cometadata/datacite-rtg-text-other-reclassification-records huggingface dataset:
Reasons and consequences of the ban on the use of 5-nitroimidazoles in food producing animals (in Polish)
Creators: name: Mitrowska, Kamila
Publisher: name: figshare
Year: 2015
Subjects: Toxicology

description: Nitroimidazoles have been used for the treatment of anaerobic bacterial and parasitic infections in animals. However, they are believed to possess genotoxic and carcinogenic properties, and this is why their use in food producing animals has been banned in many countries. At present, nitroimidazoles are approved in the European Union to use only in companion animals and human medicine although the reason for the ban of their use in food producing animals was just care about the health of the people. As a consequence of this ban each European Union country and countries wishing to export animal products to the European Union are required to implement a residue monitoring plan for nitroimidazole residues in food of animal origin which helps to ensure the safety and reduce the possible health risks to consumers. In this article the pharmacological and toxicological aspects of the most commonly used 5-nitroimidazoles in veterinary medicine are summarized.
In-silico prediction, characterization, molecular docking and dynamic simulation studies for screening potential fungicides against leaf rust of Triticum aestivum
Creators: name: Gosavi, Gokul
name: Jade, Dhananjay
name: Ponnambalam, Sreenivasan
name: Harrison, Michael A.
name: Zhou, Huanbin
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biophysics
subject: Biochemistry
subject: Biotechnology
subject: Chemical Sciences not elsewhere classified
subject: Ecology
subject: FOS: Biological sciences
subject: Biological Sciences not elsewhere classified
subject: Information Systems not elsewhere classified
subject: Plant Biology
subject: Computational Biology

description: Triticum aestivum is an important crop worldwide, which is a large source of food grain. T.aestivum demands on developed countries will grow every year, this increase in the demand is profoundly serious especially in the light climate change which would lead to a 29% reduction in final productivity. Rust fungus attacks the T.aestivum, specifically newly planted T.aestivum plants, which block the vascular system, stun, and finally damage grain and tillers. In present study we predict the 3D structure then find the binding pocket and conserved domains for MAPkinase-1 of Puccinia triticina. After that, screen the FungiPAD, PubChem, NPAtlas databases by physicochemical properties, docking, clustering, ADME (Absorption, distribution, metabolism, and excretion) and PAINS (pan assay interference compounds) filter analysis. Through this screening process screen the nine compounds, which are benzovindiflupyr, furametpyr, isopyrazam, fenaminstrobin, and flumorph from Fungicide database: zoxamide, vinclozolin, pentachloronitrobenzene, and dithianon from PubChem database, based on the binding energy, clustering, ADME and PAINS analysis. All these nine compounds bind in the same pocket and show the same pattern of interaction. Among these nine compounds, select the two compounds (PubChem:122087 (-6.96 kcal/mol) and FDBD02904 (-8.62 kcal/mol)) based on binding energy for 100 ns MD simulation and free energy calculation. MD simulation shows stability throughout the simulation, and it shows the sable interaction when compounds bind to the MAPKinase 1 protein which may help to protein kinase pathways in plant defense response. This result helps to design alternative fungicide against the wheat rust disease. Communicated by Ramaswamy H. Sarma
Chaotic Non-Symmetric Vacuum Spacetimes and Novel Traversable Wormholes Without Exotic Matter: A New Class of Solutions to the Einstein Field Equations
Creators: name: Lakshit Mathur
Publisher: name: Zenodo
Year: 2025

description: This paper proposes a groundbreaking expansion of the solution space of Einstein’s Field Equations (EFE) by exploring chaotic, non-symmetric vacuum geometries, multi-body dynamic spacetime structures, and traversable wormholes without the need for exotic matter. Unlike previous approaches, which heavily rely on symmetry assumptions (spherical, axial, or homogeneous), this framework removes symmetry constraints and investigates the impact of stochastic curvature patterns on the spacetime fabric.

Five new models are introduced, including chaotic vacua, dynamically interacting multi-body gravitational configurations, topologically complex non-exotic wormholes, variable cosmological constant landscapes, and quantum-classical hybrid spacetime structures.

The approach promises new predictions for gravitational wave signatures, dark matter analogues, and early-universe topology. This is the first systematic proposal for chaotic, non-symmetric gravitational solutions potentially observable within current and near-future astrophysical data.

The paper sets the foundation for extensive future research in mathematical relativity, gravitational wave astronomy, and high-energy cosmology.
Rozmieszczenie i kinetyka zanikania zieleni malachitowej i zieleni leukomalachitowej w tkankach i narządach karpia. Medycyna Weterynaryjna 64(8):1055-1058
Creators: name: Mitrowska, Kamila
name: Posyniak, Andrzej
name: Zmudzki, Jan
Publisher: name: figshare
Year: 2015
Subjects: Pharmacology

