scholarly journals In Silico Analysis of Effect of Non-synonymous SNPs associated with Permanent Neonatal Diabetes Mellitus on Stability and Structure of Human Insulin

2020 ◽  
Author(s):  
Nishat Tabassum
Keyword(s):  
Human Insulin ◽  
Drug Targets ◽  
In Silico Analysis ◽  
Neonatal Diabetes ◽  
Building Blocks ◽  
Permanent Neonatal Diabetes ◽  
The Impact ◽  
Potential Drug Targets ◽  
Analysis Determination

AbstractMotivationProteins are the building-blocks of life. However with the deluge of data on protein sequences and their association with diseases, it is imperative to use computational tools to aid experimental analysis. Determination of the impact of disease-causing SNPs on protein’s structure is crucial in discovering how a disease affects the functions on a fundamental level and thereafter, determining potential drug targets.ResultsSNPs associated with the genetic disease permanent neonatal diabetus mellitus (PNDM) were studied to determine their impact on human insulin. Out of 16 missense variants, eight were predicted to be deleterious. 6 of the SNPs resulted in high structural differences (RMSD > 0.9, H bonds > 35). Stability changes were also determined.

scholarly journals PANOPLY: A cloud-based platform for automated and reproducible proteogenomic data analysis

2020 ◽  
Author(s):  
D. R. Mani ◽  
Myranda Maynard ◽  
Ramani Kothadia ◽  
Karsten Krug ◽  
Karen E. Christianson ◽  
...  
Keyword(s):  
Data Analysis ◽  
Drug Targets ◽  
Complex Data ◽  
Potential Drug ◽  
Post Translational Modification ◽  
Simple Interface ◽  
The Impact ◽  
Potential Drug Targets ◽  
Insight Into ◽  
Generation Sequencing

ABSTRACTProteogenomics involves the integrative analysis of genomic, transcriptomic, proteomic and post-translational modification data produced by next-generation sequencing and mass spectrometry-based proteomics. Several publications by the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and others have highlighted the impact of proteogenomics in enabling deeper insight into the biology of cancer and identification of potential drug targets. In order to encapsulate the complex data processing required for proteogenomics, and provide a simple interface to deploy a range of algorithms developed for data analysis, we have developed PANOPLY—a cloud-based platform for automated and reproducible proteogenomic data analysis. A wide array of algorithms have been implemented, and we highlight the application of PANOPLY to the analysis of cancer proteogenomic data.

scholarly journals Low Basicity as a Characteristic for Atypical Ligands of Serotonin Receptor 5-HT2

2021 ◽  
Vol 22 (3) ◽  
pp. 1035
Author(s):  
Sabina Podlewska ◽  
Ryszard Bugno ◽  
Enza Lacivita ◽  
Marcello Leopoldo ◽  
Andrzej J. Bojarski ◽  
...  
Keyword(s):  
Serotonin Receptors ◽  
Drug Targets ◽  
Serotonin Receptor ◽  
Transmembrane Helix ◽  
In Silico Analysis ◽  
Protonated Form ◽  
Receptor Ligands ◽  
Receptor System ◽  
Native Proteins

Serotonin receptors are extensively examined by academic and industrial researchers, due to their vital roles, which they play in the organism and constituting therefore important drug targets. Up to very recently, it was assumed that the basic nitrogen in compound structure is a necessary component to make it active within this receptor system. Such nitrogen interacts in its protonated form with the aspartic acid from the third transmembrane helix (D3x32) forming a hydrogen bond tightly fitting the ligand in the protein binding site. However, there are several recent studies that report strong serotonin receptor affinity also for compounds without a basic moiety in their structures. In the study, we carried out a comprehensive in silico analysis of the low-basicity phenomenon of the selected serotonin receptor ligands. We focused on the crystallized representatives of the proteins of 5-HT1B, 5-HT2A, 5-HT2B, and 5-HT2C receptors, and examined the problem both from the ligand- and structure-based perspectives. The study was performed for the native proteins, and for D3x32A mutants. The investigation resulted in the determination of nonstandard structural requirements for activity towards serotonin receptors, which can be used in the design of new nonbasic ligands.

scholarly journals Structural Insights in Mammalian Sialyltransferases and Fucosyltransferases: We Have Come a Long Way, but It Is Still a Long Way Down

