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Feil R.,Montpellier University | Fraga M.F.,CSIC - National Center for Biotechnology | Fraga M.F.,University of Oviedo
Nature Reviews Genetics | Year: 2012

Epigenetic phenomena in animals and plants are mediated by DNA methylation and stable chromatin modifications. There has been considerable interest in whether environmental factors modulate the establishment and maintenance of epigenetic modifications, and could thereby influence gene expression and phenotype. Chemical pollutants, dietary components, temperature changes and other external stresses can indeed have long-lasting effects on development, metabolism and health, sometimes even in subsequent generations. Although the underlying mechanisms remain largely unknown, particularly in humans, mechanistic insights are emerging from experimental model systems. These have implications for structuring future research and understanding disease and development. © 2012 Macmillan Publishers Limited. All rights reserved. Source

De Juan D.,Spanish National Cancer Research Center | Pazos F.,CSIC - National Center for Biotechnology | Valencia A.,Spanish National Cancer Research Center
Nature Reviews Genetics | Year: 2013

Co-evolution is a fundamental component of the theory of evolution and is essential for understanding the relationships between species in complex ecological networks. A wide range of co-evolution-inspired computational methods has been designed to predict molecular interactions, but it is only recently that important advances have been made. Breakthroughs in the handling of phylogenetic information and in disentangling indirect relationships have resulted in an improved capacity to predict interactions between proteins and contacts between different protein residues. Here, we review the main co-evolution-based computational approaches, their theoretical basis, potential applications and foreseeable developments. © 2013 Macmillan Publishers Limited. All rights reserved. Source

Rojo F.,CSIC - National Center for Biotechnology
FEMS Microbiology Reviews | Year: 2010

Metabolically versatile free-living bacteria have global regulation systems that allow cells to selectively assimilate a preferred compound among a mixture of several potential carbon sources. This process is known as carbon catabolite repression (CCR). CCR optimizes metabolism, improving the ability of bacteria to compete in their natural habitats. This review summarizes the regulatory mechanisms responsible for CCR in the bacteria of the genus Pseudomonas, which can live in many different habitats. Although the information available is still limited, the molecular mechanisms responsible for CCR in Pseudomonas are clearly different from those of Enterobacteriaceae or Firmicutes. An understanding of the molecular mechanisms underlying CCR is important to know how metabolism is regulated and how bacteria degrade compounds in the environment. This is particularly relevant for compounds that are degraded slowly and accumulate, creating environmental problems. CCR has a major impact on the genes involved in the transport and metabolism of nonpreferred carbon sources, but also affects the expression of virulence factors in several bacterial species, genes that are frequently directed to allow the bacterium to gain access to new sources of nutrients. Finally, CCR has implications in the optimization of biotechnological processes such as biotransformations or bioremediation strategies. © 2010 Federation of European Microbiological Societies. Source

De Lorenzo V.,CSIC - National Center for Biotechnology
BioEssays | Year: 2014

The standard representation of the Central Dogma (CD) of Molecular Biology conspicuously ignores metabolism. However, both the metabolites and the biochemical fluxes behind any biological phenomenon are encrypted in the DNA sequence. Metabolism constrains and even changes the information flow when the DNA-encoded instructions conflict with the homeostasis of the biochemical network. Inspection of adaptive virulence programs and emergence of xenobiotic-biodegradation pathways in environmental bacteria suggest that their main evolutionary drive is the expansion of their metabolic networks towards new chemical landscapes rather than perpetuation and spreading of their DNA sequences. Faulty enzymatic reactions on suboptimal substrates often produce reactive oxygen species (ROS), a process that fosters DNA diversification and ultimately couples catabolism of the new chemicals to growth. All this calls for a revision of the CD in which metabolism (rather than DNA) has the leading role. © 2014 WILEY Periodicals, Inc. Source

Martin C.S.,CSIC - National Center for Biotechnology
Viruses | Year: 2012

Adenovirus (AdV) capsid organization is considerably complex, not only because of its large size (~950 Å) and triangulation number (pseudo T = 25), but also because it contains four types of minor proteins in specialized locations modulating the quasi-equivalent icosahedral interactions. Up until 2009, only its major components (hexon, penton, and fiber) had separately been described in atomic detail. Their relationships within the virion, and the location of minor coat proteins, were inferred from combining the known crystal structures with increasingly more detailed cryo-electron microscopy (cryoEM) maps. There was no structural information on assembly intermediates. Later on that year, two reports described the structural differences between the mature and immature adenoviral particle, starting to shed light on the different stages of viral assembly, and giving further insights into the roles of core and minor coat proteins during morphogenesis [1,2]. Finally, in 2010, two papers describing the atomic resolution structure of the complete virion appeared [3,4]. These reports represent a veritable tour de force for two structural biology techniques: X-ray crystallography and cryoEM, as this is the largest macromolecular complex solved at high resolution by either of them. In particular, the cryoEM analysis provided an unprecedented clear picture of the complex protein networks shaping the icosahedral shell. Here I review these latest developments in the field of AdV structural studies. © 2012 by the authors; licensee MDPI, Basel, Switzerland. Source

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