C-reactive protein exerts angiogenic effects on vascular endothelial cells and modulates associated signalling pathways and gene expression

<p>Abstract</p> <p>Background</p> <p>Formation of haemorrhagic neovessels in the intima of developing atherosclerotic plaques is thought to significantly contribute to plaque instability resulting in thrombosis. C-reactive protein (CRP) is an acute phase reactant whose expression in the vascular wall, in particular, in reactive plaque regions, and circulating levels increase in patients at high risk of cardiovascular events. Although CRP is known to induce a pro-inflammatory phenotype in endothelial cells (EC) a direct role on modulation of angiogenesis has not been established.</p> <p>Results</p> <p>Here, we show that CRP is a powerful inducer of angiogenesis in bovine aortic EC (BAEC) and human coronary artery EC (HCAEC). CRP, at concentrations corresponding to moderate/high risk (1–5 μg/ml), induced a significant increase in proliferation, migration and tube-like structure formation <it>in vitro </it>and stimulated blood vessel formation in the chick chorioallantoic membrane assay (CAM). CRP treated with detoxi-gel columns retained such effects. Western blotting showed that CRP increased activation of early response kinase-1/2 (ERK1/2), a key protein involved in EC mitogenesis. Furthermore, using TaqMan Low-density Arrays we identified key pro-angiogenic genes induced by CRP among them were vascular endothelial cell growth factor receptor-2 (VEGFR2/KDR), platelet-derived growth factor (PDGF-BB), notch family transcription factors (Notch1 and Notch3), cysteine-rich angiogenic inducer 61 (CYR61/CCN1) and inhibitor of DNA binding/differentiation-1 (ID1).</p> <p>Conclusion</p> <p>This data suggests a role for CRP in direct stimulation of angiogenesis and therefore may be a mediator of neovessel formation in the intima of vulnerable plaques.</p

XTEND: Extending the depth of field in cryo soft X-ray tomography

We have developed a new data collection method and processing framework in full field cryo soft X-ray tomography to computationally extend the depth of field (DOF) of a Fresnel zone plate lens. Structural features of 3D-reconstructed eukaryotic cells that are affected by DOF artifacts in standard reconstruction are now recovered. This approach, based on focal series projections, is easily applicable with closed expressions to select specific data acquisition parameters.This work was partially supported by MINECO grants BFU2014-54181 to JLC and AIC-A-2011-0638, BIO2013-44647-R and BIO2016-76400-R to JMC, Madrid. Regional government grants S2013/MIT-2850 to JLC and S2010/BMD-2305 to JMC, National Science Foundation grant DMS-1114901 to GTH, the European Union through BioStruct-X Project 283570 and Horizon 2020 through grant iNEXT (INFRAIA-1-2014-2015, Proposal: 653706).S

La vinculación interinstitucional y la innovación ejes del desarrollo, validación y transferencia de tecnologías relativas a la gestión de calidad y el bienestar animal.

Las “Buenas Prácticas” (BP), son pilares necesarios para una adecuada gestión de calidad. Izquierdo y Fazzone (2006) en la conferencia de la FAO “BUENAS PRÁCTICAS AGRÍCOLAS (BPA)” afirman que las BP deben posicionarse como el límite mínimo que en un futuro debe exigirse para cualquier sistema de producción de alimentos. Los representantes por nuestro país en dicha conferencia plantearon la necesidad de apoyar y colaborar en la elaboración de normas técnicas a nivel nacional y subregional e incentivar la integración de pequeños productores al proceso de BP mediante la capacitación y la implementación. Las BP tienen como objetivo lograr inocuidad en los alimentos, la seguridad de las personas, el respeto del bienestar animal y el cuidado del ambiente. Esto es importante para el sector lácteo porque permite mejorar y garantizar la calidad de sus productos y procesos, traducidos en una mejora de la rentabilidad por menores costos de la “no calidad”, y por la posibilidad de acceder a otros mercados y precios diferenciales. La innovación, desarrollo y transferencia de tecnología en gestión de calidad (GC) y bienestar animal (BA), en el sector primario de producción de leche son las temáticas de proyectos de investigación-transferencia en los que trabajamos en los últimos años. En ellos se generaron herramientas específicas para los tambos, con formatos novedosos, de fácil entendimiento e implementación. Con la preocupación por lograr que estas innovaciones llegasen efectivamente a los sistemas productivos, y con la necesidad de realizarlo con un equipo interdisciplinario e interinstitucional, se establecieron alianzas estratégicas con otras instituciones (INTA, APROCAL), cooperativas y productores. Por ello, el objetivo del proyecto fue generar aportes a las tecnologías de los sistemas de producción de leche, mediante la transferencia de herramientas innovadoras dentro de una red de vinculación interinstitucional. Los resultados esperados fueron: una red de vinculación formal en la temática de GC y BA conformada; tecnologías transferidas e implementadas en los sistemas productivos mediante actividades de vinculación; operarios de tambos, productores y profesionales capacitados en instancias en el aula, en el campo y en el puesto de trabajo.publishedVersio

