scholarly journals Telomeric G-Quadruplexes: From Human to Tetrahymena Repeats

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Erika Demkovičová ◽  
Ľuboš Bauer ◽  
Petra Krafčíková ◽  
Katarína Tlučková ◽  
Petra Tóthova ◽  
...  
Keyword(s):  
Life Cycle ◽  
Base Substitution ◽  
Telomeric Dna ◽  
Purine Base ◽  
Telomeric Sequences ◽  
G Quadruplex ◽  
The Stability ◽  
Scientific Value ◽  
The Relationship ◽  
Adenine Base

The human telomeric and protozoal telomeric sequences differ only in one purine base in their repeats; TTAGGG in telomeric sequences; and TTGGGG in protozoal sequences. In this study, the relationship between G-quadruplexes formed from these repeats and their derivatives is analyzed and compared. The human telomeric DNA sequence G3(T2AG3)3 and related sequences in which each adenine base has been systematically replaced by a guanine were investigated; the result is Tetrahymena repeats. The substitution does not affect the formation of G-quadruplexes but may cause differences in topology. The results also show that the stability of the substituted derivatives increased in sequences with greater number of substitutions. In addition, most of the sequences containing imperfections in repeats which were analyzed in this study also occur in human and Tetrahymena genomes. Generally, the presence of G-quadruplex structures in any organism is a source of limitations during the life cycle. Therefore, a fuller understanding of the influence of base substitution on the structural variability of G-quadruplexes would be of considerable scientific value.

scholarly journals Forever Young: Structural Stability of Telomeric Guanine-Quadruplexes in Presence of Oxidative DNA Lesions

2020 ◽  
Author(s):  
Tom Miclot ◽  
Camille Corbier ◽  
Alessio Terenzi ◽  
Cécilia Hognon ◽  
Stéphanie Grandemange ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Dynamics ◽  
Structural Stability ◽  
Md Simulations ◽  
Dna Lesions ◽  
Computational Investigation ◽  
Telomeric Dna ◽  
G Quadruplex ◽  
The Stability

AbstractHuman telomeric DNA (h-Telo), in G-quadruplex (G4) conformation, is characterized by a remarkable structural stability that confers it the capacity to resist to oxidative stress producing one or even clustered 8-oxoguanine lesions. We present a combined experimental/computational investigation, by using circular dichroism in aqueous solutions, cellular immunofluorescence assays and molecular dynamics (MD) simulations, that identifies the crucial role of the stability of G4s to oxidative lesions, related also to their biological role as inhibitors of telomerase, an enzyme overexpressed in most cancers associated to oxidative stress.

scholarly journals Molecular Dynamics Study of the Interaction of Carbon Nanotubes with Telomeric DNA Fragment Containing Noncanonical G-Quadruplex and i-Motif Forms

2020 ◽  
Vol 21 (6) ◽  
pp. 1925 ◽  
Author(s):  
Tomasz Panczyk ◽  
Patrycja Wojton ◽  
Pawel Wolski
Keyword(s):  
Carbon Nanotubes ◽  
Molecular Dynamics ◽  
Spatial Structure ◽  
Computational Procedure ◽  
Middle Part ◽  
Telomeric Dna ◽  
Neutral Ph ◽  
G Quadruplex ◽  
The Stability ◽  
Dynamics Simulations

