scholarly journals WALTZ-DB 2.0: an updated database containing structural information of experimentally determined amyloid-forming peptides

2019 ◽  
Vol 48 (D1) ◽  
pp. D389-D393 ◽  
Author(s):  
Nikolaos Louros ◽  
Katerina Konstantoulea ◽  
Matthias De Vleeschouwer ◽  
Meine Ramakers ◽  
Joost Schymkowitz ◽  
...  
Keyword(s):  
Open Access ◽  
Amyloid Fibrils ◽  
Amyloid Fibril ◽  
Structural Information ◽  
3D Models ◽  
Accurate Prediction ◽  
Binding Assays ◽  
Manual Curation ◽  
Open Access Database ◽  
User Friendly

Abstract Transition of soluble proteins into insoluble amyloid fibrils is driven by self-propagating short sequence stretches. However, accurate prediction of aggregation determinants remains challenging. Here, we describe WALTZ-DB 2.0, an updated and significantly expanded open-access database providing information on experimentally determined amyloid-forming hexapeptide sequences (http://waltzdb.switchlab.org/). We have updated WALTZ-DB 2.0 with new entries, including: (i) experimental validation of an in-house developed dataset of 229 hexapeptides, using electron microscopy and Thioflavin-T binding assays; (ii) manual curation of 98 amyloid-forming peptides isolated from literature. Furthermore, the content has been expanded by adding novel structural information for peptide entries, including sequences of the previous version. Using a computational methodology developed in the Switch lab, we have generated 3D-models of the putative amyloid fibril cores of WALTZ-DB 2.0 entries. Structural models, coupled with information on the energetic contributions and fibril core stabilities, can be accessed through individual peptide entries. Customized filtering options for subset selections and new modelling graphical features were added to upgrade online accessibility, providing a user-friendly interface for browsing, downloading and updating. WALTZ-DB 2.0 remains the largest open-access repository for amyloid fibril formation determinants and will continue to enhance the development of new approaches focused on accurate prediction of aggregation prone sequences.

scholarly journals Identification of Novel 1,3,5-Triphenylbenzene Derivative Compounds as Inhibitors of Hen Lysozyme Amyloid Fibril Formation

2019 ◽  
Vol 20 (22) ◽  
pp. 5558
Author(s):  
Hassan Ramshini ◽  
Reza Tayebee ◽  
Alessandra Bigi ◽  
Francesco Bemporad ◽  
Cristina Cecchi ◽  
...  
Keyword(s):  
Amyloid Fibrils ◽  
Amyloid Fibril ◽  
Inhibitory Effect ◽  
Fibril Formation ◽  
Amyloid Formation ◽  
Binding Assays ◽  
Egg White Lysozyme ◽  
Amyloid Fibril Formation ◽  
Activity Measurements ◽  
Model Protein

Deposition of soluble proteins as insoluble amyloid fibrils is associated with a number of pathological states. There is a growing interest in the identification of small molecules that can prevent proteins from undergoing amyloid fibril formation. In the present study, a series of small aromatic compounds with different substitutions of 1,3,5-triphenylbenzene have been synthesized and their possible effects on amyloid fibril formation by hen egg white lysozyme (HEWL), a model protein for amyloid formation, and of their resulting toxicity were examined. The inhibitory effect of the compounds against HEWL amyloid formation was analyzed using thioflavin T and Congo red binding assays, atomic force microscopy, Fourier-transform infrared spectroscopy, and cytotoxicity assays, such as the 3-(4,5-Dimethylthiazol)-2,5-Diphenyltetrazolium Bromide (MTT) reduction assay and caspase-3 activity measurements. We found that all compounds in our screen were efficient inhibitors of HEWL fibril formation and their associated toxicity. We showed that electron-withdrawing substituents such as –F and –NO2 potentiated the inhibitory potential of 1,3,5-triphenylbenzene, whereas electron-donating groups such as –OH, –OCH3, and –CH3 lowered it. These results may ultimately find applications in the development of potential inhibitors against amyloid fibril formation and its biologically adverse effects.

Color Data v2: a user-friendly, open-access database with hereditary cancer and hereditary cardiovascular conditions datasets

2020 ◽  
Author(s):  
Mark J. Berger ◽  
Hannah E. Williams ◽  
Ryan Barrett ◽  
Anjali D. Zimmer ◽  
Wendy McKennon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Atrial Fibrillation ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Open Access ◽  
Hereditary Cancer ◽  
Phenotypic Information ◽  
Open Access Database ◽  
Color Data ◽  
User Friendly

