scholarly journals Encounters in Three Dimensions: How Nuclear Topology Shapes Genome Integrity

2021 ◽  
Vol 12 ◽  
Author(s):  
Robin Sebastian ◽  
Mirit I. Aladjem ◽  
Philipp Oberdoerffer
Keyword(s):  
Dna Repair ◽  
Genome Instability ◽  
Three Dimensional ◽  
Three Dimensions ◽  
Histone H2ax ◽  
3D Genome ◽  
New Findings ◽  
Topologically Associated Domains ◽  
Organizational Features ◽  
The Impact

Almost 25 years ago, the phosphorylation of a chromatin component, histone H2AX, was discovered as an integral part of the DNA damage response in eukaryotes. Much has been learned since then about the control of DNA repair in the context of chromatin. Recent technical and computational advances in imaging, biophysics and deep sequencing have led to unprecedented insight into nuclear organization, highlighting the impact of three-dimensional (3D) chromatin structure and nuclear topology on DNA repair. In this review, we will describe how DNA repair processes have adjusted to and in many cases adopted these organizational features to ensure accurate lesion repair. We focus on new findings that highlight the importance of chromatin context, topologically associated domains, phase separation and DNA break mobility for the establishment of repair-conducive nuclear environments. Finally, we address the consequences of aberrant 3D genome maintenance for genome instability and disease.

scholarly journals 3DIV update for 2021: a comprehensive resource of 3D genome and 3D cancer genome

2020 ◽  
Vol 49 (D1) ◽  
pp. D38-D46
Author(s):  
Kyukwang Kim ◽  
Insu Jang ◽  
Mooyoung Kim ◽  
Jinhyuk Choi ◽  
Min-Seo Kim ◽  
...  
Keyword(s):  
Cell Line ◽  
Large Scale ◽  
Three Dimensional ◽  
Cancer Cell Line ◽  
Cancer Genome ◽  
Structural Variations ◽  
3D Genome ◽  
Tightly Coupled ◽  
Regulatory Effects ◽  
The Impact

Abstract Three-dimensional (3D) genome organization is tightly coupled with gene regulation in various biological processes and diseases. In cancer, various types of large-scale genomic rearrangements can disrupt the 3D genome, leading to oncogenic gene expression. However, unraveling the pathogenicity of the 3D cancer genome remains a challenge since closer examinations have been greatly limited due to the lack of appropriate tools specialized for disorganized higher-order chromatin structure. Here, we updated a 3D-genome Interaction Viewer and database named 3DIV by uniformly processing ∼230 billion raw Hi-C reads to expand our contents to the 3D cancer genome. The updates of 3DIV are listed as follows: (i) the collection of 401 samples including 220 cancer cell line/tumor Hi-C data, 153 normal cell line/tissue Hi-C data, and 28 promoter capture Hi-C data, (ii) the live interactive manipulation of the 3D cancer genome to simulate the impact of structural variations and (iii) the reconstruction of Hi-C contact maps by user-defined chromosome order to investigate the 3D genome of the complex genomic rearrangement. In summary, the updated 3DIV will be the most comprehensive resource to explore the gene regulatory effects of both the normal and cancer 3D genome. ‘3DIV’ is freely available at http://3div.kr.

scholarly journals A systematic study of proto-neutron star convection in three-dimensional core-collapse supernova simulations

2020 ◽  
Vol 492 (4) ◽  
pp. 5764-5779 ◽  
Author(s):  
Hiroki Nagakura ◽  
Adam Burrows ◽  
David Radice ◽  
David Vartanyan
Keyword(s):  
Neutron Star ◽  
Systematic Study ◽  
Three Dimensional ◽  
Three Dimensions ◽  
Core Collapse ◽  
Core Collapse Supernova ◽  
Tau Neutrinos ◽  
The Impact ◽  
Proto Neutron Star

