scholarly journals In-silico Exploration of Mouse Brain Dynamics by Stimulation explains Functional Networks and Sensory Processing

2019 ◽  
Author(s):  
Andreas Spiegler ◽  
Javad Karimi Abadchi ◽  
Majid Mohajerani ◽  
Viktor K. Jirsa
Keyword(s):  
Mouse Brain ◽  
In Silico ◽  
Dynamic Properties ◽  
Brain Activity ◽  
Parameter Tuning ◽  
Functional Networks ◽  
Direct Stimulation ◽  
Systematic Exploration ◽  
The Stability

ABSTRACTSensory and direct stimulation of the brain probes its functional repertoire and the information processing capacity of networks. However, a systematic exploration can only be performed in silico. Stimulation takes the system out of its attractor states and samples the environment of the flow to gain insight into the stability and multiplicity of trajectories. It is the only means of obtaining a complete understanding of the healthy brain network’s dynamic properties. We built a whole mouse brain model with connectivity derived from tracer studies. We systematically varied the stimulation location, the ratio of long- to short-range interactions, and the range of short connections. Functional networks appeared in the spatial motifs of simulated brain activity. Several motifs included the default mode network, suggesting a junction of functional networks. The model explains processing in sensory systems and replicates the in vivo dynamics after stimulation without parameter tuning, emphasizing the role of connectivity.

In-Silico Analysis to Identify Potential Inhibitors Against the Protein NSP12 of SARS-CoV-2

2021 ◽  
Vol 6 (3) ◽  
pp. 48-60
Author(s):  
Hima Vyshnavi ◽  
Gayathri S. S. ◽  
Shahanas Naisam ◽  
Suvanish Kumar ◽  
Nidhin Sreekumar
Keyword(s):  
In Silico ◽  
Interaction Analysis ◽  
In Silico Analysis ◽  
Drug Efficacy ◽  
Drug Candidate ◽  
In Vivo Analysis ◽  
The Stability ◽  
Potential Inhibitors ◽  
Silico Analysis

In this pandemic condition, a drug candidate which is effective against COVID-19 is very much desired. This study initiates an in silico analysis to screen small molecules such as phytochemicals, drug metabolites, and natural metabolites against Nsp12 (a catalytic unit for RNA transcription and replication). Molecular interaction analysis of 6M71 was carried out against 2,860 ligands using Schrodinger Glide software. After docking analysis, the top 10 molecules (Glide score) were subjected to MD simulation for validating the stability. It resulted in top 10 compounds with high binding affinities with the target molecule NSP 12. Out of these, top 3 compounds including PSID_08_LIG3 (HMDB0133544), PSID_08_LIG4 (HMDB0132898), and PSID_08_LIG9 (HMDB0128199) show better Glide scores, better H-bond interaction, better MMGBSA value and stability on dynamic simulation after analysis of the results. The suggested ligands can be postulated as effective antiviral drugs against COVID-19. Further in vivo analysis is needed for validating the drug efficacy.

In Vivo Three-photon Calcium Imaging of Brain Activity from Layer 6 Neurons in Mouse Brain

2014 ◽  
Author(s):  
Dimitre G. Ouzounov ◽  
Nicholas Horton ◽  
Tianyu Wang ◽  
Danielle Feng ◽  
Nozomi Nishimura ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Calcium Imaging ◽  
Brain Activity

In vivo Three-photon Imaging of Brain Activity from Cortical and Subcortical Neurons in Intact Mouse Brain

2015 ◽  
Author(s):  
Dimitre G. Ouzounov ◽  
Tianyu Wang ◽  
Nicholas G. Horton ◽  
Jean C. Cruz Hernández ◽  
Danielle Feng ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Brain Activity ◽  
Intact Mouse ◽  
Photon Imaging

scholarly journals Extemporaneous Compounding and Physiological Modeling of Amlodipine/Valsartan Suspension

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Wafa’ J. Aabed ◽  
Asma H. Radwan ◽  
Abdel Naser Zaid ◽  
Naser Y. Shraim
Keyword(s):  
In Silico ◽  
In Vitro Dissolution ◽  
Dissolution Properties ◽  
In Silico Modeling ◽  
Microbial Stability ◽  
The Stability ◽  
Extemporaneous Preparation ◽  
Physical And Chemical

