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Search Results: 1 - 10 of 10079 matches for " Patrick Cramer "
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A Conserved GA Element in TATA-Less RNA Polymerase II Promoters
Martin Seizl,Holger Hartmann,Friederike Hoeg,Fabian Kurth,Dietmar E. Martin,Johannes S?ding,Patrick Cramer
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0027595
Abstract: Initiation of RNA polymerase (Pol) II transcription requires assembly of the pre-initiation complex (PIC) at the promoter. In the classical view, PIC assembly starts with binding of the TATA box-binding protein (TBP) to the TATA box. However, a TATA box occurs in only 15% of promoters in the yeast Saccharomyces cerevisiae, posing the question how most yeast promoters nucleate PIC assembly. Here we show that one third of all yeast promoters contain a novel conserved DNA element, the GA element (GAE), that generally does not co-occur with the TATA box. The distance of the GAE to the transcription start site (TSS) resembles the distance of the TATA box to the TSS. The TATA-less TMT1 core promoter contains a GAE, recruits TBP, and supports formation of a TBP-TFIIB-DNA-complex. Mutation of the promoter region surrounding the GAE abolishes transcription in vivo and in vitro. A 32-nucleotide promoter region containing the GAE can functionally substitute for the TATA box in a TATA-containing promoter. This identifies the GAE as a conserved promoter element in TATA-less promoters.
MC EMiNEM Maps the Interaction Landscape of the Mediator
Theresa Niederberger,Stefanie Etzold,Michael Lidschreiber,Kerstin C. Maier,Dietmar E. Martin,Holger Fr?hlich,Patrick Cramer,Achim Tresch
PLOS Computational Biology , 2012, DOI: 10.1371/journal.pcbi.1002568
Abstract: The Mediator is a highly conserved, large multiprotein complex that is involved essentially in the regulation of eukaryotic mRNA transcription. It acts as a general transcription factor by integrating regulatory signals from gene-specific activators or repressors to the RNA Polymerase II. The internal network of interactions between Mediator subunits that conveys these signals is largely unknown. Here, we introduce MC EMiNEM, a novel method for the retrieval of functional dependencies between proteins that have pleiotropic effects on mRNA transcription. MC EMiNEM is based on Nested Effects Models (NEMs), a class of probabilistic graphical models that extends the idea of hierarchical clustering. It combines mode-hopping Monte Carlo (MC) sampling with an Expectation-Maximization (EM) algorithm for NEMs to increase sensitivity compared to existing methods. A meta-analysis of four Mediator perturbation studies in Saccharomyces cerevisiae, three of which are unpublished, provides new insight into the Mediator signaling network. In addition to the known modular organization of the Mediator subunits, MC EMiNEM reveals a hierarchical ordering of its internal information flow, which is putatively transmitted through structural changes within the complex. We identify the N-terminus of Med7 as a peripheral entity, entailing only local structural changes upon perturbation, while the C-terminus of Med7 and Med19 appear to play a central role. MC EMiNEM associates Mediator subunits to most directly affected genes, which, in conjunction with gene set enrichment analysis, allows us to construct an interaction map of Mediator subunits and transcription factors.
