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4,264 results on '"Bigas, A"'

1. Five latent factors underlie response to immunotherapy

Author

Usset, Joseph, Rosendahl Huber, Axel, Andrianova, Maria A., Batlle, Eduard, Carles, Joan, Cuppen, Edwin, Elez, Elena, Felip, Enriqueta, Gómez-Rey, Marina, Lo Giacco, Deborah, Martinez-Jimenez, Francisco, Muñoz-Couselo, Eva, Siu, Lillian L., Tabernero, Josep, Vivancos, Ana, Muiños, Ferran, Gonzalez-Perez, Abel, and Lopez-Bigas, Nuria

Published
2024
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2. The genomic landscape of 2,023 colorectal cancers

Author

Cornish, Alex J., Gruber, Andreas J., Kinnersley, Ben, Chubb, Daniel, Frangou, Anna, Caravagna, Giulio, Noyvert, Boris, Lakatos, Eszter, Wood, Henry M., Thorn, Steve, Culliford, Richard, Arnedo-Pac, Claudia, Househam, Jacob, Cross, William, Sud, Amit, Law, Philip, Leathlobhair, Maire Ni, Hawari, Aliah, Woolley, Connor, Sherwood, Kitty, Feeley, Nathalie, Gül, Güler, Fernandez-Tajes, Juan, Zapata, Luis, Alexandrov, Ludmil B., Murugaesu, Nirupa, Sosinsky, Alona, Mitchell, Jonathan, Lopez-Bigas, Nuria, Quirke, Philip, Church, David N., Tomlinson, Ian P. M., Sottoriva, Andrea, Graham, Trevor A., Wedge, David C., and Houlston, Richard S.

Published
2024
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5. Strand-resolved mutagenicity of DNA damage and repair

Author

Anderson, Craig J., Talmane, Lana, Luft, Juliet, Connelly, John, Nicholson, Michael D., Verburg, Jan C., Pich, Oriol, Campbell, Susan, Giaisi, Marco, Wei, Pei-Chi, Sundaram, Vasavi, Connor, Frances, Ginno, Paul A., Sasaki, Takayo, Gilbert, David M., López-Bigas, Núria, Semple, Colin A., Odom, Duncan T., Aitken, Sarah J., and Taylor, Martin S.

Published
2024
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6. Brill-Noether loci

Author

Bigas, Montserrat Teixidor i

Subjects
Mathematics - Algebraic Geometry, 14H10, 14H51
Abstract

Brill-Noether loci ${\mathcal M}^r_{g,d}$ are those subsets of the moduli space ${\mathcal M}_g$ determined by the existence of a linear series of degree $d$ and dimension $r$. By looking at non-singular curves in a neighborhood of a special chain of elliptic curves, we provide a new proof of the non-emptiness of the Brill-Noether loci when the expected codimension satisfies $-g+r+1\le \rho(g,r,d)\le 0$ and prove that for a generic point of a component of this locus, the Petri map is onto. As an application, we show that Brill-Noether loci of the same codimension are distinct when the codimension is not too large, substantially generalizing the known result in codimensions 1 and 2. We also provide a new technique for checking that Brill-Noether loci are not included in each other., Comment: Comments welcome

Published
2023

8. IκBα controls dormancy in hematopoietic stem cells via retinoic acid during embryonic development

Author

Thambyrajah, Roshana, Maqueda, Maria, Fadlullah, Muhammad Zaki, Proffitt, Martin, Neo, Wen Hao, Guillén, Yolanda, Casado-Pelaez, Marta, Herrero-Molinero, Patricia, Brujas, Carla, Castelluccio, Noemi, González, Jessica, Iglesias, Arnau, Marruecos, Laura, Ruiz-Herguido, Cristina, Esteller, Manel, Mereu, Elisabetta, Lacaud, Georges, Espinosa, Lluis, and Bigas, Anna

Published
2024
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9. Author Correction: Modulating the immune response to SARS-CoV-2 by different nanocarriers delivering an mRNA expressing trimeric RBD of the spike protein: COVARNA Consortium

Author

Marcos-Villar, Laura, Perdiguero, Beatriz, Anthiya, Shubaash, Borrajo, Mireya L., Lou, Gustavo, Franceschini, Lorenzo, Esteban, Ignasi, Sánchez-Cordón, Pedro J., Zamora, Carmen, Sorzano, Carlos Óscar S., Jordá, Luis, Codó, Laia, Gelpí, Josep L., Sisteré-Oró, Marta, Meyerhans, Andreas, Thielemans, Kris, Martínez-Jiménez, Francisco, López-Bigas, Núria, García, Felipe, Alonso, María J., Plana, Montserrat, Esteban, Mariano, and Gómez, Carmen Elena

Published
2024
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10. Modulating the immune response to SARS-CoV-2 by different nanocarriers delivering an mRNA expressing trimeric RBD of the spike protein: COVARNA Consortium

Author

Marcos-Villar, Laura, Perdiguero, Beatriz, Anthiya, Shubaash, Borrajo, Mireya L., Lou, Gustavo, Franceschini, Lorenzo, Esteban, Ignasi, Sánchez-Cordón, Pedro J., Zamora, Carmen, Sorzano, Carlos Óscar S., Jordá, Luis, Codó, Laia, Gelpí, Josep L., Sisteré-Oró, Marta, Meyerhans, Andreas, Thielemans, Kris, Martínez-Jiménez, Francisco, López-Bigas, Núria, García, Felipe, Alonso, María J., Plana, Montserrat, Esteban, Mariano, and Gómez, Carmen Elena

Published
2024
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12. The 1+Million Genomes Minimal Dataset for Cancer

Author

Riba, Michela, Sala, Cinzia, Culhane, Aedin C., Flobak, Åsmund, Patocs, Attila, Boye, Kjetil, Plevova, Karla, Pospíšilová, Šárka, Gandolfi, Giorgia, Morelli, Marco J., Bucci, Gabriele, Edsjö, Anders, Lassen, Ulrik, Al-Shahrour, Fátima, Lopez-Bigas, Nuria, Hovland, Randi, Cuppen, Edwin, Valencia, Alfonso, Poirel, Helene A., Rosenquist, Richard, Scollen, Serena, Arenas Marquez, Juan, Belien, Jeroen, De Nicolo, Arcangela, De Maria, Ruggero, Torrents, David, and Tonon, Giovanni

Published
2024
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13. IκBα controls dormancy in hematopoietic stem cells via retinoic acid during embryonic development

Author

Roshana Thambyrajah, Maria Maqueda, Muhammad Zaki Fadlullah, Martin Proffitt, Wen Hao Neo, Yolanda Guillén, Marta Casado-Pelaez, Patricia Herrero-Molinero, Carla Brujas, Noemi Castelluccio, Jessica González, Arnau Iglesias, Laura Marruecos, Cristina Ruiz-Herguido, Manel Esteller, Elisabetta Mereu, Georges Lacaud, Lluis Espinosa, and Anna Bigas

Subjects
Science
Abstract

Abstract Recent findings suggest that Hematopoietic Stem Cells (HSC) and progenitors arise simultaneously and independently of each other already in the embryonic aorta-gonad mesonephros region, but it is still unknown how their different features are established. Here, we uncover IκBα (Nfkbia, the inhibitor of NF-κB) as a critical regulator of HSC proliferation throughout development. IκBα balances retinoic acid signaling levels together with the epigenetic silencer, PRC2, specifically in HSCs. Loss of IκBα decreases proliferation of HSC and induces a dormancy related gene expression signature instead. Also, IκBα deficient HSCs respond with superior activation to in vitro culture and in serial transplantation. At the molecular level, chromatin regions harboring binding motifs for retinoic acid signaling are hypo-methylated for the PRC2 dependent H3K27me3 mark in IκBα deficient HSCs. Overall, we show that the proliferation index in the developing HSCs is regulated by a IκBα-PRC2 axis, which controls retinoic acid signaling.

