A model of the large-scale organization of chromatin

2013 ◽  
Vol 41 (2) ◽  
pp. 508-512 ◽  
Author(s):  
Mariano Barbieri ◽  
Mita Chotalia ◽  
James Fraser ◽  
Liron-Mark Lavitas ◽  
Josée Dostie ◽  
...  
Keyword(s):  
Experimental Data ◽  
Present Article ◽  
Cell Nucleus ◽  
Large Scale ◽  
Spatial Organization ◽  
Molecular Mechanisms ◽  
Three Dimensional ◽  
Polymer Physics ◽  
Self Organization ◽  
Dna Binding Factors

In the cell nucleus, chromosomes have a complex spatial organization, spanning several length scales, which serves vital functional purposes. It is unknown, however, how their three-dimensional architecture is orchestrated. In the present article, we review the application of a model based on classical polymer physics, the strings and binders switch model, to explain the molecular mechanisms of chromatin self-organization. We explore the scenario where chromatin architecture is shaped and regulated by the interactions of chromosomes with diffusing DNA-binding factors via thermodynamics mechanisms and compare it with available experimental data.

scholarly journals Integrating Transposable Elements in the 3D Genome

2019 ◽  
Author(s):  
Alexandros Bousios ◽  
Hans-Wilhelm Nuetzmann ◽  
Dorothy Buck ◽  
Davide Michieletto
Keyword(s):  
Transposable Elements ◽  
Cell Fate ◽  
Large Scale ◽  
Spatial Information ◽  
Experimental Studies ◽  
Three Dimensional ◽  
Predictive Modelling ◽  
Polymer Physics ◽  
Modelling Framework ◽  
Polymer Folding

Chromosome organisation is increasingly recognised as an essential component of genome regulation, cell fate and cell health. Within the realm of transposable elements (TEs) however, the spatial information of how genomes are folded is still only rarely integrated in experimental studies or accounted for in modelling. Here, we propose a new predictive modelling framework for the study of the integration patterns of TEs based on extensions of widely employed polymer models for genome organisation. Whilst polymer physics is recognised as an important tool to understand the mechanisms of genome folding, we now show that it can also offer orthogonal and generic insights into the integration and distribution profiles (or “topography”) of TEs across organisms. Here, we present polymer physics arguments and molecular dynamics simulations on TEs inserting into heterogeneously flexible polymers and show with a simple model that polymer folding and local flexibility affects TE integration patterns. The preliminary discussion presented herein lay the foundations for a large-scale analysis of TE integration dynamics and topography as a function of the three-dimensional host genome.

scholarly journals Cellular-resolution gene expression profiling in the neonatal marmoset brain reveals dynamic species- and region-specific differences

2021 ◽  
Vol 118 (18) ◽  
pp. e2020125118
Author(s):  
Yoshiaki Kita ◽  
Hirozumi Nishibe ◽  
Yan Wang ◽  
Tsutomu Hashikawa ◽  
Satomi S. Kikuchi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Neural Circuit ◽  
Expression Patterns ◽  
Three Dimensional ◽  
Control Of Gene Expression ◽  
Cellular Resolution

Precise spatiotemporal control of gene expression in the developing brain is critical for neural circuit formation, and comprehensive expression mapping in the developing primate brain is crucial to understand brain function in health and disease. Here, we developed an unbiased, automated, large-scale, cellular-resolution in situ hybridization (ISH)–based gene expression profiling system (GePS) and companion analysis to reveal gene expression patterns in the neonatal New World marmoset cortex, thalamus, and striatum that are distinct from those in mice. Gene-ontology analysis of marmoset-specific genes revealed associations with catalytic activity in the visual cortex and neuropsychiatric disorders in the thalamus. Cortically expressed genes with clear area boundaries were used in a three-dimensional cortical surface mapping algorithm to delineate higher-order cortical areas not evident in two-dimensional ISH data. GePS provides a powerful platform to elucidate the molecular mechanisms underlying primate neurobiology and developmental psychiatric and neurological disorders.

Very-large-scale motions in a turbulent boundary layer

2011 ◽  
Vol 673 ◽  
pp. 80-120 ◽  
Author(s):  
JAE HWA LEE ◽  
HYUNG JIN SUNG
Keyword(s):  
Boundary Layer ◽  
Shear Stress ◽  
Turbulent Boundary Layer ◽  
Large Scale ◽  
Spatial Organization ◽  
Reynolds Shear Stress ◽  
Three Dimensional ◽  
Hairpin Vortices ◽  
Extraction Algorithm ◽  
Normal Distance

