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Obstructive sleep apnea (OSA) is associated with increased incidence of both cerebrovascular and coronary events and of overall cardiovascular risk. However, it seems that these relationships are less clear in the elderly population. On the other hand, continuous positive airway pressure (CPAP), the treatment of choice for severe and symptomatic OSA patients, seems to be more effective in preventing cerebrovascular than coronary events, also in the elderly. This review describes the existing literature in the field and exposes the different hypotheses that try to explain these phenomena. There is a growing body of evidence showing that low-grade intermittent hypoxia (a feature that characterized OSA) is associated with increased levels of hypoxia-inducible factor 1 (HIF-1) and vascular endothelial growth factor (VEGF) which in turn lead to neovascularization in the coronary tree (preconditioning hypoxia hypothesis). However, little is known about the effect of intermittent hypoxia in the formation of new vessels in the cerebral vasculature. Moreover, the effect of intermittent hypoxia in both coronary and cerebral vessels could change with age. On the other hand, recent randomized clinical trials have shown that CPAP may not be effective in preventing cardiovascular events in the context of secondary prevention. However, a more detailed analysis of the results and subsequent meta-analyses show that this treatment exerts a protective effect in cerebrovascular disease but not in cardiovascular diseases, especially in elderly patients. Although OSA is clearly related to an increased cardiovascular risk, this seems less obvious in the elderly and in the coronary vessels. As a consequence, the effect of CPAP in the elderly with coronary disease remains controversial.

Ageritin has been recently described as the first ribotoxin-like from Basidiomycota division (mushroom Agrocybe aegerita) with known antitumor activity (BBA 2017, 1861: 1113-1121). By investigating structural, catalytic and binding properties, we demonstrate that Ageritin is a unique ribotoxin-like protein. Indeed, typical of the ribotoxin family, it shows the specific ribonucleolytic activity against the ribosomal Sarcin-Ricin Loop in a rabbit reticulocytes assay. However, it displays several elements of novelty, as this activity is strongly metal-dependent and completely suppressed in the presence of EDTA, different from other representative members of the ribotoxin family. Consistently, we prove that Ageritin is able to bind magnesium ions with low micromolar affinity. We also show that Ageritin is significantly more stable than other ribotoxins in thermal and chemical denaturation experiments. These peculiar features make Ageritin the prototype of a new ribotoxin-like family present in basidiomycetes. Finally, given its high stability, this enzyme is a promising candidate as a new tool in immunoconjugates and nanoconstructs.

The food industry confronts an enormous challenge to develop stable margarine-type water-in-vegetable oil (W/O) emulsion-based table spreads with reduced concentration of saturated fat and without trans fats. In the present work, we developed a gelled W/O emulsion (Gelled-W/O-E) containing 20% of water using a mixture of a conventional W/O emulsion (W/O-E) stabilized with glycerol monostearate (GMS), and an ethyl cellulose (EC) oleogel. The mechanical, microstructure and stability of the resulting gelled emulsion (Gelled-W/O-E) was compared with control systems consisting of conventional W/O emulsions (W/O-E) and EC-GMS oleogels (EC-GMS-O; no water added) formulated using the same GMS (0.5% and 1.0%) and EC (7%) concentration as in the Gelled-W/O-E. The Gelled-W/O-E showed higher elasticity and emulsion stability in comparison with the control systems. This in spite the EC and GMS concentrations used were below the minimal concentration required to develop a gel, and the tentatively lower solid content in the Gelled-W/O-E than in the EC-GMS-O because the presence of water. We observed that by increasing the GMS concentration in the Gelled-W/O-E, the water droplet size decreased as gel elasticity and W/O emulsion stability significantly increased. We associated this behavior to a synergistic GMS-EC interaction that kept the GMS at the water-oil droplet interface. These results showed the role of water droplets as active fillers in determining the rheological properties of the Gelled-W/O-E, and that the GMS efficiency as emulsifier increased in the presence of EC in the oil phase. After comparing the microstructural properties of commercial margarine spreads with those of the Gelled-W/O-E, we concluded that the structured W/O emulsion is a novel way to achieve similar functionality to margarine spreads, without the use of saturated and trans-fats.

A family of pentacoordinated diorganotin(IV) compounds was synthesized and characterized through the advantageous approach of a multicomponent methodology involving the reaction between 4-(diethylamino)salicylaldehyde, dibutyltin oxide and including a series of l -amino acid fragments (alanine, valine, leucine, isoleucine, phenylalanine, tyrosine and methionine), all carried out in one-step, in excellent yields. Structures were elucidated by FTIR, HRMS and solution NMR (1H, 13C and 119Sn). Diorganotin(IV) derivatives crystallized easily and five unreported molecular structures were solved and analyzed by SC-XRD experiments; depending on the orientation of the alkyl residues different isomorphic arrays were found. Finally, pentacoordinated diorganotin(IV) complexes were tested against tumoral cell lines, HCT-15 (colon adenocarcinoma), HeLa (cervical uterine adenocarcinoma), MCF-7 (breast adenocarcinoma) and PC-3 (human prostate cancer) in order to evaluate their in vitro cytotoxicity.

