EphrinA4 plays a critical role in α4 and αL mediated survival ofhuman CLL cells during extravasation

A role of endothelial cells in the survival of CLL cells during extravasation is presently unknown. Herein we show that CLL cells but not normal B cells can receive apoptotic signals through physical contact with TNF-α activated endothelium impairing survival in transendothelial migration (TEM) assays. In addition, the CLL cells of patients having lymphadenopathy (LApos) show a survival advantage during TEM that can be linked to increased expression of α4 and αL integrin chains. Within this context, ephrinA4 expressed on the surface of CLL cells sequestrates integrins and inactivates them resulting in reduced adhesion and inhibition of apoptotic/survival signals through them. In agreement, ephrinA4 silencing resulted in increased survival of CLL cells of LApos patients but not LA neg patients. Similarly was observed when a soluble ephrinA4 isoform was added to TEM assays strongly suggesting that accumulation of this isoform in the serum of LApos patients could contribute to CLL cells dissemination and survival in vivo. In supporting, CLL lymphadenopathies showed a preferential accumulation of apoptotic CLL cells around high endothelial venules lacking ephrinA4. Moreover, soluble ephrinA4 isolated from sera of patients increased the number and viability of CLL cells recovered from the lymph nodes of adoptively transferred mice. Finally, we present evidence suggesting that soluble ephrinA4 mediated survival during TEM could enhance a transcellular TEM route of the CLL cells. Together these findings point to an important role of ephrinA4 in the nodal dissemination of CLL cells governing extravasation and survival

Natural estrogens enhance the engraftment of human hematopoietic stem and progenitor cells in immunodeficient mice

Hematopoietic Stem and Progenitor Cells are crucial in the maintenance of lifelong production of all blood cells. These Stem Cells are highly regulated to maintain homeostasis through a delicate balance between quiescence, self-renewal and differentiation. However, this balance is altered during the hematopoietic recovery after Hematopoietic Stem and Progenitor Cell Transplantation. Transplantation efficacy can be limited by inadequate Hematopoietic Stem Cells number, poor homing, low level of engraftment, or limited self-renewal. As recent evidences indicate that estrogens are involved in regulating the hematopoiesis, we sought to examine whether natural estrogens (estrone or E1, estradiol or E2, estriol or E3 and estetrol or E4) modulate human Hematopoietic Stem and Progenitor Cells. Our results show that human Hematopoietic Stem and Progenitor Cell subsets express estrogen receptors, and whose signaling is activated by E2 and E4 on these cells. Additionally, these natural estrogens cause different effects on human Progenitors in vitro. We found that both E2 and E4 expand human Hematopoietic Stem and Progenitor Cells. However, E4 was the best tolerated estrogen and promoted cell cycle of human Hematopoietic Progenitors. Furthermore, we identified that E2 and, more significantly, E4 doubled human hematopoietic engraftment in immunodeficient mice without altering other Hematopoietic Stem and Progenitor Cells properties. Finally, the impact of E4 on promoting human hematopoietic engraftment in immunodeficient mice might be mediated through the regulation of mesenchymal stromal cells in the bone marrow niche. Together, our data demonstrate that E4 is well tolerated and enhances human reconstitution in immunodeficient mice, directly by modulating human Hematopoietic Progenitor properties and indirectly by interacting with the bone marrow niche. This application might have particular relevance to ameliorate the hematopoietic recovery 3 after myeloablative conditioning, especially when limiting numbers of Hematopoietic Stem and Progenitor Cells are available

The current status of mesenchymal stromal cells: controversies, unresolved issues and some promising solutions to improve their therapeutic efficacy

Mesenchymal stromal cells (MSCs) currently constitute the most frequently used cell type in advanced therapies with different purposes, most of which are related with inflammatory processes. Although the therapeutic efficacy of these cells has been clearly demonstrated in different disease animal models and in numerous human phase I/II clinical trials, only very few phase III trials using MSCs have demonstrated the expected potential therapeutic benefit. On the other hand, diverse controversial issues on the biology and clinical applications of MSCs, including their specific phenotype, the requirement of an inflammatory environment to induce immunosuppression, the relevance of the cell dose and their administration schedule, the cell delivery route (intravascular/systemic vs. local cell delivery), and the selected cell product (i.e., use of autologous vs. allogeneic MSCs, freshly cultured vs. frozen and thawed MSCs, MSCs vs. MSC-derived extracellular vesicles, etc.) persist. In the current review article, we have addressed these issues with special emphasis in the new approaches to improve the properties and functional capabilities of MSCs after distinct cell bioengineering strategies

