scholarly journals Recognition Interface of the Thrombin Binding Aptamer Requires Antiparallel Topology of the Quadruplex Core

Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1332
Author(s):  
Julia Svetlova ◽  
Makar Sardushkin ◽  
Natalia Kolganova ◽  
Edward Timofeev
Keyword(s):  
Genome Stability ◽  
Structural Parameters ◽  
Current Paper ◽  
Cellular Proteins ◽  
Protein Recognition ◽  
Specific Interactions ◽  
Biological Processes ◽  
The Core ◽  
Recent Advances ◽  
G Quadruplex

Recent advances in G-quadruplex (GQ) studies have provided evidence for their important role in key biological processes (replication, transcription, genome stability, and epigenetics). These findings imply highly specific interactions between GQ structures and cellular proteins. The details of the interaction between GQs and cellular proteins remain unknown. It is now accepted that GQ loop elements play a major role in protein recognition. It remains unclear whether and to what extent the GQ core contributes to maintaining the recognition interface. In the current paper, we used the thrombin binding aptamer as a model to study the effect of modification in the quadruplex core on the ability of aptamer to interact with thrombin. We used alpha-2′-deoxyguanosine and 8-bromo-2′-deoxyguanosine to reconfigure the core or to affect syn–anti preferences of selected dG-residues. Our data suggest that core guanines not only support a particular type of GQ architecture, but also set structural parameters that make GQ protein recognition sensitive to quadruplex topology.

scholarly journals The many roads to psychosis: recent advances in understanding risk and mechanisms

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1883 ◽  
Author(s):  
Carrie E. Bearden ◽  
Jennifer K. Forsyth
Keyword(s):  
Risk Factors ◽  
Mental Illness ◽  
Genetic Architecture ◽  
Biological Processes ◽  
The Core ◽  
The Past ◽  
Recent Advances ◽  
New Findings ◽  
The Many ◽  
Major Progress

Schizophrenia is a chronic and severe mental illness which frequently leads to substantial lifelong disability. The past five years have seen major progress in our understanding of the complex genetic architecture of this disorder. Two major barriers to understanding the core biological processes that underlie schizophrenia and developing better interventions are (1) the absence of etiologically defined biomarkers and (2) the clinical and genetic heterogeneity of the disorder. Here, we review recent advances that have led to changes in our understanding of risk factors and mechanisms involved in the development of schizophrenia. In particular, mechanistic and clinically oriented approaches have now converged on a focus on disruptions in early neurodevelopment and synaptic plasticity as being critical for both understanding trajectories and intervening to change them. Translating these new findings into treatments that substantively change the lives of patients is the next major challenge for the field.

A Dynamic Systems Approach to Personality

2001 ◽  
Vol 6 (3) ◽  
pp. 172-176 ◽  
Author(s):  
Lawrence A. Pervin
Keyword(s):  
Dynamic Systems ◽  
Systems Approach ◽  
Biological Processes ◽  
Recent Advances ◽  
Dynamic View ◽  
The Future ◽  
History Of

David Magnusson has been the most articulate spokesperson for a holistic, systems approach to personality. This paper considers three concepts relevant to a dynamic systems approach to personality: dynamics, systems, and levels. Some of the history of a dynamic view is traced, leading to an emphasis on the need for stressing the interplay among goals. Concepts such as multidetermination, equipotentiality, and equifinality are shown to be important aspects of a systems approach. Finally, attention is drawn to the question of levels of description, analysis, and explanation in a theory of personality. The importance of the issue is emphasized in relation to recent advances in our understanding of biological processes. Integrating such advances into a theory of personality while avoiding the danger of reductionism is a challenge for the future.

