scholarly journals Protein structural consequences of DNA mutational signatures: A meta-analysis of somatic variants and deep mutational scanning data

2021 ◽  
Author(s):  
Joseph Chi-Fung Ng ◽  
Franca Fraternali
Keyword(s):  
Meta Analysis ◽  
Protein Structures ◽  
Three Dimensional ◽  
Purifying Selection ◽  
Physicochemical Characteristics ◽  
Mutational Signatures ◽  
Protein Core ◽  
Dna Motif ◽  
Pathogenicity Prediction ◽  
The Stability

Signatures of DNA motifs associated with distinct mutagenic exposures have been defined for somatic variants, but little is known about the consequences different mutational processes pose to the cancer cell, particularly the distribution of the resulting variants in the implied proteins and their structural regions (surface, core, interacting interface). Here we first compare the protein-level consequences of six mutational signatures (Aging, APOBEC, POLE, UV, 5-FU and Platinum) characterised by clear DNA motif preferences. By mapping individual substitution events observed in tumours to three-dimensional protein structures, we show that these common somatic mutational signatures are biased against the protein core, consistent with the lower tolerability of substitutions at such structurally important regions. On the other hand, deep mutational scanning (DMS) data allow us to probe the "dark matter" of somatic mutational landscape, exploring variants which are otherwise removed in purifying selection. A computational DMS analysis identifies mutational contexts (5'-G/C[T>G]A/G-3') which are associated with damaging mutations, by altering physicochemical characteristics of amino acids at the protein core. We argue that comprehensive DMS analysis can contribute to classification of variants according to their true impact to the stability/activity of the affected protein, decoupling this from pathogenicity prediction offered by conventional variant impact classifiers.

scholarly journals Identification of a novel mutation in the KITLG gene in a Chinese family with familial progressive hyper- and hypopigmentation

2020 ◽  
Author(s):  
Jianbo Wang ◽  
Weisheng Li ◽  
Naihui Zhou ◽  
Jingliu Liu ◽  
Shoumin Zhang ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Protein Structures ◽  
Three Dimensional ◽  
Chinese Family ◽  
The Novel ◽  
Exon 2 ◽  
Coding Regions ◽  
Pathogenicity Prediction ◽  
Café Au Lait Spots ◽  
Genetics And Genomics

Abstract Background: Familial progressive hyper- and hypopigmentation (FPHH, MIM 145250) is a rare hereditary skin disorder that is predominantly characterized by progressive, diffuse, partly blotchy hyperpigmented lesions intermingled with scattered hypopigmented spots, lentigines and sometimes Cafe-au-lait spots (CALs). Heterozygous mutations of KIT ligand (KITLG, MIM 184745) gene is responsible for FPHH. To date, only eight KITLG mutations were reported to be associated with FPHH and no clear genotype-phenotype correlations had been well established. This study aimed to identify the causative mutations of the KITLG gene in two Chinese FPHH cases.Methods: Directly sequencing of the coding regions of KITLG was performed. The pathogenicity prediction was assessed using bioinformatics tools including SIFT, Polyphen2, and SWISS-MODEL, and further evaluated following the American College of Medical Genetics and Genomics (ACMG) guideline 2015.Results: A novel mutation c.104A>T (p.Asn35Ile) and a recurrent mutation c.101C>T (p.Thr34Ile) in KITLG were identified. As SIFT and Polyphen-2 softwares showed, both mutations identified in this study were predicted to be detrimental variations. Three-dimensional protein structures modeling indicated the mutant KITLG proteins might affect KITLG affinity to its receptor c-KIT. According to the ACMG guideline 2015, the novel mutation c.104A>T was ‘Likely Pathogenic’.Conclusions: So far, most of the KITLG mutations are clustered within the conserved VTNNV motif (amino acid 33-37) in exon 2. The known mutations are only involved in 33V, 34T, 36N, 37V but not 35N. We have now identified a novel mutation c.104A>T of KITLG, which was first reported in FPHH located within the conserved 35N of the motif. These results strengthen our understanding of FPHH and expand the mutational spectrum of the KITLG gene.

