GENYOi004-A: An induced pluripotent stem cells (iPSCs) line generated from a patient with autism-related ADNP syndrome carrying a pTyr719* mutation

ADNP syndrome is an intellectual disability associated with Autism spectrum disorder caused by mutations in ADNP. We generated an iPSC line from an ADNP syndrome pediatric patient harboring the mutation p.Trp719* (GENYOi004-A). Peripheral blood mononuclear cells were reprogrammed using a non-transmissible form of Sendai viruses expressing the four Yamanaka factors (Oct3/4, SOX2, KLF4 and c-MYC). Characterization of GENYOi004-A included mutation analysis of ADNP by allele-specific PCR, genetic identity by Short Tandem Repeats polymorphism profiling, alkaline phosphatase enzymatic activity, expression of pluripotency-associated factors and pluripotency studies in vivo. GENYOi004-A will be useful to evaluate ADNP syndrome alterations at early developmental stages.This work was supported by the Postdoctoral Subprogramme Juan de la Cierva (JCI_2012_12666) to RM and Ramon y Cajal (RYC-2015-18382) to PJR founded by the Ministry of Economy and Competitiveness; the Instituto de Salud Carlos III-FEDER (CP12/03175 and CPII17/00032) to V.R-M. and (PI12/1598, CPII15/00018 and PI16/01340) to PJR; the Instituto de Investigación Valdecilla (IDIVAL) 2014.041 to JLF-L and DG-L and APG/03 to JLF-L

Variabilidade genética de cilevirus de importância agronômica: polimorfismo do extremo 51 do RNA2 de passion fruit Green Spot Virus.

RESUMO ? O Brasil é o maior produtor mundial de maracujá (Passiflora spp.). A cultura é atingida pelo definhamento precoce e a pinta verde do maracujazeiro, duas doenças relatadas pela primeira vez no Brasil na década de 90 e que são causadas pelo cilevirus passion fruit green spot virus (PfGSV, genoma dividido em duas moléculas de fita simples de RNA (+)]). A infecção pelo PfGSV produz necrose intensa nos ramos, manchas cloróticas nas folhas, e lesões anelares verdes nos frutos. A caracterização de cinco isolados do PfGSV evidenciou um acentuado polimorfismo na região 5? do RNA2 deste vírus quando comparado a outros membros do gênero Cilevirus. A principal divergência é a presença de um marco de leitura aberto órfão (do inglês, ?orphan ORF?) que poderia ter influência na fisiopatologia das doenças causadas. Este trabalho visa aprofundar no grau de polimorfismo do extremo 5? do RNA2 de PfGSV através das análises de 20 isolados de PfGSV e amplificação por RT-PCR com iniciadores específicos. Após a amplificação do extremo 5? do RNA2 os fragmentos estão sendo sequenciados pelo método de Sanger. O genoma total de um dos isolados, detectado em plantas de orquídeas, está sendo obtido pela técnica de sequenciamento massivo de alta performance. As sequencias obtidas serão analisadas por pacotes de bioinformática visando revelar a prevalência dos ?orphan ORF? e a possível correlação entre eles e a sintomatologia das doenças causadasN. 21818

Making a better home: modulation of plant defensive response by brevipalpus mites.