Exploring the Mechanism of Lingzhu San in Treating Febrile Seizures by Using Network Pharmacology

2020 ◽  
Vol 23 ◽  
Author(s):  
Xiao Zhou ◽  
Xiao-Fei Zhang ◽  
Dong-Yan Guo ◽  
Yan-Jun Yang ◽  
Lin Liu ◽  
...  
Keyword(s):  
Febrile Seizures ◽  
Network Pharmacology ◽  
Biological Processes ◽  
Active Compounds ◽  
Potential Core ◽  
R Language ◽  
The Core ◽  
Multiple Factors ◽  
Therapeutic Mechanism

Objective: Lingzhu San (LZS) is a traditional Chinese medicine (TCM) prescription which can be effective in treating febrile seizures (FS) and has few researches on the mechanisms. In order to better guide the clinical use of LZS, we used the research ideas and methods of network pharmacology to find the potential core compounds, targets and pathways of LZS in the complex TCM system for the treatment of FS, and predict the mechanism. Materials and Methods: Databases such as BATMAN, TCMSP, TCMID, and SWISS TARGET are used to mine the active compounds and targets of LZS, and the target information of FS was obtained through GENECARDS and OMIM. Using Venny2.1.0 and Cytoscape software to locked the potential core compounds and targets of FS. The R language and ClusterProfiler software package were adopt to enrich and analyze the KEGG and GO pathways of the core targets and the biological processes and potential mechanisms of the core targets were revealed. Results: 187 active compounds and 2113 target proteins of LZS were collected. And 38 potential core compounds, 35 core targets and 775 metabolic and functional pathways were screened which involved in mediating FS. Finally, the role of the core compounds, targets and pivotal pathways of LZS regulated FS in the pathogenesis and therapeutic mechanism of FS was discussed and clarified. Conclusions: In this paper, the multi-compounds, multi-targets and multi-pathways mechanism of LZS in the treatment of FS was preliminarily revealed through the analysis of network pharmacology data, which is consistent with the principle of multi-compounds compatibility of TCM prescriptions and unified treatment of diseases from multiple angles, and it provides a new way for TCM to treat complex diseases caused by multiple factors.

scholarly journals Geometrical Scaling of Antiresonant Hollow-Core Fibers for Mid-Infrared Beam Delivery

Crystals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 420
Author(s):  
Ang Deng ◽  
Wonkeun Chang
Keyword(s):  
Structural Parameters ◽  
Transmission Band ◽  
Confinement Loss ◽  
Hollow Core ◽  
Core Size ◽  
Core Diameter ◽  
Mid Infrared ◽  
The Core ◽  
Tubular Type ◽  
Beam Delivery

We numerically investigate the effect of scaling two key structural parameters in antiresonant hollow-core fibers—dielectric wall thickness of the cladding elements and core size—in view of low-loss mid-infrared beam delivery. We demonstrate that there exists an additional resonance-like loss peak in the long-wavelength limit of the first transmission band in antiresonant hollow-core fibers. We also find that the confinement loss in tubular-type hollow-core fibers depends strongly on the core size, where the degree of the dependence varies with the cladding tube size. The loss scales with the core diameter to the power of approximately −5.4 for commonly used tubular-type hollow-core fiber designs.

scholarly journals MRE11 Is Crucial for Malaria Parasite Transmission and Its Absence Affects Expression of Interconnected Networks of Key Genes Essential for Life

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2590
Author(s):  
David S. Guttery ◽  
Abhinay Ramaprasad ◽  
David J. P. Ferguson ◽  
Mohammad Zeeshan ◽  
Rajan Pandey ◽  
...  
Keyword(s):  
Genome Stability ◽  
Malaria Parasite ◽  
Mosquito Vector ◽  
Parasite Transmission ◽  
Biological Processes ◽  
Cluster Assembly ◽  
Iron Sulfur Cluster ◽  
Iron Sulfur ◽  
Parasite Plasmodium ◽  
Damage Response

