Discrimination of biclonal B-cell chronic lymphoproliferative neoplasias by tetraspanin antigen expression

This work was supported by Grants from MEC SAF2004-02900 (PAL) and SAF 2002-03096 (AO), Fondo de Investigación Sanitaria PI02-0585 (PAL), and Fundación Memoria Samuel Solórzano Barruso (PAL).Peer Reviewe

Influencia del tratamiento «a fuego» en las características del estuco tradicional con cal

This research advances in the attempt to recover the traditional technique of stucco by fire; paradigm of indoor decoration until half of 20th century due to its high quality marbled imitations. On its implementation process, it was used lime mortars with marble aggregates, mineral pigments and greases. With these materials, masses were prepared and extended into the walls, they were painted in fresco and ended with the passage of a heated metal tool. As with any other technique, the time passing over has blurred the knowledge on the subject, making very difficult the preservation or restoration of examples in our heritage. Despite of the limited literature, the process has been recovered; subjecting the samples prepared at different trials that have characterized the finished, both in its merits and its conferred characteristics by finally protecting the samples with a layer of wax, as was done traditionally.Esta investigación avanza en el intento de recuperar la técnica tradicional del estuco a fuego, paradigma de la decoración de espacios interiores hasta la mitad del s. XX por sus imitaciones marmóreas de gran calidad. Para ejecutarlos se utilizaban morteros de cal con áridos de mármol, pigmentos minerales y grasas; con estos materiales se preparaban y tendían las masas, se pintaban al fresco y se terminaban con el paso de una herramienta metálica caliente. Como sucede con otras técnicas, el paso del tiempo ha difuminado los conocimientos sobre la materia, haciendo muy difícil la conservación o restauración de los ejemplos en nuestro patrimonio. A partir de la escasa bibliografía existente se ha recuperado el proceso, sometiendo las muestras elaboradas a diferentes ensayos que han caracterizado el acabado final, tanto en sus características intrínsecas como en las que le son conferidas al proteger finalmente las muestras con una capa de cera, tal y como se realizaba tradicionalmente

Efficient inhibition of iron superoxide dismutase and of Trypanosoma cruzi growth by benzo[g]phthalazine derivatives functionalized with one or two imidazole rings

The synthesis and trypanosomatic behavior of a new series of 1,4-bis(alkylamino)benzo[g]phthalazines 1−4 containing the biologically significant imidazole ring are reported. In vitro antiparasitic activity against Trypanosoma cruzi epimastigotes is remarkable, especially for compound 2, whereas toxicity against Vero cells is very low. Conversion of epimastigotes to metacyclic forms in the presence of the tested compounds causes significant decreases in the amastigote and trypomastigote numbers. Fe-SOD inhibition is noteworthy, whereas effect on human Cu/Zn-SOD is negligible.The authors thank the Spanish CICYT for the financial support

In vivo trypanosomicidal activity of imidazole- or pyrazole-based benzo[ g ]phthalazine derivatives against acute and chronic phases of chagas disease

The in vivo trypanosomicidal activity of the imidazole-based benzo[g]phthalazine derivatives 1−4 and of the new related pyrazole-based compounds 5 and 6 has been studied in both the acute and chronic phases of Chagas disease. As a rule, compounds 1−6 were more active and less toxic than benznidazole in the two stages of the disease, and the monosubstituted derivatives 2, 4, and 6 were more effective than their disubstituted analogs. Feasible mechanisms of action of compounds 1−6 against the parasite have been explored by considering their inhibitory effect on the Fe-SOD enzyme, the nature of the excreted metabolites and the ultrastructural alterations produced. A complementary histopathological analysis has confirmed that the monosubstituted derivatives are less toxic than the reference drug, with the behavior of the imidazole-based compound 4 being especially noteworthy.The authors thank the Santander-Universidad Complutense Research Program (Grant GR58/08-921371-891), the Spanish MEC Project (Grant CGL2008-03687-E/BOS), and the MCINN Projects (CTQ2009-14288-C04-01 and Consolider CSD2010-00065) for financial support

1,4-Bis(alkylamino)benzo[g]phthalazines able to form dinuclear complexes of Cu(II) which as free ligands behave as SOD inhibitors and show efficient in vitro activity against Trypanosoma cruzi

The synthesis of a new series of 1,4-bis(alkylamino)benzo[g]phthalazines 1–3 is reported, and their ability to form dinuclear complexes with Cu(II) assayed. The geometry of the complexes is dependent on the nature of the electron-donor sites at the sidechains. Compounds 1 and 2, that contain sp3 or sp2 nitrogens at the end of the alkylamino groups, originate monopodal dinuclear complexes which seem to include endogenous OH bridges, and the sidechains seem to actively participate in complexation. However, the substitution of nitrogen by oxygen in 3 leads to a tripodal dinuclear complex in which the sidechains are not involved. The in vitro antiparasitic activity on Trypanosoma cruzi epimastigotes and amastigotes and the SOD activity inhibition have been evaluated for compounds 1–3, and, as expected, 1 and 2 show in all cases relevant results, whereas 3 is always the less active among the three substrates tested.The authors thank the Spanish Comision Interministerial de Ciencia y Tecnologia for the economical support given to this work (SAF99-0066)

