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13 páginas, 4 figuras y 3 tablas, The widespread use of both heavy metals and antibiotics in livestock farming, followed by their subsequent arrival on agricultural soils through manure and slurry spreading, has become a problem of vital importance for human health and the environment. In the current research, a laboratory experiment was carried out for 42 d to study tolerance and co-tolerance of three tetracycline antibiotics (tetracycline, TC; oxytetracycline, OTC; chlortetracycline, CTC) in soils polluted with heavy metals (As, Cd, Zn, Cu, Ni, Cr, and Pb) at high concentrations (1000 mg kg-1 of each one, separately). Pollution induced community tolerance (PICT) of the bacterial community was estimated using the leucine incorporation technique. The log IC50 (logarithm of the concentration causing 50 % inhibition in bacterial community growth) values obtained in uncontaminated soil samples for all the heavy metals tested showed the following toxicity sequence: Cu > As > Cr ≥ Pb ≥ Cd > Zn > Ni. However, in polluted soil samples the toxicity sequence was Cu > Pb ≥ As ≥ Cd ≥ Cr ≥ Ni ≥ Zn. Moreover, at high heavy metal concentrations, the bacterial communities showed tolerance to the metal itself, this taking place in the long term for all the metals tested. The bacterial communities of the soil polluted with heavy metals showed also long-term co-tolerance to TC, OTC, and CTC. This kind of study, focusing on the eventual increases of tolerance and co-tolerance of bacterial communities in agricultural soil, favored by the presence of different kinds of pollutants, is of crucial importance, mostly bearing in mind that the appearance of antibiotic resistance genes in soil bacteria could be transmitted to human pathogens., This study has been funded by the Spanish Ministry of Economy and Competitiveness through the projects CGL2015-67333-C2-1-R and CGL2015-67333-C2-2-R (FEDER Funds). David Fernández-Calviño holds a Ramón y Cajal contract (RYC-2016-20411), financed by the Spanish Ministry of Economy, Industry and Competitiveness. Vanesa Santás-Miguel holds a pre-doctoral fellowship (ED481A-2020/089) financed by Xunta de Galicia.

Potassium (K) deficiency has consequences not only on cellular ion balance and transmembrane potential but also on metabolism. In fact, several enzymes are K-dependent including enzymes in catabolism, causing an alteration in glycolysis and respiration. In addition, K deficiency is associated with the induction of specific pathways and accumulation of metabolic biomarkers, such as putrescine. However, such drastic changes are usually observed when K deficiency is established. Here, we carried out a kinetic analysis with metabolomics to elucidate early metabolic events when nutrient conditions change from K-sufficiency to K-deficiency in Arabidopsis rosettes from both wild type and mutants affected in both K absorption and low-K signalling (hak5 akt1 cipk23). Our results show that mutants have a metabolomics pattern similar to K-deficient wild-type, showing a constitutive metabolic response to low K. In addition, shifting to low K conditions induces (i) changes in sugar metabolism and (ii) an accumulation of salicylic acid metabolites before the appearance of biomarkers of K deficiency (putrescine and aconitate), and such an accumulation is more pronounced in mutants. Our results suggest that early events in the response to low K conditions involve salicylic acid metabolism., G.T. thank the Région Pays de la Loire and Angers Loire Métropole for its financial support via the grant Connect Talent Isoseed. We thank Sergio García for his skilful assistance. This work was funded by grant number 20806/PI/18 (to FR) from Fundación Séneca de la Región de Murcia, Spain, grant PID2019-106649RB-I00 from Ministerio de Ciencia e Innovación, Spain (to FR and MN-C). This work was also supported by the Red de Excelencia BIO2016-81957-REDT from Ministerio de Economía, Industria y Competitividad. All grants from Spanish ministries were co-financed by the FEDER Fund. MN-C, is recipient of a Ramón y Cajal Fellowship (RyC-2017-21924) from Ministerio de Economía y Competitividad, Spain

Major research efforts are being carried out for the technological advancement to an energetically sustainable society. However, for the full commercial integration of electrochemical energy storage devices, not only materials with higher performance should be designed and manufactured but also more competitive production techniques need to be developed. The laser processing technology is well extended at the industrial sector for the versatile and high throughput modification of a wide range of materials. In this work, a method based on laser processing is presented for the fabrication of hybrid electrodes composed of graphene nanowalls (GNWs) coated with different transition-metal oxide nanostructures for electrochemical capacitor (EC) applications. GNW/stainless steel electrodes grown by plasma enhanced chemical vapor deposition were decorated with metal oxide nanostructures by means of their laser surface processing while immersed in aqueous organometallic solutions. The pseudocapacitive nature of the laser-induced crystallized oxide materials prompted an increase of the GNW electrodes’ capacitance by 3 orders of magnitude, up to ca. 28 F/cm3 at 10 mV/s, at both the positive and negative voltages. Finally, asymmetric aqueous and solid-state ECs revealed excellent stability upon tens of thousands of charge–discharge cycles., The authors are grateful for the financial support of the Spanish Ministry of Economy, Industry, and Competitiveness under the projects ENE2017-89210-C2-1-R and ENE2017-89210-C2-2-R and support from AGAUR of Generalitat de Catalunya through projects 2017 SGR 1086. ICMAB acknowledges the financial support from the Spanish Ministry of Economy and Competitiveness, through the ‘Severo Ochoa’ Programme for Centres of Excellence in R&D (CEX2019-000917-S). Y.E.B acknowledges the financial support from CONACyT—Mexico through the postdoctoral scholarship granted 740661. P.G.L thanks the financial support of the Spanish Ministry of Economy, Industry, and Competitiveness through the grant BES-2017-081652 for the formation of scientific researchers. The authors acknowledge the support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).

The synthesis of novel organic prototypes combining different functionalities is key to achieve operational elements for applications in organic electronics. Here we set the stage towards individually addressable magneto-optical transducers by the on-surface synthesis of optically active manganese-phthalocyanine derivatives (MnPc) obtained directly on a metallic substrate. We created these 2D nanostructures under ultra-high vacuum conditions with atomic precision starting from a simple phthalonitrile precursor with reversible photo-induced reactivity in solution. These precursors maintain their integrity after powder sublimation and coordinate with the Mn ions into tetrameric complexes and then transform into MnPcs on Ag(111) after a cyclotetramerization reaction. Using scanning tunnelling microscopy and spectroscopy together with DFT calculations, we identify the isomeric configuration of two bi-stable structures and show that it is possible to switch them reversibly by mechanical manipulation. Moreover, the robust magnetic moment brought by the central Mn ion provides a feasible pathway towards magneto-optical transducer fabrication. This work should trigger further research confirming such magneto-optical effects in MnPcs both on surfaces and in liquid environments., We gratefully acknowledge financial support from the Spanish Ministries of Economy, Industry and Competitiveness (MINECO, grants MAT2016-78293-C6-4-R and MAT2016-78293-C6-6) and of Science and Innovation (MICINN, grant no. PID2019-107338RB-C62, PID2019-107338RB-C64, PID2019-107338RB-C66/AEI/10.13039/501100011033 and RED2018-102833-T), the regional Governments of Aragon (E13-20R and E12-20R), the Xunta de Galicia (Centro de Investigación de Galicia acreditation 2019–2022, ED431G 2019/03), the Dept. of Education of the Basque Government and UPV/EHU (grant no. IT1246-19), the Spanish Research Agency (AEI), the European Regional Development Fund (ERDF) under the program Interreg V-A España-Francia-Andorra (contract no. EFA194/16 TNSI) and the European Union through Horizon 2020 (FET-Open project SPRING grant. no. 863098)., We acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).

In Press., Understanding which proteins and RNAs directly interact is crucial for revealing cellular mechanisms of gene regulation. Efficient methods allowing to detect RNA-protein interactions and dissect the underlying molecular origin for RNA-binding protein (RBP) specificity are in high demand. The recently developed recombination-Y3H screening (rec-Y3H) enabled many-by-many detection of interactions between pools of proteins and RNA fragments for the first time. Here, we test different conditions for protein-RNA interaction selection during rec-Y3H screening and provide information on the screen performance in several selection media. We further show that rec-Y3H can detect the nucleotide and amino acid sequence determinants of protein-RNA interactions by mutating residues of interacting proteins and RNAs simultaneously. We envision that systematic RNA-protein interface mutation screening will be useful to understand the molecular origin of RBP selectivity and to engineer RBPs with targeted specificities in the future., This work was funded by the Spanish Ministry of Economy and Competitiveness (MINECO) [BFU2017-85361-P] and the National Research Foundation of Korea (NRF) funded by the Ministry of Education [2018R1A6A3A11045727]. We further acknowledge support of the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) to the EMBL partnership, the ‘Centro de Excelencia Severo Ochoa’ [SEV-2012-0208] and the CERCA Programme/Generalitat de Catalunya.

The comparison of non-caloric sweeteners (stevia and sucralose) and sucrose, on the plasma concentration and cumulative effects of phenolic compounds, was achieved. A long-term intervention, consisting of the daily intake of 330 mL of healthy citrus-maqui soft drinks, for 60 days, by 138 healthy overweight adults, was followed. A total of 24 bioavailable metabolites derived from caffeic acid, 3,4-di-hydroxyphenylacetic acid, eriodictyol, homoeriodictyol, hippuric acid, naringenin, 2,4,6-tri-hydroxybenzaldehyde, and vanillic acid were detected in peripheral blood plasma. A similar augment of bioactive compounds in plasma concentrations were found for the three beverages, in the range 12.3% (day 0)- 85.3% (day 60), depending on the analyte considered. Due to this, the present study highlights sucralose and stevia as valuable alternatives to sucrose, providing and non-significantly different plasma concentration and cumulative effect in the plasma, thus contributing to prevent a diversity of metabolic disorders and health constraints., This research was funded by the Spanish MINECO, grant number (AGL2016-75332-C2-1-R AEI / FEDER UE and PID2019-104212RB-I00/ AEI/ 10.13039 / 501100011033). VA was supported by an FPI grant (BES-2017-082424)

We introduce herein the advanced application of low-pressure plasma procedures for the development of piezo and triboelectric mode I hybrid nanogenerators. Thus, plasma assisted deposition and functionalization methods are presented as key enabling technologies for the nanoscale design of ZnO polycrystalline shells, the formation of conducting metallic cores in core@shell nanowires, and for the solventless surface modification of polymeric coatings and matrixes. We show how the perfluorinated chains grafting of polydimethylsiloxane (PDMS) provides a reliable approach to increase the hydrophobicity and surface charges at the same time that keeping the PDMS mechanical properties. In this way, we produce efficient Ag/ZnO convoluted piezoelectric nanogenerators supported on flexible substrates and embedded in PDMS compatible with a contact–separation triboelectric architecture. Factors like crystalline texture, ZnO thickness, nanowires aspect ratio, and surface chemical modification of the PDMS are explored to optimize the power output of the nanogenerators aimed for harvesting from low-frequency vibrations. Just by manual triggering, the hybrid device can charge a capacitor to switch on an array of color LEDs. Outstandingly, this simple three-layer architecture allows for harvesting vibration energy in a wide bandwidth, thus, we show the performance characteristics for frequencies between 1 Hz and 50 Hz and demonstrate the successful activation of the system up to ca. 800 Hz.