The meiotic recombination 11 protein (MRE11) plays a key role in DNA damage response and maintenance of genome stability. However, little is known about its function during development of the malaria parasite Plasmodium. Here, we present a functional, ultrastructural and transcriptomic analysis of Plasmodium parasites lacking MRE11 during its life cycle in both mammalian and mosquito vector hosts. Genetic disruption of Plasmodium berghei mre11 (PbMRE11) results in significant retardation of oocyst development in the mosquito midgut associated with cytoplasmic and nuclear degeneration, along with concomitant ablation of sporogony and subsequent parasite transmission. Further, absence of PbMRE11 results in significant transcriptional downregulation of genes involved in key interconnected biological processes that are fundamental to all eukaryotic life including ribonucleoprotein biogenesis, spliceosome function and iron–sulfur cluster assembly. Overall, our study provides a comprehensive functional analysis of MRE11′s role in Plasmodium development during the mosquito stages and offers a potential target for therapeutic intervention during malaria parasite transmission.

scholarly journals ATRX promotes heterochromatin formation to protect cells from G-quadruplex DNA-mediated stress

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yu-Ching Teng ◽  
Aishwarya Sundaresan ◽  
Ryan O’Hara ◽  
Vincent U. Gant ◽  
Minhua Li ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Genome Stability ◽  
Helicase Domain ◽  
Quadruplex Dna ◽  
Heterochromatin Formation ◽  
Replicative Stress ◽  
G4 Dna ◽  
Mutation Burden ◽  
G Quadruplex ◽  
Dna Replication Stress

AbstractATRX is a tumor suppressor that has been associated with protection from DNA replication stress, purportedly through resolution of difficult-to-replicate G-quadruplex (G4) DNA structures. While several studies demonstrate that loss of ATRX sensitizes cells to chemical stabilizers of G4 structures, the molecular function of ATRX at G4 regions during replication remains unknown. Here, we demonstrate that ATRX associates with a number of the MCM replication complex subunits and that loss of ATRX leads to G4 structure accumulation at newly synthesized DNA. We show that both the helicase domain of ATRX and its H3.3 chaperone function are required to protect cells from G4-induced replicative stress. Furthermore, these activities are upstream of heterochromatin formation mediated by the histone methyltransferase, ESET, which is the critical molecular event that protects cells from G4-mediated stress. In support, tumors carrying mutations in either ATRX or ESET show increased mutation burden at G4-enriched DNA sequences. Overall, our study provides new insights into mechanisms by which ATRX promotes genome stability with important implications for understanding impacts of its loss on human disease.

scholarly journals Phase transition of the 2-Choices dynamics on core–periphery networks

2021 ◽  
Author(s):  
Emilio Cruciani ◽  
Emanuele Natale ◽  
André Nusser ◽  
Giacomo Scornavacca
Keyword(s):  
Phase Transition ◽  
Voting Behavior ◽  
Structural Parameters ◽  
Connected Subset ◽  
Transition Phenomenon ◽  
The Core ◽  
Analytical Results ◽  
Heterogeneous Behavior

AbstractThe 2-Choices dynamics is a process that models voting behavior on networks and works as follows: Each agent initially holds either opinion blue or red; then, in each round, each agent looks at two random neighbors and, if the two have the same opinion, the agent adopts it. We study its behavior on a class of networks with core–periphery structure. Assume that a densely-connected subset of agents, the core, holds a different opinion from the rest of the network, the periphery. We prove that, depending on the strength of the cut between core and periphery, a phase-transition phenomenon occurs: Either the core’s opinion rapidly spreads across the network, or a metastability phase takes place in which both opinions coexist for superpolynomial time. The interest of our result, which we also validate with extensive experiments on real networks, is twofold. First, it sheds light on the influence of the core on the rest of the network as a function of its connectivity toward the latter. Second, it is one of the first analytical results which shows a heterogeneous behavior of a simple dynamics as a function of structural parameters of the network.

scholarly journals Subtle structural alterations in G-quadruplex DNA regulate site specificity of fluorescence light-up probes

