Resultados totales (Incluyendo duplicados): 35611
Encontrada(s) 3562 página(s)
Encontrada(s) 3562 página(s)
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351822
Dataset. 2023
SUPPORTING INFORMATION FOR "MANY-BODY CONTRIBUTIONS IN WATER NANO-CLUSTERS"
- Abella, David
- Franzese, Giancarlo
- Hernández-Rojas, Javier
Many-body interactions in water are known to be important but difficult to treat in atomistic models and often are included only as a correction. Polarizable models treat them explicitly, with long-range many-body potentials, within their classical approximation. However, their calculation is computationally expensive. Here, we evaluate how relevant the contributions to the many-body interaction associated with different coordination shells are. We calculate the global energy minimum, and the corresponding configuration, for nanoclusters of up to 20 water molecules. We find that including the first coordination shell, i.e., the five-body term of the central molecule, is enough to approximate within 5% the global energy minimum and its structure. We show that this result is valid for three different polarizable models, the Dang–Chang, the MB-pol, and the Kozack–Jordan potentials. This result suggests a strategy to develop many-body potentials for water that are reliable and, at the same time, computationally efficient., Peer reviewed
Proyecto: //
DOI: http://hdl.handle.net/10261/351822
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351822
HANDLE: http://hdl.handle.net/10261/351822
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351822
PMID: http://hdl.handle.net/10261/351822
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351822
Ver en: http://hdl.handle.net/10261/351822
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351822
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351834
Dataset. 2024
SUPPLEMENTAL DATA: ARABIDOPSIS FIBRILLIN6 INFLUENCES CAROTENOID BIOSYNTHESIS BY DIRECTLY PROMOTING PHYTOENE SYNTHASE ACTIVITY
- Iglesias-Sanchez, Ariadna
- Navarro-Carcelen, Juan
- Morelli, Luca
- Rodriguez-Concepcion, Manuel
Supplemental Figure S1. Characterization of 35S:FBN6-RFP lines.-- Supplemental Table S1. Primers used in this work.-- Supplemental Table S2. Phytoene levels in control and NFZ-treated N. benthamiana leaves agroinfiltrated with FBN6 and/or PSY constructs.-- Supplemental Table S3. Photosynthetic pigment levels in N. benthamiana leaves agroinfiltrated with FBN6, PSY, and/or crtB constructs.-- Supplemental Table S4. Photosynthetic pigment levels in etiolated and de-etiolating WT and fbn6 Arabidopsis seedlings.-- Supplemental Table S5. Photosynthetic pigment levels in WT and fbn6 Arabidopsis seedlings exposed to HL., Carotenoids are health-promoting plastidial isoprenoids with essential functions in plants as photoprotectants and photosynthetic pigments in chloroplasts. They also accumulate in specialized plastids named chromoplasts, providing color to non-photosynthetic tissues such as flower petals and ripe fruit. Carotenoid accumulation in chromoplasts requires specialized structures and proteins such as fibrillins (FBNs). The FBN family includes structural components of carotenoid sequestering structures in chromoplasts and members with metabolic roles in chloroplasts and other plastid types. However, the association of FBNs with carotenoids in plastids other than chromoplasts has remained unexplored. Here, we show that Arabidopsis (Arabidopsis thaliana) FBN6 interacts with phytoene synthase (PSY), the first enzyme of the carotenoid pathway. FBN6, but not FBN4 (a FBN that does not interact with PSY), enhances the activity of plant PSY (but not of the bacterial PSY crtB) in Escherichia coli cells. Overexpression of FBN6 in Nicotiana benthamiana leaves results in a higher production of phytoene, the product of PSY activity, whereas loss of FBN6 activity in Arabidopsis mutants dramatically reduces the production of carotenoids during seedling de-etiolation and after exposure to high light. Our work hence demonstrates that FBNs promote not only the accumulation of carotenoids in chromoplasts but also their biosynthesis in chloroplasts., This work was funded by grants from Spanish MCIN/AEI/10.13039/501100011033 and European NextGeneration EU/PRTR and PRIMA programs to M.R.