False-spider mites of the genus Brevipalpus are highly polyphagous pests that attack hundreds of plant species of distinct families worldwide. Besides causing direct damage, these mites may also act as vectors of many plant viruses that threaten high-value ornamental plants like orchids and economically important crops such as citrus and coffee. To better understand the molecular mechanisms behind plant-mite interaction we used an RNA-Seq approach to assess the global response of Arabidopsis thaliana (Arabidopsis) plants along the course of the infestation with Brevipalpus yothersi, the main vector species within the genus. Mite infestation triggered a drastic transcriptome reprogramming soon at the beginning of the interaction and throughout the time course, deregulating 1755, 3069 and 2680 genes at 6 hours after infestation (hai), 2 days after infestation (dai), and 6 dai, respectively. Gene set enrichment analysis revealed a clear modulation of processes related to the plant immune system. Co-expressed genes correlated with specific classes of transcription factors regulating defense pathways and developmental processes. Up-regulation of defensive responses correlated with the down-regulation of growth-related processes, suggesting the triggering of the growthdefense crosstalk to optimize plant fitness. Biological processes (BPs) enriched at all time points were markedly related to defense against herbivores and other biotic stresses involving the defense hormones salicylic acid (SA) and jasmonic acid (JA). Levels of both hormones were higher in plants challenged with mites than in the noninfested ones, supporting the simultaneous induction of genes from both pathways. To further clarify the functional relevance of the plant hormonal pathways on the interaction, we evaluated the mite performance on Arabidopsis mutants impaired in SA- or JAmediated response. Mite oviposition was lower on mutants defective in SA biosynthesis (sid2) and signaling (npr1), showing a function for SA pathway in improving the mite reproduction, an unusual mechanism compared to closely-related spider mites. Here we provide the first report on the global and dynamic plant transcriptome triggered by Brevipalpus feeding, extending our knowledge on plant-mite interaction. Furthermore, our results suggest that Brevipalpus mites manipulate the plant defensive response to render the plant more susceptible to their colonization by inducing the SA-mediated pathway

Citrus leprosis virus C infection results in hypersensitive-like response, suppression of the JA/ET plant defense pathway and promotion of the colonization of its mite vector

Leprosis is a serious disease of citrus caused by Citrus leprosis virus C (CiLV-C, genus Cilevirus) whose transmission is mediated by false spider mites of the genus Brevipalpus. CiLV-C infection does not systemically spread in any of its known host plants, thus remaining restricted to local lesions around the feeding sites of viruliferous mites. To get insight into this unusual pathosystem, we evaluated the expression profiles of genes involved in defense mechanisms of Arabidopsis thaliana and Citrus sinensis upon infestation with non-viruliferous and viruliferous mites by using reverse-transcription qPCR. These results were analyzed together with the production of reactive oxygen species (ROS) and the appearance of dead cells as assessed by histochemical assays. After interaction with non-viruliferous mites, plants locally accumulated ROS and triggered the salicylic acid (SA) and jasmonate/ethylene (JA/ET) pathways. ERE branch of the JA/ET pathways was highly activated. In contrast, JA pathway genes were markedly suppressed upon the CiLV-C infection mediated by viruliferous mites. Viral infection also intensified the ROS burst and cell death, and enhanced the expression of genes involved in the RNA silencing mechanism and SA pathway. After 13 days of infestation of two sets of Arabidopsis plants with non-viruliferous and viruliferous mites, the number of mites in the CiLV-C infected Arabidopsis plants was significantly higher than in those infested with the non-viruliferous ones. Oviposition of the viruliferous mites occurred preferentially in the CiLV-C infected leaves. Based on these results, we postulated the first model of plant/Brevipalpus mite/cilevirus interaction in which cells surrounding the feeding sites of viruliferous mites typify the outcome of a hypersensitive-like response, whereas viral infection induces changes in the behavior of its vector7CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP573848/08-4; 375843/2012-42012/18771- 0; 2014/00366-8; 2008/57909-2; 2014/08458-

