• Genomics & Informatics
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• v.8 no.2
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• pp.70-75
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• 2010

Asp66his, Asp54Lys, and Asp50Asn are mutations in connexin 26 that are observed in the clinic and give rise to autosomal dominant syndromes. They are the result of point mutations in the human gap junction ${\beta}-2$ gene. In order to investigate the structural mechanism of Bart-Pumphrey Syndrome, Keratitis-Ichthyosis-Deafness Syndrome, and Vohwinkel Syndrome, homology modeling was carried out. Asp66 has direct contact with Asn62 by two hydrogen bonds in the wild-type protein, and in Asp66His, the biggest change observed is a tremendous energy increase caused by hydrogen bond breakage to Asn62. Shifts in the side chain and new hydrogen bond formation are observed for Lys54 compared to the wild-type protein (Asn54) and result in closer contact to Val84. Asp50Asn causes a significant decrease in bond energy, and residual charge reversal repels the ion and metabolites and, hence, inhibits their transportation. Such perturbations are likely to be a factor contributing to abnormal functioning of ion channels, resulting cell death and disease.

• Microbiology and Biotechnology Letters
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• v.47 no.2
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• pp.278-288
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• 2019

In the present investigation, we attempted to design a protocol to develop a hybrid protein with better bioremediation capacity. Using in silico approaches, a Hybrid Open Reading Frame (Hybrid ORF) is developed targeting the genes of microorganisms known for degradation of organophosphates. Out of 21 genes identified through BLAST search, 8 structurally similar genes (opdA, opd, opaA, pte RO, pdeA, parC, mpd and phnE) involved in biodegradation were screened. Gene conservational analysis categorizes these organophosphates degrading 8 genes into 4 super families i.e., Metallo-dependent hydrolases, Lactamase B, MPP and TM_PBP2 superfamily. Hybrid protein structure was modeled using multi-template homology modeling (3S07_A; 99%, 1P9E_A; 98%, 2ZO9_B; 33%, 2DXL_A; 33%) by $Schr{\ddot{o}}dinger$ software suit version 10.4.018. Structural verification of protein models was done using Ramachandran plot, it was showing 96.0% residue in the favored region, which was verified using RAMPAGE. The phosphotriesterase protein was showing the highest structural similarity with hybrid protein having raw score 984. The 5 binding sites of hybrid protein were identified through binding site prediction. The docking study shows that hybrid protein potentially interacts with 10 different organophosphates. The study results indicate that the hybrid protein designed has the capability of degrading a wide range of organophosphate compounds.

• Molecules and Cells
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• v.40 no.11
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• pp.823-827
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• 2017

Genome editing using programmable nucleases such as CRISPR/Cas9 or Cpf1 has emerged as powerful tools for gene knock-out or knock-in in various organisms. While most genetic diseases are caused by point mutations, these genome-editing approaches are inefficient in inducing single-nucleotide substitutions. Recently, Cas9-linked cytidine deaminases, named base editors (BEs), have been shown to convert cytidine to uridine efficiently, leading to targeted single-base pair substitutions in human cells and organisms. Here, we first report on the generation of Xenopus laevis mutants with targeted single-base pair substitutions using this RNA-guided programmable deaminase. Injection of base editor 3 (BE3) ribonucleoprotein targeting the tyrosinase (tyr) gene in early embryos can induce site-specific base conversions with the rates of up to 20.5%, resulting in oculocutaneous albinism phenotypes without off-target mutations. We further test this base-editing system by targeting the tp53 gene with the result that the expected single-base pair substitutions are observed at the target site. Collectively, these data establish that the programmable deaminases are efficient tools for creating targeted point mutations for human disease modeling in Xenopus.

• Korean Journal of Biological Psychiatry
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• v.30 no.1
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• pp.17-23
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• 2023

Objectives This study aims to develop valid experimental models for depression through chronic reserpine exposure to zebrafish (Danio rerio). Methods The effect of chronic reserpine on zebrafish behavior in the novel tank was examined. Changes of gene expression on telencephalon were also investigated. Results Chronic reserpine (40 mg/L, 7 days) induced overt behavioral effects, but markedly reduced activity, resembling motor retardation in depression. In telencephalon of zebrafish, gene expression associated with monoamine oxidase and norepinephrine transporter was decreased. Expression of serotonin transporter gene was increased. Conclusions Our results show that the pharmacological model of depression in zebrafish can induce not only behavioral changes, but also monoamine changes in the homology of human mood regulation centers.

• Genomics & Informatics
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• v.20 no.4
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• pp.45.1-45.7
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• 2022

Food security will be affected by climate change worldwide, particularly in the developing world, where the most important food products originate from plants. Plants are often exposed to environmental stresses that may affect their growth, development, yield, and food quality. Auxin is a hormone that plays a critical role in improving plants' tolerance of environmental conditions. Auxin controls the expression of many stress-responsive genes in plants by interacting with specific cis-regulatory elements called auxin-responsive elements (AuxREs). In this work, we performed an in silico prediction of AuxREs in promoters of five auxin-responsive genes in Zea mays. We applied a data fusion approach based on the combined use of Dempster-Shafer evidence theory and fuzzy sets. Auxin has a direct impact on cell membrane proteins. The short-term auxin response may be represented by the regulation of transmembrane gene expression. The detection of an AuxRE in the promoter of prolyl oligopeptidase (POP) in Z. mays and the 3-fold overexpression of this gene under auxin treatment for 30 min indicated the role of POP in maize auxin response. POP is regulated by auxin to perform stress adaptation. In addition, the detection of two AuxRE TGTCTC motifs in the upstream sequence of the bx1 gene suggests that bx1 can be regulated by auxin. Auxin may also be involved in the regulation of dehydration-responsive element-binding and some members of the protein kinase superfamily.

