Selecció assistida mitjançant marcadors moleculars per a la introducció de gens de resistència i creixement determinat en la mongeta del Ganxet

Per a millorar agronòmicament la varietat tradicional de mongeta catalana Ganxet (Phaseolus vulgaris L.) s’estan introduint gens de resistència a antracnosi (Colletotrichum lindemuthianum) i Virus del Mosaic Comú de la Mongeta (BCMV) en la línea pura L67 o Montcau. També es vol introduir el gen fin, d’hàbit de creixement determinat. S’està treballant amb donadors diferents, introduïnt-se el gens per retroencreuament i aplicant-se selecció assistida per marcadors (MAS): Widusa (gens Co-6 i Co-42), A-493 (gen Co-9), Sanilac (gens fin, I i Co-2). Per ampliar el procés de millora de Montcau, es va fer la caracterització dels donadors Amanda (bc-12 ) i IVT7214 (bc-1), validant-se el marcador molecular ROBD05-1300 per bc-12 i el ROH14-1100, per bc-1 i, per tant, es recomana iniciar almenys un nou procés de retroencreuament per a obtenir la combinació que dóna resistència a BCMV i BCMNV (virus necròtic): bc-12 + I. A la generació BC4 de Widusa x Montcau, 2 de 8 plantes es van seleccionar amb els al·lels Co-6 i Co-42 simultàniament, amb els marcadors ROZ04-560 i ROAS13-950 respectivament. A la generació BC3 de A493 x Montcau, 5 de 7 plantes presentaven l’al·lel Co-9. seleccionades amb el marcador SB12-350. A la generació BC1 de Sanilac x Montcau, 3 de 6 plantes presentaven els al·lels I i Co-2 simultàniament, amb els marcadors SW13-690 i ROQ04-1440, respectivament. Cap dels marcadors descrits per els al·lels bc-u van resultar útils per a seguir la seva introducció en Montcau

Protective Effects of Human and Mouse Soluble Scavenger-Like CD6 Lymphocyte Receptor in a Lethal Model of Polymicrobial Sepsis

Sepsis still constitutes an unmet clinical need, which could benefit from novel adjunctive strategies to conventional antibiotic therapy. The soluble form of the scavenger-like human CD6 lymphocyte receptor (shCD6) binds to key pathogenic components from Gram-positive and -negative bacteria and shows time- and dose-dependent efficacy in mouse models of monobacterial sepsis. The objective of the present work was to demonstrate the effectiveness of infusing mouse and human sCD6 by different systemic routes, either alone or as adjunctive therapy to gold standard antibiotics, in a lethal model of polymicrobial sepsis. To this end, C57BL/6 mice undergoing high-grade septic shock induced by cecal ligation and puncture (CLP; ≥90% lethality) were infused via the intraperitoneal (i.p.) or intravenous (i.v.) route with shCD6 at different doses and time points, either alone or in combination with imipenem/cilastatin (I/C) at a dose of 33 mg/kg of body weight every 8 h. Significantly reduced mortality and proinflammatory cytokine levels were observed by i.p. infusion of a single shCD6 dose (1.25 mg/kg) 1 h pre- or post-CLP. When using the i.v. route, mice survival was significantly extended by starting shCD6 infusion at later time points post-CLP (up to 6 h after CLP). Significant adjunctive effects on mouse survival were observed by i.p. or i.v. infusion of shCD6 in combination with i.p. I/C post-CLP. Similar results were obtained in mice expressing high sustained levels (5 to 10 μg/ml) of mouse sCD6 in serum by means of transduction with hepatotropic adeno-associated virus (AAV). Taken together, the data support the conserved antibacterial effects of human and mouse sCD6 and their use as adjunctive therapy in experimental models of complex and severe polymicrobial sepsis.Ministerio de Economía y Competitividad (España) SAF2013-46151-R PCIN-2015-070Instituto de Salud Carlos III RD12/0015/0018European Development Regional Fund RD12/0015/0018Fundació La Marató TV3 201319-30-3

Gene variation at immunomodulatory and cell adhesion molecules loci impacts primary Sjögren's syndrome

