scholarly journals Structure of the human SAGA coactivator complex

2021 ◽  
Author(s):  
Dominik A. Herbst ◽  
Meagan N. Esbin ◽  
Robert K. Louder ◽  
Claire Dugast-Darzacq ◽  
Gina M. Dailey ◽  
...  
Keyword(s):  
Chromatin Modification ◽  
Structural Elements ◽  
Saga Complex ◽  
Functional Elements ◽  
The Core ◽  
Damage Repair ◽  
Disease Mutations ◽  
Core Module ◽  
Important Therapeutic Target ◽  
Coactivator Complex

AbstractThe SAGA complex is a regulatory hub involved in gene regulation, chromatin modification, DNA damage repair and signaling. While structures of yeast SAGA (ySAGA) have been reported, there are noteworthy functional and compositional differences for this complex in metazoans. Here we present the cryogenic-electron microscopy (cryo-EM) structure of human SAGA (hSAGA) and show how the arrangement of distinct structural elements results in a globally divergent organization from that of yeast, with a different interface tethering the core module to the TRRAP subunit, resulting in a dramatically altered geometry of functional elements and with the integration of a metazoan-specific splicing module. Our hSAGA structure reveals the presence of an inositol hexakisphosphate (InsP6) binding site in TRRAP and an unusual property of its pseudo-(Ψ)PIKK. Finally, we map human disease mutations, thus providing the needed framework for structure-guided drug design of this important therapeutic target for human developmental diseases and cancer.

scholarly journals The SAGA core module is critical during Drosophila oogenesis and is broadly recruited to promoters

2021 ◽  
Author(s):  
Jelly HM Soffers ◽  
Sergio Garcia-Moreno Alcantara ◽  
Xuanying Li ◽  
Wanqing Shao ◽  
Chrisopher Seidel ◽  
...  
Keyword(s):  
Gene Activation ◽  
Start Site ◽  
Saga Complex ◽  
Drosophila Oogenesis ◽  
The Core ◽  
Core Module ◽  
Entire Complex ◽  
Active Genes ◽  
Coactivator Complex

The Spt/Ada-Gcn5 Acetyltransferase (SAGA) coactivator complex has multiple modules with different enzymatic and non-enzymatic functions. How each module contributes to gene activation in specific biological contexts is not well understood. Here we analyzed the role of the non-enzymatic core module during Drosophila oogenesis. We show that depletion of several SAGA-specific subunits belonging to the core module blocked egg chamber development during mid-oogenesis stages, resulting in stronger phenotypes than those obtained after depletion of SAGA’s histone acetyltransferase module or deubiquitination module. These results, as well as additional genetic analyses pointing to an interaction with TBP, suggested a differential role of SAGA modules at different promoter types. However, SAGA subunits co-occupied all promoter types of active genes in ChIP-seq and ChIP-nexus experiments. Thus, the SAGA complex appears to occupy promoters in its entirety, consistent with the strong biochemical integrity of the complex. The high-resolution genomic binding profiles are congruent with SAGA recruitment by activators upstream of the start site, and retention on chromatin by interactions with modified histones downstream of the start site. The stronger genetic requirement of the core module during oogenesis may therefore be explained through its interaction with TBP or its role in recruiting the enzymatic modules to the promoter. We propose the handyman principle, which posits that a distinct genetic requirement for specific components may conceal the fact that the entire complex is physically present.

Sensitivity Analysis and Selection of Check Index of Signal Intersection Simulation Model Based on VISSIM

2019 ◽  
Vol 2 (5) ◽  
Author(s):  
Mengda Zhang ◽  
Chenjing Zhou ◽  
Tian-tian Zhang ◽  
Yan Han
Keyword(s):  
Sensitivity Analysis ◽  
Simulation Model ◽  
Optimal Process ◽  
Parameter Calibration ◽  
Index Set ◽  
The Core ◽  
Core Module ◽  
Simulation Parameter ◽  
Simulation Parameters ◽  
Selection Of

Selecting check index quantitatively is the core of the calibration of micro traffic simulation parameters at signal intersection. Five indexes in the node (intersection) module of VISSIM were selected as the check index set. Twelve simulation parameters in the core module were selected as the simulation parameters set. Optimal process of parameter calibration was proposed and model of the intersection of Huangcun west street and Xinghua street in Beijing was built in VISSIM to verify it. The sensitivity analysis between each check index and simulation parameter in their own set was conducted respectively. Sensitive parameter sets of different check indices were obtained and compared. The results show that different indexes have different size of set, and average vehicle delay's is maximum, so it's necessary to select index quantitatively. The results can provide references for scientific selection of the check indexes and improve the study efficiency of parameter calibration.

scholarly journals PDTB-10. INHIBITION OF RADIATION-INDUCED DNA DAMAGE REPAIR MEDIATED CHROMATIN MODIFICATION BY HISTONE H3 DEMETHYLASE INHIBITOR IN PEDIATRIC BRAINSTEM GLIOMA

