Sce3, a suppressor of the Schizosaccharomyces pombe septation mutant cdc11, encodes a putative RNA-binding protein

In the fission yeast Schizosaccharomyces pombe, the cdc11 gene is required for the initiation of septum formation at the end of mitosis. The sce3 gene was cloned as a multi-copy suppressor of the heat-sensitive mutant cdc11-136. When over-expressed, it rescues all mutants of cdc11 and also a heat-sensitive allele of cdc14, but not the cdc14 null mutant. Deletion shows that sce3 is not essential for cell proliferation. It encodes a putative RNA-binding protein which shows homology to human eIF4B. Immunolocalisation indicates that Sce3p is located predominantly in the cytoplasm. Elevated expression of sce3 increases the steady-state level of cdc14 mRNA. Possible mechanisms of its action are discusse

An Extended, Boolean Model of the Septation Initiation Network in S.Pombe Provides Insights into Its Regulation.

Cytokinesis in fission yeast is controlled by the Septation Initiation Network (SIN), a protein kinase signaling network using the spindle pole body as scaffold. In order to describe the qualitative behavior of the system and predict unknown mutant behaviors we decided to adopt a Boolean modeling approach. In this paper, we report the construction of an extended, Boolean model of the SIN, comprising most SIN components and regulators as individual, experimentally testable nodes. The model uses CDK activity levels as control nodes for the simulation of SIN related events in different stages of the cell cycle. The model was optimized using single knock-out experiments of known phenotypic effect as a training set, and was able to correctly predict a double knock-out test set. Moreover, the model has made in silico predictions that have been validated in vivo, providing new insights into the regulation and hierarchical organization of the SIN

Analysis of S. pombe SIN protein association to the SPB reveals two genetically separable states of the SIN.

The Schizosaccharomyces pombe septation initiation network (SIN) regulates cytokinesis, and asymmetric association of SIN proteins with the mitotic spindle pole bodies (SPBs) is important for its regulation. Here, we have used semi-automated image analysis to study SIN proteins in large numbers of wild-type and mutant cells. Our principal conclusions are: first, that the association of Cdc7p with the SPBs in early mitosis is frequently asymmetric, with a bias in favour of the new SPB; second, that the early association of Cdc7p-GFP to the SPB depends on Plo1p but not Spg1p, and is unaffected by mutations that influence its asymmetry in anaphase; third, that Cdc7p asymmetry in anaphase B is delayed by Pom1p and by activation of the spindle assembly checkpoint, and is promoted by Rad24p; and fourth, that the length of the spindle, expressed as a fraction of the length of the cell, at which Cdc7p becomes asymmetric is similar in cells dividing at different sizes. These data reveal that multiple regulatory mechanisms control the SIN in mitosis and lead us to propose a two-state model to describe the SIN

Boolean network model predicts cell cycle sequence of fission yeast

A Boolean network model of the cell-cycle regulatory network of fission yeast (Schizosaccharomyces Pombe) is constructed solely on the basis of the known biochemical interaction topology. Simulating the model in the computer, faithfully reproduces the known sequence of regulatory activity patterns along the cell cycle of the living cell. Contrary to existing differential equation models, no parameters enter the model except the structure of the regulatory circuitry. The dynamical properties of the model indicate that the biological dynamical sequence is robustly implemented in the regulatory network, with the biological stationary state G1 corresponding to the dominant attractor in state space, and with the biological regulatory sequence being a strongly attractive trajectory. Comparing the fission yeast cell-cycle model to a similar model of the corresponding network in S. cerevisiae, a remarkable difference in circuitry, as well as dynamics is observed. While the latter operates in a strongly damped mode, driven by external excitation, the S. pombe network represents an auto-excited system with external damping.Comment: 10 pages, 3 figure

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Concentration and dispersion of primary care physicians and implications for access to care in Cook County, Illinois: 2000-2008

The health care system in the United States has experienced drastic changes in the recent past. Continuously growing pressures to control health care costs and the increasing corporatization of health care are changing physician decisions about how and where to provide medical care. Physicians are increasingly drawn to medical office complexes, group practices, and hospital-owned practices, resulting in a shifting landscape of physician services. The goal of this research is to analyze the changing spatial distribution and clustering of primary care physicians in Cook County, Illinois from 2000 to 2008. Using data from the American Medical Association's Physicians Master File for 2000 and 2008, primary care physician locations are geocoded, mapped, and analyzed to evaluate change over time. Spatial analysis methods such as kernel density mapping and the L-function are used to analyze changes in the spatial clustering and dispersion of primary care physician locations. Geographically weighted regression models are then used to compare primary care physician supply to the socioeconomic demographics of census tracts in Cook County. Results indicate that spatial clustering of primary care physicians increased over the eight year period. Linear regression analyses show positive relationships between primary care physician-to-population ratios and median income and percentage of the work force employed. However, geographically weighted regression shows that these relationships vary throughout the county. Implications for access to care and possible policy changes to increase primary care physician spatial accessibility are discussed

Dma1-dependent degradation of SIN proteins during meiosis in Schizosaccharomyces pombe

The Schizosaccharomyces pombe septation initiation network (SIN) is required for cytokinesis during vegetative growth and for spore formation during meiosis. Regulation of the SIN during mitosis has been studied extensively, but less is known about its meiotic regulation. Here, we show that several aspects of SIN regulation differ between mitosis and meiosis. First, the presence of GTP-bound Spg1p is not the main determinant of the timing of Cdc7p and Sid1p association with the spindle pole body (SPB) during meiosis. Second, the localisation dependencies of SIN proteins differ from those in mitotic cells, suggesting a modified functional organisation of the SIN during meiosis. Third, there is stage-specific degradation of SIN components in meiosis; Byr4p is degraded after meiosis I, whereas the degradation of Cdc7p, Cdc11p and Sid4p occurs after the second meiotic division and depends upon the ubiquitin ligase Dma1p. Finally, Dma1p-dependent degradation is not restricted to the SIN, as we show that Dma1p is needed for the degradation of Mcp6p (also known as Hrs1p) during meiosis I. Taken together, these data suggest that stage-specific targeted proteolysis plays an important role in regulating meiotic progression

Dma1-dependent degradation of Septation Initiation Network proteins during meiosis in<i>Schizosaccharomyces pombe</i>

The Schizosaccharomyces pombe septation initiation network (SIN) is required for cytokinesis during vegetative growth and spore formation during meiosis. Regulation of the SIN during mitosis has been studied extensively, but less is known about its meiotic regulation. Here, we show that several aspects of the SIN regulation differ between mitosis and meiosis. First, the presence of GTP-bound spg1p is not the main determinant of the timing of cdc7p and sid1p association with the SPB during meiosis. Second, the localisation dependencies of SIN proteins differ from those in mitotic cells, suggesting a modified functional organisation of the SIN during meiosis. Third, there is stage-specific degradation of SIN components in meiosis; byr4p is degraded after meiosis I, while the degradation of cdc7p, cdc11p and sid4p occurs after the second meiotic division and depends upon the ubiquitin ligase dma1p. Finally, dma1p-dependent degradation is not restricted to the SIN, for we show that dma1p is needed for the degradation of mcp6p/hrs1p in meiosis I. Together, these data suggest that stage-specific targetted proteolysis will play an important role in regulating meiotic progression.</jats:p