13 Páginas.-- 3 Figuras.-- 3 Tablas, The aim of this study was to determine whether hydroxytyrosol administration prevented kidney damage in an experimental model of type 1 diabetes mellitus in rats. Hydroxytyrosol was administered to streptozotocin-diabetic rats: 1 and 5 mg/kg/day p.o. for two months. After hydroxytyrosol administration, proteinuria was significantly reduced (67-73%), calculated creatinine clearance was significantly increased (26-38%), and the glomerular volume and glomerulosclerosis index were decreased (20-30%). Hydroxytyrosol reduced oxidative and nitrosative stress variables and thromboxane metabolite production. Statistical correlations were found between biochemical and kidney function variables. Oral administration of 1 and 5 mg/kg/day of hydroxytyrosol produced an antioxidant and nephroprotective effect in an experimental model of type 1-like diabetes mellitus. The nephroprotective effect was significantly associated with the systemic and renal antioxidant action of hydroxytyrosol, which also influenced eicosanoid production., This study was supported in part by the Consejería de Salud. Junta de Andalucía (Spain), Proyectos de Investigación en Salud (Regional Ministry of Health. Junta de Andalucía (Spain), Health Research Projects) (PI-0129-2017) and by Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness) (Spain), Centro para el Desarrollo Tecnológico Industrial (Center for the Development of Industrial Technology), FEDER Interconecta Pluri-Regional Program (Spain), (PS17173. NUTRADAF, ITC-20161265).

Over the years, human adenovirus (HAdV) has progressively been recognized as a significant viral pathogen. Traditionally associated with self-limited respiratory, gastrointestinal, and conjunctival infections, mainly in immunocompromised patients, HAdV is currently considered to be a pathogen presenting significant morbidity and mortality in both immunosuppressed and otherwise healthy individuals. Currently available therapeutic options are limited because of their lack of effectivity and related side effects. In this context, there is an urgent need to develop effective anti-HAdV drugs with suitable therapeutic indexes. In this work, we identified new serinol-derived benzoic acid esters as novel scaffolds for the inhibition of HAdV infections. A set of 38 compounds were designed and synthesized, and their antiviral activity and cytotoxicity were evaluated. Four compounds (13, 14, 27, and 32) inhibited HAdV infection at low micromolar concentrations (2.82–5.35 μM). Their half maximal inhibitory concentration (IC50) values were lower compared to that of cidofovir, the current drug of choice. All compounds significantly reduced the HAdV DNA replication process, while they did not block any step of the viral entry. Our results showed that compounds 13, 14, and 32 seem to be targeting the expression of the E1A early gene. Moreover, all four derivatives demonstrated a significant inhibition of human cytomegalovirus (HCMV) DNA replication. This new scaffold may represent a potential tool useful for the development of effective anti-HAdV drugs., This work has been supported by Ministerio de Ciencia, Innovación y Universidades, Plan Estatal 2017-2020 Retos-Proyectos I+D+i (PID2019-104767RB-I00), Ministerio de Economı́a y Competitividad, Plan Estatal 2013-2016 Retos-Proyectos I + D + i (CTQ2016-78580-C2-2-R) and by Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economia, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009), cofinanced by European Development Regional Fund “A way to achieve Europe”, the Instituto de Salud Carlos III, Proyectos de Investigación en Salud (PI17/01055; PI18/01191) and Proyectos de Desarrollo Tecnológico en Salud (DTS17/00130), the Spanish Adenovirus Network (AdenoNet, BIO2015/68990-REDT), and the program “Nicolás Monardes” (C-0059-2018), Servicio Andaluz de Salud, Junta de Andalucía. M.V.-H. also thanks Ministerio de Economı́a y Competitividad, Plan Estatal 2013-2016 Excelencia I+D+i (CTQ2016-78703-P).

Understanding the mechanism of molecular dissociation under applied bias is a fundamental requirement to progress in (electro)-catalysis as well as in (opto)-electronics. The working conditions of a molecular-based device and the stability of chemical bonds can be addressed in metal–organic junctions by injecting electrons in tunneling conditions. Here, we have correlated the energy of de-bromination of an aryl group with its density of states in a self-assembled dimeric structure of 4′-bromo-4-mercaptobiphenyl adsorbed on a Au(111) surface. We have observed that the electron-energy range where the molecule is chemically stable can be extended, shifting the bias threshold for the rupture of the –C–Br bond continuously from about 2.4 to 4.4 V by changing the electron current. Correspondingly, the power needed for the dissociation drops sharply at 3.6 V, identifying different reaction regimes and the contribution of different molecular resonance states., A.B. acknowledges Vicerrectorado de Investigacion of the University of the Basque Country (UPV/EHU) for the PhD fellowship (2016). R.R. and N.L. are grateful for the computer resources at Finisterrae II, the technical support provided by CESGA and the EU-FET Open H2020 Mechanics with Molecules project (grant 766864). A.B. and L.V. acknowledge the funding of Spanish Ministry of Economy, Industry and Competitiveness (MINECO Grant number MAT2016-78293-C6-5-R); Diputacion Foral de Guipuzcoa (Red/Sarea 2020-CIEN-000009-01), and the Basque Government (Proyectos de Investigación Básica y/o Aplicada grant number PIBA-2021-0026).

The presence of antibiotics in soils may increase the selection pressure on soil bacterial communities and cause tolerance to these pollutants. The temporal evolution of bacterial community tolerance to different concentrations of tetracycline (TC), oxytetracycline (OTC) and chlortetracycline (CTC) was evaluated in two soils. The results showed an increase of soil bacterial community tolerance to TC, CTC and OTC only in samples polluted with the highest antibiotic concentrations tested (2000 mg kg−1). The magnitude of those increases was higher in the soil with the lower organic carbon content (1.6%) than in the soil with an organic carbon content reaching 3.4%. In the soil with low organic carbon content, the time-course evolution showed a maximum increase in the tolerance of bacterial communities to tetracycline antibiotics between 45 and 100 incubation days, while for longer incubation times (360 days) the tolerance decreased. In the soil with high organic carbon content, a similar behavior was found for OTC. However, for CTC and TC, slightly increases and decreases (respectively) were found in the bacterial community tolerance at intermediate incubation times, followed by values close to zero for TC after 360 days of incubation, while for CTC they remained higher than in the control. In conclusion, soil pollution due to tetracyclines may cause bacterial community tolerance to these antibiotics when present at high concentrations. In addition, the risk is higher in soils with low organic matter content, and it decreases with time., This study has been funded by the Spanish Ministry of Economy and Competitiveness through the projects CGL 2015-67333-C2-1-R and -2-R (FEDER Funds) and by Xunta de Galicia via BV1 research group (ED431C 2017/62-GRC). David Fernández Calviño holds a Ramón y Cajal contract (RYC-2016-20411) financed by the Spanish Ministry of Economy, Industry and Competitiveness. Vanesa Santás-Miguel and Laura Rodríguez González holds a pre-doctoral fellowship (ED481A-2020/089 and ED481A-2021/309, respectively) financed by Xunta de Galicia.

The optimization of conditions to promote the stemness of pluripotent cells in vitro is instrumental for their use in advanced therapies. We show here that exposure of human iPSCs and human ESCs to low concentrations of the chemical NO donor DETA/NO leads to stabilization of hypoxia-inducible factors (HIF-1α and HIF-2α) under normoxia, with this effect being dependent on diminished Pro 402 hydroxylation and decreased degradation by the proteasome. Moreover, the master genes of pluripotency, NANOG and OCT-4, were upregulated. NO also induces a shift in the metabolic profile of PSCs, with an increased expression of hypoxia response genes in glycolysis. Furthermore, a reduction in the mitochondrial membrane potential with lower oxygen consumption and increased expression of mitochondrial fusion regulators, such as DRP1, was observed. The results reported here indicate that NO mimics hypoxia response in human PSCs and enhances their stemness properties when cultured under normoxic conditions.

15 Páginas.-- 3 Tablas.-- 6 Figuras, Hydroxytyrosol (HT) is the component primarily responsible for the neuroprotective effect of extra virgin olive oil (EVOO). However, it is less effective on its own than the demonstrated neuroprotective effect of EVOO, and for this reason, it can be postulated that there is an interaction between several of the polyphenols of EVOO. The objective of the study was to assess the possible interaction of four EVOO polyphenols (HT, tyrosol, dihydroxyphenylglycol, and oleocanthal) in an experimental model of hypoxia–reoxygenation in rat brain slices. The lactate dehydrogenase (LDH) efflux, lipid peroxidation, and peroxynitrite production were determined as measures of cell death, oxidative stress, and nitrosative stress, respectively. First, the polyphenols were incubated with the brain slices in the same proportions that exist in EVOO, comparing their effects with those of HT. In all cases, the cytoprotective and antioxidant effects of the combination were greater than those of HT alone. Second, we calculated the concentration–effect curves for HT in the absence or presence of each polyphenol. Tyrosol did not significantly modify any of the variables inhibited by HT. Dihydroxyphenylglycol only increased the cytoprotective effect of HT at 10 μM, while it increased its antioxidant effect at 50 and 100 μM and its inhibitory effect on peroxynitrite formation at all the concentrations tested. Oleocanthal increased the cytoprotective and antioxidant effects of HT but did not modify its inhibitory effect on nitrosative stress. The results of this study show that the EVOO polyphenols DHPG and OLC increase the cytoprotective effect of HT in an experimental model of hypoxia–reoxygenation in rat brain slices, mainly due to a possibly synergistic effect on HT’s antioxidant action. These results could explain the greater neuroprotective effect of EVOO than of the polyphenols alone., This study was supported in part by Consejería de Salud—Junta de Andalucía (Spain), Proyectos de Investigación en Salud (PI-0129-2017), and by Ministerio de Economía y Competitividad (Spain), Centro para el Desarrollo Tecnológico Industrial, Programa FEDER Interconecta Pluri-Regional (PS17173. NUTRADAF, ITC-20161265).

