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(2019). Journal club. Kidney International, 95(1), 11–13.
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Abudurexiti, A., Adkins, S., Alioto, D., Alkhovsky, S. V., Avsic-Zupanc, T., Ballinger, M. J., et al. (2019). Taxonomy of the order Bunyavirales: update 2019. Arch Virol, 164(7), 1949–1965.
Abstract: In February 2019, following the annual taxon ratification vote, the order Bunyavirales was amended by creation of two new families, four new subfamilies, 11 new genera and 77 new species, merging of two species, and deletion of one species. This article presents the updated taxonomy of the order Bunyavirales now accepted by the International Committee on Taxonomy of Viruses (ICTV).
Keywords: Bunyaviridae/*classification/*genetics; Genome, Viral/genetics; Phylogeny; RNA, Viral/genetics
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Aleixo, M. A. A., Rangel, V. L., Rustiguel, J. K., Padua, R. A. P. de, & Nonato, M. C. (2019). Structural, biochemical and biophysical characterization of recombinant human fumarate hydratase. The FEBS journal, 286(10), 1925–1940.
Abstract: Fumarate hydratases (FHs, fumarases) catalyze the reversible conversion of fumarate into l-malate. FHs are distributed over all organisms and play important roles in energy production, DNA repair and as tumor suppressors. They are very important targets both in the study of human metabolic disorders and as potential therapeutic targets in neglected tropical diseases and tuberculosis. In this study, human FH (HsFH) was characterized by using enzyme kinetics, differential scanning fluorimetry and X-ray crystallography. For the first time, the contribution of both substrates was analyzed simultaneously in a single kinetics assay allowing to quantify the contribution of the reversible reaction for kinetics. The protein was crystallized in the spacegroup C222 , with unit-cell parameters a\textbackslashtextasciitilde=\textbackslashtextasciitilde125.43, b\textbackslashtextasciitilde=\textbackslashtextasciitilde148.01, c\textbackslashtextasciitilde=\textbackslashtextasciitilde129.76. The structure was solved by molecular replacement and refined at 1.8\textbackslashtextasciitildeA resolution. In our study, a HEPES molecule was found to interact with HsFH at the C-terminal domain (Domain 3), previously described as involved in allosteric regulation, through a set of interactions that includes Lys 467. HsFH catalytic efficiency is higher when in the presence of HEPES. Mutations at residue 467 have already been implicated in genetic disorders caused by FH deficiency, suggesting that the HEPES-binding site may be important for enzyme kinetics. This study contributes to the understanding of the HsFH structure and how it correlates with mutation, enzymatic deficiency and pathology.
Keywords: Crystallography,X-Ray; Enzyme Stability; Fumarate Hydratase,chemistry,genetics,metabolism; HEPES,metabolism; Humans; Kinetics; Lysine,metabolism; Models,Molecular; Mutation; Protein Conformation; Recombinant Proteins,metabolism; enzymatic kinetics; fumarase; protein structure; thermofluor
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Bandera, A., Gori, A., Clerici, M., & Sironi, M. (2019). Phylogenies in ART: HIV reservoirs, HIV latency and drug resistance. Curr Opin Pharmacol, 48, 24–32.
Abstract: Combination antiretroviral therapy (ART) has significantly reduced the morbidity and mortality resulting from HIV infection. ART is, however, unable to eradicate HIV, which persists latently in several cell types and tissues. Phylogenetic analyses suggested that the proliferation of cells infected before ART initiation is mainly responsible for residual viremia, although controversy still exists. Conversely, it is widely accepted that drug resistance mutations (DRMs) do not appear during ART in patients with suppressed viral loads. Studies based on sequence clustering have in fact indicated that, at least in developed countries, HIV-infected ART-naive patients are the major source of drug-resistant viruses. Analysis of longitudinally sampled sequences have also shown that DRMs have variable fitness costs, which are strongly influenced by the viral genetic background.
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Baretic, D., Oliveira, T. M. de, Niess, M., Wan, P., Pollard, H., Johnson, C. M., et al. (2019). Structural insights into the critical DNA damage sensors DNA-PKcs, ATM and ATR. Progress in biophysics and molecular biology, 147, 4–16.
Abstract: ATM, ATR and DNA-PKCs are key effectors of DNA Damage response and have been extensively linked to tumourigenesis and survival of cancer cells after radio/chemotherapy. Despite numerous efforts, the structures of these proteins remained elusive until very recently. The resolution revolution in Cryo-EM allowed for molecular details of these proteins to be seen for the first time. Here we provide a comprehensive review of the structures of ATM, ATR and DNA-PKcs and their complexes and expand with observations springing from our own cryo-EM studies. These observations include a novel conformation of ATR and novel dimeric arrangements of DNA-PKcs.
