scholarly journals Analysis and characterization of a promising therapeutic target identified in Leishmania spp

2020 ◽  
pp. 99-132
Author(s):  
Fernando de Sá Ribeiro ◽  
Jéssica Barbosa de Jesus ◽  
Alessandra Mendonça Teles de Souza
Keyword(s):  
Therapeutic Target ◽  
Three Dimensional ◽  
Normal Modes ◽  
Alpha Helix ◽  
Movement Pattern ◽  
Comparative Modeling ◽  
New Drugs ◽  
Three Dimensional Model ◽  
Oligopeptidase B ◽  
Leishmania Spp

Leishmaniasis is a neglected disease caused by protozoa of the genus Leishmania spp., which affects about 1.6 million individuals each year and 500,000 present themselves in the visceral form. In Brazil there are about 30,000 new cases each year. In addition, the country is responsible for 90% of reported cases of Visceral Leishmaniasis, and this is more severe form of the disease. Allied to these facts, the current treatment is ineffective, contributing to the establishment of resistant strains. Currently, the treatment has several side effects and permanent damage to the health of patients, this fact has contributed to the search for new drugs against leishmaniasis. The enzyme oligopeptidase B (OPB) has been studied as a possible therapeutic target in the development of antiparasitic agents. Thus, the objective of this work is to construct the three-dimensional model of the enzyme Oligopeptidase B of different species of Leishmania spp. and compare them to each other. For this purpose, the comparative modeling method was used. In this method, the models of the species L. brasiliensis, L. donovani, L. infantum, L. mexicana and L. panamensis were constructed using the MODELLER program. Once the models were ready, the validation process was carried out and subsequently characterized, which was possible to verify a promising degree of similarity between the models. Finally, these models were submitted to the method of analysis by normal modes, which obtained a similar movement pattern, thus it was possible to verify a movement in a specific region of an alpha-helix, consequently leading to the triad of the enzyme being exposed, which may be indicative of a mechanism of action. Finally, it is expected to use the models built to assist in the development of a promising new therapy for the treatment of leishmaniasis.

scholarly journals sFLT-1 inhibits proliferation, migration, and invasion of colorectal cancer SW480 cells through vascular mimicry formation suppression

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831769833 ◽  
Author(s):  
Wang Jinjun ◽  
Wang Zhaowei ◽  
Li Qiang ◽  
Xue Zhijun ◽  
Zhang Juanzi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tyrosine Kinase ◽  
Three Dimensional ◽  
New Drugs ◽  
Migration And Invasion ◽  
Vascular Endothelial ◽  
Three Dimensional Model ◽  
Vascular Endothelial Cadherin ◽  
Sw480 Cells ◽  
Vascular Mimicry

To investigate the effects of soluble fms-like tyrosine kinase-1 on the vascular mimicry formation, proliferation, migration, and invasion of colorectal cancer SW480 cells. The recombinant plasmid pBLAST49-sFLT-1 or pBLAST49 control plasmid was transfected into SW480 cells to obtain hsFLT-1-SW480 or Ctrl-SW480 cells. The three-dimensional model culture, sulforhodamine B assay, scratch assay, and Transwell assay were performed to detect the vascular mimicry formation, proliferation, migration, and invasion of colorectal cancer SW480 cells, respectively. Western blotting was used to detect the expression of vascular endothelial–cadherin protein. Compared with Ctrl-SW480 cells, vascular mimicry formation ((0.85 ± 0.04) vs (7.40 ± 0.69), p < 0.05) and vascular endothelial–cadherin expression ((1.25 ± 0.08) vs (1.89 ± 0.03), p < 0.05) were significantly decreased, and the growth rate was also significantly decreased in hsFLT-1-SW480 cells ((32.54 ± 5.12) vs (88.13 ± 11.52), p < 0.05). Moreover, the migration ((0.46 ± 0.08) vs (0.94 ± 0.03), p < 0.05) and invasion capacity ((59.14 ± 3.64) vs (134.85 ± 10.16), p < 0.05) of SW480 cells were significantly inhibited upon soluble fms-like tyrosine kinase-1 transfection. soluble fms-like tyrosine kinase-1 inhibits cell proliferation, migration, and invasion of colorectal cancer SW480 cells through suppression of vascular mimicry formation, which provides a good basis for the development of new drugs for the treatment of colorectal cancer by targeting both angiogenesis and vascular mimicry formation.

scholarly journals In Silico prediction and Comparative Modeling of proteins in Creeping Fig (Ficus pumila) plant

2021 ◽  
Vol 23 (08) ◽  
pp. 898-905
Author(s):  
P. Revathi ◽  
◽  
K. Nirubama ◽  
G. Thamotharan ◽  
M. Beutline Malgija ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Transmembrane Helix ◽  
Three Dimensional ◽  
Alpha Helix ◽  
Comparative Modeling ◽  
Structural Features ◽  
Vital Role ◽  
Random Coil ◽  
Dimensional Structure ◽  
Grand Average

