scholarly journals Mechanism of How Carbamylation Reduces Albumin Binding to FcRn contributing to increased vascular clearance.

2020 ◽  
Author(s):  
Shiv Pratap S Yadav ◽  
Ruben Sandoval ◽  
Jingfu Zhao ◽  
Yifan Huang ◽  
Exing Wang ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
In Silico ◽  
Time Course ◽  
Rat Kidney ◽  
In Silico Analysis ◽  
High Serum ◽  
Binding Interaction ◽  
Liver Uptake ◽  
Critical Binding ◽  
Vascular Clearance

Chronic kidney disease results in high serum urea concentrations leading to excessive protein carbamylation, primarily albumin. This is associated with increased cardiovascular disease and mortality. Multiple methods were used to address whether carbamylation alters albumin metabolism. Intravital 2-photon imaging of the Munich Wistar Fromter (MWF) rat kidney and liver allowed us to characterize filtration and proximal tubule and liver uptake. Microscale thermophoresis enabled quantification of Cubilin (CUB7,8 domain) and FcRn binding. Finally, multiple biophysical methods including dynamic light scattering, Small-angle X-ray scattering, LC-MS/MS and in silico analyses were used to identify the critical structural alterations and amino acid modifications of rat albumin. Carbamylation of albumin reduced binding to CUB7,8 and FcRn in a dose-dependent fashion. Carbamylation markedly increased vascular clearance of carbamylated albumin (cRSA) and altered distribution of cRSA in both the kidney and liver at 16hrs post intravenous injection. By evaluating the time course of carbamylation and associated charge, size, shape and binding parameters in combination with in silico analysis and mass spectrometry, the critical binding interaction impacting carbamylated albumin's reduced FcRn binding was identified as K524. Carbamylation of RSA had no effect on glomerular filtration or proximal tubule uptake. These data indicate urea mediated time-dependent carbamylation of albumin lysine K524 resulted in reduced binding to CUB7,8 and FcRn that contribute to altered albumin transport leading to increased vascular clearance and increased liver and endothelial tissue accumulation.

scholarly journals A Novel Homozygous Missense Mutation in the Zinc Finger DNA Binding Domain of GLI1 Causes Recessive Post-Axial Polydactyly

2021 ◽  
Vol 12 ◽  
Author(s):  
Muhammad Umair ◽  
Farooq Ahmad ◽  
Saeed Ahmad ◽  
Qamre Alam ◽  
Mohd Rehan ◽  
...  
Keyword(s):  
Dna Binding ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
In Silico ◽  
Sanger Sequencing ◽  
Critical Role ◽  
In Silico Analysis ◽  
Missense Variant ◽  
Binding Interaction ◽  
Whole Exome

Background: Polydactyly is a prevalent digit abnormality characterized by having extra digits/toes. Mutations in eleven known genes have been associated to cause nonsyndromic polydactyly: GLI3, GLI1, ZRS regulating LMBR1, IQCE, ZNF141, PITX1, MIPOL1, FAM92A, STKLD1, KIAA0825, and DACH1.Method: A single affected family member (IV-4) was subjected to whole-exome sequencing (WES) to identify the causal gene. Bi-directional Sanger sequencing was performed to segregate the identified variant within the family. In silico analysis was performed to investigate the effect of the variant on DNA binding properties.Results: whole-exome sequencing identified a bi-allelic missense variant (c.1010C > T; p. Ser337Leu) in exon nine of GLI1 gene located on chromosome 12q13.3. With the use of Sanger sequencing, the identified variant segregated perfectly with the disease phenotype. Furthermore, in silico analysis of this DNA binding protein revealed that the variant weakened the DNA binding interaction, resulting in indecorous GLI1 function.Conclusion: Herein, we report a novel variant in GLI1 gene, causing autosomal recessive post-axial polydactyly type A (PAPA) type 8. This confirms the critical role of GLI1 in digit development and might help in genotype–phenotype correlation in the future.

