Immunoinformatics lessons on the current COVID-19 pandemic and future coronavirus zoonoses

This work was supported by the Spanish Ministry of Science and “Acción Estratégica en Salud” MPY 388/18.S

Tratamiento terapéutico de leucemias linfoblásticas agudas T y B y linfomas humanos por inhibición del receptor de interleuquina-7 (IL-7R)

La presente invención se refiere al tratamiento terapéutico de leucemias linfoblásticas agudas (LLA) humanas de células T y B (LLA-T y LLA-B) y linfomas humanos, por inhibición del receptor de interleuquina- 7 (IL-7R) humana. Un primer aspecto de la presente invención es un agente inhibidor o bloqueante, preferentemente un anticuerpo o un fragmento del mismo, capaz de bloquear la función de la cadena {al} del receptor de interleuquina 7 (IL-7R{al}) humano, para la prevención y/o el tratamiento de una LLA humana o de un linfoma humano. Asimismo, la presente invención hace referencia a una composición farmacéutica y a un modelo de identificación, expansión y mantenimiento in vivo de células iniciadoras de LLA-T y LLA-B primarias humanas con capacidad de iniciar el injerto de la leucemia en ratones inmunodeficientes, así como la caracterización de estas células iniciadoras de LLA-T y LLA-B como células que expresan altos niveles del IL-7RPeer reviewedConsejo Superior de investigaciones CientíficasB1 Patente sin examen previ

Parasite-host relationships of water mites (Acari: Hydrachnidia) and black flies (Diptera: Simuliidae) in southeastern Spain

Abstract Background: Documentation on water mites in Spain is scarce, as is information on the parasite-host relationship between certain water mite species and representatives of the dipteran family Simuliidae. The discomfort caused to humans and animals by black fies seems to be increasing in recent years. In this context, an investigation of parasitic water mites is of great importance, not only from the point of view of biodiversity, but also in terms of their potential to control black fy populations. Methods: Rivers across a wide region of eastern Spain were sampled to determine the specifc richness of simuliid dipterans and to investigate their possible parasites, such as water mites, mermithid nematodes and microsporidia (fungal microbes). Data on environmental variables, abundance, prevalence and intensity of parasitism on the collected specimens were analyzed. Results: In 10 streams, 15,396 simuliid pupae were collected and checked for the presence of water mite larvae; 426 pupae in seven streams were found to be associated with water mite larvae. Of the 21 simuliid species identifed based on morphological characters, eight were found to be associated with water mite larvae. Water mite infection was not equally distributed among black fy species. Also, the prevalence of parasitism was low and difered among simuliid species, ranging from one to 13 water mites per black fy pupa. Variation at the intra- and interspecifc levels was detected in terms of the number of water mites inside the black fy cocoons. Free-living deutonymphal and adult water mites representing 15 diferent species of six genera and fve families were morphologically identifed. The taxonomic identity of the parasitic mite larvae is unclear at present. Morphologically, they ft descriptions of larval Sperchon (Hispidosperchon) algeriensis Lundblad, 1942, but the possibility cannot be excluded that they represent Sperchon algeriensis, the most abundant species at the adult stage in this study and unknown at the larval stage, or even another species of the genus. A molecular analysis produced for the frst time cytochrome oxidase I gene sequences for S. algeriensis. Conclusions: Our results contribute to current knowledge on Spanish Hydrachnidia and their relationships with simuliids as hosts. However, further research is needed to evaluate the diversity, distribution, bioecology and prevalence of this parasitism

Study, mechanical characterization and mathematical modeling of compatible SEBS blends for industrial applications in orthopedics and childcare