Primary Sjögren's syndrome (pSS) is an autoimmune disease triggered by a combination of environmental and host genetic factors, which results in the focal lymphocytic infiltration of exocrine glands causing eye and mouth dryness. Glandular infiltrates include T and B cell subsets positive for CD5 and/or CD6, two surface scavenger receptors involved in the fine-tuning of intracellular signals mediated by the antigen-specific receptor complex of T (TCR) and B (BCR) cells. Moreover, the epithelial cells of inflamed glands overexpress CD166/ALCAM, a CD6 ligand involved in homo and heterotypic cell adhesion interactions. All this, together with the reported association of functionally relevant single nucleotide polymorphisms (SNPs) of CD5, CD6, and CD166/ALCAM with the risk or prognosis of some immune-mediated inflammatory disorders, led us to investigate similar associations in a local cohort of patients with pSS. The logistic regression analyses of individual SNPs showed the association of CD5 rs2241002T with anti-Ro/La positivity, CD6 rs17824933C with neutropenia, and CD6 rs11230563T with increased leukopenia and neutropenia but decreased peripheral nervous system EULAR Sjögren's syndrome disease activity index (ESSDAI). Further analyses showed the association of haplotypes from CD5 (rs2241002T-rs2229177C) with anemia and thrombocytopenia, CD6 (rs17824933G-rs11230563C-rs12360861G) with cutaneous ESSDAI, and CD166/ALCAM (rs6437585C-rs579565A-rs1044243C and rs6437585C-rs579565G-rs1044243T) with disease susceptibility and several analytical parameters (anti-nuclear antibodies, neurological ESSDAI, and hematologic cytopenias). These results support the relevance of gene variation at loci coding for cell surface receptors involved in the modulation of T and B lymphocyte activation (CD5, CD6) and epithelial-immune cell adhesion (CD166/ALCAM) in modulating the clinical and analytical outcomes in patients with pS

Conserved bacterial-binding peptides of the scavenger-like lymphocyte receptor CD6 protect from mouse experimental sepsis

Sepsis is an unmet clinical need constituting one of the most important causes of death worldwide, a fact aggravated by the appearance of multidrug resistant strains due to indiscriminate use of antibiotics. Host innate immune receptors involved in pathogen-associated molecular patterns (PAMPs) recognition represent a source of broad-spectrum therapies alternative or adjunctive to antibiotics. Among the few members of the ancient and highly conserved scavenger receptor cysteine-rich superfamily (SRCR-SF) sharing bacterial-binding properties there is CD6, a lymphocyte-specific surface receptor. Here, we analyze the bacterial-binding properties of three conserved short peptides (11-mer) mapping at extracellular SRCR domains of human CD6 (CD6.PD1, GTVEVRLEASW; CD6.PD2 GRVEMLEHGEW; and CD6.PD3, GQVEVHFRGVW). All peptides show high binding affinity for PAMPs from Gram-negative (lipopolysaccharide; Kd from 3.5 to 3,000 nM) and Gram-positive (lipoteichoic acid; Kd from 36 to 680 nM) bacteria. The CD6.PD3 peptide possesses broad bacterial-agglutination properties and improved survival of mice undergoing polymicrobial sepsis in a dose- and time-dependent manner. Accordingly, CD6.PD3 triggers a decrease in serum levels of both pro-inflammatory cytokines and bacterial load. Interestingly, CD6.PD3 shows additive survival effects on septic mice when combined with Imipenem/Cilastatin. These results illustrate the therapeutic potential of peptides retaining the bacterial-binding properties of native CD6

Relevance of CD6-Mediated interactions in the regulation of peripheral T-Cell responses and tolerance

The CD6 lymphocyte receptor has been involved in the pathophysiology of different autoimmune disorders and is now considered a feasible target for their treatment. In vitro data show the relevance of CD6 in the stabilization of adhesive contacts between T-cell and antigen-presenting cells, and the modulation of T-cell receptor signals. However, the in vivo consequences of such a function are yet undisclosed due to the lack of suitable genetically modified animal models. Here, the in vitro and in vivo challenge of CD6-deficient (CD6(-/-)) cells with allogeneic cells was used as an approach to explore the role of CD6 in immune responses under relative physiological stimulatory conditions. Mixed lymphocyte reaction (MLR) assays showed lower proliferative responses of splenocytes from CD6(-/-)mice together with higher induction of regulatory T cells (T-reg, CD4(+)CD25(+)FoxP3(+)) with low suppressive activity on T and B-cell proliferation. In line with these results, CD6(-/-)mice undergoing a lupus-like disorder induced by chronic graft-versus-host disease (cGvHD) showed higher serum titers of anti-double-stranded DNA and nucleosome autoantibodies. This occurred together with reduced splenomegaly, which was associated with lower in vivo bromodesoxyuridine incorporation of spleen cells and with increased percentages of spleen follicular B cells (B2, CD21(+)CD23(hi)) and T-reg cells. Interestingly, functional analysis of in vivo-generated CD6(-/-)T(reg) cells exhibited defective suppressive activity. In conclusion, the data from MLR and cGvHD-induced lupus-like models in CD6(-/-)mice illustrate the relevance of CD6 in T (and B) cell proliferative responses and, even more importantly, Treg induction and suppressive function in the in vivo maintenance of peripheral tolerance