Keywords: Ataxia Telangiectasia Mutated Proteins,chemistry,metabolism; DNA Damage; Humans; Site-Specific DNA-Methyltransferase (Adenine-Specific),metabolism
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Branton, A., Trivedi, M. K., Trivedi, D., Nayak, G., & Jana, S. (2019). Characterization of the Physicochemical and Thermal properties of the Biofield Energy Treated Flutamide Using PSA, PXRD, TGA/DTG, and DSC Analytical Techniques. Journal of Complementary Medicine and Alternative Healthcare, 8(5). Retrieved July 4, 2022, from http://dx.doi.org/10.19080/JCMAH.2019.08.555748
Abstract: Flutamide is an antiandrogen drug that blocks the action of testosterone by binding to the androgen receptor. This study was designed to determine the impact of the Trivedi Effect®-Energy of Consciousness Healing Treatment on the physicochemical and thermal properties of flutamide. The test sample was divided into two parts, i.e., control and treated sample. The control part was known as untreated sample, while the treated part remotely received the Biofield Energy Healing Treatment by a renowned Biofield Energy Healer, Alice Branton. The study showed that the particle size values were significantly increased by 15.82%(d10), 16.36%(d50), 1.05%(d90), and 5.10% {D (4, 3)}; thus, the specific surface area was significantly decreased by 14.56% in the treated sample compared with the control sample. The PXRD peak intensities and crystallite sizes were significantly altered ranging from 7.02% to 29.41% and -9.17% to 17.86%, along with 2.84% increase in the average crystallite size in the treated flutamide compared to the control sample. The residue weight was significantly decreased by 64.16%; however, the maximum thermal degradation temperature was increased by 10.16% in the treated sample compared to the control sample. The latent heat of the treated sample reduced by 9.37% compared with the control sample. The results revealed the significant alteration in the crystallinity, particle size and thermal stability of the treated sample as compared to the untreated sample. Thus, the Biofield Energy Treated flutamide might improve the flowability, and compatibility compared with the untreated sample, that may help in designing a better pharmaceutical formulation in terms of its performance against various diseases.
Keywords: Flutamide; The Trivedi Effect®; Energy of consciousness haling treatment; Complementary and alternative medicine; PSA; PXRD; TGA; DSC
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Branton, A., Trivedi, M. K., Trivedi, D., Nayak, G., & Jana, S. (2019). Solid State Characterization for a Comparative Evaluation of the Biofield Energy Treated and Un-treated Ascorbic Acid. Drug Designing & Intellectual Properties International Journal, 2(5). Retrieved July 4, 2022, from http://dx.doi.org/10.32474/DDIPIJ.2019.02.000149
Abstract: Ascorbic acid is a water-soluble vitamin that mainly acts as an antioxidant and helps in controlling and maintaining various body functions. The study was designed to analyze the impact of the Trivedi Effect®-Consciousness Energy Healing Treatment on the physicochemical and thermal properties of ascorbic acid by using sophisticated analytical techniques. For the study, the test sample ascorbic acid was divided into the control and treated sample. To the control sample, no Biofield Energy Treatment was provided. However, the treated sample received the Biofield Energy Treatment remotely by the renowned Biofield Energy Healer, Alice Branton, USA. The PXRD peak intensities and crystallite sizes of the treated sample significantly altered ranging from -78.43% to 1168.06% and -62.38% to 126.83%, respectively; along with 24.99% decrease in the average crystallite size as compared to the control sample. The particle size values in the treated sample by 9.59% (d10), 21.63% (d50), 16.55% (d90), and 17.97% {D(4,3)}, respectively; hence the specific surface area was increased by 16.67% compared to the control sample. The weight loss was increased by 6.67%; however, the residue amount was found to be significantly decreased by 28.59% in the treated sample compared to the control sample. The Tmax of the treated sample corresponding to 1st and 2nd peaks were decreased by 0.33% and 4.09%, respectively as compared to the control sample. Moreover, the latent heat of fusion was significantly increased by 13.74% as compared to the control sample. Besides, the degradation temperature and ΔHdecomposition of the treated sample were significantly reduced by 6.54% and 20.46%, respectively, as compared to the control sample. The Trivedi Effect® might help in forming a novel polymorphic form of ascorbic acid that may also prove to be more soluble, absorbable, and bioavailable than the untreated sample. Thus, the Trivedi Effect® might be considered as a novel approach for designing the more efficacious ascorbic acid containing nutraceutical/pharmaceutical formulations.