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5203
Author(s):  
Ravneet Kaur Grewal ◽  
Abdul Rajjak Shaikh ◽  
Suresh Gorle ◽  
Manjeet Kaur ◽  
Paula Alexendra Videira ◽  
...  
Keyword(s):  
Drug Targets ◽  
Targeted Therapeutics ◽  
Catalytic Domains ◽  
The Past ◽  
Health And Disease ◽  
Structural Architecture ◽  
Structural Insights ◽  
Potential Drug Targets ◽  
Abnormal Glycosylation

Mammalian cell surfaces are modified with complex arrays of glycans that play major roles in health and disease. Abnormal glycosylation is a hallmark of cancer; terminal sialic acid and fucose in particular have high levels in tumor cells, with positive implications for malignancy. Increased sialylation and fucosylation are due to the upregulation of a set of sialyltransferases (STs) and fucosyltransferases (FUTs), which are potential drug targets in cancer. In the past, several advances in glycostructural biology have been made with the determination of crystal structures of several important STs and FUTs in mammals. Additionally, how the independent evolution of STs and FUTs occurred with a limited set of global folds and the diverse modular ability of catalytic domains toward substrates has been elucidated. This review highlights advances in the understanding of the structural architecture, substrate binding interactions, and catalysis of STs and FUTs in mammals. While this general understanding is emerging, use of this information to design inhibitors of STs and FUTs will be helpful in providing further insights into their role in the manifestation of cancer and developing targeted therapeutics in cancer.

Assessment of sensitivity of the efficiency of regional tax spending towards investment attractiveness of the types of economic activity carried out by the residents of advanced development territory

2020 ◽  
pp. 98-110
Author(s):  
Evgeniya Mikhailovna Popova ◽  
Guzel Mukhtarovna Guseinova ◽  
Sergei Borisovich Milov
Keyword(s):  
Economic Activity ◽  
Socioeconomic Development ◽  
Federal District ◽  
Tax Incentives ◽  
Capital Investments ◽  
The Subject ◽  
Investment Process ◽  
The Impact ◽  
Advanced Development

The deficit of subnational budgets and deceleration capital investments in multiple Russian regions increase the relevance of research aimed at improvement of tax incentivizing practice of the regional investment process. The studies focused on determination of the impact of socioeconomic and institutional factors upon the efficiency of investment tax expenses obtained wide circulation within the foreign scientific literature. The subject of this article is the assessment of sensitivity of the efficiency of regional tax expanses towards investment attractiveness of the types of economic activity carried out by the residents of territories of advanced socioeconomic development, created in the subjects of Far Easter Federal District. The scientific novelty and practical values of this research consists in substantiation of the reasonableness of assessment of investment attractiveness of the types of economic activity that are stimulated by tax incentives. Methodology for assessing investment attractiveness is proposed and tested. The conclusion is made that in case of low investment attractiveness of the type of economic activity, which was planned to support by tax incentives, it is required to conduct and additional analysis to avoid unjustified tax expanses.

Mechanically-Tunable Quantum Interference in Ferrocene-Based Single-Molecule Junctions

2020 ◽  
Author(s):  
María Camarasa-Gómez ◽  
Daniel Hernangómez-Pérez ◽  
Michael S. Inkpen ◽  
Giacomo Lovat ◽  
E-Dean Fung ◽  
...  
Keyword(s):  
Single Molecule ◽  
Quantum Interference ◽  
Degrees Of Freedom ◽  
Building Blocks ◽  
Ferrocene Derivative ◽  
Single Molecule Junctions ◽  
Molecule Junction ◽  
Single Molecule Junction ◽  
The Impact ◽  
D Orbitals

Ferrocenes are ubiquitous organometallic building blocks that comprise a Fe atom sandwiched between two cyclopentadienyl (Cp) rings that rotate freely at room temperature. Of widespread interest in fundamental studies and real-world applications, they have also attracted<br>some interest as functional elements of molecular-scale devices. Here we investigate the impact of<br>the configurational degrees of freedom of a ferrocene derivative on its single-molecule junction<br>conductance. Measurements indicate that the conductance of the ferrocene derivative, which is<br>suppressed by two orders of magnitude as compared to a fully conjugated analog, can be modulated<br>by altering the junction configuration. Ab initio transport calculations show that the low conductance is a consequence of destructive quantum interference effects that arise from the hybridization of metal-based d-orbitals and the ligand-based π-system. By rotating the Cp rings, the hybridization, and thus the quantum interference, can be mechanically controlled, resulting in a conductance modulation that is seen experimentally.<br>