"This is an Accepted Manuscript of an article published by Taylor & Francis in Polymer-Plastics Technology and Engineering on JUL 15 2013, available online:www.tandfonline.com/doi/full/10.1080/03602559.2013.763363"In this work, a system of compatible blends based on two commercial grades of a thermoplastic elastomer, styrene-ethylene/ butylene-styrene (SEBS), with extreme Shore A hardness values (5 and 90), was studied in order to obtain a range of different performance blends for orthopedic and childcare applications, where usually liquid silicone rubber is used. Mechanical properties of different blends were obtained, and Equivalent Box Model (EBM) was used for the prediction of the mechanical behavior. The results show good agreement between the theoretical model and experimental data of new blends of SEBS.The authors thank "Ministerio de Ciencia y Tecnologia", Ref: DPI2007-66849-C02-02 and Generalitat Valenciana FPA/2010/027 for financial support.Juárez Varón, D.; García Sanoguera, D.; Ferrándiz Bou, S.; Peydro, MA.; Balart Gimeno, RA. (2013). Study, mechanical characterization and mathematical modeling of compatible SEBS blends for industrial applications in orthopedics and childcare. Polymer-Plastics Technology and Engineering. 52(9):862-868. https://doi.org/10.1080/03602559.2013.763363S862868529Xiao, D., Mo, Y., & Choi, M. M. F. (2003). A hand-held optical sensor for dissolved oxygen measurement. Measurement Science and Technology, 14(6), 862-867. doi:10.1088/0957-0233/14/6/323Sagripanti, J.-L., & Bonifacino, A. (1996). Comparative sporicidal effect of liquid chemical germicides on three medical devices contaminated with spores of Bacillus subtilis. 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Plastics, Rubber and Composites, 29(5), 229-234. doi:10.1179/146580100101541003Lopez, L. M., Cosgrove, A. B., Hernandez-Ortiz, J. P., & Osswald, T. A. (2007). Modeling the vulcanization reaction of silicone rubber. Polymer Engineering & Science, 47(5), 675-683. doi:10.1002/pen.20698Bose, S., Mukherjee, M., & Das, C. K. (2009). Silicone Rubber Compatibilized Syndiotactic Polystyrene and Thermotropic Liquid Crystalline Polymer (Vectra A950) Blend. Polymer-Plastics Technology and Engineering, 48(2), 158-163. doi:10.1080/03602550802577346Vijayalakshmi, N., Reddy, M. M., Naidu, S. V., Ramanjappa, T., & Appalanaidu, P. (2008). Immiscibility of Silicone Rubber and Polymethylmethacrylate. International Journal of Polymeric Materials and Polymeric Biomaterials, 57(7), 709-716. doi:10.1080/00914030801891302Wang, J., Feng, L., Chao, X., & Feng, Y. (2012). Performance of Room Temperature Vulcanized (RTV) Silicone Rubber-Based Composites: DBDPO/RTV and DBDPE/Sb2O3/RTV. Polymer-Plastics Technology and Engineering, 51(12), 1245-1250. doi:10.1080/03602559.2012.699130Wu, C., Li, W., Gao, D., & Jia, M. (2009). Study of Resistance of Silicone Resin to Heat and Irradiation. Polymer-Plastics Technology and Engineering, 48(10), 1094-1100. doi:10.1080/03602550903147213Ahmad, Z., Kumar, K. D., Saroop, M., Preschilla, N., Biswas, A., Bellare, J. R., & Bhowmick, A. K. (2009). Highly transparent thermoplastic elastomer from isotactic polypropylene and styrene/ethylene-butylene/styrene triblock copolymer: Structure-property correlations. Polymer Engineering & Science, 50(2), 331-341. doi:10.1002/pen.21540Barbe, A., Bökamp, K., Kummerlöwe, C., Sollmann, H., Vennemann, N., & Vinzelberg, S. (2005). Investigation of modified SEBS-based thermoplastic elastomers by temperature scanning stress relaxation measurements. Polymer Engineering & Science, 45(11), 1498-1507. doi:10.1002/pen.20427Masoomi, M., Katbab, A. A., & Nazockdast, H. (2006). Reduction of Noise from Disc Brake Systems Using Composite Friction Materials Containing Thermoplastic Elastomers (TPEs). Applied Composite Materials, 13(5), 305-319. doi:10.1007/s10443-006-9018-7Puskas, J. E., Foreman-Orlowski, E. A., Lim, G. T., Porosky, S. E., Evancho-Chapman, M. M., Schmidt, S. P., … Lovejoy, K. (2010). A nanostructured carbon-reinforced polyisobutylene-based thermoplastic elastomer. Biomaterials, 31(9), 2477-2488. doi:10.1016/j.biomaterials.2009.12.003Reddy, S., Arzt, E., & del Campo, A. (2007). Bioinspired Surfaces with Switchable Adhesion. Advanced Materials, 19(22), 3833-3837. doi:10.1002/adma.200700733Xu, J., Zhang, A., Zhou, T., Cao, X., & Xie, Z. (2007). A study on thermal oxidation mechanism of styrene–butadiene–styrene block copolymer (SBS). Polymer Degradation and Stability, 92(9), 1682-1691. doi:10.1016/j.polymdegradstab.2007.06.008Chow, W. S., & Neoh, S. S. (2009). Mechanical, Morphological and Thermal Properties of Polycarbonate/SEBS-G-MA/Montmorillonite Nanocomposites. Polymer-Plastics Technology and Engineering, 49(1), 62-68. doi:10.1080/03602550903283034Hong, X., Nie, G., Lin, Z., & Rong, J. (2012). Structure and Properties of PPO/PP Blends Compatibilized by Triblock Copolymer SEBS and SEPS. Polymer-Plastics Technology and Engineering, 51(10), 971-976. doi:10.1080/03602559.2012.671422Savadekar, N. R., & Mhaske, S. T. (2010). The Effect of Vulcanized Thermoplastics and SEBS on the Impact Strength of PPT. Polymer-Plastics Technology and Engineering, 49(15), 1499-1505. doi:10.1080/03602559.2010.496426Taşdemir, M., Ersoy, S., & Uluğ, E. (2012). Effects of HIPS on the Sound Absorption and Impedance Ratio of SEBS/HIPS/CaCO3Polymer Composites. Polymer-Plastics Technology and Engineering, 51(9), 954-958. doi:10.1080/03602559.2012.680563Taşdemir, M., & Uluğ, E. (2012). 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CSL–MAML-dependent Notch1 signaling controls T lineage–specific IL-7Rα gene expression in early human thymopoiesis and leukemia