-C. (PID2020-115810GB-I00 and UToPIQ-PCI2021-121941). M.R.-C. is also supported by Generalitat Valenciana (PROMETEU/2021/056 and AGROALNEXT/2022/067). Our group is a member of CaRed (Spanish Carotenoid Network) funded by MCIN/AEI (RED2022-134577-T). A.I.-S. and J.N.-C. received predoctoral fellowships from MCIN/AEI (PRE2018-083610 and PRE2021-098681, respectively)., Peer reviewed
DOI: http://hdl.handle.net/10261/351834
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351834
HANDLE: http://hdl.handle.net/10261/351834
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351834
PMID: http://hdl.handle.net/10261/351834
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351834
Ver en: http://hdl.handle.net/10261/351834
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351834
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351859
Dataset. 2014
DECAPODS ABUNDANCE, HABITAT, LANDSCAPE, AND GEOGRAPHICAL ATTRIBUTES IN THE NW MEDITERRANEAN POSIDONIA OCEANICA SEAGRASS MEADOWS [DATASET]
- Baud, Marine
- Macpherson, Enrique
- Pérez-García, Marta
- Romero, Javier
- Ricart, Aurora M.
This dataset presents the decapod species and abundance, along with the habitat (detached seagrass leaves, fine fraction of detritus, detrital macroalgae, organic matter in sediments, seagrass shoot density and height of unburried rhizomes), landscape (landscape configuration) and geographical attributes (inlet aperture and confinement) in Posidonia oceanica seagrass meadows in 5 localities accross the NW Mediterranean sea.
We found that geographical level attributes (i.e., inlet aperture, confinement) affected the most the decapod assemblages, while we only found a modest contribution from habitat (e.g., detritus biomass, sediment organic matter) and landscape attributes (e.g. fragmentation). We suggest that decapod assemblages are driven by the interaction of multiple processes occurring at different scales and other highly stochastic phenomena such as larval dispersion and recruitment, This study was supported financially by the Spanish government (projects CTM2010-22273-C02-01 and CTM2013-48027-C3-1-R). The Spanish government also supported AMR (scholarship BES-2011-046849), Table 1. Decapod species and number of total individuals of 5 randomly selected quadrat (40 cm x 40 cm) found in Aiguablava (Ag), Rustella (Ru), Giverola (Gi, Cativa (Ca) and Portlligat (Po) in continuous seagrass meadows of Posidonia oceanica (CO), patches in sand matrix (PS) and patches in rock matrix (PR). Table 2. Habitat attributes and geographical attributes of 5 randomly selected quadrat (40 cm x 40 cm) found in Aiguablava (Ag), Rustella (Ru), Giverola (Gi, Cativa (Ca) and Portlligat (Po) in continuous seagrass meadows of Posidonia oceanica (CO), patches in sand matrix (PS) and patches in rock matrix (PR), Peer reviewed
Proyecto: MINECO//CTM2013-48027-C3-1-R
DOI: http://hdl.handle.net/10261/351859, https://doi.org/10.20350/digitalCSIC/16181
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351859
HANDLE: http://hdl.handle.net/10261/351859, https://doi.org/10.20350/digitalCSIC/16181
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351859
PMID: http://hdl.handle.net/10261/351859, https://doi.org/10.20350/digitalCSIC/16181
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351859
Ver en: http://hdl.handle.net/10261/351859, https://doi.org/10.20350/digitalCSIC/16181
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351859
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351860
Dataset. 2023
SUPPLEMENTARY INFORMATION ON ”NETWORK COEVOLUTION DRIVES SEGREGATION AND ENHANCES PARETO OPTIMAL EQUILIBRIUM SELECTION IN COORDINATION GAMES”
- González Casado, Miguel A.