The phosphatidylserine receptor from Hydra is a nuclear protein with potential Fe(II) dependent oxygenase activity
Mihai Cikala, Olga Alexandrova, Charles N David, Matthias Pr?schel, Beate Stiening, Patrick Cramer, Angelika B?ttger
BMC Cell Biology , 2004, DOI: 10.1186/1471-2121-5-26
Abstract: We have cloned the PSR receptor from Hydra in order to investigate its function in this early metazoan. Bioinformatic analysis of the Hydra PSR protein structure revealed the presence of three nuclear localisation signals, an AT-hook like DNA binding motif and a putative 2-oxoglutarate (2OG)-and Fe(II)-dependent oxygenase activity. All of these features are conserved from human PSR to Hydra PSR. Expression of GFP tagged Hydra PSR in hydra cells revealed clear nuclear localisation. Deletion of one of the three NLS sequences strongly diminished nuclear localisation of the protein. Membrane localisation was never detected.Our results suggest that Hydra PSR is a nuclear 2-oxoglutarate (2OG)-and Fe(II)-dependent oxygenase. This is in contrast with the proposed function of Hydra PSR as a cell surface receptor involved in the recognition of apoptotic cells displaying phosphatidylserine on their surface. The conservation of the protein from Hydra to human infers that our results also apply to PSR from higher animals.Apoptotic cell death plays an essential role in embryogenesis, development and maintenance of tissue homeostasis in metazoan animals. The culmination of apoptosis in vivo is the phagocytosis of cellular corpses. One morphological characteristic of cells undergoing apoptosis is loss in the phospholipid asymmetry of the plasma membrane and exposure of phosphatidylserine on the outer membrane leaflet. Surface exposure of phosphatidylserine is required for phagocytosis of apoptotic cells by macrophages and fibroblasts [1,2].A putative receptor for phosphatidylserine binding was cloned from human and mouse macrophages [3]. The receptor (PSR) was identified by phage display as the antigen for a monoclonal antibody generated against stimulated human macrophages. This antibody inhibited uptake of apoptotic cells by macrophages, fibroblasts and epithelial cells.When cells that do not express the receptor and cannot engulf apoptotic cells normally, like Jurkat T, were tra
Vehicle Collisions Cause Differential Age and Sex-Specific Mortality in Mule Deer
Daniel D. Olson,John A. Bissonette,Patricia C. Cramer,Kevin D. Bunnell,Daniel C. Coster,Patrick J. Jackson
Advances in Ecology , 2014, DOI: 10.1155/2014/971809
Abstract: As roads continue to be built and expanded, it is important that managers understand the effects that vehicle-related mortality can have on the population dynamics of wildlife. Our objective was to examine the frequency of mule deer (Odocoileus hemionus) vehicle collisions to determine if different demographic groups showed differential susceptibility to mortality when compared with their proportion in the population. We also compared vehicle collision rates of mule deer, elk (Cervus canadensis), and moose (Alces alces) to determine their relative vulnerability to vehicle collisions. We found that 65% of mule deer involved in vehicle collisions were female; of those, 40% were adult does ≥2?yrs. When we compared the proportion of bucks, does, and fawns killed in vehicle collisions to surveys of live deer, we found that bucks were killed at rate of 2.1–3.0 times their proportion in the population. Additionally, when we compared vehicle collision rates for 2010 and 2011, we found that mule deer were 7.4–8.7 times more likely to be involved in collisions than elk and 1.2–2.0 times more likely than moose. However, we were unable to detect a negative correlation () between mule deer abundance and increasing traffic volume. 1. Introduction Roads are being built and expanded throughout the developed world to accommodate the increasing human population and demand for transportation of people, goods, and materials [1–3]. An IEA 2013 report [4] suggested the following: the world will need to add nearly 25 million paved road lane km (~60% increase) between 2010 and 2050; between 45?000 and 77?000?km2 of new parking spaces will be added to accommodate passenger vehicle stock growth; global travel in 2050 will double that of 2010 travel levels; passenger travel will account for 70% of this growth; and ~90% of travel growth is expected in developing countries. Laurance et al. [5] estimated that the total length of the projected new roads is equivalent to encircling the earth ~600 times. Clearly, it is increasingly important to understand the effects that roads have on wildlife; those effects appear to be overwhelming negative for most species [6–9]. Deer are commonly involved in vehicle collisions in Europe, North America, and Japan [10–12]. In the United States alone, there are an estimated 1-2 million vehicle collisions with large animals annually, most of which involve deer, that result in >$8 billion (USD) in damages and >200 human fatalities [13–15]. Additionally, vehicle collisions are nearly always fatal for deer [16]. Mule deer occur throughout western North
Cell motility and the formation of lamellipodia
Louise Cramer
Genome Biology , 2000, DOI: 10.1186/gb-2000-1-1-reports404
