scholarly journals Structural insights into synthetic ligands targeting A–A pairs in disease-related CAG RNA repeats

2019 ◽  
Vol 47 (20) ◽  
pp. 10906-10913 ◽  
Author(s):  
Sanjukta Mukherjee ◽  
Leszek Błaszczyk ◽  
Wojciech Rypniewski ◽  
Christoph Falschlunger ◽  
Ronald Micura ◽  
...  
Keyword(s):  
Structural Changes ◽  
Trinucleotide Repeat ◽  
Cag Repeats ◽  
Stacking Interactions ◽  
Base Pairs ◽  
Lead Compounds ◽  
Canonical Base ◽  
Structural Insights ◽  
Abnormal Expansion

Abstract The trinucleotide repeat expansion disorders (TREDs) constitute of a group of >40 hereditary neurodegenerative human diseases associated with abnormal expansion of repeated sequences, such as CAG repeats. The pathogenic factor is a transcribed RNA or protein whose function in the cell is compromised. The disorders are progressive and incurable. Consequently, many ongoing studies are oriented at developing therapies. We have analyzed crystal structures of RNA containing CAG repeats in complex with synthetic cyclic mismatch-binding ligands (CMBLs). The models show well-defined interactions between the molecules in which the CMBLs mimic nucleobases as they form pseudo-canonical base pairs with adenosine residues and engage in extensive stacking interactions with neighboring nucleotides. The binding of ligands is associated with major structural changes of the CAG repeats, which is consistent with results of biochemical studies. The results constitute an early characterization of the first lead compounds in the search for therapy against TREDs. The crystallographic data indicate how the compounds could be further refined in future biomedical studies.

scholarly journals RNA CoSSMos 2.0: an improved searchable database of secondary structure motifs in RNA three-dimensional structures

Database ◽  
2020 ◽  
Vol 2020 ◽  
Author(s):  
Katherine E Richardson ◽  
Charles C Kirkpatrick ◽  
Brent M Znosko
Keyword(s):  
Secondary Structure ◽  
Rna Secondary Structure ◽  
Three Dimensional ◽  
Structural Features ◽  
Stacking Interactions ◽  
Base Pairs ◽  
Search Results ◽  
Search Result ◽  
Structure Database

Abstract The RNA Characterization of Secondary Structure Motifs, RNA CoSSMos, database is a freely accessible online database that allows users to identify secondary structure motifs among RNA 3D structures and explore their structural features. RNA CoSSMos 2.0 now requires two closing base pairs for all RNA loop motifs to create a less redundant database of secondary structures. Furthermore, RNA CoSSMos 2.0 represents an upgraded database with new features that summarize search findings and aid in the search for 3D structural patterns among RNA secondary structure motifs. Previously, users were limited to viewing search results individually, with no built-in tools to compare search results. RNA CoSSMos 2.0 provides two new features, allowing users to summarize, analyze and compare their search result findings. A function has been added to the website that calculates the average and representative structures of the search results. Additionally, users can now view a summary page of their search results that reports percentages of each structural feature found, including sugar pucker, glycosidic linkage, hydrogen bonding patterns and stacking interactions. Other upgrades include a newly embedded NGL structural viewer, the option to download the clipped structure coordinates in *.pdb format and improved NMR structure results. RNA CoSSMos 2.0 is no longer simply a search engine for a structure database; it now has the capability of analyzing, comparing and summarizing search results. Database URL: http://rnacossmos.com

Thermal characterization of ABS-Graphene blended three dimensional printed functional prototypes for electro chemical energy storage

2018 ◽  
Vol 1 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Kamaljit Singh Boparai ◽  
Rupinder Singh
Keyword(s):  
Energy Storage ◽  
Structural Changes ◽  
Fused Deposition Modeling ◽  
Morphological Changes ◽  
Three Dimensional ◽  
Thermal Characterization ◽  
Chemical Energy ◽  
Flow Index ◽  
Fused Deposition