- Sánchez, Ángel
- San Miguel, Maxi
S1 Previous Results on Coordination Games.-- S2 Defrost of Frozen Configurations.-- S3 Probability Distributions: Size and Number of Fragments.-- S4 Fragmentation Transition in a General Coordination Game.-- S5 Evolution of the Transition Line (UI rule).-- S6 Cases ⟨k⟩ = 10, 20.--, Peer reviewed
Proyecto: //
DOI: http://hdl.handle.net/10261/351860
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351860
HANDLE: http://hdl.handle.net/10261/351860
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351860
PMID: http://hdl.handle.net/10261/351860
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351860
Ver en: http://hdl.handle.net/10261/351860
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351860
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351914
Dataset. 2023
SUPPLEMENTARY MATERIALS: MOMAST® REDUCES THE PLASMATIC LIPID PROFILE AND OXIDATIVE STRESS, AND REGULATES THE CHOLESTEROL METABOLISM IN HYPERCHOLESTEROLEMIC MOUSE MODEL: THE PROOF OF CONCEPT OF A SUSTAINABLE AND INNOVATIVE ANTIOXIDANT AND HYPOCHOLESTEROLEMIC INGREDIENT
- Cruz-Chamorro, Iván
- Santos-Sánchez, Guillermo
- Ponce-España, Eduardo
- Bollati, Carlotta
- d’Adduzio, Lorenza
- Bartolomei, Martina
- Li, Jianqiang
- Carrillo-Vico, Antonio
- Lammi, Carmen
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)., MOMAST® is a patented natural phenolic complex, rich in tyrosol (9.0 g/kg, Tyr), hydroxityrosol (43,5 g/kg, OH-Tyr), and verbascoside (5.0 g/Kg), which is obtained from the OVW by-product of the Coratina cultivar with potent direct antioxidant activity (measured by DPPH and FRAP assays, respectively). Indeed, MOMAST® represents an innovative sustainable bioactive ingredient which has been obtained with ethical and empowering behavior by applying the principles of a circular economy. In the framework of research aimed at fostering its health-promoting activity, in this study it was clearly demonstrated that MOMAST® treatment reduced the oxidative stress and levels of total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol, and increased the HDL levels, without changes in the triglyceride (TG) levels in Western diet (WD)-fed mice. The modulation of the plasmatic lipid profile is similar to red yeast rice (RYR) containing Monacolin K (3%). In addition, at the molecular level in liver homogenates, similarly to RYR, MOMAST® exerts cholesterol-lowering activity through the activation of LDL receptor, whereas, unlike RYR, MOMAST® reduces proprotein convertase subtilisin/kexin type 9 (PCSK9) protein levels via hepatic nuclear factor 1 (HNF1)-α activation. Hence, this study provides the proof of concept regarding the hypocholesterolemic activity of MOMAST, which could be successfully exploited as an active ingredient for the development of innovative and sustainable dietary supplements and functional foods., This research was funded by Bioenutra S.R.L. (Ginosa (TA) Italy) and Fundación de Investigación de la Universidad de Sevilla-FIUS (4588/0401). G.S.-S. was supported by a FPU grant from the Spanish Ministerio de Educación, Cultura y Deporte (FPU16/02339). E.P.-E. was supported by the VI Program of Inner Initiative for Research and Transfer of University of Seville (VI PPIT-US). I.C.-C. was supported by a postdoctoral fellowship from the Andalusian Government Ministry of Economy, Knowledge, Business, and University (DOC_00587/2020)., Peer reviewed
Proyecto: MECD//FPU16-02339
DOI: http://hdl.handle.net/10261/351914
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351914
HANDLE: http://hdl.handle.net/10261/351914
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351914
PMID: http://hdl.handle.net/10261/351914
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351914
Ver en: http://hdl.handle.net/10261/351914
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351914
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351921
Dataset. 2023
IMAGE1_FLEQ, FLEN AND C-DI-GMP COORDINATELY REGULATE CELLULOSE PRODUCTION IN PSEUDOMONAS SYRINGAE PV. TOMATO DC3000.TIF
- Martínez-Rodríguez, Laura
- López-Sánchez, Aroa
- García Alcaide, A.