description: Malachite green (MG) is a synthetic triphenylmethane dye, which has been used worldwide as fungicide and ectoparasicide in cultured fish eggs, fingerlings and adult fish since 1930s. Due to its potential animal carcinogenicity, mutagenity and teratogenicity, MG is not registered for veterinary use in many countries including the European Union. The aim of this study was to investigate the tissue distribution and persistence of MG and its main metabolite, leucomalachite green (LMG), in carp after therapeutic bath. On day 0, MG concentration in all tissues exceeded the initial concentration in therapeutic water (2 mg/l). The dye was thereafter rapidly and extensively metabolized to LMG, which was slowly eliminated from the tissues. Higher concentrations of MG and LMG were detected in gill, liver and kidney than in the spleen and muscle. The parent compound was more persistent in kidney, liver and spleen (up to 112 days) than in gill and muscle (up to 56 days). LMG concentrations declined more slowly in all tissues being still detectable in kidney and muscle 252 days after treatment.
Impact of Fe + 2 ions on structural integrity of A0A6P1CI42_RHITR NifA protein from Rhizobium tropici strain CIAT 899
Creators: name: Yadav, Pulala Raghuveer
name: Basha, Syed Hussain
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biophysics
subject: Biochemistry
subject: Physical Sciences not elsewhere classified
subject: Chemical Sciences not elsewhere classified
subject: Biological Sciences not elsewhere classified
subject: Developmental Biology
subject: Cancer
subject: Plant Biology
subject: FOS: Biological sciences
subject: Virology
subject: Computational Biology

description: A0A6P1CI42_RHITR, a protein originating from Rhizobium tropici strain CIAT 899, has emerged as a key player in leguminous plant symbiosis and nitrogen fixation processes. Understanding the intricate details of its structure and function holds immense significance for unraveling the molecular mechanisms underlying its biological activities. In this study, we employed molecular modeling and molecular dynamics (MD) simulations to investigate the A0A6P1CI42_RHITR protein, with a specific emphasis on the influence of Fe-atoms, linker structural integrity, and conformational changes within the GAF domain. Our findings unveiled noteworthy conformational changes in the A0A6P1CI42_RHITR protein, particularly within the GAF domain, when Fe-atoms were present compared to its apo form. Significant conformational rearrangements after an initial 20 ns, accompanied by the opening of the ligand substrate accommodating loop in the GAF domain influenced by Fe-atoms was observed. At the residue level, the investigation revealed substantial activity variations in individual residues, particularly in those contributing to the GAF domain from positions 51 to 223. Intriguingly, the presence of Fe-atoms led to controlled movement of conserved cysteine residues at positions 467 and 472, indicating a correlation between interlinker domain motion and the activity of the GAF domain loop responsible for substrate accommodation. Moreover, in the presence of Fe-atoms, the distance between Cys467 and Cys472 residues was maintained, ensuring the overall structural integrity of the interdomain loop necessary for protein activation. Conversely, in the apo form, a sudden flip motion of cysteine residues’ thiol groups was observed, leading to a loss of structural integration. Overall, our study utilizing molecular modeling and MD simulations offers valuable insights into the structural dynamics and functional implications of the A0A6P1CI42_RHITR protein. Communicated by Ramaswamy H. Sarma
In-silico prediction, characterization, molecular docking and dynamic simulation studies for screening potential fungicides against leaf rust of Triticum aestivum
Creators: name: Gosavi, Gokul
name: Jade, Dhananjay
name: Ponnambalam, Sreenivasan
name: Harrison, Michael A.
name: Zhou, Huanbin D.
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biophysics
subject: Biochemistry
subject: Biotechnology
subject: Chemical Sciences not elsewhere classified
subject: Ecology
subject: FOS: Biological sciences
subject: Biological Sciences not elsewhere classified
subject: Information Systems not elsewhere classified
subject: Plant Biology
subject: Computational Biology

description: Triticum aestivum is an important crop worldwide, which is a large source of food grain. T.aestivum demands on developed countries will grow every year, this increase in the demand is profoundly serious especially in the light climate change which would lead to a 29% reduction in final productivity. Rust fungus attacks the T.aestivum, specifically newly planted T.aestivum plants, which block the vascular system, stun, and finally damage grain and tillers. In present study we predict the 3D structure then find the binding pocket and conserved domains for MAPkinase-1 of Puccinia triticina. After that, screen the FungiPAD, PubChem, NPAtlas databases by physicochemical properties, docking, clustering, ADME (Absorption, distribution, metabolism, and excretion) and PAINS (pan assay interference compounds) filter analysis. Through this screening process screen the nine compounds, which are benzovindiflupyr, furametpyr, isopyrazam, fenaminstrobin, and flumorph from Fungicide database: zoxamide, vinclozolin, pentachloronitrobenzene, and dithianon from PubChem database, based on the binding energy, clustering, ADME and PAINS analysis. All these nine compounds bind in the same pocket and show the same pattern of interaction. Among these nine compounds, select the two compounds (PubChem:122087 (-6.96 kcal/mol) and FDBD02904 (-8.62 kcal/mol)) based on binding energy for 100 ns MD simulation and free energy calculation. MD simulation shows stability throughout the simulation, and it shows the sable interaction when compounds bind to the MAPKinase 1 protein which may help to protein kinase pathways in plant defense response. This result helps to design alternative fungicide against the wheat rust disease. Communicated by Ramaswamy H. Sarma
Antimicrobial, antibiofilm, docking, DFT and molecular dynamics studies on click-derived isatin-thiosemicarbazone-1,2,3-triazoles
Creators: name: Kumar, Aman
name: Lal, Kashmiri
name: Murtaza, Mohd
name: Jaglan, Sundeep
name: Rohila, Yajat
name: Singh, Prashant
name: Singh, Madhur Babu
name: Kumari, Kamlesh
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biophysics
subject: Biochemistry
subject: Microbiology
subject: FOS: Biological sciences
subject: Molecular Biology
subject: Biotechnology
subject: Chemical Sciences not elsewhere classified
subject: Ecology
subject: Developmental Biology
subject: Infectious Diseases
subject: FOS: Health sciences
subject: Virology