Published
2024
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15. Modulating the immune response to SARS-CoV-2 by different nanocarriers delivering an mRNA expressing trimeric RBD of the spike protein: COVARNA Consortium

Author

Laura Marcos-Villar, Beatriz Perdiguero, Shubaash Anthiya, Mireya L. Borrajo, Gustavo Lou, Lorenzo Franceschini, Ignasi Esteban, Pedro J. Sánchez-Cordón, Carmen Zamora, Carlos Óscar S. Sorzano, Luis Jordá, Laia Codó, Josep L. Gelpí, Marta Sisteré-Oró, Andreas Meyerhans, Kris Thielemans, Francisco Martínez-Jiménez, Núria López-Bigas, Felipe García, María J. Alonso, Montserrat Plana, Mariano Esteban, and Carmen Elena Gómez

Subjects
Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Vaccines based on mRNA technology have revolutionized the field. In fact, lipid nanoparticles (LNP) formulated with mRNA are the preferential vaccine platform used in the fight against SARS-CoV-2 infection, with wider application against other diseases. The high demand and property right protection of the most potent cationic/ionizable lipids used for LNP formulation of COVID-19 mRNA vaccines have promoted the design of alternative nanocarriers for nucleic acid delivery. In this study we have evaluated the immunogenicity and efficacy of different rationally designed lipid and polymeric-based nanoparticle prototypes against SARS-CoV-2 infection. An mRNA coding for a trimeric soluble form of the receptor binding domain (RBD) of the spike (S) protein from SARS-CoV-2 was encapsulated using different components to form nanoemulsions (NE), nanocapsules (NC) and lipid nanoparticles (LNP). The toxicity and biological activity of these prototypes were evaluated in cultured cells after transfection and in mice following homologous prime/boost immunization. Our findings reveal good levels of RBD protein expression with most of the formulations. In C57BL/6 mice immunized intramuscularly with two doses of formulated RBD-mRNA, the modified lipid nanoparticle (mLNP) and the classical lipid nanoparticle (LNP-1) were the most effective delivery nanocarriers at inducing binding and neutralizing antibodies against SARS-CoV-2. Both prototypes fully protected susceptible K18-hACE2 transgenic mice from morbidity and mortality following a SARS-CoV-2 challenge. These results highlight that modulation of mRNAs immunogenicity can be achieved by using alternative nanocarriers and support further assessment of mLNP and LNP-1 prototypes as delivery vehicles for mRNA vaccines.

Published
2024
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16. Ranks of maps of vector bundles

Author

Bigas, Montserrat Teixidor i

Subjects
Mathematics - Algebraic Geometry, 14H60
Abstract

We generalize to vector bundles the techniques introduced for line bundles in prior work of the author with Liu, Osserman and Zhang. We then use this method to prove the injectivity of the Petri map for vector bundles and the surjectivity of a map related to deformation theory of Poincar\'e sheaves., Comment: Added more detailed background material. To appear in RevMath.Comp

Published
2022

17. Successive extensions of vector bundles on curves

Author

Bigas, Montserrat Teixidor i

Subjects
Mathematics - Algebraic Geometry, 14H60
Abstract

We show that on a generic curve, a bundle obtained by successive extensions is stable. We compute the dimension of the set of such extensions. We use degeneration methods specializing the curve to a chain of elliptic components

Published
2022

18. Heterologous mRNA/MVA delivering trimeric-RBD as effective vaccination regimen against SARS-CoV-2: COVARNA Consortium

Author

Laura Marcos-Villar, Beatriz Perdiguero, María López-Bravo, Carmen Zamora, Laura Sin, Enrique Álvarez, Carlos Óscar S. Sorzano, Pedro J. Sánchez-Cordón, José M. Casasnovas, David Astorgano, Juan García-Arriaza, Shubaash Anthiya, Mireya L. Borrajo, Gustavo Lou, Belén Cuesta, Lorenzo Franceschini, Josep L. Gelpí, Kris Thielemans, Marta Sisteré-Oró, Andreas Meyerhans, Felipe García, Ignasi Esteban, Núria López-Bigas, Montserrat Plana, María J. Alonso, Mariano Esteban, and Carmen Elena Gómez

Subjects
SARS-CoV-2 vaccine, trimeric-RBD, nanocarriers, mRNA/MVA regimen, vaccine protection, Infectious and parasitic diseases, RC109-216, Microbiology, QR1-502
Abstract

Despite the high efficiency of current SARS-CoV-2 mRNA vaccines in reducing COVID-19 morbidity and mortality, waning immunity and the emergence of resistant variants underscore the need for novel vaccination strategies. This study explores a heterologous mRNA/Modified Vaccinia virus Ankara (MVA) prime/boost regimen employing a trimeric form of the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein compared to a homologous MVA/MVA regimen. In C57BL/6 mice, the RBD was delivered during priming via an mRNA vector encapsulated in nanoemulsions (NE) or lipid nanoparticles (LNP), followed by a booster with a replication-deficient MVA-based recombinant virus (MVA-RBD). This heterologous mRNA/MVA regimen elicited strong anti-RBD binding and neutralizing antibodies (BAbs and NAbs) against both the ancestral SARS-CoV-2 strain and different variants of concern (VoCs). Additionally, this protocol induced robust and polyfunctional RBD-specific CD4 and CD8 T cell responses, particularly in animals primed with mLNP-RBD. In K18-hACE2 transgenic mice, the LNP-RBD/MVA combination provided complete protection from morbidity and mortality following a live SARS-CoV-2 challenge compared with the partial protection observed with mNE-RBD/MVA or MVA/MVA regimens. Although the mNE-RBD/MVA regimen only protects half of the animals, it was able to induce antibodies with Fc-mediated effector functions besides NAbs. Moreover, viral replication and viral load in the respiratory tract were markedly reduced and decreased pro-inflammatory cytokine levels were observed. These results support the efficacy of heterologous mRNA/MVA vaccine combinations over homologous MVA/MVA regimen, using alternative nanocarriers that circumvent intellectual property restrictions of current mRNA vaccine formulations.

