Redescobrint George Perkins Marsh i l'aportació de Man and Nature a la geografia ambiental

George Perkins Marsh (1801-1882) i la seva obra, especialment la monumental Man and Nature, són un precedent avui dia de la geografia ambiental. Els seus plantejaments innovadors i les seves conclusions anticipatàries continuen vigents en l'estudi de la problemàtica relació societat-medi, malgrat I'oblit en qui: caigueren les seus escrits durant decades, l'anàlisi de la metodologia i tematica que empri és una necessitat, on es fa avinent que la geografia, com a disciplina integradora, pot recollir els seus plantejaments per respondre als reptes actuals que té plantejats la humanitat respecte a la problemàtica de la seva acció sobre el medi del planeta.George Perkins Marsh (1801-1882) y su obra, en especial la monumental Man and Nature, son en la actualidad un precedente de la geografia ambiental. Sus planteamientos innovadores y sus conclusiones anticipatorias siguen vigentes en el estudio de la problemática relación sociedad-medio, a pesar del olvido en que cayeron sus escritos durante décadas. El análisis de su metodologia y de la temática que utilizó es necesario porque pone de relieve que la geografia, como disciplina integradora, puede recoger sus planteamientos para responder a los retos actuales que tiene planteados la humanidad respecto a la problemática de su acción sobre el medio del planeta.George Perkins Marsh (1801-1882) et ses travaux, spécialement l'ouvrage monumental Man and Nature, sont considérés actuellement comme précurseurs de la géographie environnementale. Les positions innovatrices de cet auteur ainsi que ses conclusions, qui s'avancent aux problemes de son temps, ont été injustement oubliées pendent de nombreuses décades. Cependant, elles sont encore dignes d'analyse aujourd'hui, surtout en ce qui concerne le probleme de la relation societé-milieu. La méthodologie utilisée par l'auteur, ainsi que la thématique, souligne l'importance de la géographie comme discipline intégratrice. Son analyse est donc nécessaire pour récupérer une forme de penser et des arguments qui peuvent permettre de mieux répondre aux enjeux actuels de l'humanité, en ce qui concerne les problemes posés par l'accion humaine sur l'environnement de la planete.Georges Perkins Marsh (1801 - 1882) and his writtings, in particular his monumental work Man and Nature, are now considered a forerunner of environmental geography. His innovatory approaches and his conclusions ahead of his time are still valid in the study of the problematic relationship benveen humanity and his environment, even though they were forgotten about for severa1 decades. The necessary analysis of the metodology that he applied and the topics he studied makes it clear that Geography in its role as an integrating discipline can malce look to his approaches in order to find replies to the present challenges facing the human race in order to solve the problems arising as a result of an impact on the planet's environment

Identificació d'isoformes i modificacions posttraduccionals del factor GAGA de Drosophila melanogaster

Peer Reviewe

The GAGA protein of Drosophila is phosphorylated by CK2

The GAGA factor of Drosophila is a sequence-specific DNA-binding protein that contributes to multiple processes from the regulation of gene expression to the structural organisation of heterochromatin and chromatin remodelling. GAGA is known to interact with various other proteins (tramtrack, pipsqueak, batman and dSAP18) and protein complexes (PRC1, NURF and FACT). GAGA functions are likely regulated at the level of post-translational modifications. Little is known, however, about its actual pattern of modification. It was proposed that GAGA can be O-glycosylated. Here, we report that GAGA519 isoform is a phosphoprotein that is phosphorylated by CK2 at the region of the DNA-binding domain. Our results indicate that phosphorylation occurs at S388 and, to a lesser extent, at S378. These two residues are located in a region of the DNA-binding domain that makes no direct contact with DNA, being dispensable for sequence-specific recognition. Phosphorylation at these sites does not abolish DNA binding but reduces the affinity of the interaction. These results are discussed in the context of the various functions and interactions that GAGA supports. © 2005 Elsevier Ltd. All rights reserved.This work was financed by grants from the Ministerio de Ciencia y Tecnología (BMC2003-243; BMC2003-616; BIO2002-2301) and the CIRIT (2001SGR00344; 2001SGR00047). X.A. acknowledges receipt of a doctoral fellowship from the CIRIT. This work was carried out within the framework of the “Centre de Referència en Biotecnologia” of the Generalitat de CatalunyaPeer Reviewe