description: In an effort to develop new antimicrobial and antibiofilm agents, we have designed and synthesized a novel class of isatin-thiosemicarbazone-1,2,3-triazoles through the CuAAC approach. All the synthesized hybrids were characterized by several spectral techniques such as FTIR, 1H NMR, 13C NMR, 2D NMR and HRMS. All the derivatives were evaluated for their antimicrobial and antibiofilm efficacy towards various microbial species. Triazole hybrid 8d exhibited the highest efficacy towards E. coli (MIC = 0.0067 µmol/mL) and S. aureus (MIC = 0.0067 µmol/mL), whereas, compounds 8b, 8c, 8d, 8e, 9a and terminal alkyne (10) significantly inhibited biofilm formation against S. aureus, B. subtilis and E. coli. To find out the structure–activity relationship and binding interactions of synthesized hybrids with enzymes 1KZN and 5TZ1, molecular docking for all the synthesized hybrids was carried out. DFT calculations for all hybrids and the molecular dynamics studies for compounds 9e and 9f were also performed to support the biological behavior of these hybrids. Communicated by Ramaswamy H. Sarma
Rozmieszczenie i kinetyka zanikania zieleni malachitowej i zieleni leukomalachitowej w tkankach i narządach karpia. Medycyna Weterynaryjna 2008, 64(8), 1055-1058
Creators: name: Mitrowska, Kamila
name: Posyniak, Andrzej
name: Zmudzki, Jan
Publisher: name: figshare
Year: 2015
Subjects: Pharmacology

description: Malachite green (MG) is a synthetic triphenylmethane dye, which has been used worldwide as fungicide and ectoparasicide in cultured fish eggs, fingerlings and adult fish since 1930s. Due to its potential animal carcinogenicity, mutagenity and teratogenicity, MG is not registered for veterinary use in many countries including the European Union. The aim of this study was to investigate the tissue distribution and persistence of MG and its main metabolite, leucomalachite green (LMG), in carp after therapeutic bath. On day 0, MG concentration in all tissues exceeded the initial concentration in therapeutic water (2 mg/l). The dye was thereafter rapidly and extensively metabolized to LMG, which was slowly eliminated from the tissues. Higher concentrations of MG and LMG were detected in gill, liver and kidney than in the spleen and muscle. The parent compound was more persistent in kidney, liver and spleen (up to 112 days) than in gill and muscle (up to 56 days). LMG concentrations declined more slowly in all tissues being still detectable in kidney and muscle 252 days after treatment.
Additional file 1 of Alpine ecology, plant biodiversity and photosynthetic performance of marker plants in a nitrogen gradient induced by Alnus bushes
Creators: name: Kaltrina, Rexha
name: Kristi, Bego
name: Zyruku Dea
name: Shuka Lulezim
name: Husi René
name: Schneller Jakob
name: Reinhard, Bachofen
Publisher: name: figshare
Year: 2020
Subjects: subject: Ecology
subject: FOS: Biological sciences
subject: Plant Biology

description: Additional file 1: Table S1. Calculation of the mean N-value of each plot from the indicator values of Landolt et al. [17] and its frequency based on Braun-Blanquet [1]. For each plant (in this example of plot 1 (Table 1)) the Braun-Blanquet frequency was increased by 1 to obtain values from 1 to 5. This number was multiplied by the Landolt-indicator value. The mean N-value per plot results in the sum of these products divided by the sum of the new frequency values. The calculation steps are given below.
Repurposing of antiparasitic drugs against the NS2B-NS3 protease of the Zika virus
Creators: name: Pant, S.
name: Jena, N. R.
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biophysics
subject: Biochemistry
subject: Physical Sciences not elsewhere classified
subject: Medicine
subject: Pharmacology
subject: Biotechnology
subject: Chemical Sciences not elsewhere classified
subject: Biological Sciences not elsewhere classified
subject: Cancer
subject: Infectious Diseases
subject: FOS: Health sciences
subject: Computational Biology

description: To date, no approved drugs are available to treat the Zika virus (ZIKV) infection. Therefore, it is necessary to urgently identify potential drugs against the ZIKV infection. Here, the repurposing of 30 antiparasitic drugs against the NS2B-NS3 protease of the ZIKV has been carried out by using combined docking and molecular dynamics- (MD) simulations. Based on the docking results, 5 drugs, such as Amodiaquine, Primaquine, Paromomycin, Dichlorophene, and Ivermectin were screened for further analysis by MD simulations and free energy calculations. Among these drugs, Amodiaquine and Dichlorophen are found to produce the most stable complexes and possess relative binding free energies of about −44.3 ± 3.7 kcal/mol and −41.1 ± 5.3 kcal/mol respectively. Therefore, they would act as potent small-molecule inhibitors of the ZIKV protease.However, evaluations of biological and safety activities of these drugs against the ZIKV protease are required before their clinical use. Communicated by Ramaswamy H. Sarma
Identification of 1,3,4-oxadiazoles as tubulin-targeted anticancer agents: a combined field-based 3D-QSAR, pharmacophore model-based virtual screening, molecular docking, molecular dynamics simulation, and density functional theory calculation approach
Creators: name: Das, Agnidipta
name: Sarangi, Manaswini
name: Jangid, Kailash
name: Kumar, Vijay
name: Kumar, Amit
name: Singh, Praval Pratap
name: Kaur, Kamalpreet
name: Kumar, Vinod
name: Chakraborty, Sudip
name: Jaitak, Vikas
Publisher: name: Taylor & Francis
Year: 2023
Subjects: Biophysics
Biochemistry
Biotechnology
Chemical Sciences not elsewhere classified
Biological Sciences not elsewhere classified
Information Systems not elsewhere classified

