Publication List

@article{Toll-Riera2011a,
title = {Lineage-specific variation in intensity of natural selection in mammals.},
author = {Toll-Riera, Macarena and Laurie, Steve and Albà, M Mar},
url = {http://www.ncbi.nlm.nih.gov/pubmed/20688808},
issn = {1537-1719},
year = {2011},
date = {2011-01-01},
journal = {Molecular biology and evolution},
volume = {28},
number = {1},
pages = {383--98},
abstract = {The molecular clock hypothesis states that protein-coding genes evolve at an approximately constant rate. However, this is only expected to be true as long as the function and the tertiary structure of the molecule remain unaltered. An important implication of this statement is that significant deviations in the rate of evolution of a gene with respect to the species clock are likely to reflect functional and/or structural alterations. Here, we present a method to identify such deviations and apply it to a data set of 2,929 high-quality coding sequence alignments corresponding to one-to-one orthologous genes from six mammalian species--human, macaque, mouse, rat, cow, and dog. Deviated branches are defined as those that present significant alterations in both the rate of nonsynonymous substitutions (dN) and the selective pressure (dN/dS). Strikingly, we find that as many as 24.5% of the genes show branch-specific deviations in dN and dN/dS, though this is a relatively well-conserved set of genes. Around half of these genes show branch-specific acceleration of evolutionary rates. Positive selection (PS) tests based on divergence data only identify 17.7% of the accelerated branches. Failure to identify PS in accelerated branches with an excess of radical amino acid replacements suggests that these tests are conservative. Interestingly, genes with accelerated branches are significantly enriched in neural proteins, indicating that this type of protein might play a more important role than previously thought in species diversification, although they are generally not detected by PS tests. We discuss in detail several examples of genes that show lineage-specific evolutionary rate acceleration and are involved in synaptic transmission, chemosensory perception, and ubiquitination.},
keywords = {Amino Acid Sequence, Amino Acid Substitution, Animals, Evolution, F-Box Proteins, F-Box Proteins: genetics, G-Protein-Coupled, G-Protein-Coupled: genetics, Genetic, Genetic Variation, Humans, Mammals, Mammals: genetics, Molecular, Molecular Sequence Data, N-Methyl-D-Aspartate, N-Methyl-D-Aspartate: genetics, Odorant, Odorant: genetics, Receptors, Selection, Sequence Alignment}
}

@article{Rodilla2009,
title = {Jagged1 is the pathological link between Wnt and Notch pathways in colorectal cancer.},
author = {Rodilla, Verónica and Villanueva, Alberto and Obrador-Hevia, Antonia and Robert-Moreno, Alex and Fernández-Majada, Vanessa and Grilli, Andrea and López-Bigas, Nuria and Bellora, Nicolás and Albà, M Mar and Torres, Ferran and Duñach, Mireia and Sanjuan, Xavier and Gonzalez, Sara and Gridley, Thomas and Capella, Gabriel and Bigas, Anna and Espinosa, Lluís},
url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2669348&tool=pmcentrez&rendertype=abstract},
issn = {1091-6490},
year = {2009},
date = {2009-01-01},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {106},
number = {15},
pages = {6315--20},
abstract = {Notch has been linked to beta-catenin-dependent tumorigenesis; however, the mechanisms leading to Notch activation and the contribution of the Notch pathway to colorectal cancer is not yet understood. By microarray analysis, we have identified a group of genes downstream of Wnt/beta-catenin (down-regulated when blocking Wnt/beta-catenin) that are directly regulated by Notch (repressed by gamma-secretase inhibitors and up-regulated by active Notch1 in the absence of beta-catenin signaling). We demonstrate that Notch is downstream of Wnt in colorectal cancer cells through beta-catenin-mediated transcriptional activation of the Notch-ligand Jagged1. Consistently, expression of activated Notch1 partially reverts the effects of blocking Wnt/beta-catenin pathway in tumors implanted s.c. in nude mice. Crossing APC(Min/+) with Jagged1(+/Delta) mice is sufficient to significantly reduce the size of the polyps arising in the APC mutant background indicating that Notch is an essential modulator of tumorigenesis induced by nuclear beta-catenin. We show that this mechanism is operating in human tumors from Familial Adenomatous Polyposis patients. We conclude that Notch activation, accomplished by beta-catenin-mediated up-regulation of Jagged1, is required for tumorigenesis in the intestine. The Notch-specific genetic signature is sufficient to block differentiation and promote vasculogenesis in tumors whereas proliferation depends on both pathways.},
keywords = {Alleles, Animals, beta Catenin, beta Catenin: metabolism, Calcium-Binding Proteins, Calcium-Binding Proteins: genetics, Calcium-Binding Proteins: metabolism, Cell Line, Cell Nucleus, Cell Nucleus: metabolism, Colorectal Neoplasms, Colorectal Neoplasms: blood supply, Colorectal Neoplasms: genetics, Colorectal Neoplasms: metabolism, Colorectal Neoplasms: pathology, Gene Expression Profiling, Gene Expression Regulation, Genetic, Genetic: genetics, Humans, Intercellular Signaling Peptides and Proteins, Intercellular Signaling Peptides and Proteins: gen, Intercellular Signaling Peptides and Proteins: met, Membrane Proteins, Membrane Proteins: genetics, Membrane Proteins: metabolism, Mice, Neoplastic, Notch, Notch: metabolism, Receptors, Signal Transduction, TCF Transcription Factors, TCF Transcription Factors: metabolism, Transcription, Transgenic, Wnt Proteins, Wnt Proteins: metabolism}
}