scholarly journals Mining 3D genome structure populations identifies major factors governing the stability of regulatory communities

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Chao Dai ◽  
Wenyuan Li ◽  
Harianto Tjong ◽  
Shengli Hao ◽  
Yonggang Zhou ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Genome Structure ◽  
Protein Structures ◽  
Three Dimensional ◽  
Expression Variability ◽  
3D Genome ◽  
Significant Challenge ◽  
The Stability ◽  
Major Factors ◽  
3D Genome Structure

Abstract Three-dimensional (3D) genome structures vary from cell to cell even in an isogenic sample. Unlike protein structures, genome structures are highly plastic, posing a significant challenge for structure-function mapping. Here we report an approach to comprehensively identify 3D chromatin clusters that each occurs frequently across a population of genome structures, either deconvoluted from ensemble-averaged Hi-C data or from a collection of single-cell Hi-C data. Applying our method to a population of genome structures (at the macrodomain resolution) of lymphoblastoid cells, we identify an atlas of stable inter-chromosomal chromatin clusters. A large number of these clusters are enriched in binding of specific regulatory factors and are therefore defined as ‘Regulatory Communities.’ We reveal two major factors, centromere clustering and transcription factor binding, which significantly stabilize such communities. Finally, we show that the regulatory communities differ substantially from cell to cell, indicating that expression variability could be impacted by genome structures.

scholarly journals Effects of Phosphorus on Loosely Bound and Tightly Bound Extracellular Polymer Substances in Aerobic Granular Sludge

2019 ◽  
Vol 33 (1) ◽  
pp. 59-68 ◽  
Author(s):  
L. L. Yan ◽  
X. L. Zhang ◽  
Z. L. Chen ◽  
Y. Ren ◽  
S. Liu ◽  
...  
Keyword(s):  
Zeta Potential ◽  
Extracellular Polymeric Substances ◽  
Three Dimensional ◽  
Granular Sludge ◽  
Physicochemical Characteristics ◽  
Aerobic Granular Sludge ◽  
Phosphorus Concentration ◽  
Quenching Effect ◽  
The Stability ◽  
Extracellular Polymer

The stability of aerobic granular sludge (AGS) is closely related to its extracellular polymeric substances (EPS). In this study, the composition and physicochemical characteristics of EPS in AGS were determined to evaluate their roles in AGS stability. The study evaluated the influence of influent phosphorus concentration on EPS protein (PN), polysaccharide (PS) and orthophosphate content, zeta potential (ζ) and fluorescence spectrum (EEM) in loosely bound EPS (LB-EPS) and tightly bound EPS (TB-EPS). With higher influent phosphorus concentration, the PN, PS and orthophosphate content were higher, as was the zeta potential in TB-EPS, but it had less influence on LB-EPS. Three-dimensional, synchronous fluorescence spectroscopy and fluorescence region integral (FRI) showed that protein-like substances were the primary components of LB-EPS and TB-EPS. Phosphorus had a dynamic quenching effect on EPS at a concentration between 0 mg L–1 and 17.5 mg L–1, which is the indirect production of phosphorus by cations. An increased concentration of influent phosphorus was beneficial to AGS stability

A Liquid Metal Flow Between Two Coaxial Cylinders System

2019 ◽  
Vol 11 (1) ◽  
pp. 79-86
Author(s):  
Abdelkrim Merah ◽  
Ridha Kelaiaia ◽  
Faiza Mokhtari
Keyword(s):  
Couette Flow ◽  
Metal Flow ◽  
Three Dimensional ◽  
Liquid Sodium ◽  
Taylor Vortex ◽  
Turbulent Regime ◽  
Coaxial Cylinders ◽  
Concentric Cylinders ◽  
Ideal Tool ◽  
The Stability

Abstract The Taylor-Couette flow between two rotating coaxial cylinders remains an ideal tool for understanding the mechanism of the transition from laminar to turbulent regime in rotating flow for the scientific community. We present for different Taylor numbers a set of three-dimensional numerical investigations of the stability and transition from Couette flow to Taylor vortex regime of a viscous incompressible fluid (liquid sodium) between two concentric cylinders with the inner one rotating and the outer one at rest. We seek the onset of the first instability and we compare the obtained results for different velocity rates. We calculate the corresponding Taylor number in order to show its effect on flow patterns and pressure field.

