Using the Viable Systems Model to Structure a System Dynamics Mapping and Modeling Project for the Australian Taxation Office

This paper is a case study of a major System Dynamics (SD) intervention in policy design in the Australian Taxation Office. The project, which lasted two years, tested a number of hypotheses regarding the application of Stafford Beer's Viable Systems Model (VSM) to the structure and process of the project. The paper reports that the success of the VSM within the ATO was qualified by political changes in the external environment.     

Growth mechanisms of Ag and Cu nanodendrites via Galvanic replacement reactions

Dendritic silver and copper crystals were produced via Galvanic replacement reactions on zinc and aluminum plates, respectively. The growth orientations of these metals were determined using electron microscopy. The results showed that a fast crystal growth associated with a high concentration of metal cations led to kinetically controlled growth along the <112> axes of the cubic close-packed structures. However, a slow growth rate resulted in thermodynamically controlled growth along the ...     

The genome sequence of the rice blast fungus Magnaporthe grisea

Magnaporthe grisea is the most destructive pathogen of rice worldwide and the principal model organism for elucidating the molecular basis of fungal disease of plants. Here, we report the draft sequence of the M. grisea genome. Analysis of the gene set provides an insight into the adaptations required by a fungus to cause disease. The genome encodes a large and diverse set of secreted proteins, including those defined by unusual carbohydrate-binding domains. This fungus also possesses an expanded family of G-protein-coupled receptors, several new virulence-associated genes and large suites of enzymes involved in secondary metabolism. Consistent with a role in fungal pathogenesis, the expression of several of these genes is upregulated during the early stages of infection-related development. The M. grisea genome has been subject to invasion and proliferation of active transposable elements, reflecting the clonal nature of this fungus imposed by widespread rice cultivation.     

A paleoecologic perspective on past plant invasions in Yellowstone

The role of climate and natural disturbance in the past provides a context for understanding present and future changes in biota. The vegetation history of the Yellowstone region, like that of North America as a whole, is largely one of plant invasions and extinctions in response to changes in climate and environment. When Holocene plant migrations are examined on multiple spatial and temporal scales, several generalities are apparent. First, at a continental and regional scale, plant migration patterns followed the direction of climate change, whereas at local scales plant colonization was governed by site-specific conditions and possibly by biotic interactions. Second, species were individualistic in their response to climate change, and, as their ranges shifted across the landscape, existing communities were dismantled and new ones were formed. Individual species met little resistance from existing communities. Third, rates of species invasion were astonishingly rapid, suggesting that rare long-distance dispersal events were critical. Fourth, fire during periods of climate change was an important catalyst in allowing the invasion of new species, but it is unlikely that a single fire event triggered irreversible vegetation change. Regional climate and biotic changes in response to projected increases in atmospheric CO 2 in the next century suggest an even more complex picture than in the past. Model simulations portray changes in temperature and precipitation in the Yellowstone region that have not occurred in the last 20,000 years. Likewise, projected changes in species ranges, including latitudinal, longitudinal, and elevational shifts, require faster rates than anything observed in the fossil record. Increased fire occurrence may help maintain some native taxa but promote the decline of others. Thus, future conditions are likely to create evermore opportunities for exotic species to invade and establish within the Yellowstone region.     

Nonmuscle myosin-2: mix and match

Members of the nonmuscle myosin-2 (NM-2) family of actin-based molecular motors catalyze the conversion of chemical energy into directed movement and force thereby acting as central regulatory components of the eukaryotic cytoskeleton. By cyclically interacting with adenosine triphosphate and F-actin, NM-2 isoforms promote cytoskeletal force generation in established cellular processes like cell migration, shape changes, adhesion dynamics, endo- and exo-cytosis, and cytokinesis. Novel functions of the NM-2 family members in autophagy and viral infection are emerging, making NM-2 isoforms regulators of nearly all cellular processes that require the spatiotemporal organization of cytoskeletal scaffolding. Here, we assess current views about the role of NM-2 isoforms in these activities including the tight regulation of NM-2 assembly and activation through phosphorylation and how NM-2-mediated changes in cytoskeletal dynamics and mechanics affect cell physiological functions in health and disease.     

Opposing effects on the cell cycle of T lymphocytes by Fbxo7 via Cdk6 and p27

G₁ phase cell cycle proteins, such as cyclin-dependent kinase 6 (Cdk6) and its activating partners, the D-type cyclins, are important regulators of T-cell development and function. An F-box protein, called F-box only protein 7 (Fbxo7), acts as a cell cycle regulator by enhancing cyclin D-Cdk6 complex formation and stabilising levels of p27, a cyclin-dependent kinase inhibitor. We generated a murine model of reduced Fbxo7 expression to test its physiological role in multiple tissues and found that these mice displayed a pronounced thymic hypoplasia. Further analysis revealed that Fbxo7 differentially affected proliferation and apoptosis of thymocytes at various stages of differentiation in the thymus and also mature T-cell function and proliferation in the periphery. Paradoxically, Fbxo7-deficient immature thymocytes failed to undergo expansion in the thymus due to a lack of Cdk6 activity, while mature T cells showed enhanced proliferative capacity upon T-cell receptor engagement due to reduced p27 levels. Our studies reveal differential cell cycle regulation by Fbxo7 at different stages in T-cell development.     

Disruption of calcitonin gene-related peptide signaling accelerates muscle denervation and dampens cytotoxic neuroinflammation in SOD1 mutant mice

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease. Neuronal vacuolization and glial activation are pathologic hallmarks in the superoxide dismutase 1 (SOD1) mouse model of ALS. Previously, we found the neuropeptide calcitonin gene-related peptide (CGRP) associated with vacuolization and astrogliosis in the spinal cord of these mice. We now show that CGRP abundance positively correlated with the severity of astrogliosis, but not vacuolization, in several motor and non-motor areas throughout the brain. SOD1 mice harboring a genetic depletion of the βCGRP isoform showed reduced CGRP immunoreactivity associated with vacuolization, while motor functions, body weight, survival, and astrogliosis were not altered. When CGRP signaling was completely disrupted through genetic depletion of the CGRP receptor component, receptor activity-modifying protein 1 (RAMP1), hind limb muscle denervation, and loss of muscle performance were accelerated, while body weight and survival were not affected. Dampened neuroinflammation, i.e., reduced levels of astrogliosis in the brain stem already in the pre-symptomatic disease stage, and reduced microgliosis and lymphocyte infiltrations during the late disease phase were additional neuropathology features in these mice. On the molecular level, mRNA expression levels of brain-derived neurotrophic factor (BDNF) and those of the anti-inflammatory cytokine interleukin 6 (IL-6) were elevated, while those of several pro-inflammatory cytokines found reduced in the brain stem of RAMP1-deficient SOD1 mice at disease end stage. Our results thus identify an important, possibly dual role of CGRP in ALS pathogenesis.