Acetylation of GAGA factor modulates its interaction with DNA

GAGA is a Drosophila transcription factor that shows a high degree of post-translational modification. Here, we show that GAGA factor is acetylated in vivo. Lysine residues K325 and K373 on basic regions BR1 and BR3 of the DNA binding domain, respectively, are shown to be acetylated by PCAF. While BR1 is strictly required to stabilize DNA binding, BR3 is dispensable. However, acetylation of both lysine residues, either alone or in combination, weakens the binding to DNA. Despite the high degree of conservation of K325 and K373 in flies, their mutation to glutamine does not affect DNA binding. Molecular dynamics simulations, using acetylated K325 and a K325Q mutant of GAGA DNA binding domain in complex with DNA, are fully consistent with these results and provide a thermodynamic explanation for this observation. We propose that while K325 and K373 are not essential for DNA binding they have been largely conserved for regulatory purposes, thus highlighting a key regulatory system for GAGA factor in flies. © 2010 American Chemical Society.Este trabajo fue financiado por el Ministerio de Ciencia e Innovación del Gobierno de España (concesiones BFU2006-09761 y BFU2007-64395/BMC para Jordi Benués), y fue llevado a cabo dentro del marco del “Centre de Referència en Biotecnologia” de la Generalitat de Catalunya.Peer Reviewe

Regulation of the MLH1-MLH3 endonuclease in meiosis

During prophase of the first meiotic division, cells deliberately break their DNA1. These DNA breaks are repaired by homologous recombination, which facilitates proper chromosome segregation and enables the reciprocal exchange of DNA segments between homologous chromosomes2. A pathway that depends on the MLH1–MLH3 (MutLγ) nuclease has been implicated in the biased processing of meiotic recombination intermediates into crossovers by an unknown mechanism3,4,5,6,7. Here we have biochemically reconstituted key elements of this pro-crossover pathway. We show that human MSH4–MSH5 (MutSγ), which supports crossing over8, binds branched recombination intermediates and associates with MutLγ, stabilizing the ensemble at joint molecule structures and adjacent double-stranded DNA. MutSγ directly stimulates DNA cleavage by the MutLγ endonuclease. MutLγ activity is further stimulated by EXO1, but only when MutSγ is present. Replication factor C (RFC) and the proliferating cell nuclear antigen (PCNA) are additional components of the nuclease ensemble, thereby triggering crossing-over. Saccharomyces cerevisiae strains in which MutLγ cannot interact with PCNA present defects in forming crossovers. Finally, the MutLγ–MutSγ–EXO1–RFC–PCNA nuclease ensemble preferentially cleaves DNA with Holliday junctions, but shows no canonical resolvase activity. Instead, it probably processes meiotic recombination intermediates by nicking double-stranded DNA adjacent to the junction points9. As DNA nicking by MutLγ depends on its co-factors, the asymmetric distribution of MutSγ and RFC–PCNA on meiotic recombination intermediates may drive biased DNA cleavage. This mode of MutLγ nuclease activation might explain crossover-specific processing of Holliday junctions or their precursors in meiotic chromosomes4

HSP70-HSP90 chaperone networking in protein-misfolding disease

Molecular chaperones and their associated co-chaperones are essential in health and disease as they are key facilitators of protein-folding, quality control and function. In particular, the heat-shock protein (HSP) 70 and HSP90 molecular chaperone networks have been associated with neurodegenerative diseases caused by aberrant protein-folding. The pathogenesis of these disorders usually includes the formation of deposits of misfolded, aggregated protein. HSP70 and HSP90, plus their co-chaperones, have been recognised as potent modulators of misfolded protein toxicity, inclusion formation and cell survival in cellular and animal models of neurodegenerative disease. Moreover, these chaperone machines function not only in folding but also in proteasome-mediated degradation of neurodegenerative disease proteins. This chapter gives an overview of the HSP70 and HSP90 chaperones, and their respective regulatory co-chaperones, and explores how the HSP70 and HSP90 chaperone systems form a larger functional network and its relevance to counteracting neurodegenerative disease associated with misfolded proteins and disruption of proteostasis

Activation of autophagy depends on Atg1/Ulk1-mediated phosphorylation and inhibition of the Hsp90 chaperone machinery

Cellular homeostasis relies on both the chaperoning of proteins and the intracellular degradation system that delivers cytoplasmic constituents to the lysosome, a process known as autophagy. The crosstalk between these processes and their underlying regulatory mechanisms is poorly understood. Here, we show that the molecular chaperone heat shock protein 90 (Hsp90) forms a complex with the autophagy-initiating kinase Atg1 (yeast)/Ulk1 (mammalian), which suppresses its kinase activity. Conversely, environmental cues lead to Atg1/Ulk1-mediated phosphorylation of a conserved serine in the amino domain of Hsp90, inhibiting its ATPase activity and altering the chaperone dynamics. These events impact a conformotypic peptide adjacent to the activation and catalytic loop of Atg1/Ulk1. Finally, Atg1/Ulk1-mediated phosphorylation of Hsp90 leads to dissociation of the Hsp90:Atg1/Ulk1 complex and activation of Atg1/Ulk1, which is essential for initiation of autophagy. Our work indicates a reciprocal regulatory mechanism between the chaperone Hsp90 and the autophagy kinase Atg1/Ulk1 and consequent maintenance of cellular proteostasis.</p