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Ramiro almudena

Ángel F Álvarez-Prado, Pablo Pérez-Durán, Arantxa Pérez-García, Alberto Benguria, Carlos Torroja, Virginia G de Yébenes, Almudena R Ramiro
Activation-induced deaminase (AID) initiates antibody diversification in germinal center (GC) B cells through the deamination of cytosines on immunoglobulin genes. AID can also target other regions in the genome, triggering mutations or chromosome translocations, with major implications for oncogenic transformation. However, understanding the specificity of AID has proved extremely challenging. We have sequenced at very high depth >1,500 genomic regions from GC B cells and identified 275 genes targeted by AID, including 30 of the previously known 35 AID targets...
January 26, 2018: Journal of Experimental Medicine
Teresa Nebreda-Mayoral, M Fé Brezmes-Valdivieso, Nieves Gutiérrez-Zufiaurre, Susana García-de Cruz, Cristina Labayru-Echeverría, Ramiro López-Medrano, Luis López-Urrutia-Lorente, Almudena Tinajas-Puertas, Octavio Rivero-Lezcano
INTRODUCTION: The annual incidence of tuberculosis (TB) from Mycobacterium bovis in humans has considerably declined in industrialised countries since the early twentieth century. The objective of this study was to determine the epidemiological, clinical and microbiological characteristics of patients with this illness in Castile and León (CyL). METHODS: Retrospective study of all M. bovis TB cases in CyL over a 10-year period, comparing the risk factors, the epidemiology and the clinical course between pulmonary (PTB) and extrapulmonary TB (EPTB)...
December 20, 2017: Enfermedades Infecciosas y Microbiología Clínica
Ester Marina-Zárate, Arantxa Pérez-García, Almudena R Ramiro
In response to antigenic stimulation B cells undergo class switch recombination (CSR) at the immunoglobulin heavy chain (IgH) to replace the primary IgM/IgD isotypes by IgG, IgE, or IgA. CSR is initiated by activation-induced cytidine deaminase (AID) through the deamination of cytosine residues at the switch (S) regions of IgH. B cell stimulation promotes germline transcription (GLT) of specific S regions, a necessary event prior to CSR because it facilitates AID access to S regions. Here, we show that CCCTC-binding factor (CTCF)-deficient mice are severely impaired in the generation of germinal center B cells and plasma cells after immunization in vivo, most likely due to impaired cell survival...
2017: Frontiers in Immunology
Virginia C Rodríguez-Cortez, Paloma Martínez-Redondo, Francesc Català-Moll, Javier Rodríguez-Ubreva, Antonio Garcia-Gomez, Ganesh Poorani-Subramani, Laura Ciudad, Henar Hernando, Arantxa Pérez-García, Carlos Company, José M Urquiza, Almudena R Ramiro, Javier M Di Noia, Alejandro Vaquero, Esteban Ballestar
Activation-induced cytidine deaminase (AID) triggers antibody diversification in B cells by catalysing deamination and subsequently mutating immunoglobulin (Ig) genes. Association of AID with RNA Pol II and occurrence of epigenetic changes during Ig gene diversification suggest participation of AID in epigenetic regulation. AID is mutated in hyper-IgM type 2 (HIGM2) syndrome. Here, we investigated the potential role of AID in the acquisition of epigenetic changes. We discovered that AID binding to the IgH locus promotes an increase in H4K20me3...
August 8, 2017: Scientific Reports
Arantxa Pérez-García, Ester Marina-Zárate, Ángel F Álvarez-Prado, Jose M Ligos, Niels Galjart, Almudena R Ramiro
In germinal centres (GC) mature B cells undergo intense proliferation and immunoglobulin gene modification before they differentiate into memory B cells or long-lived plasma cells (PC). GC B-cell-to-PC transition involves a major transcriptional switch that promotes a halt in cell proliferation and the production of secreted immunoglobulins. Here we show that the CCCTC-binding factor (CTCF) is required for the GC reaction in vivo, whereas in vitro the requirement for CTCF is not universal and instead depends on the pathways used for B-cell activation...