Carbon dioxide (CO2) plays a key role in controlling the temperature of the Earth. But the increase in the concentration of CO2 in the atmosphere brings with it a series of consequences, originating several environmental problems. The use of electrochemical, spectroscopic and molecular dynamics techniques are useful toolkits to valorize carbon dioxide, and to know the reduction mechanism as a function of CO2 concentration, the cathode nature, and the electrolyte. This manuscript will be mainly centered in the use of ionic liquids (IL) for efficient CO2 capture and valorization into different valuable products thanks to the CO2 electrochemical reduction. In this sense, spectroelectrochemistry based on cyclic voltammetry coupled with Polarization Modulation-Infrared Reflection-Absorption Spectroscopy (PM-IRRAS) and Infrared Reflection-Absorption Spectroscopy (IRRAS) appear to be an efficient instrument to follow the CO2 reactivity in imidazolium ionic liquids. Finally, we present molecular dynamics paired with cyclic voltammetry in order to calculate the diffusion coefficient of CO2 and the number of electrons involved in its reduction process, respectively. Therefore, the current research opens the door to the use of theoretical-experimental approaches altogether to determine how is the CO2 reduction mechanism. The CO2 reduction products in function of the solvent and nature of the cathode is suggested, proving that the product obtained from the electrochemical reduction of CO2 depends on the electrode material and the solvent., The authors thank the Ministerio de Ciencia e Innovación of Spain for financial support though the projects CTQ 2015-65439-R and PID2019-106171RB-I00. SM acknowledges the Autonomous University of Barcelona for her predoctoral PIF grant. SKS thanks the University of Iowa Department of Chemistry for support of this project. The invitation by the E3TECH Spanish Network of Excellence (CTQ2017-90659-REDT (MEIC/AEI)) is also kindly acknowledged. JF acknowledges CESGA supercomputing center for computer time and technical support at the Finisterrae supercomputer and financial support from MINECO Severo Ochoa programme, Grant CEX2019-000917-S. We thank Dr Piotr Kubisiak for sharing his datafiles with us.

The effect of oil droplet size (ODS) on the oxidative stability (OS) of dried microencapsulated oils has been scarcely studied, and results are contradictory. A few studies have shown increased OS when the ODS was reduced and this was attributed to a decrease in the surface oil content (SOC). Yet, in such studies, only the total oil fraction was evaluated. In the present work, the free (FO) and encapsulated oil (EO) fractions of freeze‐dried microencapsulated sunflower oil were analysed to study the effect of changes in the ODS by using different homogenisation pressure (15 or 70 MPa) in the emulsification step. The OS of both the free and encapsulated fractions increased when the ODS was significantly reduced in two samples with different encapsulation matrix, namely caseinate/lactose and maltodextrin/sucrose/gelatine. A reduction in the SOC would explain the increased stability of the FO, but not that of the EO. An additional protective role of the interfacial film could have been involved. In conclusion, if the encapsulation matrix and the interfacial region are effective as oxygen barriers, a reduction in the ODS of the parent emulsion by an increase in the homogenisation pressure will result in capsules more stable against lipid oxidation., This work was funded by the Spanish Ministry of Economy, Industry and Competitiveness through project AGL2013‐45110‐R.

Peri-urban agriculture provides environmental benefits to the nearby urban areas. However, domestic and industrial infrastructures can be sources of pollution that can affect agricultural production. In this work, the diffusive gradient in thin film (DGT) technique was used to assess the bioavailability of mercury (Hg) in organic-amended agricultural soils, and uptake by lettuce. Two different amendments were studied individually in three different sets using a wood-based biochar at two rates (3% and 6%, w/w), and compost at one rate (30% w/w). The effect of the amendments on Hg bioavailability, mobility and uptake was investigated by means of both DGT analyses and accumulation of Hg by lettuce. DGT manufactured in-house devices with polyacrylamide gel using both open and restricted diffusive layers (ODL and RDL, respectively) were used to determine organic and inorganic Hg labile species in soils, respectively. The Hg concentration in lettuce leaves and roots were analyzed and compared with DGT measurements to predict the uptake of Hg from the different organic-amended soils and the non-amended soils. Results show that the application of biochar reduces the bioavailability of Hg in soil and, in consequence, the Hg uptake by lettuce. Inorganic Hg species were predominant in all the different sets of the experiment (62–97%), although the addition of the different amendments reduced the free ionic species in soil. © 2019, The authors gratefully acknowledge the financial support of the Spanish Ministry of Economy, Industry, and Competitiveness (MEIC) through Project AGL2017-89518-R and CTM2016-78798-C2-2-P (AEI/FEDER/UE). The authors would further like to thank the officers and farmers of the Baix Llobregat Agrarian Park for their assistance, as well as Ms. Yolanda Rodríguez and Ms. Rui You for their technical assistance with the sampling and sample preparation.

12 páginas.- 8 figuras.- 52 referencias.- Suplemental data in http://www.plantphysiol.org/content/suppl/2019/05/03/pp.19.00255.DC1, Recent investigations have revealed that, in addition to monolignols, some phenolic compounds derived from the flavonoid and hydroxystilbene biosynthetic pathways can also function as true lignin monomers in some plants. In this study, we found that the hydroxystilbene glucosides isorhapontin (isorhapontigenin-O-glucoside) and, at lower levels, astringin (piceatannol-O-glucoside) and piceid (resveratrol-O-glucoside), are incorporated into the lignin polymer in Norway spruce (Picea abies) bark. The corresponding aglycones isorhapontigenin, piceatannol, and resveratrol, along with glucose, were released by derivatization followed by reductive cleavage (DFRC), a chemical degradative method that cleaves β-ether bonds in lignin, indicating that the hydroxystilbene glucosides are (partially) incorporated into the lignin structure through β-ether bonds. 2D-NMR analysis confirmed the occurrence of hydroxystilbene glucosides in this lignin, and provided additional information regarding their modes of incorporation into the polymer. The hydroxystilbene glucosides, particularly isorhapontin and astringin, can therefore be considered genuine lignin monomers that participate in coupling and cross-coupling reactions during lignification in Norway spruce bark., J.C.d.R, J.Re., G.M. and A.G. were funded by the Spanish projects CTQ2014-60764-JIN and AGL2017-83036-R (financed by Ministerio de Economía y Competitividad, Agencia Estatal de Investigación, AEI, and Fondo Europeo de Desarrollo Regional, FEDER), and the CSIC project 2014-40E-097; J.Ra. and H.K. were funded by the DOE Great Lakes Bioenergy Research Center (DOE BER Office of Science DE-SC0018409); J.G. and H.P. were funded by Fundação para a Ciência e a Tecnologia (FCT) under UID/AGR/00239/2013; D.N. was funded by FCT through a PhD scholarship (PD/BD/52697/2014) under the SUSFOR doctoral program.

7 páginas.- 3 figuras.- 2 tabla.- 30 referencias, [ES]: Containerized ornamental plant production is facing several environmental challenges. One of them is to replace the widely used, but with questionable sustainability, peat based substrates and another is to avoid water contamination by chemicals leaching from the nursery. Therefore, as have been verified that petunia and pelargonium plants can be produced in peat-based growing media partially replaced by vermicompost (V) and biochar (B) without decreasing commercial quality, this study has focused on analyzing the leachate from a standard peat-based substrate as a control, used for producing these two ornamental species, and those from the same substrate to which different proportions in volume of V (10% and 20%) and B (4% and 12%) have been added. The amount of nitrogen leached from the mixed substrates was reduced compared to the control one in both species (on average 37%). Nitrogen was leached mainly as nitrate-nitrogen (89% in Petunia and 97% in Pelargonium). In Petunia phosphorous leaching was also decreased (30%) for the treatment with 10% V and 4% B, while potassium leaching in substrate containing 20% V and 12% B increased by 100%. Our results show that these two organic materials tested (V and B) can help producers to reduce the use of peat and chemical fertilizers as well as the risk of contamination by chemicals, mainly nitrate., [PO]: A produção de plantas ornamentais em contêineres está enfrentando vários desafios ambientais. Um deles é substituir os substratos amplamente utilizados, mas com sustentabilidade questionável, baseados em turfa, e outro é evitar a contaminação da água por produtos químicos lixiviados do viveiro. Verificou-se que as plantas de petúnia e gerânio podem ser produzidas em meios de crescimento baseados em turfa parcialmente substituídos por vermicomposto (V) e biochar (B) sem diminuir a sua qualidade comercial. Este estudo concentrou-se na análise do lixiviado de uma turfa padrão como controle, utilizado para a produção destas duas espécies ornamentais, e o mesmo substrato ao qual foram adicionados diferentes proporções em volume de V (10% e 20%) e B (4% e 12%). Verificou-se que a quantidade de nitrogenio lixiviado dos substratos misturados foi reduzida em comparação com a testemunha em ambas as espécies (em média 37%). O nitrogênio foi lixiviado principalmente como nitrato-nitrogênio (89% em Petunia e 97% em Pelargonium). Na Petunia a lixiviação de fósforo também foi reduzida (30%) para o tratamento com 10% de V e 4% de B, enquanto a lixiviação de potássio em substrato contendo 20% de V e 12% de B aumentou em 100%. Nossos resultados mostram que esses dois materiais orgânicos testados (V e B) podem ajudar os produtores a reduzir o uso de turfa e fertilizantes químicos, bem como diminuir o risco de contaminação por substâncias químicas, principalmente nitrato., This work was partially supported by the project CTQ 2013-46804-C2-1-R, CTQ 2017-85251-C2-2-R and CGL2016-76498-R of the Spanish Ministry of Economy and Competitiveness and the European Regional Development Funds (ERDF)

The present paper evaluates the efficiency of sustainable activated carbons obtained from the valorization of lignocellulosic waste in removing siloxanes and volatile organic compounds for the purification of anaerobic digester biogas. Pyrolized and non-pyrolized lignocellulosic residues generated in food and wood industries were used as precursor materials to obtain experimental adsorbents by a chemical activation process using several activating agents. The highest porosity was obtained by non-pyrolized residue activated by K2CO3 at 900 °C. The performance of the experimental materials was compared with that of commercial activated carbons in gas adsorption tests of siloxanes (octamethylcyclotetrasiloxane and hexamethyldisiloxane) and volatile organic compounds (toluene and limonene). The waste-based activated carbons developed in this work proved to be more efficient for the removal of both siloxanes and VOCs than the commercial samples in most of the conditions tested. Adsorption capacities correlated with porosity, while the more relevant pore size depends on the adsorbate., This work was funded by MINECO – Spain (CTQ2014-53718-R) co-funded by FEDER and University of Girona. Eric Santos-Clotas thanks Universitat de Girona for his predoctoral grant (IFUdG-2015/51). Alba Cabrera-Codony acknowledges support from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 712949 (TECNIOspring PLUS) and from the Agency for Business Competitiveness of the Government of Catalonia (TECSPR16-1-0045). LEQUIA has been recognized as consolidated research group by the Catalan Government (2017-SGR-1552).