Peppermint (Mentha piperita) is a plant widely consumed as infusion due to its beneficial health properties that are related to its phytochemical profile, which has been shown to improve with the foliar application of salicylic acid to the plants during their cultivation. However, analysis of transcriptome changes induced by the application of salicylic acid in peppermint, have not been previously reported. In order to identify the genes involved in salicylic acid signaling, the RNA sequencing strategy was employed to evaluate the transcriptional profiles in peppermint. Results showed 178,723,476 high-quality reads, of which, 77.89% corresponded to the salicylic acid elicited peppermint, whereas the remaining 22.11% was from controls plants. We found that foliar treatment with salicylic acid in peppermint plants had an important influence in many relevant biological processes, mainly photosynthesis, light response, transport of protons and phenylpropanoid pathway. Therefore, these results might explain the improvement of the bioactive metabolites concentration and nutraceutical properties induced by salicylic acid in peppermint observed in previous studies.

Spanish Sleep Network., [Introduction] Short-term treatment with continuous positive airway pressure (CPAP) produces a clinically significant reduction in blood pressure (BP) in patients with obstructive sleep apnea (OSA) and resistant hypertension. However, it is unknown whether this effect continues over the long-term. Our objective was to assess the effect of long-term CPAP on BP in patients with OSA and resistant hypertension., [Methods] The study included 161 patients diagnosed with both OSA [apnea--hypopnea index (AHI) ≥15] and resistant hypertension diagnosed via 24-hour ambulatory BP measurement (24-h ABPM), in whom a second analysis via 24-h ABPM was performed at the end of the follow-up., [Results] Patients were followed up within 59 months [interquartile range (IQR): 44–70]. CPAP treatment was prescribed to 82% of the patients (70% with good adherence to CPAP defined as use of CPAP at least 4 h/night). A comparison between the adherent group and nonadherent group (including those with CPAP not prescribed) showed that CPAP adherents had a significant drop in the 24-h BP, both systolic [−3.9 mmHg; 95% confidence interval (CI): −8.1 to 0.3] and diastolic pressure (−3.5 mmHg [95% [CI]: −6.4–0.5]), with a higher magnitude during the night (−5.5 and −4.9 mmHg, respectively). The CPAP adherent group needed a mean of 1.1 less antihypertensive drugs (particularly spironolactone). Finally, there was a positive correlation between the drop in 24-h SBP and the hours of CPAP use (r = 0.24; P = 0.01)., [Conclusion] Good adherence to long-term CPAP treatment largely succeeded in significantly reducing BP in those patients with OSA and resistant hypertension, despite the use of a lower number of antihypertensive drugs.

Local microviscosity monitoring in living cells is a powerful tool to determine their healthy status in either a specific organelle or in the cytosol. Here is presented the rational design of a new family of self-calibrating dual-microviscosity probes as a strategy to improve the probe response at low viscosity ranges. We found one of the probes is useful to determine low viscosity variations in living cells where subtle stiffening of the rotor group in the probe can increase its viscosity sensitivity. Further X-ray structure analysis, fluorescence anisotropic measurements, and quantum chemical calculations of the electronic excitation by means of a natural transition orbital (NTO) analysis confirmed the observed response. The present work demonstrates that small viscosity variations (0.01–0.1 cP) in cells require improved analytical sensitivity to be properly monitored.

Plants require effective sensing and responses to environmental stimuli, for example in the case of biotic and abiotic stresses. Reactive oxygen species (ROS) are well-recognised key signal molecules for the stress response. In previous work in our group, several transgenic tobacco lines were generated constitutively expressing a germin-like gene from Capsicum chinense (CchGLP), producing higher endogen levels of hydrogen peroxide that correlated with tolerance to geminivirus infections and drought stress. Differential transcriptomic analysis between transgenic tobacco lines of low (L1) and high (L8) CchGLP gene expression showed key changes in differential profiles related to the crosstalk between basal metabolism, biochemical and stress-related pathways that might explain the observed tolerant phenotype. Our results suggested that hydrogen peroxide levels modified transcriptomic pattern allowing tolerance in these tobaccos towards biotic and abiotic stresses. Constitutive production of endogen h...

A chelating coumarin-derived ligand sensitizes all emitting lanthanide ions in the solid state and gives high absolute quantum yields for ethanol solutions of complexes of Sm, Eu, Tb, and Dy, above 20% for the last two. Crystal structures of these four complexes are [Ln(Cum)3(H2O)(X)]·X where X = MeOH or EtOH.

Chromophoric coumarin-BODIPY derivatives bridged by an ethynyl π-bridge were investigated as supramolecular building blocks of organic semiconducting solids through X-ray analysis, UV/Vis and fluorescence measurements, and quantum chemical calculations of the frontier orbital energy depending on the chemical environment. Based on a push-pull architecture, the molecular properties of 7-(diethylamino)coumarin core end-capped with BODIPYs as well as the supramolecular self-assembly can be directed through the modification of the ethyny-aryl π-bridge and the intermolecular interactions it generates. Frontier orbital energy changes depending on chemical environment were performed, in particular, upon adsorption on a flat semiconducting surface. Coumarin-BODIPY building-blocks self-assemble into molecular crystals and highly-ordered thin-films with desirable periodic π-stacking interactions for semiconducting applications. The present work represents a convenient alternative to engineer organic semiconducting solids based on coumarin-BODIPY systems for organic electronics.