In the present study, the Ficus pumila have taken to analyze the proteins by their preliminary characters from the database and predicted vital role of different sequences. The F. pumila (Creeping fig) is a prostrate/climbing shrub, experiments proved various active phytochemicals and antioxidant, antimicrobial, antimutagenic, analgesic, anti-inflammatory, antiproliferative, hypoglycemic, hypolipidemic, antihyperprolactinemic, anticholinesterase, nephroprotective properties. In addition to all metabolites, it also constitutes specific proteins that were evaluated through insilico homology modeling. Though it is considered as a poisonous weed, the protein present in this plant is evaluated by physicochemical, phylogeny and amino acid proportions by protparam, Swiss model, SOPMA, Clustal omega tools to describe its structural features and to understand molecular function. The computed theoretical isoelectric point (pI) found to be more than 7 indicates basic nature of proteins. The aliphatic index ranges 67-113 indicates thermal stability of proteins. The predicted Grand average hydropathy(GRAVY) shows possibilities of enhanced interaction of these proteins with water by lowest value. Functional analysis of these proteins was performed by SOSUI server which predicted transmembrane helix and solubility. Secondary structure analysis was carried out by SOPMA revealed that Alpha helix and random coil dominated followed by extended strand, and beta turns among secondary structure elements. The modelling of three-dimensional structure of proteins was performed by Swiss model. The model was validated using protein structure checking tool- VADAR. Particularly, NAD(P)H –quinoneoxidoreductase and Glyceraldehyde-3-phosphate dehydrogenase structures were analysed by phylogenetic analysis to trace relationship and reported. The results suggesting its possible role in cellular and metabolic functions.

scholarly journals The Amino Terminus of Pseudomonas aeruginosaOuter Membrane Protein OprF Forms Channels in Lipid Bilayer Membranes: Correlation with a Three-Dimensional Model

2000 ◽  
Vol 182 (18) ◽  
pp. 5251-5255 ◽  
Author(s):  
Fiona S. L. Brinkman ◽  
Manjeet Bains ◽  
Robert E. W. Hancock
Keyword(s):  
Lipid Bilayer ◽  
Lipid Bilayers ◽  
Three Dimensional ◽  
Comparative Modeling ◽  
Three Dimensions ◽  
Amino Terminus ◽  
Lipid Bilayer Membranes ◽  
Three Dimensional Model ◽  
Sequence Comparisons ◽  
Bilayer Membranes

ABSTRACT Pseudomonas aeruginosa OprF forms 0.36-nS channels and, rarely, 2- to 5-nS channels in lipid bilayer membranes. We show that a protein comprising only the N-terminal 162-amino-acid domain of OprF formed the smaller, but not the larger, channels in lipid bilayers. Circular dichroism spectroscopy indicated that this protein folds into a β-sheet-rich structure, and three-dimensional comparative modeling revealed that it shares significant structural similarity with the amino terminus of the orthologous protein Escherichia coliOmpA, which has been shown to form a β-barrel. OprF and OmpA share only 15% identity in this domain, yet these results support the utility of modeling such widely divergent β-barrel domains in three dimensions in order to reveal similarities not readily apparent through primary sequence comparisons. The model is used to further hypothesize why porin activity differs for the N-terminal domains of OprF and OmpA.

Three-Dimensional Model for Virtual Surgical Simulation, during Complex Skull Base Surgery and Aneurysm Surgery

Skull Base ◽  
2008 ◽  
Vol 18 (S 01) ◽  
Author(s):  
Akio Morita ◽  
Toshikazu Kimura ◽  
Shigeo Sora ◽  
Kengo Nishimura ◽  
Hisayuki Sugiyama ◽  
...  
Keyword(s):  
Skull Base ◽  
Surgical Simulation ◽  
Skull Base Surgery ◽  
Three Dimensional ◽  
Aneurysm Surgery ◽  
Dimensional Model ◽  
Three Dimensional Model

Digitalization system of ancient architecture decoration art based on neural network and image features

2020 ◽  
pp. 1-12
Author(s):  
Wu Xin ◽  
Qiu Daping
Keyword(s):  
Neural Network ◽  
Construction Industry ◽  
Three Dimensional ◽  
Performance Testing ◽  
Image Features ◽  
Three Dimensional Model ◽  
Performance Effect ◽  
Data Process ◽  
And Performance ◽  
Construction Mode

The inheritance and innovation of ancient architecture decoration art is an important way for the development of the construction industry. The data process of traditional ancient architecture decoration art is relatively backward, which leads to the obvious distortion of the digitalization of ancient architecture decoration art. In order to improve the digital effect of ancient architecture decoration art, based on neural network, this paper combines the image features to construct a neural network-based ancient architecture decoration art data system model, and graphically expresses the static construction mode and dynamic construction process of the architecture group. Based on this, three-dimensional model reconstruction and scene simulation experiments of architecture groups are realized. In order to verify the performance effect of the system proposed in this paper, it is verified through simulation and performance testing, and data visualization is performed through statistical methods. The result of the study shows that the digitalization effect of the ancient architecture decoration art proposed in this paper is good.

Phonetic iconicity in the evaluative morphology of a sample of Indo-European, Niger-Congo and Austronesian languages

2010 ◽  
Vol 3 (2) ◽  
pp. 156-180 ◽  
Author(s):  
Renáta Gregová ◽  
Lívia Körtvélyessy ◽  
Július Zimmermann
Keyword(s):  
Three Dimensional ◽  
Sound Symbolism ◽  
Three Dimensional Model ◽  
Austronesian Languages ◽  
Place Of Articulation ◽  
European Languages ◽  
Phonetic Symbolism ◽  
The Individual ◽  
Core Vocabulary

Universals Archive (Universal #1926) indicates a universal tendency for sound symbolism in reference to the expression of diminutives and augmentatives. The research ( Štekauer et al. 2009 ) carried out on European languages has not proved the tendency at all. Therefore, our research was extended to cover three language families – Indo-European, Niger-Congo and Austronesian. A three-step analysis examining different aspects of phonetic symbolism was carried out on a core vocabulary of 35 lexical items. A research sample was selected out of 60 languages. The evaluative markers were analyzed according to both phonetic classification of vowels and consonants and Ultan's and Niewenhuis' conclusions on the dominance of palatal and post-alveolar consonants in diminutive markers. Finally, the data obtained in our sample languages was evaluated by means of a three-dimensional model illustrating the place of articulation of the individual segments.

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