Microvertebrates preserved in mammal burrows from the Holocene of the Argentine Pampas: a taphonomic and paleoecological approach

Microvertebrates are a major component of many assemblages recovered from the Quaternary of the Argentine Pampas. The main goal of this paper is to analyse the taphonomic history of a Holocene microfossil bonebed, recovered from the infilling of a burrow. Evidences suggest the plains vizcacha Lagostomus maximus as the putative producer of the burrow. The assemblage includes individuals belonging to different taxa of mammals (marsupials and rodents) and reptiles (snakes). Taphonomic features suggest that the accumulation inside the burrow was related to flooding processes in the plain. The burrow was a natural trap that favoured the accumulation and preservation of remains corresponding to individuals from different sources. According to the taphonomic evidence, some individuals (Lagostomus maximus, Lestodelphys halli and Serpentes indet.) died inside the burrow, whereas others (Microcavia australis, Reithrodon auritus and Ctenomys sp.) died outside the burrow, and after a time of being exposed on the surface their remains were transported by surface run-offs into the burrow. The record of Lestodelphys halli and Serpentes indet. in the burrow produced by Lagostomus maximus could be related to a circumstantial use. Mammal burrows are a significant taphonomic mode for the late Cenozoic of the Argentine Pampas

Atlas de las praderas marinas de España

Knowledge of the distribution and extent of seagrass habitats is currently the basis of management and conservation policies of the coastal zones in most European countries. This basic information is being requested through European directives for the establishment of monitoring programmes and the implementation of specific actions to preserve the marine environment. In addition, this information is crucial for the quantification of the ecological importance usually attributed to seagrass habitats due to, for instance, their involvement in biogeochemical cycles, marine biodiversity and quality of coastal waters or global carbon budgets. The seagrass atlas of Spain represents a huge collective effort performed by 84 authors across 30 Spanish institutions largely involved in the scientific research, management and conservation of seagrass habitats during the last three decades. They have contributed to the availability of the most precise and realistic seagrass maps for each region of the Spanish coast which have been integrated in a GIS to obtain the distribution and area of each seagrass species. Most of this information has independently originated at a regional level by regional governments, universities and public research organisations, which explain the elevated heterogeneity in criteria, scales, methods and objectives of the available information. On this basis, seagrass habitats in Spain occupy a total surface of 1,541,63 km2, 89% of which is concentrated in the Mediterranean regions; the rest is present in sheltered estuarine areas of the Atlantic peninsular regions and in the open coastal waters of the Canary Islands, which represents 50% of the Atlantic meadows. Of this surface, 71.5% corresponds to Posidonia oceanica, 19.5% to Cymodocea nodosa, 3.1% to Zostera noltii (=Nanozostera noltii), 0.3% to Zostera marina and 1.2% to Halophila decipiens. Species distribution maps are presented (including Ruppia spp.), together with maps of the main impacts and pressures that has affected or threatened their conservation status, as well as the management tools established for their protection and conservation. Despite this considerable effort, and the fact that Spain has mapped wide shelf areas, the information available is still incomplete and with weak precision in many regions, which will require an investment of major effort in the near future to complete the whole picture and respond to demands of EU directives

4to. Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad. Memoria académica

Este volumen acoge la memoria académica de la Cuarta edición del Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad, CITIS 2017, desarrollado entre el 29 de noviembre y el 1 de diciembre de 2017 y organizado por la Universidad Politécnica Salesiana (UPS) en su sede de Guayaquil. El Congreso ofreció un espacio para la presentación, difusión e intercambio de importantes investigaciones nacionales e internacionales ante la comunidad universitaria que se dio cita en el encuentro. El uso de herramientas tecnológicas para la gestión de los trabajos de investigación como la plataforma Open Conference Systems y la web de presentación del Congreso http://citis.blog.ups.edu.ec/, hicieron de CITIS 2017 un verdadero referente entre los congresos que se desarrollaron en el país. La preocupación de nuestra Universidad, de presentar espacios que ayuden a generar nuevos y mejores cambios en la dimensión humana y social de nuestro entorno, hace que se persiga en cada edición del evento la presentación de trabajos con calidad creciente en cuanto a su producción científica. Quienes estuvimos al frente de la organización, dejamos plasmado en estas memorias académicas el intenso y prolífico trabajo de los días de realización del Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad al alcance de todos y todas

Dopamine mobilizes mesenchymal progenitor cells through D2-class receptors and their PI3K/AKT pathway.