July 5, 2017: Nature Communications
Cristina Gutiérrez-Vázquez, Anton J Enright, Ana Rodríguez-Galán, Arantxa Pérez-García, Paul Collier, Matthew R Jones, Vladimir Benes, Joseph P Mizgerd, María Mittelbrunn, Almudena R Ramiro, Francisco Sánchez-Madrid
Activation of T lymphocytes requires a tight regulation of microRNA (miRNA) expression. Terminal uridyltransferases (TUTases) catalyze 3' nontemplated nucleotide addition (3'NTA) to miRNAs, which may influence miRNA stability and function. Here, we investigated 3'NTA to mature miRNA in CD4 T lymphocytes by deep sequencing. Upon T-cell activation, miRNA sequences bearing terminal uridines are specifically decreased, concomitantly with down-regulation of TUT4 and TUT7 enzymes. Analyzing TUT4-deficient T lymphocytes, we proved that this terminal uridyltransferase is essential for the maintenance of miRNA uridylation in the steady state of T lymphocytes...
June 2017: RNA
Nahikari Bartolomé-Izquierdo, Virginia G de Yébenes, Angel F Álvarez-Prado, Sonia M Mur, Juan A Lopez Del Olmo, Sergio Roa, Jesus Vazquez, Almudena R Ramiro
Non-Hodgkin lymphoma comprises a variety of neoplasms, many of which arise from germinal center (GC)-experienced B cells. microRNA-28 (miR-28) is a GC-specific miRNA whose expression is lost in numerous mature B-cell neoplasms. Here we show that miR-28 regulates the GC reaction in primary B cells by impairing class switch recombination and memory B and plasma cell differentiation. Deep quantitative proteomics combined with transcriptome analysis identified miR-28 targets involved in cell-cycle and B-cell receptor signaling...
April 27, 2017: Blood
Ramiro López-Medrano, Teresa Nebreda-Mayoral, M Fé Brezmes-Valdivieso, Susana García-de Cruz, Begoña Nogueira-González, Rafael Sánchez-Arroyo, Almudena Tinajas-Puertas, Nieves Gutiérrez-Zufiaurre, Cristina Labayru-Echeverría, Susana Hernando-Real, Luis López-Urrutia, Octavio Rivero-Lezcano, Belén Ullivarri-Francia, Raquel Rodríguez-Tarazona, Isabel Antolín-Ayala
INTRODUCTION AND OBJECTIVES: A retrospective study was conducted by collecting microbiological tuberculosis (TB) data in Castile and León during the year 2013 in order to determine the incidence and distribution of TB, and resistance to the tuberculostatic drug, and compare them with the epidemiological data provided by the Department of Epidemiological Surveillance (SIVE). MATERIAL AND METHODS: Microbiologists of the 14 hospitals of the Castile and León public health network (GRUMICALE) collected epidemiological, microbiological, and management data from the Microbiology laboratories in the community during the year 2013...
January 10, 2017: Enfermedades Infecciosas y Microbiología Clínica
Alba Azagra, Lidia Román-González, Olga Collazo, Javier Rodríguez-Ubreva, Virginia G de Yébenes, Bruna Barneda-Zahonero, Jairo Rodríguez, Manuel Castro de Moura, Joaquim Grego-Bessa, Irene Fernández-Duran, Abul B M M K Islam, Manel Esteller, Almudena R Ramiro, Esteban Ballestar, Maribel Parra
Class IIa histone deacetylase (HDAC) subfamily members are tissue-specific gene repressors with crucial roles in development and differentiation processes. A prominent example is HDAC7, a class IIa HDAC that shows a lymphoid-specific expression pattern within the hematopoietic system. In this study, we explored its potential role in B cell development by generating a conditional knockout mouse model. Our study demonstrates for the first time that HDAC7 deletion dramatically blocks early B cell development and gives rise to a severe lymphopenia in peripheral organs, while also leading to pro-B cell lineage promiscuity...