This work deals with molecular dynamics simulations of systems composed of telomeric dsDNA fragments, iG, and functionalized carbon nanotubes, fCNT. The iG contains 90 nucleotides in total and in its middle part the noncanonical i-motif and G-quadruplex are formed. Two chiralities of the fCNT were used, i.e., (10,0) and (20,0) and these nanotubes were either on-tip functionalized by guanine containing functional groups or left without functionalization. We proposed a dedicated computational procedure, based on the replica exchange concept, for finding a thermodynamically optimal conformation of iG and fCNT without destroying the very fragile noncanonical parts of the iG. We found that iG forms a V-shape spatial structure with the noncanonical fragments located at the edge and the remaining dsDNA strands forming the arms of V letter. The optimal configuration of iG in reference to fCNT strongly depends on the on-tip functionalization of the fCNT. The carbon nanotube without functionalization moves freely between the dsDNA arms, while the presence of guanine residues leads to immobilization of the fCNT and preferential location of the nanotube tip near the junction between the dsDNA duplex and i-motif and G-quadruplex. We also studied how the presence of fCNT affects the stability of the i-motif at the neutral pH when the cytosine pairs are nonprotonated. We concluded that carbon nanotubes do not improve the stability of the spatial structure of i-motif also when it is a part of a bigger structure like the iG. Such an effect was described in literature in reference to carboxylated nanotubes. Our current results suggest that the stabilization of i-motif is most probably related to easy formation of semiprotonated cytosine pairs at neutral pH due to interaction with carboxylated carbon nanotubes.

scholarly journals Interrogating accessibility of telomeric sequences with FRET-PAINT: evidence for length-dependent telomere compaction

2021 ◽  
Author(s):  
Golam Mustafa ◽  
Sajad Shiekh ◽  
Keshav GC ◽  
Sanjaya Abeysirigunawardena ◽  
Hamza Balci
Keyword(s):  
Dna Damage ◽  
Telomere Length ◽  
Dna Damage Response ◽  
Single Molecule ◽  
Telomeric Repeat ◽  
Dna Molecules ◽  
Telomeric Dna ◽  
Telomeric Sequences ◽  
G Quadruplex ◽  
Damage Response

Abstract Single-stranded telomeric overhangs are ∼200 nucleotides long and can form tandem G-quadruplex (GQ) structures, which reduce their accessibility to nucleases and proteins that activate DNA damage response. Whether these tandem GQs further stack to form compact superstructures, which may provide better protection for longer telomeres, is not known. We report single-molecule measurements where the accessibility of 24–144 nucleotide long human telomeric DNA molecules is interrogated by a short PNA molecule that is complementary to a single GGGTTA repeat, as implemented in the FRET-PAINT method. Binding of the PNA strand to available GGGTTA sequences results in discrete FRET bursts which were analyzed in terms of their dwell times, binding frequencies, and topographic distributions. The binding frequencies were greater for binding to intermediate regions of telomeric DNA compared to 3′- or 5′-ends, suggesting these regions are more accessible. Significantly, the binding frequency per telomeric repeat monotonically decreased with increasing telomere length. These results are consistent with telomeres forming more compact structures at longer lengths, reducing accessibility of these critical genomic sites.

scholarly journals Stabilization of Telomere G-Quadruplexes Interferes with Human Herpesvirus 6A Chromosomal Integration

2017 ◽  
Vol 91 (14) ◽  
Author(s):  
Shella Gilbert-Girard ◽  
Annie Gravel ◽  
Sara Artusi ◽  
Sara N. Richter ◽  
Nina Wallaschek ◽  
...  
Keyword(s):  
Tertiary Structure ◽  
Human Herpesvirus ◽  
Telomerase Activity ◽  
Chromosomal Integration ◽  
Telomeric Dna ◽  
Telomeric Sequences ◽  
Telomere Elongation ◽  
Alternative Lengthening ◽  
G Quadruplex ◽  
Infected Cells