EUSO-Balloon is a pathfinder mission for the Extreme Universe Space Observatory onboard the Japanese Experiment Module (JEM-EUSO). It was launched on the moonless night of the 25th of August 2014 from Timmins, Canada. The flight ended successfully after maintaining the target altitude of 38 km for five hours. One part of the mission was a 2.5 hour underflight using a helicopter equipped with three UV light sources (LED, xenon flasher and laser) to perform an inflight calibration and examine the detectors capability to measure tracks moving at the speed of light. We describe the helicopter laser system and details of the underflight as well as how the laser tracks were recorded and found in the data. These are the first recorded laser tracks measured from a fluorescence detector looking down on the atmosphere. Finally, we present a first reconstruction of the direction of the laser tracks relative to the detector., 0, SCOPUS: ar.j, info:eu-repo/semantics/published

The industrial process of producing tomato paste generates approximately 4% of subproducts, namely seeds and peels, which is currently removed by specialist industries and typically repurposed as animal feed and also more recently for the extraction of lycopene. The objective of this study was the repurposing of these subproducts through the creation of an intermediary food product (IFP). This IFP is to be used as a food enricher, for use in a variety of products, primarily for the tomato industry. The process used a previously prepared mixture concentrated to 20-22 °Brix, and using a blend of up to 20% fresh seeds and peels to 80% paste. These IFPs not only add nutritive value through increased fiber, lycopene and polyunsaturated fats, but also add sensorial value to both the tomato paste and subsequent end products.

The industrial processing of tomato concentrate produces roughly 4% of byproducts, in the form of skins and seeds, which is typically collected by specialist companies for the production of animal feed, or subjected to chemical extraction processes to obtain lycopene compounds. The health benefits of lycopene have been well documented in terms of antioxidant properties and dietary fiber. The objective of this study was the repurposing of these byproducts from the industrial tomato industry through the creation of new tomato sauces with the addition of an intermediary food product (IFP), in the form of a food texturizer, while also improving dietary fiber and lycopene content. For this purpose, a series of trials was undertaken with the aim of producing fried tomato to which the IFPs had been added as a partial or total replacement for starch as a texturizing agent. After sensorial trials, it was determined that the most suitable IFPs for the replacement of starch were IFPs using a HOT tomato concentrate with 5 and 10% fresh skins and seeds, and IFPs prepared from a mixture of fresh juice, seeds and skins in ratios of 20 and 30%, which were subsequently concentrated. All of the fried tomato sauces that were produced were deemed to be acceptable to the sensorial tasting panels. For this reason, the use of IFPs obtained from tomato byproducts and subsequently reused for the production of sauces can be considered as an ingredient that acts as an effective texturizing agent, improving both dietary fiber and lycopene values.

In this work, we describe the synthesis of meso-(9-ethyl-9H-carbazol-3-yl)-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene and its incorporation as thin film by vapor deposition on indium tin oxide. The morphology of the film was analyzed by scanning electron microscopy and atomic force microscopy showing a granular and homogeneous structure, contact angle measurements revealed that this film exhibits a hydrophobic surface. Packing of the compound was simulated through molecular dynamics and Monte Carlo sampling, and the electronic features of aggregates were modeled with plane-wave DFT. A semiconductor behavior for the featured compound in aggregated state, which compares well with systems applied on electronic devices, is predicted for the featured F-BODIPY.

International audience; Nonlinear optical (NLO) properties of push-pull Mo complexes with ONO tridentate ligands have been studied. The compounds were obtained in high yields using multicomponent reactions and their structures were confirmed by NMR, IR and HRMS analysis. Furthermore, TGA studies revealed good thermal stability of the Mo complexes. The linear and NLO properties evidenced enhanced responses compared with their boron and tin analogs, indicating that Mo complexes should be further investigated as robust building blocks for NLO materials.

Molecular crystals of meso-(5-((4-formylphenyl)ethynyl)thiophen-2-yl)-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene 4a and meso-(4-((4-formylphenyl)ethynyl)phenyl)-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene 4b were synthesized using palladium(0)-catalyzed Sonogashira cross coupling reactions and characterized using an experimental-theoretical approach. The crystal structures of F-BODIPYs 4a-b are structurally analogous, yet their crystal packing motifs displayed remarkable differences due to contrasting hydrogen-bonding interactions. A CASTEP study of the unit cell for each compound provided the theoretical band structure and density-of-states (DOS) diagrams for each molecular crystal, suggesting a semiconductor character for both solids. Analysis of the computed electron density with Bader's QTAIM describes the intermolecular-contact network within each periodic system, while Natural Bonding Orbitals (NBO) display in-phase overlap between stacked units, denoting intermolecular delocalization of the electron density via stacking. TDDFT analysis of solution UV-Vis spectra gives insight into the nature of the observed excitations along with the effects derived from the relative rotation of π-subsystems in solution.

Tomato is one of the principal crops worldwide due to its large consumption. In this work, biofertilization treatments, based on Bacillus licheniformis, with different nitrogen fertilization doses were investigated to improve the functional quality of tomato under greenhouse conditions. Treatments tested used nitrogen fertilization only (NF) or nitrogen combined with biofertilization (BF) with the following nitrogen doses: 0, 25, 50, 75 and 100% of the recommended nitrogen dose. The lycopene content increased with the nitrogen dose with the BF treatments resulting in lower lycopene contents in comparison with the NF counterparts. The contents of hydrophilic antioxidant compounds (vitamin C and total phenols), as well as antioxidant activity (DPPH scavenging capacity and FRAP) increased as the nitrogen dose was reduced. The biosynthesis of the hydrophilic antioxidant compounds appears to be an induced resistance mechanism caused by the nitrogen-deficiency stress. In addition, B. licheniformis had a positive net effect on the synthesis of flavonoids by the plant at a 75% nitrogen dose. A two-factorial ANOVA (nitrogen fertilizer dose × biofertilizer addition) evidenced that the greatest contribution of the nitrogen fertilizer dose was to the total phenols content and antioxidant activity, while the biofertilizer mainly contributed to the vitamin C and lycopene contents. In general, the content of antioxidant compounds was affected by the interaction of the two factors. Significantly, this is the first report about the combined effect of the nitrogen fertilization dose and biofertilization addition during tomato cultivation, on the content of antioxidant compounds in tomato fruits.