The Fine Structure of Rat Renal Microbodies and Cytoplasmic Bodies Following Perfusion Fixation

1973 ◽  
Vol 31 ◽  
pp. 620-621
Author(s):  
J. M. Barrett ◽  
P. M. Heidger
Keyword(s):  
Fine Structure ◽  
Proximal Tubule ◽  
Rat Kidney ◽  
Renal Proximal Tubule ◽  
Convincing Evidence ◽  
Cytoplasmic Bodies ◽  
Rat Renal Proximal Tubule ◽  
Renal Proximal Tubule Cells ◽  
Perfusion Fixation

Microbodies have received extensive morphological and cytochemical investigation since they were first described by Rhodin in 1954. To our knowledge, however, all investigations of microbodies and cytoplasmic bodies of rat renal proximal tubule cells have employed immersion fixation. Tisher, et al. have shown convincing evidence of fine structural alteration of microbodies in rhesus monkey kidney following immersion fixation; these alterations were not encountered when in vivo intravascular perfusion was employed. In view of these studies, and the fact that techniques for perfusion fixation have been established specifically for the rat kidney by Maunsbach, it seemed desirable to employ perfusion fixation to study the fine structure and distribution of microbodies and cytoplasmic bodies within the rat renal proximal tubule.

A systematic review with in silico analysis on transcriptomic profile of gallbladder carcinoma

2020 ◽  
Vol 47 (6) ◽  
pp. 398-408
Author(s):  
Sonam Tulsyan ◽  
Showket Hussain ◽  
Balraj Mittal ◽  
Sundeep Singh Saluja ◽  
Pranay Tanwar ◽  
...  
Keyword(s):  
Systematic Review ◽  
Gallbladder Carcinoma ◽  
In Silico ◽  
In Silico Analysis ◽  
Transcriptomic Profile ◽  
Silico Analysis

Enalos Suite of Tools: Enhancing Cheminformatics and Nanoinfor - matics through KNIME

2020 ◽  
Vol 27 (38) ◽  
pp. 6523-6535 ◽  
Author(s):  
Antreas Afantitis ◽  
Andreas Tsoumanis ◽  
Georgia Melagraki
Keyword(s):  
Data Analysis ◽  
Virtual Screening ◽  
In Silico ◽  
Model Development ◽  
In Silico Analysis ◽  
Material Design ◽  
Efficient Solutions ◽  
Biological Data ◽  
Cost Efficient ◽  
Silico Analysis

Drug discovery as well as (nano)material design projects demand the in silico analysis of large datasets of compounds with their corresponding properties/activities, as well as the retrieval and virtual screening of more structures in an effort to identify new potent hits. This is a demanding procedure for which various tools must be combined with different input and output formats. To automate the data analysis required we have developed the necessary tools to facilitate a variety of important tasks to construct workflows that will simplify the handling, processing and modeling of cheminformatics data and will provide time and cost efficient solutions, reproducible and easier to maintain. We therefore develop and present a toolbox of >25 processing modules, Enalos+ nodes, that provide very useful operations within KNIME platform for users interested in the nanoinformatics and cheminformatics analysis of chemical and biological data. With a user-friendly interface, Enalos+ Nodes provide a broad range of important functionalities including data mining and retrieval from large available databases and tools for robust and predictive model development and validation. Enalos+ Nodes are available through KNIME as add-ins and offer valuable tools for extracting useful information and analyzing experimental and virtual screening results in a chem- or nano- informatics framework. On top of that, in an effort to: (i) allow big data analysis through Enalos+ KNIME nodes, (ii) accelerate time demanding computations performed within Enalos+ KNIME nodes and (iii) propose new time and cost efficient nodes integrated within Enalos+ toolbox we have investigated and verified the advantage of GPU calculations within the Enalos+ nodes. Demonstration data sets, tutorial and educational videos allow the user to easily apprehend the functions of the nodes that can be applied for in silico analysis of data.