Compared to the replication of double-stranded RNA and DNA viruses, the replication of single-stranded viruses requires the production of a number of intermediate strands that serve as templates for the synthesis of genomic-sense strands. Two theoretical extreme mechanisms for replication for such single-stranded viruses have been proposed; one extreme being represented by the so-called linear stamping machine and the opposite extreme by the exponential growth. Of course, real systems are more complex and examples have been described in which a combination of such extreme mechanisms can also occur: a fraction of the produced progeny resulting from a stamping-machine type of replication that uses the parental genome as template, whereas other fraction of the progeny results from the replication of other progeny genomes. Martínez et al., Sardanyés et al. and Fornés et al. suggested and analyzed a deterministic model of single-stranded RNA (ssRNA) virus intracellular replication that incorporated variability in the replication mechanisms. To explore how stochasticity can affect this mixed-model principal properties, in this paper, we consider the stability of a stochastically perturbed model of ssRNA virus replication within a cell. Using the direct Lyapunov method, we found sufficient conditions for the stability in probability of equilibrium states for this model. This result confirms that this heterogeneous model of single-stranded RNA virus replication is stable with respect to stochastic perturbations of the environment., Leonid Shaikhet is supported by the Israel Science Foundation via grant No. 1128/14 and the Israeli Ministry of Absorption. Santiago F. Elena is supported by Spain's Ministerio de Economía, Industria y Competitividad grant BFU2015-65037-P and by Generalitat Valenciana grant PROMETEOII/2014/021. Andrei Korobeinikov is supported by the Spain's Ministerio de Economía, Industria y Competitividad grant MTM2015-71509-C2-1-R.

Plants respond to the loss of vertical growth re-orientating their affected organs. In trees, this phenomenon has received the scientific attention due to its importance for the forestry industry. Nowadays it is accepted that auxin distribution is involved in the modulation of the tilting response, but how this distribution is controlled is not fully clear. Auxin transporters that determine the spatio-temporal auxin distribution in radiate pine seedlings exposed to 45° of tilting were identified. Additionally, based on indications for an intimate plant hormone crosstalk in this process, IAA and JA contents were evaluated. The experiments revealed that expression of the auxin transporters was down-regulated in the upper half of the tilted stem, while being induced in the lower half. Moreover, transporter-coding genes were first induced at the apical zone of the stem. IAA was consistently redistributed toward the lower half, which is in accordance with the expression profile of the auxin transporters. In contrast, JA was mainly accumulated in the upper half of tilted stems. Finally, lignin content and monomeric composition were analyzed in both sides of stem and along the time course of tilting. As expected, lignin accumulation was higher at the lower half of stem at longer times of tilting. However, the most marked difference was the accumulation of the H-lignin monomer in the lower half, while the G-lignin unit was more dominant in the upper half. Here, we provide detailed insight in the distribution of IAA and JA, affecting the lignin composition during the tilting response in Pinus radiata seedlings., FONDECYT #11121170 supported this work. P. Ramos acknowledges ‘Núcleo Científico Multidisciplinario’ from Universidad de Talca. S. Pollmann is supported by project BFU2014-55575-R by the Spanish Ministry of Economy, Industry and Competitiveness (MINECO). David Caparrós-Ruiz was supported by the Spanish Ministry of Economy and Competitiveness (AGL2014-58126-R and SEV-2015-0533 from the Severo Ochoa Programme for Centres of Excellence in R&D 2016–2019) and by CERCA Programme/Generalitat de Catalunya, and the Suport a Grups de Recerca Programme (SGR2014-1434) from the Autonomous Government of Catalonia.

The influence of high-pressure processing (HPP) (400, 500 and 600 MPa at 35 °C for 5 min) on different classes of phenolic compounds and antioxidant activity (AA) of ‘Golden Delicious’ apple from two different growing regions, northeastern of Spain (lowland climate) (S-apples) and north of Italy (mid-mountain climate) (I-apples) was investigated. Total hydroxycinnamic acids, total dihydrochalcones and total flavan-3-ols content were higher in S-apple (untreated and HPP-treated) than in I-apples and total flavonols content was higher in I-apples. HPP affected phenolic compounds and AA depending on the apple geographical origin. 400 MPa/35 °C/5 min increased total flavonols (30%) and maintained total phenolic compounds determined by HPLC (TP-HPLC) in S-apples. The higher increase of TP-HPLC (54%) was achieved when I-apple was treated at 600 MPa. Untreated and HPP-treated I-apples displayed higher AA than S-apples. HPP (400 and 600 MPa) increased AA in I-apple. Positive correlations were found between TP-HPLC and AA (TP-FC, DPPH·, ABTS·+ and FRAP) in both Italian and Spanish apples., This study has been funded by the Spanish projects AGL2013-46326-R and AGL2016-76817-R (Ministry of Economy, Industry and Competitiveness).

22 Páginas; 5 Figuras; 3 Tablas, Food nutritional labeling is compulsory in the European Union since 13 December 2016. The olive oil fatty acid composition shows high variation depending mainly on the variety. Thus, olive oil nutritional labeling is problematic for the industry. Besides, the analysis of all batches of olive oil using the official methods is expensive. Therefore, the olive oil industry is seriously concerned about solutions for nutritional labeling. In this study, a new rapid technique to measure the nutrients for the olive oil nutritional labeling, is assessed. A novel partial least squares (PLS) calibration model using log-ratio coordinates has been formulated and successfully tested for predicting the percentages of monounsaturated, saturated, and polyunsaturated fatty acids based on visible and near infrared spectroscopy. The model provided accuracy suitable for labeling, under the rules in force in the European Union. The error was generally much lower than the tolerance., J. A. Cayuela expresses gratitude to the European Regional Development Fund, aswell to the Ministry of Economy and Competitiveness of Spain for funding parts of this study, which was developed within the project Recupera 2020 1.4.4., and to the Spanish Council for Scientific Research, for co-funding the grant 20137R065 corresponding to this project. J. Palarea-Albaladejo was partly supported by the Scottish Government's Rural and Environment Science and Analytical Services Division (RESAS) and by the Spanish Ministry of Economy and Competitiveness under the project CODA-RETOS MTM2015-65016-C2-1(2)-R.

[Background]: Colorectal cancer (CRC) is the second most common cause of cancer death worldwide. It is broadly described that cyclooxygenase-2 (COX-2) is mainly overexpressed in CRC but less is known regarding post-translational modifications of this enzyme that may regulate its activity, intracellular localization and stability. Since metabolic and proteomic profile analysis is essential for cancer prognosis and diagnosis, our hypothesis is that the analysis of correlations between these specific parameters and COX-2 state in tumors of a high number of CRC patients could be useful for the understanding of the basis of this cancer in humans., [Aim]: To analyze COX-2 regulation in colorectal cancer and to perform a detailed analysis of their metabolic and proteomic profile., [Methods]: Biopsies from both healthy and pathological colorectal tissues were taken under informed consent from patients during standard colonoscopy procedure in the University Hospital of Bellvitge (Barcelona, Spain) and Germans Trias i Pujol University Hospital (Campus Can Ruti) (Barcelona, Spain). Western blot analysis was used to determine COX-2 levels. Deglycosylation assays were performed in both cells and tumor samples incubating each sample with peptide N-glycosidase F (PNGase F). Prostaglandin E2 (PGE2) levels were determined using a specific ELISA. 1H high resolution magic angle spinning (HRMAS) analysis was performed using a Bruker AVIII 500 MHz spectrometer and proteomic analysis was performed in a nano-liquid chromatography-tandem mass spectrometer (nano LC-MS/MS) using a QExactive HF orbitrap MS., [Results]: Our data show that COX-2 has a differential expression profile in tumor tissue of CRC patients vs the adjacent non-tumor area, which correspond to a glycosylated and less active state of the protein. This fact was associated to a lesser PGE2 production in tumors. These results were corroborated in vitro performing deglycosylation assays in HT29 cell line where COX-2 protein profile was modified after PNGase F incubation, showing higher PGE2 levels. Moreover, HRMAS analysis indicated that tumor tissue has altered metabolic features vs non-tumor counterparts, presenting increased levels of certain metabolites such as taurine and phosphocholine and lower levels of lactate. In proteomic experiments, we detected an enlarged number of proteins in tumors that are mainly implicated in basic biological functions like mitochondrial activity, DNA/RNA processing, vesicular trafficking, metabolism, cytoskeleton and splicing., [Conclusion]: In our colorectal cancer cohort, tumor tissue presents a differential COX-2 expression pattern with lower enzymatic activity that can be related to an altered metabolic and proteomic profile., MINECO, No. SAF2017-82436R, SAF2016-75004R, RTC-2017-6283-1, PRB3 (IPT17/0019-ISCIII-SGEFI/ERDF) and BIO2015-67580P; Comunidad de Madrid, No. S2017/BMD-3686; Fundación Ramón Areces, No. 2016/CIVP18A3864; Instituto de Salud Carlos III, Spain, CIBERCV, No. CB/11/00222 and CB16/11/00277; FEDER, CIBEREHD; the Ministerio de Ciencia, Innovación y Universidades (MCNU); the Pro CNIC Foundation; and Severo Ochoa Center of Excellence, No. SEV-2015-0505.

Here, we present an exploratory study on the fluorous-assisted synthesis of chondroitin sulfate (CS) oligosaccharides. Following this approach, a CS tetrasaccharide was prepared. However, in contrast to our previous results, a significant loss of β-selectivity was observed in [2 + 2] glycosylations involving N-trifluoroacetyl-protected D-galactosamine donors and D-glucuronic acid (GlcA) acceptors. These results, together with those obtained from experiments employing model monosaccharide building blocks, highlight the impact of the glycosyl acceptor structure on the stereoselectivity of glycosylation reactions. Our study provides useful data about the substitution pattern of GlcA units for the efficient synthesis of CS oligomers

Sugar alcohols, such as xylitol, sorbitol and inositols, are added-value carbohydrates with relevant bioactive and technological properties. These features make their extraction from natural sources of great interest both from the scientific and industrial points of view. However, due to the similarity of the chemical structures of the different carbohydrates and the complexity of the extracted mixtures, the subsequent isolation of these sugar alcohols from other coextracted low molecular weight carbohydrates (LMWC) is still considered a challenging task. In this article, the solubility of linear sugar alcohols and inositols in selected ionic liquids (ILs), i.e., 1-hexyl-3-methylimidazolium chloride ([HMIM][Cl]), 1-ethyl-3-methylimidazolium dicyanamide ([EMIM][DCA]), 1-ethyl-3-methylimidazolium acetate ([EMIM][OAc]) and 1,3-dimethylimidazolium dimethylphosphate ([MMIM][MePO]), has been investigated. The experimental results demonstrated widely divergent solubilities (in the 1.7–84.7%, w/w, range) for the several targeted carbohydrates in the different ILs evaluated, with [EMIM][OAc] and [MMIM][MePO] providing the highest solubility values. These ILs gave also the best results when applied to the selective fractionation of sugar alcohols from other LMWC in 1:1 (w/w) binary mixtures (yields in the 60–98% range). These results show ILs as promising non-volatile and environmental friendly solvents for this type of fractionation process and suggest the interest of further investigation in this particular application field., This work has been funded by Fundación Ramón Areces (project CIVP17A2843), by Ministerio de Economía y Competitividad (project CTQ2012-32957) and by Ministerio de Economía, Industria y Competitividad (MINECO) of Spain (project AGL2016-80475-R, AEI/ FEDER, UE). Authors also thank financial support from the Comunidad Autónoma of Madrid and European funding from FEDER program (project S2013/ABI-3028, AVANSECAL).