Published
2024
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19. Systemic inflammation biomarkers during angioedema attacks in hereditary angioedema

Author

Johana Gil-Serrano, Moisés Labrador-Horrillo, Paula Galvan-Blasco, Anna Sala-Cunill, Patricia Bigas, Javier Pereira-González, Olga Luengo, Victoria Cardona, and Mar Guilarte

Subjects
hereditary angioedema, HAE-C1INH, HAE-FXII, inflammation, acute phase reactants, d-dimer, Immunologic diseases. Allergy, RC581-607
Abstract

BackgroundHereditary angioedema (HAE) is a rare disease characterized by localized and self-limited angioedema (AE) attacks. A local increase of bradykinin (BK) mediates AE attacks in HAE, however the role of inflammation in HAE has been poorly explored We aim to analyze the role of inflammatory mediators in HAE patients during AE attacks.MethodsPatients with a confirmed HAE diagnosis due to C1 inhibitor deficiency (HAE-C1INH) or patients F12 gene mutations (HAE-FXII) attending to our outpatient clinic between November-2019 and May-2022 were included. Demographic and clinical characteristics were analyzed. Blood samples were collected both during symptom-free periods (baseline) and during HAE attacks, and acute phase reactants (APR), such as serum amyloid A (SAA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), D-Dimer and white blood cells were measured.ResultsSeventy-eight patients were enrolled in the study, with a predominant representation of women (76%, n=59), and a mean age of 47.8 years (range 6–88). Among them, 67% (n=52) of patients had HAE-C1INH (46 classified as type 1 and 6 as type 2) while 33% (n=26) had HAE-FXII. During attack-free periods, the majority of patients exhibited normal levels of SAA, ESR, D-dimer, ACE and WCC. However, in a subset of patients (16% for SAA, 18% for ESR, and 14.5% for D-dimer), elevations were noted at baseline. Importantly, during HAE attacks, significant increases were observed in SAA in 88% of patients (p< 0.0001 vs. baseline), in ESR in 65% (p= 0.003 vs. baseline) and D-dimer in 71% (p=0.001 vs. baseline) of the patients. A comparison between baseline and acute attack levels in 17 patients revealed significant differences in SAA AA (p

Published
2024
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20. Cis inhibition of NOTCH1 through JAGGED1 sustains embryonic hematopoietic stem cell fate

Author

Roshana Thambyrajah, Maria Maqueda, Wen Hao Neo, Kathleen Imbach, Yolanda Guillén, Daniela Grases, Zaki Fadlullah, Stefano Gambera, Francesca Matteini, Xiaonan Wang, Fernando J. Calero-Nieto, Manel Esteller, Maria Carolina Florian, Eduard Porta, Rui Benedito, Berthold Göttgens, Georges Lacaud, Lluis Espinosa, and Anna Bigas

Subjects
Science
Abstract

Abstract Hematopoietic stem cells (HSCs) develop from the hemogenic endothelium (HE) in the aorta- gonads-and mesonephros (AGM) region and reside within Intra-aortic hematopoietic clusters (IAHC) along with hematopoietic progenitors (HPC). The signalling mechanisms that distinguish HSCs from HPCs are unknown. Notch signaling is essential for arterial specification, IAHC formation and HSC activity, but current studies on how Notch segregates these different fates are inconsistent. We now demonstrate that Notch activity is highest in a subset of, GFI1 + , HSC-primed HE cells, and is gradually lost with HSC maturation. We uncover that the HSC phenotype is maintained due to increasing levels of NOTCH1 and JAG1 interactions on the surface of the same cell (cis) that renders the NOTCH1 receptor from being activated. Forced activation of the NOTCH1 receptor in IAHC activates a hematopoietic differentiation program. Our results indicate that NOTCH1-JAG1 cis-inhibition preserves the HSC phenotype in the hematopoietic clusters of the embryonic aorta.

Published
2024
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21. Metabolic rewiring induced by ranolazine improves melanoma responses to targeted therapy and immunotherapy

Author

Redondo-Muñoz, Marta, Rodriguez-Baena, Francisco Javier, Aldaz, Paula, Caballé-Mestres, Adriá, Moncho-Amor, Verónica, Otaegi-Ugartemendia, Maddalen, Carrasco-Garcia, Estefania, Olias-Arjona, Ana, Lasheras-Otero, Irene, Santamaria, Eva, Bocanegra, Ana, Chocarro, Luisa, Grier, Abby, Dzieciatkowska M, Monika, Bigas, Claudia, Martin, Josefina, Urdiroz-Urricelqui, Uxue, Marzo, Florencio, Santamaria, Enrique, Kochan, Grazyna, Escors, David, Larrayoz, Ignacio Marcos, Heyn, Holger, D’Alessandro, Angelo, Attolini, Camille Stephan-Otto, Matheu, Ander, Wellbrock, Claudia, Benitah, Salvador Aznar, Sanchez-Laorden, Berta, and Arozarena, Imanol

Published
2023
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22. Implications of noncoding regulatory functions in the development of insulinomas

Author

Ramos-Rodríguez, Mireia, Subirana-Granés, Marc, Norris, Richard, Sordi, Valeria, Fernández, Ángel, Fuentes-Páez, Georgina, Pérez-González, Beatriz, Berenguer Balaguer, Clara, Raurell-Vila, Helena, Chowdhury, Murad, Corripio, Raquel, Partelli, Stefano, López-Bigas, Núria, Pellegrini, Silvia, Montanya, Eduard, Nacher, Montserrat, Falconi, Massimo, Layer, Ryan, Rovira, Meritxell, González-Pérez, Abel, Piemonti, Lorenzo, and Pasquali, Lorenzo

Published
2024
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24. Brill-Noether loci with ramification at two points

Author

Bigas, Montserrat Teixidor i

Subjects
Mathematics - Algebraic Geometry, 14H
Abstract

We prove the injectivity of the Petri map for linear series on a general curve with given ramification at two generic points. We also describe the components of such a set of linear series on a chain of elliptic curves., Comment: Comments welcome

Published
2021

28. eProcessor: European, Extendable, Energy-Efficient, Extreme-Scale, Extensible, Processor Ecosystem.

Author

Lluc Alvarez, Abraham Ruiz, Arnau Bigas-Soldevilla, Pavel Kuroedov, Alberto González 0004, Hamsika Mahale, Noe Bustamante, Albert Aguilera, Francesco Minervini, Javier Salamero, Oscar Palomar, Vassilis Papaefstathiou, Antonis Psathakis, Nikolaos Dimou, Michalis Giaourtas, Iasonas Mastorakis, Georgios Ieronymakis, Georgios-Michail Matzouranis, Vassilis Flouris, Nick Kossifidis, Manolis Marazakis, Bhavishya Goel, Madhavan Manivannan, Ahsen Ejaz, Panagiotis Strikos, Mateo Vázquez, Ioannis Sourdis, Pedro Trancoso, Per Stenström, Jens Hagemeyer, Lennart Tigges, Nils Kucza, Jean-Marc Philippe, and Ioannis Papaefstathiou

Published
2023
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29. Multiomic analysis of malignant pleural mesothelioma identifies molecular axes and specialized tumor profiles driving intertumor heterogeneity

