Influencia de IBA y SEFEL en el enraizamiento de esquejes terminales y subterminales de Leucospermum `"Ayoba Peach".

Las Proteaceas son plantas originarias de África del Sur y Australia siendo de gran interés ornamental como flor cortada y follaje compuestas por unos 80 géneros y más de 1700 especies. En Canarias estos cultivos se han extendido, sobre todo en La Palma, Tenerife y Gran Canaria, la floración de estas variedades es en épocas invernales lo que es importante para revalorizar la comercialización de este cultivo y por lo tanto la actividad agrícola de las islas. En concreto, la isla de La Palma, posee una mayor superficie de cultivo y unas condiciones de clima, humedad y características de los suelos que son adecuadas para desarrollar cultivares de Leucospermum como `Tango´, `Succession II´ entre otros y `Ayoba Peach´ objeto de este estudio. La creación de una cooperativa entre los propios agricultores (Sociedad Cooperativa de Próteas de La Palma) y la colaboración conjunta con la Universidad de La Laguna, ha hecho posible la realización de este ensayo. Debido al uso que se está haciendo en los últimos años de la aplicación de diferentes tipos de enraizantes químicos y orgánicos como IBA y SEFEL (Sistema de Elaboración de Fertilizantes Ecológicos Líquidos), se decidió realizar este ensayo para estudiar la influencia de los mismos, así como, comparar cuál de ellos muestra un mayor potencial de enraizamiento bajo las mismas condiciones y el mismo medio de enraizamiento. En este ensayo se emplearon estacas apicales y subapicales con lesionado o sin él. Los datos obtenidos se sometieron a un estudio estadístico sobre el porcentaje de estacas con raíces trasplantables y el índice de enraizamiento, determinando cuál de los tratamientos ofrecía mejor comportamiento. El enraizante que proporcionó mejores resultados respecto al porcentaje de estacas con raíz trasplantable fue el tratamiento con SEFEL + 4000 ppm de IBA lesionado tanto en esquejes apicales como en subapicales.Proteaceas are a family of Angiosperms in the order Proteales. It consists of 80 genera and some 1,700 species native to South Africa and Australia. Among the most prominent genera we can mention: Leucospermum, Leucadendron and Protea. This crop came to our islands through the Botanical Garden of La Orotava in the seventies through a program of introduction of Australian and African plants, but it was not until 1982 when field plantations were carried out in some mid-range areas of the island of Tenerife. Its interest is ornamental, the most important characteristic being the floral stem, blooming in autumn-winter when other flowers are scarce. Another aspect to highlight is the long duration of the flower, which makes it very suitable for export (Rodríguez Pérez, 2007). The main producing areas of economic importance are located in the southern hemisphere: South Africa, Australia, New Zealand, Zimbabwe; As for the northern hemisphere, they are located in Israel, California, Hawaii, Portugal and Spain, particularly in the Canary Islands. This crop began in the Canary Islands in the 80s, with Tenerife and La Palma being the islands with the most cultivated area. On the island of La Palma it has been growing with greater boom due to the fact that farmers have joined with cooperatives, which has allowed it to promote its commercialization abroad and also because of the promotion by the Island Council, providing technical advice. The cultivation of these for cut flower or for cut green (as floral complement plants) are an interesting alternative. For this reason, there are already more than 50 hectares in the Canary Islands, with Proteacea crops on the islands of Tenerife, La Palma and Gran Canaria. Consequently, with the increase in cultivation areas, a better knowledge of the crop, in all its aspects, including propagation, is necessary. The rooting of cuttings is highly influenced by the environmental conditions in which it is carried out, such as high relative humidity, an adequate temperature of the substrate and air, aeration and availability of water in the substrate, air renewal and correct lighting, it is necessary control them as a mismatch could lead to total failure (Loach, 1988). In addition to optimizing environmental conditions, the percentage of rooting of cuttings can be increased by making use of a number of additional techniques both physical and chemical. In different studies it is concluded that Leucospermum responds very well to propagation through terminal cuttings treated with 4000 ppm of IBA, in a rooting substrate composed of peat-polystyrene in the ratio 4: 6 (v / v). However, due to the use that is being made lately with other growth regulators and with substances of proven efficacy on the rooting of some woody species, in addition to 4000 ppm of IBA was used, SEFEL (System for the Preparation of Liquid Ecological Fertilizers) ( Acosta, 2013). That is why the new exclusive variety of this project, Leucospermum “Ayoba peah”, whose parents are L. lineare x L. cordifollium x L glabrum, was the object of study, since there are no works yet that can demonstrate its capacity rooting in apical and subapical cuttings. Currently, the use of organically grown products is also more demanding in the floriculture sector. For this reason, this study has experimented with the use of biofertilizers prepared according to the SEFEL methodology. Based on a previous work on the application of IBA and SEFEL as rooting stimulants in the propagation of cuttings of the Proteas genus (Soriano Martín, B 2017.) it is concluded to carry out this study to compare how these rooting stimulants influence, in the cultivar of Leucospermum `Ayoba Peach´