BODIPY-derived molecular fluorescent rotors are one of the most useful families of fluorescent probes for the quantitative measurement of microviscosity. Here, we report the photophysical properties of two molecular rotors as ratiometric viscosity sensors, meso-(4-(9H-fluoren-2-yl)ethynyl)phenyl-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (1) and meso-(5-(9H-fluoren-2-yl)ethynyl)thiophen-2-yl-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (2) having two independent chromophores; one (fluorene) is not influenced by viscosity and is used to determine concentration properties, and the other chromophore (BODIPY) acts as a molecular rotor. The fluorescence ratiometric calibration against microviscosity for the most sensitive probe (1), was obtained in a wide linear dynamic range. The sensitivity of the spectroscopic observables for 1 and 2 towards solvent viscosity and the typical analytical interfering solvent polarity and polarizability parameters were investigated by means of two different solvent scales, namely Lippert–Mataga and Catalan, finding consistent results. Quantum chemical calculations were conducted to analyze the probe mechanism in terms of Natural Transition Orbitals (NTOs) and the spatial extent of charge transfer excitations.

Isoniazid is used as anti-tuberculosis drug which possesses functional groups capable of forming hydrogen bonds. A series of cocrystals of isoniazid (INH) with polyphenolic coformers such as catechol (CAT), orcinol (ORC), 2-methylresorcinol (MER), pyrogallol (PYR), and phloroglucinol (PLG) were prepared by solvent-assisted grinding. Powder cocrystals were characterized by infrared (IR) spectroscopy and X-ray powder diffraction. The crystal structure of the cocrystals revealed the unexpected hydration of the INH-MER cocrystal and the preference of the (phenol) O&ndash, H∙∙∙N (pyridine) and (terminal) N-H∙∙∙O (phenol) heterosynthons in the stabilization of the structures. The supramolecular architecture of the cocrystals is affected by the conformation and the substitution pattern of the hydroxyl groups of the polyphenols.

Ribotoxins are a family of fungal ribosome-inactivating proteins displaying highly specific ribonucleolytic activity against the sarcin/ricin loop (SRL) of the larger rRNA, with a-sarcin as its best-characterized member. Their toxicity arises from the combination of this activity with their ability to cross cell membranes. The involvement of a-sarcin's loops 2 and 3 in SRL and ribosomal proteins recognition, as well as in the ribotoxin-lipid interactions involving cell penetration, has been suggested some time ago. In the work presented now different mutants have been prepared in order to study the role of these loops in their ribonucleolytic and lipid-interacting properties. The results obtained confirm that loop 3 residues Lys 111, 112, and 114 are key actors of the specific recognition of the SRL. In addition, it is also shown that Lys 114 and Tyr 48 conform a network of interactions which is essential for the catalysis. Lipid-interaction studies show that this Lys-rich region is indeed involved in the phospholipids recognition needed to cross cell membranes. Loop 2 is shown to be responsible for the conformational change which exposes the region establishing hydrophobic interactions with the membrane inner leaflets and eases penetration of ribotoxins target cells.

The crystal packing of the compound is described by an inter­molecular arrangement with the mol­ecules as inter­laced layers in a zigzag fashion, denoting inter­acting self-complementary dimers mainly by the localization of weak hydrogen bonds in a head-to-tail arrangement., The title chalcone derivative, C13H10O2, adopts an E conformation about the C=C double bond. The mol­ecule is composed of a furanyl and a phenyl ring, bridged by an α,β-unsaturated carbonyl system, which are inclined to one another by 24.07 (7)°. In the crystal, mol­ecules are connected by weak C—H⋯O hydrogen bonds involving the carbonyl O atom acting as a trifurcated acceptor and C—H⋯π inter­actions, forming ribbons extending along the c-axis direction.

Fungal ribotoxins are highly specific extracellular RNases which cleave a single phosphodiester bond at the ribosomal sarcin-ricin loop, inhibiting protein biosynthesis by interfering with elongation factors. Most ribotoxins show high degree of conservation, with similar sizes and amino acid sequence identities above 85%. Only two exceptions are known: Hirsutellin A and anisoplin, produced by the entomopathogenic fungi Hirsutella thompsonii and Metarhizium anisopliae, respectively. Both proteins are similar but smaller than the other known ribotoxins (130 vs 150 amino acids), displaying only about 25% sequence identity with them. They can be considered minimized natural versions of their larger counterparts, best represented by α-sarcin. The conserved α-sarcin active site residue Tyr48 has been replaced by the geometrically equivalent Asp, present in the minimized ribotoxins, to produce and characterize the corresponding mutant. As a control, the inverse anisoplin mutant (D43Y) has been also studied. The results show how the smaller versions of ribotoxins represent an optimum compromise among conformational freedom, stability, specificity, and active-site plasticity which allow these toxic proteins to accommodate the characteristic abilities of ribotoxins into a shorter amino acid sequence and more stable structure of intermediate size between that of other nontoxic fungal RNases and previously known larger ribotoxins.

