scholarly journals Translocation of flexible and tensioned ssDNA through in silico designed hydrophobic nanopores with two constrictions

2020 ◽  
Author(s):  
Punam Rattu ◽  
Taylor Haynes ◽  
E. Jayne Wallace ◽  
Syma Khalid
Keyword(s):  
Dna Bases ◽  
Dna Conformation ◽  
Window Of Opportunity ◽  
Pore Width ◽  
Dna Translocation ◽  
Aromatic Residues ◽  
Dna Strands ◽  
Dna Backbone ◽  
The Impact ◽  
Constriction Region

ABSTRACTProtein-inspired nanopores with hydrophobic constriction regions have previously been shown to offer some promise for DNA sequencing. Here we explore a series of pores with two hydrophobic constrictions. The impact of nanopore radius, the nature of residues that define the constriction region and the flexibility of the ssDNA is explored. Our results show that aromatic residues slow down DNA translocation, and in the case of short DNA strands, they cause deviations from a linear DNA conformation. When DNA is under tension, translocation is once again slower when aromatic residues are present in the constriction. However, the lack of flexibility in the DNA backbone provides a narrower window of opportunity for the DNA bases to be retained inside the pore via interaction with the aromatic residues, compared to more flexible strands. Consequently, there is more variability in translocation rates for strands under tension. DNA entry into the pores is correlated to pore width, but no such correlation between width and translocation rate is observed.

scholarly journals DNA Translocation Through Vertically Stacked 2D Layers of Graphene & Hexagonal Boron Nitride Heterostructure Nanopore

2020 ◽  
Author(s):  
Ramkumar Balasubramanian ◽  
Sohini Pal ◽  
Anjana Rao ◽  
Akshay Naik ◽  
Banani Chakraborty ◽  
...  
Keyword(s):  
Boron Nitride ◽  
Single Molecule ◽  
Hexagonal Boron Nitride ◽  
Membrane Surface ◽  
Cost Effective ◽  
Dna Bases ◽  
Dna Translocation ◽  
Sensing Applications ◽  
Dna Strands ◽  
Signal Variability

Cost effective, fast and reliable DNA sequencing can be enabled by advances in nanopore based methods, such as the use of atomically thin graphene membranes. However, strong interaction of DNA bases with graphene leads to undesirable effects such as sticking of DNA strands to the membrane surface. While surface functionalization is one way to counter this problem, here we present another solution based on a heterostructure nanopore system, consisting of a monolayer of graphene and hexagonal Boron Nitride (hBN) each. Molecular dynamics studies of DNA translocation through this heterostructure nanopore revealed a surprising and crucial influence of heterostructure layer order in controlling the base specific signal variability. Specifically, the heterostructure with graphene on top of hBN had nearly 3-10x lower signal variability than the one with hBN on top of graphene. Simulations point to the role of differential underside sticking of DNA bases as a possible reason for the observed influence of layer order. Our studies can guide the development of experimental systems to study and exploit DNA translocation through two-dimensional heterostructure nanopores for single molecule sequencing and sensing applications.

scholarly journals DNA Translocation Through Vertically Stacked 2D Layers of Graphene & Hexagonal Boron Nitride Heterostructure Nanopore

2020 ◽  
Author(s):  
Ramkumar Balasubramanian ◽  
Sohini Pal ◽  
Anjana Rao ◽  
Akshay Naik ◽  
Banani Chakraborty ◽  
...  
Keyword(s):  
Boron Nitride ◽  
Single Molecule ◽  
Hexagonal Boron Nitride ◽  
Membrane Surface ◽  
Cost Effective ◽  
Dna Bases ◽  
Dna Translocation ◽  
Sensing Applications ◽  
Dna Strands ◽  
Signal Variability