Role of a cryptic tRNA gene operon in survival under translational stress

As compared to eukaryotes, bacteria have a reduced tRNA gene set encoding between 30 and 220 tRNAs. Although in most bacterial phyla tRNA genes are dispersed in the genome, many species from distinct phyla also show genes forming arrays. Here, we show that two types of arrays with distinct evolutionary origins exist. This work focuses on long tRNA gene arrays (L-arrays) that encompass up to 43 genes, which disseminate by horizontal gene transfer and contribute supernumerary tRNA genes to the host. Although in the few cases previously studied these arrays were reported to be poorly transcribed, here we show that the L-array of the model cyanobacterium Anabaena sp. PCC 7120, encoding 23 functional tRNAs, is largely induced upon impairment of the translation machinery. The cellular response to this challenge involves a global reprogramming of the transcriptome in two phases. tRNAs encoded in the array are induced in the second phase of the response, directly contributing to cell survival. Results presented here show that in some bacteria the tRNA gene set may be partitioned between a housekeeping subset, which constantly sustains translation, and an inducible subset that is generally silent but can provide functionality under particular conditions.Ministerio de Ciencia, Innovación y Universidades [BFU2016-77097-P to I.L., A.H.; BIO2017-84066-R to F.J.R-C.]; Agencia Estatal de Investigación [PID2019-104784RJ-100/AEI/10.13039/501100011033 to R.L.I.]; National Science Foundation [MCB-1715840 to M.I.]. RB-M's lab at University of Alicante is a member of Proteored, PRB3 and is supported by grant PT17/0019, of the PE I+D+i 2013-2016, funded by ISCIII and ERDF. Funding for open access charge: Consejo Superior de Investigaciones Científicas

Metabolomics analysis of type 2 diabetes remission identifies 12 metabolites with predictive capacity: a CORDIOPREV clinical trial study.

Type 2 diabetes mellitus (T2DM) is one of the most widely spread diseases, affecting around 90% of the patients with diabetes. Metabolomics has proven useful in diabetes research discovering new biomarkers to assist in therapeutical studies and elucidating pathways of interest. However, this technique has not yet been applied to a cohort of patients that have remitted from T2DM. All patients with a newly diagnosed T2DM at baseline (n = 190) were included. An untargeted metabolomics approach was employed to identify metabolic differences between individuals who remitted (RE), and those who did not (non-RE) from T2DM, during a 5-year study of dietary intervention. The biostatistical pipeline consisted of an orthogonal projection on the latent structure discriminant analysis (O-PLS DA), a generalized linear model (GLM), a receiver operating characteristic (ROC), a DeLong test, a Cox regression, and pathway analyses. The model identified a significant increase in 12 metabolites in the non-RE group compared to the RE group. Cox proportional hazard models, calculated using these 12 metabolites, showed that patients in the high-score tercile had significantly (p-value < 0.001) higher remission probabilities (Hazard Ratio, HR, high versus low = 2.70) than those in the lowest tercile. The predictive power of these metabolites was further studied using GLMs and ROCs. The area under the curve (AUC) of the clinical variables alone is 0.61, but this increases up to 0.72 if the 12 metabolites are considered. A DeLong test shows that this difference is statistically significant (p-value = 0.01). Our study identified 12 endogenous metabolites with the potential to predict T2DM remission following a dietary intervention. These metabolites, combined with clinical variables, can be used to provide, in clinical practice, a more precise therapy. ClinicalTrials.gov, NCT00924937.The CORDIOPREV study is supported by the Ministerio de Economia y Competitividad, Spain, under the grants AGL2012/39615, PIE14/00005, and PIE14/00031 associated to J.L.-M.; AGL2015-67896-P to J.L.-M. and A.C.; CP14/00114 to A.C.; PI19/00299 to A.C.; DTS19/00007 to A.C.; FIS PI13/00023 to J.D.-L., PI16/01777 to F.P.-J. and P.P.-M.; Antonio Camargo is supported by an ISCIII research contract (Programa Miguel-Servet CPII19/00007); Marina Mora-Ortiz has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 847468; ‘Fundacion Patrimonio Comunal Olivarero’, Junta de Andalucía (Consejería de Salud, Consejeria de Agricultura y Pesca, Consejería de Innovacion, Ciencia y Empresa), ‘Diputaciones de Jaen y Cordoba’, ‘Centro de Excelencia en Investigación sobre Aceite de Oliva y Salud’ and ‘Ministerio de Medio Ambiente, Medio Rural y Marino’, Gobierno de España; ‘Consejeria de Innovación, Ciencia y Empresa, Proyectos de Investigación de Excelencia’, Junta de Andalucía under the grant CVI-7450 obtaiend by J.L.-M.; and we would also like to thank the ‘Fondo Europeo de Desarrollo Regional (FEDER)’.S

