PABPN1 gene therapy for oculopharyngeal muscular dystrophy

International audienceOculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant, late-onset muscle disorder characterized by ptosis, swallowing difficulties, proximal limb weakness and nuclear aggregates in skeletal muscles. OPMD is caused by a trinucleotide repeat expansion in the PABPN1 gene that results in an N-terminal expanded polyalanine tract in polyA-binding protein nuclear 1 (PABPN1). Here we show that the treatment of a mouse model of OPMD with an adeno-associated virus-based gene therapy combining complete knockdown of endogenous PABPN1 and its replacement by a wild-type PABPN1 substantially reduces the amount of insoluble aggregates, decreases muscle fibrosis, reverts muscle strength to the level of healthy muscles and normalizes the muscle transcriptome. The efficacy of the combined treatment is further confirmed in cells derived from OPMD patients. These results pave the way towards a gene replacement approach for OPMD treatment

Bluenome: A novel developmental model of artificial morphogenesis

Abstract. The Bluenome Model of Development is introduced. The Bluenome model is a developmental model of Artificial Morphogenesis, inspired by biological development, instantiating a subset of two-dimensional Cellular Automata. The Bluenome model is cast as a general model, one which generates organizational topologies for finite sets of component types, assuming only local interactions between components. Its key feature is that there exists no relation between genotypic complexity and phenotypic complexity, implying its potential application in high-dimensional evolutionary problems. Additionally, genomes from the Bluenome Model are shown to be capable of re-development in differing environments, retaining many relevant phenotypic properties.

N.: Environment as a spatial constraint on the growth of structural form

We explore the use of the developmental environment as a spatial constraint on a model of Artificial Embryogeny, applied to the growth of structural forms. A Deva model is used to translate genotype to phenotype, allowing a Genetic Algorithm to evolve Plane Trusses. Genomes are expressed in one of several developmental environments, and selected using a fitness function favouring stability, height, and distribution of pressure. Positive results are found in nearly all cases, demonstrating that environment can be used as an effective spatial constraint on development. Further experiments take genomes evolved in some environment and transplant them into different environments, or re-grow them at different phenotypic sizes; It is shown that while some genomes are highly specialized for the particular environment in which they evolved, others may be re-used in a different context without significant re-design, retaining the majority of their original utility. This strengthens the notion that growth via Artificial Embryogeny can be resistant to perturbations in environment, and that good designs may be re-used in a variety of contexts

Modeling of Heat and Moisture Transfer in Wood in Finish Drying by the Energy of a Microwave Field

Гринчик Н. Н. Моделирование переноса тепла и влаги в древесине при завершении сушки энергией микроволнового поля / Н. Н. Гринчик, А. Л. Адамович, О. А. Кизина, У. М. Харма // Журнал технической физики и теплофизики - 2015. 88, № 1. - С. 35-41A physicomathematical model of heat and moisture transfer in drying materials in the region below the hygroscopicity limit, including also the heating by the energy of a microwave field, has been developed. The developed system of equations has been solved numerically for three cases of drying of a wooden plate: convective drying, drying by the microfield-field energy, and drying combining the above two methods, i.e., combined drying. Results of numerical calculations of the temperature, vapor-pressure, and moisture-content distributions in the cross section of the plate at different instants of time, and also of the change in the average moisture content and temperature in the process of drying, have been presented. The calculation results have been analyzed; conclusions on the differences and distinctive features of convective, microwave, and combined heating and drying have been drawn

Project CellNet: Evolving an Autonomous Pattern Recogniser

We describe the desire for a black box approach to pattern classification: a generic Autonomous Pattern Recognizer, which is capable of self-adapting to specific alphabets without human intervention. The CellNet software system is introduced, an evolutionary system that optimizes a set of pattern-recognizing agents relative to a provided set of features and a given pattern database. CellNet utilizes a new genetic operator designed to facilitate a canalization of development: Merger. CellNet utilizes our own set of arbitrarily chosen features, and is applied to the CEDAR Database of handwritten Latin characters, as well as to a database of handwritten Indian digits provided by CENPARMI. CellNet's cooperative co-evolutionary approach shows significant improvement over a more standard Genetic Algorithm, both in terms of efficiency and in nearly eliminating over-fitting (to the training set). Additionally, the binary classifiers autonomously evolved by CellNet return validation accuracies approaching 98% for both Latin and Indian digits, with no global changes to the system between the two trials