ABSTRACTHuman herpesviruses 6A and 6B (HHV-6A/B) can integrate their genomes into the telomeres of human chromosomes using a mechanism that remains poorly understood. To achieve a better understanding of the HHV-6A/B integration mechanism, we made use of BRACO-19, a compound that stabilizes G-quadruplex secondary structures and prevents telomere elongation by the telomerase complex. First, we analyzed the folding of telomeric sequences into G-quadruplex structures and their binding to BRACO-19 using G-quadruplex-specific antibodies and surface plasmon resonance. Circular dichroism studies indicate that BRACO-19 modifies the conformation and greatly stabilizes the G-quadruplexes formed in G-rich telomeric DNA. Subsequently we assessed the effects of BRACO-19 on the HHV-6A initial phase of infection. Our results indicate that BRACO-19 does not affect entry of HHV-6A DNA into cells. We next investigated if stabilization of G-quadruplexes by BRACO-19 affected HHV-6A's ability to integrate its genome into host chromosomes. Incubation of telomerase-expressing cells with BRACO-19, such as HeLa and MCF-7, caused a significant reduction in the HHV-6A integration frequency (P< 0.002); in contrast, BRACO-19 had no effect on HHV-6 integration frequency in U2OS cells that lack telomerase activity and elongate their telomeres through alternative lengthening mechanisms. Our data suggest that the fluidity of telomeres is important for efficient chromosomal integration of HHV-6A and that interference with telomerase activity negatively affects the generation of cellular clones containing integrated HHV-6A.IMPORTANCEHHV-6A/B can integrate their genomes into the telomeres of infected cells. Telomeres consist of repeated hexanucleotides (TTAGGG) of various lengths (up to several kilobases) and end with a single-stranded 3′ extension. To avoid recognition and induce a DNA damage response, the single-stranded overhang folds back on itself and forms a telomeric loop (T-loop) or adopts a tertiary structure, referred to as a G-quadruplex. In the current study, we have examined the effects of a G-quadruplex binding and stabilizing agent, BRACO-19, on HHV-6A chromosomal integration. By stabilizing G-quadruplex structures, BRACO-19 affects the ability of the telomerase complex to elongate telomeres. Our results indicate that BRACO-19 reduces the number of clones harboring integrated HHV-6A. This study is the first of its kind and suggests that telomerase activity is essential to restore a functional telomere of adequate length following HHV-6A integration.

An Experimental Investigation on Thermal Conductivity and Viscosity of Graphene doped CNTs /TiO2 Nanofluid

2020 ◽  
Vol 17 (3) ◽  
Author(s):  
A.M. Zetty Akhtar ◽  
M.M. Rahman ◽  
K. Kadirgama ◽  
M.A. Maleque
Keyword(s):  
Thermal Conductivity ◽  
Zeta Potential ◽  
Base Fluid ◽  
Minimum Quantity Lubrication ◽  
Cutting Fluid ◽  
Cutting Zone ◽  
Observation Method ◽  
The Stability ◽  
The Relationship ◽  
Zeta Potential Analysis

This paper presents the findings of the stability, thermal conductivity and viscosity of CNTs (doped with 10 wt% graphene)- TiO2 hybrid nanofluids under various concentrations. While the usage of cutting fluid in machining operation is necessary for removing the heat generated at the cutting zone, the excessive use of it could lead to environmental and health issue to the operators. Therefore, the minimum quantity lubrication (MQL) to replace the conventional flooding was introduced. The MQL method minimises the usage of cutting fluid as a step to achieve a cleaner environment and sustainable machining. However, the low thermal conductivity of the base fluid in the MQL system caused the insufficient removal of heat generated in the cutting zone. Addition of nanoparticles to the base fluid was then introduced to enhance the performance of cutting fluids. The ethylene glycol used as the base fluid, titanium dioxide (TiO2) and carbon nanotubes (CNTs) nanoparticle mixed to produce nanofluids with concentrations of 0.02 to 0.1 wt.% with an interval of 0.02 wt%. The mixing ratio of TiO2: CNTs was 90:10 and ratio of SDBS (surfactant): CNTs was 10:1. The stability of nanofluid checked using observation method and zeta potential analysis. The thermal conductivity and viscosity of suspension were measured at a temperature range between 30˚C to 70˚C (with increment of 10˚C) to determine the relationship between concentration and temperature on nanofluid’s thermal physical properties. Based on the results obtained, zeta potential value for nanofluid range from -50 to -70 mV indicates a good stability of the suspension. Thermal conductivity of nanofluid increases as an increase of temperature and enhancement ratio is within the range of 1.51 to 4.53 compared to the base fluid. Meanwhile, the viscosity of nanofluid shows decrements with an increase of the temperature remarks significant advantage in pumping power. The developed nanofluid in this study found to be stable with enhanced thermal conductivity and decrease in viscosity, which at once make it possible to be use as nanolubricant in machining operation.

