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Search Results: 1 - 10 of 4406 matches for " Marcus Smolka "
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Chronic DNA Replication Stress Reduces Replicative Lifespan of Cells by TRP53-Dependent, microRNA-Assisted MCM2-7 Downregulation
Gongshi Bai?,Marcus B. Smolka,John C. Schimenti
PLOS Genetics , 2016, DOI: 10.1371/journal.pgen.1005787
Abstract: Circumstances that compromise efficient DNA replication, such as disruptions to replication fork progression, cause a state known as DNA replication stress (RS). Whereas normally proliferating cells experience low levels of RS, excessive RS from intrinsic or extrinsic sources can trigger cell cycle arrest and senescence. Here, we report that a key driver of RS-induced senescence is active downregulation of the Minichromosome Maintenance 2–7 (MCM2-7) factors that are essential for replication origin licensing and which constitute the replicative helicase core. Proliferating cells produce high levels of MCM2-7 that enable formation of dormant origins that can be activated in response to acute, experimentally-induced RS. However, little is known about how physiological RS levels impact MCM2-7 regulation. We found that chronic exposure of primary mouse embryonic fibroblasts (MEFs) to either genetically-encoded or environmentally-induced RS triggered gradual MCM2-7 repression, followed by inhibition of replication and senescence that could be accelerated by MCM hemizygosity. The MCM2-7 reduction in response to RS is TRP53-dependent, and involves a group of Trp53-dependent miRNAs, including the miR-34 family, that repress MCM expression in replication-stressed cells before they undergo terminal cell cycle arrest. miR-34 ablation partially rescued MCM2-7 downregulation and genomic instability in mice with endogenous RS. Together, these data demonstrate that active MCM2-7 repression is a physiologically important mechanism for RS-induced cell cycle arrest and genome maintenance on an organismal level.
The Dung Beetle Dance: An Orientation Behaviour?
Emily Baird,Marcus J. Byrne,Jochen Smolka,Eric J. Warrant,Marie Dacke
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0030211
Abstract: An interesting feature of dung beetle behaviour is that once they have formed a piece of dung into a ball, they roll it along a straight path away from the dung pile. This straight-line orientation ensures that the beetles depart along the most direct route, guaranteeing that they will not return to the intense competition (from other beetles) that occurs near the dung pile. Before rolling a new ball away from the dung pile, dung beetles perform a characteristic “dance,” in which they climb on top of the ball and rotate about their vertical axis. This dance behaviour can also be observed during the beetles' straight-line departure from the dung pile. The aim of the present study is to investigate the purpose of the dung beetle dance. To do this, we explored the circumstances that elicit dance behaviour in the diurnal ball-rolling dung beetle, Scarabaeus (Kheper) nigroaeneus. Our results reveal that dances are elicited when the beetles lose control of their ball or lose contact with it altogether. We also find that dances can be elicited by both active and passive deviations of course and by changes in visual cues alone. In light of these results, we hypothesise that the dung beetle dance is a visually mediated mechanism that facilitates straight-line orientation in ball-rolling dung beetles by allowing them to 1) establish a roll bearing and 2) return to this chosen bearing after experiencing a disturbance to the roll path.
The Co-Repressor SMRT Delays DNA Damage-Induced Caspase Activation by Repressing Pro-Apoptotic Genes and Modulating the Dynamics of Checkpoint Kinase 2 Activation
Claudio Scafoglio, Marcus Smolka, Huilin Zhou, Valentina Perissi, Michael G. Rosenfeld
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0059986
Abstract: Checkpoint kinase 2 (Chk2) is a major regulator of DNA damage response and can induce alternative cellular responses: cell cycle arrest and DNA repair or programmed cell death. Here, we report the identification of a new role of Chk2 in transcriptional regulation that also contributes to modulating the balance between survival and apoptosis following DNA damage. We found that Chk2 interacts with members of the NCoR/SMRT transcriptional co-regulator complexes and serves as a functional component of the repressor complex, being required for recruitment of SMRT on the promoter of pro-apoptotic genes upon DNA damage. Thus, the co-repressor SMRT exerts a critical protective action against genotoxic stress-induced caspase activation, repressing a functionally important cohort of pro-apoptotic genes. Amongst them, SMRT is responsible for basal repression of Wip1, a phosphatase that de-phosphorylates and inactivates Chk2, thus affecting a feedback loop responsible for licensing the correct timing of Chk2 activation and the proper execution of the DNA repair process.