ABSTRACT This paper presents the first systematic study of proto-neutron star (PNS) convection in three dimensions (3D) based on our latest numerical fornax models of core-collapse supernova (CCSN). We confirm that PNS convection commonly occurs, and then quantify the basic physical characteristics of the convection. By virtue of the large number of long-term models, the diversity of PNS convective behaviour emerges. We find that the vigour of PNS convection is not correlated with CCSN dynamics at large radii, but rather with the mass of PNS − heavier masses are associated with stronger PNS convection. We find that PNS convection boosts the luminosities of νμ, ντ, $\bar{\nu }_{\mu }$, and $\bar{\nu }_{\tau }$ neutrinos, while the impact on other species is complex due to a competition of factors. Finally, we assess the consequent impact on CCSN dynamics and the potential for PNS convection to generate pulsar magnetic fields.

Three-dimensional effects in low-strain integrity testing of piles: analytical solution

2016 ◽  
Vol 53 (2) ◽  
pp. 225-235 ◽  
Author(s):  
Changjie Zheng ◽  
George P. Kouretzis ◽  
Xuanming Ding ◽  
Hanlong Liu ◽  
Harry G. Poulos
Keyword(s):  
Impact Load ◽  
Three Dimensional ◽  
Three Dimensions ◽  
Integrity Testing ◽  
Integrity Tests ◽  
The One ◽  
Propagation Of Waves ◽  
The Impact ◽  
Pile Integrity ◽  
Elastic Soil

The interpretation of low-strain integrity tests of piles is commonly based on methods developed around the one-dimensional wave propagation theory. In reality, waves resulting from the impact of a hammer on a pile head propagate in three dimensions, and the validity of the plane-front assumption is rather questionable for cases where the size of the hammer is small relative to that of the pile. This paper presents an analytical model of the dynamic response of a pile to an impact load on its head, considering propagation of waves in both vertical and radial directions. The proposed formulation applies to a pile of finite length embedded in multilayered elastic soil, and allows for considering both shape and material pile defects, by reducing locally the radius of the pile cross section or the Young’s modulus of its material. Arithmetic examples are used to depict the effect of high-frequency interferences on the interpretation of pile integrity tests, which can only be accounted for in the three-dimensional formulation of the problem, and lead to practical suggestions for the interpretation of such tests.

scholarly journals Chromatin spatial organization of wild type and mutant peanuts reveals high-resolution genomic architecture and interaction alterations

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xingguo Zhang ◽  
Manish K. Pandey ◽  
Jianping Wang ◽  
Kunkun Zhao ◽  
Xingli Ma ◽  
...  
Keyword(s):  
Spatial Organization ◽  
Gene Expression Regulation ◽  
Three Dimensional ◽  
Active Regions ◽  
Mutant Line ◽  
Binding Motif ◽  
Wild Type ◽  
3D Genome ◽  
Topologically Associated Domains ◽  
High Gene

Abstract Background Three-dimensional (3D) chromatin organization provides a critical foundation to investigate gene expression regulation and cellular homeostasis. Results Here, we present the first 3D genome architecture maps in wild type and mutant allotetraploid peanut lines, which illustrate A/B compartments, topologically associated domains (TADs), and widespread chromatin interactions. Most peanut chromosomal arms (52.3%) have active regions (A compartments) with relatively high gene density and high transcriptional levels. About 2.0% of chromosomal regions switch from inactive to active (B-to-A) in the mutant line, harboring 58 differentially expressed genes enriched in flavonoid biosynthesis and circadian rhythm functions. The mutant peanut line shows a higher number of genome-wide cis-interactions than its wild-type. The present study reveals a new TAD in the mutant line that generates different chromatin loops and harbors a specific upstream AP2EREBP-binding motif which might upregulate the expression of the GA2ox gene and decrease active gibberellin (GA) content, presumably making the mutant plant dwarf. Conclusions Our findings will shed new light on the relationship between 3D chromatin architecture and transcriptional regulation in plants.

scholarly journals Pemahaman Konsep Siswa pada Materi Bangun Datar Terhadap Hasil Belajar Dimensi Tiga