Multiple Folding Pathways of the SH3 domain

Experimental observations suggest that proteins follow different pathways under different environmental conditions. We perform molecular dynamics simulations of a model of the SH3 domain over a broad range of temperatures, and identify distinct pathways in the folding transition. We determine the kinetic partition temperature --the temperature for which the SH3 domain undergoes a rapid folding transition with minimal kinetic barriers-- and observe that below this temperature the model protein may undergo a folding transition via multiple folding pathways. The folding kinetics is characterized by slow and fast pathways and the presence of only one or two intermediates. Our findings suggest the hypothesis that the SH3 domain, a protein for which only two-state folding kinetics was observed in previous experiments, may exhibit intermediates states under extreme experimental conditions, such as very low temperatures. A very recent report (Viguera et al., Proc. Natl. Acad. Sci. USA, 100:5730--5735, 2003) of an intermediate in the folding transition of the Bergerac mutant of the alpha-spectrin SH3 domain protein supports this hypothesis.Comment: 16 pages, 4 figures To be published in the "Journal of Molecular Biology

The regulatory subunit of PKA-I remains partially structured and undergoes β-aggregation upon thermal denaturation

Background: The regulatory subunit (R) of cAMP-dependent protein kinase (PKA) is a modular flexible protein that responds with large conformational changes to the binding of the effector cAMP. Considering its highly dynamic nature, the protein is rather stable. We studied the thermal denaturation of full-length RIα and a truncated RIα(92-381) that contains the tandem cyclic nucleotide binding (CNB) domains A and B. Methodology/Principal Findings: As revealed by circular dichroism (CD) and differential scanning calorimetry, both RIα proteins contain significant residual structure in the heat-denatured state. As evidenced by CD, the predominantly α-helical spectrum at 25°C with double negative peaks at 209 and 222 nm changes to a spectrum with a single negative peak at 212-216 nm, characteristic of β-structure. A similar α→β transition occurs at higher temperature in the presence of cAMP. Thioflavin T fluorescence and atomic force microscopy studies support the notion that the structural transition is associated with cross-β-intermolecular aggregation and formation of non-fibrillar oligomers. Conclusions/Significance: Thermal denaturation of RIα leads to partial loss of native packing with exposure of aggregation-prone motifs, such as the B' helices in the phosphate-binding cassettes of both CNB domains. The topology of the β-sandwiches in these domains favors inter-molecular β-aggregation, which is suppressed in the ligand-bound states of RIα under physiological conditions. Moreover, our results reveal that the CNB domains persist as structural cores through heat-denaturation. © 2011 Dao et al

Theory and simulation of quantum photovoltaic devices based on the non-equilibrium Green's function formalism

This article reviews the application of the non-equilibrium Green's function formalism to the simulation of novel photovoltaic devices utilizing quantum confinement effects in low dimensional absorber structures. It covers well-known aspects of the fundamental NEGF theory for a system of interacting electrons, photons and phonons with relevance for the simulation of optoelectronic devices and introduces at the same time new approaches to the theoretical description of the elementary processes of photovoltaic device operation, such as photogeneration via coherent excitonic absorption, phonon-mediated indirect optical transitions or non-radiative recombination via defect states. While the description of the theoretical framework is kept as general as possible, two specific prototypical quantum photovoltaic devices, a single quantum well photodiode and a silicon-oxide based superlattice absorber, are used to illustrated the kind of unique insight that numerical simulations based on the theory are able to provide.Comment: 20 pages, 10 figures; invited review pape