- Govantes, Fernando
- Gallegos, María Trinidad
The second messenger cyclic di-GMP (c-di-GMP) controls the transition between motility and sessility in many bacterial species by a variety of mechanisms, including the production of multiple exopolysaccharides. Pseudomonas syringae pv. tomato (Pto) DC3000 is a plant pathogenic bacteria able to synthesize acetylated cellulose under high c-di-GMP levels thanks to the expression of the wssABCDEFGHI operon. Increased cellulose production enhances air-liquid biofilm formation and generates a wrinkled colony phenotype on solid media. We previously showed that under low levels of c-di-GMP, the regulators FleQ and AmrZ bound to adjacent sequences at the wss promoter inhibiting its expression, but only FleQ responded to the presence of c-di-GMP by activating cellulose production. In the present work, we advance in the knowledge of this complex regulation in Pto DC3000 by shedding light over the role of FleN in this process. The distinctive features of this system are that FleN and FleQ are both required for repression and activation of the wss operon under low and high c-di-GMP levels, respectively. We have also identified three putative FleQ binding sites at the wss promoter and show that FleQ/FleN-ATP binds at those sites under low c-di-GMP levels, inducing a distortion of DNA, impairing RNA polymerase binding, and repressing wss transcription. However, binding of c-di-GMP induces a conformational change in the FleQ/FleN-ATP complex, which relieves the DNA distortion, allows promoter access to the RNA polymerase, and leads to activation of wss transcription. On the other hand, AmrZ is always bound at the wss promoter limiting its expression independently of FleQ, FleN and c-di-GMP levels., Peer reviewed
Proyecto: //
DOI: http://hdl.handle.net/10261/351921
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351921
HANDLE: http://hdl.handle.net/10261/351921
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351921
PMID: http://hdl.handle.net/10261/351921
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351921
Ver en: http://hdl.handle.net/10261/351921
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351921
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351929
Dataset. 2023
IMAGE2_FLEQ, FLEN AND C-DI-GMP COORDINATELY REGULATE CELLULOSE PRODUCTION IN PSEUDOMONAS SYRINGAE PV. TOMATO DC3000.TIF [DATASET]
- Martínez-Rodríguez, Laura
- López-Sánchez, Aroa
- García Alcaide, A.
- Govantes, Fernando
- Gallegos, María Trinidad
The second messenger cyclic di-GMP (c-di-GMP) controls the transition between motility and sessility in many bacterial species by a variety of mechanisms, including the production of multiple exopolysaccharides. Pseudomonas syringae pv. tomato (Pto) DC3000 is a plant pathogenic bacteria able to synthesize acetylated cellulose under high c-di-GMP levels thanks to the expression of the wssABCDEFGHI operon. Increased cellulose production enhances air-liquid biofilm formation and generates a wrinkled colony phenotype on solid media. We previously showed that under low levels of c-di-GMP, the regulators FleQ and AmrZ bound to adjacent sequences at the wss promoter inhibiting its expression, but only FleQ responded to the presence of c-di-GMP by activating cellulose production. In the present work, we advance in the knowledge of this complex regulation in Pto DC3000 by shedding light over the role of FleN in this process. The distinctive features of this system are that FleN and FleQ are both required for repression and activation of the wss operon under low and high c-di-GMP levels, respectively. We have also identified three putative FleQ binding sites at the wss promoter and show that FleQ/FleN-ATP binds at those sites under low c-di-GMP levels, inducing a distortion of DNA, impairing RNA polymerase binding, and repressing wss transcription. However, binding of c-di-GMP induces a conformational change in the FleQ/FleN-ATP complex, which relieves the DNA distortion, allows promoter access to the RNA polymerase, and leads to activation of wss transcription. On the other hand, AmrZ is always bound at the wss promoter limiting its expression independently of FleQ, FleN and c-di-GMP levels., Peer reviewed
Proyecto: //
DOI: http://hdl.handle.net/10261/351929
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351929
HANDLE: http://hdl.handle.net/10261/351929
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351929
PMID: http://hdl.handle.net/10261/351929
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351929
Ver en: http://hdl.handle.net/10261/351929
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351929
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351934
Dataset. 2023
IMAGE3_FLEQ, FLEN AND C-DI-GMP COORDINATELY REGULATE CELLULOSE PRODUCTION IN PSEUDOMONAS SYRINGAE PV. TOMATO DC3000.TIF [DATASET]
- Martínez-Rodríguez, Laura
- López-Sánchez, Aroa
- García Alcaide, A.