Cost effective, fast and reliable DNA sequencing can be enabled by advances in nanopore based methods, such as the use of atomically thin graphene membranes. However, strong interaction of DNA bases with graphene leads to undesirable effects such as sticking of DNA strands to the membrane surface. While surface functionalization is one way to counter this problem, here we present another solution based on a heterostructure nanopore system, consisting of a monolayer of graphene and hexagonal Boron Nitride (hBN) each. Molecular dynamics studies of DNA translocation through this heterostructure nanopore revealed a surprising and crucial influence of heterostructure layer order in controlling the base specific signal variability. Specifically, the heterostructure with graphene on top of hBN had nearly 3-10x lower signal variability than the one with hBN on top of graphene. Simulations point to the role of differential underside sticking of DNA bases as a possible reason for the observed influence of layer order. Our studies can guide the development of experimental systems to study and exploit DNA translocation through two-dimensional heterostructure nanopores for single molecule sequencing and sensing applications.

scholarly journals Multivariate Analysis as a Tool for Quantification of Conformational Transitions in DNA Thin Films

2021 ◽  
Vol 11 (13) ◽  
pp. 5895
Author(s):  
Kristina Serec ◽  
Sanja Dolanski Babić
Keyword(s):  
Thin Films ◽  
Learning Algorithm ◽  
Principal Component Regression ◽  
Principal Component ◽  
Conformational Transitions ◽  
Cancer Diagnostics ◽  
Dna Conformation ◽  
Support Vector ◽  
Multivariate Statistical ◽  
The Impact

The double-stranded B-form and A-form have long been considered the two most important native forms of DNA, each with its own distinct biological roles and hence the focus of many areas of study, from cellular functions to cancer diagnostics and drug treatment. Due to the heterogeneity and sensitivity of the secondary structure of DNA, there is a need for tools capable of a rapid and reliable quantification of DNA conformation in diverse environments. In this work, the second paper in the series that addresses conformational transitions in DNA thin films utilizing FTIR spectroscopy, we exploit popular chemometric methods: the principal component analysis (PCA), support vector machine (SVM) learning algorithm, and principal component regression (PCR), in order to quantify and categorize DNA conformation in thin films of different hydrated states. By complementing FTIR technique with multivariate statistical methods, we demonstrate the ability of our sample preparation and automated spectral analysis protocol to rapidly and efficiently determine conformation in DNA thin films based on the vibrational signatures in the 1800–935 cm−1 range. Furthermore, we assess the impact of small hydration-related changes in FTIR spectra on automated DNA conformation detection and how to avoid discrepancies by careful sampling.

scholarly journals Nanopore design for exceptional rectification of DNA translocation

2021 ◽  
Author(s):  
Ngan Pham ◽  
Yao Yao ◽  
Chenyu Wen ◽  
Shiyu Li ◽  
Shuangshuang Zeng ◽  
...  
Keyword(s):  
Numerical Simulation ◽  
Solid State ◽  
Surface Charge ◽  
Dna Translocation ◽  
Sensor Applications ◽  
Sensor Performance ◽  
On Demand ◽  
Dna Strands ◽  
Large Opening ◽  
Shape And Size

Abstract Solid-state nanopores (SSNPs) of on-demand shape and size can facilitate desired sensor performance. However, reproducible production of arrayed nanopores of predefined geometry is yet to demonstrate despite of numerous methods explored. Here, bowl-shape SSNPs combining unique properties of ultrathin membrane and tapering geometry are demonstrated. The bowl-SSNP upper opening is 100-120 nm in diameter, with the bottom opening reaching sub-5 nm. Numerical simulation reveals the formation of multiple electroosmotic vortexes (EOVs) originating from distributed surface charge around the pore-bowl. The EOVs determine, collaboratively with electrophoretic force, how nanoscale objects translocate the bowl-SSNPs. Exceptional rectification with higher frequencies, longer duration and larger amplitude is found when DNA strands translocate downwards from the upper large opening than upwards from the bottom smallest restriction. The rectification is a manifestation of the interplay between electrophoresis and electroosmosis. The resourceful silicon nanofabrication technology is ingeniously shown to enable innovative nanopore designs targeting unprecedented sensor applications.

scholarly journals A biophysical and structural analysis of DNA binding by oligomeric hSSB1 (NABP2/OBFC2B)