2018 ◽  
Vol 2 (2) ◽  
pp. 132
Author(s):  
Malik Ibrahim
Keyword(s):  
Learning Outcomes ◽  
Three Dimensional ◽  
Positive Influence ◽  
Three Dimensions ◽  
Ex Post ◽  
Ex Post Facto ◽  
Third Dimension ◽  
Level Of Understanding ◽  
The Impact ◽  
The Relationship

Abstrak: Penelitian ini bertujuan untuk mengetahui seberapa besar pengaruh pemahaman konsep siswa pada materi bangun datar terhadap hasil belajar dimensi tiga kelas X MA. Hidayatul Muhsinin Labulia. Penelitian ini menggunakan pendekatan  kuantitatif jenis Ex Post Facto desain hubungan kausalitas yaitu hubungan yang bersifat sebab akibat. Penelitian ini menggunakan penelitian populasi yang jumlah keseluruhannya adalah 109 siswa terdiri dari kelas XA, XB dan XC.         Hasil penelitian menunjukkan pengaruh pemahaman konsep bangun datar cukup berpengaruh positif terhadap hasil belajar dimensi tiga. Hal ini terlihat pada hasil penelitian dengan melakukan pemberian tes kepada 109 siswa. Hubungan antara pemahaman konsep bangun datar dan hasil belajar dimensi tiga sebesar 0,668 atau 66,8%, ini berarti korelasi antara pemahaman konsep bangun datar dan hasil belajar dimensi tiga adalah cukup, sesuai dengan kriteria yang telah ada. Adapun pengaruh antara pemahaman konsep bangun datar dan hasil belajar dimensi tiga  sebesar 0,447 atau 44,7%. Sedangkan persamaan regresi antara pemahaman konsep bangun datar dan hasil belajar dimensi tiga adalah Y = 8,831 + 0,934 X, ini menjelasakan bahwa keterkaitan antara pemahaman konsep bangun datar dengan hasil belajar dimensi tiga bersifat searah (positif) atau dengan kata lain bahwa, jika tingkat pemahman konsep bangun datar tinggi maka akan mengakibatkan hasil belajar dimensi tiga tinggi pula, dan demikian pula sebaliknya. Berdasarkan penjelasan tersebut dapat disimpulkan bahwa terdapat pengaruh positif pemahaman konsep bangun datar terhadap hasil belajar dimensi tiga.Abstract:  This research aims to find out how much impact the students' conceptual understanding of the material is flat on the learning outcomes of the three dimensions of class X MA. Hidayatul Muhsinin Labulia. This study uses a quantitative approach to the type of Ex Post Facto design causality relationship that is causal relationships. This study uses a population research whose total number is 109 students consisting of classes XA, XB and XC. The results of the study showed that the impact of understanding the flat wake concept was quite a positive effect on the learning outcomes of three dimensions. This can be seen in the results of the study by giving tests to 109 students. The relationship between understanding the concept of flat wake and three dimensional learning outcomes is 0.668 or 66.8%, this means that the correlation between understanding the concept of flat wake and three dimensional learning outcomes is sufficient, according to existing criteria. The influence between the understanding of the concept of flat wake and the third dimension of learning outcomes is 0.447 or 44.7%. While the regression equation between understanding the concept of flat wake and three dimensional learning outcomes is Y = 8.831 + 0.934 X, this explains that the relationship between understanding the concept of flat wake with learning outcomes of three dimensions is unidirectional (positive) or in other words that, if the level of understanding concept wake up high then it will result in high three dimensional learning outcomes too, and vice versa. Based on these explanations, it can be concluded that there is a positive influence on understanding the concept of flat building on the results of three dimensional learning.

scholarly journals Chrom3D: three-dimensional genome modeling from Hi-C and nuclear lamin-genome contacts