Author

Mangiante, Lise, Alcala, Nicolas, Sexton-Oates, Alexandra, Di Genova, Alex, Gonzalez-Perez, Abel, Khandekar, Azhar, Bergstrom, Erik N., Kim, Jaehee, Liu, Xiran, Blazquez-Encinas, Ricardo, Giacobi, Colin, Le Stang, Nolwenn, Boyault, Sandrine, Cuenin, Cyrille, Tabone-Eglinger, Severine, Damiola, Francesca, Voegele, Catherine, Ardin, Maude, Michallet, Marie-Cecile, Soudade, Lorraine, Delhomme, Tiffany M., Poret, Arnaud, Brevet, Marie, Copin, Marie-Christine, Giusiano-Courcambeck, Sophie, Damotte, Diane, Girard, Cecile, Hofman, Veronique, Hofman, Paul, Mouroux, Jérôme, Cohen, Charlotte, Lacomme, Stephanie, Mazieres, Julien, de Montpreville, Vincent Thomas, Perrin, Corinne, Planchard, Gaetane, Rousseau, Nathalie, Rouquette, Isabelle, Sagan, Christine, Scherpereel, Arnaud, Thivolet, Francoise, Vignaud, Jean-Michel, Jean, Didier, Ilg, Anabelle Gilg Soit, Olaso, Robert, Meyer, Vincent, Boland-Auge, Anne, Deleuze, Jean-Francois, Altmuller, Janine, Nuernberg, Peter, Ibáñez-Costa, Alejandro, Castaño, Justo P., Lantuejoul, Sylvie, Ghantous, Akram, Maussion, Charles, Courtiol, Pierre, Hernandez-Vargas, Hector, Caux, Christophe, Girard, Nicolas, Lopez-Bigas, Nuria, Alexandrov, Ludmil B., Galateau-Salle, Françoise, Foll, Matthieu, and Fernandez-Cuesta, Lynnette

Published
2023
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30. Mutational signature dynamics shaping the evolution of oesophageal adenocarcinoma

Author

Sujath Abbas, Oriol Pich, Ginny Devonshire, Shahriar A. Zamani, Annalise Katz-Summercorn, Sarah Killcoyne, Calvin Cheah, Barbara Nutzinger, Nicola Grehan, Nuria Lopez-Bigas, OCCAMS Consortium, Rebecca C. Fitzgerald, and Maria Secrier

Subjects
Science
Abstract

Abstract A variety of mutational processes drive cancer development, but their dynamics across the entire disease spectrum from pre-cancerous to advanced neoplasia are poorly understood. We explore the mutagenic processes shaping oesophageal adenocarcinoma tumorigenesis in 997 instances comprising distinct stages of this malignancy, from Barrett Oesophagus to primary tumours and advanced metastatic disease. The mutational landscape is dominated by the C[T > C/G]T substitution enriched signatures SBS17a/b, which are linked with TP53 mutations, increased proliferation, genomic instability and disease progression. The APOBEC mutagenesis signature is a weak but persistent signal amplified in primary tumours. We also identify prevalent alterations in DNA damage repair pathways, with homologous recombination, base and nucleotide excision repair and translesion synthesis mutated in up to 50% of the cohort, and surprisingly uncoupled from transcriptional activity. Among these, the presence of base excision repair deficiencies show remarkably poor prognosis in the cohort. In this work, we provide insights on the mutational aetiology and changes enabling the transition from pre-neoplastic to advanced oesophageal adenocarcinoma.

Published
2023
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31. Rational Curves on Moduli Spaces of Vector Bundles

Author

Mustopa, Yusuf and Bigas, Montserrat Teixidor i

Subjects
Mathematics - Algebraic Geometry
Abstract

We completely describe the components of expected dimension of the Hilbert Scheme of rational curves of fixed degree $k$ in the moduli space ${\rm SU}_{C}(r,L)$ of semistable vector bundles of rank $r$ and determinant $L$ on a curve $C$. We show that for every $k \geq 1$ there are ${\rm gcd}(r, \deg L)$ unobstructed components. In addition, if $k$ is divisible by $r_1(r-r_1)(g-1)$ for $1\le r_1\le r-1$, there is an additional obstructed component of the expected dimension for each such $r_1$. We construct families of obstructed components and show that their generic point is not the generic vector bundle of given rank and determinant. Finally, we also obtain an upper bound on the degree of rational connectedness of ${\rm SU}_{C}(r,L)$ which is linear in the dimension., Comment: 18 pages, comments welcome

Published
2020

32. Coherent systems on the projective line

Author

Newstead, P. E. and Bigas, Montserrat Teixidor i

Subjects
Mathematics - Algebraic Geometry, 14H60
Abstract

It is well known that there are no stable bundles of rank greater than 1 on the projective line. In this paper, our main purpose is to study the existence problem for stable coherent systems on the projective line when the number of sections is larger than the rank. We include a review of known results, mostly for a small number of sections., Comment: Typos corrected. To appear in Quarterly J. Math. (Atiyah Memorial Volume)

Published
2020

33. GENOTYPE/PHENOTYPE ASSOCIATIONS IN 174 INDIVIDUALS WITH GERMLINE GATA2 MUTATIONS

Author

Lili Kotmayer, Emilia Kozyra, Maximilian Kaiser, Michael Dworzak, Barbara De Moerloose, Jan Starý, Henrik Hasle, Kirsi Jahnukainen, Sophia Polychronopoulou, Krisztián Kállay, Owen Smith, Shlomit Barzilai, Riccardo Masetti, Jochen Buechner, Marek Ussowicz, Paula Kjollerstrom, Ivana Boďová, Marko Kavcic, Albert Catala, Dominik Turkiewicz, Markus Schmugge, Valérie De Haas, Rebecca Voss, Anna Bigas, Damia Romero, Csaba Bödör, Miriam Erlacher, Alessandra Giorgetti, Charlotte Niemeyer, and Marcin Wlodarski

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2023
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34. Teacher Development Structured around Reasoning about Functions

Author

Schliemann, Analúcia D., Carraher, David W., and Teixidor-i-Bigas, Montserrat

Abstract

We report on a teacher development program aimed at improving mathematics teaching and learning from grades 5-9. The 18-month largely online program arose from a partnership of mathematics education researchers, mathematicians, physicists, and nine school districts. The program employed functions as a lens to reinterpret and interconnect content topics in the mathematics curriculum. It was designed to promote a deep understanding of mathematics while drawing upon students' spontaneous reasoning, generalizations, representations, and discussions about relations between physical quantities and numbers. We describe the program's foundations and activities and analyze changes in teaching and in student learning during 3 years of implementation. Results suggest that the teacher development program contributed to improved teaching in the target districts and to positive changes in the performance of target district students on state-mandated tests.

Published
2022
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35. Author Correction: Modulating the immune response to SARS-CoV-2 by different nanocarriers delivering an mRNA expressing trimeric RBD of the spike protein: COVARNA Consortium

Author

Laura Marcos-Villar, Beatriz Perdiguero, Shubaash Anthiya, Mireya L. Borrajo, Gustavo Lou, Lorenzo Franceschini, Ignasi Esteban, Pedro J. Sánchez-Cordón, Carmen Zamora, Carlos Óscar S. Sorzano, Luis Jordá, Laia Codó, Josep L. Gelpí, Marta Sisteré-Oró, Andreas Meyerhans, Kris Thielemans, Francisco Martínez-Jiménez, Núria López-Bigas, Felipe García, María J. Alonso, Montserrat Plana, Mariano Esteban, and Carmen Elena Gómez

Subjects
Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2024
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36. Theta divisors and Ulrich bundles on Geometrically ruled surfaces

Author

Aprodu, M., Casnati, G., Costa, L., Miró-Roig, R. M., and Bigas, M. Teixidor i

Subjects
Mathematics - Algebraic Geometry, Primary 14J60, Secondary 14J26
Abstract

We consider the following question: for which invariants $g$ and $e$ is there a geometrically ruled surface $S \rightarrow C$ over a curve $C$ of genus $g$ with invariant $e$ such that $S$ is the support of an Ulrich line bundle with respect to a very ample line bundle? A surprising relation between the existence of certain proper Theta divisors on some moduli spaces of vector bundles on $C$ with the existence of Ulrich line bundles on $S$ will be the key to completely solve the above question. The relation is realized by translating the vanishing conditions characterizing Ulrich line bundles to specific geometric conditions on the symmetric powers of the defining vector bundle of a given ruled surface. This general principle leads to some finer existence results of Ulrich line bundles in particular cases. Another focus is on the rank two case where, with very few exceptions, we show the existence of large families of special Ulrich bundles on arbitrary polarized ruled surfaces.

