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Articles 1 - 30 of 46
Full-Text Articles in Medicine and Health Sciences
Are The Functions Of Milk Exosomes Restricted To Their Protein Cargoes?, Elrashdy M. Redwan, Vladimir N. Uversky
Are The Functions Of Milk Exosomes Restricted To Their Protein Cargoes?, Elrashdy M. Redwan, Vladimir N. Uversky
Molecular Medicine Faculty Publications
No abstract provided.
Mechanism Of Phase Separation In Aqueous Two-Phase Systems, Amber R. Titus, Pedro P. Madeira, Luisa A. Ferreira, Vladimir Y. Chernyak, Vladimir N. Uversky, Boris Y. Zaslavsky
Mechanism Of Phase Separation In Aqueous Two-Phase Systems, Amber R. Titus, Pedro P. Madeira, Luisa A. Ferreira, Vladimir Y. Chernyak, Vladimir N. Uversky, Boris Y. Zaslavsky
Molecular Medicine Faculty Publications
Liquid-liquid phase separation underlies the formation of membrane-less organelles inside living cells. The mechanism of this process can be examined using simple aqueous mixtures of two or more solutes, which are able to phase separate at specific concentration thresholds. This work presents the first experimental evidence that mesoscopic changes precede visually detected macroscopic phase separation in aqueous mixtures of two polymers and a single polymer and salt. Dynamic light scattering (DLS) analysis indicates the formation of mesoscopic polymer agglomerates in these systems. These agglomerates increase in size with increasing polymer concentrations prior to visual phase separation. Such mesoscopic changes are …
A Study On The Nature Of Sars-Cov-2 Using The Shell Disorder Models: Reproducibility, Evolution, Spread, And Attenuation, Gerard Kian-Meng Goh, A. Keith Dunker, James A. Foster, Vladimir N. Uversky
A Study On The Nature Of Sars-Cov-2 Using The Shell Disorder Models: Reproducibility, Evolution, Spread, And Attenuation, Gerard Kian-Meng Goh, A. Keith Dunker, James A. Foster, Vladimir N. Uversky
Molecular Medicine Faculty Publications
The basic tenets of the shell disorder model (SDM) as applied to COVID-19 are that the harder outer shell of the virus shell (lower PID—percentage of intrinsic disorder—of the membrane protein M, PIDM) and higher flexibility of the inner shell (higher PID of the nucleocapsid protein N, PIDN) are correlated with the contagiousness and virulence, respectively. M protects the virion from the anti-microbial enzymes in the saliva and mucus. N disorder is associated with the rapid replication of the virus. SDM predictions are supported by two experimental observations. The first observation demonstrated lesser and greater presence of the Omicron particles …
Editorial: Emerging And Re-Emerging Viral Zoonoses, Naveen Kumar, Vladimir N. Uversky, Shailly Tomar, Kenneth S. M. Li, Keith Chappell, Susanna K. P. Lau
Editorial: Emerging And Re-Emerging Viral Zoonoses, Naveen Kumar, Vladimir N. Uversky, Shailly Tomar, Kenneth S. M. Li, Keith Chappell, Susanna K. P. Lau
Molecular Medicine Faculty Publications
No abstract provided.