Direct numerical simulation of a turbulent boundary layer was performed to investigate the spatially coherent structures associated with very-large-scale motions (VLSMs). The Reynolds number was varied in the range Reθ = 570–2560. The main simulation was conducted by using a computational box greater than 50δo in the streamwise domain, where δo is the boundary layer thickness at the inlet, and inflow data was obtained from a separate inflow simulation based on Lund's method. Inspection of the three-dimensional instantaneous fields showed that groups of hairpin vortices are coherently arranged in the streamwise direction and that these groups create significantly elongated low- and high-momentum regions with large amounts of Reynolds shear stress. Adjacent packet-type structures combine to form the VLSMs; this formation process is attributed to continuous stretching of the hairpins coupled with lifting-up and backward curling of the vortices. The growth of the spanwise scale of the hairpin packets occurs continuously, so it increases rapidly to double that of the original width of the packets. We employed the modified feature extraction algorithm developed by Ganapathisubramani, Longmire & Marusic (J. Fluid Mech., vol. 478, 2003, p. 35) to identify the properties of the VLSMs of hairpin vortices. In the log layer, patches with the length greater than 3δ–4δ account for more than 40% of all the patches and these VLSMs contribute approximately 45% of the total Reynolds shear stress included in all the patches. The VLSMs have a statistical streamwise coherence of the order of ~6δ; the spatial organization and coherence decrease away from the wall, but the spanwise width increases monotonically with the wall-normal distance. Finally, the application of linear stochastic estimation demonstrated the presence of packet organization in the form of a train of packets in the log layer.

scholarly journals Detection of functional protein domains by unbiased genome-wide forward genetic screening

2017 ◽  
Author(s):  
Mareike Herzog ◽  
Fabio Puddu ◽  
Julia Coates ◽  
Nicola Geisler ◽  
Josep V Forment ◽  
...  
Keyword(s):  
Drug Targets ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Gene Knockout ◽  
Mammalian Cell Culture ◽  
Three Dimensional ◽  
Embryonic Stem ◽  
Protein Domains ◽  
Functional Protein ◽  
Suppressor Mutations

ABSTRACTGenetic and chemo-genetic interactions have played key roles in elucidating the molecular mechanisms by which certain chemicals perturb cellular functions. Many studies have employed gene knockout collections or gene disruption/depletion strategies to identify routes for evolving resistance to chemical agents. By contrast, searching for point-mutational genetic suppressors that can identify separation- or gain-of-function mutations, has been limited even in simpler, genetically amenable organisms such as yeast, and has not until recently been possible in mammalian cell culture systems. Here, by demonstrating its utility in identifying suppressors of cellular sensitivity to the drugs camptothecin or olaparib, we describe an approach allowing systematic, large-scale detection of spontaneous or chemically-induced suppressor mutations in yeast and in haploid mouse embryonic stem cells in a short timeframe, and with potential applications in essentially any other haploid system. In addition to its utility for molecular biology research, this protocol can be used to identify drug targets and to predict mechanisms leading to drug resistance. Mapping suppressor mutations on the primary sequence or three-dimensional structures of protein suppressor hits provides insights into functionally relevant protein domains, advancing our molecular understanding of protein functions, and potentially helping to improve drug design and applicability.

scholarly journals Gut bacterial aggregates as living gels

2021 ◽  
Author(s):  
Brandon H Schlomann ◽  
Raghuveer Parthasarathy
Keyword(s):  
Large Scale ◽  
Spatial Organization ◽  
Three Dimensional ◽  
Intestinal Transport ◽  
Power Laws ◽  
Soft Materials ◽  
Dependent Manner ◽  
Bacterial Strains ◽  
Host Microbe Interactions ◽  
Bacterial Aggregates

The spatial organization of gut microbiota influences both microbial abundances and host-microbe interactions, but the underlying rules relating bacterial dynamics to large-scale structure remain unclear. To this end we studied experimentally and theoretically the formation of three-dimensional bacterial clusters, a key parameter controlling susceptibility to intestinal transport and access to the epithelium. Inspired by models of structure formation in soft materials, we sought to understand how the distribution of gut bacterial cluster sizes emerges from bacterial-scale kinetics. Analyzing imaging-derived data on cluster sizes for eight different bacterial strains in the larval zebrafish gut, we find a common family of size distributions that decay approximately as power laws with exponents close to -2, becoming shallower for large clusters in a strain-dependent manner. We show that this type of distribution arises naturally from a Yule-Simons-type process in which bacteria grow within clusters and can escape from them, coupled to an aggregation process that tends to condense the system toward a single massive cluster, reminiscent of gel formation. Together, these results point to the existence of general, biophysical principles governing the spatial organization of the gut microbiome that may be useful for inferring fast-timescale dynamics that are experimentally inaccessible.