Doce miradas del conflicto colombiano

Esta publicación es uno de los resultados de la concesión al Instituto de estudios internacionales y europeos Francisco de Vitoria de la Universidad Carlos III del proyecto Difusión y aplicación del Derecho internacional humanitario en Colombia, del que ha sido Investigador Principal el Prof. Carlos R. Fernández Liesa.Este libro es el resultado del proyecto de investigación Difusión y aplicación del Derecho internacional humanitario en Colombia, de la convocatoria CAP de la Agencia española de cooperación internacional (2012-2103) adscrito al Instituto de estudios internacionales y europeos Francisco de Vitoria de la Universidad Carlos III de Madrid. Esta edición ha contado con el apoyo de la Cátedra Iberoamericana Santander y de la Cátedra Mario Villarroel de Derecho internacional humanitario y de derechos humanos.Dirección de la colección, Carlos R. Fernández Liesa y Montserrat Huguet SantosEn este volumen de doce contribuciones hay cuatro de españoles, tres catedráticos de Derecho internacional (Manuel Pérez González, Antonio Pigrau y Carlos R. Fernández Liesa) y un Magistrado del Tribunal Supremo, general togado, Fernando Pignatelli. Por parte colombiana han realizado seis ponencias a cargo de profesores de Uninorte (Gabriel Orozco, Rosemary Suárez, José Luis Ramos, Roberto González Arana, Luis Fernando Trejos, Pedro Montero, Cecilia Giovanneti Lugo, Jessyka Manotas e Ivonne Molinero) y dos a cargo de importantes expertos. De un lado, Armando Borrero, profesor y antiguo Consejero de Seguridad Nacional de Colombia y, de otra, Saúl Ramírez Quesada, Presidente del Colegio de abogados de ColombiaPalabras previas / Carlos R. Fernández Liesa. -- Impacto Humanitario de la violencia armada en Colombia / Gabriel Orozco y Rosmery Suárez. -- Impacto del conflicto armado en el desempeño económico de las regiones: el caso del Caribe colombiano / José L. Ramos R. -- Derecho internacional humanitario y derechos humanos. Reflexiones sobre el conflicto colombiano / Carlos R. Fernández Liesa. -- Tipos de conflictos y aplicación del derecho internacional humanitario, con especial referencia a los conflictos armados internacionales / Manuel Pérez González. -- La crisis del derecho en los conflictos armados confusos y desregulados / Armando Borrero Mansilla. -- Nuevas perspectivas del conflicto armado colombiano / Roberto González Arana. -- La diplomacia insurgente. Otra forma de internacionalización del conflicto armado colombiano: el caso de las FARC-EP / Luis Fernando Trejos Rosero. -- La aplicación del derecho internacional humanitario en Colombia / Saúl Ramírez Quesada. -- Derechos de las víctimas en el tránsito hacia la normalización judicial (la verdad, la justicia, la reparación y las garantías de no repetición) / Pedro Montero Linares. -- La mujer y su doble condición: víctima de los conflictos internos y protagonista en los procesos de justicia transicional. El caso de Colombia / Cecilia Giovannetti Lugo, Jessyka Manota Muñoz e Ivonne Molinares Guerrero. -- El sistema de eficacia del derecho internacional humanitario, en especial la protección penal de las víctimas en los conflictos armados internos / Fernando Pignatelli y Meca. -- Colombia: la investigación pendiente de la Corte Penal Internacional / Antoni Pigrau

Profibrotic role of inducible heat shock protein 90α isoform in systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune disease that affects skin and multiple internal organs. TGF-β, a central trigger of cutaneous fibrosis, activates fibroblasts with the involvement of the stress-inducible chaperone heat shock protein 90 isoform α (Hsp90α). Available evidence supports overexpression and secretion of Hsp90α as a feature in profibrotic pathological conditions. The aim of this work is to investigate the expression and function of Hsp90α in experimental models of skin fibrosis such as human fibroblasts, C57BL/6 mice, and in human SSc. For this purpose, we generated a new experimental model based on doxorubicin administration with improved characteristics with respect to the bleomycin model. We visualized disease progression in vivo by fluorescence imaging. In this work, we obtained Hsp90α mRNA overexpression in human skin fibroblasts, in bleomycin- and doxorubicin-induced mouse fibrotic skin, and in lungs of bleomycin- and doxorubicin-treated mice. Hsp90α-deficient mice showed significantly decreased skin thickness compared with wild-type mice in both animal models. In SSc patients, serum Hsp90α levels were increased in patients with lung involvement and in patients with the diffuse form of SSc (dSSc) compared with patients with the limited form of SSc. The serum Hsp90α levels of patients dSSc were correlated with the Rodnan score and the forced vital capacity variable. These results provide new supportive evidence of the contribution of the Hsp90α isoform in the development of skin fibrosis. In SSc, these results indicated that higher serum levels were associated with dSSc and lung fibrosis.This work was supported by Spanish Ministerio de Economía, Industria y Competitividad, Gobierno de España Grant RTI2018-095214-B-I00, as well as by the Instituto de Formación e Investigación Marqués de Valdecilla IDIVAL (InnVal 17/22; InnVal 20/34), 2020UCI22-PUB-0003 Gobierno de Cantabria (to A.V.V.), SAF2016-75195-R (to J.M.), SAF2017-82905-R (to R.M.), and (NextVal 18/14) to A.P

