Integrins: A flexible platform for endothelial vascular tyrosine kinase receptors.

Compared to lower metazoans, vertebrates built up an exclusively new set of adhesion-related genes involved in the tissue development and in their functions. They include a large variety of extracellular matrix proteins and their heterodimeric integrin adhesive receptors. Integrins control the adhesive state of the cell through complex molecular mechanisms. Outside-in signalling informs the cell about the extracellular matrix environment, while Inside-out signalling results in changes in integrin functional activity. In the last 10 years it has well established a reciprocal integration of signals originating from integrins and receptors for soluble growth factors. This review summarizes the current understanding of this connection in vascular endothelial cells and highlights how integrins regulate a genetic program triggered by angiogenic inducers during embryo development and in adult life

Stable interaction between α5β1 integrin and Tie2 tyrosine kinase receptor regulates endothelial cell response to Ang-1

During angiogenic remodeling, Ang-1, the ligand of Tie2 tyrosine kinase, is involved in vessel sprouting and stabilization through unclear effects on nascent capillaries and mural cells. In our study, we hypothesized that the Ang-1/Tie2 system could crosstalk with integrins, and be influenced by the dynamic interactions between extracellular matrix and endothelial cells (ECs). Here, we show that α5β1 specifically sensitizes and modulates Tie2 receptor activation and signaling, allowing EC survival at low concentrations of Ang-1 and inducing persistent EC motility. Tie2 and α5β1 interact constitutively; α5β1 binding to fibronectin increases this association, whereas Ang-1 stimulation recruits p85 and FAK to this complex. Furthermore, we demonstrate that Ang-1 is able to mediate selectively α5β1 outside-in FAK phosphorylation. Thus, Ang-1 triggers signaling pathways through Tie2 and α5β1 receptors that could crosstalk when Tie2/α5β1 interaction occurs in ECs plated on fibronectin. By using blocking antibodies, we consistently found that α5β1, but not αvβ3 activation, is essential to Ang-1-dependent angiogenesis in vivo. © The Rockefeller University Press

lipid oxidation in buffalo meat from animals with dietary supplementation of vitamin e

Buffalo (Bubalus bubalis) meat is not widely used in the diet, but it is recently reconsidered due to its valuable nutritional qualities. New strategies aiming to improve the quality of buffalo meat have to be applied particularly to face the problem of lipid peroxidation, one of the most important causes of meat food deterioration. The aim of this study was to evaluate the lipid oxidation of buffalo meat (muscles Caput longum tricipitis brachii, Longissimus dorsi and Semimembranosus), coming from animals fed with two different amount of vitamin E (600 IU/die and 1500 IU/die for 102 -123 days) considering, as markers for lipid oxidation, the concentration of malondialdehyde (MDA) by HPLC-UV and TBA test. Moreover it was evaluated, by HPLC-DAD, vitamin E concentration in the meat samples. Muscles coming from animals with vitamin E supplementation were in mean 2 times more enriched of vitamin E than control (p < 0.05). Meat from buffalo fed with 600 IU/die vitamin E had significant lower MDA concentration in comparison with control (in mean -53%, n= 4). Both for MDA and vitamin E concentrations not significant differences were found between the supplementation of 600 IU/die and 1500 IU/die. It is concluded that dietary supplementation with Vitamin E is a promising strategy to prevent lipid oxidation of buffalo meat and to prolong its shelf-life

Recursos didácticos para el aprendizaje complejo de la geometría analítica

En la asignatura geometría analítica en Facultad de Ingeniería de la Universidad Nacional de Cuyo, se implementa un modelo pedagógico enmarcado dentro de la metodología de Investigación - Acción, que promueve el desarrollo de habilidades asociadas al pensamiento complejo y capacidades que aportan a competencias profesionales. El trabajo en el espacio tridimensional exige el manejo apropiado y simultáneo de aspectos gráficos y analíticos que implican grandes dificultades para los alumnos ingresantes. Se plantea así el desafío de abrir nuevas puertas al aprendizaje, que lo potencien y enriquezcan a partir de intervenciones educativas con el uso de materiales didácticos especialmente diseñados para tal fin. Se presentan en este trabajo recursos para el aprendizaje complejo de contenidos de la geometría analítica espacial, que se integran en los diferentes escenarios de interacción e interaprendizaje del mencionado modelo pedagógico. Dichos recursos se clasifican en cinco grupos en función de las intencionalidades educativas priorizadas para su utilización: recursos para el desarrollo de contenidos, para la exploración y la experimentación, para la articulación con otros espacios curriculares, para la integración de contenidos y para promover la autonomía en el aprendizaje. A partir de una apropiada selección de actividades para su empleo, se busca potenciar la comprensión profunda de conceptos y la resolución de problemas en el espacio tridimensional que involucran a los lugares geométricos en estudio.Fil: Raichman, Silvia Raquel. Universidad Nacional de Cuyo. Facultad de Ingeniería.Fil: Totter, Eduardo. Universidad Nacional de Cuyo. Facultad de Ingeniería.Fil: Videla, D.. Universidad Nacional de Cuyo. Facultad de Ingeniería.Fil: Collado, L.. Universidad Nacional de Cuyo. Facultad de Ingeniería.Fil: Codina, F.. Universidad Nacional de Cuyo. Facultad de Ingeniería.Fil: Molina, G.. Universidad Nacional de Cuyo. Facultad de Ingeniería.Fil: Cascone, I.. Universidad Nacional de Cuyo. Facultad de Ingeniería

Trichoderma atroviride P1 Colonization of Tomato Plants Enhances Both Direct and Indirect Defense Barriers Against Insects