Background and Objectives. In case of absent liquid dosage form, crushing a tablet or dispersing a capsule would be the most convenient option for using these drugs in patients with dysphagia difficulties. The aims of the study were to prepare an extemporaneous suspension of amlodipine and valsartan from the available commercial tablets and to evaluate the stability and dissolution properties of the compounded suspension. Method. Amlodipine/valsartan extemporaneous suspension was prepared from available commercial tablets such as Valzadepine®. The dissolution profiles for the extemporaneous preparation and the commercial tablet were determined in different pH media. The physical, chemical, and microbial stability of the compounded formulation was evaluated over one-month period at room temperature. Moreover, in silico modeling using GastroPlus™ software was used to build absorption models for both drugs based on the in vitro dissolution data. The simulated plasma profiles for both active ingredients were compared with the in vivo plasma profiles to examine the similarity of the extemporaneous suspension and the commercial tablets. Results. The amlodipine/valsartan extemporaneous suspension was successfully prepared with acceptable organoleptic properties. The suspension was stable for four-week period preserving its physical and chemical features. The release profiles of valsartan and amlodipine from the suspension were similar to those from source tablet Valzadepine®. In silico modeling predicted the similarity of the extemporaneous suspension and the commercial tablets. Conclusion. Amlodipine/valsartan extemporaneous suspension could be prepared from available commercial tablets. Moreover, GastroPlus™ can be applied along with the in vitro dissolution in order to affirm similarity in extemporaneous compounding situations.

scholarly journals In-Silico Evaluation of Tiryaq-E-Wabai, an Unani Formulation for its Potency against SARS-CoV-2 Spike Glycoprotein and Main Protease

2021 ◽  
Vol 11 (4-S) ◽  
pp. 86-100
Author(s):  
N ZAHEER AHMED ◽  
DICKY JOHN DAVIS ◽  
NOMAN ANWAR ◽  
ASIM ALI KHAN ◽  
RAM PRATAP MEENA ◽  
...  
Keyword(s):  
In Silico ◽  
Dynamics Simulation ◽  
In Vivo Studies ◽  
Spike Glycoprotein ◽  
Unani Medicine ◽  
Main Protease ◽  
Pubchem Database ◽  
The Stability

COVID-19 was originated in Wuhan, China, in December 2019 and has been declared a pandemic disease by WHO. The number of infected cases continues unabated and so far, no specific drug approved for targeted therapy. Hence, there is a need for drug discovery from traditional medicine. Tiryaq-e-Wabai is a well-documented formulation in Unani medicine for its wide use as prophylaxis during epidemics of cholera, plague and other earlier epidemic diseases. The objective of the current study is to generate in-silico evidence and evaluate the potency of Tiryaq-e-Wabai against SARS-CoV-2 spike (S) glycoprotein and main protease (3CLpro). The structures of all phytocompounds used in this study were retrieved from PubChem database and some were built using Marvin Sketch. The protein structure of the SARS-CoV-2 S glycoprotein and 3CLpro was retrieved from the PDB ID: 6LZG and 7BQY respectively. AutoDock Vina was used to predict top ranking poses with best scores. The results of the molecular docking showed that phytocompounds of Tiryaq-e-Wabai exhibited good docking power with spike glycoprotein and 3CLpro. Among tested compounds Crocin from Zafran and Aloin A from Sibr showed strong binding to spike glycoprotein and 3CLpro respectively. Molecular dynamics simulation confirmed the stability of the S glycoprotein-Crocin and 3CLpro-Aloin A complexes. The Unani formulation Tiryaq-e-Wabai has great potential to inhibit the SARS-CoV-2, which have to be substantiated with further in-vitro and in-vivo studies. Keywords: In-silico study, SARS-CoV-2, Tiryaq-e-Wabai, Unani formulation, Crocin, Aloin A

scholarly journals Conformational Selection Mechanism Provides Structural Insights into the Optimization of APC-Asef Inhibitors

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 962
Author(s):  
Xinheng He ◽  
Ning Huang ◽  
Yuran Qiu ◽  
Jian Zhang ◽  
Yaqin Liu ◽  
...  
Keyword(s):  
Binding Free Energy ◽  
Dynamic Properties ◽  
Md Simulations ◽  
Selection Mechanism ◽  
Nucleotide Exchange ◽  
Nucleotide Exchange Factor ◽  
Broad Array ◽  
Ligand Interactions ◽  
The Stability