Published
2019

38. The repertoire of mutational signatures in human cancer

Author

Alexandrov, Ludmil B, Kim, Jaegil, Haradhvala, Nicholas J, Huang, Mi Ni, Tian Ng, Alvin Wei, Wu, Yang, Boot, Arnoud, Covington, Kyle R, Gordenin, Dmitry A, Bergstrom, Erik N, Islam, SM Ashiqul, Lopez-Bigas, Nuria, Klimczak, Leszek J, McPherson, John R, Morganella, Sandro, Sabarinathan, Radhakrishnan, Wheeler, David A, Mustonen, Ville, Getz, Gad, Rozen, Steven G, and Stratton, Michael R

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Human Genome, Cancer, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Age Factors, Base Sequence, Exome, Genome, Human, Humans, Mutation, Neoplasms, Sequence Analysis, DNA, PCAWG Mutational Signatures Working Group, PCAWG Consortium, General Science & Technology
Abstract

Somatic mutations in cancer genomes are caused by multiple mutational processes, each of which generates a characteristic mutational signature1. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium2 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we characterized mutational signatures using 84,729,690 somatic mutations from 4,645 whole-genome and 19,184 exome sequences that encompass most types of cancer. We identified 49 single-base-substitution, 11 doublet-base-substitution, 4 clustered-base-substitution and 17 small insertion-and-deletion signatures. The substantial size of our dataset, compared with previous analyses3-15, enabled the discovery of new signatures, the separation of overlapping signatures and the decomposition of signatures into components that may represent associated-but distinct-DNA damage, repair and/or replication mechanisms. By estimating the contribution of each signature to the mutational catalogues of individual cancer genomes, we revealed associations of signatures to exogenous or endogenous exposures, as well as to defective DNA-maintenance processes. However, many signatures are of unknown cause. This analysis provides a systematic perspective on the repertoire of mutational processes that contribute to the development of human cancer.

Published
2020

39. Analyses of non-coding somatic drivers in 2,658 cancer whole genomes.

Author

Rheinbay, Esther, Nielsen, Morten Muhlig, Abascal, Federico, Wala, Jeremiah A, Shapira, Ofer, Tiao, Grace, Hornshøj, Henrik, Hess, Julian M, Juul, Randi Istrup, Lin, Ziao, Feuerbach, Lars, Sabarinathan, Radhakrishnan, Madsen, Tobias, Kim, Jaegil, Mularoni, Loris, Shuai, Shimin, Lanzós, Andrés, Herrmann, Carl, Maruvka, Yosef E, Shen, Ciyue, Amin, Samirkumar B, Bandopadhayay, Pratiti, Bertl, Johanna, Boroevich, Keith A, Busanovich, John, Carlevaro-Fita, Joana, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Craft, David, Dhingra, Priyanka, Diamanti, Klev, Fonseca, Nuno A, Gonzalez-Perez, Abel, Guo, Qianyun, Hamilton, Mark P, Haradhvala, Nicholas J, Hong, Chen, Isaev, Keren, Johnson, Todd A, Juul, Malene, Kahles, Andre, Kahraman, Abdullah, Kim, Youngwook, Komorowski, Jan, Kumar, Kiran, Kumar, Sushant, Lee, Donghoon, Lehmann, Kjong-Van, Li, Yilong, Liu, Eric Minwei, Lochovsky, Lucas, Park, Keunchil, Pich, Oriol, Roberts, Nicola D, Saksena, Gordon, Schumacher, Steven E, Sidiropoulos, Nikos, Sieverling, Lina, Sinnott-Armstrong, Nasa, Stewart, Chip, Tamborero, David, Tubio, Jose MC, Umer, Husen M, Uusküla-Reimand, Liis, Wadelius, Claes, Wadi, Lina, Yao, Xiaotong, Zhang, Cheng-Zhong, Zhang, Jing, Haber, James E, Hobolth, Asger, Imielinski, Marcin, Kellis, Manolis, Lawrence, Michael S, von Mering, Christian, Nakagawa, Hidewaki, Raphael, Benjamin J, Rubin, Mark A, Sander, Chris, Stein, Lincoln D, Stuart, Joshua M, Tsunoda, Tatsuhiko, Wheeler, David A, Johnson, Rory, Reimand, Jüri, Gerstein, Mark, Khurana, Ekta, Campbell, Peter J, López-Bigas, Núria, PCAWG Drivers and Functional Interpretation Working Group, PCAWG Structural Variation Working Group, Weischenfeldt, Joachim, Beroukhim, Rameen, Martincorena, Iñigo, Pedersen, Jakob Skou, Getz, Gad, and PCAWG Consortium

Subjects
PCAWG Drivers and Functional Interpretation Working Group, PCAWG Structural Variation Working Group, PCAWG Consortium, Humans, Neoplasms, Gene Expression Regulation, Neoplastic, Mutation, Genome, Human, Databases, Genetic, DNA Breaks, INDEL Mutation, Genome-Wide Association Study, Gene Expression Regulation, Neoplastic, Genome, Human, Databases, Genetic, General Science & Technology
Abstract

The discovery of drivers of cancer has traditionally focused on protein-coding genes1-4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5' region of TP53, in the 3' untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.

Published
2020

40. β‐Catenin activity induces an RNA biosynthesis program promoting therapy resistance in T‐cell acute lymphoblastic leukemia

Author

Violeta García‐Hernández, David Arambilet, Yolanda Guillén, Teresa Lobo‐Jarne, María Maqueda, Christos Gekas, Jessica González, Arnau Iglesias, Nerea Vega‐García, Inés Sentís, Juan L Trincado, Ian Márquez‐López, Holger Heyn, Mireia Camós, Lluis Espinosa, and Anna Bigas

Subjects
chemotherapy resistance, Kaiso, RNA processing, T‐ALL, β‐catenin, Medicine (General), R5-920, Genetics, QH426-470
Abstract

Abstract Understanding the molecular mechanisms that contribute to the appearance of chemotherapy resistant cell populations is necessary to improve cancer treatment. We have now investigated the role of β‐catenin/CTNNB1 in the evolution of T‐cell Acute Lymphoblastic Leukemia (T‐ALL) patients and its involvement in therapy resistance. We have identified a specific gene signature that is directly regulated by β‐catenin, TCF/LEF factors and ZBTB33/Kaiso in T‐ALL cell lines, which is highly and significantly represented in five out of six refractory patients from a cohort of 40 children with T‐ALL. By subsequent refinement of this gene signature, we found that a subset of β‐catenin target genes involved with RNA‐processing function are sufficient to segregate T‐ALL refractory patients in three independent cohorts. We demonstrate the implication of β‐catenin in RNA and protein synthesis in T‐ALL and provide in vitro and in vivo experimental evidence that β‐catenin is crucial for the cellular response to chemotherapy, mainly in the cellular recovery phase after treatment. We propose that combination treatments involving chemotherapy plus β‐catenin inhibitors will enhance chemotherapy response and prevent disease relapse in T‐ALL patients.

