Glycosylated Cell Penetrating Peptides, GCPPs

This is the peer reviewed version of the following article: Gallego, I. , Rioboo, A. , Reina, J. ., Díaz, B. , Canales, Á., Cañada, F. ., Guerra-Varela, J. , Sánchez, L. and Montenegro, J. (2019), Glycosylated Cell Penetrating Peptides, GCPPs. ChemBioChem. doi:10.1002/cbic.201800720, which has been published in final form at https://doi.org/10.1002/cbic.201800720. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsThe cell membrane regulates the exchange of molecules and information with the external environment. However, this control barrier hinders the delivery of exogenous bioactive molecules that can be applied to correct cellular malfunctions. Therefore, the traffic of macromolecules across the cell membrane represents a great challenge for the development of the next generation of therapies and diagnostic methods. Cell penetrating peptides are short peptide sequences capable of delivering a broad range of biomacromolecules across the cellular membrane. However, penetrating peptides still suffer from limitations mainly related with their lack of specificity and potential toxicity. Glycosylation has emerged as a potential promising strategy for the biological improvement of synthetic materials. In this work we have developed a new convergent strategy for the synthesis of penetrating peptides functionalized with glycan residues by an oxime bond connection. We have systematically characterized the uptake efficiency and the intracellular distribution of these glycopeptides by flow cytometry, confocal microscopy and in zebrafish animal models. The incorporation of these glycan residues into the peptide structure influenced the internalization efficiency and the cellular toxicity of the resulting glycopeptide hybrids in the different cell lines tested. The results reported here highlight the potential of the glycosylation of penetrating peptides to modulate their activityWe acknowledge funding from the Spanish Agencia Estatal de Investigación (AEI) [CTQ2014-59646-R, SAF2017-89890-R, CTQ2016-76263-P, CTQ2015-64597-C2-2P], the Xuntade Galicia (ED431G/09, ED431C 2017/25 and 2016-AD031) and the ERDF. I. G. received a predoctoral fellowship from the Xunta de Galicia (ED481A-2018/116). A. R. received a predoctoral fellowship from the Fundación Segundo Gil Dávila. J.G.-V. and L.S. acknowledge the financial support received from the Xunta de Galicia (Galicia, Spain) under the Grupos de Referencia Competitiva Programme: Project GRC2014/010. J. M. received a Ramón y Cajal (RYC-2013-13784), an ERC Starting Investigator Grant (DYNAP-677786) and a Young Investigator Grant from the HFSP (RGY0066/2017)S

Generación de Mallas y Simulación Numérica en Medioambiente

[ES]En esta conferencia se introducen ideas básicas sobre la simulación numérica, mediante el método de los elementos finitos (MEF), de problemas medioambientales que han sido abordados por nuestro grupo en diversos proyectos de investigación sobre simulación de campos de viento, radiación solar, contaminación atmosférica y la modelización de yacimientos de petróleo

First Sagittarius A* Event Horizon Telescope results. II. EHT and multiwavelength observations, data processing, and calibration

We present Event Horizon Telescope (EHT) 1.3 mm measurements of the radio source located at the position of the supermassive black hole Sagittarius A* (Sgr A*), collected during the 2017 April 5–11 campaign. The observations were carried out with eight facilities at six locations across the globe. Novel calibration methods are employed to account for Sgr A*'s flux variability. The majority of the 1.3 mm emission arises from horizon scales, where intrinsic structural source variability is detected on timescales of minutes to hours. The effects of interstellar scattering on the image and its variability are found to be subdominant to intrinsic source structure. The calibrated visibility amplitudes, particularly the locations of the visibility minima, are broadly consistent with a blurred ring with a diameter of ∼50 μas, as determined in later works in this series. Contemporaneous multiwavelength monitoring of Sgr A* was performed at 22, 43, and 86 GHz and at near-infrared and X-ray wavelengths. Several X-ray flares from Sgr A* are detected by Chandra, one at low significance jointly with Swift on 2017 April 7 and the other at higher significance jointly with NuSTAR on 2017 April 11. The brighter April 11 flare is not observed simultaneously by the EHT but is followed by a significant increase in millimeter flux variability immediately after the X-ray outburst, indicating a likely connection in the emission physics near the event horizon. We compare Sgr A*'s broadband flux during the EHT campaign to its historical spectral energy distribution and find that both the quiescent emission and flare emission are consistent with its long-term behavior.http://iopscience.iop.org/2041-8205Physic