Fluoride toothpastes have long been recommended as part of the measures to prevent dental caries. Controversial findings suggest that an inappropriate use of this type of dentifrices can significantly contribute to the total intake of fluoride by children younger than 3 years, being one of the reasons why they have been linked to the development of dental fluorosis. The cost-benefit relationship of using fluoride dentifrices in children has been controversial and has allowed the evolution of concepts that reinforce the recommendations to use them. This topic review discusses some aspects that determine the preventive potential of fluoride toothpastes, the academic recommendations to use them, the various policies in Latin American countries on the issue, and a brief description of the availability of products in the Colombian market. This article seeks to contribute to a better understanding of this issue and therefore to a better orientation of patients. Keywords: dentifrices, fluoride, child, dosage, toothpaste. RESUMEN: Las cremas dentales fluoradas han sido recomendadas ampliamente como parte de la prevención de la caries dental. Resultados controversiales sugieren que su uso inadecuado puede contribuir de manera importante a la ingesta total de fluoruros en niños menores de 3 años, siendo ésta una de las razones por las que han sido relacionadas con el desarrollo de fluorosis dental. La relación costo-beneficio del uso de los dentífricos fluorados en los niños ha generado controversia y ha permitido la evolución de conceptos que cimientan las recomendaciones de uso. En esta revisión de tema se presentan algunos aspectos que determinan el potencial preventivo de las cremas dentales fluoradas, las recomendaciones académicas sobre su uso, distintas normativas gubernamentales de países de América Latina en torno al tema, y una breve descripción de la disponibilidad de productos en el mercado colombiano. Se pretende contribuir así a una mayor comprensión del tema y por tanto a una mejor orientación individual de los pacientes. Palabras clave: flúor, niño, formas de dosificación, pastas de dientes

Here is reported the use of a titanium oxide:fullerene (TiO x :PC 71 BM) composite film as electron collector layer in organic photovoltaic devices (OPV cells). OPV cells were fabricated under the bulk heterojunction architecture: the active layer was a blend of either the photoconductor polymer MEH–PPV or P3HT with the fullerene derivative PC 71 BM. As cathode the eutectic alloy of Bi, In and Sn, known as Field’s metal, was used. The melting point of this alloy is above 62 °C, which makes it suitable for a vacuum-free deposition process and easy and fast device test. Cell fabrication and testing were carried out at normal room conditions. For OPV cells based on MEH–PPV, the composite thin electron collector layer improved the power conversion efficiency ( η ) from 1.12% to 2.07%, thus the η increase was about 85%. Meanwhile, for devices based on P3HT the use of the composite film improved the photocurrent in almost 1 mA/cm 2 and the efficiency slightly increase from 2.48% to 2.68%.

The neurokinin B/NK3 receptor (NK3R) and kisspeptin/kisspeptin receptor (KISS1R), two systems which are essential for reproduction, are coexpressed in human mural granulosa (MGC) and cumulus cells (CCs). However, little is known about the presence of other members of the tachykinin family in the human ovary. In the present study, we analyzed the expression of substance P (SP), hemokinin-1 (HK-1), NK1 receptor (NK1R), and NK2 receptor (NK2R) in MGCs and CCs collected from preovulatory follicles of oocyte donors at the time of oocyte retrieval. RT-PCR, quantitative RT-PCR, immunocytochemistry, and Western blotting were used to investigate the patterns of expression of tachykinin and tachykinin receptor mRNAs and proteins and the possible interaction between the tachykinin family and kisspeptin. Intracellular free Ca2+ levels ([Ca2+]i) in MGCs after exposure to SP or kisspeptin in the presence of SP were also measured. We found that SP, HK-1, the truncated NK1R isoform NK1R-Tr, and NK2R were all expressed in MGCs and CCs. NK1R-Tr mRNA and NK2R mRNA and protein levels were higher in MGCs than in CCs from the same patients. Treatment of cells with kisspeptin modulated the expression of HK-1, NK3R, and KISS1R mRNAs, whereas treatment with SP regulated kisspeptin mRNA levels and reduced the [Ca2+]i response produced by kisspeptin. These data demonstrate that the whole tachykinin system is expressed and acts in coordination with kisspeptin to regulate granulosa cell function in the human ovary.

The synthesis and structural characterization of six 1,4-diazepanes prepared by condensation of 2,2′-(1,3-propanediyldiimino)diphenols with glyoxal or 2,3-butanedione to give bisbenzoxazolidines and subsequent reduction with BH3–DMS is reported. The new 1,4-diazepanes were obtained in yields between 75% and 83% and characterized by NMR, IR, and HRMS. In addition, the crystal structure analysis showed that the seven-membered ring in 1,4-diazepanes (12a, 12e, and 12d) and bisbenzoxazolidines (11a, 11c, 11f) adopt in all cases twisted chair conformation. Compounds 12a and 12e show disorder in the seven member ring, as a result of the conformational flexibility of the seven-membered ring.