Metastasis is the major cause of death in colorectal cancer and it has been proven that inhibiting an interaction between adenomatous polyposis coli (APC) and Rho guanine nucleotide exchange factor 4 (Asef) efficaciously restrain metastasis. However, current inhibitors cannot achieve a satisfying effect in vivo and need to be optimized. In the present study, we applied molecular dynamics (MD) simulations and extensive analyses to apo and holo APC systems in order to reveal the inhibitor mechanism in detail and provide insights into optimization. MD simulations suggested that apo APC takes on a broad array of conformations and inhibitors stabilize conformation selectively. Representative structures in trajectories show specific APC-ligand interactions, explaining the different binding process. The stability and dynamic properties of systems elucidate the inherent factors of the conformation selection mechanism. Binding free energy analysis quantitatively confirms key interface residues and guide optimization. This study elucidates the conformation selection mechanism in APC-Asef inhibition and provides insights into peptide-based drug design.

scholarly journals An In-Silico, In-Vitro and In-Vivo Combined Approach to Identify NMNATs as Potential Protein Targets of ProEGCG for Treatment of Endometriosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Sze Wan Hung ◽  
Bo Liang ◽  
Yating Gao ◽  
Ruizhe Zhang ◽  
Zhouyurong Tan ◽  
...  
Keyword(s):  
In Silico ◽  
Epigallocatechin Gallate ◽  
Uterine Cavity ◽  
Redox Status ◽  
Therapeutic Effects ◽  
Combined Approach ◽  
Protein Targets ◽  
The Stability

Endometriosis is defined as endometrial tissues found outside the uterine cavity. ProEGCG is a prodrug of Epigallocatechin gallate (EGCG), a potent polyphenol found in green tea. It inhibits the development of endometriotic lesions of mouse model in vivo, with higher efficacy and more remarkable anti-oxidative ability than EGCG. Our study aims to identify the molecular binding targets and pharmacological actions of ProEGCG in treating endometriosis. Protein target interaction study is essential to fully characterize the mechanism of actions, related therapeutic effects, and side effects. We employed a combined approach, starting with an in silico reverse screening of protein targets and molecular docking, followed by in vitro cellular thermal shift assay (CESTA) to assess the stability of protein-small molecule complexes. Then microarray and immunostaining of endometriotic lesions in mice in vivo confirmed the molecular interaction of the selected targets after treatment. Our study identified enzymes nicotinamide nucleotide adenylyltransferase (NMNAT)1 and NMNAT3 as protein targets of ProEGCG in silico and in vitro and were overexpressed after ProEGCG treatment in vivo. These findings suggested that participation in nicotinate and nicotinamide metabolism potentially regulated the redox status of endometriosis via its antioxidative capacities through binding to the potential therapeutic targets of ProEGCG.

scholarly journals Characteristics of Neurokinin-3 Receptor and Its Binding Sites by Mutational Analysis

Biology ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 968
Author(s):  
Ishwar Atre ◽  
Naama Mizrahi ◽  
Berta Levavi-Sivan
Keyword(s):  
In Silico ◽  
Crucial Role ◽  
Mutational Analysis ◽  
Inhibitory Effect ◽  
Sperm Volume ◽  
Neurokinin 3 Receptor ◽  
The Stability ◽  
And Function

NKB (Neurokinin B) is already known to play a crucial role in fish reproduction, but little is known about the structure and function of NKB receptors. Based on an in silico model of the tilapia NKB receptor Tachykinin 3 receptor a (tiTac3Ra) found in the current study, we determined the key residues involved in binding to tilapia NKB and its functional homologue NKF (Neurokinin F). Despite studies in humans suggesting the crucial role of F2516.44 and M2897.43 in NKB binding, no direct peptide interaction was observed in tilapia homologs. In-silico, Ala mutations on residues F2516.44 and M2897.43 did not influence binding affinity, but significantly affected the stability of tiTac3Ra. Moreover, in vitro studies indicated them to be critical to tiNKB/tiNKF-induced receptor activity. The binding of NKB antagonists to tiTac3Ra both in-vitro and in vivo inhibits FSH (follicle stimulating hormone) and LH (luteinizing hormone) release and sperm production in mature tilapia males. Non-peptide NKB antagonist SB-222200 had a strong inhibitory effect on the Tac3Ra activation. SB-222200 also decreased LH plasma levels; two hours post intraperitoneal injection, changed sperm volume and the ratios of the different stages along the spermatogenesis in tilapia testes.

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