144 research outputs found

    A Pipeline for Volume Electron Microscopy of the Caenorhabditis elegans Nervous System.

    Get PDF
    The "connectome," a comprehensive wiring diagram of synaptic connectivity, is achieved through volume electron microscopy (vEM) analysis of an entire nervous system and all associated non-neuronal tissues. White et al. (1986) pioneered the fully manual reconstruction of a connectome using Caenorhabditis elegans. Recent advances in vEM allow mapping new C. elegans connectomes with increased throughput, and reduced subjectivity. Current vEM studies aim to not only fill the remaining gaps in the original connectome, but also address fundamental questions including how the connectome changes during development, the nature of individuality, sexual dimorphism, and how genetic and environmental factors regulate connectivity. Here we describe our current vEM pipeline and projected improvements for the study of the C. elegans nervous system and beyond

    Gain-of-function mutations in the UNC-2/CaV2α channel lead to excitation-dominant synaptic transmission in C. elegans

    Get PDF
    Mutations in pre-synaptic voltage gated calcium channels can lead to familial hemiplegic migraine type 1 (FHM1). While mammalian studies indicate that the migraine brain is hyperexcitable due to enhanced excitation or reduced inhibition, the molecular and cellular mechanisms underlying this excitatory/inhibitory (E/I) imbalance are poorly understood. We identified a gain-of-function (gf) mutation in the Caenorhabditis elegans CaV2 channel α1 subunit, UNC-2, which leads to increased calcium currents. unc-2(zf35gf) mutants exhibit hyperactivity and seizure-like motor behaviors. Expression of the unc-2 gene with FHM1 substitutions R192Q and S218L leads to hyperactivity similar to that of unc-2(zf35gf) mutants. unc-2(zf35gf) mutants display increased cholinergic-and decreased GABAergic-transmission. Moreover, increased cholinergic transmission in unc-2(zf35gf) mutants leads to an increase of cholinergic synapses and a TAX-6/calcineurin dependent reduction of GABA synapses. Our studies reveal mechanisms through which CaV2 gain-of-function mutations disrupt excitation-inhibition balance in the nervous system.Fil: Huang, Yung Chi. University of Massachussets; Estados UnidosFil: Pirri, Jennifer K.. University of Massachussets; Estados UnidosFil: Rayes, Diego Hernån. University of Massachussets; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Gao, Shangbang. Mount Sinai Hospital; Estados UnidosFil: Mulcahy, Ben. Mount Sinai Hospital; Estados UnidosFil: Grant, Jeff. University of Massachussets; Estados UnidosFil: Saheki, Yasunori. The Rockefeller University; Estados UnidosFil: Francis, Michael M.. University of Massachussets; Estados UnidosFil: Zhen, Mei. University of Toronto; Canadå. Mount Sinai Hospital; Estados UnidosFil: Alkema, Mark J.. University of Massachussets; Estados Unido

    Teach-out, MAT in Art Education Thesis Exhibit

    Get PDF
    Artist statements and samples of artwork by the 2020 MAT in Art Education Professional Licensure students

    Electrical Components for Marine Renewable Energy Arrays: A Techno-Economic Review

    Get PDF
    This paper presents a review of the main electrical components that are expected to be present in marine renewable energy arrays. The review is put in context by appraising the current needs of the industry and identifying the key components required in both device and array-scale developments. For each component, electrical, mechanical and cost considerations are discussed; with quantitative data collected during the review made freely available for use by the community via an open access online repository. This data collection updates previous research and addresses gaps specific to emerging offshore technologies, such as marine and floating wind, and provides a comprehensive resource for the techno-economic assessment of offshore energy arrays

    Implementation of U.K. Earth system models for CMIP6

    Get PDF
    We describe the scientific and technical implementation of two models for a core set of experiments contributing to the sixth phase of the Coupled Model Intercomparison Project (CMIP6). The models used are the physical atmosphere-land-ocean-sea ice model HadGEM3-GC3.1 and the Earth system model UKESM1 which adds a carbon-nitrogen cycle and atmospheric chemistry to HadGEM3-GC3.1. The model results are constrained by the external boundary conditions (forcing data) and initial conditions.We outline the scientific rationale and assumptions made in specifying these. Notable details of the implementation include an ozone redistribution scheme for prescribed ozone simulations (HadGEM3-GC3.1) to avoid inconsistencies with the model's thermal tropopause, and land use change in dynamic vegetation simulations (UKESM1) whose influence will be subject to potential biases in the simulation of background natural vegetation.We discuss the implications of these decisions for interpretation of the simulation results. These simulations are expensive in terms of human and CPU resources and will underpin many further experiments; we describe some of the technical steps taken to ensure their scientific robustness and reproducibility

    The role of anthropogenic aerosols in the anomalous cooling from 1960 to 1990 in the CMIP6 Earth System Models

    Get PDF
    The Earth system models (ESMs) that participated in the sixth Coupled Model Intercomparison Project (CMIP6) tend to simulate excessive cooling in surface air temperature (TAS) between 1960 and 1990. The anomalous cooling is pronounced over the Northern Hemisphere (NH) midlatitudes, coinciding with the rapid growth of anthropogenic sulfur dioxide (SO2) emissions, the primary precursor of atmospheric sulfate aerosols. Structural uncertainties between ESMs have a larger impact on the anomalous cooling than internal variability. Historical simulations with and without anthropogenic aerosol emissions indicate that the anomalous cooling in the ESMs is attributed to the higher aerosol burden in these models. The aerosol forcing sensitivity, estimated as the outgoing shortwave radiation (OSR) response to aerosol concentration changes, cannot well explain the diversity of pothole cooling (PHC) biases in the ESMs. The relative contributions to aerosol forcing sensitivity from aerosol–radiation interactions (ARIs) and aerosol–cloud interactions (ACIs) can be estimated from CMIP6 simulations. We show that even when the aerosol forcing sensitivity is similar between ESMs, the relative contributions of ARI and ACI may be substantially different. The ACI accounts for between 64 % and 87 % of the aerosol forcing sensitivity in the models and is the main source of the aerosol forcing sensitivity differences between the ESMs. The ACI can be further decomposed into a cloud-amount term (which depends linearly on cloud fraction) and a cloud-albedo term (which is independent of cloud fraction, to the first order), with the cloud-amount term accounting for most of the inter-model differences

    A Pipeline for Volume Electron Microscopy of the Caenorhabditis elegans Nervous System

    Get PDF
    The “connectome,” a comprehensive wiring diagram of synaptic connectivity, is achieved through volume electron microscopy (vEM) analysis of an entire nervous system and all associated non-neuronal tissues. White et al. (1986) pioneered the fully manual reconstruction of a connectome using Caenorhabditis elegans. Recent advances in vEM allow mapping new C. elegans connectomes with increased throughput, and reduced subjectivity. Current vEM studies aim to not only fill the remaining gaps in the original connectome, but also address fundamental questions including how the connectome changes during development, the nature of individuality, sexual dimorphism, and how genetic and environmental factors regulate connectivity. Here we describe our current vEM pipeline and projected improvements for the study of the C. elegans nervous system and beyond
    • 

    corecore