The optical and electrical properties of twofold SRO films were analyzed. MOS-like structures with twofold SRO films as the active layer were fabricated. The twofold SRO layer is composed by a silicon rich and a near stoichiometric silicon oxide films in order to have a barrier to isolate the silicon substrate from the active SRO layer. These devices show an enhanced conductivity under different illumination conditions. Results show that all structures have a higher current when light shines on them than that obtained under dark conditions. A possible application of this photo-effect can be used to increase the response of photodetectors and silicon solar cells.

A single-chain fusion protein that directed the cytolytic activity of α-sarcin to A33 tumor antigen expressing cells was constructed and shown to effectively kill targeted cells. Glycoprotein A33 (GPA33) is a well-known colon cancer marker and a humanized antibody against it was used to target the α-sarcin. The fungal ribotoxin α-sarcin is one of the most potent and specific toxins known. It is small, protease resistant, thermostable and highly efficient towards the inactivation of ribosomes. This work describes the production and characterization of an immunotoxin resulting from fusing the single-chain variable fragment (scFv) of the monoclonal antibody that targets GPA33 to fungal α-sarcin. This chimeric protein (scFvA33αsarcin), produced in Pichia pastoris and purified in high yield was proven to be properly folded, active, specific and stable. It showed high specific toxicity against GPA33-positive tumoral cell lines providing scientific evidence to sustain that scFvA33αsarcin is a good immunotherapeutic candidate against GPA33-positive colon carcinomas.

Ribotoxins are a family of toxic proteins that exert a highly specific cleavage at the universally conserved sarcin/ricin loop (SRL) of the larger rRNA molecule. Before this ribonucleolytic action, passage through the cell membrane is a necessary step for ribotoxin internalization and the limiting factor for cytotoxicity. Although extensive knowledge of their ribonucleolytic activity and substrate recognition has been accumulated, little is known about the mechanisms of cell entry of ribotoxins. Hirsutellin A (HtA) is a recently described member of this family, which accommodates the main abilities of previously characterized ribotoxins into a shorter sequence, but exhibits some differences regarding membrane interaction properties. This work investigates the contribution of tryptophan (Trp) residues 71 and 78 to both endoribonucleolytic activity and cellular toxicity of this ribotoxin. Substitution mutants W71F and W78F, as well as the double mutant W71/78F, were obtained and assayed against isolated ribosomes, synthetic SRL, and human tumor cells. The results provide evidence that cell membrane passage and internalization, as well as substrate-specific recognition, require the participation of the region involving both Trp 71 and Trp 78. Additionally, the mutant W71/78F is the first non-cytotoxic but specific ribosome-cleaving ribotoxin mutant obtained to date.

N-heterocyclic norbornene Dicarboximides were synthesized by reacting the exo-norbornene-5,6-dicarboxylic anhydride with 2-, 3-, and 4-aminopyridine. The amides resulting from 3 and 4-aminopyridine derivatives were converted into the corresponding betaines via Menshutkin reaction using ethyl-bromoacetate. The chemical structures of the obtained products were confirmed by FT-IR and 1 H and 13 C NMR spectroscopy, EA and MS as well as by calculation of 1 H and 13 C NMR chemical shifts using the GIAO method (PW91/6-311G++ (3df, 3pd) approximation by GAUSSIAN and PW91/IGLO-III approximation by deMon2k).

The ribosomal sarcin/ricin loop (SRL) is the target of ribosome-inactivating proteins like the N-glycosidase ricin and the fungal ribotoxin α-sarcin. The eukaryotic ribosomal stalk directly interacts with several members of the N-glycosidase family, favoring their disruption of the SRL. Here we tested this hypothesis for the ribotoxin α-sarcin. Experiments with isolated ribosomes, cell-free translation systems, and viability assays with Saccharomyces cerevisiae strains defective in acidic stalk proteins showed that the inactivation exerted by α-sarcin is independent of the composition of the ribosomal stalk. Therefore, α-sarcin, with the same ribosomal target as ricin, seems to access the SRL by a different pathway.

In this work we report the synthesis and spectroscopic characterization of twenty new pentacoordinated diorganotin(IV) compounds. These compounds have been prepared in good yields by multicomponent reactions (MCRs) of α-amino acids (isoleucine, leucine, methionine, phenylalanine and aminophenylacetic acid), 2,4-dihydroxybenzaldehyde, 2-hydroxy-4-methoxybenzaldehyde and either di-n-butyltin(IV) oxide or diphenyltin(IV) oxide. All compounds were characterized by IR spectroscopy, 1H, 119Sn and 13C NMR spectroscopy and mass spectrometry. Each compound has a coordinative N→Sn bond and shows the expected 119Sn NMR chemical shift indicative of a pentacoordinated or hexacoordinated tin atom in CDCl3 and DMSO-d6, respectively. These compounds were also tested in tumoral cell lines, HeLa, HCT-15 and MCF-7, in order to evaluate the antiproliferative activity and to obtain the medial inhibitory concentrations (IC50) values.

The synthesis and characterization of a set of poly(aryl ether) dendrimers with tetraphenylporphyrin as the core and 4, 8, 16, or 32 closo-carborane clusters are described. A regioselective hydrosilylation reaction on the allyl-terminated functions with carboranylsilanes in the presence of Karstedt’s catalyst leads to different generations of boron-enriched dendrimers. This versatile approach allows the incorporation of a large number of boron atoms in the dendrimers’ periphery. Translational diffusion coefficients (D) determined by DOSY NMR experiments permit estimation of the hydrodynamic radius (RH) and molecular size for each dendrimer. Furthermore, a notable correlation between D and the molecular weight (MW) is found and can be used to predict their overall size and folding properties. The UV–vis and emission behavior are not largely affected by the functionalization, therefore implying that the presence of carboranes does not alter their photoluminescence properties.

