A quantitative model of the initiation of DNA replication in Saccharomyces cerevisiae predicts the effects of system perturbations.

BackgroundEukaryotic cell proliferation involves DNA replication, a tightly regulated process mediated by a multitude of protein factors. In budding yeast, the initiation of replication is facilitated by the heterohexameric origin recognition complex (ORC). ORC binds to specific origins of replication and then serves as a scaffold for the recruitment of other factors such as Cdt1, Cdc6, the Mcm2-7 complex, Cdc45 and the Dbf4-Cdc7 kinase complex. While many of the mechanisms controlling these associations are well documented, mathematical models are needed to explore the network's dynamic behaviour. We have developed an ordinary differential equation-based model of the protein-protein interaction network describing replication initiation.ResultsThe model was validated against quantified levels of protein factors over a range of cell cycle timepoints. Using chromatin extracts from synchronized Saccharomyces cerevisiae cell cultures, we were able to monitor the in vivo fluctuations of several of the aforementioned proteins, with additional data obtained from the literature. The model behaviour conforms to perturbation trials previously reported in the literature, and accurately predicts the results of our own knockdown experiments. Furthermore, we successfully incorporated our replication initiation model into an established model of the entire yeast cell cycle, thus providing a comprehensive description of these processes.ConclusionsThis study establishes a robust model of the processes driving DNA replication initiation. The model was validated against observed cell concentrations of the driving factors, and characterizes the interactions between factors implicated in eukaryotic DNA replication. Finally, this model can serve as a guide in efforts to generate a comprehensive model of the mammalian cell cycle in order to explore cancer-related phenotypes

Spitzer Infrared Spectrograph Detection of Molecular Hydrogen Rotational Emission towards Translucent Clouds

Using the Infrared Spectrograph on board the Spitzer Space Telescope, we have detected emission in the S(0), S(1), and S(2) pure-rotational (v = 0-0) transitions of molecular hydrogen (H_2) toward six positions in two translucent high Galactic latitude clouds, DCld 300.2–16.9 and LDN 1780. The detection of these lines raises important questions regarding the physical conditions inside low-extinction clouds that are far from ultraviolet radiation sources. The ratio between the S(2) flux and the flux from polycyclic aromatic hydrocarbons (PAHs) at 7.9 μm averages 0.007 for these six positions. This is a factor of about four higher than the same ratio measured toward the central regions of non-active Galaxies in the Spitzer Infrared Nearby Galaxies Survey. Thus, the environment of these translucent clouds is more efficient at producing rotationally excited H_2 per PAH-exciting photon than the disks of entire galaxies. Excitation analysis finds that the S(1) and S(2) emitting regions are warm (T ≳ 300 K), but comprise no more than 2% of the gas mass. We find that UV photons cannot be the sole source of excitation in these regions and suggest mechanical heating via shocks or turbulent dissipation as the dominant cause of the emission. The clouds are located on the outskirts of the Scorpius-Centaurus OB association and may be dissipating recent bursts of mechanical energy input from supernova explosions. We suggest that pockets of warm gas in diffuse or translucent clouds, integrated over the disks of galaxies, may represent a major source of all non-active galaxy H_2 emission

Radar studies of the planets

The radar measurements phase of the lunar studies involving reflectivity and topographic mapping of the visible lunar surface was ended in December 1972, but studies of the data and production of maps have continued. This work was supported by Manned Spacecraft Center, Houston. Topographic mapping of the equatorial regions of Mars has been carried out during the period of each opposition since that of 1967. The method comprised extended precise traveling time measurements to a small area centered on the subradar point. As measurements continued, planetary motions caused this point to sweep out extensive areas in both latitude and longitude permitting the development of a fairly extensive topographical map in the equatorial region. Radar observations of Mercury and Venus have also been made over the past few years. Refinements of planetary motions, reflectivity maps and determinations of rotation rates have resulted

1863-03-14 Francis P. Ingalls writes J.L. Parker, Esq. regarding lack of commissioned officers in Company H

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Comparative analysis of the growth and biological activity of a respiratory and atheroma isolate of reveals strain-dependent differences in inflammatory activity and innate immune evasion

En el año 2010, como contraparte de los festejos del centenario de la Revolución mexicana, el poeta Jorge Esquinca invitó a treinta y cuatro poetas a participar en una antología titulada País de sombra y fuego. La relevancia de este ejercicio poético proviene de la pregunta que lo estructura: ¿Existe todavía en el vocablo Patria un núcleo generador de significado?A través del análisis de estos poemas y de los tópicos que prevalecen en ellos, es posible conocer el doloroso México que perciben los poetas mexicanos y la forma en que la poesía mexicana contemporánea del siglo XXI lo nombra.In 2010, as a counterpart to the festivities related to the 100th anniversary of the Mexican Revolution, the poet Jorge Esquinica invited thirty-four poets to participate in an anthology titled País de sombra y fuego. The relevance of this poetic exercise stems from the very question which gives it structure. Is the word Motherland still relevant in today's world?Through an analysis of these poems and the themes that prevail in them, it is possible to discover how these anthologized Mexican poets view their country nowadays and how they address its main issues.A l’any 2010, com a contrapart dels festejos del centenari de la Revolució mexicana, el poeta Jorge Esquinca va convidar trenta-quatre poetes a participar en una antologia titulada País de sombra y fuego. La rellevància d’aquest exercici poètic prové de la pregunta que l’estructura: existeix encara en el terme Pàtria un nucli generador de significat? A través de l’anàlisi d’aquests poemes i dels tòpics que prevalen en ells, és possible conèixer el dolorós Mèxic que perceben els poetes mexicans i la forma en què la poesia mexicana contamporània del segle XXI ho nombra