Orogenias paleozoicas en los Andes de Argentina y Chile y en la Península Antártica

Congreso Geológico Argentino (20º. 2017. San Miguel de Tucumán, Argentina). Simposio de Téctonica pre-andinaDurante el Neoproterozoico y Paleozoico, los Andes de Argentina y Chile, y desde fines del Paleozoico también la Península Antártica, formaron parte del margen SO de Gondwana. Durante este tiempo se acrecionaron a dicho margen varios fragmentos continentales de tamaño y aloctonía variable; denominados de N a S: Antofalla, Chi-Cu, Patagonia Occidental y Antártida Occidental. Estos fragmentos formaban parte de placas litosféricas, en ocasiones divididas en subplacas. La colisión de dichos fragmentos continentales con Gondwana y una última subducción bajo dicho margen, dieron lugar a 6 orogenias de extensión temporal y espacial limitada.Instituto Geológico y Minero de España, EspañaDepartamento de Geología, Universidad de Oviedo, EspañaUniversidad de Río Negro, ArgentinaServicio Geológico y Minero Argentino, ArgentinaInstituto De Bio y Geociencias Del NOA, Consejo Nacional de Investigaciones Científicas y Técnicas, ArgentinaInstituto De Bio y Geociencias Del NOA, Universidad Nacional de Salta, ArgentinaDepartamento de Geodinámica, Universidad del País Vasco, EspañaFacultad de Geología, Universidad de Barcelona, EspañaDepartamento de Geología, Universidad de Chile, ChileUniversidad Andrés Bello, ChileUnidad de Tectónica, Consejo Nacional de Investigaciones Científicas y Técnicas, ArgentinaFacultad de Geología, Universidad de Buenos Aires, ArgentinaÁrea de Geología, Universidad Rey Juan Carlos, EspañaUniversidad de Salta, ArgentinaInstituto de Investigación en Paleobiología y Geología, Universidad de Río Negro, ArgentinaInstituto de Investigación en Paleobiología y Geología, Consejo Nacional de Investigaciones Científicas y Técnicas, ArgentinaCentro de Investigaciones Geológicas, Universidad de La Plata, ArgentinaUniversidad de San Juan, ArgentinaPeer reviewe

Effect of parathyroid-hormone-related protein on human platelet activation

A B S T R A C T Evidence suggests that PTHrP [PTH (parathyroid hormone)-related protein] can act as an inflammatory mediator in several pathological settings including cardiovascular disease. The aim of the present study was to determine whether PTHrP might be involved in human platelet activation. We used a turbidimetric method to determine platelet aggregation. The expression of PTH1R (PTH type 1 receptor) in human platelets was analysed by Western blot and flow cytometry analyses. PTHrP-(1-36) (10 −7 mol/l) by itself failed to modify the activation of platelets. However, it significantly enhanced ADP-induced platelet activation, and also increased the ability of other agonists (thrombin, collagen and arachidonic acid) to induce platelet aggregation. H89 (10 −6 mol/l) and 25 × 10 −6 mol/l Rp-cAMPS (adenosine 3 ,5 -cyclic monophosphorothioate Rp-isomer), two protein kinase A inhibitors, and 25 × 10 −9 mol/l bisindolylmaleimide I, a protein kinase C inhibitor, partially decreased the enhancing effect of PTHrP-(1-36) on ADP-induced platelet activation. Meanwhile, 10 −6 mol/l PTHrP-(7-34), a PTH1R antagonist, as well as 10 −5 mol/l PD098059, a MAPK (mitogen-activated protein kinase) inhibitor, or a farnesyltransferase inhibitor abolished this effect of PTHrP-(1-36). Moreover, 10 −7 mol/l PTHrP-(1-36) increased (2-fold over control) MAPK activation in human platelets. PTH1R was detected in platelets, and the number of platelets expressing it on their surface in patients during AMI (acute myocardial infarction) was not different from that in a group of patients with similar cardiovascular risk factors without AMI. Western blot analysis showed that total PTH1R protein levels were markedly higher in platelets from control than those from AMI patients. PTH1R was found in plasma, where its levels were increased in AMI patients compared with controls. In conclusion, human platelets express the PTH1R. PTHrP can interact with this receptor to enhance human platelet activation induced by several agonists through a MAPK-dependent mechanism

