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Search Results: 1 - 10 of 53244 matches for " David Talavera "
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Analysis of Genetic Interaction Networks Shows That Alternatively Spliced Genes Are Highly Versatile
David Talavera, Ritika Sheoran, Simon C. Lovell
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0055671
Abstract: Alternative splicing has the potential to increase the diversity of the transcriptome and proteome. Where more than one transcript arises from a gene they are often so different that they are quite unlikely to have the same function. However, it remains unclear if alternative splicing generally leads to a gene being involved in multiple biological processes or whether it alters the function within a single process. Knowing that genetic interactions occur between functionally related genes, we have used them as a proxy for functional versatility, and have analysed the sets of genes of two well-characterised model organisms: Caenorhabditis elegans and Drosophila melanogaster. Using network analyses we find that few genes are functionally homogenous (only involved in a few functionally-related biological processes). Moreover, there are differences between alternatively spliced genes and genes with a single transcript; specifically, genes with alternatively splicing are, on average, involved in more biological processes. Finally, we suggest that factors other than specific functional classes determine whether a gene is alternatively spliced.
Characterization of Protein-Protein Interaction Interfaces from a Single Species
David Talavera, David L. Robertson, Simon C. Lovell
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0021053
Abstract: Most proteins attain their biological functions through specific interactions with other proteins. Thus, the study of protein-protein interactions and the interfaces that mediate these interactions is of prime importance for the understanding of biological function. In particular the precise determinants of binding specificity and their contributions to binding energy within protein interfaces are not well understood. In order to better understand these determinants an appropriate description of the interaction surface is needed. Available data from the yeast Saccharomyces cerevisiae allow us to focus on a single species and to use all the available structures, correcting for redundancy, instead of using structural representatives. This allows us to control for potentially confounding factors that may affect sequence propensities. We find a significant contribution of main-chain atoms to protein-protein interactions. These include interactions both with other main-chain and side-chain atoms on the interacting chain. We find that the type of interaction depends on both amino acid and secondary structure type involved in the contact. For example, residues in α-helices and large amino acids are the most likely to be involved in interactions through their side-chain atoms. We find an intriguing homogeneity when calculating the average solvation energy of different areas of the protein surface. Unexpectedly, homo- and hetero-complexes have quite similar results for all analyses. Our findings demonstrate that the manner in which protein-protein interactions are formed is determined by the residue type and the secondary structure found in the interface. However the homogeneity of the desolvation energy despite heterogeneity of interface properties suggests a complex relationship between interface composition and binding energy.
The Role of Protein Interactions in Mediating Essentiality and Synthetic Lethality
David Talavera, David L. Robertson, Simon C. Lovell
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0062866
Abstract: Genes are characterized as essential if their knockout is associated with a lethal phenotype, and these “essential genes” play a central role in biological function. In addition, some genes are only essential when deleted in pairs, a phenomenon known as synthetic lethality. Here we consider genes displaying synthetic lethality as “essential pairs” of genes, and analyze the properties of yeast essential genes and synthetic lethal pairs together. As gene duplication initially produces an identical pair or sets of genes, it is often invoked as an explanation for synthetic lethality. However, we find that duplication explains only a minority of cases of synthetic lethality. Similarly, disruption of metabolic pathways leads to relatively few examples of synthetic lethality. By contrast, the vast majority of synthetic lethal gene pairs code for proteins with related functions that share interaction partners. We also find that essential genes and synthetic lethal pairs cluster in the protein-protein interaction network. These results suggest that synthetic lethality is strongly dependent on the formation of protein-protein interactions. Compensation by duplicates does not usually occur mainly because the genes involved are recent duplicates, but is more commonly due to functional similarity that permits preservation of essential protein complexes. This unified view, combining genes that are individually essential with those that form essential pairs, suggests that essentiality is a feature of physical interactions between proteins protein-protein interactions, rather than being inherent in gene and protein products themselves.
Alternative Splicing of Transcription Factors' Genes: Beyond the Increase of Proteome Diversity
David Talavera,Modesto Orozco,Xavier de la Cruz
Comparative and Functional Genomics , 2009, DOI: 10.1155/2009/905894
Abstract: Functional modification of transcription regulators may lead to developmental changes and phenotypical differences between species. In this work, we study the influence of alternative splicing on transcription factors in human and mouse. Our results show that the impact of alternative splicing on transcription factors is similar in both species, meaning that the ways to increase variability should also be similar. However, when looking at the expression patterns of transcription factors, we observe that they tend to diverge regardless of the role of alternative splicing. Finally, we hypothesise that transcription regulation of alternatively spliced transcription factors could play an important role in the phenotypical differences between species, without discarding other phenomena or functional families.