ABSTRACTPublicly-available genetic databases promote data sharing and fuel scientific discoveries for the prevention, treatment, and management of disease. In 2018, we built Color Data, a user-friendly, open access database containing genotypic and self-reported phenotypic information from 50,000 individuals who were sequenced for 30 genes associated with hereditary cancer. In a continued effort to promote access to these types of data, we launched Color Data v2, an updated version of the Color Data database. This new release includes additional clinical genetic testing results from more than 18,000 individuals who were sequenced for 30 genes associated with hereditary cardiovascular conditions, as well as polygenic risk scores for breast cancer, coronary artery disease, and atrial fibrillation. In addition, we used self-reported phenotypic information to implement the following four clinical risk models: Gail Model for five-year risk of breast cancer, Claus Model for lifetime risk of breast cancer, simple office-based Framingham Coronary Heart Disease Risk Score for ten-year risk of coronary heart disease, and CHARGE-AF simple score for five-year risk of atrial fibrillation. These new features and capabilities are highlighted through two sample queries in the database. We hope that the broad dissemination of this data will help researchers continue to explore genotype-phenotype correlations and identify novel variants for functional analysis, enabling scientific discoveries in the field of population genomics.Database URL: https://data.color.com/

scholarly journals Color Data v2: a user-friendly, open-access database with hereditary cancer and hereditary cardiovascular conditions datasets

Database ◽  
2020 ◽  
Vol 2020 ◽  
Author(s):  
Mark J Berger ◽  
Hannah E Williams ◽  
Ryan Barrett ◽  
Anjali D Zimmer ◽  
Wendy McKennon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Atrial Fibrillation ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Open Access ◽  
Hereditary Cancer ◽  
Phenotypic Information ◽  
Open Access Database ◽  
Color Data ◽  
User Friendly

Abstract Publicly available genetic databases promote data sharing and fuel scientific discoveries for the prevention, treatment and management of disease. In 2018, we built Color Data, a user-friendly, open access database containing genotypic and self-reported phenotypic information from 50 000 individuals who were sequenced for 30 genes associated with hereditary cancer. In a continued effort to promote access to these types of data, we launched Color Data v2, an updated version of the Color Data database. This new release includes additional clinical genetic testing results from more than 18 000 individuals who were sequenced for 30 genes associated with hereditary cardiovascular conditions as well as polygenic risk scores for breast cancer, coronary artery disease and atrial fibrillation. In addition, we used self-reported phenotypic information to implement the following four clinical risk models: Gail Model for 5-year risk of breast cancer, Claus Model for lifetime risk of breast cancer, simple office-based Framingham Coronary Heart Disease Risk Score for 10-year risk of coronary heart disease and CHARGE-AF simple score for 5-year risk of atrial fibrillation. These new features and capabilities are highlighted through two sample queries in the database. We hope that the broad dissemination of these data will help researchers continue to explore genotype–phenotype correlations and identify novel variants for functional analysis, enabling scientific discoveries in the field of population genomics. Database URL: https://data.color.com/

scholarly journals The Ultrastructure of Tissue Damage by Amyloid Fibrils

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4611
Author(s):  
Haruki Koike ◽  
Masahisa Katsuno
Keyword(s):  
Tissue Damage ◽  
Amyloid Fibrils ◽  
Amyloid Fibril ◽  
Prion Diseases ◽  
Nerve Biopsy ◽  
Al Amyloidosis ◽  
Amyloid Fibril Formation ◽  
Autopsy Specimens ◽  
Fibril Aggregates ◽  
Interfering Rna

Amyloidosis is a group of diseases that includes Alzheimer’s disease, prion diseases, transthyretin (ATTR) amyloidosis, and immunoglobulin light chain (AL) amyloidosis. The mechanism of organ dysfunction resulting from amyloidosis has been a topic of debate. This review focuses on the ultrastructure of tissue damage resulting from amyloid deposition and therapeutic insights based on the pathophysiology of amyloidosis. Studies of nerve biopsy or cardiac autopsy specimens from patients with ATTR and AL amyloidoses show atrophy of cells near amyloid fibril aggregates. In addition to the stress or toxicity attributable to amyloid fibrils themselves, the toxicity of non-fibrillar states of amyloidogenic proteins, particularly oligomers, may also participate in the mechanisms of tissue damage. The obscuration of the basement and cytoplasmic membranes of cells near amyloid fibrils attributable to an affinity of components constituting these membranes to those of amyloid fibrils may also play an important role in tissue damage. Possible major therapeutic strategies based on pathophysiology of amyloidosis consist of the following: 1) reducing or preventing the production of causative proteins; 2) preventing the causative proteins from participating in the process of amyloid fibril formation; and/or 3) eliminating already-deposited amyloid fibrils. As the development of novel disease-modifying therapies such as short interfering RNA, antisense oligonucleotide, and monoclonal antibodies is remarkable, early diagnosis and appropriate selection of treatment is becoming more and more important for patients with amyloidosis.