Modeling arsenic in European topsoils with a coupled semiparametric (GAMLSS-RF) model for censored data

Arsenic (As) is a versatile heavy metalloid trace element extensively used in industrial applications. As is carcinogen, poses health risks through both inhalation and ingestion, and is associated with an increased risk of liver, kidney, lung, and bladder tumors. In the agricultural context, the repeated application of arsenical products leads to elevated soil concentrations, which are also affected by environmental and management variables. Since exposure to As poses risks, effective assessment tools to support environmental and health policies are needed. However, the most comprehensive soil As data available, the Land Use/Cover Area frame statistical Survey (LUCAS) database, contains severe limitations due to high detection limits. Although within International Or- ganization for Standardization standards, the detection limits preclude the adoption of standard methodologies for data analysis. The present work focused on developing a new method to model As contamination in European soils using LUCAS soil samples. We introduce the GAMLSS-RF model, a novel approach that couples Random Forests with Generalized Additive Models for Location, Scale, and Shape. The semiparametric model can capture non-linear interactions among input variables while accommodating censored and non-censored observations and can be calibrated to include information from other campaign databases. After fitting and validating a spatial model, we produced European-scale As concentration maps at a 250 m spatial resolution and evaluated the patterns against reference values (i.e., two action levels and a background concentration). We found a significant variability of As concentration across the continent, with lower concentrations in Northern countries and higher concentrations in Portugal, Spain, Austria, France and Belgium. By overcoming limitations in existing databases and methodologies, the present approach provides an alternative way to handle highly censored data. The model also consists of a valuable probabilistic tool for assessing As contamination risks in soils, contributing to informed policy-making for environmental and health protection

Proteomic analysis of a media conditioned by growing deer antler tissues: identification of its neurite growth promoting proteins

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Three-dimensional cardiac fibre disorganization as a novel parameter for ventricular arrhythmia stratification after myocardial infarction

Aims: Myocardial infarction (MI) alters cardiac fibre organization with unknown consequences on ventricular arrhythmia. We used diffusion tensor imaging (DTI) of three-dimensional (3D) cardiac fibres and scar reconstructions to identify the main parameters associated with ventricular arrhythmia inducibility and ventricular tachycardia (VT) features after MI. Methods and results: Twelve pigs with established MI and three controls underwent invasive electrophysiological characterization of ventricular arrhythmia inducibility and VT features. Animal-specific 3D scar and myocardial fibre distribution were obtained from ex vivo high-resolution contrast-enhanced T1 mapping and DTI sequences. Diffusion tensor imaging-derived parameters significantly different between healthy and scarring myocardium, scar volumes, and left ventricular ejection fraction (LVEF) were included for arrhythmia risk stratification and correlation analyses with VT features. Ventricular fibrillation (VF) was the only inducible arrhythmia in 4 out of 12 infarcted pigs and all controls. Ventricular tachycardia was also inducible in the remaining eight pigs during programmed ventricular stimulation. A DTI-based 3D fibre disorganization index (FDI) showed higher disorganization within dense scar regions of VF-only inducible pigs compared with VT inducible animals (FDI: 0.36; 0.36-0.37 vs. 0.32; 0.26-0.33, respectively, P = 0.0485). Ventricular fibrillation induction required lower programmed stimulation aggressiveness in VF-only inducible pigs than VT inducible and control animals. Neither LVEF nor scar volumes differentiated between VF and VT inducible animals. Re-entrant VT circuits were localized within areas of highly disorganized fibres. Moreover, the FDI within heterogeneous scar regions was associated with the median VT cycle length per animal (R2 = 0.5320). Conclusion: The amount of scar-related cardiac fibre disorganization in DTI sequences is a promising approach for ventricular arrhythmia stratification after MI.The CNIC (Madrid, Spain) is supported by the Ministry of Science, Innovation and Universities and the Pro CNIC Foundation. The CNIC and the BSC (Barcelona, Spain) are Severo Ochoa Centers of Excellence (SEV-2015-0505 and SEV-2011-0067, respectively). This study was supported by grants from Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional (RD12/0042/0036, CB16/11/00458), Spanish Ministry of Science, Innovation and Universities (SAF2016-80324-R, PI16/02110, and DTS17/00136), and by the European Commission [ERA-CVD Joint Call (JTC2016/APCIN-ISCIII-2016), grant#AC16/00021]. The study was also partially supported by the Fundacion Interhospitalaria para la Investigacion Cardiovascular (FIC, Madrid, Spain), the Spanish Society of Cardiology (Dr. Pedro Zarco award) and the Heart Rhythm section of the Spanish Society of Cardiology (DFR). J.J. is supported by R01 Grant HL122352 from the National Heart Lung and Blood Institute, USA National Institutes of Health. J.A.S. is funded by the CompBioMed project, H2020-EU.1.4.1.3 European Union's Horizon 2020 research and innovation programme, grant#675451. D.G.L. has received financial support through the 'la Caixa' Fellowship Grant for Doctoral Studies, 'la Caixa' Banking Foundation, Barcelona, Spain.S