Whi5 Regulation by Site Specific CDK-Phosphorylation in Saccharomyces cerevisiae
Michelle V. Wagner, Marcus B. Smolka, Rob A. M. de Bruin, Huilin Zhou, Curt Wittenberg, Steven F. Dowdy
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0004300
Abstract: The Whi5 transcriptional repressor is a negative regulator of G1 cell cycle progression in Saccharomyces cerevisiae and is functionally equivalent to the Retinoblastoma (Rb) tumor suppressor protein in mammals. In early G1, Whi5 binds to and inhibits SBF (Swi4/Swi6) transcriptional complexes. At Start, Cln:Cdc28 kinases phosphorylate and inactivate Whi5, causing its dissociation from SBF promoters and nuclear export, allowing activation of SBF transcription and entry into late G1. In an analysis of Whi5 phosphorylation, we found that 10 of the 12 putative CDK phosphorylation sites on Whi5 were occupied in vivo in asynchronously growing cells. In addition, we identified 6 non-CDK Whi5 phosphorylation sites. Whi5 CDK and non-CDK phosphorylation mutants were functional and able to rescue the small cell size of whi5Δ cells. However, the Whi5 CDK mutant with all 12 putative CDK sites changed to alanine causes a dramatic cell cycle phenotype when expressed with a Swi6 CDK phosphorylation mutant. Mutational analysis of Whi5 determined that only four C-terminal CDK sites were necessary and sufficient for Whi5 inactivation when Swi6 CDK sites were also mutated. Although these four Whi5 CDK sites do not wholly determine Whi5 nuclear export, they do impact regulation of cell size. Taken together, these observations begin to dissect the regulatory role of specific phosphorylation sites on Whi5.
Extraction, purification and biochemical characterization of a peroxidase from Copaifera langsdorffii leaves
Maciel, Hermelinda Penha Freire;Gouvêa, Cibele Marli Ca??o Paiva;Toyama, Marcos;Smolka, Marcus;Marangoni, Sergio;Pastore, Gláucia Maria;
Química Nova , 2007, DOI: 10.1590/S0100-40422007000500003
Abstract: the aim of this work is to obtain, purify and characterize biochemically a peroxidase from copaifera langsdorffii leaves (cop). cop was obtained by acetone precipitation followed by ion-exchange chromatography. purification yielded 3.5% of peroxidase with the purification factor of 46.86. the cop optimum ph is 6.0 and the temperature is 35 oc. cop was stable in the ph range of 4.5 to 9.3 and at temperatures below 50.0 oc. the apparent michaelis-menten constants (km) for guaiacol and h2o2 were 0.04 mm and 0.39 mm respectively. enzyme turnover was 0.075 s-1 for guaiacol and 0.28 s-1 for hydrogen peroxide. copaifera langsdorffii leaves showed to be a rich source of active peroxidase (cop) during the whole year. cop could replace hrp, the most used peroxidase, in analytical determinations and treatment of industrial effluents at low cost.
Recuperación de plusvalías para el desarrollo urbano: una comparación inter-americana
Smolka,Martim; Amborski,David;
EURE (Santiago) , 2003, DOI: 10.4067/S0250-71612003008800003
Abstract: local governments design a broad range of fiscal or regulatory policies that have been inspired by the idea that land value increment may be mobilized to the benefit of the community -that is of land value capture. this paper compares the experiences of north america (us and canada) and latin america with value capture tools and discusses the reasons why different policies have been favored and different results and degrees of success obtained in their implementation. focusing on broad categories of value capture policies, the first part of the paper compares the overall performance and/or experience of the two regions with the capturing of land value increment through conventional taxes, fees and regulatory urban policy instruments. the second part of the paper shows that the same "value capture principle" to address similar problems (to deepen land value taxation; to finance urban infrastructure; to control land use) result in different outcomes (sometimes even opposite) in different contexts, most notably those presented in north america and latin america, respectively. the paper?s concluding section provides some evaluative comments regarding the apparent lag between the intentions and outcomes of value capture policies as experienced by the two regions
A memória em quest?o: uma perspectiva histórico-cultural
Smolka, Ana Luiza Bustamante;
Educa??o & Sociedade , 2000, DOI: 10.1590/S0101-73302000000200008
Abstract: this article brings to the fore the issue of memory as social practice. it focuses on the many historically constituted ways of thinking and speaking about memory. it looks for the understanding of the collective modes of elaboration of memory, searching for signs or marks of this constitution at the level of the individual and inquiring about the discursive dimension and the status of language in this constitution.