International audience; Molybdenum complexes of type [MoO2L](n) (L = tridentate ONO Schiff base ligands based on the salicylidene-2-aminophenolato structure) have been synthesized and used as catalysts for the solvent-free epoxidation of olefins. The effect of donor (diethylamino) and/or acceptor (nitro) substituents has been studied.

To quantify the impact of organophosphate pesticides on aquatic ecosystems requires a mechanistic understanding of their behaviour in a range of environmental matrices. The objective of this study was to compare the sorption/desorption, biodegradation and toxic effects of the Pestanal grade and commercial formulation (Ectomort Centenary) of the organophosphate insecticide propetamphos in river and estuarine sediments. For both formulations, the sorption of propetamphos onto sediment was initially very rapid followed by a slower sorption phase. Similarly, the initial rate of desorption was rapid, followed by a much slower rate. In both sorption and desorption experiments, the level of sorbed propetamphos was considerably higher for the commercial formulation of propetamphos (Kd=7-11) than for the Pestanal grade (Kd=4-10). The rate of propetamphos biodegradation was sediment dependent but was most rapid where microbial activity and nutrients were the highest and sorption was the lowest. Propetamphos was more rapidly degraded in sediments under aerobic (t(1/2)=15 d) compared to anaerobic conditions (t(1/2)=19 d). However, no significant difference in the biodegradation rates of the Pestanal grade and commercial formulations of propetamphos were observed. The toxic effect of propetamphos on sediment microbial communities was significantly greater for the commercial formulation than for the Pestanal grade of propetamphos based on EC50 (21 versus 236 microg g(-1)) and EC10 values (0.3 versus 54 microg g(-1)). In conclusion, our results highlight the importance of using commercial pesticide formulations when carrying out ecotoxicological testing.

Hatchery-produced Sphoeroides annulatus were studied from fertilized egg until day 32 post-hatch to examine the digestive tract development and to evaluate its digestive capacity during the larval period. Fish larvae were progressively fed microalgae, rotifers, Artemia nauplii and a formulated microdiet. Digestive tract development, trypsin activity, and trypsinogen gene expression in fish samples were analyzed by histology, histochemistry and reverse-transcription coupled to the polymerase chain reaction (RT–PCR) respectively. The intestine and liver started to develop on day 1 after hatch, followed by the pancreas. The mouth opened at day 4 after hatch, which was the start of rotifer feeding. Trypsinogen gene expression was detected very early in development, starting in the fertilized egg, showing a sharp increase in eggs at 75 h after fertilization, and then a gradual increase after hatching as the larvae developed. Trypsin activity by histochemistry was first detected at day 2 post-hatch, and maximum expression and activity were observed at days 16 to 24 after hatch, which corresponded to the period of Artemia nauplii feeding. No gastric glands were observed during the whole period of study. From day 28 onwards the fish were fed with a formulated microdiet, at this time both trypsin synthesis and activity decreased, suggesting a more important role for other enzymes in the digestion process.

The three-dimensional structures of the α-sarcin ribotoxin and its Δ(7–22) deletion mutant, both complexed with a 20-mer oligonucleotide mimicking the sarcin/ricin loop (SRL) of the ribosome, have been docked into the structure of the Halobacterium marismortui ribosome by fitting the nucleotide atomic coordinates into those of the ribosomal SRL. This study has revealed that two regions of the ribotoxin, residues 11–16 and 84–85, contact the ribosomal proteins L14 (residues 99–105) and L6 (residues 88–92), respectively. The first of these two ribotoxin regions appears to be crucial for its specific ribosome recognition., This work was supported by Grants BMC2003/03227 and BIO2002/720 from the Ministerio de Ciencia y Tecnología (Spain). F.G-M., L.G-O., and E.A-G. were recipients of fellowships from the Comunidad Autónoma de Madrid and Ministerio de Educación (Spain).

Ribonuclease U2 is a low-molecular-weight acidic protein with three disulfide bridges. This protein displays an anomalous electrophoretic behavior on standard SDS-PAGE. The electrophoretic mobility of the nonreduced protein roughly corresponds to its molecular mass while the migration of the reduced protein would be in accordance with the expected molecular mass of the protein dimer. This study reveals that the protein does not bind SDS under the SDS-PAGE conditions, its electrophoretic mobility being only determined by its electrostatic charge and hydrodynamic properties. In addition, the nonreduced protein cannot be blotted to a membrane. Unfolding of the protein upon reduction of its disulfide bridges enables electrotransference to membranes due to a restricted diffusion along the electrophoresis gel.

The excited triplet states of a set of water-soluble 4-sulfonatophenyl meso-bis and meso-tetrakis substituted porphyrinoids were studied in a wide range of concentrations. All of these porphyrinoids show the formation of π-stacked aggregates (H aggregates). As a consequence of the 5,15-diaryl substitution, and of aggregation, two excited triplet states can be detected, the more stable being accessible only by internal conversion of the current excited-state T1. The aggregates showed a significant singlet oxygen quantum yield [1O2 (1Δg), determined by the phosphorescence method], which in most cases was of the same order as the monomeric forms.