Soluble mutant huntingtin drives early human pathogenesis in Huntington’s disease

Huntington's disease (HD) is an incurable inherited brain disorder characterised by massive degeneration of striatal neurons, which correlates with abnormal accumulation of misfolded mutant huntingtin (mHTT) protein. Research on HD has been hampered by the inability to study early dysfunction and progressive degeneration of human striatal neurons in vivo. To investigate human pathogenesis in a physiologically relevant context, we transplanted human pluripotent stem cell-derived neural progenitor cells (hNPCs) from control and HD patients into the striatum of new-born mice. Most hNPCs differentiated into striatal neurons that projected to their target areas and established synaptic connexions within the host basal ganglia circuitry. Remarkably, HD human striatal neurons first developed soluble forms of mHTT, which primarily targeted endoplasmic reticulum, mitochondria and nuclear membrane to cause structural alterations. Furthermore, HD human cells secreted extracellular vesicles containing mHTT monomers and oligomers, which were internalised by non-mutated mouse striatal neurons triggering cell death. We conclude that interaction of mHTT soluble forms with key cellular organelles initially drives disease progression in HD patients and their transmission through exosomes contributes to spread the disease in a non-cell autonomous manner. Graphical abstract

SpadaHC: a database to improve the classification of variants in hereditary cancer genes in the Spanish population

Accurate classification of genetic variants is crucial for clinical decision-making in hereditary cancer. In Spain, genetic diagnostic laboratories have traditionally approached this task independently due to the lack of a dedicated resource. Here we present SpadaHC, a web-based database for sharing variants in hereditary cancer genes in the Spanish population. SpadaHC is implemented using a three-tier architecture consisting of a relational database, a web tool and a bioinformatics pipeline. Contributing laboratories can share variant classifications and variants from individuals in Variant Calling Format (VCF) format. The platform supports open and restricted access, flexible dataset submissions, automatic pseudo-anonymization, VCF quality control, variant normalization and liftover between genome builds. Users can flexibly explore and search data, receive automatic discrepancy notifications and access SpadaHC population frequencies based on many criteria. In February 2024, SpadaHC included 18 laboratory members, storing 1.17 million variants from 4306 patients and 16 343 laboratory classifications. In the first analysis of the shared data, we identified 84 genetic variants with clinically relevant discrepancies in their classifications and addressed them through a three-phase resolution strategy. This work highlights the importance of data sharing to promote consistency in variant classifications among laboratories, so patients and family members can benefit from more accurate clinical management.Database URL: https://spadahc.ciberisciii.es/ Overview of SpadaHC and its main views. (A) List of existing variants in SpadaHC (in the image, search for the ATM gene). The 'Expert Cl.' column shows the classification made by a group of experts; the 'Lab Cl.' column shows a summary of the classifications made by the laboratories. (B) Allele frequency of a variant in the SpadaHC population according to clinical suspicion and sex. (C) Classifications provided by the laboratories for a variant. (D) List of patients carrying a variant. (E) Histogram showing the coverage and frequency (allele balance) with which the variant was detected in carrier patients. Alt text: SpadaHC overview; laboratories can share datasets of variant classifications (Excel) and variants from individuals (VCFs + Excel). The datasets undergo quality control, bioinformatics pipeline annotation and database integration before being displayed in SpadaHC. The graphical abstract also shows five views of SpadaHC

