A novel identification approach for discovery of 5-HydroxyTriptamine 2A antagonists: combination of 2D/3D similarity screening, molecular docking and molecular dynamics

<p>5-HydroxyTriptamine 2A antagonists are potential targets for treatment of various cerebrovascular and cardiovascular disorders. In this study, we have developed and performed a unique screening pipeline for filtering ZINC database compounds on the basis of similarities to known antagonists to determine novel small molecule antagonists of 5-HydroxyTriptamine 2A. The screening pipeline is based on 2D similarity, 3D dissimilarity and a combination of 2D/3D similarity. The shortlisted compounds were docked to a 5-HydroxyTriptamine 2A homology-based model, and complexes with low binding energies (287 complexes) were selected for molecular dynamics (MD) simulations in a lipid bilayer. The MD simulations of the shortlisted compounds in complex with 5-HydroxyTriptamine 2A confirmed the stability of the complexes and revealed novel interaction insights. The receptor residues S239, N343, S242, S159, Y370 and D155 predominantly participate in hydrogen bonding. <i>π</i>–<i>π</i> stacking is observed in F339, F340, F234, W151 and W336, whereas hydrophobic interactions are observed amongst V156, F339, F234, V362, V366, F340, V235, I152 and W151. The known and potential antagonists shortlisted by us have similar overlapping molecular interaction patterns. The 287 potential 5-HydroxyTriptamine 2A antagonists may be experimentally verified.</p

Introducing a simple model system for binding studies of known and novel inhibitors of AMPK: a therapeutic target for prostate cancer

<p>Prostate cancer (PC) is one of the leading cancers in men, raising a serious health issue worldwide. Due to lack of suitable biomarker, their inhibitors and the platform for testing those inhibitors result in poor prognosis of PC. AMP-activated protein kinase (AMPK) is a highly conserved protein kinase found in eukaryotes that is involved in growth and development, and also acts as a therapeutic target for PC. The aim of the present study is to identify novel potent inhibitors of AMPK and propose a simple cellular model system for understanding its biology. Structural modelling and MD simulations were performed to construct and refine the 3D models of <i>Dictyostelium</i> and human AMPK. Binding mechanisms of different drug compounds were studied by performing molecular docking, molecular dynamics and MM-PBSA methods. Two novel drugs were isolated having higher binding affinity over the known drugs and hydrophobic forces that played a key role during protein–ligand interactions. The study also explored the simple cellular model system for drug screening and understanding the biology of a therapeutic target by performing <i>in vitro</i> experiments.</p

Metal-Free Synthesis of 2‑Substituted 3‑(2-Hydroxyaryl)quinolines and 4‑(2-Hydroxyaryl)acridines via Benzyne Chemistry

A metal-free approach for the synthesis of 3-aryl-2-substituted quinolines and 4-arylacridines has been developed via the 1,3-dipolar cycloaddition reactions of arynes with <i>N</i>-oxides. Reactions of various 2-substitued quinoline <i>N</i>-oxides with <i>ortho</i>-(trimethylsilyl)­aryltriflates in the presence of KF gave 3-(2-hydroxyaryl)­quinoline derivatives in good yields. Acridine <i>N</i>-oxides also reacted with arynes to furnish 4-(2-hydroxyaryl)­acridines, albeit in moderate yields

Artificial neural networks for the wavelet analysis of Lane-Emden equations: exploration of astrophysical enigma

The equations of Lane-Emden (LE) can be visualized in various phenomena of astrophysics, fluid mechanics, polymer science and material science, thus the main concern of the present study is to put a novel effort to resolve these equations by utilizing the artificial neural networking approach incorporation with Vieta-Lucas wavelets called as VLW-ANN method. This unique combination of neural networking and Vieta-Lucas wavelets has been prepared to reduce the computational challenges as well as to overcome the obstacles while dealing with singularity. Many examples of the LE variety are solved by this approach. The effectiveness, accuracy and simplicity of the VLW-ANN scheme are demonstrated by a comparative study between the VLW-ANN results and existing results. Additionally, the results are shown in tables and figures, which give a more favorable impression of the scheme’s dependability. VLW-ANN scheme will provide interesting results for other non-linear models.</p