description: Cancer is one of the most prominent causes of death worldwide and tubulin is a crucial protein of cytoskeleton that maintains essential cellular functions including cell division as well as cell signalling, that makes an attractive drug target for cancer drug development. 1,3,4-oxadiazoles disrupt microtubule causing G2-M phase cell cycle arrest and provide anti-proliferative effect. In this study, field-based 3D-QSAR models were developed using 62 bioactive anti-tubulin 1,3,4-oxadiazoles. The best model characterized by PLS factor 7 was rigorously validated using various statistical parameters. Generated 3D-QSAR model having high degree of confidence showed favourable and unfavourable contours around 1,3,4-oxadiazole core that assisted in defining proper spatial positioning of desired functional groups for better bioactivity. A five featured pharmacophore model (AAHHR_1) was developed using same ligand library and validated through enrichment analysis (BEDROC160.9 value = 0.59, Average EF 1% = 27.05, and AUC = 0.74). Total 30,212 derivatives of 1,3,4-oxadiazole obtained from PubChem database was prefiltered through validated pharmacophore model and docked in XP mode on binding cavity of tubulin protein (PDB code: 1SA0) which led into the identification of 11 HITs having docking scores between −7.530 and −9.719 kcal/mol while the reference compound Colchicine exerted docking score of −7.046 kcal/mol. Following the analysis of MM-GBSA and ADME studies, HIT1 and HIT4 emerged as the two promising hits. To verify their thermodynamic stability at the target site, molecular dynamic simulations were carried out. Both HITs were further subjected to DFT analysis to determine their HOMO-LUMO energy gap for ensuring their biological feasibility. Finally, molecular docking based structural exploration for 1,3,4-oxadiazoles to set up a lead of Formula I for further advancements of tubulin polymerization inhibitors as anti-cancer agents. Communicated by Ramaswamy H. Sarma
Sirtuin 1 inhibition: a promising avenue to suppress cancer progression through small inhibitors design
Creators: name: Ullah, Atta
name: Waqas, Muhammad
name: Halim, Sobia Ahsan
name: Daud, Muhammad
name: Jan, Afnan
name: Khan, Ajmal
name: Al-Harrasi, Ahmed
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biophysics
subject: Biochemistry
subject: Cell Biology
subject: Genetics
subject: FOS: Biological sciences
subject: Pharmacology
subject: Chemical Sciences not elsewhere classified
subject: Biological Sciences not elsewhere classified
subject: Cancer

description: SIRT1 is a protein associated with vital cell functions such as gene regulation, metabolism, ageing, and cellular energy restoration. Its association with the tumor suppressor protein p53 is essential for controlling the growth of cells, apoptosis, and response to DNA damage. By raising p53 acetylation, encouraging apoptosis, and reducing cell proliferation, inhibiting SIRT1's catalytic domain, which interacts with p53, shows potential as a cancer treatment. The aim of the study is to find compounds that could inhibit SIRT1 and thus lower the proliferation of cancer cells. Employing molecular docking techniques, a virtual screening of ∼900 compounds (isolated from medicinal plants and derivatives) gave us 13 active compounds with good binding affinity. Additional evaluation of pharmacokinetic and pharmacodynamic properties led to the selection of eight compounds with desirable properties. Docking analysis confirmed stable interactions between the final eight compounds (C1–C8) and the SIRT1 catalytic domain. Molecular dynamics simulations show overall stability and moderate changes in protein structure upon compound binding. The compactness of the protein indicated the protein’s tight packing upon the inhibitors binding. Binding free energy calculations revealed that compounds C2 (−49.96 ± 0.073 kcal/mol and C1 (−44.79 ± 0.077 kcal/mol) exhibited the highest energy, indicating strong binding affinity to the SIRT1 catalytic domain. These compounds, along with C8, C5, C6, C3, C4 and C7, showed promising potential as SIRT1 inhibitors. Based on their ability to reduce SIRT1 activity and increase apoptosis, the eight chemicals discovered in this work may be useful in treating cancer. Communicated by Ramaswamy H. Sarma
Tissue distribution and persistence of malachite green and leucomalachite green in common carp. Medycyna Weterynaryjna 2008, 64(8), 1055-1058
Creators: name: Mitrowska, Kamila
name: Posyniak, Andrzej
name: Zmudzki, Jan
Publisher: name: figshare
Year: 2015
Subjects: Pharmacology