Notch1 activation is essential for T-lineage specification of lymphomyeloid progenitors seeding the thymus. Progression along the T cell lineage further requires cooperative signaling provided by the interleukin 7 receptor (IL-7R), but the molecular mechanisms responsible for the dynamic and lineage-specific regulation of IL-7R during thymopoiesis are unknown. We show that active Notch1 binds to a conserved CSL-binding site in the human IL7R gene promoter and critically regulates IL7R transcription and IL-7R α chain (IL-7Rα) expression via the CSL–MAML complex. Defective Notch1 signaling selectively impaired IL-7Rα expression in T-lineage cells, but not B-lineage cells, and resulted in a compromised expansion of early human developing thymocytes, which was rescued upon ectopic IL-7Rα expression. The pathological implications of these findings are demonstrated by the regulation of IL-7Rα expression downstream of Notch1 in T cell leukemias. Thus, Notch1 controls early T cell development, in part by regulating the stage- and lineage-specific expression of IL-7Rα

Regulation of the transcriptional program by DNA methylation during human αβ T-cell development

© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. Thymocyte differentiation is a complex process involving well-defined sequential developmental stages that ultimately result in the generation of mature T-cells. In this study, we analyzed DNA methylation and gene expression profiles at successive human thymus developmental stages. Gain and loss of methylation occurred during thymocyte differentiation, but DNA demethylation was much more frequent than de novo methylation and more strongly correlated with gene expression. These changes took place in CpG-poor regions and were closely associated with T-cell differentiation and TCR function. Up to 88 genes that encode transcriptional regulators, some of whose functions in T-cell development are as yet unknown, were differentially methylated during differentiation. Interestingly, no reversion of accumulated DNA methylation changes was observed as differentiation progressed, except in a very small subset of key genes (RAG1, RAG2, CD8A, PTCRA, etc.), indicating that methylation changes are mostly unique and irreversible events. Our study explores the contribution of DNA methylation to T-cell lymphopoiesis and provides a fine-scale map of differentially methylated regions associated with gene expression changes. These can lay the molecular foundations for a better interpretation of the regulatory networks driving human thymopoiesis.Plan Nacional de [I+D+I 2008–2011]; Instituto de Salud Carlos III [grant number PI12/02587]; Red Española de Investigación Renal (REDinREN) [grant number RD12/0021/0018 and RD12/0021/0021]; Spanish Ministry of Science and Innovation [grant number SAF2010- 15106 and PLE2009-0110]; European Union [Fondos FEDER]Peer Reviewe