An Ayurgenomics Approach: Prakriti-Based Drug Discovery And Development For Personalized Care, Zoufang Huang, Vivek P. Chavda, Rajashri Bezbaruah, Vladimir N. Uversky, Sucharitha Palagati, Aayushi B. Patel, Zhe-Sheng Chen
An Ayurgenomics Approach: Prakriti-Based Drug Discovery And Development For Personalized Care, Zoufang Huang, Vivek P. Chavda, Rajashri Bezbaruah, Vladimir N. Uversky, Sucharitha Palagati, Aayushi B. Patel, Zhe-Sheng Chen
Molecular Medicine Faculty Publications
Originating in ancient India, Ayurveda is an alternative medicinal approach that provides substantial evidence for a theoretical-level analysis of all aspects of life. Unlike modern medicine, Ayurveda is based upon tridoshas (Vata, pitta, and Kapha) and Prakriti. On the other hand, the research of all the genes involved at the proteomics, metabolomics, and transcriptome levels are referred to as genomics. Geoclimatic regions (deshanupatini), familial characteristics (kulanupatini), and ethnicity (jatiprasakta) have all been shown to affect phenotypic variability. The combination of genomics with Ayurveda known as ayurgenomics provided new insights into tridosha that may pave the way for precision medicine (personalized …
Α-Synuclein Fibrils As Penrose Machines: A Chameleon In The Gear, Francesca De Giorgi, Vladimir N. Uversky, François Ichas
Α-Synuclein Fibrils As Penrose Machines: A Chameleon In The Gear, Francesca De Giorgi, Vladimir N. Uversky, François Ichas
Molecular Medicine Faculty Publications
In 1957, Lionel Penrose built the first man-made self-replicating mechanical device and illustrated its function in a series of machine prototypes, prefiguring our current view of the genesis and the proliferation of amyloid fibrils. He invented and demonstrated, with the help of his son Roger, the concepts that decades later, would become the fundamentals of prion and prion-like neurobiology: nucleation, seeding and conformational templating of monomers, linear polymer elongation, fragmentation, and spread. He published his premonitory discovery in a movie he publicly presented at only two conferences in 1958, a movie we thus reproduce here. By making a 30-year-jump in …
Biapss: A Comprehensive Physicochemical Analyzer Of Proteins Undergoing Liquid–Liquid Phase Separation, Aleksandra E. Badaczewska-Dawid, Vladimir N. Uversky, Davit A. Potoyan
Biapss: A Comprehensive Physicochemical Analyzer Of Proteins Undergoing Liquid–Liquid Phase Separation, Aleksandra E. Badaczewska-Dawid, Vladimir N. Uversky, Davit A. Potoyan
Molecular Medicine Faculty Publications
The liquid–liquid phase separation (LLPS) of biomolecules is a phenomenon which is nowadays recognized as the driving force for the biogenesis of numerous functional membraneless organelles and cellular bodies. The interplay between the protein primary sequence and phase separation remains poorly understood, despite intensive research. To uncover the sequence-encoded signals of protein capable of undergoing LLPS, we developed a novel web platform named BIAPSS (Bioinformatics Analysis of LLPS Sequences). This web server provides on-the-fly analysis, visualization, and interpretation of the physicochemical and structural features for the superset of curated LLPS proteins.
Fundamental Clock Of Biological Aging: Convergence Of Molecular, Neurodegenerative, Cognitive And Psychiatric Pathways: Non-Equilibrium Thermodynamics Meet Psychology, Victor V. Dyakin, Nuka V. Dyakina-Fagnano, Laura B. Mcintire, Vladimir N. Uversky
Fundamental Clock Of Biological Aging: Convergence Of Molecular, Neurodegenerative, Cognitive And Psychiatric Pathways: Non-Equilibrium Thermodynamics Meet Psychology, Victor V. Dyakin, Nuka V. Dyakina-Fagnano, Laura B. Mcintire, Vladimir N. Uversky
Molecular Medicine Faculty Publications
In humans, age-associated degrading changes, widely observed in molecular and cellular processes underly the time-dependent decline in spatial navigation, time perception, cognitive and psychological abilities, and memory. Cross-talk of biological, cognitive, and psychological clocks provides an integrative contribution to healthy and advanced aging. At the molecular level, genome, proteome, and lipidome instability are widely recognized as the primary causal factors in aging. We narrow attention to the roles of protein aging linked to prevalent amino acids chirality, enzymatic and spontaneous (non-enzymatic) post-translational modifications (PTMs SP), and non-equilibrium phase transitions. The homochirality of protein synthesis, resulting in the steady-state non-equilibrium condition …
Theater In The Self-Cleaning Cell: Intrinsically Disordered Proteins Or Protein Regions Acting With Membranes In Autophagy, Hana Popelka, Vladimir N. Uversky
Theater In The Self-Cleaning Cell: Intrinsically Disordered Proteins Or Protein Regions Acting With Membranes In Autophagy, Hana Popelka, Vladimir N. Uversky
Molecular Medicine Faculty Publications
Intrinsically disordered proteins and protein regions (IDPs/IDPRs) are mainly involved in signaling pathways, where fast regulation, temporal interactions, promiscuous interactions, and assemblies of structurally diverse components including membranes are essential. The autophagy pathway builds, de novo, a membrane organelle, the autophagosome, using carefully orchestrated interactions between proteins and lipid bilayers. Here, we discuss molecular mechanisms related to the protein disorder-based interactions of the autophagy machinery with membranes. We describe not only membrane binding phenomenon, but also examples of membrane remodeling processes including membrane tethering, bending, curvature sensing, and/or fragmentation of membrane organelles such as the endoplasmic reticulum, which is an …
Editorial: Intrinsically Disordered Proteins And Regions: The Challenge To The Structure-Function Relationship, Angelo Toto, Pietro Sormanni, Cristina Paissoni, Vladimir N. Uversky
Editorial: Intrinsically Disordered Proteins And Regions: The Challenge To The Structure-Function Relationship, Angelo Toto, Pietro Sormanni, Cristina Paissoni, Vladimir N. Uversky
Molecular Medicine Faculty Publications
No abstract provided.