2020 ◽  
Vol 48 (3) ◽  
pp. 1108-1119 ◽  
Author(s):  
Rajendra Kumar ◽  
Karam Chand ◽  
Sudipta Bhowmik ◽  
Rabindra Nath Das ◽  
Snehasish Bhattacharjee ◽  
...  
Keyword(s):  
Rational Design ◽  
Dna Structure ◽  
Biological Processes ◽  
Chemical Research ◽  
Quadruplex Dna ◽  
Dna Structures ◽  
Future Studies ◽  
G4 Dna ◽  
G Quadruplex ◽  
Fluorescence Light

Abstract G-quadruplex (G4) DNA structures are linked to key biological processes and human diseases. Small molecules that target specific G4 DNA structures and signal their presence would therefore be of great value as chemical research tools with potential to further advance towards diagnostic and therapeutic developments. However, the development of these types of specific compounds remain as a great challenge. In here, we have developed a compound with ability to specifically signal a certain c-MYC G4 DNA structure through a fluorescence light-up mechanism. Despite the compound's two binding sites on the G4 DNA structure, only one of them result in the fluorescence light-up effect. This G-tetrad selectivity proved to originate from a difference in flexibility that affected the binding affinity and tilt the compound out of the planar conformation required for the fluorescence light-up mechanism. The intertwined relation between the presented factors is likely the reason for the lack of examples using rational design to develop compounds with turn-on emission that specifically target certain G4 DNA structures. However, this study shows that it is indeed possible to develop such compounds and present insights into the molecular details of specific G4 DNA recognition and signaling to advance future studies of G4 biology.

scholarly journals Effects of Structural Parameters on Seismic Behaviour of Historical Masonry Minaret

2017 ◽  
Author(s):  
Barış Erdil ◽  
Mücip Tapan ◽  
İsmail Akkaya ◽  
Fuat Korkut
Keyword(s):  
Modal Analysis ◽  
Structural Parameters ◽  
Masonry Structure ◽  
Operational Modal Analysis ◽  
Shear Cracks ◽  
Seismic Behaviour ◽  
New Model ◽  
The Core ◽  
Historical Masonry ◽  
Stiffness Distribution

The October 23, 2011 (Mw = 7.2) and November 9, 2011 (Mw = 5.6) earthquakes increased the damage in the minaret of Van Ulu Mosque, an important historical masonry structure built with solid bricks in Eastern Turkey, resulting in significant shear cracks. It was found that since the door and window openings are not symmetrically placed, they result in unsymmetrical stiffness distribution. The contribution of staircase and the core on stiffness is ignorable but its effect on the mass is significant. The pulpit with chamfered corner results in unsymmetrical transverse displacements. Brace wall improves the stiffness however contributes to the unsymmetrical behaviour considerably. The reason for the diagonal cracks can be attributed to the unsymmetrical brace wall and the chamfered pulpit but the effect of brace wall is more pronounced. After introducing the cracks, a new model was created and calibrated according to the results of Operational Modal Analysis. Diagonal cracks were found to be likely to develop under earthquake loading. Drifts are observed to increase significantly upon the introduction of the cracks.

Recent advances in multivalent carbon nanoform-based glycoconjugates

2021 ◽  
Vol 28 ◽  
Author(s):  
Javier Ramos-Soriano ◽  
Mattia Ghirardello ◽  
M. Carmen Galan
Keyword(s):  
Carbon Nanotubes ◽  
Molecular Level ◽  
Biological Processes ◽  
Biologically Relevant ◽  
Disease Mechanisms ◽  
Recent Advances

: Multivalent carbohydrate-mediated interactions are fundamental to many biological processes, including disease mechanisms. To study these significant glycan-mediated interactions at a molecular level, carbon nanoforms such as fullerenes, carbon nanotubes, or graphene and their derivatives have been identified as promising biocompatible scaffolds that can mimic the multivalent presentation of biologically relevant glycans. In this minireview, we will summarize the most relevant examples of the last few years in the context of their applications.

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