Impact of stratospheric air and surface emissions on tropospheric nitrous oxide during ATom

We measured the global distribution of tropospheric N2O mixing ratios during the NASA airborne Atmospheric Tomography (ATom) mission. ATom measured concentrations of ∼ 300 gas species and aerosol properties in 647 vertical profiles spanning the Pacific, Atlantic, Arctic, and much of the Southern Ocean basins, nearly from pole to pole, over four seasons (2016–2018). We measured N2O concentrations at 1 Hz using a quantum cascade laser spectrometer (QCLS). We introduced a new spectral retrieval method to account for the pressure and temperature sensitivity of the instrument when deployed on aircraft. This retrieval strategy improved the precision of our ATom QCLS N2O measurements by a factor of three (based on the standard deviation of calibration measurements). Our measurements show that most of the variance of N2O mixing ratios in the troposphere is driven by the influence of N2O-depleted stratospheric air, especially at mid- and high latitudes. We observe the downward propagation of lower N2O mixing ratios (compared to surface stations) that tracks the influence of stratosphere–troposphere exchange through the tropospheric column down to the surface. The highest N2O mixing ratios occur close to the Equator, extending through the boundary layer and free troposphere. We observed influences from a complex and diverse mixture of N2O sources, with emission source types identified using the rich suite of chemical species measured on ATom and the geographical origin calculated using an atmospheric transport model. Although ATom flights were mostly over the oceans, the most prominent N2O enhancements were associated with anthropogenic emissions, including from industry (e.g., oil and gas), urban sources, and biomass burning, especially in the tropical Atlantic outflow from Africa. Enhanced N2O mixing ratios are mostly associated with pollution-related tracers arriving from the coastal area of Nigeria. Peaks of N2O are often associated with indicators of photochemical processing, suggesting possible unexpected source processes. In most cases, the results show how difficult it is to separate the mixture of different sources in the atmosphere, which may contribute to uncertainties in the N2O global budget. The extensive data set from ATom will help improve the understanding of N2O emission processes and their representation in global models.This research has been supported by the National Aeronautics and Space Administration (grant nos. NNX15AJ23G, NNX17AF54G, NNX15AG58A, NNX15AH33A, and 80NSSC19K0124) and the National Science Foundation (grant nos. 1852977, AGS-1547626, and AGS-1623745)

Setting performance indicators for coastal marine protected areas: An expert-based methodology

Marine Protected Areas (MPAs) require effective indicators to assess their performance, in compliance with the goals of relevant national and international commitments. Achieving and prioritizing shortlists of multidisciplinary indicators demands a significant effort from specialists to depict the multiple conservation and socioeconomic interests, and the large complexity of natural systems. The present paper describes a structured expert-based methodology (process and outputs) to co-define a list of multidisciplinary MPA performance indicators. This work was promoted by the management authority of coastal MPAs in mainland Portugal to gather a consensual and feasible list of indicators that would guide the design of a future national monitoring program. Hence, Portuguese coastal MPAs served as a case study to develop such a process between 2019 and 2020. In the end, participants (1) agreed on a shortlist of prioritized indicators (i.e., environmental, governance, and socioeconomic indicators) and (2) defined minimum monitoring frequencies for the indicators in this list, compatible with the potential replicability of the associated survey methods. The present approach recommends that management plans incorporate monitoring procedures and survey methods, with a validated list of indicators and associated monitoring periodicity, agreed among researchers, MPA managers and governance experts. The proposed methodology, and the lessons learned from it, can support future processes aiming to define and prioritize MPA performance indicatorsFundação para a Ciência e Tecnologia - FCT, European Maritime and Fisheries Fund (EMFF)info:eu-repo/semantics/publishedVersio