Published
2023
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41. Key Factors Associated With Pulmonary Sequelae in the Follow-Up of Critically Ill COVID-19 Patients

Author

Cabello, María Aguilar, Alcaraz-Serrano, Victoria, Aldecoa, Cesar, Alegre, Cynthia, Calderón, Ángela Algaba, Álvarez, Sergio, Ruiz, Antonio Álvarez, Andrea, Ruth, Aparicio, Maria de Alba, Arrieta, Marta, Ayestarán, J. Ignacio, Badia, Joan Ramon, Badía, Mariona, Pravia, Orville Báez, Mariño, Ana Balan, Balsera, Begoña, Barbena, Laura, Barbeta, Enric, Bardi, Tommaso, Segade, Patricia Barral, Barroso, Marta, García, José Ángel Berezo, Bermejo, Jesus, Bigas, Judit, Blancas, Rafael, Cortés, María Luisa Blasco, Saera, María Bodi, Bofill, Neus, Vieiro, María Teresa Bouza, Bueno, Leticia, Bustamante-Munguira, Juan, Martínez, Cecilia del Busto, Hermoso, David Campi, Fernández, Sandra Campos, Cano, Iosune, Canseco, Joan, Fernández, Pablo Cardinal, García, Laura Carrión, Carvalho, Sulamita, Castellà, Manuel, Castellví, Andrea, Castro, Pedro, Centelles-Serrano, María José, Ávila, Ramon Cicuendez, Cillóniz, Catia, Clar, Luisa, Climent, Cristina, Codina, Jordi, Conde, Pamela, Contreras, Sofía, Parra, Raul de Frutos, Sánchez, Raul de Pablo, Mendoza, Diego De, Díaz, Yolanda, Vilas, María Digna Rivas, Moreno, Cristina Dólera, Dot, Irene, Giraudo, Pedro Enríquez, Arijón, Inés Esmorís, Monjo, Teresa Farre, Fernández, Javier, Ferrando, Carlos, Figueras, Albert, Espina, Lorena Forcelledo, Franquesa, Enric, Furro, Àngels, Gabarrus, Albert, Galbán, Cristóbal, García, Felipe, García, Beatriz, Prieto, Emilio García, Redruello, Carlos García, Sagastume, Amaia García, Castillo, Maria Luisa Gascón, Gomà, Gemma, Casal, Vanesa Gómez, Gómez, Silvia, Gonzalez, Carmen Gómez, Gordo, Federico, Gracia, Maria Pilar, Fernández, María José Gutierrez, Herraiz, Alba, Herrán-Monge, Rubén, Ibarz, Mercedes, Iglesias, Silvia, Janer, Maria Teresa, Jiménez, Gabriel, Díaz, Mar Juan, Kiarostami, Karsa, Álvarez, Juan I. Lazo, León, Miguel, López-Gavín, Alexandre, Guerrero, Desiree Macias, Herrera, Nuria Mamolar, Mendiluce, Rafael Mañez, Mantellini, Cecilia L., Naya, Gregorio Marco, Barcos, Iris Marco, Marcos, Pilar, Peis, Enrique Marmol, Cuadrado, Marta Martín, Delgado, María Cruz Martin, Vicente, Paula Martín, Martínez, María, Fernández, Carmen Eulalia Martínez, Juan, Maria Dolores Martínez, Palacios, Basilisa Martínez, Jimenez, Juan Fernando Masa, Masclans, Joan Ramon, Maseda, Emilio, Fernández, Eva María Menor, Banderas, Priscila Metora, Minguez, Olga, Miralbés, Mar, Monclou, Josman, Montejo-González, Juan Carlos, Montserrat, Neus, Aznar, María Mora, Morales, Dulce, Cano, Sara Guadalupe Moreno, Rodríguez, David Mosquera, Muñoz-Bermúdez, Rosana, Nicolás, José María, Bou, Ramon Nogue, Salinas, Rafaela Nogueras, Ocón, Marta, Ortega, Ana, Ossa, Sergio, Pagliarani, Pablo, Parrilla, Francisco, Pedregosa-Díaz, José, Bastida, Leire Pérez, Pérez, Purificación, Pérez-García, Felipe, Planelles, Gloria Pérez, Rubio, Eva Pérez, Laguna, David Pestaña, Prados, Javier, Pujol, Andrés, Coll, Núria Ramon, Sanchez-Giron, Gloria Renedo, Roche-Campo, Ferran, Rodriguez, Laura, Castro, Felipe Rodríguez de, Rodríguez, Silvia, Ruiz, Covadonga Rodríguez, Rubio, Jorge, López, Alberto Rubio, Ruiz-García, Ángela Leonor, Miralles, Miriam Ruiz, Murúa, Pablo Ryan, Paz, Eva Saborido, Degracia, Ana Salazar, Sanchez, Miguel, Sánchez, Ana, Chinesta, Susana Sancho, Santacoloma, Bitor, Sariñena, Maria Teresa, Pensado, Marta Segura, Serra, Lidia, Serra-Fortuny, Mireia, Lázaro, Ainhoa Serrano, Servià, Lluís, Soliva, Laura, Speziale, Carla, Tormos, Adrián, Torres, Mateu, Tranque-Liberal, Celia, Trefler, Sandra, Trujillano, Javier, Vaca, Rafaela, Val, Estela, Ruiz, Luis Valdivia, Vallverdú, Montserrat, Martin-Montalvo, Maria Van der Hofstadt, Adrio, Sabela Vara, Vázquez, Nil, Vengoechea, Javier, Vilà-Vilardel, Clara, Vilanova, Judit, Warrington, Tatiana Villada, Yang, Hua, Yang, Minlan, Zapatero, Ana, González, Jessica, de Batlle, Jordi, Benítez, Iván D., Torres, Gerard, Santisteve, Sally, Targa, Adriano D.S., Gort-Paniello, Clara, Moncusí-Moix, Anna, Aguilà, Maria, Seck, Fatty, Ceccato, Adrián, Ferrer, Ricard, Motos, Anna, Riera, Jordi, Fernández, Laia, Menéndez, Rosario, Lorente, José Ángel, Peñuelas, Oscar, Garcia-Gasulla, Dario, Peñasco, Yhivian, Ricart, Pilar, Abril Palomares, Elena, Aguilera, Luciano, Rodríguez, Alejandro, Boado Varela, Maria Victoria, Beteré, Belén, Pozo-Laderas, Juan Carlos, Solé-Violan, Jordi, Salvador-Adell, Inmaculada, Novo, Mariana Andrea, Barberán, José, Amaya Villar, Rosario, Garnacho-Montero, José, Gómez, José M., Blandino Ortiz, Aaron, Tamayo Lomas, Luis, Úbeda, Alejandro, Catalán-González, Mercedes, Sánchez-Miralles, Angel, Martínez Varela, Ignacio, Jorge García, Ruth Noemí, Franco, Nieves, Gumucio-Sanguino, Víctor D., Bustamante-Munguira, Elena, Valdivia, Luis Jorge, Caballero, Jesús, Gallego, Elena, Rodríguez, Covadonga, Castellanos-Ortega, Álvaro, Trenado, Josep, Marin-Corral, Judith, Albaiceta, Guillermo M., de la Torre, Maria del Carmen, Loza-Vázquez, Ana, Vidal, Pablo, Añón, Jose M., Carbajales Pérez, Cristina, Sagredo, Victor, Carbonell, Nieves, Socias, Lorenzo, Barberà, Carme, Estella, Angel, Diaz, Emili, de Gonzalo-Calvo, David, Torres, Antoni, and Barbé, Ferran