First Sagittarius A* Event Horizon Telescope Results. II. EHT and Multiwavelength Observations, Data Processing, and Calibration

We present Event Horizon Telescope (EHT) 1.3 mm measurements of the radio source located at the position of the supermassive black hole Sagittarius A* (Sgr A*), collected during the 2017 April 5–11 campaign. The observations were carried out with eight facilities at six locations across the globe. Novel calibration methods are employed to account for Sgr A*'s flux variability. The majority of the 1.3 mm emission arises from horizon scales, where intrinsic structural source variability is detected on timescales of minutes to hours. The effects of interstellar scattering on the image and its variability are found to be subdominant to intrinsic source structure. The calibrated visibility amplitudes, particularly the locations of the visibility minima, are broadly consistent with a blurred ring with a diameter of ∼50 μas, as determined in later works in this series. Contemporaneous multiwavelength monitoring of Sgr A* was performed at 22, 43, and 86 GHz and at near-infrared and X-ray wavelengths. Several X-ray flares from Sgr A* are detected by Chandra, one at low significance jointly with Swift on 2017 April 7 and the other at higher significance jointly with NuSTAR on 2017 April 11. The brighter April 11 flare is not observed simultaneously by the EHT but is followed by a significant increase in millimeter flux variability immediately after the X-ray outburst, indicating a likely connection in the emission physics near the event horizon. We compare Sgr A*’s broadband flux during the EHT campaign to its historical spectral energy distribution and find that both the quiescent emission and flare emission are consistent with its long-term behavior

Antifeedant effect of polygodial and drimenol derivatives against Spodoptera frugiperda and Epilachna paenulata and quantitative structure-activity analysis

The antifeedant activity of 18 sesquiterpenoids of the drimane family (polygodial, drimenol and derivatives) was investigated. RESULTS: Polygodial, drimanic and nordrimanic derivatives were found to exert antifeedant effects against two insect species, Spodoptera frugiperda and Epilachna paenulata, which are pests of agronomic interest, indicating that they have potential as biopesticide agents. Among the 18 compounds tested, the epoxynordrimane compound (11) and isonordrimenone (4) showed the highest activity [50% effective concentration (EC50)=23.28 and 25.63nmol cm- 2, respectively, against S. frugiperda, and 50.50 and 59.00nmol/cm2, respectively, against E. paenulata]. The results suggest that drimanic compounds have potential as new agents against S. frugiperda and E. paenulata. A quantitative structure-activity relationship (QSAR) analysis of the whole series, supported by electronic studies, suggested that drimanic compounds have structural features necessary for increasing antifeedant activity, namely a C-9 carbonyl group and an epoxide at C-8 and C-9.Fil: Montenegro, Iván J. Universidad de Valparaiso; ChileFil: del Corral, Soledad. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; ArgentinaFil: Diaz Napal, Georgina Natalia. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; ArgentinaFil: Carpinella, Maria Cecilia. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; ArgentinaFil: Mellado, Marco. Pontificia Universidad Católica de Valparaíso; ChileFil: Madrid, Alejandro M. Universidad de Playa Ancha; ChileFil: Villena, Joan. Unversidad de Valparaíso; ChileFil: Palacios, Sara Maria. Unversidad de Valparaíso; Chile. Area de Ciencias Agrarias, Ingeniería, Ciencias Biológicas y de la Salud de la Universidad Católica de Córdoba; ArgentinaFil: Cuellar, Mauricio A. Universidad de Valparaíso; Chil

Durability of concrete structures: DURACON, an iberoamerican project. Preliminary results

