Forward and Backward Modelling: From Single Cells to Neural Population and Back

Some aspects of forward and backward neural modelling are discussed, showing, that the neural mass models may provide a “golden midway” between the detailed conductance based neuron models and the oversimplified models, dealing with the input–output transformations only. Our analysis combines historical perspectives and recent developments concerning neural mass models as a third option for modelling large neural populations and inclusion of detailed anatomical data into them. The current source density analysis and the geometrical assumption behind the different methods, as an inverse modelling tool for determination of the sources of the local field potential is discussed, with special attention to the recent results about source localization on single neurons. These new applications may pave the way to the emergence of a new field of micro-electric imaging

Recognition of Emerging Technology Trends. Class-selective study of citations in the U.S. Patent Citation Network

By adopting a citation-based recursive ranking method for patents the evolution of new fields of technology can be traced. Specifically, it is demonstrated that the laser / inkjet printer technology emerged from the recombination of two existing technologies: sequential printing and static image production. The dynamics of the citations coming from the different "precursor" classes illuminates the mechanism of the emergence of new fields and give the possibility to make predictions about future technological development. For the patent network the optimal value of the PageRank damping factor is close to 0.5; the application of d=0.85 leads to unacceptable ranking results.Comment: 8 pages, 2 tables, 1 figure , (accepted). in Scientometrics 201

Hierarchically Organized Minority Games

In this paper a hierarchical extension of the Minority Game is defined and studied. Numerical simulations show a special type of emergent global behavior between separated parts of the hierarchical structure, connected only through a normalized mean field quantity.Comment: 8 page

Advantages and limitations of different p62-based assays for estimating autophagic activity in Drosophila.

Levels of the selective autophagy substrate p62 have been established in recent years as a specific readout for basal autophagic activity. Here we compared different experimental approaches for using this assay in Drosophila larvae. Similar to the more commonly used western blots, quantifying p62 dots in immunostained fat body cells of L3 stage larvae detected a strong accumulation of endogenous p62 aggregates in null mutants for Atg genes and S6K. Importantly, genes whose mutation or silencing results in early stage lethality can only be analyzed by microscopy using clonal analysis. The loss of numerous general housekeeping genes show a phenotype in large-scale screens including autophagy, and the p62 assay was potentially suitable for distinguishing bona fide autophagy regulators from silencing of a DNA polymerase subunit or a ribosomal gene that likely has a non-specific effect on autophagy. p62 accumulation upon RNAi silencing of known autophagy regulators was dependent on the duration of the knockdown effect, unlike in the case of starvation-induced autophagy. The endogenous p62 assay was more sensitive than a constitutively overexpressed p62-GFP reporter, which showed self-aggregation and large-scale accumulation even in control cells. We recommend western blots for following the conversion of overexpressed p62-GFP reporters to estimate autophagic activity if sample collection from mutant larvae or adults is possible. In addition, we also showed that overexpressed p62 or Atg8 reporters can strongly influence the phenotypes of each other, potentially giving rise to false or contradicting results. Overexpressed p62 aggregates also incorporated Atg8 reporter molecules that might lead to a wrong conclusion of strongly enhanced autophagy, whereas expression of an Atg8 reporter transgene rescued the inhibitory effect of a dominant-negative Atg4 mutant on basal and starvation-induced autophagy

Loss of the starvation-induced gene Rack1 leads to glycogen deficiency and impaired autophagic responses in Drosophila

Autophagy delivers cytoplasmic material for lysosomal degradation in eukaryotic cells. Starvation induces high levels of autophagy to promote survival in the lack of nutrients. We compared genome-wide transcriptional profiles of fed and starved control, autophagy-deficient Atg7 and Atg1 null mutant Drosophila larvae to search for novel regulators of autophagy. Genes involved in catabolic processes including autophagy were transcriptionally upregulated in all cases. We also detected repression of genes involved in DNA replication in autophagy mutants compared with control animals. The expression of Rack1 (receptor of activated protein kinase C 1) increased 4.1- to 5.5-fold during nutrient deprivation in all three genotypes. The scaffold protein Rack1 plays a role in a wide range of processes including translation, cell adhesion and migration, cell survival and cancer. Loss of Rack1 led to attenuated autophagic response to starvation, and glycogen stores were decreased 11.8-fold in Rack1 mutant cells. Endogenous Rack1 partially colocalized with GFP-Atg8a and early autophagic structures on the ultrastructural level, suggesting its involvement in autophagosome formation. Endogenous Rack1 also showed a high degree of colocalization with glycogen particles in the larval fat body, and with Shaggy, the Drosophila homolog of glycogen synthase kinase 3B (GSK-3B). Our results, for the first time, demonstrated the fundamental role of Rack1 in autophagy and glycogen synthesis