Published
2023
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42. Colorectal Cancer

Author

Tan, Cher Heng, primary, Morris, Van K., additional, Das, Prajnan, additional, Rodriguez-Bigas, Miguel, additional, and Iyer, Revathy B., additional

Published
2023
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43. Contributors

Author

Abdalla, Eddie K., primary, Ahuja, Jitesh, additional, Aluja-Jaramillo, Felipe, additional, Amaria, Rodabe N., additional, Amini, Behrang, additional, Avram, Anca, additional, Avritscher, Rony, additional, Bedrosian, Isabelle, additional, Betancourt-Cuellar, Sonia L., additional, Bhosale, Priya R., additional, Bishop, Andrew J., additional, Bronstein, Yulia, additional, Burgan, Constantine M., additional, Tran Cao, Hop S., additional, Chainitikun, Sudpreeda, additional, Chang, Joe Y., additional, J.Chery, Lisly, additional, Chuang, Hubert H., additional, Coleman, Aaron, additional, Costelloe, Colleen M., additional, Das, Prajnan, additional, DeJesus, Reordan, additional, Devine, Catherine, additional, Eifel, Patricia J., additional, Erasmus, Jeremy J., additional, C.Faria, Silvana, additional, Fleming, Jason B., additional, Galgano, Samuel J., additional, Ganeshan, Dhakshinamoorthy, additional, Garg, Naveen, additional, Garvey, Patrick B., additional, Gladish, Gregory, additional, Guo, Chunxiao, additional, Gutiérrez, Fernando R., additional, Halperin, Daniel M., additional, Hanafy, Abdelrahman K., additional, Hoffman, Karen, additional, Hofstetter, Wayne L., additional, Hwu, Wen-Jen, additional, Ibarra Rovira, Juan J., additional, Ibrahim, Mohannad, additional, Ikoma, Naruhiko, additional, Iyer, Revathy B., additional, Javadi, Sanaz, additional, Javle, Milind, additional, Jensen, Corey T., additional, Jonasch, Eric, additional, Kamat, Aparna, additional, Kamat, Ashish, additional, Kambadakone, Avinash R., additional, Kaufman, Gregory P., additional, Kaur, Amritjot, additional, Kaur, Harmeet, additional, Rao Korivi, Brinda, additional, Kumar, Rajendra, additional, Kundra, Vikas, additional, Kuperman Benveniste, Marcelo F., additional, Le, Ott, additional, Lee, Jeffrey H., additional, LePetross, Huang, additional, Lin, Patrick P., additional, Ludwig, Joseph A., additional, Macapinlac, Homer A., additional, Madewell, John E., additional, Mansfield, Paul, additional, Marcal, Leonardo P., additional, Marom, Edith M., additional, Massini, Tara, additional, Matamoros, Aurelio, additional, Frances McAleer, Mary, additional, Mehran, Reza J., additional, Menias, Christine, additional, Morani, Ajaykumar C., additional, Morris, Van K., additional, Moulder-Thompson, Stacy L., additional, Mujtaba, Bilal, additional, Mukherji, Suresh K., additional, Nassar, Sameh, additional, Nguyen, Quynh-Nhu, additional, Noda, Yoshifumi, additional, Onn, Amir, additional, Overman, Michael J., additional, C. Pagliaro, Lance, additional, Palacio, Diana P., additional, Parakh, Anushri, additional, Parmar, Hemant A., additional, Patel, Shreyaskumar, additional, Patnana, Madhavi, additional, Phan, Alexandria, additional, Pokhylevych, Halyna, additional, Porter, Kristin K., additional, Rauch, Gaiane M., additional, Raval, Bharat, additional, Rodriguez-Bigas, Miguel, additional, Rohren, Eric M., additional, Roland, Christina L., additional, Ross, Jeremy, additional, Sabloff, Bradley S., additional, Sagebiel, Tara, additional, Sahani, Dushant V., additional, Schmeler, Kathleen M., additional, Shroff, Girish, additional, Siefker-Radtke, Arlene O, additional, Smith, Elainea N., additional, Jason Stafford, R., additional, Stewart, David J., additional, Strange, Chad D., additional, Swisher, Stephen G., additional, Taher, Ahmed, additional, Heng Tan, Cher, additional, Truong, Mylene T., additional, Ueno, Naoto T., additional, Varadhachary, Gauri R., additional, Venkatesan, Aradhana M., additional, Verschraegen, Claire F., additional, Vikram, Raghunandan, additional, J.Vinnicombe, Sarah, additional, Virarkar, Mayur K., additional, Viswanathan, Chitra, additional, Westin, Jason R., additional, Woodward, Wendy A., additional, and Kuan Yu, T., additional

Published
2023
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44. Author Correction: Modulating the immune response to SARS-CoV-2 by different nanocarriers delivering an mRNA expressing trimeric RBD of the spike protein: COVARNA Consortium

Author

Marcos-Villar, Laura [0000-0002-8635-6432], Perdiguero, Beatriz [0000-0001-6276-7766], Anthiya, Shubaash [0000-0002-5137-1990], Borrajo, Mireya L. [0000-0002-1012-9444], Lou, Gustavo [0000-0001-5590-3096], Franceschini, Lorenzo [0000-0001-9013-9513], Esteban, Ignasi [0000-0001-8630-4117], Sánchez-Cordón, P. J. [0000-0002-7202-6475], Sorzano, Carlos Óscar S. [0000-0002-9473-283X], Codó, Laia [0000-0002-6797-8746], Gelpí, Josep L. [0000-0002-0566-7723], Sisteré-Oró, Marta [0000-0003-0214-6348], Meyerhans, Andreas [0000-0003-0620-5317], Thielemans, Kris [0000-0001-6353-9538], López-Bigas, Nuria [0000-0003-4925-8988], Plana, Montserrat [0000-0002-0767-4329], Esteban, Mariano [0000-0003-0846-2827], Gómez, Carmen E. [0000-0002-5414-7935], Marcos-Villar, Laura, Perdiguero, Beatriz, Anthiya, Shubaash, Borrajo, Mireya L., Lou, Gustavo, Franceschini, Lorenzo, Esteban, Ignasi, Sánchez-Cordón, P. J., Zamora, Carmen, Sorzano, Carlos Óscar S., Jordá, Luis, Codó, Laia, Gelpí, Josep L., Sisteré-Oró, Marta, Meyerhans, Andreas, Thielemans, Kris, Martínez-Jiménez, Francisco, López-Bigas, Nuria, García, Felipe, Alonso, María J., Plana, Montserrat, Esteban, Mariano, Gómez, Carmen E., Marcos-Villar, Laura [0000-0002-8635-6432], Perdiguero, Beatriz [0000-0001-6276-7766], Anthiya, Shubaash [0000-0002-5137-1990], Borrajo, Mireya L. [0000-0002-1012-9444], Lou, Gustavo [0000-0001-5590-3096], Franceschini, Lorenzo [0000-0001-9013-9513], Esteban, Ignasi [0000-0001-8630-4117], Sánchez-Cordón, P. J. [0000-0002-7202-6475], Sorzano, Carlos Óscar S. [0000-0002-9473-283X], Codó, Laia [0000-0002-6797-8746], Gelpí, Josep L. [0000-0002-0566-7723], Sisteré-Oró, Marta [0000-0003-0214-6348], Meyerhans, Andreas [0000-0003-0620-5317], Thielemans, Kris [0000-0001-6353-9538], López-Bigas, Nuria [0000-0003-4925-8988], Plana, Montserrat [0000-0002-0767-4329], Esteban, Mariano [0000-0003-0846-2827], Gómez, Carmen E. [0000-0002-5414-7935], Marcos-Villar, Laura, Perdiguero, Beatriz, Anthiya, Shubaash, Borrajo, Mireya L., Lou, Gustavo, Franceschini, Lorenzo, Esteban, Ignasi, Sánchez-Cordón, P. J., Zamora, Carmen, Sorzano, Carlos Óscar S., Jordá, Luis, Codó, Laia, Gelpí, Josep L., Sisteré-Oró, Marta, Meyerhans, Andreas, Thielemans, Kris, Martínez-Jiménez, Francisco, López-Bigas, Nuria, García, Felipe, Alonso, María J., Plana, Montserrat, Esteban, Mariano, and Gómez, Carmen E.

