Plakophilin-3 Is Required for Late Embryonic Amphibian Development, Exhibiting Roles in Ectodermal and Neural Tissues

The p120-catenin family has undergone a significant expansion during the evolution of vertebrates, resulting in varied functions that have yet to be discerned or fully characterized. Likewise, members of the plakophilins, a related catenin subfamily, are found throughout the cell with little known about their functions outside the desmosomal plaque. While the plakophilin-3 (Pkp3) knockout mouse resulted in skin defects, we find larger, including lethal effects following its depletion in Xenopus. Pkp3, unlike some other characterized catenins in amphibians, does not have significant maternal deposits of mRNA. However, during embryogenesis, two Pkp3 protein products whose temporal expression is partially complimentary become expressed. Only the smaller of these products is found in adult Xenopus tissues, with an expression pattern exhibiting distinctions as well as overlaps with those observed in mammalian studies. We determined that Xenopus Pkp3 depletion causes a skin fragility phenotype in keeping with the mouse knockout, but more novel, Xenopus tailbud embryos are hyposensitive to touch even in embryos lacking outward discernable phenotypes, and we additionally resolved disruptions in certain peripheral neural structures, altered establishment and migration of neural crest, and defects in ectodermal multiciliated cells. The use of two distinct morpholinos, as well as rescue approaches, indicated the specificity of these effects. Our results point to the requirement of Pkp3 in amphibian embryogenesis, with functional roles in a number of tissue types

Regulatory sites for splicing in human basal ganglia are enriched for disease-relevant information

Genome-wide association studies have generated an increasing number of common genetic variants associated with neurological and psychiatric disease risk. An improved understanding of the genetic control of gene expression in human brain is vital considering this is the likely modus operandum for many causal variants. However, human brain sampling complexities limit the explanatory power of brain-related expression quantitative trait loci (eQTL) and allele-specific expression (ASE) signals. We address this, using paired genomic and transcriptomic data from putamen and substantia nigra from 117 human brains, interrogating regulation at different RNA processing stages and uncovering novel transcripts. We identify disease-relevant regulatory loci, find that splicing eQTLs are enriched for regulatory information of neuron-specific genes, that ASEs provide cell-specific regulatory information with evidence for cellular specificity, and that incomplete annotation of the brain transcriptome limits interpretation of risk loci for neuropsychiatric disease. This resource of regulatory data is accessible through our web server, http://braineacv2.inf.um.es/

Convergence of Powers of a Fuzzy Matrix

Often, and certainly in the early stages of a design, the knowledge about delays is imprecise. Stochastic programming is not an adequate means to account for this imprecision. Not only is a probability distribution seldom a correct translation of the designer's delay knowledge, it also leads to inefficient algorithms. In this paper possibilistic programming is proposed for handling the retiming problem where delays are modelled as (triangular) possibilistic numbers. Beside the capability of optimizing the most possible clock cycle time and generating its possibility distribution, it allows for trade-offs between reducing clock cycle time and chances for obtaining worse solutions. It is shown that the computational complexity is the same as for retiming with exact circuit delays. Introduction Most synthesis methods use estimated values for the coefficients of the constraints and cost functions guiding the design. Especially in the early design phases these estimates may be far from th..

Moldable pellet based on a combination of natural fibers and thermoplastic polymer

A moldable material comprising a core of sized natural fibers (1), forming a continuous natural fiber strand sheathed in a sheath of thermoplastic (10), or optionally, may be chopped into pellets (14). Also disclosed are sized natural fiber products, natural fiber-containing products, and processes for making natural-fiber containing products and fiber-reinforced composite articles

FAFNIR: Strategy and Risk Reduction in Accelerator Driven Neutron Sources for Fusion Materials Irradiation Data FAFNIR: Strategy and Risk Reduction in Accelerator Driven Neutron Sources for Fusion Materials Irradiation Data FAFNIR: strategy and risk reduc

Abstract-The need to populate the fusion materials engineering data base has long been recognized, the IFMIF facility being the present proposed neutron source for this purpose. Re-evaluation of the regulatory approach for the EU proposed DEMO device shows that the specification of the neutron source can be reduced with respect to IFMIF, allowing lower risk technology solutions to be considered. The justification for this approach is presented and a description of a proposed facility, FAFNIR, is presented with more detailed discussion of the accelerator and target designs