description: Malachite green (MG) is a synthetic triphenylmethane dye, which has been used worldwide as fungicide and ectoparasicide in cultured fish eggs, fingerlings and adult fish since 1930s. Due to its potential animal carcinogenicity, mutagenity and teratogenicity, MG is not registered for veterinary use in many countries including the European Union. The aim of this study was to investigate the tissue distribution and persistence of MG and its main metabolite, leucomalachite green (LMG), in carp after therapeutic bath. On day 0, MG concentration in all tissues exceeded the initial concentration in therapeutic water (2 mg/l). The dye was thereafter rapidly and extensively metabolized to LMG, which was slowly eliminated from the tissues. Higher concentrations of MG and LMG were detected in gill, liver and kidney than in the spleen and muscle. The parent compound was more persistent in kidney, liver and spleen (up to 112 days) than in gill and muscle (up to 56 days). LMG concentrations declined more slowly in all tissues being still detectable in kidney and muscle 252 days after treatment.
Assessment of antidiabetic activity of three Phenylspirodrimanes from fungus Stachybotrys chartarum MUT 3308 by ADME, QSAR, molecular docking and molecular dynamics simulation studies against protein tyrosine phosphatase 1B (PTP1B)
Creators: name: Bhowmik, Prasenjit
name: Baezid, Hossain Mohammad
name: Arabi, Ishmam Ibnul
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biophysics
subject: Biochemistry
subject: Genetics
subject: FOS: Biological sciences
subject: Molecular Biology
subject: Chemical Sciences not elsewhere classified
subject: Biological Sciences not elsewhere classified
subject: Cancer

description: Phenylspirodrimanes (PSD) are the sesquiterpene quinone type meroterpenoids found in nature. PSDs are found to exhibit inhibitory activity against immunocomplex diseases, and tyrosine kinase receptors. Three of the different PSDs C1, C2, and C3 that have been reported to be isolated from the sponge-associated fungus Stachybotrys chartarum MUT 3308 are selected for studying their possible inhibitory effect against type 2 diabetes mellitus. Mechanistically, blocking protein tyrosine phosphatase 1B (PTP1B) helps to reduce the insulin resistance induction caused by the high expression of PTP1B. The QSAR, ADME, toxicity (T) study was carried out to predict the pharmacokinetic properties and the biological activities of the PSDs. PASS prediction web tool was used to find and select the target proteins 1NNY, and 2HNP. According to the molecular docking simulations, C1 and C2 showed better binding affinity of −8.5 kcal/mol, and −8.1 kcal/mol respectively against 1NNY compared to the control ligand. RMSD, RMSF, Rg, and SASA analysis revealed that both C1, and C2 showed better stability, minor conformational changes, and minor fluctuation upon binding to PTP1B. Protein contact analysis was carried out to validate the residues that are in contact with the ligands according to molecular docking studies. Overall, C1, and C2 could be proposed as novel natural hits to be developed and small modifications of these PSDs could result in inducing the binding affinity significantly, although experimental validation is required for further evaluation of the work. Communicated by Ramaswamy H. Sarma
title: A minimal model of self-consistent partial synchrony
Creators: name: Clusella, Pau
name: Politi, Antonio
name: Rosenblum, Michael
Publisher: name: Universität Potsdam
Year: 2020

description: We show that self-consistent partial synchrony in globally coupled oscillatory ensembles is a general phenomenon. We analyze in detail appearance and stability properties of this state in possibly the simplest setup of a biharmonic Kuramoto-Daido phase model as well as demonstrate the effect in limit-cycle relaxational Rayleigh oscillators. Such a regime extends the notion of splay state from a uniform distribution of phases to an oscillating one. Suitable collective observables such as the Kuramoto order parameter allow detecting the presence of an inhomogeneous distribution. The characteristic and most peculiar property of self-consistent partial synchrony is the difference between the frequency of single units and that of the macroscopic field.
description: Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe, 890
title: Using ESTs for phylogenomics
title: can one accurately infer a phylogenetic tree from a gappy alignment?
titleType: Subtitle
Creators: name: Hartmann, Stefanie
name: Vision, Todd J.
Publisher: name: Universität Potsdam
Year: 2020

description: Background While full genome sequences are still only available for a handful of taxa, large collections of partial gene sequences are available for many more. The alignment of partial gene sequences results in a multiple sequence alignment containing large gaps that are arranged in a staggered pattern. The consequences of this pattern of missing data on the accuracy of phylogenetic analysis are not well understood. We conducted a simulation study to determine the accuracy of phylogenetic trees obtained from gappy alignments using three commonly used phylogenetic reconstruction methods (Neighbor Joining, Maximum Parsimony, and Maximum Likelihood) and studied ways to improve the accuracy of trees obtained from such datasets. Results We found that the pattern of gappiness in multiple sequence alignments derived from partial gene sequences substantially compromised phylogenetic accuracy even in the absence of alignment error. The decline in accuracy was beyond what would be expected based on the amount of missing data. The decline was particularly dramatic for Neighbor Joining and Maximum Parsimony, where the majority of gappy alignments contained 25% to 40% incorrect quartets. To improve the accuracy of the trees obtained from a gappy multiple sequence alignment, we examined two approaches. In the first approach, alignment masking, potentially problematic columns and input sequences are excluded from from the dataset. Even in the absence of alignment error, masking improved phylogenetic accuracy up to 100-fold. However, masking retained, on average, only 83% of the input sequences. In the second approach, alignment subdivision, the missing data is statistically modelled in order to retain as many sequences as possible in the phylogenetic analysis. Subdivision resulted in more modest improvements to alignment accuracy, but succeeded in including almost all of the input sequences. Conclusion These results demonstrate that partial gene sequences and gappy multiple sequence alignments can pose a major problem for phylogenetic analysis. The concern will be greatest for high-throughput phylogenomic analyses, in which Neighbor Joining is often the preferred method due to its computational efficiency. Both approaches can be used to increase the accuracy of phylogenetic inference from a gappy alignment. The choice between the two approaches will depend upon how robust the application is to the loss of sequences from the input set, with alignment masking generally giving a much greater improvement in accuracy but at the cost of discarding a larger number of the input sequences.
description: Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe, 889
Metabolic deregulation associated with aging modulates protein aggregation in the yeast model of Huntington’s disease
Creators: name: Pradhan, Sai Sanwid
name: R., Sai Swaroop
name: Kanikaram, Sai Phalguna
name: V.M., Datta Darshan
name: Pargaonkar, Ashish
name: Dandamudi, Rajesh Babu
name: Sivaramakrishnan, Venketesh
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Biochemistry
subject: Microbiology
subject: FOS: Biological sciences
subject: Cell Biology
subject: Genetics
subject: Molecular Biology
subject: Neuroscience
subject: Chemical Sciences not elsewhere classified
subject: Cancer