Jardins per a la salut

Facultat de Farmàcia, Universitat de Barcelona. Ensenyament: Grau de Farmàcia. Assignatura: Botànica farmacèutica. Curs: 2014-2015. Coordinadors: Joan Simon, Cèsar Blanché i Maria Bosch.Els materials que aquí es presenten són el recull de les fitxes botàniques de 128 espècies presents en el Jardí Ferran Soldevila de l’Edifici Històric de la UB. Els treballs han estat realitzats manera individual per part dels estudiants dels grups M-3 i T-1 de l’assignatura Botànica Farmacèutica durant els mesos de febrer a maig del curs 2014-15 com a resultat final del Projecte d’Innovació Docent «Jardins per a la salut: aprenentatge servei a Botànica farmacèutica» (codi 2014PID-UB/054). Tots els treballs s’han dut a terme a través de la plataforma de GoogleDocs i han estat tutoritzats pels professors de l’assignatura. L’objectiu principal de l’activitat ha estat fomentar l’aprenentatge autònom i col·laboratiu en Botànica farmacèutica. També s’ha pretès motivar els estudiants a través del retorn de part del seu esforç a la societat a través d’una experiència d’Aprenentatge-Servei, deixant disponible finalment el treball dels estudiants per a poder ser consultable a través d’una Web pública amb la possibilitat de poder-ho fer in-situ en el propi jardí mitjançant codis QR amb un smartphone

TFG 2012/2013

Amb aquesta publicació, EINA, Centre universitari de Disseny i Art adscrit a la Universitat Autònoma de Barcelona, dóna a conèixer el recull dels Treballs de Fi de Grau presentats durant el curs 2012-2013. Voldríem que un recull com aquest donés una idea més precisa de la tasca que es realitza a EINA per tal de formar nous dissenyadors amb capacitat de respondre professionalment i intel·lectualment a les necessitats i exigències de la nostra societat. El treball formatiu s’orienta a oferir resultats que responguin tant a paràmetres de rigor acadèmic i capacitat d’anàlisi del context com a l’experimentació i la creació de nous llenguatges, tot fomentant el potencial innovador del disseny.Con esta publicación, EINA, Centro universitario de diseño y arte adscrito a la Universidad Autónoma de Barcelona, da a conocer la recopilación de los Trabajos de Fin de Grado presentados durante el curso 2012-2013. Querríamos que una recopilación como ésta diera una idea más precisa del trabajo que se realiza en EINA para formar nuevos diseñadores con capacidad de responder profesional e intelectualmente a las necesidades y exigencias de nuestra sociedad. El trabajo formativo se orienta a ofrecer resultados que respondan tanto a parámetros de rigor académico y capacidad de análisis, como a la experimentación y la creación de nuevos lenguajes, al tiempo que se fomenta el potencial innovador del diseño.With this publication, EINA, University School of Design and Art, ascribed to the Autonomous University of Barcelona, brings to the public eye the Final Degree Projects presented during the 2012-2013 academic year. Our hope is that this volume might offer a more precise idea of the task performed by EINA in training new designers, able to speak both professionally and intellectually to the needs and demands of our society. The educational task is oriented towards results that might respond to the parameters of academic rigour and the capacity for contextual analysis, as well as to considerations of experimentation and the creation of new languages, all the while reinforcing design’s innovative potential

Selecció assistida mitjançant marcadors moleculars per a la introducció de gens de resistència i creixement determinat en la mongeta del Ganxet

Per a millorar agronòmicament la varietat tradicional de mongeta catalana Ganxet (Phaseolus vulgaris L.) s’estan introduint gens de resistència a antracnosi (Colletotrichum lindemuthianum) i Virus del Mosaic Comú de la Mongeta (BCMV) en la línea pura L67 o Montcau. També es vol introduir el gen fin, d’hàbit de creixement determinat. S’està treballant amb donadors diferents, introduïnt-se el gens per retroencreuament i aplicant-se selecció assistida per marcadors (MAS): Widusa (gens Co-6 i Co-42), A-493 (gen Co-9), Sanilac (gens fin, I i Co-2). Per ampliar el procés de millora de Montcau, es va fer la caracterització dels donadors Amanda (bc-12 ) i IVT7214 (bc-1), validant-se el marcador molecular ROBD05-1300 per bc-12 i el ROH14-1100, per bc-1 i, per tant, es recomana iniciar almenys un nou procés de retroencreuament per a obtenir la combinació que dóna resistència a BCMV i BCMNV (virus necròtic): bc-12 + I. A la generació BC4 de Widusa x Montcau, 2 de 8 plantes es van seleccionar amb els al·lels Co-6 i Co-42 simultàniament, amb els marcadors ROZ04-560 i ROAS13-950 respectivament. A la generació BC3 de A493 x Montcau, 5 de 7 plantes presentaven l’al·lel Co-9. seleccionades amb el marcador SB12-350. A la generació BC1 de Sanilac x Montcau, 3 de 6 plantes presentaven els al·lels I i Co-2 simultàniament, amb els marcadors SW13-690 i ROQ04-1440, respectivament. Cap dels marcadors descrits per els al·lels bc-u van resultar útils per a seguir la seva introducció en Montcau