Complementary transcriptomic, lipidomic, and targeted functional genetic analyses in cultured Drosophila cells highlight the role of glycerophospholipid metabolism in Flock House virus RNA replication

Abstract Background Cellular membranes are crucial host components utilized by positive-strand RNA viruses for replication of their genomes. Published studies have suggested that the synthesis and distribution of membrane lipids are particularly important for the assembly and function of positive-strand RNA virus replication complexes. However, the impact of specific lipid metabolism pathways in this process have not been well defined, nor have potential changes in lipid expression associated with positive-strand RNA virus replication been examined in detail. Results In this study we used parallel and complementary global and targeted approaches to examine the impact of lipid metabolism on the replication of the well-studied model alphanodavirus Flock House virus (FHV). We found that FHV RNA replication in cultured Drosophila S2 cells stimulated the transcriptional upregulation of several lipid metabolism genes, and was also associated with increased phosphatidylcholine accumulation with preferential increases in lipid molecules with longer and unsaturated acyl chains. Furthermore, targeted RNA interference-mediated downregulation of candidate glycerophospholipid metabolism genes revealed a functional role of several genes in virus replication. In particular, we found that downregulation of Cct1 or Cct2, which encode essential enzymes for phosphatidylcholine biosynthesis, suppressed FHV RNA replication. Conclusion These results indicate that glycerophospholipid metabolism, and in particular phosphatidylcholine biosynthesis, plays an important role in FHV RNA replication. Furthermore, they provide a framework in which to further explore the impact of specific steps in lipid metabolism on FHV replication, and potentially identify novel cellular targets for the development of drugs to inhibit positive-strand RNA viruses.http://deepblue.lib.umich.edu/bitstream/2027.42/78268/1/1471-2164-11-183.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78268/2/1471-2164-11-183-S3.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78268/3/1471-2164-11-183-S2.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78268/4/1471-2164-11-183.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78268/5/1471-2164-11-183-S4.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78268/6/1471-2164-11-183-S1.XLSPeer Reviewe

Analysis of Linsker's simulations of Hebbian rules

Linsker has reported the development of center-surround receptive fields and oriented receptive fields in simulations of a Hebb-type equation in a linear network. The dynamics of the learning rule are analyzed in terms of the eigenvectors of the covariance matrix of cell activities. Analytic and computational results for Linsker's covariance matrices, and some general theorems, lead to an explanation of the emergence of center-surround and certain oriented structures. We estimate criteria for the parameter regime in which center-surround structures emerge

2-D Compass Codes

The compass model on a square lattice provides a natural template for building subsystem stabilizer codes. The surface code and the Bacon-Shor code represent two extremes of possible codes depending on how many gauge qubits are fixed. We explore threshold behavior in this broad class of local codes by trading locality for asymmetry and gauge degrees of freedom for stabilizer syndrome information. We analyze these codes with asymmetric and spatially inhomogeneous Pauli noise in the code capacity and phenomenological models. In these idealized settings, we observe considerably higher thresholds against asymmetric noise. At the circuit level, these codes inherit the bare-ancilla fault-tolerance of the Bacon-Shor code.Comment: 10 pages, 7 figures, added discussion on fault-toleranc

"Macroeconomic Market Incentive Plans: History and Theoretical Rationale"

This paper explores the contemporary debate among economists on the means to move the economy toward high employment without inflation-beyond the traditional instruments of monetary and fiscal policy. The authors pay particular attention to the Market Anti-Inflation Plan (MAP), submitted by Lerner and Colander in 1980. The reasons economists have searched for alternative measures relate to the problems associated with wage and price controls. MAP is an anti-inflation plan that allows relative prices to adjust: The scheme increases costs to firms that raise prices, and contains an added incentive to lower prices. Since MAP is designed to fight macroeconomic inflation by changing the incentives of individual price setters, the relationship between microeconomic behavior and macroeconomic outcomes must be addressed. The theoretical justification for MAP is that there is a macroeconomic externality, and MAP can mitigate the ramifications of the externality. However, efforts to more clearly define the nature of this externality require a better understanding of transaction costs. Consequently, there will be the need for a mechanism to integrate such costs into microeconomic and macroeconomic models.

Socio-demographic constraints to travel behavior

Purpose &ndash; This study aims to ascertain the effect of socio-demographic constraints on dimension of travel choice. This study also seeks to derive personal ecological explanations for variation in travel preference, travel intention and travel choice behavior of a wide range of destinations. Design/methodology/approach &ndash; A large representative sample of 49,105 Australian respondents is utilized. Binary logistic regression is used to determine the impact of constraint variables. Findings &ndash; Age, income and life stage have significant differential and interactive effects on travel behavior. Socio-demographic variables act in different ways to constrain/free different types of travel behavior. However there are significant levels of travel by even the most constrained groups as well as significant amounts of non-travel by the least constrained sectors of our society. These impacts are country specific. Research limitations/implications &ndash; The travel motivations of constraint groups need to be considered to order better understand travel behavior. Investigation of psychological and ecological facilitators and constraints to travel is needed. Practical implications &ndash; This information is most useful for market segmentation and the development of constraint group destination marketing plans. Managers can use utilize such results to minimize the barriers to travel by particular groups. Originality/value &ndash; This paper utilizes a large database to provide insights into the personal ecological constraints to travel.<br /

The Role of Constraints in Hebbian Learning

Models of unsupervised, correlation-based (Hebbian) synaptic plasticity are typically unstable: either all synapses grow until each reaches the maximum allowed strength, or all synapses decay to zero strength. A common method of avoiding these outcomes is to use a constraint that conserves or limits the total synaptic strength over a cell. We study the dynamic effects of such constraints. Two methods of enforcing a constraint are distinguished, multiplicative and subtractive. For otherwise linear learning rules, multiplicative enforcement of a constraint results in dynamics that converge to the principal eigenvector of the operator determining unconstrained synaptic development. Subtractive enforcement, in contrast, typically leads to a final state in which almost all synaptic strengths reach either the maximum or minimum allowed value. This final state is often dominated by weight configurations other than the principal eigenvector of the unconstrained operator. Multiplicative enforcement yields a “graded” receptive field in which most mutually correlated inputs are represented, whereas subtractive enforcement yields a receptive field that is “sharpened” to a subset of maximally correlated inputs. If two equivalent input populations (e.g., two eyes) innervate a common target, multiplicative enforcement prevents their segregation (ocular dominance segregation) when the two populations are weakly correlated; whereas subtractive enforcement allows segregation under these circumstances. These results may be used to understand constraints both over output cells and over input cells. A variety of rules that can implement constrained dynamics are discussed