Image_1_Transient suppression of Wnt signaling in poor-quality buffalo oocytes improves their developmental competence.tif

IntroductionOne of the most evolutionary conserved communication systems, the Wnt signaling pathway is a major gene regulatory pathway that affects the developmental competence of oocytes and regulates most embryonic developmental processes. The present study was undertaken to modulate the canonical Wnt (Wingless/integration) signaling pathway in the poor-quality (colorless cytoplasm after Brilliant Cresyl Blue staining, BCB-) buffalo cumulus-oocyte complexes (COCs) to improve their in vitro maturation (IVM) and embryo production (IVEP) rates.MethodsThe expression of key Wnt pathway genes was initially assessed in the good (blue cytoplasm after Brilliant Cresyl Blue staining, BCB+) and poor quality (BCB-) buffalo COCs to establish a differential activity of the Wnt pathway. The BCB- COCs were supplemented with the Wnt pathway inhibitor, Dickkopf-related protein 1 (DKK1) and later subjected to IVM and IVEP along with the BCB+ and BCB- controls. The cumulus expansion index (CEI), rate of nuclear maturation (mean percentage of oocytes in the MII stage) and embryo production, and the expression of developmentally important genes were evaluated to assess the effect of Wnt pathway inhibition on the development competence of these poor-quality oocytes.ResultsThe Wnt pathway genes exhibited a significantly higher expression (p ConclusionThese data indicate that inhibition of the Wnt pathway during the initial course of oocyte maturation can improve the development competence of poor-quality buffalo oocytes.</p

Table_1_Transient suppression of Wnt signaling in poor-quality buffalo oocytes improves their developmental competence.docx

IntroductionOne of the most evolutionary conserved communication systems, the Wnt signaling pathway is a major gene regulatory pathway that affects the developmental competence of oocytes and regulates most embryonic developmental processes. The present study was undertaken to modulate the canonical Wnt (Wingless/integration) signaling pathway in the poor-quality (colorless cytoplasm after Brilliant Cresyl Blue staining, BCB-) buffalo cumulus-oocyte complexes (COCs) to improve their in vitro maturation (IVM) and embryo production (IVEP) rates.MethodsThe expression of key Wnt pathway genes was initially assessed in the good (blue cytoplasm after Brilliant Cresyl Blue staining, BCB+) and poor quality (BCB-) buffalo COCs to establish a differential activity of the Wnt pathway. The BCB- COCs were supplemented with the Wnt pathway inhibitor, Dickkopf-related protein 1 (DKK1) and later subjected to IVM and IVEP along with the BCB+ and BCB- controls. The cumulus expansion index (CEI), rate of nuclear maturation (mean percentage of oocytes in the MII stage) and embryo production, and the expression of developmentally important genes were evaluated to assess the effect of Wnt pathway inhibition on the development competence of these poor-quality oocytes.ResultsThe Wnt pathway genes exhibited a significantly higher expression (p ConclusionThese data indicate that inhibition of the Wnt pathway during the initial course of oocyte maturation can improve the development competence of poor-quality buffalo oocytes.</p

Image_2_Transient suppression of Wnt signaling in poor-quality buffalo oocytes improves their developmental competence.tif