November 14, 2016: Journal of Experimental Medicine
Ana V Marin, Anaïs Jiménez-Reinoso, Alejandro C Briones, Miguel Muñoz-Ruiz, Cigdem Aydogmus, Luke J Pasick, Jorge Couso, Marina S Mazariegos, Angel F Alvarez-Prado, Alfonso Blázquez-Moreno, Funda E Cipe, Sule Haskologlu, Figen Dogu, Matías Morín, Miguel A Moreno-Pelayo, Félix García-Sánchez, Juana Gil-Herrera, Edgar Fernández-Malavé, Hugh T Reyburn, Almudena R Ramiro, Aydan Ikinciogullari, Maria J Recio, Jose R Regueiro, Beatriz Garcillán
No abstract text is available yet for this article.
August 20, 2016: Journal of Allergy and Clinical Immunology
Almudena R Ramiro, Vasco M Barreto
No abstract text is available yet for this article.
April 2016: Trends in Biochemical Sciences
Tina M Thornton, Pilar Delgado, Liang Chen, Beatriz Salas, Dimitry Krementsov, Miriam Fernandez, Santiago Vernia, Roger J Davis, Ruth Heimann, Cory Teuscher, Michael S Krangel, Almudena R Ramiro, Mercedes Rincón
Variable, diversity and joining (V(D)J) recombination and immunoglobulin class switch recombination (CSR) are key processes in adaptive immune responses that naturally generate DNA double-strand breaks (DSBs) and trigger a DNA repair response. It is unclear whether this response is associated with distinct survival signals that protect T and B cells. Glycogen synthase kinase 3β (GSK3β) is a constitutively active kinase known to promote cell death. Here we show that phosphorylation of GSK3β on Ser(389) by p38 MAPK (mitogen-activated protein kinase) is induced selectively by DSBs through ATM (ataxia telangiectasia mutated) as a unique mechanism to attenuate the activity of nuclear GSK3β and promote survival of cells undergoing DSBs...
January 29, 2016: Nature Communications
Arantxa Pérez-García, Pablo Pérez-Durán, Thomas Wossning, Isora V Sernandez, Sonia M Mur, Marta Cañamero, Francisco X Real, Almudena R Ramiro
Activation-induced deaminase (AID) initiates secondary antibody diversification in germinal center B cells, giving rise to higher affinity antibodies through somatic hypermutation (SHM) or to isotype-switched antibodies through class switch recombination (CSR). SHM and CSR are triggered by AID-mediated deamination of cytosines in immunoglobulin genes. Importantly, AID activity in B cells is not restricted to Ig loci and can promote mutations and pro-lymphomagenic translocations, establishing a direct oncogenic mechanism for germinal center-derived neoplasias...
October 2015: EMBO Molecular Medicine
Ferdinando Scavizzi, Edward Ryder, Stuart Newman, Marcello Raspa, Diane Gleeson, Hannah Wardle-Jones, Lluis Montoliu, Almudena Fernandez, Marie-Laure Dessain, Vanessa Larrigaldie, Zuzana Khorshidi, Reetta Vuolteenaho, Raija Soininen, Philippe André, Sylvie Jacquot, Yi Hong, Martin Hrabe de Angelis, Ramiro Ramirez-Solis, Brendan Doe
With the advent of modern developmental biology and molecular genetics, the scientific community has generated thousands of newly genetically altered strains of laboratory mice with the aim of elucidating gene function. To this end, a large group of Institutions which form the International Mouse Phenotyping Consortium is generating and phenotyping a knockout mouse strain for each of the ~20,000 protein-coding genes using the mutant ES cell resource produced by the International Knockout Mouse Consortium. These strains are made available to the research community via public repositories, mostly as cryopreserved sperm or embryos...