2017 ◽  
Vol 18 (1) ◽  
Author(s):  
Jonas Paulsen ◽  
Monika Sekelja ◽  
Anja R. Oldenburg ◽  
Alice Barateau ◽  
Nolwenn Briand ◽  
...  
Keyword(s):  
Single Cells ◽  
Nuclear Periphery ◽  
Three Dimensional ◽  
Modeling Framework ◽  
Chromosome Conformation ◽  
3D Genome ◽  
Spatial Features ◽  
Nuclear Lamin ◽  
Topologically Associated Domains ◽  
User Friendly

Abstract Current three-dimensional (3D) genome modeling platforms are limited by their inability to account for radial placement of loci in the nucleus. We present Chrom3D, a user-friendly whole-genome 3D computational modeling framework that simulates positions of topologically-associated domains (TADs) relative to each other and to the nuclear periphery. Chrom3D integrates chromosome conformation capture (Hi-C) and lamin-associated domain (LAD) datasets to generate structure ensembles that recapitulate radial distributions of TADs detected in single cells. Chrom3D reveals unexpected spatial features of LAD regulation in cells from patients with a laminopathy-causing lamin mutation. Chrom3D is freely available on github.

scholarly journals Detection of therapeutic radiation in three-dimensions

2017 ◽  
Vol 13 ◽  
pp. 1325-1331 ◽  
Author(s):  
John A Adamovics
Keyword(s):  
State Of The Art ◽  
Three Dimensional ◽  
The State ◽  
Three Dimensions ◽  
Radical Initiator ◽  
Radiation Delivery ◽  
Dimensional Shape ◽  
Therapeutic Radiation ◽  
The Impact ◽  
Three Dimensional Shape

For over the last twenty years there has been a multitude of sophisticated three-dimensional radiation delivery procedures developed which requires a corresponding verification of the impact on patients. This article reviews the state of the art in the development of chemical detectors used to characterize the three-dimensional shape of therapeutic radiation. These detectors are composed of polyurethane, radical initiator and a leuco dye, which is radiolytically oxidized to a dye absorbing at 630 nm.

scholarly journals Rice 3D chromatin structure correlates with sequence variation and meiotic recombination rate

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Agnieszka A. Golicz ◽  
Prem L. Bhalla ◽  
David Edwards ◽  
Mohan B. Singh
Keyword(s):  
Meiotic Recombination ◽  
Recombination Rate ◽  
Sequence Variation ◽  
Genome Structure ◽  
Rice Genome ◽  
Three Dimensional ◽  
3D Genome ◽  
Cellular Processes ◽  
Eukaryotic Species ◽  
Topologically Associated Domains

AbstractGenomes of many eukaryotic species have a defined three-dimensional architecture critical for cellular processes. They are partitioned into topologically associated domains (TADs), defined as regions of high chromatin inter-connectivity. While TADs are not a prominent feature of A. thaliana genome organization, they have been reported for other plants including rice, maize, tomato and cotton and for which TAD formation appears to be linked to transcription and chromatin epigenetic status. Here we show that in the rice genome, sequence variation and meiotic recombination rate correlate with the 3D genome structure. TADs display increased SNP and SV density and higher recombination rate compared to inter-TAD regions. We associate the observed differences with the TAD epigenetic landscape, TE composition and an increased incidence of meiotic crossovers.

scholarly journals Folate rescues vitamin B12 depletion-induced inhibition of nuclear thymidylate biosynthesis and genome instability

2017 ◽  
Vol 114 (20) ◽  
pp. E4095-E4102 ◽  
Author(s):  
Ashley M. Palmer ◽  
Elena Kamynina ◽  
Martha S. Field ◽  
Patrick J. Stover
Keyword(s):  
De Novo ◽  
Genome Instability ◽  
Megaloblastic Anemia ◽  
Tight Binding ◽  
Vitamin B ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Histone H2ax ◽  
Inhibition Of Dna Synthesis ◽  
The Impact