Self-diffusion in model Al and Ni has been studied by molecular static and molecular dynamic techniques. The structure of defect-lattice configurations has been obtained with the former technique. With the latter, the vacancy diffusion mechanism has been analysed over a wide temperature range, and particular attention has been paid to multiple jumps in the high temperature region. The possible contribution of divacancies, within the limits imposed by the interatomic potentials used, has also been considered.

A family of 15 N-substituted phenothiazines was designed, synthesized and their acaricidal activity against Rhipicephalus microplus was determined in vitro. The synthetic methodology is simple and can be employed in multigram scale. The rationale for the structure-based design of these compounds is the potential for azines and phenothiazine to engage in π–π interactions; these fragments, joined together by a short, flexible alkoxide linker, structurally resemble phenothiazine-based cholinesterase inhibitors, while their weak basicity implies a neutral active form, rather than a cationic one, thus facilitating penetration of the cuticle of ticks. One compound displayed excellent acaricidal activity (LD 50 = 0.58 μg/mL). Preliminary SAR analysis suggests that the activity is influenced by the presence of a weakly basic nitrogen atom, as well as the substitution pattern within the heterocycles.

The effect of the addition of β- and γ-cyclodextrin (β-CD, γ-CD) to water solutions ( D 2 O ) of the 4'-sulfonato derivatives of meso-tetraphenylporphyrin (TPPS4, TPPS3, TPPS2o and TPPS2a) was studied by 1 H NMR at several temperatures. In all cases the disaggregation of the porphyrin homoassociates was detected, although in most cases it was only partial. Nuclear Overhauser signals (ROESY) show that cyclodextrin inclusion complexes were formed with TPPS4, TPPS3, and TPPS2o, but not with TPPS2a. These complexes include the sulfonatophenyl groups as guest, but not the hydrophobic phenyl substituents. The geometry of the complexes corresponds to that in which the sulfonatophenyl substituent is introduced through the secondary face of β-CD and through the primary face of γ-CD. In the inclusion complexes the polar sulfonato group is inside the cyclodextrin cavity but near to the hydrophilic interface with the bulk water. This explains the absence of complexation in the case of cationic porphyrins such as 5,10,15,20-tetrakis(N-methylpyridin-4-yl)porphyrin (TMPyP), and the decrease in the solubility when the β-CD complex of 5,15-bis(4-sulfonatophenyl)porphyrin (DPPS2o) forms. Complexes of the cyclodextrins with porphyrin homoassociates were also detected. This indicates that the heteroassociation avoids the formation of staggered stacks of porphyrin homoassociates, but has less effect on the association through the hydrophobic region of the phenyl substituents. This last type of aggregation, which is not significantly affected by the addition of α-CD, explains why the hydrophobic phenyl substituents are not complexed by the cyclodextrins.

The sulfonation of 5,15-bis(phenyl)porphyrin (DPP) in concentrated sulfuric acid results in substitution on the β-pyrrolic positions and the expected sulfonation on the para positions of the phenyl substituents. The sodium salt of 5,15-bis(4-sulfonatophenyl)porphyrin-2-sulfonic acid ( S 3 DPP ) was prepared in good yield, the sodium salts of 5,15-bis(4-sulfonatophenyl)porphyrin ( S 2 A DPP ), 5-phenyl-15-(4-sulfonatophenyl)porphyrin-2-sulfonic acid ( S 2 B DPP ) and 15-phenyl-5-(4-sulfonatophenyl)porphyrin ( S 1 A DPP ) were isolated, and 5,15-bis(phenyl)porphyrin-2-sulfonic acid ( S 1 B DPP ) was detected in a mixture with S 1 A DPP . The β-pyrrole sulfonato substituents are stable and their potential synthetic use is shown by the preparation of the trisodium salt of 10-bromo-5,15-bis(4-sulfonatophenyl)porphyrin-2-sulfonic acid ( BrS 3 DPP ) by NBS bromination of S 3 DPP . In a methanol/sulfuric acid mixture the sulfonation occurs on the meso positions, and the tetrasodium salt of 10,20-bis (4-sulfonatophenyl)porphyrin-5,15-disulfonic acid ( S 4 DPP ) was obtained.

Both the general principle and the historical development of the Constant Rate Thermal Analysis (CRTA) and of the TG technique are described. It is shown that CRTA, whose aim is to reduce at will pressure and temperature gradients inside the sample, has a much more effective control on heat and mass transfer phenomena than conventional TG. The successes and failures of TG is shown. It is shown also how the field of CRTA is as broad as that of conventional TG since it uses the same technique and the same equipment but in a basically different way: CRTA is in some respects the opposite of TG.

The actual kinetics of a solid state reaction cannot be discerned by means of the kinetic analysis of a single TG curve. The cause of this relates to the fact that different kinetic equations appear to fit a set of kinetic data. This paper shows the advantage of a choice of method based on comparing data from several experiments at the same degree of conversion. But this procedure must be carried out with great care. The limitations are discussed.

The errors in the activation energy of solid-state reactions calculated using “temperature criterion” method have been calculated; errors in the kinetic parameters are strongly dependent on the kinetic law obeyed by the reaction. A theoretical explanation of this behaviour is given.

The influence of the pressure of carbon dioxide on the thermal decomposition kinetics of calcium carbonate is studied. It is shown that it is possible to obtain meaningful and reliable kinetic parameters from isothermal and non-isothermal data provided that the pressure correction term is included in the kinetic equation.