[EN] The purpose of this work is to fabricate self-assembled microstructures by the sol–gel method and study the morphological, structural and compositional dependence of 3-Fe2O3 nanoparticles embedded in silica when glycerol (GLY) and cetyl-trimethylammonium bromide (CTAB) are added as steric agents simultaneously. The combined action of a polyalcohol and a surfactant significantly modifies the morphology of the sample giving rise to a different microstructure in each of the studied cases (1, 3 and 7 days of magnetic stirring time). This is due to the fact that the addition of these two compounds leads to a considerable increase in gelation time as GLY can interact with the alkoxide group on the surface of the iron oxide precursor micelle and/or be incorporated into the hydrophilic chains of CTAB. This last effect causes the iron oxide precursor micelles to be interconnected forming aggregates whose size and structure depend on the magnetic stirring time of the sol–gel synthetic route. In this paper, crystalline structure, composition, purity and morphology of the sol–gel coatings densified at 960 ºC are examined. Emphasis is placed on the nominal percentage of the different iron oxides found in the samples and on the morphological and structural differences. This work implies the possibility of patterning 3-Fe2O3 nanoparticles in coatings and controlling their purity by an easy one-pot sol–gel method., Spanish Ministry of Industry, Economy and Competitiveness for financing the project MAT2015-65445-C2-1-R, MAT2017-86450-C4-1-R, MAT2015-67557-C2-1-P, by the Comunidad de Madrid S2013/MIT-2850 NANOFRONTMAG and H2020 AMPHIBIAN Project ID: 720853. The authors are also grateful to the BM25-SpLine staff for their valuable technical support beyond their duties and for the financial support from the Spanish Ministry of Science, Innovation and Universities (MICIU) and The Spanish National Research Council (CSIC) under Grant No. PIE 2010- 6OE-013, The ESRF – The European Synchrotron, MICIU and CSIC are acknowledged for provision of synchrotron radiation facilities. A. S. acknowledges the Financial support from the Comunidad de Madrid for an “Atracción de Talento Investigador” contract (No. 2017-t2/IND5395).

This Article constitutes part of the PhD thesis of Claudia Torno., The replacement of the finite and costly resource fish oil is an important task for aquaculture nutrition. A promising approach could be the use of plant bioactives that may have the potential to influence the metabolism and the synthesis of n-3 long chain polyunsaturated fatty acids, especially EPA (20:5n-3) and DHA (22:6n-3). In this study, the two phytochemicals resveratrol (RV) and genistein (G) were investigated for their effects on fish growth, nutrient utilization and body nutrient composition alongside their effects on whole body fatty acid (FA) composition. In a feeding trial lasting 8 weeks, rainbow trout (initial BW: 81.4±0.5 g) were held in a recirculating aquaculture system and fed six experimental diets with varying fish oil levels as plain variants or supplemented with 0.3% of dry matter (DM) of either RV or G. The six diets were as follows: diet F4 had 4% DM fish oil, diet F0 had 0% DM fish oil, diets F4+RV, F4+G, F0+RV and F0+G were equal to the diets F4 and F0, respectively, and supplemented with the phytochemicals RV and G. The feeding of the F0+RV diet resulted in reduced feed intake, growth rate and slightly reduced whole body lipid levels. At the same time, the amount of polyunsaturated FA and the n-3/n-6 ratio were significantly increased in whole body homogenates of rainbow trout fed diet F0+RV in comparison to the F0 control. The feeding of the F0+G diet led to reduced feed intake, slightly increased protein utilization but did not significantly affect the whole body FA composition. Overall, feeding the fish oil-free diet supplemented with the phytochemicals resulted in more pronounced effects on fish performance and FA composition than the single factors per se (dietary fish oil level or phytochemical). Present data indicate that G might not be of profitable use for trout nutrition. In terms of FA composition, RV could be a potentially useful complement for fish oil. However, the impairment of growth and performance parameters as observed in the present study discourages its use in trout diets., This work was supported by the DFG – Deutsche Forschungsgemeinschaft (grant nos: RI 884/8-1; SCHU 2308/4-1). We are grateful to the Analysis Service Unit facilities of ICTAN for the GC-FID analysis and Spanish Ministerio de Economía, Industria y Competitividad for grant AGL2016-76832-R.

Microstructure, viscosity and their relationship with bioaccessibility of phenolic compounds in onion and apple products (untreated and HPP) and commercial quercetin supplement throughout a dynamic gastrointestinal digestion (GID) model were investigated. In non-digested (ND) samples, untreated and HPP-onion presented higher total phenolic and flavonol content (TFC-HPLC and TPC-FC) than apple counterparts. TFC-HPLC decreased throughout GID phases in all samples studied. TFC-HPLC bioaccessibility was higher in onion (~17.6%) than in apple (~10%) and in quercetin supplement (0.027%). HPP did not improve TFC-HPLC bioaccessibility. Throughout GID, onion and apple showed a significant decrease in both consistency (K) and apparent viscosity at 10 s−1 but higher values were found in apple. These data agree with TFC-HPLC and TPC-FC decrease and with the lower bioaccessibilities of apple compared with onion. Food matrix had a more significant effect than HPP on TFC-HPLC bioaccessibility, which is related to the rheological behavior of the GID-phases., This study has been funded by the Spanish projects AGL2013-46326-R and AGL2016-76817-R (Ministry of Economy, Industry and Competitiveness).

D-Pinitol (DPIN) is a natural occurring inositol capable of activating the insulin pathway in peripheral tissues, whereas this has not been thoroughly studied in the central nervous system. The present study assessed the potential regulatory effects of DPIN on the hypothalamic insulin signaling pathway. To this end we investigated the Phosphatidylinositol-3-kinase (PI3K)/Protein Kinase B (Akt) signaling cascade in a rat model following oral administration of DPIN. The PI3K/Akt-associated proteins were quantified by Western blot in terms of phosphorylation and total expression. Results indicate that the acute administration of DPIN induced time-dependent phosphorylation of PI3K/Akt and its related substrates within the hypothalamus, indicating an activation of the insulin signaling pathway. This profile is consistent with DPIN as an insulin sensitizer since we also found a decrease in the circulating concentration of this hormone. Overall, the present study shows the pharmacological action of DPIN in the hypothalamus through the PI3K/Akt pathway when giving in fasted animals. These findings suggest that DPIN might be a candidate to treat brain insulin-resistance associated disorders by activating insulin response beyond the insulin receptor., This work was supported by grants from the following institutions: Ministerio de Economía y Competitividad, Gobierno de España (Grant RTC-2016-4983-1), EU-ERDF-Instituto de Salud Carlos III (Grant PI19/01577), and Consejería de Economía, Conocimiento y Universidad, Junta de Andalucía (Grant P18-TP-5194), Proyecto de Investigación en Salud, Consejería de Salud y Familias (PI-0139-2018). D.M-V. (FI20/00227) holds a “PFIS” predoctoral contract from the National System of Health, EU-ERDF-Instituto de Salud Carlos III

The endocannabinoid system is involved in the regulation of the stress response, but the relative contribution of N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) and their mechanisms have to be elucidated. In this study, we compared the effects of the pharmacological inhibition of the two major endocannabinoid-degrading enzymes [fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) for AEA and 2-AG, respectively] on stress-coping [forced swim test (FST) and tail suspension test (TST)] and anxiety-like [elevated-plus maze (EPM) and light-dark test (LDT)] behaviors in wild-type and FAAH knockout mice. In vivo microdialysis estimated the effects of FAAH and MAGL inhibition on dopamine (DA) and serotonin (5-HT) levels in the medial prefrontal cortex (mPFC) during an FST. Mice were treated with PF-3845 (FAAH inhibitor), JZL184 (MAGL inhibitor), JZL195 (dual FAAH/MAGL inhibitor) or vehicle. Our data showed that PF-3845 increased latency to immobility and decreased total immobility time in FST, but no effects were observed in TST compared with vehicle-treated wild-type mice. By contrast, JZL184 decreased latency and increased immobility in TST and FST. JZL195 in wild-type mice and JZL184 in FAAH knockout mice reproduced the same passive coping behaviors as JZL184 in wild-type mice in TST and FST. In the microdialysis experiment, FST was associated with increased DA and 5-HT levels in the mPFC. However, JZL184-treated wild-type mice displayed a significant attenuation of forced swim stress-induced DA release compared with vehicle-treated wild-type mice and PF-3845-treated wild-type mice. Finally, FAAH and/or MAGL inhibitors induced robust and consistent anxiolytic-like effects in EPM and LDT. These results suggested differences between FAAH and MAGL inhibition in stress-coping behaviors. Notably, MAGL inhibition induced a consistent avoidant coping behavior and attenuated the stress-induced mPFC DA response in FST. However, more investigation is needed to elucidate the functional association between DA and 2-AG signaling pathways, and the molecular mechanism in the regulation of passive coping strategies during inescapable stress., Highlights • FAAH and/or MAGL inhibition induce opposite changes in stress-coping behaviors. • MAGL inhibition increases passive stress-coping behaviors in mice. • Passive stress-coping behaviors are regulated by 2-AG rather than AEA signaling. • MAGL inhibition attenuates mPFC dopamine increase in the forced swim test. • FAAH and/or MAGL inhibitors are associated with anxiolytic-like effects.