2020 ◽  
Author(s):  
Serene El-Kamand ◽  
Slobodan Jergic ◽  
Teegan Lawson ◽  
Ruvini Kariawasam ◽  
Derek J. Richard ◽  
...  
Keyword(s):  
Dna Binding ◽  
Oxidative Dna Damage ◽  
Genomic Stability ◽  
Dna Binding Protein ◽  
Oxidative Modification ◽  
Dna Bases ◽  
Genome Integrity ◽  
Oligomeric Proteins ◽  
Ssdna Binding ◽  
Dna Strands

AbstractThe oxidative modification of DNA can result in the loss of genome integrity and must be repaired to maintain overall genomic stability. We have recently demonstrated that human single stranded DNA binding protein 1 (hSSB1/NABP2/OBFC2B) plays a crucial role in the removal of 8-oxo-7,8-dihydro- guanine (8-oxoG), the most common form of oxidative DNA damage. The ability of hSSB1 to form disulphide-bonded tetramers and higher oligomers in an oxidative environment is critical for this process. In this study, we have used nuclear magnetic resonance (NMR) spectroscopy and surface plasmon resonance (SPR) experiments to determine the molecular details of ssDNA binding by oligomeric hSSB1. We reveal that hSSB1 oligomers interact with single DNA strands containing damaged DNA bases; however, our data also show that oxidised bases are recognised in the same manner as undamaged DNA bases. We further demonstrate that oxidised hSSB1 interacts with ssDNA with a significantly higher affinity than its monomeric form confirming that oligomeric proteins such as tetramers can bind directly to ssDNA. NMR experiments provide evidence that oligomeric hSSB1 is able to bind longer ssDNA in both binding polarities using a distinct set of residues different to those of the related SSB from Escherichia coli.

Corruption Scandals, the Evolution of Anti-Corruption Institutions, and Their Impact on Brazil’s Economy

2018 ◽  
Author(s):  
Mariana Mota Prado ◽  
Lindsey Carson
Keyword(s):  
Institutional Change ◽  
Economic Performance ◽  
Window Of Opportunity ◽  
Institutional Reforms ◽  
Government Reforms ◽  
The Impact

This chapter considers corruption in the Brazilian context and the impact this may have had on economic performance. It is first suggested that a corruption scandal can create a window of opportunity for reforms, such that a government’s action or inaction in the aftermath of a scandal may signify its commitment to institutional change. The chapter assesses the impacts of past scandals and responsive institutional reforms on perceptions of corruption. Finally, the chapter considers how foreign and domestic investors may react to government reforms, as well as perception-based indicators of corruption. It is argued that some corruption scandals have had significant impact on institutional reforms and corruption indicators in Brazil.

scholarly journals Sequence-Specific Detection of DNA Strands Using a Solid-State Nanopore Assisted by Microbeads

Micromachines ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1097
Author(s):  
Yin Zhang ◽  
Zengdao Gu ◽  
Jiabin Zhao ◽  
Liying Shao ◽  
Yajing Kan
Keyword(s):  
Low Cost ◽  
Local Concentration ◽  
Dna Molecules ◽  
Dna Translocation ◽  
Specific Sequence ◽  
Free Dna ◽  
Target Dna ◽  
Dna Strands ◽  
Ionic Pulse ◽  
Biotinylated Probes

Simple, rapid, and low-cost detection of DNA with specific sequence is crucial for molecular diagnosis and therapy applications. In this research, the target DNA molecules are bonded to the streptavidin-coated microbeads, after hybridizing with biotinylated probes. A nanopore with a diameter significantly smaller than the microbeads is used to detect DNA molecules through the ionic pulse signals. Because the DNA molecules attached on the microbead should dissociate from the beads before completely passing through the pore, the signal duration time for the target DNA is two orders of magnitude longer than free DNA. Moreover, the high local concentration of target DNA molecules on the surface of microbeads leads to multiple DNA molecules translocating through the pore simultaneously, which generates pulse signals with amplitude much larger than single free DNA translocation events. Therefore, the DNA molecules with specific sequence can be easily identified by a nanopore sensor assisted by microbeads according to the ionic pulse signals.