Handheld Laser Scanner Research

2019 ◽  
Vol 952 (10) ◽  
pp. 47-54
Author(s):  
A.V. Komissarov ◽  
A.V. Remizov ◽  
M.M. Shlyakhova ◽  
K.K. Yambaev
Keyword(s):  
Point Cloud ◽  
Three Dimensional ◽  
Laser Scanner ◽  
Test Site ◽  
Optical Systems ◽  
Advantages And Disadvantages ◽  
Site Survey ◽  
Laser Scanners ◽  
Three Dimensional Models ◽  
The Stability

The authors consider hand-held laser scanners, as a new photogrammetric tool for obtaining three-dimensional models of objects. The principle of their work and the newest optical systems based on various sensors measuring the depth of space are described in detail. The method of simultaneous navigation and mapping (SLAM) used for combining single scans into point cloud is outlined. The formulated tasks and methods for performing studies of the DotProduct (USA) hand-held laser scanner DPI?8X based on a test site survey are presented. The accuracy requirements for determining the coordinates of polygon points are given. The essence of the performed experimental research of the DPI?8X scanner is described, including scanning of a test object at various scanner distances, shooting a test polygon from various scanner positions and building point cloud, repeatedly shooting the same area of the polygon to check the stability of the scanner. The data on the assessment of accuracy and analysis of research results are given. Fields of applying hand-held laser scanners, their advantages and disadvantages are identified.

scholarly journals Aortic Annular Sizing Using Novel Software in Three-Dimensional Transesophageal Echocardiography for Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis

Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 751
Author(s):  
Chanrith Mork ◽  
Minjie Wei ◽  
Weixi Jiang ◽  
Jianli Ren ◽  
Haitao Ran
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Replacement ◽  
Transesophageal Echocardiography ◽  
Valve Replacement ◽  
Transcatheter Aortic Valve Replacement ◽  
Meta Analysis ◽  
Three Dimensional ◽  
Minimum Diameter ◽  
Transcatheter Aortic Valve ◽  
Mean Differences

(1) Background: We performed this study to evaluate the agreement between novel automated software of three-dimensional transesophageal echocardiography (3D-TEE) and multidetector computed tomography (MDCT) for aortic annular measurements of preprocedural transcatheter aortic valve replacement (TAVR); (2) Methods: PubMed, EMBASE, Web of Science, and Cochrane Library (Wiley) databases were systematically searched for studies that compared 3D-TEE and MDCT as the reference standard for aortic annular measurement of the following parameters: annular area, annular perimeter, area derived-diameter, perimeter derived-diameter, maximum and minimum diameter. Meta-analytic methods were utilized to determine the pooled correlations and mean differences between 3D-TEE and MDCT. Heterogeneity and publication bias were also assessed. Meta-regression analyses were performed based on the potential factors affecting the correlation of aortic annular area; (3) Results: A total of 889 patients from 10 studies were included in the meta-analysis. Pooled correlation coefficients between 3D-TEE and MDCT of annulus area, perimeter, area derived-diameter, perimeter derived-diameter, maximum and minimum diameter measurements were strong 0.89 (95% CI: 0.84–0.92), 0.88 (95% CI: 0.83–0.92), 0.87 (95% CI: 0.77–0.93), 0.87 (95% CI: 0.77–0.93), 0.79 (95% CI: 0.64–0.87), and 0.75 (95% CI: 0.61–0.84) (Overall p < 0.0001), respectively. Pooled mean differences between 3D-TEE and MDCT of annulus area, perimeter, area derived-diameter, perimeter derived-diameter, maximum and minimum diameter measurements were −20.01 mm2 ((95% CI: −35.37 to −0.64), p = 0.011), −2.31 mm ((95% CI: −3.31 to −1.31), p < 0.0001), −0.22 mm ((95% CI: −0.73 to 0.29), p = 0.40), −0.47 mm ((95% CI: −1.06 to 0.12), p = 0.12), −1.36 mm ((95% CI: −2.43 to −0.30), p = 0.012), and 0.31 mm ((95% CI: −0.15 to 0.77), p = 0.18), respectively. There were no statistically significant associations with the baseline patient characteristics of sex, age, left ventricular ejection fraction, mean transaortic gradient, and aortic valve area to the correlation between 3D-TEE and MDCT for aortic annular area sizing; (4) Conclusions: The present study implies that 3D-TEE using novel software tools, automatically analysis, is feasible to MDCT for annulus sizing in clinical practice.