Aislamiento, identificación y daños asociados al síndrome de la muerte súbita en el cultivo de soja en Argentina

358-362The main objectives of this work were to isolate and identify the causal agents of sudden death syndrome (SDS) from samples collected in different Argentinean localities, to quantify its incidence, and to estimate yield losses. Two hundred and ffteen roots from plants with typical SDS foliar symptoms were analyzed. In order to perform pathogenicity tests, two bioassays were conducted in the greenhouse. Yield losses were estimated in a feld trial located in Pergamino by quantifcation and comparison of yield of paired samples. Thirty-six percent of total roots (78 roots) presented signs of Fusarium, compatible with signs caused by SDS. Morphological studies allowed the identifcation of 35 isolates as F. tucumaniae and 18 as F. virguliforme. Other eight isolates could not be identifed. All isolates that were inoculated reproduced typical SDS foliar symptoms. Signifcant differences were observed between healthy and diseased plants for 1000-grain weight and between potential and real yield (p less than 0.05). Average yield loss was 1514 kg/ha (range 192-3770 kg/ha). These results corroborated the distribution and predominance of F. tucumaniae and F. viguliforme in the area under study and its destructive potential

Identification and characterization of Diaporthe spp. associated with twig cankers and shoot blight of almonds in Spain

[EN] Two hundred and twenty-fiveDiaportheisolates were collected from 2005 to 2019 in almond orchards showing twig cankers and shoot blight symptoms in five different regions across Spain. Multilocus DNA sequence analysis with five loci (ITS,tub,tef-1 alpha,calandhis), allowed the identification of four knownDiaporthespecies, namely:D. amygdali,D. eres,D. foeniculinaandD. phaseolorum. Moreover, a novel phylogenetic species,D. mediterranea, was described.Diaportheamygdaliwas the most prevalent species, due to the largest number of isolates (85.3%) obtained from all sampled regions. The second most frequent species wasD. foeniculina(10.2%), followed byD. mediterranea(3.6%),D.eresandD. phaseolorum, each with only one isolate. Pathogenicity tests were performed using one-year-old almond twigs cv. Vayro and representative isolates of the different species. Except forD. foeniculinaandD. phaseolorum, allDiaporthespecies were able to cause lesions significantly different from those developed on the uninoculated controls.Diaporthe mediterraneacaused the most severe symptoms. These results confirmD. amygdalias a key pathogen of almonds in Spain. Moreover, the new species,D. mediterranea, should also be considered as a potential important causal agent of twig cankers and shoot blight on this crop.Research funded by the Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria (INIA), grants RTA2017-00009-C04-01, -02, -03 and -04 and with matching funds from the European Regional Development Fund (ERDF). G. Elena and C. Agusti-Brisach were supported by the Spanish post-doctoral grants "Juan de la Cierva-Formacion" and "Juan de la Cierva-Incorporacion", respectively. J. Luque and X. Miarnau were partially supported by the CERCA program, Generalitat de Catalunya. D. Gramaje was supported by the Ramon y Cajal program, Spanish Government (RYC-2017-23098).León Santana, M.; Berbegal Martinez, M.; Rodríguez-Reina, JM.; Elena, G.; Abad Campos, P.; Ramón-Albalat, A.; Olmo, D.... (2020). Identification and characterization of Diaporthe spp. associated with twig cankers and shoot blight of almonds in Spain. Agronomy. 10(8):1-23. https://doi.org/10.3390/agronomy10081062S123108Food and Agriculture Organization of the United Nationshttp://www.fao.org/faostat/es/#datDiogo, E. L. F., Santos, J. M., & Phillips, A. J. L. (2010). Phylogeny, morphology and pathogenicity of Diaporthe and Phomopsis species on almond in Portugal. Fungal Diversity, 44(1), 107-115. doi:10.1007/s13225-010-0057-xTuset, J. J., & Portilla, M. A. T. (1989). Taxonomic status of Fusicoccum amygdali and Phomopsis amygdalina. Canadian Journal of Botany, 67(5), 1275-1280. doi:10.1139/b89-168TUSET, J. J., HINAREJOS, C., & PORTILLA, M. T. (1997). 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