Nestinþ cells direct inflammatory cell migration in atherosclerosis

Atherosclerosis is a leading death cause. Endothelial and smooth muscle cells participate in atherogenesis, but it is unclear whether other mesenchymal cells contribute to this process. Bone marrow (BM) nestinþ cells cooperate with endothelial cells in directing monocyte egress to bloodstream in response to infections. However, it remains unknown whether nestinþ cells regulate inflammatory cells in chronic inflammatory diseases, such as atherosclerosis. Here, we show that nestinþ cells direct inflammatory cell migration during chronic inflammation. In Apolipoprotein E (ApoE) knockout mice fed with high-fat diet, BM nestinþ cells regulate the egress of inflammatory monocytes and neutrophils. In the aorta, nestinþ stromal cells increase B30 times and contribute to the atheroma plaque. Mcp1 deletion in nestinþ cells—but not in endothelial cells only— increases circulating inflammatory cells, but decreases their aortic infiltration, delaying atheroma plaque formation and aortic valve calcification. Therefore, nestin expression marks cells that regulate inflammatory cell migration during atherosclerosis.Pro-CNIC FoundationSevero Ochoa Center of Excellence award SEV-2015-0505 to CNICWellcome Trust and MRC to the Cambridge Stem Cell InstituteMinisterio de Economía y Competitividad (RETIC Grant RD12/0042/0028 to V.A.; SAF2012-40127 to J.M-G.; Plan Nacional Grant SAF-2011-30308, Ramón y Cajal Program Grant RYC-2009-04703 and Spanish Cell Therapy Network TerCel to S.M-F.)Marie Curie Career Integration Program Grant (FP7-PEOPLE-2011-294096)ConSEPOC-Comunidad de Madrid Grant (S2010/BMD-2542)National Health Institute Blood and Transplant (United Kingdom)Horizon2020 (ERC-2014-CoG-64765)Horizon2020 (ERC-2014-CoG-64765

Regulation of oxygen sensing by ion channels

O2 sensing is of critical importance for cell survival and adaptation of living organisms to changing environments or physiological conditions. O2-sensitive ion channels are major effectors of the cellular responses to hypoxia. These channels are preferentially found in excitable neurosecretory cells (glomus cells of the carotid body, cells in the neuroepithelial bodies of the lung, and neonatal adrenal chromaffin cells), which mediate fast cardiorespiratory adjustments to hypoxia. O2- sensitive channels are also expressed in the pulmonary and systemic arterial smooth muscle cells where they participate in the vasomotor responses to low O2 tension (particularly in hypoxic pulmonary vasoconstriction). The mechanisms underlying O2 sensing and how the O2 sensors interact with the ion channels remain unknown. Recent advances in the field give different support to the various current hypotheses. Besides the participation of ion channels in acute O2 sensing, they also contribute to the gene program developed under chronic hypoxia. Gene expression of T-type calcium channels is upregulated by hypoxia through the same hypoxiainducible factor-dependent signaling pathway utilized by the classical O2-regulated genes. Alteration of acute or chronic O2 sensing by ion channels could participate in the pathophysiology of human diseases, such as sudden infant death syndrome or primary pulmonary hypertension