October 2015: Transgenic Research
Almudena R Ramiro, Vasco M Barreto
The regulation of demethylation in vertebrates has begun to be elucidated in the past decade. However, a possible involvement of activation-induced cytidine deaminase (AID) in this process remains uncertain. We survey the data supporting or casting doubt on such a role, and propose that there is no strong evidence for an involvement of AID in genome-wide active demethylation processes. Conversely, we present evidence that favors AID involvement in gene-specific demethylation events underlying cell differentiation...
March 2015: Trends in Biochemical Sciences
Virginia G de Yébenes, Nahikari Bartolomé-Izquierdo, Rubén Nogales-Cadenas, Pablo Pérez-Durán, Sonia M Mur, Nerea Martínez, Lorena Di Lisio, Davide F Robbiani, Alberto Pascual-Montano, Marta Cañamero, Miguel A Piris, Almudena R Ramiro
microRNAs are a class of regulators of gene expression that have been shown critical for a great number of biological processes; however, little is known of their role in germinal center (GC) B cells. Although the GC reaction is crucial to ensure a competent immune response, GC B cells are also the origin of most human lymphomas, presumably due to bystander effects of the immunoglobulin gene remodeling that takes place at these sites. Here we report that miR-217 is specifically upregulated in GC B cells. Gain- and loss-of-function mouse models reveal that miR-217 is a positive modulator of the GC response that increases the generation of class-switched antibodies and the frequency of somatic hypermutation...
July 10, 2014: Blood
Almudena Burillo, Belén Rodríguez-Sánchez, Ana Ramiro, Emilia Cercenado, Marta Rodríguez-Créixems, Emilio Bouza
Microbiological confirmation of a urinary tract infection (UTI) takes 24-48 h. In the meantime, patients are usually given empirical antibiotics, sometimes inappropriately. We assessed the feasibility of sequentially performing a Gram stain and MALDI-TOF MS mass spectrometry (MS) on urine samples to anticipate clinically useful information. In May-June 2012, we randomly selected 1000 urine samples from patients with suspected UTI. All were Gram stained and those yielding bacteria of a single morphotype were processed for MALDI-TOF MS...
2014: PloS One
Virginia G de Yébenes, Nahikari Bartolomé-Izquierdo, Almudena R Ramiro
MicroRNAs (miRNAs) have emerged as a new class of gene expression regulators whose functions influence a myriad of biological processes, from developmental decisions through immune responses and numerous pathologies, including cancer and autoimmunity. miRNAs are small RNA molecules that drive post-transcriptional negative regulation of gene expression by promoting the degradation or translational block of their target mRNAs. Here, we review some of the data relating to the role of miRNAs in the regulation of the B-cell lineage, with a special focus on results obtained in vivo...
May 2013: Immunological Reviews
Pablo Pérez-Durán, Laura Belver, Virginia G de Yébenes, Pilar Delgado, David G Pisano, Almudena R Ramiro
Secondary diversification of antibodies through somatic hypermutation (SHM) and class switch recombination (CSR) is a critical component of the immune response. Activation-induced deaminase (AID) initiates both processes by deaminating cytosine residues in immunoglobulin genes. The resulting U:G mismatch can be processed by alternative pathways to give rise to a mutation (SHM) or a DNA double-strand break (CSR). Central to this processing is the activity of uracil-N-glycosylase (UNG), an enzyme normally involved in error-free base excision repair...
July 2, 2012: Journal of Experimental Medicine
Laura Belver, F Nina Papavasiliou, Almudena R Ramiro
MicroRNAs (miRNAs) are a class of endogenous, non-coding regulatory RNAs that control gene regulation by guiding silencing protein complexes to mRNA in a sequence-dependent manner. In this way miRNAs are able to repress gene expression post-transcriptionally by affecting mRNA stability or translation. These ubiquitous molecules play central roles in a wide range of biological processes, including cell proliferation, differentiation and apoptosis. Within the context of the immune system, genetic studies have identified distinct roles for specific miRNAs in gene regulation during development, activation and maturation...
June 2011: Current Opinion in Immunology
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