description: Huntington’s disease is associated with increased CAG repeat resulting in an expanded polyglutamine tract in the protein Huntingtin (HTT) leading to its aggregation resulting in neurodegeneration. Previous studies have shown that N-terminal HTT with 46Q aggregated in the stationary phase but not the logarithmic phase in the yeast model of HD. We carried out a metabolomic analysis of logarithmic and stationary phase yeast model of HD expressing different polyQ lengths attached to N-terminal HTT tagged with enhanced green fluorescent protein (EGFP). The results show significant changes in the metabolic profile and deregulated pathways in stationary phase cells compared to logarithmic phase cells. Comparison of metabolic pathways obtained from logarithmic phase 46Q versus 25Q with those obtained for presymptomatic HD patients from our previous study and drosophila model of HD showed considerable overlap. The arginine biosynthesis pathway emerged as one of the key pathways that is common in stationary phase yeast compared to logarithmic phase and HD patients. Treatment of yeast with arginine led to a significant decrease, while transfer to arginine drop-out media led to a significant increase in the size of protein aggregates in both logarithmic and stationary phase yeast model of HD. Knockout of arginine transporters in the endoplasmic reticulum and vacuole led to a significant decrease in mutant HTT aggregation. Overall our results highlight arginine as a critical metabolite that modulates the aggregation of mutant HTT and disease progression in HD. Communicated by Ramaswamy H. Sarma
Structure of amino acid sequence-reversed wtRop protein: insights from atomistic molecular dynamics simulations
Creators: name: Arnittali, Maria
name: Rissanou, Anastassia N.
name: Kefala, Aikaterini
name: Kokkinidis, Michael
name: Harmandaris, Vagelis
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biophysics
subject: Biochemistry
subject: Physical Sciences not elsewhere classified
subject: Genetics
subject: FOS: Biological sciences
subject: Molecular Biology
subject: Evolutionary Biology
subject: Chemical Sciences not elsewhere classified
subject: Biological Sciences not elsewhere classified
subject: Information Systems not elsewhere classified

description: This study aims to the investigation of the advantages of designing new proteins presume upon a ‘bias’ sequence of amino acids, based on the reversed sequence of parent proteins, such as the retro ones. The structural simplicity of wtRop offers a very attractive model system to study these aspects. The current work is based on all-atom Molecular Dynamics (MD) simulations and corresponding experimental evidence on two different types of reversed wtRop protein, one with a fully reversed sequence of amino acids (rRop) and another with a partially reversed sequence (prRop), where only the five residues of the loop region (30ASP-34GLN) were not reversed. The exploration of the structure of the two retro proteins is performed highlighting the similarities and the differences with their parent protein, by employing various measures. Two models have been studied for both reversed proteins, a dimeric and a monomeric with the former one found to be more stable than the latter. Preferable equilibrium structures that the protein molecule can attain are explored, indicating the equilibration pathway. Simulation findings indicate a disruption of the α-helical structure and the appearance of additional secondary structures for both retro proteins. Reduced structural stability compared to their parent protein (wtRop) is also found. A corruption of the hydrophobic core is observed in the dimeric models. Furthermore, the simulations findings are consistent with the experimental characterization of prRop by circular dichroism spectroscopy (CD) which highlights an unstable, highly α-helical protein. Communicated by Ramaswamy H. Sarma
Investigating the role of Sterol C24-Methyl transferase mutation on drug resistance in leishmaniasis and identifying potential inhibitors
Creators: name: Khan, Huma
name: Waqas, Muhammad
name: Khurshid, Beenish
name: Ullah, Nazif
name: Khalid, Asaad
name: Abdalla, Ashraf N.
name: Alamri, Mubarak A.
name: Wadood, Abdul
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biophysics
subject: Biochemistry
subject: Physical Sciences not elsewhere classified
subject: Medicine
subject: Microbiology
subject: FOS: Biological sciences
subject: Genetics
subject: Molecular Biology
subject: Pharmacology
subject: Chemical Sciences not elsewhere classified
subject: Immunology
subject: FOS: Clinical medicine
subject: Biological Sciences not elsewhere classified
subject: Cancer
subject: Hematology