scholarly journals Gum Tragacanth (GT): A Versatile Biocompatible Material beyond Borders

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1510 ◽  
Author(s):  
Mohammad Ehsan Taghavizadeh Yazdi ◽  
Simin Nazarnezhad ◽  
Seyed Hadi Mousavi ◽  
Mohammad Sadegh Amiri ◽  
Majid Darroudi ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Food Packaging ◽  
Three Dimensional ◽  
Great Promise ◽  
Anionic Polymer ◽  
Gum Tragacanth ◽  
New Horizons ◽  
Tissue Healing ◽  
The Stability ◽  
Therapeutic Substance

The use of naturally occurring materials in biomedicine has been increasingly attracting the researchers’ interest and, in this regard, gum tragacanth (GT) is recently showing great promise as a therapeutic substance in tissue engineering and regenerative medicine. As a polysaccharide, GT can be easily extracted from the stems and branches of various species of Astragalus. This anionic polymer is known to be a biodegradable, non-allergenic, non-toxic, and non-carcinogenic material. The stability against microbial, heat and acid degradation has made GT an attractive material not only in industrial settings (e.g., food packaging) but also in biomedical approaches (e.g., drug delivery). Over time, GT has been shown to be a useful reagent in the formation and stabilization of metal nanoparticles in the context of green chemistry. With the advent of tissue engineering, GT has also been utilized for the fabrication of three-dimensional (3D) scaffolds applied for both hard and soft tissue healing strategies. However, more research is needed for defining GT applicability in the future of biomedical engineering. On this object, the present review aims to provide a state-of-the-art overview of GT in biomedicine and tries to open new horizons in the field based on its inherent characteristics.

scholarly journals Blood eosinophil count-guided corticosteroid therapy and as a prognostic biomarker of exacerbations of chronic obstructive pulmonary disease: a systematic review and meta-analysis

2021 ◽  
Vol 12 ◽  
pp. 204062232110287
Author(s):  
Tao Liu ◽  
Zi-Jian Xiang ◽  
Xiao-Meng Hou ◽  
Jing-Jing Chai ◽  
Yan-Li Yang ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Prognostic Biomarker ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Chronic Obstructive ◽  
Blood Eosinophil ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
The Stability

Background: Chronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms and dyspnea, as well as an increase in the number of leukocytes in the airways, lungs, and pulmonary vessels. A ‘One size fits all’ approach to COPD patients with different clinical features may be considered outdated. The following are the two major objectives of this meta-analysis: the first is to determine if blood eosinophil counts (BEC) can serve as a prognostic biomarker of COPD outcomes, and the second is to determine which level of BEC is effective for inhaled corticosteroid (ICS) treatment. Methods: We searched articles published before 15 May 2021 in the following four electronic databases: Web of Science, Cochrane Library, EMBASE, and PubMed. Results: A total of 42 studies, comprising a sampling of 188,710 subjects, were summarized and compared in this meta-analysis. The rate ratio (RR) of exacerbations of COPD (ECOPD) between ICS and non-ICS treatment was statistically significant for the COPD patients with a baseline BEC ⩾ 2% or ⩾ 200 cells/μl, RR = 0.82 (0.73, 0.93) or 0.79 (0.70, 0.89) respectively, while the RR of ECOPD between ICS and non-ICS treatment was statistically insignificant for the COPD patients with baseline BEC < 2% or <200 cells/μl, RR = 0.97 (0.87, 1.08) or 0.97 (0.86, 1.08), suggested that ICS therapy was beneficial to the improvement of ECOPD in patients with a baseline BEC ⩾ 2% or BEC ⩾ 200 cells/μl. Conclusion: Our research shows that a BEC ⩾ 200 cells/μl or ⩾2% is likely to become the cutoff value of ICS treatment for ECOPD. Moreover, we believe that the baseline BEC can be used as a biomarker for predicting ECOPD. The stability of BEC requires special attention.