A FORECAST OF PRODUCTIVE LONGEVITY OF HOLSTEIN COWS BY INDIRECT SIGNS

2020 ◽  
Author(s):  
З.С. САНОВА
Keyword(s):  
Correlation Coefficient ◽  
Aging Process ◽  
Direct Relationship ◽  
Stability Index ◽  
Age At First Calving ◽  
Group I ◽  
Predicted Values ◽  
The Stability ◽  
Relationship Of ◽  
The Relationship

В статье представлены материалы о взаимосвязи продолжительности продуктивного использования коров с характеристикой устойчивости к деградации, с возрастом отела и удоем. В исследованной, разнородной по происхождению, группе животных для прогноза продуктивного периода коров, обусловленного устойчивостью к деградации и возрастом первого отела, пригодно уравнение регрессии, аргументами в котором являются индекс устойчивости, возраст первого отела в первой и второй степенях. Коэффициент корреляции межу предсказанными значениями продуктивного периода и его фактическими величинами в I группе составляет 0,502, во II - 0,604. При этом крайние варианты прогнозируются со статистическими ошибками 5 мес при оценке индекса устойчивости по 2 лактациям и 4,1 мес по 3, а средние варианты, соответственно, 1,6 и 1,51 мес. Индекс устойчивости к процессу старения является важной характеристикой биологических особенностей коров, определяющий их продуктивное долголетие. Его оценка по первым 2 и 3 лактациям имеет прямолинейную связь с продуктивным периодом (r=0,4109 и r=0,5270), соответственно. Зависимость продуктивного периода от возраста первого отела криволинейная — с увеличением возраста первого отела сокращается срок продуктивного использования, при возрасте первого отела более 1400 дней срок продуктивного использования колеблется от 1,33 до 1,41 лактации. Коэффициент корреляции между этими характеристиками коров составляет - 0,2164 в I и - 0,2620 во II группах. The article presents materials about the relationship of the duration of productive use of cows with the characteristic of resistance to degradation, with the age of calving and milk yield. In the studied group of animals, which is heterogeneous in origin, the regression equation is suitable for predicting the productive period of cows due to resistance to degradation and the age of the first calving, the arguments of which are the stability index, the age of the first calving in the first and second degrees. The correlation coefficient between the predicted values of the productive period and its actual values in group I is 0.502, in group II - 0.604. At the same time, the extreme variants are predicted with statistical errors of 5 months when evaluating the stability index for 2 lactations and 4.1 months for 3, and the average variants, respectively, are 1.6 and 1.51 months. The index of resistance to the aging process is an important characteristic of the biological characteristics of cows, which determines their productive longevity. Its estimate for the first 2 and 3 lactations has a direct relationship with the productive period (r=0.4109 and r=0.5270), respectively. The dependence of the productive period age at first calving curvilinear with increasing age at first calving reduces the time to productive use, while age at first calving of more than 1400 days, the period of productive use ranges from 1.33 to 1.41 lactation. The correlation coefficient between these characteristics of cows is-0.2164 in I and-0.2620 in II groups.

Substantiation the machine with a basket for the application of mineral fertilizers and other bulk materials with the upper arrangement of the feeding device

2019 ◽  
pp. 37-43
Author(s):  
Fesenko, H.
Keyword(s):  
Fat Body ◽  
Mineral Fertilizer ◽  
The Body ◽  
Mineral Fertilizers ◽  
Analytical Mechanics ◽  
Bulk Materials ◽  
The Stability ◽  
Working Bodies ◽  
The Relationship ◽  
Stable Flow