Multistage Simulation by an Adaptive Finite Element Approach Using Structured Grids

1999 ◽  
Vol 121 (2) ◽  
pp. 450-459 ◽  
Author(s):  
M. Sleiman ◽  
A. Tam ◽  
M. P. Robichaud ◽  
M. F. Peeters ◽  
W. G. Habashi
Keyword(s):  
Experimental Data ◽  
Finite Element ◽  
Large Scale ◽  
Three Dimensional ◽  
Mesh Adaptation ◽  
Navier Stokes ◽  
Interface Plane ◽  
Adaptive Finite Element ◽  
Local Flow ◽  
Edge Based

This paper presents the application of a three-dimensional Navier-Stokes finite element code (NS3D) in the context of turbomachinery rotor-stator multistage interaction. A mixing-plane approach is used, in which boundary conditions at a common interface plane between adjacent blade rows are iteratively adjusted to yield a flow satisfying the continuity, momentum, and energy conservation equations, in an average sense. To further improve the solutions, a mesh adaptation technique then redistributes the mesh points of the structured grid within each component, according to an a posteriori edge-based error estimate based on the Hessian of the local flow solution. This matrix of second derivatives controls both the magnitude and direction of the required mesh movement at each node, is then implemented using an edge-based spring analogy. The methodology is demonstrated for two test cases with two types of data: a well-instrumented experimental large-scale rotating rig for a second stage compressor at UTRC and an actual engine. The latter, a two-stage compressor of a turboprop, has been only tested as a single-stage configuration, because of the quality of the experimental data available. All results compare well to the data and demonstrate the utility of the approach. In Particular, the mesh adaptation shows large improvements in agreement between the calculations and the experimental data.

Computational simulation of steel moment frame to resist progressive collapse in fire

2016 ◽  
Vol 7 (4) ◽  
pp. 286-305 ◽  
Author(s):  
Ha Nguyen ◽  
Ann E. Jeffers ◽  
Venkatesh Kodur
Keyword(s):  
Experimental Data ◽  
Large Scale ◽  
Progressive Collapse ◽  
Computational Simulation ◽  
Three Dimensional ◽  
Fe Model ◽  
Moment Frame ◽  
Steel Moment Frame ◽  
Fixed Temperature ◽  
Content Type

Purpose This paper aims to address a need for improving the structural resilience to multi-hazard threats including fire and progressive collapse caused by the loss of a column. Design/methodology/approach The focus is on a steel moment frame that uses welded-unreinforced flange-bolted web connections between the beams and columns. A three-dimensional finite element (FE) model was created in ABAQUS with temperature-dependent properties for steel based on the Eurocode. The model was validated against experimental data at ambient and elevated temperature. Findings The failure mechanisms in the FE model were consistent with experimental observations. Two scenarios were considered: fixed load with increasing temperature (i.e. simulating column failure prior to fire) and fixed temperature with increasing load (i.e. simulating column failure during fire). Originality/value A macro element (or component-based) model was also introduced and validated against the FE model and the experimental data, offering the possibility of analyzing large-scale structural systems with reasonable accuracy and improved computational efficiency.

scholarly journals The domain-within-domain packing of euchromatin can be described as multiplicative cascades

2020 ◽  
Author(s):  
Amra Noa ◽  
Hui-Shun Kuan ◽  
Vera Aschmann ◽  
Vasily Zaburdaev ◽  
Lennart Hilbert
Keyword(s):  
Cell Nucleus ◽  
Large Scale ◽  
Microphase Separation ◽  
Three Dimensional ◽  
Super Resolution ◽  
Theoretical Models ◽  
Theoretical Physics ◽  
Domain Organization ◽  
Multiplicative Cascades ◽  
Microscopy Images

ABSTRACTThe genome is packed into the cell nucleus in the form of chromatin. Biochemical approaches have revealed that chromatin is packed within domains, which group into larger domains, and so forth. Such domain-within-domain packing, also called hierarchical packing, is equally visible in super-resolution microscopy images of large-scale chromatin organization. While previous work has suggested that chromatin is partitioned into distinct domains via microphase separation, it is unclear how these domains organize into a hierarchical packing. A particular challenge is to find an image analysis approach that fully incorporates such hierarchical packing, so that hypothetical governing mechanisms of euchromatin packing can be compared against the results of such an analysis. Here, we obtain 3D STED super-resolution images from pluripotent zebrafish embryos labeled with improved DNA fluorescence stains, and demonstrate how the hierarchical packing of euchromatin in these images can be described as multiplicative cascades. Multiplicative cascades are an established theoretical concept to describe the placement of ever-smaller structures within bigger structures. Importantly, these cascades can generate artificial image data by applying a single rule again and again, and can be fully specified using only four parameters. Here, we show how the typical patterns of euchromatin organization are reflected in the values of these four parameters. In particular, we can pinpoint the values required to mimic a microphase-separated configuration of euchromatin. We suspect that the concept of multiplicative cascades can also be applied to images of other types of chromatin. In particular, cascade parameters could serve as test quantities to assess whether microphase separation or other theoretical models accurately reproduce the hierarchical packing of chromatin.SIGNIFICANCEDNA is stored inside the cell nucleus in the form of chromatin. Chromatin exhibits a striking three-dimensional organization, where small domains group into larger domains, which again group into larger domains, and so forth. While this hierarchical domain-within-domain organization is obvious from microscopy images, it is still not entirely clear how it is established, or how it should be properly characterized. Here, we demonstrate that multiplicative cascades – a concept from theoretical physics used to characterize for example cloud patterns, galaxy locations, or soil patterns – are also ideally suited to describe the domain-within-domain organization of chromatin. This description is rather simple, using only four numbers, and can thus facilitate testing of competing theories for the domain-within-domain organization of chromatin.

