The Function of Cortactin in the Clustering of Acetylcholine Receptors at the Vertebrate Neuromuscular Junction

Background: Postsynaptic enrichment of acetylcholine receptors (AChRs) at the vertebrate neuromuscular junction (NMJ) depends on the activation of the muscle receptor tyrosine MuSK by neural agrin. Agrin-stimulation of MuSK is known to initiate an intracellular signaling cascade that leads to the clustering of AChRs in an actin polymerization-dependent manner, but the molecular steps which link MuSK activation to AChR aggregation remain incompletely defined. Methodology/Principal Findings: In this study we used biochemical, cell biological and molecular assays to investigate a possible role in AChR clustering of cortactin, a protein which is a tyrosine kinase substrate and a regulator of F-actin assembly and which has also been previously localized at AChR clustering sites. We report that cortactin was co-enriched at AChR clusters in situ with its target the Arp2/3 complex, which is a key stimulator of actin polymerization in cells. Cortactin was further preferentially tyrosine phosphorylated at AChR clustering sites and treatment of myotubes with agrin significantly enhanced the tyrosine phosphorylation of cortactin. Importantly, forced expression in myotubes of a tyrosine phosphorylation-defective cortactin mutant (but not wild-type cortactin) suppressed agrin-dependent AChR clustering, as did the reduction of endogenous cortactin levels using RNA interference, and introduction of the mutant cortactin into muscle cells potently inhibited synaptic AChR aggregation in response to innervation. Conclusion: Our results suggest a novel function of phosphorylation-dependent cortactin signaling downstream fro

Unstable Inheritance of 45S rRNA Genes in Arabidopsis thaliana

The considerable genome size variation in Arabidopsis thaliana has been shown largely to be due to copy number variation (CNV) in 45S ribosomal RNA (rRNA) genes. Surprisingly, attempts to map this variation by means of genome-wide association studies (GWAS) failed to identify either of the two likely sources, namely the nucleolus organizer regions (NORs). Instead, GWAS implicated a trans-acting locus, as if rRNA gene CNV was a phenotype rather than a genotype. To explain these results, we investigated the inheritance and stability of rRNA gene copy number using the variety of genetic resources available in A. thaliana — F2 crosses, recombinant inbred lines, the multiparent advanced-generation inter-cross population, and mutation accumulation lines. Our results clearly show that rRNA gene CNV can be mapped to the NORs themselves, with both loci contributing equally to the variation. However, NOR size is unstably inherited, and dramatic copy number changes are visible already within tens of generations, which explains why it is not possible to map the NORs using GWAS. We did not find any evidence of trans-acting loci in crosses, which is also expected since changes due to such loci would take very many generations to manifest themselves. rRNA gene copy number is thus an interesting example of “missing heritability”—a trait that is heritable in pedigrees, but not in the general population

Use of the Pass-through Method to Solve Sound Radiation Problems of A Spherical Electro-elastic Source of Zero Order

In the article was solved the problem of radiation of a sound by the electroacoustic transducer which is executed in the form of a thin spherical cover, using a pass-through method. The outer and inner surfaces of the shell are completely electroded. The application of this method provides an opportunity to avoid inaccuracies that arise during the traditional formulation of boundary conditions for acoustic mechanical fields, the use of equivalent substitution schemes and the absence of boundary conditions for the electric field in general. Given methodology eliminates these shortcomings by applying conjugation conditions, taking into account the types of electroding of the surfaces of piezoceramic transducers, the introduction of boundary conditions for current and voltage. The results of the solution demonstrate the high capabilities of this pass-through method, in terms of taking into account the peculiarities of determining the characteristics of these fields, values and dependences of the main complex characteristics of the electroelastic transducer, and auxiliary material constants of the piezoelectric material. The proposed approach is relevant, because it allows to increase the reliability of modeling the operating conditions of acoustic transducers in the context of wave problems of acoustics. Aim is to enhance the range of performances and build algorithms solving problems of stationary mode hydroelectroelasticity sound radiation. The expected results are presented in terms of improving approaches to studying the features of the oscillatory process of the active elements of sound-emitting systems and the accompanying effects of the transformation of interconnected fields involved in the formation of the acoustic signal in the liqui

The Aquilegia genome: adaptive radiation and an extraordinarily polymorphic chromosome with a unique history

The columbine genus Aquilegia is a classic example of an adaptive radiation, involving a wide variety of pollinators and habitats. Here we present the genome assembly of A. coerulea "Goldsmith", complemented by high-coverage sequencing data from 10 wild species covering the world-wide distribution. Our analysis reveals extensive allele sharing among species, and sheds light on the complex process of radiation. We also present the remarkable discovery that the evolutionary history of an entire chromosome differed from that of the rest of the genome --- a phenomenon which we do not fully understand, but which highlights the need to consider chromosomes in an evolutionary context

1,135 Genomes Reveal the Global Pattern of Polymorphism in Arabidopsis thaliana

Arabidopsis thaliana serves as a model organism for the study of fundamental physiological, cellular, and molecular processes. It has also greatly advanced our understanding of intraspecific genome variation. We present a detailed map of variation in 1,135 high-quality re-sequenced natural inbred lines representing the native Eurasian and North African range and recently colonized North America. We identify relict populations that continue to inhabit ancestral habitats, primarily in the Iberian Peninsula. They have mixed with a lineage that has spread to northern latitudes from an unknown glacial refugium and is now found in a much broader spectrum of habitats. Insights into the history of the species and the fine-scale distribution of genetic diversity provide the basis for full exploitation of A. thaliana natural variation through integration of genomes and epigenomes with molecular and non-molecular phenotypes.Peer Reviewe

1,135 Genomes Reveal the Global Pattern of Polymorphism in Arabidopsis thaliana

Arabidopsis thaliana serves as a model organism for the study of fundamental physiological, cellular, and molecular processes. It has also greatly advanced our understanding of intraspecific genome variation. We present a detailed map of variation in 1,135 high-quality re-sequenced natural inbred lines representing the native Eurasian and North African range and recently colonized North America. We identify relict populations that continue to inhabit ancestral habitats, primarily in the Iberian Peninsula. They have mixed with a lineage that has spread to northern latitudes from an unknown glacial refugium and is now found in a much broader spectrum of habitats. Insights into the history of the species and the fine-scale distribution of genetic diversity provide the basis for full exploitation of A. thaliana natural variation through integration of genomes and epigenomes with molecular and non-molecular phenotypes