Structural analysis of base mispairing in DNA containing oxidative guanine lesion

Open Physics ◽  
2007 ◽  
Vol 5 (1) ◽  
Author(s):  
Hirofumi Fujimoto ◽  
Miroslav Pinak ◽  
Toshiyuki Nemoto ◽  
Juraj Bunta
Keyword(s):  
Base Pair ◽  
Dna Bases ◽  
Pyrimidine Base ◽  
Normal Bases ◽  
Dna Molecule ◽  
Molecular Dynamics Methods ◽  
Opposite Strand ◽  
Base Mispairing ◽  
The Impact ◽  
Anti Form

AbstractClassical molecular dynamics methods were used to analyze the importance of 8-oxoguanine (8-oxoG) pairing with other DNA bases in order to determine the impact of oxidative guanine lesions on DNA structure. Six lesioned molecules, each containing 8-oxoG mispaired with one of the four normal bases on the the opposite strand at the center of 40-mer DNA, and one non-damaged DNA molecule, were simulated for 2 nanoseconds of real time. The 8-oxoG lesioned bases were found to incorporate opposite all normal bases. There are observed conformational and energetical differences among these parings. 8-oxoG in anti-form creates firm hydrogen bonds with cytosine and this bonding has a strong attractive electrostatic interaction energy similar to that of a native base pair-guanine to cytosine. Meanwhile, it does not form a stable base pair with purine bases (adenine and guanine) nor with the pyrimidine base thymine. On the other hand, the 8-oxoG in syn-form was found to pair with adenine.

Normalization and the Limits of the Law: The Case of the Czech Jazz Section

2008 ◽  
Vol 22 (2) ◽  
pp. 282-318
Author(s):  
Peter Bugge
Keyword(s):  
Legal Status ◽  
Social Activism ◽  
Social Discourse ◽  
Window Of Opportunity ◽  
Cultural Institutions ◽  
Law And Order ◽  
The Social ◽  
The Law ◽  
The Impact

The Jazz Section was one of the most remarkable cultural institutions in “normalized” Czechoslovakia. Established in 1971 as part of the official Musicians' Union, the Jazz Section used its legal status to arrange jazz and rock concerts and to publish a variety of books without the permission or consent of the Communist authorities. From the late 1970s, the regime strove hard to close the Section; however, it survived until 1984. Only in 1986 did the regime find a way to prosecute its leading activists. This article investigates why persecution proved so troublesome. It focuses on the impact of the Jazz Section's legalistic strategy, and on the role of legal concerns in regime behavior. It argues that references to “law and order” had a central legitimizing function in the social discourse of the Husák regime, and that the resulting need to translate policies of repression into legal measures inhibited the authorities in their assertion of power and created an ambiguous window of opportunity for independent social activism.

scholarly journals A Scintillator and Radio Enhancement of the IceCube Surface Detector Array

2019 ◽  
Vol 210 ◽  
pp. 06009
Author(s):  
Andreas Haungs
Keyword(s):  
Galactic Center ◽  
Cosmic Ray ◽  
Snow Accumulation ◽  
Mass Composition ◽  
Scintillation Detectors ◽  
Window Of Opportunity ◽  
Hadronic Interaction ◽  
Surface Detector ◽  
The Impact ◽  
Minimal Effort

An upgrade of the present IceCube surface array (IceTop) with scintillation detectors and possibly radio antennas is foreseen. The enhanced array will calibrate the impact of snow accumulation on the reconstruction of cosmic-ray showers detected by IceTop as well as improve the veto capabilities of the surface array. In addition, such a hybrid surface array of radio antennas, scintillators and Cherenkov tanks will enable a number of complementary science targets for IceCube such as enhanced accuracy to mass composition of cosmic rays, search for PeV photons from the Galactic Center, or more thorough tests of the hadronic interaction models. Two prototype stations with 7 scintillation detectors each have been already deployed at the South Pole in January 2018. These R&D studies provide a window of opportunity to integrate radio antennas with minimal effort.

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