Model Pembelajaran Teams Games Tournaments (TGT) untuk Meningkatkan Hasil Belajar Siswa

2019 ◽  
Vol 3 (2) ◽  
pp. 110
Author(s):  
Suwarno Suwarno
Keyword(s):  
Social Capital ◽  
Academic Success ◽  
Service Learning ◽  
Learning Outcomes ◽  
School Effectiveness ◽  
Social Trust ◽  
Building Blocks ◽  
Learning Model ◽  
Committee Report ◽  
The Impact

<p><strong>A</strong><strong>bstract</strong><strong>. </strong>This study aims to determine the effectiveness of the Teams Games Tournament (TGT) learning model to improve student learning outcomes. This research is important because the lecture learning model makes learning meaningless so it impacts on low learning outcomes. This research uses quasi experiment using control class and experimental class. Respondents in this study were students of class X SMK 8 Semarang Academic Year 2017/2018. Sample selection using random sampling, class X1 is <em>used</em> as a control class and X2 is an experimental class. The experimental class was given an intervention by learning Teams Games Tournaments (TGT), while the control class used lecture learning. The effectiveness of the model was measured by the student test analysis method. then analyzed by completeness test and average difference test. The findings of this study are the learning outcomes of experimental class students achieving better learning outcomes than classes using the lecture method.</p><p><strong><em>Keywords</em></strong><em>: Learning Model, Teams Games Tournaments (TGT)</em><em>. Students</em></p><p><strong><br /></strong></p><p><strong>Daftar Pustaka</strong></p><p align="center"> </p><p>Bofota, Y. B., &amp; Bofota, Y. B. (2017). <em>The impact of social capital on children educational outcomes : the case of Tanzania The impact of social capital on children educational outcomes : The case of Tanzania</em>.</p><p>Cahuc, P., Shleifer, A., &amp; Algan, Y. (2014). <em>Teaching Practices and Social Capital</em>. (6052).</p><p>Catts, R., &amp; Ozga, J. (2015). <em>What is Social Capital and how might it be used in Scotland ’ s Schools ?</em> (36).</p><p>Flint, N. (2017). <em>Full report Schools , communities and social capital : building blocks in the ’ Big Society ’ Contents</em>.</p><p>Goddard, R. D. (2016). <em>Relational Networks , Social Trust , and Norms : A Social Capital Perspective on Students ’ Chances of Academic Success</em>. <em>25</em>(1), 59–74.</p><p>Eddy Prasongko, 2017. Team Game Tournament. Bandung. Jawa Barat</p><p>Endang Poerwanti, dkk. 2008. <em>Asesmen Pembelajaran SD.</em> Jakarta: Direktorat Jendral Pendidikan Tinggi Departemen Pendidikan Nasional</p><p>Hargreaves, A. (2015). <em>School Social Capital and School Effectiveness</em>. <em>37</em>, 119–136.</p><p>Kurnia, Inggridwati. dkk. 2018. <em>Perkembangan belajar peserta didik</em><em>.</em> Jakarta: Direktorat Jendral Pendidikan Tinggi Departemen Pendidikan Nasional</p><p>Purwanto. M Ngalim. 2015. <em>Psikologi Pendidikan</em>. Bandung: PT Remaja Rosdakarya</p><p>Siddiq, M. Djauhar. 2018. <em>Pengembangan Bahan Pembelajaran SD</em>. Jakarta: Direktorat Jendral Pendidikan Tinggi Departemen Pendidikan Nasional.</p><p>Sugiyono, 2005. Metode Penelitian Kuantitatif, Kualitatif dan Rn D, Bandung Aftabeta</p><p>Lash, D., &amp; Belfiore, G. (2017). <em>5 Essentials in Building Social Capital Report 4 of the MyWays Student Success Series</em>. (October).</p><p>Mikiewicz, P., Jonasson, J. T., Gudmundsson, G., Blondal, K. S., &amp; Korczewska, D. M. (2011). <em>Comparative research between Poland and Iceland</em>.</p><p>Schlesselman, L., Borrego, M., Bloom, T. J., Mehta, B., Drobitch, R. K., &amp; Smith, T. (2015). An Assessment Of Service-Learning In 34 US Schools Of Pharmacy Follow Up On The 2001 Professional Affairs Committee Report. <em>American Journal of Pharmaceutical Education</em>, <em>79</em>(8). https://doi.org/10.5688/ajpe798116</p><p><em><br /></em></p>

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