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Ramiro almudena

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...
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
Laura Belver, Virginia G de Yébenes, Almudena R Ramiro
MicroRNAs have been shown to be critical for a number of aspects of immune system regulation and function. Here, we have examined the role of microRNAs in terminal B cell differentiation by analyzing Cd19-Cre(ki/+) Dicer1(fl/fl) mice. We found that in the absence of Dicer, the transitional and marginal zone (MZ) B cell compartments were overrepresented and follicular (FO) B cell generation was impaired. microRNA analysis revealed that miR185, a microRNA overexpressed in FO cells, dampened B cell receptor (BCR) signaling through Bruton tyrosine kinase downregulation...
November 24, 2010: Immunity
Virginia G de Yébenes, Almudena R Ramiro
Gene expression regulation by miRNAs has been reported to control key aspects of B cell differentiation and function (Chen et al., Science 303:83-86, 2004; Xiao et al., Cell 131:146-159, 2007; O'Carroll et al., Genes Dev. 21:1999-2004, 2007; Koralov et al. Cell 132:860-874, 2008; Rodriguez et al., Science 316:608-611, 2007; Costinean et al., Proc Natl Acad Sci USA 103:7024-7029, 2006; Thai et al., Science 316:604-608, 2007; Vigorito et al., Immunity 27:847-859, 2007; Dorsett et al., Immunity 28:630-638, 2008; Teng et al...
2010: Methods in Molecular Biology
Siim Pauklin, Isora V Sernández, Gudrun Bachmann, Almudena R Ramiro, Svend K Petersen-Mahrt
The immunological targets of estrogen at the molecular, humoral, and cellular level have been well documented, as has estrogen's role in establishing a gender bias in autoimmunity and cancer. During a healthy immune response, activation-induced deaminase (AID) deaminates cytosines at immunoglobulin (Ig) loci, initiating somatic hypermutation (SHM) and class switch recombination (CSR). Protein levels of nuclear AID are tightly controlled, as unregulated expression can lead to alterations in the immune response...
January 16, 2009: Journal of Experimental Medicine
Isora V Sernández, Virginia G de Yébenes, Yair Dorsett, Almudena R Ramiro
The humoral immune response critically relies on the secondary diversification of antibodies. This diversification takes places through somatic remodelling of the antibody genes by two molecular mechanisms, Class Switch Recombination (CSR) and Somatic Hypermutation (SHM). The enzyme Activation Induced Cytidine Deaminase (AID) initiates both SHM and CSR by deaminating cytosine residues on the DNA of immunoglobulin genes. While crucial for immunity, AID-catalysed deamination is also the triggering event for the generation of lymphomagenic chromosome translocations...
2008: PloS One
Virginia G de Yébenes, Laura Belver, David G Pisano, Susana González, Aranzazu Villasante, Carlo Croce, Lin He, Almudena R Ramiro
Activated B cells reshape their primary antibody repertoire after antigen encounter by two molecular mechanisms: somatic hypermutation (SHM) and class switch recombination (CSR). SHM and CSR are initiated by activation-induced cytidine deaminase (AID) through the deamination of cytosine residues on the immunoglobulin loci, which leads to the generation of DNA mutations or double-strand break intermediates. As a bystander effect, endogenous AID levels can also promote the generation of chromosome translocations, suggesting that the fine tuning of AID expression may be critical to restrict B cell lymphomagenesis...
September 29, 2008: Journal of Experimental Medicine
Pablo Pérez-Durán, Virginia G de Yebenes, Almudena R Ramiro
The generation of an efficient immune response depends on highly refined mechanisms of antibody diversification. Two of these mechanisms, somatic hypermutation (SHM) and class switch recombination (CSR), are initiated by activation-induced cytidine deaminase (AID) upon antigen stimulation of mature B cells. AID deaminates cytosines on the DNA of Ig genes thereby generating a lesion that can be processed into a mutation (SHM) or a DNA double-strand break followed by a recombination reaction (CSR). A number of mechanisms are probably responsible for regulating AID function, such as transcriptional regulation, subcellular localization, post-transcriptional modifications and target specificity, but the issue remains of how unwanted DNA damage is fully prevented...
December 2007: Carcinogenesis
Almudena Ramiro, Bernardo Reina San-Martin, Kevin McBride, Mila Jankovic, Vasco Barreto, André Nussenzweig, Michel C Nussenzweig
Although B and T lymphocytes are similar in many respects including diversification of their antigen receptor genes by V(D)J recombination, 95% of all lymphomas diagnosed in the western world are of B-cell origin. Many of these are derived from mature B cells [Kuppers, R. (2005). Mechanisms of B-cell lymphoma pathogenesis. Nat. Rev. Cancer 5, 251-262] and display hallmark chromosome translocations involving immunoglobulin genes and a proto-oncogene partner whose expression becomes deregulated as a result of the translocation reaction [Kuppers, R...
2007: Advances in Immunology
Almudena R Ramiro, Michel C Nussenzweig, André Nussenzweig
Activation-induced deaminase initiates three different antibody diversification reactions: class switch recombination, somatic hypermutation (SHM), and gene conversion. We have shown that, in addition to antibody diversification, activation-induced deaminase can also initiate Burkitt's lymphoma-like c-myc/IgH translocations. However, distinct DNA damage- and oncogene-induced checkpoints operate in B cells to produce a normal intrachromosomal class switch recombination event or an aberrant interchromosomal fusion...
August 15, 2006: Cancer Research
Virginia G de Yébenes, Almudena R Ramiro
Activation-induced deaminase (AID) is required for class switch recombination (CSR) and somatic hypermutation (SHM), which are responsible for secondary diversification of antibodies in germinal centers. AID initiates these processes by deamination of cytosines on the immunoglobulin (Ig) locus, a potentially mutagenic activity. AID expression is restricted to germinal-center B cells, but the mechanisms that regulate its target specificity are not completely understood. Here, we review the most recent findings on the regulation of AID targeting and discuss how AID activity on non-Ig genes is relevant to the generation of chromosome translocations and to lymphomagenesis...
September 2006: Trends in Molecular Medicine
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