Inhibition of Amyloid Fibril Growth and Dissolution of Amyloid Fibrils by Curcumin-Gold Nanoparticles

2014 ◽  
Vol 20 (20) ◽  
pp. 6184-6191 ◽  
Author(s):  
Sharbari Palmal ◽  
Amit Ranjan Maity ◽  
Brijesh Kumar Singh ◽  
Sreetama Basu ◽  
Nihar R. Jana ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Amyloid Fibrils ◽  
Amyloid Fibril

scholarly journals Molecular dynamics simulations of mechanical failure in polymorphic arrangements of amyloid fibrils containing structural defects

2013 ◽  
Vol 4 ◽  
pp. 429-440 ◽  
Author(s):  
Hlengisizwe Ndlovu ◽  
Alison E Ashcroft ◽  
Sheena E Radford ◽  
Sarah A Harris
Keyword(s):  
Mechanical Properties ◽  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Amyloid Fibrils ◽  
Amyloid Fibril ◽  
Steered Molecular Dynamics ◽  
Mechanical Failure ◽  
Structural Defects ◽  
Dynamics Simulations

We examine how the different steric packing arrangements found in amyloid fibril polymorphs can modulate their mechanical properties using steered molecular dynamics simulations. Our calculations demonstrate that for fibrils containing structural defects, their ability to resist force in a particular direction can be dominated by both the number and molecular details of the defects that are present. The simulations thereby suggest a hierarchy of factors that govern the mechanical resilience of fibrils, and illustrate the general principles that must be considered when quantifying the mechanical properties of amyloid fibres containing defects.

Examining the structure of the mature amyloid fibril

2002 ◽  
Vol 30 (4) ◽  
pp. 521-525 ◽  
Author(s):  
O. S. Makin ◽  
L. C. Serpell
Keyword(s):  
Self Assembly ◽  
Rational Design ◽  
Amyloid Fibrils ◽  
Structural Information ◽  
X Ray ◽  
X Ray Crystallography ◽  
Cryo Electron Microscopy ◽  
Fibre Diffraction ◽  
Complementary Techniques ◽  
Mature Fibril

The pathogenesis of the group of diseases known collectively as the amyloidoses is characterized by the deposition of insoluble amyloid fibrils. These are straight, unbranching structures about 70–120 å (1 å = 0.1 nm) in diameter and of indeterminate length formed by the self-assembly of a diverse group of normally soluble proteins. Knowledge of the structure of these fibrils is necessary for the understanding of their abnormal assembly and deposition, possibly leading to the rational design of therapeutic agents for their prevention or disaggregation. Structural elucidation is impeded by fibril insolubility and inability to crystallize, thus preventing the use of X-ray crystallography and solution NMR. CD, Fourier-transform infrared spectroscopy and light scattering have been used in the study of the mechanism of fibril formation. This review concentrates on the structural information about the final, mature fibril and in particular the complementary techniques of cryo-electron microscopy, solid-state NMR and X-ray fibre diffraction.

scholarly journals Benchmarking framework for myocardial tracking and deformation algorithms: An open access database

2013 ◽  
Vol 17 (6) ◽  
pp. 632-648 ◽  
Author(s):  
C. Tobon-Gomez ◽  
M. De Craene ◽  
K. McLeod ◽  
L. Tautz ◽  
W. Shi ◽  
...  
Keyword(s):  
Open Access ◽  
Open Access Database ◽  
Access Database

scholarly journals Gcorn fungi: A Web Tool for Detecting Biases between Gene Evolution and Speciation in Fungi

2021 ◽  
Vol 7 (11) ◽  
pp. 959
Author(s):  
Taiga Kawachi ◽  
Yuta Inuki ◽  
Yoshiyuki Ogata
Keyword(s):  
Amino Acid ◽  
Open Access ◽  
Horizontal Gene Transfer ◽  
Gene Evolution ◽  
Gene Mutations ◽  
Amino Acid Sequences ◽  
Web Tool ◽  
Homologous Genes ◽  
Open Access Database ◽  
Fungal Genes

(1) Background: Fungi contain several millions of species, and the diversification of fungal genes has been achieved by speciation, gene duplication, and horizontal gene transfer. Although several databases provide information on orthologous and paralogous events, these databases show no information on biases between gene mutation and speciation. Here, we designed the Gcorn fungi database to better understand such biases. (2) Methods: Amino acid sequences of fungal genes in 249 species, which contain 2,345,743 sequences, were used for this database. Homologous genes were grouped at various thresholds of the homology index, which was based on the percentages of gene mutations. By grouping genes that showed highly similar homology indices to each other, we showed functional and evolutionary traits in the phylogenetic tree depicted for the gene of interest. (3) Results: Gcorn fungi provides well-summarized information on the evolution of a gene lineage and on the biases between gene evolution and speciation, which are quantitatively identified by the Robinson–Foulds metric. The database helps users visualize these traits using various depictions. (4) Conclusions: Gcorn fungi is an open access database that provides a variety of information with which to understand gene function and evolution.

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