Clinical vitamin B12 deficiency can result in megaloblastic anemia, which results from the inhibition of DNA synthesis by trapping folate cofactors in the form of 5-methyltetrahydrofolate (5-methylTHF) and subsequent inhibition of de novo thymidylate (dTMP) biosynthesis. In the cytosol, vitamin B12 functions in the remethylation of homocysteine to methionine, which regenerates THF from 5-methylTHF. In the nucleus, THF is required for de novo dTMP biosynthesis, but it is not understood how 5-methylTHF accumulation in the cytosol impairs nuclear dTMP biosynthesis. The impact of vitamin B12 depletion on nuclear de novo dTMP biosynthesis was investigated in methionine synthase-null human fibroblast and nitrous oxide-treated HeLa cell models. The nucleus was the most sensitive cellular compartment to 5-methylTHF accumulation, with levels increasing greater than fourfold. Vitamin B12 depletion decreased de novo dTMP biosynthesis capacity by 5–35%, whereas de novo purine synthesis, which occurs in the cytosol, was not affected. Phosphorylated histone H2AX (γH2AX), a marker of DNA double-strand breaks, was increased in vitamin B12 depletion, and this effect was exacerbated by folate depletion. These studies also revealed that 5-formylTHF, a slow, tight-binding inhibitor of serine hydroxymethyltransferase (SHMT), was enriched in nuclei, accounting for 35% of folate cofactors, explaining previous observations that nuclear SHMT is not a robust source of one-carbons for de novo dTMP biosynthesis. These findings indicate that a nuclear 5-methylTHF trap occurs in vitamin B12 depletion, which suppresses de novo dTMP biosynthesis and causes DNA damage, accounting for the pathophysiology of megaloblastic anemia observed in vitamin B12 and folate deficiency.

scholarly journals Streptococcus pneumoniaesecretes hydrogen peroxide leading to DNA damage and apoptosis in lung cells

2015 ◽  
Vol 112 (26) ◽  
pp. E3421-E3430 ◽  
Author(s):  
Prashant Rai ◽  
Marcus Parrish ◽  
Ian Jun Jie Tay ◽  
Na Li ◽  
Shelley Ackerman ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Critical Role ◽  
Alveolar Epithelial Cells ◽  
Dna Double Strand Breaks ◽  
Histone H2ax ◽  
Alveolar Epithelial ◽  
Time Required ◽  
The Impact

Streptococcus pneumoniaeis a leading cause of pneumonia and one of the most common causes of death globally. The impact ofS. pneumoniaeon host molecular processes that lead to detrimental pulmonary consequences is not fully understood. Here, we show thatS. pneumoniaeinduces toxic DNA double-strand breaks (DSBs) in human alveolar epithelial cells, as indicated by ataxia telangiectasia mutated kinase (ATM)-dependent phosphorylation of histone H2AX and colocalization with p53-binding protein (53BP1). Furthermore, results show that DNA damage occurs in a bacterial contact-independent fashion and that Streptococcus pyruvate oxidase (SpxB), which enables synthesis of H2O2, plays a critical role in inducing DSBs. The extent of DNA damage correlates with the extent of apoptosis, and DNA damage precedes apoptosis, which is consistent with the time required for execution of apoptosis. Furthermore, addition of catalase, which neutralizes H2O2, greatly suppressesS. pneumoniae-induced DNA damage and apoptosis. Importantly,S. pneumoniaeinduces DSBs in the lungs of animals with acute pneumonia, and H2O2production byS. pneumoniaein vivo contributes to its genotoxicity and virulence. One of the major DSBs repair pathways is nonhomologous end joining for which Ku70/80 is essential for repair. We find that deficiency of Ku80 causes an increase in the levels of DSBs and apoptosis, underscoring the importance of DNA repair in preventingS. pneumoniae-induced genotoxicity. Taken together, this study shows thatS. pneumoniae-induced damage to the host cell genome exacerbates its toxicity and pathogenesis, making DNA repair a potentially important susceptibility factor in people who suffer from pneumonia.

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