As the nervous system exerts direct and indirect effects on stem cells mobilization and catecholamines mobilize hematopoietic stem cells, we hypothesized that dopamine might induce mesenchymal progenitor cells (MPCs) mobilization. We show that dopamine induced in vitro MPCs migration through D2-class receptors, and their alternative phosphoinositide 3-kinase/Akt pathways. Also, administration of catecholamines induced in vivo mobilization of colony-forming unit-fibroblast in mice. In contrast, in vitro and in vivo MPCs migration was suppressed by D2-class receptors antagonists and blocking antibodies, consistent with dopamine signaling pathway implication. In humans, patients treated with L-dopa or catecholaminergic agonists showed a significant increase of a MPC-like population (CD45-CD31-CD34-CD105+) in their peripheral blood. These findings reveal a new link between catecholamines and MPCs mobilization and suggest the potential use of D2-class receptors agonists for mobilization of MPCs in clinical settings.We thank Iván Gutierrez, Ander Abarrategi, Manuel Masip, Mar Arriero, and Daniel Pérez for his assistance in several techniques. This work was supported by grants from the Fondo de Investigaciones Sanitarias (FIS; PI05/2217 and PI08/0029), the Madrid Regional Government (S‐BIO‐0204–2006, MesenCAM; P2010/BMD‐2420, CellCAM) in Spain, and Consejería de Salud de la Junta de Andalucía (0027/2006) to J.G.‐C. The experiments were approved by the appropriate committees.S

Provenance of oligocene conglomerates and associated sandstones from the Siamaná Formation, Serranía de Jarara, Guajira, Colombia: implications for Oligocene Caribbean-South American Tectonics

Analyses of composition and sedimentological attributes of conglomerate clasts together with petrographical and heavy mineral analyses and detrital geochronology from sandstones of the Oligocene Siamaná Formation in the Serranía de Jarara, are presented in order to reconstruct de provenance of this sedimentary sequence and contribute to the knowledge of the tectonosedimentary evolution of the Guajira Peninsula and the Caribbean. The results indicate that the source areas are proximal and are located to the southeast. The presence of plutonic igneous and mediumto Lowgrade metamorphic rocks, as well as highpressure metamorphic rocks, indicate that the lithostratigraphic units (Parashi Stock and Jarara Formation) of the Serranía de Jarara and an unidentified unit to the southeast, are the main rock sources. The heavy minerals and the detrital zircon distribution with peaks at approximately 50 Ma, 207Ma, 245 Ma, 463 Ma, 963 Ma and 1044 Ma, confirm that this is the source area. The extremely proximate sources and the rapid burying of the basin, which is evident due to the presence of marine sediments that overlie this sequence, indicate that this siliciclastic unit is related to the initial phases of a pullapart basin. This basin was probably formed as a result of the movement of the Caribbean plate towards the east. The origin of the highpressure clasts is unknown, and is possibly linked to a tectonic mélange. The U-Pb ages of approximately 50 Ma and the presence of fragments from the Parashi Stock, suggest exhumation during the Eocene and Upper Oligocene, possibly linked to the formation of the basin

Geochemistry and Geochronology of the Guajira Eclogites, northern Colombia: evidence of a metamorphosed primitive Cretaceus Caribbean Island-arc

The chemical composition of eclogites, found as boulders in a Tertiary conglomerate from the Guajira Peninsula, Colombia suggests that these rocks are mainly metamorphosed basaltic andesites. They are depleted in LILE elements compared to MORB, have a negative Nb-anomaly and flat to enriched REE patterns, suggesting that their protoliths evolved in a subduction related tectonic setting. They show island-arc affinities and are similar to primitive islandarc rocks described in the Caribbean. The geochemical characteristics are comparable to low-grade greenschists from the nearby Etpana Terrane, which are interpreted as part of a Cretaceous intra-oceanic arc. These data support evidence that the eclogites and the Etpana terrane rocks formed from the same volcano-sedimentary sequence. Part of this sequence was accreted onto the margin and another was incorporated into the subduction channel and metamorphosed at eclogite facies conditions. 40Ar-39Ar ages of 79.2±1.1Ma and 82.2±2.5Ma determined on white micas, separated from two eclogite samples, are interpreted to be related to the cooling of the main metamorphic event. The formation of a common volcano-sedimentary protolith and subsequent metamorphism of these units record the ongoing Late Cretaceous continental subduction of the South American margin within the Caribbean intra-oceanic arc subduction zone. This gave way to an arc-continent collision between the Caribbean and the South American plates, where this sequence was exhumed after the Campanian