Respuesta agronómica de diferentes cultivares tintos de vid en zona templada

Se presenta la respuesta varietal de 6 cultivares tintos de vid, con riego deficitario controlado, en zona cálida: Barbera, Graciano, Mencía, Pinot noir, Petit verdot y Tempranillo. Teniendo en cuenta que en zona cálida hay que escoger cultivares de ciclo largo, recolección tardía, capaces de madurar manteniendo alta la acidez real y total, se concluye que los más idóneos para su cultivo en zona cálida son Barbera, por su alta acidez y Petit verdot y Graciano por su larga maduración y acidez equilibrada. Tempranillo, si bien en este trabajo presenta una respuesta adecuada, para equivalente maduración sacarimétrica a las anteriores posee menor acidez e IPT. Mencía madura mejor en situaciones frescas que en zona cálid

Using Gene Editing Approaches to Fine-Tune the Immune System

Genome editing technologies not only provide unprecedented opportunities to study basic cellular system functionality but also improve the outcomes of several clinical applications. In this review, we analyze various gene editing techniques used to finetune immune systems from a basic research and clinical perspective. We discuss recent advances in the development of programmable nucleases, such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas-associated nucleases. We also discuss the use of programmable nucleases and their derivative reagents such as base editing tools to engineer immune cells via gene disruption, insertion, and rewriting of T cells and other immune components, such natural killers (NKs) and hematopoietic stem and progenitor cells (HSPCs). In addition, with regard to chimeric antigen receptors (CARs), we describe how different gene editing tools enable healthy donor cells to be used in CAR T therapy instead of autologous cells without risking graft-versus-host disease or rejection, leading to reduced adoptive cell therapy costs and instant treatment availability for patients. We pay particular attention to the delivery of therapeutic transgenes, such as CARs, to endogenous loci which prevents collateral damage and increases therapeutic effectiveness. Finally, we review creative innovations, including immune system repurposing, that facilitate safe and efficient genome surgery within the framework of clinical cancer immunotherapies.Spanish ISCIII Health Research FundEuropean Union (EU) PI12/01097 PI15/02015 PI18/00337 PI18/00330CECEyU and CSyF councils of the Junta de Andalucia FEDER/European Cohesion Fund (FSE) 2016000073391-TRA 2016000073332-TRA PI-57069 PAIDI-Bio326 PI-0014-2016Nicolas Monardes regional Ministry of Health 0006/2018Spanish Government FPU16/05467 FPU17/02268Industrial Doctorate Plan MCI DIN2018-010180SMSI PEJ-2018-001760-ALentiStem Biotec

Physiological lentiviral vectors for the generation of improved CAR-T cells.

Anti-CD19 chimeric antigen receptor (CAR)-T cells have achieved impressive outcomes for the treatment of relapsed and refractory B-lineage neoplasms. However, important limitations still remain due to severe adverse events (i.e., cytokine release syndrome and neuroinflammation) and relapse of 40%-50% of the treated patients. Most CAR-T cells are generated using retroviral vectors with strong promoters that lead to high CAR expression levels, tonic signaling, premature exhaustion, and overstimulation, reducing efficacy and increasing side effects. Here, we show that lentiviral vectors (LVs) expressing the transgene through a WAS gene promoter (AW-LVs) closely mimic the T cell receptor (TCR)/CD3 expression kinetic upon stimulation. These AW-LVs can generate improved CAR-T cells as a consequence of their moderate and TCR-like expression profile. Compared with CAR-T cells generated with human elongation factor α (EF1α)-driven-LVs, AW-CAR-T cells exhibited lower tonic signaling, higher proportion of naive and stem cell memory T cells, less exhausted phenotype, and milder secretion of tumor necrosis factor alpha (TNF-α) and interferon (IFN)-ɣ after efficient destruction of CD19+ lymphoma cells, both in vitro and in vivo. Moreover, we also showed their improved efficiency using an in vitro CD19+ pancreatic tumor model. We finally demonstrated the feasibility of large-scale manufacturing of AW-CAR-T cells in guanosine monophosphate (GMP)-like conditions. Based on these data, we propose the use of AW-LVs for the generation of improved CAR-T products