This study highlights the thermal characterization of ABS-Graphene blended three dimensional (3D) printed functional prototypes by fused deposition modeling (FDM) process. These functional prototypes have some applications as electro-chemical energy storage devices (EESD). Initially, the suitability of ABS-Graphene composite material for FDM applications has been examined by melt flow index (MFI) test. After establishing MFI, the feedstock filament for FDM has been prepared by an extrusion process. The fabricated filament has been used for printing 3D functional prototypes for printing of in-house EESD. The differential scanning calorimeter (DSC) analysis was conducted to understand the effect on glass transition temperature with the inclusion of Graphene (Gr) particles. It has been observed that the reinforced Gr particles act as a thermal reservoir (sink) and enhances its thermal/electrical conductivity. Also, FT-IR spectra realized the structural changes with the inclusion of Gr in ABS matrix. The results are supported by scanning electron microscopy (SEM) based micrographs for understanding the morphological changes.

scholarly journals Patients With Extreme Early Onset Juvenile Huntington Disease Can Have Delays in Diagnosis: A Case Report and Literature Review

2021 ◽  
Vol 8 ◽  
pp. 2329048X2110361
Author(s):  
Ashley A. Moeller ◽  
Marcia V. Felker ◽  
Jennifer A. Brault ◽  
Laura C. Duncan ◽  
Rizwan Hamid ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Huntington Disease ◽  
Early Onset ◽  
Trinucleotide Repeat ◽  
Cerebellar Atrophy ◽  
Cag Repeats ◽  
Ataxic Gait ◽  
Repeat Expansions ◽  
Delays In Diagnosis ◽  
Juvenile Huntington Disease

Huntington disease (HD) is caused by a pathologic cytosine-adenine-guanine (CAG) trinucleotide repeat expansion in the HTT gene. Typical adult-onset disease occurs with a minimum of 40 repeats. With more than 60 CAG repeats, patients can have juvenile-onset disease (jHD), with symptom onset by the age of 20 years. We report a case of a boy with extreme early onset, paternally inherited jHD, with symptom onset between 18 and 24 months. He was found to have 250 to 350 CAG repeats, one of the largest repeat expansions published to date. At initial presentation, he had an ataxic gait, truncal titubation, and speech delay. Magnetic resonance imaging showed cerebellar atrophy. Over time, he continued to regress and became nonverbal, wheelchair-bound, gastrostomy-tube dependent, and increasingly rigid. His young age at presentation and the ethical concerns regarding HD testing in minors delayed his diagnosis.

scholarly journals Characterization of a Novel Thermobifida fusca Bacteriophage P318

Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1042
Author(s):  
Cheepudom ◽  
Lin ◽  
Lee ◽  
Meng
Keyword(s):  
Plant Cell Wall ◽  
Hydrolytic Enzymes ◽  
Thermobifida Fusca ◽  
Genome Replication ◽  
Putative Orfs ◽  
Base Pairs ◽  
Double Stranded Dna ◽  
Virion Morphogenesis ◽  
Genome Information

Thermobifida fusca is of biotechnological interest due to its ability to produce an array of plant cell wall hydrolytic enzymes. Nonetheless, only one T. fusca bacteriophage with genome information has been reported to date. This study was aimed at discovering more relevant bacteriophages to expand the existing knowledge of phage diversity for this host species. With this end in view, a thermostable T. fusca bacteriophage P318, which belongs to the Siphoviridae family, was isolated and characterized. P318 has a double-stranded DNA genome of 48,045 base pairs with 3′-extended COS ends, on which 52 putative ORFs are organized into clusters responsible for the order of genome replication, virion morphogenesis, and the regulation of the lytic/lysogenic cycle. In comparison with T. fusca and the previously discovered bacteriophage P1312, P318 has a much lower G+C content in its genome except at the region encompassing ORF42, which produced a protein with unknown function. P1312 and P318 share very few similarities in their genomes except for the regions encompassing ORF42 of P318 and ORF51 of P1312 that are homologous. Thus, acquisition of ORF42 by lateral gene transfer might be an important step in the evolution of P318.