ALK1 Signaling Inhibits Angiogenesis by Cooperating with the Notch Pathway

SummaryActivin receptor-like kinase 1 (ALK1) is an endothelial-specific member of the TGF-β/BMP receptor family that is inactivated in patients with hereditary hemorrhagic telangiectasia (HHT). How ALK1 signaling regulates angiogenesis remains incompletely understood. Here we show that ALK1 inhibits angiogenesis by cooperating with the Notch pathway. Blocking Alk1 signaling during postnatal development in mice leads to retinal hypervascularization and the appearance of arteriovenous malformations (AVMs). Combined blockade of Alk1 and Notch signaling further exacerbates hypervascularization, whereas activation of Alk1 by its high-affinity ligand BMP9 rescues hypersprouting induced by Notch inhibition. Mechanistically, ALK1-dependent SMAD signaling synergizes with activated Notch in stalk cells to induce expression of the Notch targets HEY1 and HEY2, thereby repressing VEGF signaling, tip cell formation, and endothelial sprouting. Taken together, these results uncover a direct link between ALK1 and Notch signaling during vascular morphogenesis that may be relevant to the pathogenesis of HHT vascular lesions

Circulating miR-320a as a Predictive Biomarker for Left Ventricular Remodelling in STEMI Patients Undergoing Primary Percutaneous Coronary Intervention

Restoration of epicardial coronary blood flow, achieved by early reperfusion with primary percutaneous coronary intervention (PPCI), is the guideline recommended to treat patients with ST-segment-elevation myocardial infarction (STEMI). However, despite successful blood restoration, increasing numbers of patients develop left ventricular adverse remodelling (LVAR) and heart failure. Therefore, reliable prognostic biomarkers for LVAR in STEMI are urgently needed. Our aim was to investigate the role of circulating microRNAs (miRNAs) and their association with LVAR in STEMI patients following the PPCI procedure. We analysed the expression of circulating miRNAs in blood samples of 56 patients collected at admission and after revascularization (at 3, 6, 12 and 24 h). The associations between miRNAs and left ventricular end diastolic volumes at 6 months were estimated to detect LVAR. miRNAs were also analysed in samples isolated from peripheral blood mononuclear cells (PBMCs) and human myocardium of failing hearts. Kinetic analysis of miRNAs showed a fast time-dependent increase in miR-133a, miR-133b, miR-193b, miR-499, and miR-320a in STEMI patients compared to controls. Moreover, the expression of miR-29a, miR-29b, miR-324, miR-208, miR-423, miR-522, and miR-545 was differentially expressed even before PPCI in STEMI. Furthermore, the increase in circulating miR-320a and the decrease in its expression in PBMCs were significantly associated with LVAR and correlated with the expression of miR-320a in human failing myocardium from ischaemic origin. In conclusion, we determined the time course expression of new circulating miRNAs in patients with STEMI treated with PPCI and we showed that miR-320a was positively associated with LVAR

TRP Channels: Current Perspectives in the Adverse Cardiac Remodeling

Calcium is an important second messenger required not only for the excitation-contraction coupling of the heart but also critical for the activation of cell signaling pathways involved in the adverse cardiac remodeling and consequently for the heart failure. Sustained neurohumoral activation, pressure-overload, or myocardial injury can cause pathologic hypertrophic growth of the heart followed by interstitial fibrosis. The consequent heart’s structural and molecular adaptation might elevate the risk of developing heart failure and malignant arrhythmia. Compelling evidences have demonstrated that Ca2+ entry through TRP channels might play pivotal roles in cardiac function and pathology. TRP proteins are classified into six subfamilies: TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPA (ankyrin), TRPML (mucolipin), and TRPP (polycystin), which are activated by numerous physical and/or chemical stimuli. TRP channels participate to the handling of the intracellular Ca2+ concentration in cardiac myocytes and are mediators of different cardiovascular alterations. This review provides an overview of the current knowledge of TRP proteins implication in the pathologic process of some frequent cardiac diseases associated with the adverse cardiac remodeling such as cardiac hypertrophy, fibrosis, and conduction alteration