Abstract

In this article, the author name Núria López-Bigas was incorrectly written as Nuria López-Vigas. The original article has been corrected.

Published
2024

45. Characterization of the spectrum of trivalent VAV1‐mutation‐driven tumours using a gene‐edited mouse model

Author

Javier Robles‐Valero, Lucía Fernández‐Nevado, Myriam Cuadrado, Luis Francisco Lorenzo‐Martín, Isabel Fernández‐Pisonero, Antonio Abad, Esther Redín, Luis Montuenga, Dionisio Martín‐Zanca, Anna Bigas, Moisés Mallo, Mercedes Dosil, and Xosé R. Bustelo

Subjects
angioimmunoblastic T cell lymphoma, follicular helper T cells, nonsmall‐cell lung cancer, peripheral T cell lymphoma, RAC1, TP53, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Mutations in the VAV1 guanine nucleotide exchange factor 1 have been recently found in peripheral T cell lymphoma and nonsmall‐cell lung cancer (NSCLC). To understand their pathogenic potential, we generated a gene‐edited mouse model that expresses a VAV1 mutant protein that recapitulates the signalling alterations present in the VAV1 mutant subclass most frequently found in tumours. We could not detect any overt tumourigenic process in those mice. However, the concurrent elimination of the Trp53 tumour suppressor gene in them drives T cell lymphomagenesis. This process represents an exacerbation of the normal functions that wild‐type VAV1 plays in follicular helper T cells. We also found that, in combination with the Kras oncogene, the VAV1 mutant version favours progression of NSCLC. These data indicate that VAV1 mutations play critical, although highly cell‐type‐specific, roles in tumourigenesis. They also indicate that such functions are contingent on the mutational landscape of the tumours involved.

Published
2022
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46. High p16 expression and heterozygous RB1 loss are biomarkers for CDK4/6 inhibitor resistance in ER+ breast cancer

Author

Marta Palafox, Laia Monserrat, Meritxell Bellet, Guillermo Villacampa, Abel Gonzalez-Perez, Mafalda Oliveira, Fara Brasó-Maristany, Nusaibah Ibrahimi, Srinivasaraghavan Kannan, Leonardo Mina, Maria Teresa Herrera-Abreu, Andreu Òdena, Mònica Sánchez-Guixé, Marta Capelán, Analía Azaro, Alejandra Bruna, Olga Rodríguez, Marta Guzmán, Judit Grueso, Cristina Viaplana, Javier Hernández, Faye Su, Kui Lin, Robert B. Clarke, Carlos Caldas, Joaquín Arribas, Stefan Michiels, Alicia García-Sanz, Nicholas C. Turner, Aleix Prat, Paolo Nuciforo, Rodrigo Dienstmann, Chandra S. Verma, Nuria Lopez-Bigas, Maurizio Scaltriti, Monica Arnedos, Cristina Saura, and Violeta Serra

Subjects
Science
Abstract

CDK4/6 inhibitor resistance is common in breast cancer. Here, the authors show that p16 overexpression may be linked to reduced efficacy of CDK4/6 inhibition, and show that the combination with PI3K inhibitors may increase anti-tumour effects.

Published
2022
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47. P718: EPIGENOME PROFILING REVEALS ABERRANT DNA METHYLATION SIGNATURE IN GATA2 DEFICIENCY

Author

Oskar Marin-Bejar, Damia Romero-Moya, Javier Rodriguez-Ubreva, Maximiliano Distefano, Francesca Lessi, Paolo Aretini, Alessandro Liquori, Julio Castaño, Emilia Kozyra, Lili Kotmayer, Clara Bueno, José Cervera, José Carlos Rodriguez-Gallego, Josep F Nomdedeu, Laura Murillo-Sanjuán, Cristina Díaz de Heredia, Antonio Pérez-Martinez, Félix López-Cardenas, Carolina Martínez-Laperche, Nieves Dorado-Herrero, Francisco M Marco, Felipe Prósper, Pablo Menendez, David Valcárcel, Esteban Ballestar, Csaba Bödör, Anna Bigas, Albert Catalá, Marcin W Wlodarski, and Alessandra Giorgetti

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2023
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50. Abrogation of stemness in osteosarcoma by the mithramycin analog EC-8042 is mediated by its ability to inhibit NOTCH-1 signaling

Author

Óscar Estupiñán, Verónica Rey, Juan Tornín, Dzohara Murillo, Borja Gallego, Carmen Huergo, Verónica Blanco-Lorenzo, M. Victoria González, Aida Rodríguez, Francisco Moris, Jessica González, Verónica Ayllón, Verónica Ramos-Mejía, Anna Bigas, and René Rodríguez

Subjects
NOTCH1, HES1, EC-8042, Mithramycin, Sarcoma, Osteosarcoma, Therapeutics. Pharmacology, RM1-950
Abstract

Osteosarcomas are frequently associated to a poor prognosis and a modest response to current treatments. EC-8042 is a well-tolerated mithramycin analog that has demonstrated an efficient ability to eliminate tumor cells, including cancer stem cell subpopulations (CSC), in sarcomas. In transcriptomic and protein expression analyses, we identified NOTCH1 signaling as one of the main pro-stemness pathways repressed by EC-8042 in osteosarcomas. Overexpression of NOTCH-1 resulted in a reduced anti-tumor effect of EC-8042 in CSC-enriched 3D tumorspheres cultures. On the other hand, the depletion of the NOTCH-1 downstream target HES-1 was able to enhance the action of EC-8042 on CSCs. Moreover, HES1 depleted cells failed to recover after treatment withdrawal and showed reduced tumor growth potential in vivo. In contrast, mice xenografted with NOTCH1-overexpressing cells responded worse than parental cells to EC-8042. Finally, we found that active NOTCH1 levels in sarcoma patients was associated to advanced disease and lower survival. Overall, these data highlight the relevant role that NOTCH1 signaling plays in mediating stemness in osteosarcoma. Moreover, we demonstrate that EC-8042 is powerful inhibitor of NOTCH signaling and that the anti-CSC activity of this mithramycin analog highly rely on its ability to repress this pathway.

Published
2023
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