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

Homoeostasis between the GTPase Spg1p and its GAP in the regulation of cytokinesis in S. pombe

Cytokinesis in Schizosaccharomyces pombe begins at mitotic entry, when the site of division is defined by formation of the contractile acto-myosin ring (CAR) at the cell cortex. Contraction of the CAR and formation of the division septum are triggered at the end of mitosis by septation initiation network (SIN) proteins associated with the spindle pole body (SPB). SIN signalling requires activation of the GTPase Spg1p, which is regulated by the bipartite GTPase-activating protein (GAP) Byr4p-Cdc16p. We show that, for Spg1p to associate with the SPB, it must be bound to its GAP or to its mitotic effector, the protein kinase Cdc7p. Analysis of the GAP proteins reveals that the steady-state level of Byr4p reflects that of Spg1p. Furthermore, if the interaction of Byr4p with Spg1p is compromised, the level of Byr4p decreases dramatically. The adaptation of the level of Byr4p to that of Spg1p requires the presence of Cdc16p and is mediated by proteasome-dependent destruction. It requires neither association with the SPB nor an active SIN. We propose a mechanism that limits the amount of the Byr4p-Cdc16p GAP to the amount required to inhibit Spg1p signalling

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

The Schizosaccharomyces pombe septation initiation network (SIN) is required for spore formation in meiosis

When nutrients are abundant, S. pombe cells grow as rods, dividing by fission after formation of a medially placed cell wall or division septum. Septum formation is triggered by a group of proteins, called the septation initiation network or SIN, that trigger contraction of the acto-myosin contractile ring at the end of mitosis. Ectopic activation of the SIN can uncouple septum formation from other cell-cycle events, whereas loss of SIN signalling gives rise to multinucleated cells due to the failure of cytokinesis. When starved, S. pombe cells of opposite mating types fuse to form a diploid zygote that undergoes meiosis and produces four spores. No septa or contractile rings are formed during meiosis. In this study, we have investigated the role of the SIN in meiosis. Our data show that, whereas the meiotic divisions appear normal, SIN mutants cannot form spores. Forespore membrane formation is initiated, but the nuclei are not encapsulated properly. The SIN proteins localise to the spindle pole body in meiosis. The protein kinases Sid1p and Cdc7p do not associate with the spindle pole body until meiosis II, when forespore membrane deposition begins. These data indicate a role for the SIN in regulating spore formation during meiosis

Remaking Africa's informal economies: youth, entrepreneurship and the promise of inclusion at the bottom of the pyramid

In recent years, the quest for 'inclusive markets' that incorporate Africa's youth has become a key focus of national and international development efforts, with so-called bottom of the pyramid (BoP) initiatives increasingly seen as a way to draw the continent's poor into new networks of global capitalism. SSA has become a fertile frontier for such systems, as capital sets its sights on the continents vast 'under-served' informal economies, harnessing the entrepreneurial mettle of youth to create new markets for a range of products, from solar lanterns and shampoo to cook stoves and sanitary pads. Drawing on ethnographic research with youth entrepreneurs, we trace the prcesses of individual and collective 'transformation' that the mission of (self-) empowerment through entrepreneurship seeks to bring about. We argue that, while such systems are meant to bring those below the poverty line above it, the 'line' is reified and reinforced through a range of discursive and strategic practices that actively construct and embed distinctions between the past and the future, valuable and valueless, and the idle and productive in Africa's informal economies

Budding Yeast Dma Proteins Control Septin Dynamics and the Spindle Position Checkpoint by Promoting the Recruitment of the Elm1 Kinase to the Bud Neck

The first step towards cytokinesis in budding yeast is the assembly of a septin ring at the future site of bud emergence. Integrity of this ring is crucial for cytokinesis, proper spindle positioning, and the spindle position checkpoint (SPOC). This checkpoint delays mitotic exit and cytokinesis as long as the anaphase spindle does not properly align with the division axis. SPOC signalling requires the Kin4 protein kinase and the Kin4-regulating Elm1 kinase, which also controls septin dynamics. Here, we show that the two redundant ubiquitin-ligases Dma1 and Dma2 control septin dynamics and the SPOC by promoting the efficient recruitment of Elm1 to the bud neck. Indeed, dma1 dma2 mutant cells show reduced levels of Elm1 at the bud neck and Elm1-dependent activation of Kin4. Artificial recruitment of Elm1 to the bud neck of the same cells is sufficient to re-establish a normal septin ring, proper spindle positioning, and a proficient SPOC response in dma1 dma2 cells. Altogether, our data indicate that septin dynamics and SPOC function are intimately linked and support the idea that integrity of the bud neck is crucial for SPOC signalling

An Empirical Comparison of Consumer Innovation Adoption Models: Implications for Subsistence Marketplaces

So called “pro-poor” innovations may improve consumer wellbeing in subsistence marketplaces. However, there is little research that integrates the area with the vast literature on innovation adoption. Using a questionnaire where respondents were asked to provide their evaluations about a mobile banking innovation, this research fills this gap by providing empirical evidence of the applicability of existing innovation adoption models in subsistence marketplaces. The study was conducted in Bangladesh among a geographically dispersed sample. The data collected allowed an empirical comparison of models in a subsistence context. The research reveals the most useful models in this context to be the Value Based Adoption Model and the Consumer Acceptance of Technology model. In light of these findings and further examination of the model comparison results the research also shows that consumers in subsistence marketplaces are not just motivated by functionality and economic needs. If organizations cannot enhance the hedonic attributes of a pro-poor innovation, and reduce the internal/external constraints related to adoption of that pro-poor innovation, then adoption intention by consumers will be lower

Hidden inequalities amongst the international workforce

This chapter focuses on low status expatriates who have been largely ‘hidden’ from managerial scholarship. They are ‘hidden’ because they are ignored by the migrant literature which looks at people trying to remain in their new society and gain citizenship; and ignored by the expatriation literature which is mainly concerned with high-status ‘top’ talent. These hidden expatriates are typically maids, drivers, security guards, and construction workers - low status and low paid, unable to obtain citizenship, and liable to be sent home, unemployed, at the whim of their employer. If we, as scholars, are to contribute to the betterment of society by elevating the health and well-being of those who live in it, then we must recognise the existence of and address the management issues and concerns of those at the ‘bottom of the pyramid’. We use Organisational Justice theory and draw on examples from Turkey, Singapore and the Middle East to examine the position, the concerns, and the issues of such workers and their often-unequal place in the workforce

Cytokinesis: Closure resets your SIN

A new study of fission yeast cell division has revealed a coupling between cytoplasmic partitioning and the turning-off of cytokinesis signalling that may be mediated by asymmetric protein distribution