description: Leishmaniasis is a fatal disease caused by the leishmania parasite. For the survival of the leishmania parasite, Sterol C24-Methyl Transferase (SMT) is essential which is an enzyme of the ergosterol pathway. SMT protein mutation is responsible for Amphotericin-B drug resistance in Leishmania, which is the main treatment for visceral leishmaniasis. Amphotericin-B resistance is caused by three mutated residues V131I, V321I and F72C. The underlying mechanisms and structural changes in SMT enzymes responsible for resistance due to mutation are still not well understood. In the current study, the potential mechanism of resistance due to these mutations and the structure variation of wild and mutant SMT proteins were investigated through molecular dynamics simulations and molecular docking analysis. The results showed that AmB established strong bonding interaction with wild SMT as compare to mutants SMT. The binding energy calculation showed that binding energy of AmB with mutants SMT increases as compare to the wild SMT. Further structural based virtual screening was carried out to design potential inhibitors for the mutant SMT. On the basis of structural-based virtual screening four inhibitors (SANC01057, SANC00882, SANC00414, SANC01047) were computationally identified as potential mutant SMT (F72C) inhibitors. This work provides valuable information for improved management of drug resistant Leishmaniasis. Communicated by Ramaswamy H. Sarma
Masoprocol: a promising candidate for targeting insulin resistance by inhibiting resistin with optimal druglikeness Potentials: an in silico approach
Creators: name: Al-Shuhaib, Mohammed Baqur S.
name: Alam, Sarfaraz
name: Khan, Salman Ali
name: Hashim, Hayder O.
name: Obayes, Daniel H.
name: Al-Shuhaib, Jafar M. B.
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biophysics
subject: Biochemistry
subject: Genetics
subject: FOS: Biological sciences
subject: Pharmacology
subject: Biotechnology
subject: Chemical Sciences not elsewhere classified
subject: Biological Sciences not elsewhere classified
subject: Information Systems not elsewhere classified
subject: Cancer
subject: Virology

description: Resistin is a cysteine-rich secretory hormone that induces resistance to insulin, and its elevated expression is correlated with the onset of diabetes and several related metabolic disorders. Resistin performs its inhibitory role by connecting three identical subunits through Cys22-based disulfide linkages. The necessity to inhibit the formation of resistin trimer is one of the essential means to prevent the aggravation of diabetes mellitus type 2, obesity, and atherosclerosis. This study was conducted to screen the clinically approved drugs to find the most potent one to inhibit resistin with the best pharmacokinetics and drug-likeness properties. A total of 4654 clinically approved drugs were docked against the Cys22 residue of resistin. The top ten drugs with the highest high-precision (XP) docking scores were selected. Ioversol and masoprocol showed the highest XP docking and Molecular Mechanics-Generalized Born Surface Area (MMGBSA) scores, respectively, with double hydrogen bonding with the targeted Cys22. Molecular dynamics (MD) simulations showed that the masoprocol-resistin complex exhibited lower root mean square deviation (RMSD), radius of gyration, and root mean square fluctuation (RMSF) values than those observed in the ioversol-resistin complex. Both drugs induced drastic conformational changes in resistin monomer interactions. However, ioversol did not prove satisfying drug-likeness properties, while masoprocol showed the most favourable pharmacokinetic and drug-likeness properties. This study has demonstrated that masoprocol offers a novel inhibitory effect on resistin with the highest ligand affinity, making it a promising drug for combating insulin resistance. Communicated by Ramaswamy H. Sarma
Mutational analyses, pharmacophore-based inhibitor design and in silico validation for Zika virus NS3-helicase
Creators: name: Durgam, Laxman
name: Pagag, Jishu
name: Neela, Y. Indra
name: Guruprasad, Lalitha
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biochemistry
subject: Medicine
subject: Microbiology
subject: FOS: Biological sciences
subject: Genetics
subject: Molecular Biology
subject: Pharmacology
subject: Chemical Sciences not elsewhere classified
subject: Biological Sciences not elsewhere classified
subject: Infectious Diseases
subject: FOS: Health sciences
subject: Virology

description: Zika virus is responsible for causing Zika infections and was declared as a public health emergency of international concern in February 2016. The Zika virus NS3-helicase is a viable drug target for the design of inhibitors due to its essential role in the replication of viral genome. The viral RNA is unwound by the NS3-helicase in order to enable the reproduction of viral genome by the NS5 protein. Zika virus infections in humans are being reported for the last 15 years. We have therefore carried out amino acid mutational analyses of NS3-helicase. NS3-helicase has two crucial binding sites: the ATP and RNA binding sites. The cofactor-ATP based pharmacophore was generated for virtual screening of ZINC database using Pharmit server, that is followed by molecular docking and molecular dynamics simulations of potential hits as probable Zika virus NS3-helicase inhibitors at the cofactor binding site. The drug-like properties of the molecules were analysed and, DFT calculations were performed on the five best molecules to reveal their stability in solvent phase compared to gas phase, the HOMO and LUMO and electrostatic potential maps to analyze the electronic and geometric characteristics. These are significant findings towards the discovery of new inhibitors of Zika virus NS3-helicase, a promising drug target to treat the Zika virus infection. Communicated by Ramaswamy H. Sarma
Structure of amino acid sequence-reversed wtRop protei: insights from atomistic molecular dynamics simulations
Creators: name: Arnittali, Maria
name: Rissanou, Anastassia N.
name: Kefala, Aikaterini
name: Kokkinidis, Michael
name: Harmandaris, Vagelis
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biophysics
subject: Biochemistry
subject: Physical Sciences not elsewhere classified
subject: Genetics
subject: FOS: Biological sciences
subject: Molecular Biology
subject: Evolutionary Biology
subject: Chemical Sciences not elsewhere classified
subject: Biological Sciences not elsewhere classified
subject: Information Systems not elsewhere classified