© 2021 Ramírez, Torrecilla-Parra, Pardo-Marqués, de-Frutos, Pérez-García, Tabraue, de la Rosa, Martín-Rodriguez, Díaz-Sarmiento, Nuñez, Orizaola, Través, Camps, Boscá and Castrillo., Macrophages are immune cells that play crucial roles in host defense against pathogens by triggering their exceptional phagocytic and inflammatory functions. Macrophages that reside in healthy tissues also accomplish important tasks to preserve organ homeostasis, including lipid uptake/efflux or apoptotic-cell clearance. Both homeostatic and inflammatory functions of macrophages require the precise stability of lipid-rich microdomains located at the cell membrane for the initiation of downstream signaling cascades. Caveolin-1 (Cav-1) is the main protein responsible for the biogenesis of caveolae and plays an important role in vascular inflammation and atherosclerosis. The Liver X receptors (LXRs) are key transcription factors for cholesterol efflux and inflammatory gene responses in macrophages. Although the role of Cav-1 in cellular cholesterol homeostasis and vascular inflammation has been reported, the connection between LXR transcriptional activity and Cav-1 expression and function in macrophages has not been investigated. Here, using gain and loss of function approaches, we demonstrate that LXR-dependent transcriptional pathways modulate Cav-1 expression and compartmentation within the membrane during macrophage activation. As a result, Cav-1 participates in LXR-dependent cholesterol efflux and the control of inflammatory responses. Together, our data show modulation of the LXR-Cav-1 axis could be exploited to control exacerbated inflammation and cholesterol overload in the macrophage during the pathogenesis of lipid and immune disorders, such as atherosclerosis., We thank MINECO FPI predoctoral fellowship granted to MCO (BES-2015-075339). Experimental work was supported by grants from Ministerio de Ciencia, Investigación y Universidades, y Fondo Europeo de Desarrollo Regional (FEDER) Grant REF: PID2019-104284RB-I00/AEI/10.13039/501100011033 (to AC) and support from Networks of Excellence from MINECO (Nuclear Receptors in Cancer, Metabolism and Inflammation [NuRCaMeIn] SAF2017-90604-REDT to AC. Ministerio de Economía, Industria y Competitividad, Ministerio de Ciencia, Investigación y Universidades, and Agencia Estatal de Investigación (SAF2017-82436-R, RTC2017-6283-1), Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CB16/11/00222), Consorcio de Investigación en Red de la Comunidad de Madrid, S2017/BMD-3686 and Fondo Europeo de Desarrollo Regional (to LB). Ministerio de Ciencia, Investigación y Universidades, and Agencia Estatal de Investigación Proyectos de I+D+i Retos Investigación 2018 (RTI2018-095061-B-I00); TALENTO Grant from Madrid Government, Spain (2017-T1/BMD-5333); Consejería de Ciencia, Universidades e Innovación Comunidad de Madrid, Spain (PEJD-2018-POST/BMD-8900 and PEDJ-2018-AI/BDM-9724) to CMR.

Hydrodynamic escape is the most efficient atmospheric mechanism of planetary mass loss and has a large impact on planetary evolution. Three hydrodynamic escape regimes have been identified theoretically: energy-limited, recombination-limited, and photon-limited. However, no evidence of these regimes had been reported until now. Here, we report evidence of these three regimes via an analysis of a helium I triplet at 10 830 Å and Lyα absorption involving a 1D hydrodynamic model that allows us to estimate hydrogen recombination and advection rates. In particular, we show that HD 209458 b is in the energy-limited regime, HD 189733 b is in the recombination-limited regime, and GJ 3470 b is in the photon-limited regime. These exoplanets can be considered as benchmark cases for their respective regimes. © ESO 2021., CARMENES is an instrument for the Centro Astronomico Hispano-Aleman (CAHA) at Calar Alto (Almeria, Spain), operated jointly by the Junta de Andalucia and the Instituto de Astrofisica de Andalucia (CSIC). CARMENES was funded by the Max-Planck-Gesellschaft (MPG), the Consejo Superior de Investigaciones Cientificas (CSIC), the Ministerio de Economia y Competitividad (MINECO) and the European Regional Development Fund (ERDF) through projects FICTS-2011-02, ICTS-2017-07-CAHA-4, and CAHA16-CE-3978, and the members of the CARMENES Consortium (Max-Planck-Institut fur Astronomie, Instituto de Astrofisica de Andalucia, Landessternwarte Konigstuhl, Institut de Ciencies de l'Espai, Institut fur Astrophysik Gottingen, Universidad Complutense de Madrid, Thuringer Landessternwarte Tautenburg, Instituto de Astrofisica de Canarias, Hamburger Sternwarte, Centro de Astrobiologia and Centro Astronomico Hispano-Aleman), with additional contributions by the MINECO, the Deutsche Forschungsgemeinschaft through the Major Research Instrumentation Programme and Research Unit FOR2544 "Blue Planets around Red Stars", the Klaus Tschira Stiftung, the states of Baden-Wurttemberg and Niedersachsen, and by the Junta de Andalucia. We acknowledge financial support from the Agencia Estatal de Investigacion of the Ministerio de Ciencia, Innovacion y Universidades and the ERDF through projects ESP2016-76076-R, ESP2017-87143-R, BES-2015-074542, PID2019-110689RB-I00/AEI/10.13039/501100011033, PGC2018-099425-B-I00, PID2019-109522GB-C51/2/3/4, PGC2018-098153-B-C33, AYA2016-79425-C3-1/2/3-P, ESP2016-80435-C2-1-R, and the Centre of Excellence "Severo Ochoa" and "Maria de Maeztu" awards to the Instituto de Astrofisica de Canarias (SEV-2015-0548), Instituto de Astrofisica de Andalucia (SEV-2017-0709), and Centro de Astrobiologia (MDM-2017-0737), and the Generalitat de Catalunya/CERCA programme. T.H. acknowledges support from the European Research Council under the Horizon 2020 Framework Program via the ERC Advanced Grant Origins 832428. A.S.L. acknowledges funding from the European Research Council under the European Union's Horizon 2020 research and innovation program under grant agreement No 694513.

Dietary fatty acids play a role in the pathogenesis of obesity-associated non-alcoholic fatty liver disease (NAFLD), which is associated with insulin resistance (IR). Fatty acid composition is critical for IR and subsequent NAFLD development. Extra-virgin olive oil (EVOO) is the main source of monounsaturated fatty acids (MUFA) in Mediterranean diets. This study examined whether EVOO-containing high fat diets may prevent diet-induced NAFLD using Ldlr−/−. Leiden mice. In female Ldlr−/−.Leiden mice, the effects of the following high fat diets (HFDs) were examined: a lard-based HFD (HFD-L); an EVOO-based HFD (HFD-EVOO); a phenolic compounds-rich EVOO HFD (HFD-OL). We studied changes in body weight (BW), lipid profile, transaminases, glucose homeostasis, liver pathology and transcriptome. Both EVOO diets reduced body weight (BW) and improved insulin sensitivity. The EVOOs did not improve transaminase values and increased LDL-cholesterol and liver collagen content. EVOOs and HFD-L groups had comparable liver steatosis. The profibrotic effects were substantiated by an up-regulation of gene transcripts related to glutathione metabolism, chemokine signaling and NF-kappa-B activation and down-regulation of genes relevant for fatty acid metabolism. Collectivelly, EVOO intake improved weight gain and insulin sensitivity but not liver inflammation and fibrosis, which was supported by changes in hepatic genes expression., This work was supported by the grants AGL2014-54585-R, AGL-2017-86927-R, CP14/ 00105, PI18/01590 (Ministerio de Economía y Competitividad), PAI-BIO311 (Junta de Andalucía), CB07/08/0006 (Instituto de Salud Carlos III) and by the TNO research programs “Body Brain Interactions ERP 020” and “Functional Biomarkers PMC13”.

Summary Accumulation of topological stress in the form of DNA supercoiling is inherent to the advance of RNA polymerase II (Pol II) and needs to be resolved by DNA topoisomerases to sustain productive transcriptional elongation. Topoisomerases are therefore considered positive facilitators of transcription. Here, we show that, in contrast to this general assumption, human topoisomerase IIα (TOP2A) activity at promoters represses transcription of immediate early genes such as c-FOS, maintaining them under basal repressed conditions. Thus, TOP2A inhibition creates a particular topological context that results in rapid release from promoter-proximal pausing and transcriptional upregulation, which mimics the typical bursting behavior of these genes in response to physiological stimulus. We therefore describe the control of promoter-proximal pausing by TOP2A as a layer for the regulation of gene expression, which can act as a molecular switch to rapidly activate transcription, possibly by regulating the accumulation of DNA supercoiling at promoter regions., Graphical abstract, Highlights • Catalytic inhibition of TOP2A results in a global reduction in promoter-proximal pausing • Catalytic inhibition of TOP2A upregulates transcription of immediate early genes (IEGs) • IEG upregulation occurs independently of DNA breaks or cellular stress • IEG upregulation depends on the accumulation of negative supercoiling at promoter regions, Herrero-Ruiz et al. analyze the function of DNA topoisomerase II in transcriptional regulation. The results reveal that TOP2A activity favors promoter-proximal pausing of RNA polymerase II and repression of immediate early genes in a mechanism that is independent of DNA break formation and involves the control of DNA supercoiling at promoters.

The effect of high hydrostatic pressure (HHP) combined with enzymatic methods or gelatin incorporation in the gelation process of protein isolated from Acheta domesticus was investigated. The results indicate that transglutaminase (TGasa) or glucose oxidase (GOx) enzymes can induce reversible aggregation in dispersions of insoluble protein fractions and increase viscosity in dispersions of soluble fractions, but does not induce gel formation even after HHP treatment; in consequence, enzymatic treatment on cricket protein can be used to increase viscosity but not to form gels. It is technically feasible to obtain gels by adding 2% porcine gelatin to dispersions of protein fractions and subjecting them to HHP. The firmness and syneresis variation values of those gels during storage depended on the protein extracted fraction (insoluble or soluble protein) and on the concentration of protein used. The highest hardness and lowest syneresis was found with the gels obtained from the insoluble fraction at 11 and 15% (w/w) protein concentration. Color difference (ΔE* > 3) appreciable to the naked eye was observed along the storage period and no noticeable pH variations were found after 28 days of storage. Results indicate that new raw materials of interest can be developed for the food industry based on cricket protein isolates, to make high-protein foods which could be applied in a wide variety of different food applications including 3D printing or fat substitution., Financial support of the projects AGL2013-48993-C2-2-R and AGL2017-86840-C2-2-R from the Spanish Ministry of Economy, Industry and Competiveness, FEDER funds.

The administration of microbial neuraminidase into the brain ventricular cavities of rodents represents a model of acute aseptic neuroinflammation. Ependymal cell death and hydrocephalus are unique features of this model. Here we demonstrate that activated microglia participates in ependymal cell death. Co-cultures of pure microglia with ependymal cells (both obtained from rats) were performed, and neuraminidase or lipopolysaccharide were used to activate microglia. Ependymal cell viability was unaltered in the absence of microglia or inflammatory stimulus (neuraminidase or lipopolysaccharide). The constitutive expression by ependymal cells of receptors for cytokines released by activated microglia, such as IL-1β, was demonstrated by qPCR. Besides, neuraminidase induced the overexpression of both receptors in ventricular wall explants. Finally, ependymal viability was evaluated in the presence of functional blocking antibodies against IL-1β and TNFα. In the co-culture setting, an IL-1β blocking antibody prevented ependymal cell death, while TNFα antibody did not. These results suggest that activated microglia are involved in the ependymal damage that occurs after the administration of neuraminidase in the ventricular cavities, and points to IL-1β as possible mediator of such effect. The relevance of these results lies in the fact that brain infections caused by neuraminidase-bearing pathogens are frequently associated to ependymal death and hydrocephalus.