- Govantes, Fernando
- Gallegos, María Trinidad
The second messenger cyclic di-GMP (c-di-GMP) controls the transition between motility and sessility in many bacterial species by a variety of mechanisms, including the production of multiple exopolysaccharides. Pseudomonas syringae pv. tomato (Pto) DC3000 is a plant pathogenic bacteria able to synthesize acetylated cellulose under high c-di-GMP levels thanks to the expression of the wssABCDEFGHI operon. Increased cellulose production enhances air-liquid biofilm formation and generates a wrinkled colony phenotype on solid media. We previously showed that under low levels of c-di-GMP, the regulators FleQ and AmrZ bound to adjacent sequences at the wss promoter inhibiting its expression, but only FleQ responded to the presence of c-di-GMP by activating cellulose production. In the present work, we advance in the knowledge of this complex regulation in Pto DC3000 by shedding light over the role of FleN in this process. The distinctive features of this system are that FleN and FleQ are both required for repression and activation of the wss operon under low and high c-di-GMP levels, respectively. We have also identified three putative FleQ binding sites at the wss promoter and show that FleQ/FleN-ATP binds at those sites under low c-di-GMP levels, inducing a distortion of DNA, impairing RNA polymerase binding, and repressing wss transcription. However, binding of c-di-GMP induces a conformational change in the FleQ/FleN-ATP complex, which relieves the DNA distortion, allows promoter access to the RNA polymerase, and leads to activation of wss transcription. On the other hand, AmrZ is always bound at the wss promoter limiting its expression independently of FleQ, FleN and c-di-GMP levels., Peer reviewed
Proyecto: //
DOI: http://hdl.handle.net/10261/351934
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351934
HANDLE: http://hdl.handle.net/10261/351934
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351934
PMID: http://hdl.handle.net/10261/351934
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351934
Ver en: http://hdl.handle.net/10261/351934
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351934
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351945
Dataset. 2023
SUPPLEMENTAL MATERIAL. NICHE OVERLAP AND HOPFIELD-LIKE INTERACTIONS IN GENERALISED RANDOM LOTKA–VOLTERRA SYSTEMS
- Rozas Garcia, Enrique
- Crumpton, Mark J.
- Galla, Tobias
Peer reviewed
Proyecto: //
DOI: http://hdl.handle.net/10261/351945
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351945
HANDLE: http://hdl.handle.net/10261/351945
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351945
PMID: http://hdl.handle.net/10261/351945
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351945
Ver en: http://hdl.handle.net/10261/351945
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351945
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351949
Dataset. 2023
SUPPLEMENTARY MATERIAL: MONITORING OF KINETICS AND EXHAUSTION MARKERS OF CIRCULATING CAR-T CELLS AS EARLY PREDICTIVE FACTORS IN PATIENTS WITH B-CELL MALIGNANCIES
- García-Calderón, Clara B.
- Sierro-Martínez, Belén
- García-Guerrero, Estefanía
- Sanoja-Flores, Luzalba
- Muñoz García, Raquel
- Ruiz-Maldonado, Victoria
- Jiménez-León, María Reyes
- Delgado-Serrano, Javier
- Molinos-Quintana, A.
- Guijarro-Albaladejo, Beatriz
- Carrasco-Brocal, Inmaculada
- Lucena-Soto, José Manuel
- García-Lozano, José Raúl
- Blázquez-Goñi, Cristina
- Reguera-Ortega, Juan Luis
- González-Escribano, María Francisca
- Reinoso-Segura, Marta
- Briones, Javier
- Pérez-Simón, José A.