Numerous microbial root symbionts are known to induce different levels of enhanced plant protection against a variety of pathogens. However, more recent studies have demonstrated that beneficial microbes are able to induce plant systemic resistance that confers some degree of protection against insects. Here, we report how treatments with the fungal biocontrol agent Trichoderma atroviride strain P1 in tomato plants induce responses that affect pest insects with different feeding habits: the noctuid moth Spodoptera littoralis (Boisduval) and the aphid Macrosiphum euphorbiae (Thomas). We observed that the tomato plant–Trichoderma P1 interaction had a negative impact on the development of moth larvae and on aphid longevity. These effects were attributed to a plant response induced by Trichoderma that was associated with transcriptional changes of a wide array of defense-related genes. While the impact on aphids could be related to the up-regulation of genes involved in the oxidative burst reaction, which occur early in the defense reaction, the negative performance of moth larvae was associated with the enhanced expression of genes encoding for protective enzymes (i.e., Proteinase inhibitor I (PI), Threonine deaminase, Leucine aminopeptidase A1, Arginase 2, and Polyphenol oxidase) that are activated downstream in the defense cascade. In addition, Trichoderma P1 produced alterations in plant metabolic pathways leading to the production and release of volatile organic compounds (VOCs) that are involved in the attraction of the aphid parasitoid Aphidius ervi, thus reinforcing the indirect plant defense barriers. Our findings, along with the evidence available in the literature, indicate that the outcome of the tripartite interaction among plant, Trichoderma, and pests is highly specific and only a comprehensive approach, integrating both insect phenotypic changes and plant transcriptomic alterations, can allow a reliable prediction of its potential for plant protectio

Characterizing HR3549B using SPHERE

Aims. In this work, we characterize the low mass companion of the A0 field star HR3549. Methods. We observed HR3549AB in imaging mode with the the NIR branch (IFS and IRDIS) of SPHERE@VLT, with IFS in YJ mode and IRDIS in the H band. We also acquired a medium resolution spectrum with the IRDIS long slit spectroscopy mode. The data were reduced using the dedicated SPHERE GTO pipeline, purposely designed for this instrument. We employed algorithms such as PCA and TLOCI to reduce the speckle noise. Results. The companion was clearly visible both with IRDIS and IFS.We obtained photometry in four different bands as well as the astrometric position for the companion. Based on our astrometry, we confirm that it is a bound object and put constraints on its orbit. Although several uncertainties are still present, we estimate an age of ~100-150 Myr for this system, yielding a most probable mass for the companion of 40-50MJup and T_eff ~300-2400 K. Comparing with template spectra points to a spectral type between M9 and L0 for the companion, commensurate with its position on the color-magnitude diagram.Comment: Accepted by A&A, 13 pages, 10 Figures (Figures 9 and 10 degraded to reduce the dimension

Mitochondrial clearance by the STK38 kinase supports oncogenic Ras-induced cell transformation.

Oncogenic Ras signalling occurs frequently in many human cancers. However, no effective targeted therapies are currently available to treat patients suffering from Ras-driven tumours. Therefore, it is imperative to identify downstream effectors of Ras signalling that potentially represent promising new therapeutic options. Particularly, considering that autophagy inhibition can impair the survival of Ras-transformed cells in tissue culture and mouse models, an understanding of factors regulating the balance between autophagy and apoptosis in Ras-transformed human cells is needed. Here, we report critical roles of the STK38 protein kinase in oncogenic Ras transformation. STK38 knockdown impaired anoikis resistance, anchorage-independent soft agar growth, and in vivo xenograft growth of Ras-transformed human cells. Mechanistically, STK38 supports Ras-driven transformation through promoting detachment-induced autophagy. Even more importantly, upon cell detachment STK38 is required to sustain the removal of damaged mitochondria by mitophagy, a selective autophagic process, to prevent excessive mitochondrial reactive oxygen species production that can negatively affect cancer cell survival. Significantly, knockdown of PINK1 or Parkin, two positive regulators of mitophagy, also impaired anoikis resistance and anchorage-independent growth of Ras-transformed human cells, while knockdown of USP30, a negative regulator of PINK1/Parkin-mediated mitophagy, restored anchorage-independent growth of STK38-depleted Ras-transformed human cells. Therefore, our findings collectively reveal novel molecular players that determine whether Ras-transformed human cells die or survive upon cell detachment, which potentially could be exploited for the development of novel strategies to target Ras-transformed cells

N6L pseudopeptide interferes with nucleophosmin protein-protein interactions and sensitizes leukemic cells to chemotherapy.

Abstract NPM1 is a multifunctional nucleolar protein implicated in several processes such as ribosome maturation and export, DNA damage response and apoptotic response to stress stimuli. The NPM1 gene is involved in human tumorigenesis and is found mutated in one third of acute myeloid leukemia patients, leading to the aberrant cytoplasmic localization of NPM1. Recent studies indicated that the N6L multivalent pseudopeptide, a synthetic ligand of cell–surface nucleolin, is also able to bind NPM1 with high affinity. N6L inhibits cell growth with different mechanisms and represents a good candidate as a novel anticancer drug for a number of malignancies of different histological origin. In this study we investigated whether N6L treatment could drive antitumor effect in acute myeloid leukemia cell lines. We found that N6L binds NPM1 at the N-terminal domain, co-localizes with cytoplasmic, mutated NPM1, and interferes with its protein-protein associations. N6L toxicity appears to be p53 dependent but interestingly, the leukemic cell line harbouring the mutated form of NPM1 is more resistant to treatment, suggesting that NPM1 cytoplasmic delocalization confers protection from p53 activation. Moreover, we show that N6L sensitizes AML cells to doxorubicin and cytarabine treatment. These studies suggest that N6L may be a promising option in combination therapies for acute myeloid leukemia treatment