Purpose. Increasing the uniformity of distribution of mineral fertilizers and other bulk materials due to the stability of their feed from the body to the spreading working bodies using the top feeder. Methods. The following methods are used to achieve this aim: the method of comparing the differences between individual groups of fertilizers, the method of analyzing the properties of a new technical system, the method of functional inventiveness, and the methods of theoretical and analytical mechanics. Results. The traction body of the conveyor of the upper feed of the body fat body machine for mineral fertilizers and other bulk materials was substantiated and the relationship between the height of its scrapers and the distance between them was established, as well as the nature of the mineral fertilizer pressure on the curvilinear wall of the body. In addition, the design of the advanced body fertilizer spreader is justified, which ensures a stable flow of fertilizers from the body due to the improvement of the top feeder. Conclusions. Because of the conducted researches, the advantages of machines equipped with top feeder are found. They create the conditions for the forced feeding mineral fertilizers and other loose materials from the container to the distribution bodies, which is a prerequisite for their evenness on the surface. With this, the imperfection of known machines with the top feeder constrains their introduction into agricultural production. On this account, a more thoroughly constructed solution of the body feeder of the top feed is substantiated, in which the conveyor provides a stable supply of fertilizers from the body with reduced energy consumption during operation. Keywords: analysis, feed, upper device, conveyor, stability, fertilizers, flow ability, body.

FINANCIAL CRISES AND THE PUBLICATION OF THE FINANCIAL STATEMENTS OF BANKS IN SPAIN, 1844–1868

2004 ◽  
Vol 31 (2) ◽  
pp. 1-26 ◽  
Author(s):  
Mercedes Bernal Lloréns
Keyword(s):  
19Th Century ◽  
Financial Reporting ◽  
Economic Performance ◽  
Financial Crises ◽  
Limited Liability ◽  
Financial Statements ◽  
Early Response ◽  
Banking Regulations ◽  
The Stability ◽  
The Relationship

Financial crises have had a decisive influence on banking regulations in Spain. During the mid-19th century the publication of the financial statements of banks was considered key to the stability of the financial system. All new joint stock banking companies were to publish their statements in the Madrid Gazette in return for the privilege of limited liability. Similar obligations were placed on issuing banks. The copious publication of financial statements coincided with a period of financial prosperity. However, the crises that followed from 1864 to 1868 led to a reduction in the official publication of statements. This paper is concerned with an early response to crises in financial reporting. The study focuses on the relationship between the publication of accounting statements by banks and the GDP in Spain during the mid-19th century. The results suggest that the frequency of publication of financial statements may be an indicator of economic performance.

scholarly journals PhenQE8, a Novel Ligand of the Human Telomeric Quadruplex

2021 ◽  
Vol 22 (2) ◽  
pp. 749
Author(s):  
Patricia B. Gratal ◽  
Julia G. Quero ◽  
Adrián Pérez-Redondo ◽  
Zoila Gándara ◽  
Lourdes Gude
Keyword(s):  
Equilibrium Dialysis ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
The Novel ◽  
X Ray Diffraction ◽  
Telomeric Dna ◽  
Healthy Human ◽  
Quadruplex Dna ◽  
Step Procedure ◽  
G Quadruplex

A novel quadruplex ligand based on 1,10-phenanthroline and incorporating two guanyl hydrazone functionalities, PhenQE8, is reported herein. Synthetic access was gained in a two-step procedure with an overall yield of 61%. X-ray diffraction studies revealed that PhenQE8 can adopt an extended conformation that may be optimal to favor recognition of quadruplex DNA. DNA interactions with polymorphic G-quadruplex telomeric structures were studied by different techniques, such as Fluorescence resonance energy transfer (FRET) DNA melting assays, circular dichroism and equilibrium dialysis. Our results reveal that the novel ligand PhenQE8 can efficiently recognize the hybrid quadruplex structures of the human telomeric DNA, with high binding affinity and quadruplex/duplex selectivity. Moreover, the compound shows significant cytotoxic activity against a selected panel of cultured tumor cells (PC-3, HeLa and MCF-7), whereas its cytotoxicity is considerably lower in healthy human cells (HFF-1 and RPWE-1).

Sign in / Sign up

Export Citation Format

Share Document