Abstract: Conference website: http://www.faseb.org/ascb/meetings/am99/main99mtg.htm webciteIn eukaryotic motile cells, protrusion of the lamellipodium - a type of cell margin - requires the assembly of free actin monomers into actin filaments at the cell margin. Less well understood, however, is the importance of actin-filament disassembly in this process, and this was addressed in several studies reported at the American Society of Cell Biology annual meeting [http://www.faseb.org/ascb/meetings/am99/main99mtg.htm webcite]. When filament disassembly in migrating chick fibroblasts is inhibited with jasplakinolide, protrusion of the lamellipodium is rapidly blocked (my own work). In non-migrating chick fibroblasts, there is a delay in the onset of jasplakinolide-induced inhibition of lamellipodia protrusion, during which lamellipodium length increases linearly with no increase in protrusion rate. When cofilin activity, which severs and disassembles filamentous actin, is inhibited in rat carcinoma cells with antibodies (Maryse Bailly, Albert Einstein College of Medicine) or by phosphorylation (Noureddine Zebda, Albert Einstein College of Medicine), lamellipodium protrusion stimulated by epidermal growth factor (EGF) is blocked. These data show that there is coupling between filament disassembly and lamellipodium protrusion in at least two distinct cell types. That this coupling is rapid in migrating fibroblasts may reflect a situation whereby actin filament assembly directly uses free actin monomer derived from filament disassembly in preference to stored monomer. In contrast, slower coupling in non-migrating fibroblasts implies that free actin monomer is instead derived from stored monomer. The situation in the rat carcinoma cells has not yet - as far as I can tell - been assessed. Irrespective of the source of free monomer, the authors of the cofilin work favour a model where the severing activity of cofilin also provides the free 'plus ends' (barbed, or rapidly growing) requi
Determining the cellular function of myosin VI
Lousie Cramer
Genome Biology , 2000, DOI: 10.1186/gb-2000-1-1-reports405
Abstract: Conference website: http://www.faseb.org/ascb/meetings/am99/main99mtg.htm webciteThe myosin superfamily of actin-based molecular motor proteins comprises an ever growing number of subfamilies (15 or more classes to date). These have been identified biochemically, genetically and by cloning technology. An exciting development in the myosin field is the discovery that in vitro myosins of class VI are a 'reverse' actin motor (Wells AL et al. Nature, 1999, 401:505-508). This new information, combined with the already established importance of myosin VI in cells, will aid interpretation of the cellular function of this myosin.For a myosin to move 'backwards', theoretical, structure-based considerations either require the redesigning of the actin-binding interface on myosin so that the myosin head domain faces the minus end of the actin filament, or the repositioning of the lever arm (light chain binding domain) such that the myosin head moves in the opposite direction. Redesigning the actin-binding interface would require huge changes to myosin protein structure, and if such a protein exists, it is more likely to be a member of a distinct family of actin motors than a recognisable myosin. Discovering such a new protein family in the future remains a possibility, considering that there are already two known distinct families of microtubule-based motor proteins. In contrast, repositioning the lever arm is plausible with only minor structural modifications, placing the protein within the myosin superfamily.Myosin VI is the only known subfamily of myosins with a repositioned light chain binding domain (IQ motif), due to an extra 50 amino acids inserted in the 'converter domain' (domain between the catalytic head and light chain binding domain). Interestingly this does not appear to change the predicted protein structure of this region, remaining α-helical as observed for other classes of myosins. Potentially there are important amino acid changes in this insert sufficient to
Racionalidad Económica Y Terrorismo: Una Fórmula Explosiva
Christopher,Cramer;
Análisis Político , 2010,
Abstract: this paper is more about economics as social science than about terrorism. the main argument is as follows. once upon a time a creature called homo economicus went to war but shot himself in the foot (cramer, 2002). in other words, the extension of neoclassical economics to 'explain' the causes of civil wars has thus far not been a great success in either theoretical or empirical terms. then, returning wounded and vengeful from the front, homo economicus weighed up the costs and benefits of conflict versus cooperation, assessed the constraints, underwent some training in behavioural psychology, and made the rational choice to engage in terrorism, but she blew herself up accidentally. in other words, neo-classical economic explanations of terrorism are very interesting, in some ways more so than those explaining civil war, but they are selfdefeating in their efforts and they reveal the weaknesses of neo-classical economics as a foundation for social science.