Functional architecture in the cell nucleus

2001 ◽  
Vol 356 (2) ◽  
pp. 297-310 ◽  
Author(s):  
Miroslav DUNDR ◽  
Tom MISTELI
Keyword(s):  
Gene Expression ◽  
Cell Nucleus ◽  
Molecular Mechanisms ◽  
Dynamic Properties ◽  
Three Dimensional ◽  
Nuclear Architecture ◽  
Structural Framework ◽  
And Function ◽  
Biological Methods

The major functions of the cell nucleus, including transcription, pre-mRNA splicing and ribosome assembly, have been studied extensively by biochemical, genetic and molecular methods. An overwhelming amount of information about their molecular mechanisms is available. In stark contrast, very little is known about how these processes are integrated into the structural framework of the cell nucleus and how they are spatially and temporally co-ordinated within the three-dimensional confines of the nucleus. It is also largely unknown how nuclear architecture affects gene expression. In order to understand how genomes are organized, and how they function, the basic principles that govern nuclear architecture and function must be uncovered. Recent work combining molecular, biochemical and cell biological methods is beginning to shed light on how the nucleus functions and how genes are expressed in vivo. It has become clear that the nucleus contains distinct compartments and that many nuclear components are highly dynamic. Here we describe the major structural compartments of the cell nucleus and discuss their established and proposed functions. We summarize recent observations regarding the dynamic properties of chromatin, mRNA and nuclear proteins, and we consider the implications these findings have for the organization of nuclear processes and gene expression. Finally, we speculate that self-organization might play a substantial role in establishing and maintaining nuclear organization.

Space–time formation of very-large-scale motions in turbulent pipe flow

2019 ◽  
Vol 881 ◽  
pp. 1010-1047 ◽  
Author(s):  
Jae Hwa Lee ◽  
Hyung Jin Sung ◽  
Ronald J. Adrian
Keyword(s):  
Pipe Flow ◽  
Large Scale ◽  
Spatial Organization ◽  
Three Dimensional ◽  
Streamwise Velocity ◽  
Turbulent Pipe Flow ◽  
Strain Component ◽  
Spatial Correlations ◽  
Correlation Pattern ◽  
Using Data

We examine the origin of very-large-scale motions (VLSMs) in fully developed turbulent pipe flow at friction Reynolds number, $\mathit{Re}_{\unicode[STIX]{x1D70F}}=934$, using data from a direct numerical simulation. The VLSMs and the packet-like large-scale motions (LSMs) found in this study are very similar to those found in earlier studies. Three-dimensional time-evolving instantaneous fields show that one component of the process leading to the large streamwise length of VLSMs is the concatenation of adjacent streamwise LSMs caused by the continuous elongation of LSMs due to the strain component of the mean shear. Spatial organization patterns of the VLSMs and LSMs and their properties are studied by separating auto-correlation of the streamwise velocity fluctuations into the components of the VLSM and the LSM defined by low-pass/high-pass filtering in the streamwise direction. The structures of the two-point spatial correlations of the streamwise velocity component of the VLSMs and the LSMs in the streamwise-azimuthal plane are characterized by multiple maxima and complex patterns that beg explanation in terms of patterned coherent arrangements of the LSMs. Using proper orthogonal decomposition (POD), it is found that the X-shape correlation pattern of the VLSMs results from the superposition of very long helically inclined structures and streamwise-aligned structures. Further explanation of the patterns in the correlations of the VLSMs and LSMs is provided through the study of synthetically constructed arrangements of simple hairpin packet models of the LSM. Head-to-tail alignment of the model packets along streamwise and helical directions suggested by the eigenvalues of the POD creates a pair of long roll-cells centred above the logarithmic layer, and bracketing the LSMs. These roll-cells are pure kinematic consequences of the induction within the LSM packets, but they may also serve to organize smaller packets.

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