2016 ◽  
Vol 18 (suppl_6) ◽  
pp. vi151-vi152
Author(s):  
Quanhong Ma ◽  
Andrea Plunti ◽  
Amanda Saratsis ◽  
Rishi Lulla ◽  
Jason R Fangusaro ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Repair ◽  
Chromatin Modification ◽  
Histone H3 ◽  
Brainstem Glioma ◽  
Damage Repair ◽  
Radiation Induced

scholarly journals Using a Core Scientific Metadata Model in Large-Scale Facilities

2010 ◽  
Vol 5 (1) ◽  
pp. 106-118 ◽  
Author(s):  
Brian Matthews ◽  
Shoaib Sufi ◽  
Damian Flannery ◽  
Laurent Lerusse ◽  
Tom Griffin ◽  
...  
Keyword(s):  
Large Scale ◽  
Materials Science ◽  
Production Quality ◽  
Scientific Study ◽  
Quality Data ◽  
Structural Elements ◽  
Metadata Model ◽  
The Core ◽  
Future Developments ◽  
The Relationship

In this paper, we present the Core Scientific Metadata Model (CSMD), a model for the representation of scientific study metadata developed within the Science & Technology Facilities Council (STFC) to represent the data generated from scientific facilities. The model has been developed to allow management of and access to the data resources of the facilities in a uniform way, although we believe that the model has wider application, especially in areas of “structural science” such as chemistry, materials science and earth sciences. We give some motivations behind the development of the model, and an overview of its major structural elements, centred on the notion of a scientific study formed by a collection of specific investigations. We give some details of the model, with the description of each investigation associated with a particular experiment on a sample generating data, and the associated data holdings are then mapped to the investigation with the appropriate parameters. We then go on to discuss the instantiation of the metadata model within a production quality data management infrastructure, the Information CATalogue (ICAT), which has been developed within STFC for use in large-scale photon and neutron sources. Finally, we give an overview of the relationship between CSMD, and other initiatives, and give some directions for future developments.    

scholarly journals Alarm fatigue in the ward: An acoustical problem?

2016 ◽  
Vol 6 (1) ◽  
pp. 88-104 ◽  
Author(s):  
Michael Sonne Kristensen ◽  
Judy Edworthy ◽  
Elif Özcan
Keyword(s):  
Focal Point ◽  
Generic Model ◽  
Structural Elements ◽  
Alarm Fatigue ◽  
The Core ◽  
Dynamic Relations

This article addresses the need of including acoustical perspectives in the debate on alarm fatigue within the healthcare domain. We show how conceptualisations and proposed solutions to alarm fatigue are unequally distributed across what could be called the ‘alarm chain’: a generic model of the core structural elements and dynamic relations that constitute any alarm scenario. A focal point in the alarm chain – the ‘alarm mediation cleft’ – seems to divide the alarm fatigue literature from the segment of the alarm literature that deals with auditory alarm design. The current healthcare discourse on alarm fatigue is centred around the ‘premediated alarm phase’, which has the consequence of an unfortunate dichotomous approach to the functionality of sound. We address some shortcomings of this approach and outline some methodological implications and potentials of searching for signs of alarm fatigue in the ‘post-mediated alarm phase’.

Analysis of the Realization Approach to the Eco-Friendly Transportation Management

2010 ◽  
Vol 40-41 ◽  
pp. 659-668
Author(s):  
Jin Ming Yuan ◽  
Ju Yang
Keyword(s):  
Social Economy ◽  
Environmental Issues ◽  
Developed Countries ◽  
Scientific Management ◽  
Transportation Industry ◽  
Functional Elements ◽  
Transportation Management ◽  
The Public ◽  
The Core ◽  
The Government

The transportation is the core functional elements in the logistics activities. If not focusing on implementation of eco-friendly management in the process of logistic transportation, it is impossible to build an eco-friendly logistic system as a whole. Developed countries attach great importance to environmental issues and spare no effort in promoting the reform of logistics transportation. In order to comply with sustainable development in society and economy, China's transportation industry is urgently in need of more scientific management. Based on the relevant issues of current logistic transportation, from the perspectives of multi-subject such as the government, the enterprises and the public, this article analyzes the feasible approach to achieving the eco-friendly transportation management to ensure harmonious development of efficient transportation, social economy, environment and resources.