Keywords: Ascorbic acid; Consciousness Energy Healing Treatment; The Trivedi Effect®; PXRD; Particle size; TGA/DTG
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Branton, A., Trivedi, M. K., Trivedi, D., Nayak, G., & Jana, S. (2019). Study of the Effect of Consciousness Energy Healing Treatment on the Natural Product Berberine Chloride. International Journal of Pharmacognosy and Chinese Medicine, 3(1). Retrieved July 4, 2022, from http://dx.doi.org/10.23880/ipcm-16000154
Abstract: Berberine chloride is an isoquinoline alkaloid that has antimicrobial activity against bacteria, viruses, chlamydia, fungi, protozoans, and helminths, etc. The study was designed with the aim to evaluate the influence of the Trivedi Effect®- Consciousness Energy Healing Treatment on the physicochemical and thermal properties of berberine chloride by using modern analytical techniques. For this study, the berberine chloride sample was divided into two parts among which, one part was named as control as no Biofield Energy Treatment was given to it; while the other part received the Consciousness Energy Healing Treatment remotely by a renowned Biofield Energy Healer, Alice Branton and named as the Biofield Energy Treated sample. The PXRD results revealed some changes in the Bragg’s angle of peaks along with -7.24% to 188.78% alterations in the peak intensities and -65.88% to 135.42% changes in the crystallite sizes of the treated sample. Also, there was 1.91% decrease in the average crystallite size of the treated sample compared to the control sample. The particle size of the treated sample was significantly reduced by 20.16% (d10), 17.21% (d50), 27.53% (d90), and 27.36% {D(4,3)}; along with 15.31% increase in the specific surface area compared with the control sample. The total weight loss was significantly reduced by 25.81%; however, the residue amount was significantly increased by 55.04% in the treated sample compared to the control sample. Besides, the DSC thermogram showed four peaks, in which the peak temperatures of the treated sample corresponding to 1st, 2nd, 3rd, and 4th peak were altered by -2.26%, 3.55%, -4.50%, and -0.69%, respectively. Moreover, the latent heat for 1st, 2nd, 3rd, and 4th peak of the treated sample were significantly reduced by 24.04%, 42.44%, 44.26%, and 47.78%, respectively, compared with the control sample. The results showed that the Trivedi Effect®-Consciousness Energy Healing Treatment might help in improving the solubility, absorption, and bioavailability of berberine chloride compared with the control sample. Hence, the Consciousness Energy Healing Treatment would be useful for designing the novel nutraceutical/pharmaceutical formulations of berberine chloride with improved drug profile for the treatment of various microbial diseases and disorders such as diarrhea, gastroenteritis, hypertension, tumor, malaria, hyperglycemia, inflammation, arrhythmia, infections, etc.
Keywords: Berberine Chloride; Consciousness Energy Healing Treatment; Complementary and Alternative Medicine; The Trivedi Effect®; PXRD; Particle Size; TGA/DTG; DSC
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Cagliani, R., Forni, D., & Sironi, M. (2019). Mode and tempo of human hepatitis virus evolution. Comput Struct Biotechnol J, 17, 1384–1395.
Abstract: Human viral hepatitis, a major cause of morbidity and mortality worldwide, is caused by highly diverse viruses with different genetic, ecological, and pathogenetic features. Technological advances that allow throughput sequencing of viral genomes, as well as the development of computational tools to analyze such genome data, have largely expanded our knowledge on the host range and evolutionary history of human hepatitis viruses. Thus, with the exclusion of hepatitis D virus, close or distant relatives of these human pathogens were identified in a number of domestic and wild mammals. Also, sequences of human viral strains isolated from different geographic locations and over different time-spans have allowed the application of phylogeographic and molecular dating approaches to large viral phylogenies. In this review, we summarize the most recent insights into our understanding of the evolutionary events and ecological contexts that determined the origin and spread of human hepatitis viruses.
Keywords: Host switch; Human hepatitis virus; Molecular dating; NHP, non-human primates; ORF, open reading frame; RdRp, RNA-dependent RNA polymerase; STI, sexually transmitted infection; TDRP, time-dependent rate phenomenon; TMRCA, time to the most recent common ancestor; Zoonosis
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Geng, C., Vangone, A., Folkers, G. E., Xue, L. C., & Bonvin, A. M. J. J. (2019). iSEE: Interface structure, evolution, and energy-based machine learning predictor of binding affinity changes upon mutations. Proteins, 87(2), 110–119.
Abstract: Abstract Quantitative evaluation of binding affinity changes upon mutations is crucial for protein engineering and drug design. Machine learning-based methods are gaining increasing momentum in this field. Due to the limited number of experimental data, using a small number of sensitive predictive features is vital to the generalization and robustness of such machine learning methods. Here we introduce a fast and reliable predictor of binding affinity changes upon single point mutation, based on a random forest approach. Our method, iSEE, uses a limited number of interface Structure, Evolution, and Energy-based features for the prediction. iSEE achieves, using only 31 features, a high prediction performance with a Pearson correlation coefficient (PCC) of 0.80 and a root mean square error of 1.41?kcal/mol on a diverse training dataset consisting of 1102 mutations in 57 protein-protein complexes. It competes with existing state-of-the-art methods on two blind test datasets. Predictions for a new dataset of 487 mutations in 56 protein complexes from the recently published SKEMPI 2.0 database reveals that none of the current methods perform well (PCC?<?0.42), although their combination does improve the predictions. Feature analysis for iSEE underlines the significance of evolutionary conservations for quantitative prediction of mutation effects. As an application example, we perform a full mutation scanning of the interface residues in the MDM2?p53 complex.
Keywords: ppi,modelling,variant assessment,in silico tool
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