Role of VHL, HIF1A and SDH on the expression of miR-210: Implications for tumoral pseudo-hypoxic fate

The hypoxia-inducible factor 1a (HIF-1a) and its microRNA target, miR-210, are candidate tumor-drivers of metabolic reprogramming in cancer. Neuroendocrine neoplasms such as paragangliomas (PGLs) are particularly appealing for understanding the cancer metabolic adjustments because of their associations with deregulations of metabolic enzymes, such as succinate dehydrogenase (SDH), and the von Hippel Lindau (VHL) gene involved in HIF-1α stabilization. However, the role of miR-210 in the pathogenesis of SDH-related tumors remains an unmet challenge. Herein is described an in vivo genetic analysis of the role of VHL, HIF1A and SDH on miR-210 by using knockout murine models, siRNA gene silencing, and analyses of human tumors. HIF-1a knockout abolished hypoxia-induced miR-210 expression in vivo but did not alter its constitutive expression in paraganglia. Normoxic miR-210 levels substantially increased by complete, but not partial, VHL silencing in paraganglia of knockout VHL-mice and by over-expression of p76del-mutated pVHL. Similarly, VHLmutated PGLs, not those with decreased VHL-gene/mRNA dosage, over-expressed miR-210 and accumulate HIF-1a in most tumor cells. Ablation of SDH activity in SDHD-null cell lines or reduction of the SDHD or SDHB protein levels elicited by siRNA-induced gene silencing did not induce miR-210 whereas the presence of SDH mutations in PGLs and tumor-derived cell lines was associated with mild increase of miR-210 and the presence of a heterogeneous, HIF-1a-positive and HIF-1a-negative, tumor cell population. Thus, activation of HIF-1a is likely an early event in VHLdefective PGLs directly linked to VHL mutations, but it is a late event favored but not directly triggered by SDHx mutations. This combined analysis provides insights into the mechanisms of HIF-1a/miR-210 regulation in normal and tumor tissues potentially useful for understanding the pathogenesis of cancer and other diseases sharing similar underpinnings.Instituto de Salud Carlos III FIS PI11/929Red Temática de Investigación Cooperativa en Cáncer RD12/0036/0015 Instituto de Salud Carlos III (ISCIII)Ministerio de Economía y Competitividad y Fondo Europeo de Desarrollo RegionalFondo Europeo de Desarrollo Regional (FEDER) (CIBERONC

TRP Channels: Current Perspectives in the Adverse Cardiac Remodeling

Calcium is an important second messenger required not only for the excitation-contraction coupling of the heart but also critical for the activation of cell signaling pathways involved in the adverse cardiac remodeling and consequently for the heart failure. Sustained neurohumoral activation, pressure-overload, or myocardial injury can cause pathologic hypertrophic growth of the heart followed by interstitial fibrosis. The consequent heart’s structural and molecular adaptation might elevate the risk of developing heart failure and malignant arrhythmia. Compelling evidences have demonstrated that Ca2+ entry through TRP channels might play pivotal roles in cardiac function and pathology. TRP proteins are classified into six subfamilies: TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPA (ankyrin), TRPML (mucolipin), and TRPP (polycystin), which are activated by numerous physical and/or chemical stimuli. TRP channels participate to the handling of the intracellular Ca2+ concentration in cardiac myocytes and are mediators of different cardiovascular alterations. This review provides an overview of the current knowledge of TRP proteins implication in the pathologic process of some frequent cardiac diseases associated with the adverse cardiac remodeling such as cardiac hypertrophy, fibrosis, and conduction alteration.Spanish Ministry of Economy and Competitiveness BFU2016–74932-C2Institute of Carlos III PI15/00203; PI16/00259; CB16/11/00431Andalusia Government PI-0313-201

Nestin(+) cells direct inflammatory cell migration in atherosclerosis.