This work presents preliminary results of the international project: “Effect of the environment on reinforced concrete durability: DURACON”, which shows the physical, mechanical and chemical characterization of two different concrete mixtures prepared in the participating countries, as well as the environment to which the specimens are exposed. These results show the potentiality and probability of future reinforcement corrosion, depending on the type of mixture and the environment to which the structure is exposed. To that effect, concrete specimens, with and without reinforcement, were prepared for electrochemical and physical/mechanical/chemical testing using the existing materials in each participating country, following premises that enabled the preparation of similar concrete specimens. Two water/cement ratios (0.45 and 0.65) were selected, where the concrete with w/c=0.45 had to have a minimum cement content of 400 kg m−3, and the other with w/c=0.65, a minimum compressive strength of 21 MPa. Ordinary Portland Cement (OPC), crushed coarse aggregate, and silica sand were used for concrete preparation. The specimens were exposed to several microenvironments including urban and marine conditions (at least two testing sites in each country), resulting into a total of 46 test sites distributed among 11 countries (Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Mexico, Spain, Uruguay, Portugal, and Venezuela). The environment was evaluated using ISO Standard 9223 and the concrete was characterized by measuring compressive strength, modulus of elasticity, total and effective porosity, and rapid chloride permeability according to ASTM standards, as well as resistance to water absorption, using the Fagerlund method. After 1-year exposure, some results of the corrosion potentiality and probability analysis of the reinforcement in several test sites based on environmental meteorochemical parameters show that, for specific microclimates like those in marine atmospheres, the most aggressive environment is that at Cabo Raso test site in Portugal, inducing the greater steel-corrosion probability. The least aggressive is the one at Valparaíso in Chile. It was also determined that Maracaibo, Venezuela, is the one that has the greatest probability of early rebar corrosion initiation by carbonation, with the test site at Cali, Colombia being the one that would induce the least corrosion probability.Peer reviewe

Effect of the marine environment on reinforced concrete durability in Iberoamerican countries: DURACON project/CYTED

[EN] This work presents some of the results from the project: “Effect of the environment on reinforcement durability” (DURACON) in its first two-years period, which investigates the influence of urban and marine meteorochemical parameters on the performance of reinforced concrete structures. The results presented in this investigation are from 21 marine test sites only (no urban environments are included), distributed among 11 countries (Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Mexico, Spain, Uruguay, Portugal and Venezuela). The environment was evaluated using ISO Standard 9223 and the concrete was characterized by measuring compressive strength, elastic modulus, total and effective porosity, chloride permeability according to ASTM standards, as well as the effective porosity and resistance to water absorption using the Fagerlund method. To that effect, concrete specimens (with and without reinforcement) were prepared for electrochemical and physical/mechanical/chemical tests using the existing materials in each participating country, following strict procedures which enabled the preparation of similar concrete samples. Two water/cement (w/c) ratios (0.45 and 0.65) were selected, where the concrete with 0.45 w/c ratio had to have a minimum cement content of 400 kg/m3 and the one with 0.65 w/c ratio a compressive strength of 210 kg/cm2. Type I Portland cement, siliceous sand, and crushed rock as coarse aggregates (13-mm maximum nominal size) were used. After a one-year exposure, the results of the corrosion potentiality and probability analysis of the reinforcement in the different test stations showed that, for marine atmospheres, the most aggressive environment to induce steel corrosion was at Portugal’s Cabo Raso station, and the least aggressive one was at Chile’s Valparaíso station. These results are comparable with the ones found using electrochemical measurements, after a two-year exposure.Peer reviewe

A molecular barcode and web-based data analysis tool to identify imported Plasmodium vivax malaria.

Traditionally, patient travel history has been used to distinguish imported from autochthonous malaria cases, but the dormant liver stages of Plasmodium vivax confound this approach. Molecular tools offer an alternative method to identify, and map imported cases. Using machine learning approaches incorporating hierarchical fixation index and decision tree analyses applied to 799 P. vivax genomes from 21 countries, we identified 33-SNP, 50-SNP and 55-SNP barcodes (GEO33, GEO50 and GEO55), with high capacity to predict the infection's country of origin. The Matthews correlation coefficient (MCC) for an existing, commonly applied 38-SNP barcode (BR38) exceeded 0.80 in 62% countries. The GEO panels outperformed BR38, with median MCCs > 0.80 in 90% countries at GEO33, and 95% at GEO50 and GEO55. An online, open-access, likelihood-based classifier framework was established to support data analysis (vivaxGEN-geo). The SNP selection and classifier methods can be readily amended for other use cases to support malaria control programs