A procedure for identifying homologous alternative splicing events
David Talavera, Adam Hospital, Modesto Orozco, Xavier de la Cruz
BMC Bioinformatics , 2007, DOI: 10.1186/1471-2105-8-260
Abstract: We have developed a method for identifying homologous, or equivalent, alternative splicing events, based on the combined use of neural networks and sequence searches. The procedure comprises four steps: (i) BLAST search for homologues of the two isoforms defining the target alternative splicing event; (ii) construction of all possible candidate events; (iii) scoring of the latter with a series of neural networks; and (iv) filtering of the results. When tested in a set of 473 manually annotated pairs of homologous events, our method showed a good performance, with an accuracy of 0.99, a precision of 0.98 and a sensitivity of 0.93. When no candidates were available, the specificity of our method varied between 0.81 and 0.91.The method described in this article allows the identification of homologous alternative splicing events, with a good success rate, indicating that such method could be used for the development of functional annotation of alternative splice isoforms.In recent years, understanding the contribution of alternative splicing (AS) to biological processes has become an active area of research in many fields of biology and biomedicine [1-9]. This has been motivated by the biological relevance of AS, a process shown by a large fraction of human genes (~74%[10]), which results in the diversification of the nature and expression pattern of their corresponding products [2,8]. For instance, it has been found that different alternative splice isoforms of the DSCAM protein are involved in the development of neuronal interconnections by choosing the proper interaction partners [2]. AS is also able to alter the substrate specificity of enzymes by modifying their active site, as previously shown for Anopheles dirus's glutathione S-transferase [3]. In the case of transcription factors, AS plays a regulatory role that has a clear impact on the levels of gene expression [11,12]. The roles of transcription factors isoforms are very broad, and depend on the nature of the
La objeción de conciencia sanitaria en el ámbito penitenciario
Talavera,P.;
Revista Espa?ola de Sanidad Penitenciaria , 2010, DOI: 10.4321/S1575-06202010000100005
Abstract: to be fully in accordance with constitutional doctrines the notion of conscientious objection must be understood as a manifestation of the fundamental right to ideological freedom as contained in art. 16.1 ce (assuming of course that all objecting conduct is legitimate), but it must also be understood as a principle. that is to say, any conflict between the subject's fundamental right and legal duty that he rejects must be resolved by the judge who must make a careful judgement of values and property. this fundamental right still exists and may invoked and exercised by inmates and health personnel in the prison context in the face of predictions of the forcible imposition of medical treatment as stated in the logp and rp, with no more limit than public order itself.
La objeción de conciencia sanitaria en el ámbito penitenciario Conscientous health objection in the prison environment
P. Talavera
Revista Espa?ola de Sanidad Penitenciaria , 2010,
Abstract: Lo más coherente con la doctrina constitucional es concebir la objeción de conciencia como una manifestación del derecho fundamental a la libertad ideológica del art. 16.1 CE (asumiendo, por tanto, la legitimidad de toda conducta objetora), pero entendida como un principio; es decir: cualquier conflicto entre el derecho fundamental del sujeto y el deber jurídico que se rehúsa debe ser resuelto por el juez realizando un juicio ponderativo de bienes y valores. Este derecho fundamental persiste y puede ser invocado y ejercido por reclusos y personal sanitario en el contexto penitenciario, frente a las previsiones de imposición coactiva de tratamientos médico previstas por la LOGP y el RP, sin más límite que el orden público. To be fully in accordance with constitutional doctrines the notion of conscientious objection must be understood as a manifestation of the fundamental right to ideological freedom as contained in art. 16.1 CE (assuming of course that all objecting conduct is legitimate), but it must also be understood as a principle. That is to say, any conflict between the subject's fundamental right and legal duty that he rejects must be resolved by the judge who must make a careful judgement of values and property. This fundamental right still exists and may invoked and exercised by inmates and health personnel in the prison context in the face of predictions of the forcible imposition of medical treatment as stated in the LOGP and RP, with no more limit than public order itself.