scholarly journals Molecular characterization of a beta zero-thalassemia resulting from a 1.4 kilobase deletion

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 636-641 ◽  
Author(s):  
R Anand ◽  
CD Boehm ◽  
HH Jr Kazazian ◽  
EF Vanin
Keyword(s):  
Transcriptional Start Site ◽  
Globin Gene ◽  
Event Analysis ◽  
Beta Globin ◽  
Base Pairs ◽  
Dna Polymerase Alpha ◽  
Beta Globin Gene ◽  
American Black ◽  
The Individual

Abstract We report the characterization of a beta zero-thalassemia in an American Black with unusually high HbA2 and HbF levels. Genomic southern analysis indicated that the individual was heterozygous for a deletion that began within the second intervening sequence of the beta- globin gene and extended approximately 1.4 kb in the 5′ direction. A clone spanning the breakpoint on the abnormal chromosome was isolated and further mapped, and the deletion joint was sequenced. Comparison of the normal beta-globin gene and its 5′ flanking region with the deletion joint sequence indicated that the 5′ breakpoint for this deletion was 484 base pairs (bp) 5′ to the transcriptional start site for the beta-globin gene and the 3′ breakpoint was 908 bp into the beta- globin gene; the deletion removed a total of 1,393 bp. Comparison of the normal 5′ and 3′ breakpoint sequences indicated that this deletion was the result of a “clean” nonhomologous breakage and reunion event; ie, no spurious bases were added during the recombinational event. Analysis of the breakpoints of this deletion together with the breakpoints of two other small deletions involving the beta-globin gene suggests that the breakpoints may occur at DNA polymerase alpha pause sites.

A computational characterization of the hydrogen-bonding and stacking interactions of hypoxanthine

2007 ◽  
Vol 9 (4) ◽  
pp. 497-509 ◽  
Author(s):  
Lesley R. Rutledge ◽  
Craig A. Wheaton ◽  
Stacey D. Wetmore
Keyword(s):  
Hydrogen Bonding ◽  
Stacking Interactions

Characterization of Structural Changes of Poly(vinyl methyl ether) γ-Irradiated in Diluted Aqueous Solutions

Langmuir ◽  
2004 ◽  
Vol 20 (7) ◽  
pp. 2883-2889 ◽  
Author(s):  
Claudia Querner ◽  
Thomas Schmidt ◽  
Karl-Friedrich Arndt
Keyword(s):  
Aqueous Solutions ◽  
Methyl Ether ◽  
Structural Changes ◽  
Vinyl Methyl ◽  
Vinyl Methyl Ether

Thermo-Optical Properties of Perfluorinated Sulfonic Acid Membranes: An Investigation of Hydration Based on Absorption Spectra

2017 ◽  
Vol 71 (11) ◽  
pp. 2504-2511 ◽  
Author(s):  
Daniele T. Dias ◽  
Guy Lopes ◽  
Tales Ferreira ◽  
Ivanir L. Oliveira ◽  
Caroline D. Rosa
Keyword(s):  
Sulfonic Acid ◽  
Room Temperature ◽  
Water Retention ◽  
Structural Changes ◽  
Optical Characterization ◽  
Scanning Calorimetry ◽  
Experimental Procedure ◽  
Nafion Membranes ◽  
Perfluorinated Sulfonic Acid

The Nafion membranes are widely used in electrochemical applications such as fuel cells, chlor-alkali cells, and actuators–sensors. In this work, the thermal-optical characterization of Nafion in acid form was performed by photoacoustic spectroscopy, thermogravimetry, and differential scanning calorimetry. In the experimental procedure three distinct hydration levels were considered: (1) pristine membrane (λ ≅ H2O/–SO3H ≅ 5.6); (2) swelling process (λ ≅ 17.4); and (3) drying at controlled room temperature after swelling process (λ ≅ 6.5). The discovered behaviors showed significant irreversible structural changes induced by water retention in the membrane. These structural changes depend on the water population present in the clusters and also affect the directional thermal diffusivity of the membrane irreversibly.

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