IntroductionOne of the most evolutionary conserved communication systems, the Wnt signaling pathway is a major gene regulatory pathway that affects the developmental competence of oocytes and regulates most embryonic developmental processes. The present study was undertaken to modulate the canonical Wnt (Wingless/integration) signaling pathway in the poor-quality (colorless cytoplasm after Brilliant Cresyl Blue staining, BCB-) buffalo cumulus-oocyte complexes (COCs) to improve their in vitro maturation (IVM) and embryo production (IVEP) rates.MethodsThe expression of key Wnt pathway genes was initially assessed in the good (blue cytoplasm after Brilliant Cresyl Blue staining, BCB+) and poor quality (BCB-) buffalo COCs to establish a differential activity of the Wnt pathway. The BCB- COCs were supplemented with the Wnt pathway inhibitor, Dickkopf-related protein 1 (DKK1) and later subjected to IVM and IVEP along with the BCB+ and BCB- controls. The cumulus expansion index (CEI), rate of nuclear maturation (mean percentage of oocytes in the MII stage) and embryo production, and the expression of developmentally important genes were evaluated to assess the effect of Wnt pathway inhibition on the development competence of these poor-quality oocytes.ResultsThe Wnt pathway genes exhibited a significantly higher expression (p ConclusionThese data indicate that inhibition of the Wnt pathway during the initial course of oocyte maturation can improve the development competence of poor-quality buffalo oocytes.</p

Aero-Gel Based Cerium Doped Iron Oxide Solid Solution for Ultrafast Removal of Arsenic

A solid solution of aero-gel based cerium doped iron oxide nanoparticles has been utilized for the first time for ultrasonic wave assisted adsorptive removal of arsenic from aqueous medium. The FE-SEM and HR-TEM images revealed a novel morphology of hollow architectures with irregular distribution in sizes in which the particles are interconnected with each other in a long-range network. The HR-XRD analysis indicated the cubic fluorite type structure with <i>Fm</i>3̅<i>m</i> space group which is retained even after adsorption of As­(III). The Raman study and Lebail refinement confirmed the formation of solid solution of Fe and Ce oxide nanoparticles. The room temperature ferromagnetism was observed for CeO₂ NPs (Ms 0.0209 emu g^–1) which is attributed to higher concentration of oxygen vacancies and increased (Ms 0.0287 emu g^–1) after doping of iron. The adsorption pattern of As­(III) is well-defined by Redlich–Peterson isotherm while the adsorption is governed by pseudo-second-order kinetics. The HR-XPS and diffuse reflectance spectroscopy revealed the formation of variable oxidation state of metal ions which facilitate the oxidation of As­(III) (more toxic) to As­(V) (less toxic) during adsorption process. The effective removal of arsenic (more than 80%) was observed within 2.5 min of initial adsorption process and approximately 99% removal was achieved within 10 min of adsorption. The adsorption capacity of our best adsorbent was found to be 263 mg g^–1. The effect of pH and interfering ions on adsorption capacities of synthesized adsorbents revealed its efficacy over the wide range of pH

Emission from open burning of municipal solid waste in India

<p>Open burning of Municipal Solid Waste (MSW) is a potential non-point source of emission, which causes greater concern especially in developing countries such as India. Lack of awareness about environmental impact of open burning, and ignorance of the fact, i.e. ‘Open burning is a source of emission of carcinogenic substances’ are major hindrances towards an appropriate municipal solid waste management system in India. The paper highlights the open burning of MSW practices in India, and the current and projected emission of 10 major pollutants (dioxin, furans, particulate matter, carbon monoxide, sulphur oxides, nitrogen oxides, benzene, toluene, ethyl benzene and 1-hexene) emitted due to the open burning of MSW. Waste to Energy potential of MSW was also estimated adopting effective biological and thermal techniques. Statistical techniques were applied to analyse the data and current and projected emission of various pollutants were estimated. Data pertaining to population, MSW generation and its collection efficiency were compiled for 29 States and 7 Union Territories. Thereafter, emission of 10 pollutants was measured following methodology prescribed in Intergovernmental <i>Panel on Climate Change</i> guideline for National Greenhouse Gas Inventories, 2006. The study revealed that people living in Metropolitan cities are more affected by emissions from open burning.</p

Additional file 1: of A model for the use of blended learning in large group teaching sessions

Perceived Utility of Learning Technologies Scale (PULTS) survey. An example of the questions from the online Perceived Utility of Learning Technologies Scale (PULTS) survey (PDF file). Links to online surveys, via the Qualtrics survey engine, were presented to students at the completion of online modules relevant to specific topics (e.g. Acute Inflammation). (PDF 234 kb