scholarly journals Can Vaccination Trigger Autoimmune Disorders? A Meta-Analysis

Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 821
Author(s):  
Marek Petráš ◽  
Ivana Králová Lesná ◽  
Jana Dáňová ◽  
Alexander M. Čelko
Keyword(s):  
Meta Analysis ◽  
Autoimmune Disorders ◽  
Risk Of Bias ◽  
Extensive Literature ◽  
Primary Analysis ◽  
Measures Of Association ◽  
Assessment Development ◽  
Extensive Literature Search ◽  
The Stability

Vaccination as an important tool in the fight against infections has been suggested as a possible trigger of autoimmunity over the last decades. To confirm or refute this assumption, a Meta-analysis of Autoimmune Disorders Association With Immunization (MADAWI) was conducted. Included in the meta-analysis were a total of 144 studies published in 1968–2019 that were available in six databases and identified by an extensive literature search conducted on 30 November 2019. The risk of bias classification of the studies was performed using the Newcastle–Ottawa Quality Assessment Scale. The strength of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation. While our primary analysis was conducted in terms of measures of association employed in studies with a low risk of bias, the robustness of the MADAWI outcome was tested using measures independent of each study risk of bias. Additionally, subgroup analyses were performed to determine the stability of the outcome. The pooled association of 0.99 (95% confidence interval, 0.97–1.02), based on a total of 364 published estimates, confirmed an equivalent occurrence of autoimmune disorders in vaccinated and unvaccinated persons. The same level of association reported by studies independently of the risk of bias was supported by a sufficient number of studies, and no serious limitation, inconsistency, indirectness, imprecision, and publication bias. A sensitivity analysis did not reveal any discrepancy in the primary result. Current common vaccination is not the cause of any of the examined autoimmune disorders in the medium and long terms.

scholarly journals Emergent chiral symmetry in a three-dimensional interacting Dirac liquid

2021 ◽  
Vol 2021 (1) ◽  
Author(s):  
András L. Szabó ◽  
Bitan Roy
Keyword(s):  
Fixed Points ◽  
Chiral Symmetry ◽  
Rotational Symmetry ◽  
Three Dimensional ◽  
Spatial Dimension ◽  
Dirac Fermions ◽  
Electronic Interactions ◽  
Emergent Phenomena ◽  
Ordered Phases ◽  
The Stability

Abstract We compute the effects of strong Hubbardlike local electronic interactions on three-dimensional four-component massless Dirac fermions, which in a noninteracting system possess a microscopic global U(1) ⊗ SU(2) chiral symmetry. A concrete lattice realization of such chiral Dirac excitations is presented, and the role of electron-electron interactions is studied by performing a field theoretic renormalization group (RG) analysis, controlled by a small parameter ϵ with ϵ = d−1, about the lower-critical one spatial dimension. Besides the noninteracting Gaussian fixed point, the system supports four quantum critical and four bicritical points at nonvanishing interaction couplings ∼ ϵ. Even though the chiral symmetry is absent in the interacting model, it gets restored (either partially or fully) at various RG fixed points as emergent phenomena. A representative cut of the global phase diagram displays a confluence of scalar and pseudoscalar excitonic and superconducting (such as the s-wave and p-wave) mass ordered phases, manifesting restoration of (a) chiral U(1) symmetry between two excitonic masses for repulsive interactions and (b) pseudospin SU(2) symmetry between scalar or pseudoscalar excitonic and superconducting masses for attractive interactions. Finally, we perturbatively study the effects of weak rotational symmetry breaking on the stability of various RG fixed points.

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