In Silico Study of 1, 4 Alpha Glucan Branching Enzyme and Substrate Docking Studies

2020 ◽  
Vol 17 (1) ◽  
pp. 40-50
Author(s):  
Farzane Kargar ◽  
Amir Savardashtaki ◽  
Mojtaba Mortazavi ◽  
Masoud Torkzadeh Mahani ◽  
Ali Mohammad Amani ◽  
...  
Keyword(s):  
Phylogenetic Tree ◽  
In Silico ◽  
Alpha Helix ◽  
In Silico Analysis ◽  
Glycogen Storage ◽  
Docking Studies ◽  
Random Coil ◽  
Special Topic ◽  
Industrial Biotechnology ◽  
In Silico Study

Background: The 1,4-alpha-glucan branching protein (GlgB) plays an important role in the glycogen biosynthesis and the deficiency in this enzyme has resulted in Glycogen storage disease and accumulation of an amylopectin-like polysaccharide. Consequently, this enzyme was considered a special topic in clinical and biotechnological research. One of the newly introduced GlgB belongs to the Neisseria sp. HMSC071A01 (Ref.Seq. WP_049335546). For in silico analysis, the 3D molecular modeling of this enzyme was conducted in the I-TASSER web server. Methods: For a better evaluation, the important characteristics of this enzyme such as functional properties, metabolic pathway and activity were investigated in the TargetP software. Additionally, the phylogenetic tree and secondary structure of this enzyme were studied by Mafft and Prabi software, respectively. Finally, the binding site properties (the maltoheptaose as substrate) were studied using the AutoDock Vina. Results: By drawing the phylogenetic tree, the closest species were the taxonomic group of Betaproteobacteria. The results showed that the structure of this enzyme had 34.45% of the alpha helix and 45.45% of the random coil. Our analysis predicted that this enzyme has a potential signal peptide in the protein sequence. Conclusion: By these analyses, a new understanding was developed related to the sequence and structure of this enzyme. Our findings can further be used in some fields of clinical and industrial biotechnology.

In silico approach for designing a novel recombinant fusion protein as a Candidate Vaccine against HPV

2020 ◽  
Vol 17 ◽  
Author(s):  
Mohsen Sisakht ◽  
Amir Mahmoodzadeh ◽  
Mohammadsaeid Zahedi ◽  
Davood Rostamzadeh ◽  
Amin Moradi Hasan-Abad ◽  
...  
Keyword(s):  
Immune Responses ◽  
Fusion Protein ◽  
In Silico ◽  
Precancerous Lesions ◽  
Candidate Vaccine ◽  
T Cell Epitopes ◽  
Binding Interaction ◽  
Hpv16 E6 ◽  
E7 Proteins

Background: Human papillomavirus (HPV) is the main biological agent causing sexually transmitted diseases (STDs), including precancerous lesions and several types of prevalent cancers. To date, numerous types of vaccines are designed to prevent high-risk HPV. However, their prophylactic effect is not the same and does not clear previous infections. Therefore, there is an urgent need for developing therapeutic vaccines that trigger cell-mediated immune responses for the treatment of HPV. The HPV16 E6 and E7 proteins are ideal targets for vaccine therapy against HPV. Fusion protein vaccines, which include both immunogenic interest protein and an adjuvant for augmenting the immunogenicity effects, are theoretically capable of guarantee the power of the immune system against HPV. Method: A vaccine construct, including HPV16 E6/E7 proteins along with a heat shock protein GP96 (E6/E7-NTGP96 construct), was designed using in silico methods. By the aid of the SWISS-MODEL server, the optimal 3D model of the designed vaccine was selected, followed by physicochemical and molecular parameters were performed using bioinformatics tools. Docking studies were done to evaluate the binding interaction of the vaccine. Allergenicity, immunogenicity, B, and T cell epitopes of the designed construct were predicted. Results: Immunological and structural computational results illustrated that our designed construct is potentially proper for stimulation of cellular and humoral immune responses against HPV. Conclusion: Computational studies showed that the E6/E7-NTGP96 construct is a promising candidate vaccine that needs further in vitro and in vivo evaluations.

Sign in / Sign up

Export Citation Format

Share Document