Atherosclerosis is a leading death cause. Endothelial and smooth muscle cells participate in atherogenesis, but it is unclear whether other mesenchymal cells contribute to this process. Bone marrow (BM) nestin(+) cells cooperate with endothelial cells in directing monocyte egress to bloodstream in response to infections. However, it remains unknown whether nestin(+) cells regulate inflammatory cells in chronic inflammatory diseases, such as atherosclerosis. Here, we show that nestin(+) cells direct inflammatory cell migration during chronic inflammation. In Apolipoprotein E (ApoE) knockout mice fed with high-fat diet, BM nestin(+) cells regulate the egress of inflammatory monocytes and neutrophils. In the aorta, nestin(+) stromal cells increase ∼30 times and contribute to the atheroma plaque. Mcp1 deletion in nestin(+) cells-but not in endothelial cells only- increases circulating inflammatory cells, but decreases their aortic infiltration, delaying atheroma plaque formation and aortic valve calcification. Therefore, nestin expression marks cells that regulate inflammatory cell migration during atherosclerosis.This work was supported by core support grants from the Pro-CNIC Foundation, Severo Ochoa Center of Excellence award SEV-2015-0505 to CNIC, and the Wellcome Trust and MRC to the Cambridge Stem Cell Institute, Spanish Ministry of Economy and Competitiveness (RETIC grant RD12/0042/0028 to VA; SAF2012-40127 to JM-G; Plan Nacional grant SAF-2011-30308, Ramón y Cajal Program grant RYC-2009-04703 and Spanish Cell Therapy Network TerCel to SM-F); Marie Curie Career Integration Program grant (FP7-PEOPLE-2011-294096) and ConSEPOC-Comunidad de Madrid grant (S2010/BMD-2542), National Health Institute Blood and Transplant (United Kingdom), Horizon2020 (ERC-2014-CoG-64765) and an International Early Career Scientist grant of the Howard Hughes Medical Institute to SM-F.This is the author accepted manuscript. The final version is available from Nature Publishing Group at https://dx.doi.org/10.1038/ncomms1270

Natural history of patients with venous thromboembolism and hereditary hemorrhagic telangiectasia. Findings from the RIETE registry

Background: Limited data exist about the clinical presentation, ideal therapy and outcomes of patients with hereditary hemorrhagic telangiectasia (HHT) who develop venous thromboembolism (VTE). Methods: We used the data in the RIETE Registry to assess the clinical characteristics, therapeutic approaches and clinical outcomes during the course of anticoagulant therapy in patients with HHT according to initial presentation as pulmonary embolism (PE) or deep venous thrombosis (DVT). Results: Of 51,375 patients with acute VTE enrolled in RIETE from February 2009 to January 2019, 23 (0.04%) had HHT: 14 (61%) initially presented with PE and 9 (39%) with DVT alone. Almost half (47.8%) of the patients with VTE had a risk factor for VTE. Most PE and DVT patients received low-molecular-weight heparin for initial (71 and 100%, respectively) and long-term therapy (54 and 67%, respectively). During anticoagulation for VTE, the rate of bleeding events (major 2, non-major 6) far outweighed the rate of VTE recurrences (recurrent DVT 1): 50.1 bleeds per 100 patient-years (95%CI: 21.6-98.7) vs. 6.26 recurrences (95%CI: 0.31-30.9; p = 0.020). One major and three non-major bleeding were epistaxis. No patient died of bleeding. One patient died shortly after being diagnosed with acute PE. Conclusions: During anticoagulation for VTE in HHT patients, there were more bleeding events than VTE recurrences. Most bleeding episodes were non-major epistaxis