• Structural Engineering and Mechanics
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• v.91 no.6
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• pp.643-656
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• 2024

The prediction of the moment rotation behavior of semi-rigid connections has been the subject of extensive research. However, to improve the accuracy of these predictions, there is a growing interest in employing machine learning algorithms. This paper investigates the effectiveness of using Multi-gene genetic programming (MGGP) to predict the moment-rotation behavior of flush-end plate connections compared to that of artificial neural networks (ANN) and previous studies. It aims to automate the process of determining the most suitable equations to accurately describe the behavior of these types of connections. Experimental data was used to train ANN and MGGP. The performance of the models was assessed by comparing the values of coefficient of determination (R²), maximum absolute error (MAE), and root-mean-square error (RMSE). The results showed that MGGP produced more accurate, reliable, and general predictions compared to ANN and previous studies with an R² exceeding 0.99, an RMSE of 6.97, and an MAE of 38.68, highlighting its advantages over other models. The use of MGGP can lead to better modeling and more precise predictions in structural design. Additionally, an experimentally-based regression analysis was conducted to obtain the rotational capacity of FECs. A new equation was proposed and compared to previous ones, showing significant improvement in accuracy with an R² score of 0.738, an RMSE of 0.014, and an MAE of 0.024.

• International Journal of Stem Cells
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• v.15 no.3
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• pp.233-246
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• 2022

Background and Objectives: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease mainly affecting young women of childbearing age. SLE affects the skin, joints, muscles, kidneys, lungs, and heart. Cardiovascular complications are common causes of death in patients with SLE. However, the complexity of the cardiovascular system and the rarity of SLE make it difficult to investigate these morbidities. Patient-derived induced pluripotent stem cells (iPSCs) serve as a novel tool for drug screening and pathophysiological studies in the absence of patient samples. Methods and Results: We differentiated CMs from HC- and SLE-iPSCs using 2D culture platforms. SLE-CMs showed decreased proliferation and increased levels of fibrosis and hypertrophy marker expression; however, HC-and SLE-monolayer CMs reacted differently to SLE serum treatment. HC-iPSCs were also differentiated into CMs using 3D spheroid culture and anti-Ro autoantibody was treated along with SLE serum. 3D-HC-CMs generated more mature CMs compared to the CMs generated using 2D culture. The treatment of anti-Ro autoantibody rapidly increased the gene expression of fibrosis, hypertrophy, and apoptosis markers, and altered the calcium signaling in the CMs. Conclusions: iPSC derived cardiomyocytes with patient-derived serum, and anti-Ro antibody treatment could serve in effective autoimmune disease modeling including SLE. We believe that the present study might briefly provide possibilities on the application of a combination of patient-derived materials and iPSCs in disease modeling of autoimmune diseases.

• East Asian mathematical journal
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• v.36 no.3
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• pp.365-376
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• 2020

Nonalcoholic fatty liver is a type of fatty liver in which fat accumulates in the liver without alcohol. In the accumulation, Nrf1 and miR-378 genes play very important role, so called negative feedback loop, in which the two genes suppress the other's production. In other words, Nrf1 activates fatty acid oxidation which promotes fat consumption in the liver, while miR-378 deactivates fatty acid oxidation. Thus, both genes regulate nonalcoholic fatty liver. In this paper, the negative feedback loop of Nrf1 and miR-378 are expressed by a system of ordinary differential equations. And, bifurcation simulation shows the change in the amount of each gene with significant parameter range changes. Bifurcation simulation has also used to determine the thresholds for transit between disease and steady state.

• Computers and Concrete
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• v.17 no.4
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• pp.489-498
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• 2016

In this paper, the flexural strength ($f_{fs}$) and splitting tensile strength ($f_{sts}$) of concrete containing different proportions of fly ash have been modeled by using gene expression programming (GEP). Two GEP models called GEP-I and GEP-II are constituted to predict the $f_{fs}$ and $f_{sts}$ values, respectively. In these models, the age of specimen, cement, water, sand, aggregate, superplasticizer and fly ash are used as independent input parameters. GEP-I model is constructed by 292 experimental data and trisected into 170, 86 and 36 data for training, testing and validating sets, respectively. Similarly, GEP-II model is constructed by 278 experimental data and trisected into 142, 70 and 66 data for training, testing and validating sets, respectively. The experimental data used in the validating set of these models are independent from the training and testing sets. The results of the statistical parameters obtained from the models indicate that the proposed empirical models have good prediction and generalization capability.

• Computers and Concrete
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• v.17 no.1
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• pp.87-106
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• 2016

This paper deals with the reliability analysis of design formulations derived for predicting the punching shear capacity of FRP-reinforced two-way slabs. Firstly, a new design code formulation was derived by means of gene expression programming. This formulation differs from the existing ones as the slab length (L) was introduced in the equation. Next, the proposed formulation was tested for its generalization capability by a parametric study. Then, the stochastic analyses of derived and existing formulations were performed by Monte Carlo simulation. Finally, the reliability analyses of these equations were carried out based on the results of stochastic analysis and the ultimate state function of ASCE-7 and ACI-318 (2011). The results indicate that the prediction performance of new formulation is significantly higher as compared to available design equations and its reliability index is within acceptable limits.