Software review for estimating the injection moulding cost

Accurate estimates of moulding and mould costs are a must for injection moulders. They make all the difference between profit and loss. Estimates can be prepared manually but it is a laborious process, prone to error and omission. Software solutions, on the other hand, do away with calculation errors, prompt for the right steps, store algorithms and data, ensure that all estimates are prepared on a common basis, encourage what-if experiments, and store and recall past work. It should be an open-and-shut case for software. This review has revealed the diversity of approach displayed by injection moulding cost estimating programs.Sellés Cantó, MÁ.; Pérez Bernabeu, E.; Sánchez Caballero, S.; Parres García, FJ.; Peydro Rasero, MÁ. (2011). Software review for estimating the injection moulding cost. Annals of The University of Oradea. 10(20):60-63. http://hdl.handle.net/10251/35907S6063102

Efficient preclinical treatment of cortical T cell acute lymphoblastic leukemia with T lymphocytes secreting anti-CD1a T cell engagers

BACKGROUND: The dismal clinical outcome of relapsed/refractory (R/R) T cell acute lymphoblastic leukemia (T-ALL) highlights the need for innovative targeted therapies. Although chimeric antigen receptor (CAR)-engineered T cells have revolutionized the treatment of B cell malignancies, their clinical implementation in T-ALL is in its infancy. CD1a represents a safe target for cortical T-ALL (coT-ALL) patients, and fratricide-resistant CD1a-directed CAR T cells have been preclinically validated as an immunotherapeutic strategy for R/R coT-ALL. Nonetheless, T-ALL relapses are commonly very aggressive and hyperleukocytic, posing a challenge to recover sufficient non-leukemic effector T cells from leukapheresis in R/R T-ALL patients. METHODS: We carried out a comprehensive study using robust in vitro and in vivo assays comparing the efficacy of engineered T cells either expressing a second-generation CD1a-CAR or secreting CD1a x CD3 T cell-engaging Antibodies (CD1a-STAb). RESULTS: We show that CD1a-T cell engagers bind to cell surface expressed CD1a and CD3 and induce specific T cell activation. Recruitment of bystander T cells endows CD1a-STAbs with an enhanced in vitro cytotoxicity than CD1a-CAR T cells at lower effector:target ratios. CD1a-STAb T cells are as effective as CD1a-CAR T cells in cutting-edge in vivo T-ALL patient-derived xenograft models. CONCLUSIONS: Our data suggest that CD1a-STAb T cells could be an alternative to CD1a-CAR T cells in coT-ALL patients with aggressive and hyperleukocytic relapses with limited numbers of non-leukemic effector T cellsResearch in LA-V laboratory is funded by the Spanish Ministry of Science and Innovation (PID2020-117323RB-100 and PDC2021-121711-100), and the Carlos III Health Institute (DTS20/00089), with European Regional Development Fund (FEDER) cofinancing; the Spanish Association Against Cancer (AECC PROYE19084ALVA) and the CRIS Cancer Foundation (FCRIS-2018-0042 and FCRIS2021-0090). Research in PM laboratory is supported by CERCA/Generalitat de Catalunya and Fundació Josep Carreras-Obra Social la Caixa for core support; 'la Caixa' Foundation under the agreement LCF/PR/HR19/52160011; the European Research Council grant (ERC-PoC-957466); the Spanish Ministry of Science and Innovation (PID2019-108160RB-I00); and the ISCIII-RICORS within the Next Generation EU program (plan de Recuperación, Transformación y Resilencia). MLT is supported by Spanish Ministry of Science and Innovation (PID2019-105623RB-I00) and the Spanish Association Against Cancer (CICPF18030TORI). PP is supported by Carlos III Health Institute (PI21-01834), with FEDER cofinancing and Fundación Ramón Areces. NT was supported by an FPU PhD fellowship from Spain's Ministerio de Universidades (FPU19/00039). OH was supported by an industrial PhD fellowship from the Comunidad de Madrid (IND2020/BMD-17668). LD-A was supported by a Rio Hortega fellowship from the Carlos III Health Institute (CM20/00004). VMD is supported by the Torres Quevedo subprogram of the State Research Agency of the Ministry of Science, Innovation and Universities (Ref. PTQ2020-011056). DSM is partially founded by a Sara Borrell fellowship from Carlos III Health Institute (CD19/00013

Base molecular y modulación del reconocimiento aloespecífico de HLA-B27 por linfocitos T citotóxicos

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 15-02-200