The (In)dependence of Alternative Splicing and Gene Duplication
David Talavera ,Christine Vogel ,Modesto Orozco,Sarah A Teichmann,Xavier de la Cruz
PLOS Computational Biology , 2007, DOI: 10.1371/journal.pcbi.0030033
Abstract: Alternative splicing (AS) and gene duplication (GD) both are processes that diversify the protein repertoire. Recent examples have shown that sequence changes introduced by AS may be comparable to those introduced by GD. In addition, the two processes are inversely correlated at the genomic scale: large gene families are depleted in splice variants and vice versa. All together, these data strongly suggest that both phenomena result in interchangeability between their effects. Here, we tested the extent to which this applies with respect to various protein characteristics. The amounts of AS and GD per gene are anticorrelated even when accounting for different gene functions or degrees of sequence divergence. In contrast, the two processes appear to be independent in their influence on variation in mRNA expression. Further, we conducted a detailed comparison of the effect of sequence changes in both alternative splice variants and gene duplicates on protein structure, in particular the size, location, and types of sequence substitutions and insertions/deletions. We find that, in general, alternative splicing affects protein sequence and structure in a more drastic way than gene duplication and subsequent divergence. Our results reveal an interesting paradox between the anticorrelation of AS and GD at the genomic level, and their impact at the protein level, which shows little or no equivalence in terms of effects on protein sequence, structure, and function. We discuss possible explanations that relate to the order of appearance of AS and GD in a gene family, and to the selection pressure imposed by the environment.
A new species of Astragalus L. sect. Sesamei DC. (Leguminosae) from the southeast of Spain: Astragalus castroviejoi
Talavera Lozano, Salvador,Sánchez-Gómez, Pedro,López García, David,Jiménez Martínez, Juan Francisco
Anales del Jardín Botánico de Madrid , 2010,
Abstract: We describe a new species of Astragalus section Sesamei from the semiarid zone of SE Spain: Astragalus castroviejoi. Morphologically the new species resembles A. sesameus L. and A. stella L. and we provide a key to distinguish the three species. A. castroviejoi is a diploid species with 2n = 16, the same chromosome number as A. sesameus and A. stella. We provide an image of the karyotype, together with an illustration of the new species and a map of its distribution. Since the existing populations are restricted in area, we also provide an estimate of the conservartion status of this species according to the criteria of the IUCN. En este trabajo se describe una especie nueva de la zona semiárida del SE de Espa a perteneciente a la sección Sesamei del género Astragalus: Astragalus castroviejoi. En lo morfológico, esta especie se parece a A. sesameus L. y A. stella L., por lo que se aporta una clave para la identificación de estas tres especies. A. castroviejoi es una especie diploide con 2n = 16, el mismo número cromosomático de A. sesameus y A. stella. Se da la descripción del cariótipo y se aporta la iconografía de la especie y un mapa de distribución. Como los núcleos poblacionales son peque os se hace también una valoración, siguiendo los criterios de la IUCN, del estado de conservación de la especie.
The Relationship between Gene Isoform Multiplicity, Number of Exons and Protein Divergence
Jordi Morata, Santi Béjar, David Talavera, Casandra Riera, Sergio Lois, Gemma Mas de Xaxars, Xavier de la Cruz
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0072742
Abstract: At present we know that phenotypic differences between organisms arise from a variety of sources, like protein sequence divergence, regulatory sequence divergence, alternative splicing, etc. However, we do not have yet a complete view of how these sources are related. Here we address this problem, studying the relationship between protein divergence and the ability of genes to express multiple isoforms. We used three genome-wide datasets of human-mouse orthologs to study the relationship between isoform multiplicity co-occurrence between orthologs (the fact that two orthologs have more than one isoform) and protein divergence. In all cases our results showed that there was a monotonic dependence between these two properties. We could explain this relationship in terms of a more fundamental one, between exon number of the largest isoform and protein divergence. We found that this last relationship was present, although with variations, in other species (chimpanzee, cow, rat, chicken, zebrafish and fruit fly). In summary, we have identified a relationship between protein divergence and isoform multiplicity co-occurrence and explained its origin in terms of a simple gene-level property. Finally, we discuss the biological implications of these findings for our understanding of inter-species phenotypic differences.
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