Thomas Ballhausen, Thomas Edlinger, Linda Henschel, Katherina Zakrawsky: The Porn Identity. Expeditionen in die Dunkelzone. Nürnberg: Verlag für Moderne Kunst 2009.
Florian Cramer
querelles-net , 2010,
Abstract: Die Ausstellung The Porn Identity“ und ihr begleitender Katalog- und Essayband kartografieren die Schnittmengen von Pornografie, zeitgen ssischer Kunst und Kulturtheorie umfassend genug, um als Einführungen ins Themengebiet nützlich zu sein. Indem der Katalog Pornobilder und -lifestyle zugleich schwelgerisch zelebriert und genderpolitisch-korrekt verbr mt, ist er jedoch so schmierig wie kommerzielle Pornografie. Dies macht ihn zum Konzeptkunstwerk – und setzt Fragezeichen hinter den Diskurs der porn studies. The exhibition and catalogue “The Porn Identity” provides an exhausting overview over the intersections between pornography, contemporary art and cultural studies. The book thus serves as a useful introduction into the field. At the same time, its indulgence in in-your-face pornographical imagery combined with seemingly gender-politically correct statements is just sleazy as actual pornography. This turns the catalogue into a coherent conceptual art work, and puts some question marks behind the porn studies discourse.
Dos premios Nobel para el RNA
Paula Cramer
Química Viva , 2006,
Abstract:
Racionalidad Económica Y Terrorismo: Una Fórmula Explosiva Rationality Economic and Terrorism
Cramer Christopher
Análisis Político , 2010,
Abstract: Este documento trata más de la economía como ciencia social que del terrorismo. El argumento princi pal es el siguiente: había una vez una criatura llamada homo economicus que fue a la guerra pero se disparó a sí misma en el pie. En otras palabras, la extensión de la economía neoclásica para explicar las causas de las guerras civiles no ha sido realmente exitosa en términos teóricos y empíricos. Así pues, al regresar herido y con sed de venganza del frente de batalla, el homo economicus sopesó los costos y beneficios del conflicto versus la cooperación, calculó las consecuencias, realizó algún entrenamiento en psicología conductual, e hizo la elección racional de emplear el terrorismo, pero accidentalmente se hizo volar en pedazos. En efecto, las explicaciones económicas neoclásicas del terrorismo son muy interesantes, en algunas formas lo son más que aquellas que explican la guerra civil, pero se derrotan a sí mismas en sus esfuerzos y revelan las debilidades de la economía neoclásica como base para la ciencia social. This paper is more about economics as social science than about terrorism. The main argument is as follows. Once upon a time a creature called homo economicus went to war but shot himself in the foot (Cramer, 2002). In other words, the extension of neoclassical economics to 'explain' the causes of civil wars has thus far not been a great success in either theoretical or empirical terms. Then, returning wounded and vengeful from the front, homo economicus weighed up the costs and benefits of conflict versus cooperation, assessed the constraints, underwent some training in behavioural psychology, and made the rational choice to engage in terrorism, but she blew herself up accidentally. In other words, neo-classical economic explanations of terrorism are very interesting, in some ways more so than those explaining civil war, but they are selfdefeating in their efforts and they reveal the weaknesses of neo-classical economics as a foundation for social science.
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