Structural-Acoustic Optimization of Sandwich Panels

2005 ◽  
Author(s):  
Francesco Franco ◽  
Kenneth A. Cunefare ◽  
Massimo Ruzzene
Keyword(s):  
Numerical Optimization ◽  
Composite Structures ◽  
Gradient Methods ◽  
Sandwich Panels ◽  
Relative Importance ◽  
Structural Elements ◽  
Acoustic Response ◽  
The Core ◽  
Design Flexibility ◽  
The Face

Sandwich panels, comprising face sheets enclosing a core, are increasingly common structural elements in a variety of applications, including aircraft fuselages and flight surfaces, vehicle panels, lightweight enclosures, and bulkheads. The design flexibility associated with such composite structures provides significant opportunities for tailoring the structure to the load and dynamic response requirements for the particular application. Design flexibility encompasses the details of the face sheets and the core. This paper deals with the numerical optimization of different sandwich configurations for the purposes of achieving reduced structural acoustic response. Laminated face sheets and core geometries, comprising honeycomb and truss-like structures, are considered. The relative importance of the mass and stiffening properties of the core and face sheets are discussed. The optimization work is carried out using commercial codes. Benefits and limits of using an optimization algorithm based on gradient methods are highlighted.

The ‘hero archetype’ in the neo-mythological context of contemporary screen culture

2019 ◽  
Vol 11 (2) ◽  
pp. 116-126
Author(s):  
Olesya V. Stroeva
Keyword(s):  
Technical Progress ◽  
Mass Culture ◽  
Structural Elements ◽  
Cultural Meanings ◽  
Happy Ending ◽  
The Core ◽  
The Media ◽  
The Senses ◽  
Hero Archetype ◽  
Formal Properties

The essay examines the image of the hero in the contemporary neo-mythological field of mass screen culture. The author identifies the main features of the hero archetype and the core cultural meanings forming this concept and analyzes images of the neo-mythological heroes of our time, taking examples of mass cinema and authorial cinema and revealing differences between these two categories. According to the author, mass culture creates the hero model according to the principle of bricolage, remaining within the framework of the Christian eschatological paradigm and synthesizing it with scientific and technical progress or other elements but not reproducing the structure of the archaic myth. When the stereotype of happy ending replaces tragedy, it completely changes the true archetype of the hero more characteristic of art-house or authorial cinema. Examining the films of Jim Jarmusch and Alejandro Gonzlez Irritu, the author analyzes the method of deconstruction in authorial cinema, a cinema which seeks to reveal the meanings of the archaic hero archetype. If mass cinema acts within the simulacrum system without transcending its limits endlessly repeating the same models and often using only superficial formal properties authorial cinema tries to explode the structure in such a way as to widen the boundaries of the senses or to discover them under the layers of simulacra. Thus, screen culture has the characteristics of a neo-mythology, forming the neo-myth and developing its elements and structures, producing a stream of neo-mythological images in the media landscape. The conglomerate of various structural elements borrowed from different traditions fully reflects the postmodern situation that turns symbols and archetypes into a set of simulacra. The era of postmodernism is a stage in the development of culture characterized by the problem of the impossibility of creating anything new. Postmodernism is a creative crisis which leads to excessive visuality and, paradoxically, to visualitys death.

Research on System Planning of Retired or Scrap Weaponry and Equipment Recycling

2014 ◽  
Vol 1010-1012 ◽  
pp. 979-983 ◽  
Author(s):  
Tao Xin ◽  
Yuan Yuan Han ◽  
Kai Kai Hu
Keyword(s):  
Circular Economy ◽  
Structural Model ◽  
Economic Benefits ◽  
System Framework ◽  
Functional Elements ◽  
System Planning ◽  
Recycling System ◽  
The Core ◽  
Resource And Environment ◽  
Concrete Operation

Nowadays, being confronted with the decreasingly nature resource and environment polluted, effectively mining the potential economic benefits of retired or scrap equipment, studying on planning retired or scrap equipment recycling system, is a very important matter. This paper puts forward an ideology of the recycling of retired or scrap weaponry and equipment based on 3R, by introducing 3R principle which is the core ideology of circular economy. This paper presents a retired or scrap equipment recycling system planning thought, analyzes the system framework which consists of recycling targets, recycling objects, functional elements and participating subject. The preliminary structural Model is established, as well as the concrete operation processes are studied.

scholarly journals Geometry and Modeling of the Oval Strand of n0+(2n0+4)+n2 Type

2012 ◽  
Vol 7 (2) ◽  
pp. 33-40 ◽  
Author(s):  
Eva Stanová
Keyword(s):  
Initial Data ◽  
Geometric Modeling ◽  
Geometrical Model ◽  
Wire Rope ◽  
Mathematical Representation ◽  
Structural Elements ◽  
The Core ◽  
Different Shapes ◽  
The Wire ◽  
Wire Strand

Abstract A wire rope is a structure composed of many individual wires. The wires form two major structural elements: the strand core and the layers of the strand. There may be different shapes of strands in the rope depending on the shape of strand core. The paper deals with the mathematical geometric modeling of the oval wire strand created of n0 + (2n0 + 4) + n2 wires. The number and diameter of the core wires are the initial data. The mathematical representation is in form of parametric equations of the wire axes. The equations are implemented in the Pro/Engineer Wildfire V5 software for creating the geometrical model of the strand.

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