic plagiogranites or high pressure/low-temperature metamorphic rocks in general. U-Pb data implies a lower Cretaceous age for zircon not yet described as assimilant in Eocene to Oligocene magmatic rocks of the Central Southern Alps. The distribution of post-plutonic dykes in large batholiths such as the Adamello is one of the key features for understanding the regional stress field during the post-batholith emplacement cooling history. The emplacement of the regional dyke swarm covering the southern part of the Adamello massif was associated with consistent left lateral strike-slip movement along magma dilatation planes, leading to en echelon segmentation of dykes. Through the dilation by magma of pre-existing weaknesses and cracks in an otherwise uniform host rock, the dyke propagation and according orientation in the horizontal plane adjusted continuously perpendicular to least compressive remote stress σ3, resulting in an inferred rotation of the remote principal stress field. Les magmas issus des zones de subduction contribuent substantiellement à la formation de la croûte continentale. Les plutons tonalitiques et granitiques représentent, en effet, une partie importante de la croûte continentale. Des magmas primaires produits dans le 'mantle wedge ', partie du manteau se trouvant au-dessus de la plaque plongeante dans des zones de subduction, migrent à travers le manteau puis la croûte. Pendant ce transfert, le magma peut s'accumuler dans des réservoirs intermédiaires à différentes profondeurs. Le stockage de magma dans ces réservoirs engendre, d'une part, la différentiation des magmas par cristallisation fractionnée et, d'autre part, une fusion partielle la croûte continentale préexistante associée au transfert de la chaleur des magmas vers l'encaissant. Ces liquides magmatiques issus de la croûte peuvent, ensuite, se mélanger avec des magmas primaires. Le transport du magma dans la croûte implique notamment un flux de magma à travers différentes fractures recoupant les roches encaissantes élastiques. Au cours de ce processus de migration, des cumulats de cristaux ou des agrégats de cristaux encore non-solidifiés, peuvent être recyclés et réactivés pour être transportés à des niveaux supérieures de la croûte. Le terrain d'étude est situé dans le massif d'Adamello. Celui-ci est composé de plusieurs plutons mis en place entre 42 et 29 millions d'années. Dans une phase tardive de l'activité magmatique liée à ce batholite, une série de filons de composition variable allant de picrobasalte à des compositions dacitiques s'est mise en place la partie sud du massif. Deux modèles sont proposés dans la littérature, pour expliquer la formation des magmas dacitiques caractérisés par des compositions peralumineux (i.e. à corindon normatif). Le premier modèle propose que ces magmas soient issus de la fusion de matériel mafique et pélitique présent dans la partie inférieur de la croûte, alors que le deuxième modèle suggère une évolution par cristallisation fractionnée à partir de liquides primaires issus du manteau. Un modèle de cristallisation fractionnée a pu être développé pour expliquer l'évolution des filons de l'Adamello. Ce modèle explique la formation des filons dacitiques par la cristallisation fractionnée de 17% olivine, 2% spinelle riche en Cr, 18% clinopyroxène, 41% amphibole, 4% plagioclase et 0.1% magnetite à partir de liquide de compositions picrobasaltiques. Ce modèle prend en considération les contraintes pétrologiques déduites de l'observation des différents filons ainsi que du champ de stabilité des différentes phases en fonction de la température. Ces roches montrent une évolution géochimique similaire aux données expérimentales simulant la cristallisation fractionnée de magmas évoluant à des niveaux inférieurs de la croûte (7-10 kbar). Le modèle montre, en particulier, le rôle prépondérant de l'amphibole, une phase qui contrôle en particulier le caractère peralumineux des magmas différentiés ainsi que leurs compositions en éléments en traces. Des phénomènes de fusion partielle de l'encaissant tonalitique lors de la mise en place de _lons mafiques sont observée sur le terrain. L'injection du magma basaltique chaud (~1050°C) sous forme de filons rapprochés augmente la surface du contact avec l'encaissante tonalitique. Une telle situation produit la fusion partielle des roches encaissantes nécessaire à l'incorporation d'enclaves mafiques observés au sein des tonalites. Pour comprendre les conditions nécessaires pour la fusion partielle des roches encaissantes, des modèles de conduction thermique pour une injection simultanée d'une série de filons ont été développées. Des données géochimiques sur les minéraux et sur les roches totales soulignent qu'au niveau supérieur de la croûte, l'assimilation sélective ou totale de l'encaissante tonalitique modifie la composition du liquide primaire pour les éléments lithophiles tel que le Sr, Ba et Rb. Un autre aspect important concernant la pétrologie des filons de l'Adamello est la présence d'enclaves felsiques dans les filons les plus primitifs. Ces enclaves montrent, en particulier, des textures proches de celles rencontrées dans des plagiogranites océaniques ou dans des roches métamorphiques de haute pression/basse température. Ces enclaves contiennent du zircon et du rutile. La datations de ces zircons à l'aide du géochronomètre U-Pb indique un âge Crétacé inférieur. Cet âge est important, car aucune roche de cet âge n'a été considérée comme un assimilant potentiel pour des roches magmatiques d'âge Eocène à Oligocène dans les Alpes Sud Centrales. La réparation spatiale des filons post-plutoniques dans des grands batholites tel que l'Adamello, est une caractéristique clé pour la compréhension des champs de contraintes lors du refroidissement du batholite. L'orientation des filons va, en particulier, indiqué la contrainte minimal au sein des roches encaissante. La mise en place de la série de filon recoupant la partie Sud du massif de l'Adamello est associée à un décrochement senestre, un décrochement que l'on peut lié aux contraintes tectoniques régionales auxquelles s'ajoutent l'effet de la dilatation produite par la mise en place du batholite lui-même. Ce décrochement senestre produit une segmentation en échelon des filons.

NFκB activation by modified vaccinia virus as a novel strategy to enhance neutrophil migration and HIV-specific T-cell responses.

Neutrophils are antigen-transporting cells that generate vaccinia virus (VACV)-specific T-cell responses, yet how VACV modulates neutrophil recruitment and its significance in the immune response are unknown. We generated an attenuated VACV strain that expresses HIV-1 clade C antigens but lacks three specific viral genes (A52R, K7R, and B15R). We found that these genes act together to inhibit the NFκB signaling pathway. Triple ablation in modified virus restored NFκB function in macrophages. After virus infection of mice, NFκB pathway activation led to expression of several cytokines/chemokines that increased the migration of neutrophil populations (Nα and Nβ) to the infection site. Nβ cells displayed features of antigen-presenting cells and activated virus-specific CD8 T cells. Enhanced neutrophil trafficking to the infection site correlated with an increased T-cell response to HIV vector-delivered antigens. These results identify a mechanism for poxvirus-induced immune response and alternatives for vaccine vector design.

Effects of Cement on Moisture Migration in Concrete, Phase A, Laboratory Study of Moisture Migration in Hardened Cement Paste, HR-141, 1972

The Columbus Laboratories of Battelle Memorial Institute is currently conducting a study of the effect of cement on moisture migration in concrete as related to the problem of D-cracking of portland cement concrete pavements. The study began on December 31, 1970, and is planned as a 3-year program. The work plan, approved by the policy committee of the members of the Iowa, Kansas, and Missouri highway departments and the Federal Highway Administration, is composed of four parts. The first phase (A) of the investigation concerned the movement of moisture into and from hardened cement pastes and the dimensional changes accompanying the moisture changes. Small slab specimens of hardened neat cement pastes were prepared from 32 different cements which were prepared at the same water/cement ratio and hydrated to the same maturity factor.