Maqui-berry is characterised by presenting a high concentration of (poly)phenols, accounting anthocyanins (cyanidin and delphinidin) for over 85% of the total. These coloured flavonoids have demonstrated potential neurological activity, but the evidence of their antinociceptive properties is scarce. In order to cover this gap, different doses (suitable for human administration) of a maqui-berry powder (1.6% anthocyanin), using enteral and parenteral routes of administration, were compared at central and peripheral levels using a nociceptive pain model (formalin test) in mice. Gastric damage analysis as possible adverse effects of analgesic and anti-inflammatory drugs was also explored. Dose-antinociceptive response was confirmed using both routes of administration and in both neurogenic and inflammatory phases of the formalin test, without gastric damage. In conclusion, these preliminary data provide evidence of pharmacological properties of maqui-berry to alleviate nociceptive pain., This work was partially supported by Consejo Nacional de Ciencia y Tecnologıa (CONACYT) grant numbers 226454 and 256448 and Institutional projects numbers INPNC123280.0 and INP-NC17073.0. Also, was partially funded by the Spanish MINECO through Research Project AGL2016-75332-C2-1-R (AEI/FEDER, UE), the Spanish MICIN through Research Project PID2019-104212RD-100, and VA by a FPI [grant number BES-2017-079754

Previously, we identified that a cyclic hexapeptide AOA-2 inhibited the interaction of Gram-negative bacilli (GNB) like Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli to host cells thereby preventing the development of infection in vitro and in a murine sepsis peritoneal model. In this work, we aimed to evaluate in vitro a library of AOA-2 derivatives in order to improve the effect of AOA-2 against GNB infections. Ten AOA-2 derivatives were synthetized for the in vitro assays. Their toxicities to human lung epithelial cells (A549 cells) for 24 h were evaluated by determining the A549 cells viability using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The effect of these peptide derivatives and AOA-2 at 250, 125, 62.5, and 31.25 μg/mL on the attachment of A. baumannii ATCC 17978, P. aeruginosa PAO1 and E. coli ATCC 25922 strains to A549 cells was characterized by adherence and viability assays. None of the 10 derivatives showed toxicity to A549 cells. RW01 and RW06 have reduced more the adherence of ATCC 17978, PAO1 and ATCC 2599 strains to A549 cells when compared with the original compound AOA-2. Moreover, both peptides have increased slightly the viability of infected A549 cells by PAO1 and ATCC 25922 than those observed with AOA-2. Finally, RW01 and RW06 have potentiated the activity of colistin against ATCC 17978 strain in the same level with AOA-2. The optimization program of AOA-2 has generated two derivatives (RW01 and RW06) with best effect against interaction of GNB with host cells, specifically against P. aeruginosa and E. coli., This study was supported by the Instituto de Salud Carlos III, Proyectos de Investigación en Salud (Grants PI15/01358 and PI16/01378) and by Plan Nacional de I + D + i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Inno-vación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009)—co-financed by the European Development Regional Fund “A way to achieve Europe,” Operative program Intelligent Growth 2014–2020. YS was supported by the Subprograma Miguel Servet Tipo I from the Ministerio de Economía y Competitividad of Spain (CP15/00132).

The increase of concentrations of tetracycline antibiotics in agricultural soils worldwide is of special concern, due to its potential toxic effects on soil bacterial communities. In the present work, the reuse of two waste/by-product materials as soil amendments was tested as a preventive practice for reducing tetracycline antibiotics toxicity in soils. Pine bark (PB), with high percentage of organic carbon, and crushed mussel shell (CMS), a frequent natural liming material, were added to 4 soils in doses 0, 6, 12 and 48 g of by-product per kg−1 of soil (dry weight) of each one (separately). The soils and soil-waste mixtures were then spiked with tetracycline (TC), oxytetracycline (OTC) and chlortetracycline (CTC). After one day of incubation, the bacterial growth was estimated in soils and soil-mixtures using the leucine incorporation technique. The addition of PB to the soils showed two different behaviors, depending on the antibiotics. The toxicity of TC and OTC decreased with the addition of PB (toxicities going from 6 to 25% and from 5 to 36%, respectively). However, CTC toxicity did not change, or even increased in response to the PB amendment. Regarding soil amendment with CMS, it was not effective to prevent the toxicity of any of the three antibiotics studied., This study has been funded by the Spanish Ministry of Economy and Competitiveness through the projects CGL 2015-67333-C2-1-R and -2-R (FEDER Funds), and by Xunta de Galicia CITACA Strategic Partnership (ED431E 2018/07) and BV1 research group (ED431C 2017/62-GRC). David Fernández Calviño holds a Ramón y Cajal contract (RYC-2016-20411) financed by the Spanish Ministry of Economy, Industry and Competitiveness. Vanesa Santás Miguel holds a pre-doctoral fellowship founded by the University of Vigo.

Protein functional interactions could explain the biological response of secoiridoids (SECs), main phenolic compounds in virgin olive oil (VOO). The aim was to assess protein¿protein interactions (PPIs) of the aorta gap junction alpha-1 (GJA1) and the heart peptidyl-prolyl cis-trans isomerase (FKBP1A), plus the phosphorylated heart proteome, to describe new molecular pathways in the cardiovascular system in rats using nanoliquid chromatography coupled with mass spectrometry. PPIs modified by SECs and associated with GJA1 in aorta rat tissue were calpain, TUBA1A, and HSPB1. Those associated with FKBP1A in rat heart tissue included SUCLG1, HSPE1, and TNNI3. In the heart, SECs modulated the phosphoproteome through the main canonical pathways PI3K/mTOR signaling (AKT1S1 and GAB2) and gap junction signaling (GAB2 and GJA1). PPIs associated with GJA1 and with FKBP1A, the phosphorylation of GAB2, and the dephosphorylation of GJA1 and AKT1S1 in rat tissues are promising protein targets promoting cardiovascular protection to explain the health benefits of VOO., The work summarized in this paper was supported in part by grants (grant nos. MEFOPC Project, AGL2012-40144-C03-02 and AGL2012-40144-C03-03, and AppleCOR Project, AGL2016-76943-C2-2-R) from the Ministerio de Economía, Industria y Competitividad, the Agencia Estatal de Investigación (AEI), and the European Regional Development Fund (ERDF). L.R. is supported by a Sara Borrell postdoctoral grant (CD14/00275; Spain), A.P. is supported by a postdoctoral grant (PTQ-15-08068; Spain), and Ú.C. is supported by a Pla Estratègic de Recerca i Innovació en Salut (PERIS) postdoctoral grant (SLT002/16/00239; Catalunya, Spain).

The observation of electronic phase separation textures in vanadium dioxide, a prototypical electron‐correlated oxide, has recently added new perspectives on the long standing debate about its metal–insulator transition and its applications. Yet, the lack of atomically resolved information on phases accompanying such complex patterns still hinders a comprehensive understanding of the transition and its implementation in practical devices. In this work, atomic resolution imaging and spectroscopy unveils the existence of ferroelastic tweed structures on ≈5 nm length scales, well below the resolution limit of currently used spectroscopic imaging techniques. Moreover, density functional theory calculations show that this pretransitional fine‐scale tweed, which on average looks and behaves like the standard metallic rutile phase, is in fact weaved by semi‐dimerized chains of vanadium in a new monoclinic phase that represents a structural bridge to the monoclinic insulating ground state. These observations provide a multiscale perspective for the interpretation of existing data, whereby phase coexistence and structural intermixing can occur all the way down to the atomic scale., The authors thank Prof. Enric Canadell for enlightening discussions. The authors also thank Prof. Etienne Snoeck and Dr. Christophe Gatel for obtaining HRTEM images of the 80 nm‐thick film at CEMES (Toulouse), and Dr. Belén Ballesteros for assistance during preliminary TEM observations. F.S. acknowledges the Spanish Ministry of Industry, Economy and Competitiveness (MINECO) for financial support through the “Severo Ochoa” programme for Centers of Excellence in R&D (SEV‐2015‐0496) and Project No. RTI2018‐098537‐B‐C21. G.C., J.S., and L.R. acknowledge financial support from MINECO (Grant No. MAT2016‐77100‐C2‐1‐P) and the Catalan Government (Generalitat de Catalunya, Grant No. 2017 SGR 579). M.P. acknowledges financial support from Spanish MICIU, AEI and EU FEDER (Grant No. PGC2018‐096955‐B‐C43) and Generalitat de Catalunya (Grant No. 2017SGR1506). Research at ICN2 was also supported by the CERCA programme (Generalitat de Catalunya) and by the “Severo Ochoa” programme for Centers of Excellence in R&D of MINECO (Grant No. SEV‐2017‐0706). C.M. acknowledges funding from MINECO under Project No. MAT2017‐82970‐C2‐R and from the European's Union Horizon 2020 research and innovation programme under Grant No. 823717‐ESTEEM3.

Novel composite materials are being investigated for improving the energy storage performance of electrochemical capacitors. For this goal, synergistic effects via the combination of diverse types of materials are crucial. In this work, electrodes composed of reduced graphene oxide, multiwall carbon nanotubes, as well as cerium and manganese oxides were fabricated through reactive inverse matrix-assisted pulsed laser evaporation (RIMAPLE). UV-pulsed laser irradiation of frozen aqueous dispersions containing graphene oxide sheets, carbon nanotubes, and ceria nanoentities, besides manganese acetate precursor, led to the simultaneous chemical transformation and co-deposition of hybrid electrodes onto flexible metallic substrates via photothermal and photochemical processes. Thorough morphological and compositional studies of the electrodes demonstrated the laser-induced reduction of graphene oxide, besides the crystallization of a mixture of cerium and manganese oxide nanostructures decorating the carbon nanoentities during the deposition process. Electrochemical analyses revealed a remarkable improvement of performance with the combination of electrochemical double layer in the porous nanocarbon framework with pseudocapacitance from the oxide nanostructures, obtaining excellent volumetric capacitances of up to 140 F cm−3 at 10 mV s−1 with the combination of all four materials. The attained results are the best ones yet published regarding RIMAPLE of hybrid nanocarbon-based electrodes with micrometric thickness. Finally, symmetric electrochemical capacitors were fabricated using aqueous electrolyte, revealing excellent stability upon tens of thousands of charge–discharge cycles., The authors thank the financial support of the Spanish Ministry of Economy, Industry and Competitiveness under the project ENE2017-89210-C2-1-R and support from AGAUR of Generalitat de Catalunya through projects 2017 SGR 1086 and 2017 SGR 1771. PGL thanks the financial support of the Spanish Ministry of Economy, Industry and Competitiveness through the grant BES-2017-081652 for the formation of scientific researchers. ICMAB acknowledges financial support from the Spanish Ministry of Economy and Competitiveness, through Severo Ochoa FUNFUTURE (CEX2019-000917-S). The FTIRM experiments were performed at MIRAS beamline at ALBA Synchrotron with the collaboration of ALBA staff. We acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).