O (im)próprio e o (im)pertinente na apropria??o das práticas sociais
Smolka, Ana Luiza Bustamante;
Cadernos CEDES , 2000, DOI: 10.1590/S0101-32622000000100003
Abstract: in the present paper we aim at bringing the issue of internalization/appropriation again into discussion, exploring possibilities and limits of such terms, departing from an analysis of the notions historically condensed and stabilized in such words, and commenting on the ways they merge in the cultural-historical perspective. we focus on some inherent contradictions which provoke theoretical difficulties and require conceptual refinement. we show how internalization/appropriation has usually implied the notions of accomplishment and adequacy in the incorporation of social practices, being inevitably positively oriented. we analyze how the (im)proper and the (im)pertinent - hence, the inappropriate - in such practices might be seen as locus of resistance, mobility and change, arguing for the need of considering appropriation as an essentially relational category.
A memória em quest o: uma perspectiva histórico-cultural
Smolka Ana Luiza Bustamante
Educa??o & Sociedade , 2000,
Abstract: Este texto tematiza a memória enquanto prática social, enfocando os muitos modos, historicamente constituídos, de pensar e de falar sobre memória. Procura compreender os modos de elabora o coletiva da memória, buscando indícios da constitui o da memória no nível individual e indagando sobre a dimens o discursiva, sobre o estatuto da linguagem nessa constitui o.
Recuperación de plusvalías para el desarrollo urbano: una comparación inter-americana
Martim Smolka,David Amborski
EURE (Santiago) , 2003,
Abstract: Los gobiernos locales desarrollan una amplia gama de políticas fiscales o regulatorias inspiradas en la idea de que el incremento en el valor de la tierra puede ser utilizado en beneficio de la comunidad, esto es, en la recuperación de plusvalías inmobiliarias. Este trabajo compara las experiencias de recuperación de plusvalías en América del Norte (Estados Unidos y Canadá) y América Latina, discutiendo las razones que han llevado a la utilización de distintas herramientas y los diferentes resultados y grados de éxito obtenidos en su implementación. En primer término, el texto identifica categorías amplias de políticas de recuperación de plusvalías y compara los resultados y/o la experiencia de las dos regiones en la recuperación de los incrementos en el valor de la tierra por medio de impuestos convencionales, contribuciones fiscales e instrumentos urbanísticos. La segunda parte del texto muestra que el mismo principio de recuperación de plusvalías utilizado para abordar problemas similares (profundizar la tributación sobre el valor de la tierra, financiar infraestructura urbana, controlar el uso del suelo) tiene resultados diferentes -e incluso contradictorios- en diversos contextos, principalmente en los de América del Norte y América Latina. La sección final contiene algunos comentarios evaluatorios relativos a la aparente brecha entre las intenciones y los resultados de las políticas de recuperación de plusvalía observadas en ambas Américas Local governments design a broad range of fiscal or regulatory policies that have been inspired by the idea that land value increment may be mobilized to the benefit of the community -that is of land value capture. This paper compares the experiences of North America (US and Canada) and Latin America with value capture tools and discusses the reasons why different policies have been favored and different results and degrees of success obtained in their implementation. Focusing on broad categories of value capture policies, the first part of the paper compares the overall performance and/or experience of the two regions with the capturing of land value increment through conventional taxes, fees and regulatory urban policy instruments. The second part of the paper shows that the same "value capture principle" to address similar problems (to deepen land value taxation; to finance urban infrastructure; to control land use) result in different outcomes (sometimes even opposite) in different contexts, most notably those presented in North America and Latin America, respectively. The paper’s concluding section provides
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