An Amphioxus Gli Gene Reveals Conservation of Midline Patterning and the Evolution of Hedgehog Signalling Diversity in Chordates

Background. Hedgehog signalling, interpreted in receiving cells by Gli transcription factors, plays a central role in the development of vertebrate and Drosphila embryos. Many aspects of the signalling pathway are conserved between these lineages, however vertebrates have diverged in at least one key aspect: they have evolved multiple Gli genes encoding functionally-distinct proteins, increasing the complexity of the hedgehog-dependent transcriptional response. Amphioxus is one of the closest living relatives of the vertebrates, having split from the vertebrate lineage prior to the widespread gene duplication prominent in early vertebrate evolution. Principal findings. We show that amphioxus has a single Gli gene, which is deployed in tissues adjacent to sources of hedgehog signalling derived from the midline and anterior endoderm. This shows the duplication and divergence of the Gli family, and hence the origin of vertebrate Gli functional diversity, was specific to the vertebrate lineage. However we also show that the single amphioxus Gli gene produces two distinct transcripts encoding different proteins. We utilise three tests of Gli function to examine the transcription regulatory capacities of these different proteins, demonstrating one has activating activity similar to Gli2, while the other acts as a weak repressor, similar to Gli3. Conclusions. These data show that the vertebrates and amphioxus have evolved functionally-similar repertoires of Gli proteins using parallel molecular routes; vertebrates via gene duplication and divergence, and amphioxus via alternate splicing of a single gene. Our results demonstrate that similar functional complexity of intercellular signalling can be achieved via different evolutionary pathways

Evidence-based Kernels: Fundamental Units of Behavioral Influence

This paper describes evidence-based kernels, fundamental units of behavioral influence that appear to underlie effective prevention and treatment for children, adults, and families. A kernel is a behavior–influence procedure shown through experimental analysis to affect a specific behavior and that is indivisible in the sense that removing any of its components would render it inert. Existing evidence shows that a variety of kernels can influence behavior in context, and some evidence suggests that frequent use or sufficient use of some kernels may produce longer lasting behavioral shifts. The analysis of kernels could contribute to an empirically based theory of behavioral influence, augment existing prevention or treatment efforts, facilitate the dissemination of effective prevention and treatment practices, clarify the active ingredients in existing interventions, and contribute to efficiently developing interventions that are more effective. Kernels involve one or more of the following mechanisms of behavior influence: reinforcement, altering antecedents, changing verbal relational responding, or changing physiological states directly. The paper describes 52 of these kernels, and details practical, theoretical, and research implications, including calling for a national database of kernels that influence human behavior

Design of the ECCE Detector for the Electron Ion Collider

Preprint submitted to Nuclear Instruments and Methods A. The file archived on this institutional repository has not been certified by peer review.32 pages, 29 figures, 9 tablesThe EIC Comprehensive Chromodynamics Experiment (ECCE) detector has been designed to address the full scope of the proposed Electron Ion Collider (EIC) physics program as presented by the National Academy of Science and provide a deeper understanding of the quark-gluon structure of matter. To accomplish this, the ECCE detector offers nearly acceptance and energy coverage along with excellent tracking and particle identification. The ECCE detector was designed to be built within the budget envelope set out by the EIC project while simultaneously managing cost and schedule risks. This detector concept has been selected to be the basis for the EIC project detector.Office of Science in the Department of Energy, the National Science Foundation, and the Los Alamos National Laboratory Laboratory Directed Research and Development (LDRD) 20200022DR; This research used resources of the Compute and Data Environment for Science (CADES) at the Oak Ridge National Laboratory, which is supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC05- 00OR22725. The work of AANL group are supported by the Science Committee of RA, in the frames of the research project # 21AG-1C028. And we gratefully acknowledge that support of Brookhaven National Lab and the Thomas Jefferson National Accelerator Facility which are operated under contracts DESC0012704 and DE-AC05-06OR23177 respectivel

Gene amplification of atypical PKC-binding PARD3 in raditation-transformed neoplastic retinal pigment epithelial cell lines

Neoplastic transformation induced by ionizing radiation was studied using a human retinal pigment epithelial cell line immortalized by telomerase. Radiation-transformed cell clones were tumorigenic in athymic mice and were analyzed by G-banding and comparative genomic hybridization (CGH). Radiation-transformed cloned cell lines and cell lines derived from tumors produced in athymic nude mice following transplantation exhibited a recurrent karyotype:45,XX,der(10),-13. CGH showed an amplification of 10p11.2 and a deletion of the remaining 10p. Positional cloning of the amplified region by FISH analysis and subsequent sequence analysis of BAC clones showing amplified FISH signals identified the candidate gene PARD3. This gene also was found to be transcriptionally expressed at an increased level. The findings indicate that PARD3 may play an important role in radiation-induced carcinogenesis of RPE cells. This is the first evidence for PARD3 amplification in human cancer cells. (C) 2004 Wiley-Liss, Inc.</p

Binding and differentiation in multisensory object perception

Cognitive scientists have long known that the modalities interact during perceptual processing. Cross-modal illusions like the ventriloquism effect show that the course of processing in one modality can alterthe course of processing in another. But how do the modalities interact in the specific domain of object perception?This paper distinguishes and analyzes two kinds of multisensoryinteraction in object perception. First, the modalities may bind features to a single object or event. Second, the modalities may cooperatewhendifferentiating an object or event from its surroundings.I critically evaluate evidence for various forms of multisensory binding. I then consider the case for multisensory differentiation. I argue that existing evidence for multisensory differentiation is inconclusive. I highlight ways that the issue might be empirically resolved