A series of mesoporous carbonaceous materials were synthesized by the nanocasting technique using boehmite as a template and glucose as a carbon precursor. After pyrolysis and template removal, the resulting material is a mesoporous carbon that can be additionally doped with N, B and K during prepyrolysis impregnation. In addition, the influence of doping on the morphology, crystallinity and stability of the synthesized carbons was studied using X-ray diffraction, nitrogen physisorption, thermogravimetry, Raman and IR spectroscopy and transmission electron microscopy. While the nanocasting process is effective for the formation of mesopores, KOH and urea do not modify the textural properties of carbon. The use of H3PO4 as a dopant, however, led to the formation of an AlPO4 compound and resulted in a solid with a lower specific surface area and higher microporosity. All doped solids present higher thermal stability as a positive effect of the introduction of heteroatoms to the carbon skeleton. The phosphorus-doped sample has better oxidation resistance, with a combustion temperature 120–150 C higher than those observed for the other materials.

PrimPol is the second primase in human cells, the first with the ability to start DNA chains with dNTPs. PrimPol contributes to DNA damage tolerance by restarting DNA synthesis beyond stalling lesions, acting as a TLS primase. Multiple alignment of eukaryotic PrimPols allowed us to identify a highly conserved motif, WxxY near the invariant motif A, which contains two active site metal ligands in all members of the archeo-eukaryotic primase (AEP) superfamily. In vivo and in vitro analysis of single variants of the WFYY motif of human PrimPol demonstrated that the invariant Trp87 and Tyr90 residues are essential for both primase and polymerase activities, mainly due to their crucial role in binding incoming nucleotides. Accordingly, the human variant F88L, altering the WFYY motif, displayed reduced binding of incoming nucleotides, affecting its primase/polymerase activities especially during TLS reactions on UV-damaged DNA. Conversely, the Y89D mutation initially associated with High Myopia did not affect the ability to rescue stalled replication forks in human cells. Collectively, our data suggest that the WFYY motif has a fundamental role in stabilizing the incoming 3′-nucleotide, an essential requisite for both its primase and TLS abilities during replication fork restart., BFU2015-65880-P (MINECO) and PGC2018-093576-B.C21 (MCI/AEI/FEDER,UE) to L.B., BFU2016-80402-R (MINECO/FEDER, UE) and PID2019-106707RB-100 (AEI/10.13039/501100011033) to J.M., Kempe JCK 1831 to G.S, Knut och Alice Wallenbergs Foundation KAW 2019.0307, VR-2018-02781, to S.W., and by institutional grants from Fundación Ramón Areces and Banco de Santander

7 figures.-- Supplementary material available on line (6 figures).-- This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder., Carbon nanomaterials offer excellent prospects as therapeutic agents, and among them, graphene quantum dots (GQDs) have gained considerable interest thanks to their aqueous solubility and intrinsic fluorescence, which enable their possible use in theranostic approaches, if their biocompatibility and favorable pharmacokinetic are confirmed. We prepared ultra-small GQDs using an alternative, reproducible, top-down synthesis starting from graphene oxide with a nearly 100% conversion. The materials were tested to assess their safety, demonstrating good biocompatibility and ability in passing the ultrafiltration barrier using an in vitro model. This leads to renal excretion without affecting the kidneys. Moreover, we studied the GQDs in vivo biodistribution confirming their efficient renal clearance, and we demonstrated that the internalization mechanism into podocytes is caveolae-mediated. Therefore, considering the reported characteristics, it appears possible to vehiculate compounds to kidneys by means of GQDs, overcoming problems related to lysosomal degradation., J. M. G.-D. acknowledges Spanish Ministry of Science, Innovation and Universities for his Juan de la Cierva Incorporación research contract (No. IJCI-2016-27789). This project has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie Grant Agreement No. 734834 (INFUSION) and No. 734381 (CARBO-IMmap), and from MIUR. ICN2 is supported by the Severo Ochoa program from Spanish MINECO (No. SEV-2017-0706)., Funding note : Open Access funding provided by Università degli Studi di Trieste within the CRUICARE Agreement.

The objectives of this study were to characterize the role of the uhpT, glpT, and fosA genes in fosfomycin resistance in Klebsiella pneumoniae and evaluate the use of sodium phosphonoformate (PPF) in combination with fosfomycin. Seven clinical isolates of K. pneumoniae and the reference strain (ATCC 700721) were used, and their genomes were sequenced. ΔuhpT, ΔglpT, and ΔfosA mutants were constructed from two isolates and K. pneumoniae ATCC 700721. Fosfomycin susceptibility testing was done by the gradient strip method. Synergy between fosfomycin and PPF was studied by checkerboard assay and analyzed using SynergyFinder. Spontaneous fosfomycin mutant frequencies at 64 and 512 mg/liter, in vitro activity using growth curves with fosfomycin gradient concentrations (0 to 256mg/liter), and time-kill assays at 64 and 307 mg/liter were evaluated with and without PPF (0.623 mM). The MICs of fosfomycin against the clinical isolates ranged from 16 to ≥1,024 mg/liter. The addition of 0.623 mM PPF reduced fosfomycin MIC between 2- and 8-fold. Deletion of fosA led to a 32-fold decrease. Synergistic activities were observed with the combination of fosfomycin and PPF (most synergistic area at 0.623 mM). The lowest fosfomycin-resistant mutant frequencies were found in ΔfosA mutants, with decreases in frequency from 1.69 × 10−1 to 1.60 × 10−5 for 64 mg/liter of fosfomycin. In the final growth monitoring and time-kill assays, fosfomycin showed a bactericidal effect only with the deletion of fosA and not with the addition of PPF. We conclude that fosA gene inactivation leads to a decrease in fosfomycin resistance in K. pneumoniae. The pharmacological approach using PPF did not achieve enough activity, and the effect decreased with the presence of fosfomycin-resistant mutations., Miriam Ortiz-Padilla is supported by a PFIS fellowship from Instituto de Salud Carlos III. This study was supported by the Plan Nacional de I+D+i 2013‐2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (PI16/01824, REIPI RD12/0015/0010, and REIPI RD16/0016/0001), cofinanced by European Development Regional Fund A Way To Achieve Europe, Operative Program Intelligent Growth 2014‐2020, and the Consejería de Igualdad, Salud y Políticas Sociales, Junta de Andalucía (PI-0044 to 2013). The funders had no role in the design, collection of data, analysis and writing of the manuscript, or the decision to publish.

Glutathione (GSH) is a useful biomarker in the development, diagnosis and treatment of cancer. However, most of the reported GSH biosensors are expensive, time-consuming and often require complex sample treatment, which limit its biological applications. Herein, a nanobiosensor for the detection of GSH using folic acid-functionalized reduced graphene oxide-modified BSA gold nanoclusters (FA-rGO-BSA/AuNCs) based on the fluorescence quenching interactions is presented. Firstly, a facile and optimized protocol for the fabrication of BSA/AuNCs is developed. Functionalization of rGO with folic acid is performed using EDC/NHS cross-linking reagents, and their interaction after loading with BSA/AuNCs is demonstrated. The formation of FA-rGO, BSA/AuNCs and FA-rGO-BSA/AuNCs are confirmed by the state-of-art characterization techniques. Finally, a fluorescence turn-off sensing strategy is developed using the as-synthesized FA-rGO-BSA/AuNCs for the detection of GSH. The nanobiosensor revealed an excellent sensing performance for the detection of GSH with high sensitivity and desirable selectivity over other potential interfering species. The fluorescence quenching is linearly proportional to the concentration of GSH between 0 and 1.75 µM, with a limit of detection of 0.1 µM under the physiological pH conditions (pH 7.4). Such a sensitive nanobiosensor paves the way to fabricate a “turn-on” or “turn-off” fluorescent sensor for important biomarkers in cancer cells, presenting potential nanotheranostic applications in biological detection and clinical diagnosis., This work was supported by the Fundamental Research Grant Scheme (FRGS), Ministry of Higher Education (MOHE), Malaysia [FRGS/1/2016/STG07/UNIM/02/1] and by the CERCA Programme/Generalitat de Catalunya. ICN2 is supported by the Severo Ochoa Centres of Excellence programme, funded by the Spanish Research Agency (AEI, Grant no. SEV-2017-0706). We acknowledge support from Ministerio de Economía, Industria y Competitividad (MINECO), Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER) for funding the project MAT2017-87202-P. Authors acknowledge the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No. 881603 (Graphene Flagship Core 3).

Nowadays there is not an effective drug for the treatment of infections caused by human adenovirus (HAdV) which supposes a clinical challenge, especially for paediatric and immunosuppressed patients. Here, we describe the design, synthesis and biological evaluation as anti-adenovirus agents of a new library (57 compounds) of diester, monoester and triazole derivatives based on 3-amino-1,2-propanediol skeleton. Seven compounds (17, 20, 26, 34, 44, 60 and 66) were selected based on their high anti-HAdV activity at low micromolar concentration (IC50 from 2.47 to 5.75 µM) and low cytotoxicity (CC50 from 28.70 to >200 µM). In addition, our mechanistic assays revealed that compounds 20 and 44 might be targeting specifically the HAdV DNA replication process, and compound 66 would be targeting HAdV E1A mRNA transcription. For compounds 17, 20, 34 and 60, the mechanism of action seems to be associated with later steps after HAdV DNA replication., This work has been supported by Ministerio de Ciencia, Innovación y Universidades, Plan Estatal 2017-2020 Retos - Proyectos I + D + i (PID2019-104767RB-I00); Ministerio de Economía y Competitividad, Plan Nacional I + D + i 2013-2016, Retos-Proyectos (CTQ2016-78580-C2-2-R); Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009), cofinanced by European Development Regional Fund “A way to achieve Europe”, the Instituto de Salud Carlos III, Proyectos de Investigación en Salud (PI17/01055; PI18/01191) and Proyectos de Desarrollo Tecnológico en Salud (DTS17/00130), the Spanish Adenovirus Network (AdenoNet, BIO2015/68990-REDT), and the program “Nicolás Monardes” (C-0059-2018), Servicio Andaluz de Salud, Junta de Andalucía.

This work was supported by grants from the following institutions: Grant for international postdoctoral stay. Jose Castillejo Program (Grant CAS15/00257), Ministerio de Educación Cultura y Deporte. Gobierno de España. Proyecto de Investigación en Salud, Consejería de Salud y Familias (Grant PI-0139-2018). EU-ERDF-Instituto de Salud Carlos III (Grant PI19/01577). Proyectos dedesarrollo tecnológico, Ministerio de Ciencia e Innovación (Grant DTS19/00125). Ministerio de Economía, Industria y Competitividad (Grant RTC-2019-007329-1).