Global optimization techniques learning and more science details? The mitotic spindle assembly checkpoint (MSAC) is an important regulatory mechanism of the cell cycle, ensuring proper chromosome segregation in mitosis. It delays the transition to anaphase until all chromosomes are properly attached to the mitotic spindle by emitting a diffusible “wait anaphase”-signal from unattached kinetochores. Current models of the checkpoint disregard important spatial properties like localization, diffusion and realistic numbers of kinetochores. To allow for in silico studies of the dynamics of these models in a more realistic environment, we introduce a mathematical framework for quasi-spatial simulation of localized biochemical processes that are typically observed during checkpoint activation and maintenance.
Diabetes is a major and growing public health challenge which threatens to overwhelm medical services in the future. Type 2 diabetes confers significant morbidity and mortality, most notably with target organ damage to the eyes, kidneys, nerves and heart. The magnitude of cardiovascular risk associated with diabetes is best illustrated by its position as a coronary heart disease risk equivalent. Complications related to neuropathy are also vast, often working in concert with vascular abnormalities and resulting in serious clinical consequences such as foot ulceration. Increased understanding of the natural history of this disorder has generated the potential to intervene and halt pathological progression before overt disease ensues, after which point management becomes increasingly challenging. The concept of prediabetes as a formal diagnosis has begun to be translated from the research setting to clinical practice.
Budding yeast asymmetric cell division relies upon the precise coordination of spindle orientation and cell cycle progression. The spindle position checkpoint (SPOC) is a surveillance mechanism that prevents cells with misoriented spindles from exiting mitosis. The cortical kinase Kin4 acts near the top of this network. How Kin4 kinase activity is regulated and maintained in respect to spindle positional cues remains to be established. Here, we show that the bud neck–associated kinase Elm1 participates in Kin4 activation and SPOC signaling by phosphorylating a conserved residue within the activation loop of Kin4. Blocking Elm1 function abolishes Kin4 kinase activity in vivo and eliminates the SPOC response to spindle misalignment. These findings establish a novel function for Elm1 in the coordination of spindle positioning with cell cycle progression via its control of Kin4. Read extra information at Bifurcation analysis by Bashar Ibrahim.
Cycles are abundant in most kinds of networks, especially in biological ones. Here, we investigate their role in the evolution of a chemical reaction system from one self-sustaining composition of molecular species to another and their influence on the stability of these compositions. While it is accepted that, from a topological standpoint, they enhance network robustness, the consequence of cycles to the dynamics are not well understood. In a former study, we developed a necessary criterion for the existence of a fixed point, which is purely based on topological properties of the network. The structures of interest we identified were a generalization of closed autocatalytic sets, called chemical organizations.