- Caballero-Velázquez, Teresa
Supplementary Figures: Supplementary Figure 1. Evaluation of the specificity of the detection reagents for the identification of academic CAR-T cells by flow cytometry.-- Supplementary figure 2. Evaluation of the specificity of the detection reagents for the identification of commercial CAR-T cells by flow cytometry.-- Supplementary Figure 3. Commercial CD19 CAR-T cell expansion in the blood of patients with lymphoma.-- Supplementary Figure 4. Comparison of the expansion dynamics of different commercial CD19 CAR-T cell products.-- Supplementary Figure 5. Immunophenotype characterization of non-modified T cells and CAR-T cells at the time of peak expansion in blood of patients with lymphoma.-- Supplementary Figure 6. Immunophenotype characterization of non-modified T cells and CAR-T cells at the time of peak expansion in blood of patients infused with Tisa-cel vs Axi-cel.-- Supplementary Figure 7. Comparison of T cell subsets between leukapheresis and non-modified T and CAR-T cells at the time of peak expansion.-- Supplementary Figure 8. Quantitative determination of the TCR Vβ repertoire of human T lymphocytes by flow cytometry.-- Supplementary Figure 9. Correlation between CAR-T cell expansion in blood of patients with lymphoma and toxicity or response.-- Supplementary Figure 10. Comparison of the toxicity and efficacy of Tisa-cel and Axi-cel products. // Supplementary Table 1. Flow cytometry reagents for the validation of the detection and immune-phenotype characterization of academic and commercial CD19 CAR-T cells, Purpose: CAR-T cell therapy has proven to be a disruptive treatment in the hematology field, however, less than 50% of patients maintain long-term response and early predictors of outcome are still inconsistently defined. Here, we aimed to optimize the detection of CD19 CAR-T cells in blood and to identify phenotypic features as early biomarkers associated with toxicity and outcomes., Experimental design: In this study, monitoring by flow cytometry and digital PCR (dPCR), and immunophenotypic characterization of circulating CAR-T cells from 48 patients treated with Tisa-cel or Axi-cel was performed., Results: Validation of the flow cytometry reagent for the detection of CAR-T cells in blood revealed CD19 protein conjugated with streptavidin as the optimal detection method. Kinetics of CAR-T cell expansion in blood confirmed median day of peak expansion at seven days post-infusion by both flow cytometry and digital PCR. Circulating CAR-T cells showed an activated, proliferative, and exhausted phenotype at the time of peak expansion. Patients with increased expansion showed more severe CRS and ICANs. Immunophenotypic characterization of CAR-T cells at the peak expansion identified the increased expression of co-inhibitory molecules PD1 and LAG3 and reduced levels of the cytotoxicity marker CD107a as predictors of a better long-term disease control., Conclusions: These data show the importance of CAR-T cells in vivo monitoring and identify the expression of PD1LAG3 and CD107a as early biomarkers of long-term disease control after CAR-T cell therapy., This work has been supported by the Instituto de Salud Carlos III (ISCIII), Project RD21/0017/0021, Red Española de Terapias Avanzadas TERAV funded by European Union-NextGenerationEU. “Plan de Recuperación Transformación y Resiliencia” and Consejería de Salud y Familia, Junta de Andalucía PECART-0185-2020-7, PECART-0185-2020 CSYF 2021 – Proyectos Fondos FEDER. Proyectos estratégicos en Investigación en CAR-T. “Monitorización inmune tras tratamiento con células CAR-T: búsqueda de biomarcadores y medición de la actividadmetabólica como predictores de respuesta”., Peer reviewed
Proyecto: //
DOI: http://hdl.handle.net/10261/351949
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351949
HANDLE: http://hdl.handle.net/10261/351949
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351949
PMID: http://hdl.handle.net/10261/351949
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351949
Ver en: http://hdl.handle.net/10261/351949
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351949
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