@article{Racz2008,
title = {Interferon-gamma is a critical modulator of CB(2) cannabinoid receptor signaling during neuropathic pain.},
author = {Racz, Ildiko and Nadal, Xavier and Alferink, Judith and Baños, Josep E and Rehnelt, Jennifer and Martín, Miquel and Pintado, Belén and Gutierrez-Adan, Alfonso and Sanguino, Elena and Bellora, Nicolas and Manzanares, Jorge and Zimmer, Andreas and Maldonado, Rafael},
url = {http://www.ncbi.nlm.nih.gov/pubmed/19005078},
issn = {1529-2401},
year = {2008},
date = {2008-01-01},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
volume = {28},
number = {46},
pages = {12136--45},
abstract = {Nerve injuries often lead to neuropathic pain syndrome. The mechanisms contributing to this syndrome involve local inflammatory responses, activation of glia cells, and changes in the plasticity of neuronal nociceptive pathways. Cannabinoid CB(2) receptors contribute to the local containment of neuropathic pain by modulating glial activation in response to nerve injury. Thus, neuropathic pain spreads in mice lacking CB(2) receptors beyond the site of nerve injury. To further investigate the mechanisms leading to the enhanced manifestation of neuropathic pain, we have established expression profiles of spinal cord tissues from wild-type and CB(2)-deficient mice after nerve injury. An enhanced interferon-gamma (IFN-gamma) response was revealed in the absence of CB(2) signaling. Immunofluorescence stainings demonstrated an IFN-gamma production by astrocytes and neurons ispilateral to the nerve injury in wild-type animals. In contrast, CB(2)-deficient mice showed neuronal and astrocytic IFN-gamma immunoreactivity also in the contralateral region, thus matching the pattern of nociceptive hypersensitivity in these animals. Experiments in BV-2 microglia cells revealed that transcriptional changes induced by IFN-gamma in two key elements for neuropathic pain development, iNOS (inducible nitric oxide synthase) and CCR2, are modulated by CB(2) receptor signaling. The most direct support for a functional involvement of IFN-gamma as a mediator of CB(2) signaling was obtained with a double knock-out mouse strain deficient in CB(2) receptors and IFN-gamma. These animals no longer show the enhanced manifestations of neuropathic pain observed in CB(2) knock-outs. These data clearly demonstrate that the CB(2) receptor-mediated control of neuropathic pain is IFN-gamma dependent.},
keywords = {Animals, Astrocytes, Astrocytes: immunology, Cannabinoid, CB2, CB2: genetics, CB2: immunology, CB2: metabolism, CCR2, CCR2: immunology, CCR2: metabolism, Cells, Cultured, Gene Knockout Techniques, Gene Knockout Techniques: methods, Hyperalgesia, Hyperalgesia: immunology, Hyperalgesia: physiopathology, Interferon-gamma, Interferon-gamma: genetics, Interferon-gamma: immunology, Interferon-gamma: metabolism, Knockout, Male, Mice, Microglia, Microglia: drug effects, Microglia: immunology, Microglia: metabolism, Neuralgia, Neuralgia: genetics, Neuralgia: immunology, Neuralgia: metabolism, Neurons, Neurons: immunology, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type II: immunology, Nitric Oxide Synthase Type II: metabolism, Peripheral Nerves, Peripheral Nerves: immunology, Peripheral Nerves: injuries, Peripheral Nerves: physiopathology, Peripheral Nervous System Diseases, Peripheral Nervous System Diseases: genetics, Peripheral Nervous System Diseases: immunology, Peripheral Nervous System Diseases: metabolism, Receptor, Receptors, Signal Transduction, Signal Transduction: genetics, Signal Transduction: immunology, Spinal Cord, Spinal Cord: immunology, Spinal Cord: metabolism, Spinal Cord: physiopathology, Up-Regulation, Up-Regulation: immunology}
}