description: This study aims to the investigation of the advantages of designing new proteins presume upon a ‘bias’ sequence of amino acids, based on the reversed sequence of parent proteins, such as the retro ones. The structural simplicity of wtRop offers a very attractive model system to study these aspects. The current work is based on all-atom Molecular Dynamics (MD) simulations and corresponding experimental evidence on two different types of reversed wtRop protein, one with a fully reversed sequence of amino acids (rRop) and another with a partially reversed sequence (prRop), where only the five residues of the loop region (30ASP-34GLN) were not reversed. The exploration of the structure of the two retro proteins is performed highlighting the similarities and the differences with their parent protein, by employing various measures. Two models have been studied for both reversed proteins, a dimeric and a monomeric with the former one found to be more stable than the latter. Preferable equilibrium structures that the protein molecule can attain are explored, indicating the equilibration pathway. Simulation findings indicate a disruption of the α-helical structure and the appearance of additional secondary structures for both retro proteins. Reduced structural stability compared to their parent protein (wtRop) is also found. A corruption of the hydrophobic core is observed in the dimeric models. Furthermore, the simulations findings are consistent with the experimental characterization of prRop by circular dichroism spectroscopy (CD) which highlights an unstable, highly α-helical protein. Communicated by Ramaswamy H. Sarma
In silico design and identification of new peptides for mitigating hIAPP aggregation in type 2 diabetes
Creators: name: Kaur, Apneet
name: Goyal, Bhupesh
Publisher: name: Taylor & Francis
Year: 2023
Subjects: Biophysics
Biochemistry
Physical Sciences not elsewhere classified
Pharmacology
Biotechnology
Environmental Sciences not elsewhere classified
Chemical Sciences not elsewhere classified
Biological Sciences not elsewhere classified
Cancer

description: The aberrant misfolding and self-aggregation of human islet amyloid polypeptide (hIAPP or amylin) into cytotoxic aggregates are implicated in the pathogenesis of type 2 diabetes (T2D). Among various inhibitors, short peptides derived from the amyloidogenic regions of hIAPP have been employed as hIAPP aggregation inhibitors due to their low immunogenicity, biocompatibility, and high chemical diversity. Recently, hIAPP fragment HSSNN18-22 was identified as an amyloidogenic sequence and displayed higher antiproliferative activity to RIN-5F cells. Various hIAPP aggregation inhibitors have been designed by chemical modifications of the highly amyloidogenic sequence (NFGAIL) of hIAPP. In this work, a library of pentapeptides based on fragment HSSNN18-22 was designed and assessed for their efficacy in blocking hIAPP aggregation using an integrated computational screening approach. The binding free energy calculations by molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method identified HSSQN and HSSNQ that bind to hIAPP monomer with a binding affinity of −21.25 ± 4.90 and −19.73 ± 3.10 kcal/mol, respectively, which is notably higher as compared to HSSNN (–11.90 ± 4.12 kcal/mol). The sampling of the non aggregation-prone helical conformation was notably increased from 23.5 ± 3.0 in the hIAPP monomer to 38.1 ± 3.6, and 33.8 ± 3.0% on the incorporation of HSSQN, and HSSNQ, respectively, which indicate reduced aggregation propensity of hIAPP monomer. The pentapeptides, HSSQN and HSSNQ, identified as hIAPP aggregation inhibitors in this work can be further conjugated with various metal chelating peptides to yield more efficacious and clinically relevant multifunctional modulators for targeting various pathological hallmarks of T2D. Communicated by Ramaswamy H. Sarma
Exudative cloacitis in the kakapo (Strigops habroptilus) potentially linked to Escherichia coli infection
Creators: name: J Wang
name: DJ White
name: RJ Hall
name: R Jakob-Hoff
name: B Jackson
name: DM Tompkins
Publisher: name: Taylor & Francis
Year: 2015
Subjects: subject: 60506 Virology
subject: FOS: Biological sciences
subject: 110309 Infectious Diseases
subject: FOS: Health sciences
subject: Cancer
subject: Biological Sciences
subject: Immunology
subject: FOS: Clinical medicine
subject: Ecology
subject: Molecular Biology
subject: Microbiology
subject: Biochemistry

description: AIM: To investigate the initiating causes of cloacitis (inflammation of the cloaca) in kakapo (Strigops habroptilus).METHODS: Metagenomics using unbiased RNA or DNA sequencing was applied to faecal material from an 11-year-old female kakapo with exudative cloacitis, and a pool of eight birds (male and female aged 1–20 years) with no current signs or history of the disease. Faecal material from the diseased bird was collected pre- and post-treatment. For RNA sequencing, extracted RNA/DNA was subject to DNase, and the remaining RNA reverse transcribed to cDNA and subject to multiple displacement amplification prior to sequencing.RESULTS: No significant alignment to any known avian virus sequence was obtained from any faecal samples. However significant BLAST alignments to five bacteriophages known to infect enterobacteria were obtained. Strong evidence was obtained for the presence of the bacteriophage Escherichia phage TL-2011b, a bacteriophage known to occur in Escherichia coli causing outbreaks of foodborne disease in humans, in the sample from the diseased bird, but not the non-diseased pool. Differences in E. coli community structure between the diseased bird and the non-diseased pool were also apparent.CONCLUSIONS: Escherichia coli infection of human origin is suggested as a possible cause of exudative cloacitis, although confirmatory work is required to test this hypothesis.