Sars-Cov-2 Intermittent Virulence As A Result Of Natural Selection, Alberto Rubio-Casillas, Elrashdy M. Redwan, Vladimir N. Uversky
Sars-Cov-2 Intermittent Virulence As A Result Of Natural Selection, Alberto Rubio-Casillas, Elrashdy M. Redwan, Vladimir N. Uversky
Molecular Medicine Faculty Publications
For the first time in history, we have witnessed the origin and development of a pandemic. To handle the accelerated accumulation of viral mutations and to comprehend the virus’ evolutionary adaptation in humans, an unparalleled program of genetic sequencing and monitoring of SARS-CoV-2 variants has been undertaken. Several scientists have theorized that, with the Omicron surge producing a more contagious but less severe disease, the end of COVID-19 is near. However, by analyzing the behavior shown by this virus for 2 years, we have noted that pandemic viruses do not always show decreased virulence. Instead, it appears there is an …
Shell Disorder Models Detect That Omicron Has Harder Shells With Attenuation But Is Not A Descendant Of The Wuhan-Hu-1 Sars-Cov-2, Gerard Kian-Meng Goh, A. Keith Dunker, James A. Foster, Vladimir N. Uversky
Shell Disorder Models Detect That Omicron Has Harder Shells With Attenuation But Is Not A Descendant Of The Wuhan-Hu-1 Sars-Cov-2, Gerard Kian-Meng Goh, A. Keith Dunker, James A. Foster, Vladimir N. Uversky
Molecular Medicine Faculty Publications
Before the SARS-CoV-2 Omicron variant emergence, shell disorder models (SDM) suggested that an attenuated precursor from pangolins may have entered humans in 2017 or earlier. This was based on a shell disorder analysis of SARS-CoV-1/2 and pangolin-Cov-2017. The SDM suggests that Omicron is attenuated with almost identical N (inner shell) disorder as pangolin-CoV-2017 (N-PID (percentage of intrinsic disorder): 44.8% vs. 44.9%—lower than other variants). The outer shell disorder (M-PID) of Omicron is lower than that of other variants and pangolin-CoV-2017 (5.4% vs. 5.9%). COVID-19-related CoVs have the lowest M-PIDs (hardest outer shell) among all CoVs. This is likely to be …
Arrow Of Time, Entropy, And Protein Folding: Holistic View On Biochirality, Victor V. Dyakin, Vladimir N. Uversky
Arrow Of Time, Entropy, And Protein Folding: Holistic View On Biochirality, Victor V. Dyakin, Vladimir N. Uversky
Molecular Medicine Faculty Publications
Chirality is a universal phenomenon, embracing the space–time domains of non-organic and organic nature. The biological time arrow, evident in the aging of proteins and organisms, should be linked to the prevalent biomolecular chirality. This hypothesis drives our exploration of protein aging, in relation to the biological aging of an organism. Recent advances in the chirality discrimination methods and theoretical considerations of the non-equilibrium thermodynamics clarify the fundamental issues, concerning the biphasic, alternative, and stepwise changes in the conformational entropy associated with protein folding. Living cells represent open, non-equilibrium, self-organizing, and dissipative systems. The non-equilibrium thermodynamics of cell biology are …
Would New Sars-Cov-2 Variants Change The War Against Covid-19?, Elrashdy M. Redwan, Fatma Elrashdy, Alaa A.A. Aljabali, Wagner Baetas-Da-Cruz, Debmalya Barh, Adam M. Brufsky, Sk. Sarif Hassan, Kenneth Lundstrom, Ángel Serrano-Aroca, Kazuo Takayama, Murtaza M. Tambuwala, Bruce D. Uhal, Vladimir N. Uversky
Would New Sars-Cov-2 Variants Change The War Against Covid-19?, Elrashdy M. Redwan, Fatma Elrashdy, Alaa A.A. Aljabali, Wagner Baetas-Da-Cruz, Debmalya Barh, Adam M. Brufsky, Sk. Sarif Hassan, Kenneth Lundstrom, Ángel Serrano-Aroca, Kazuo Takayama, Murtaza M. Tambuwala, Bruce D. Uhal, Vladimir N. Uversky
Molecular Medicine Faculty Publications
The scientific, private, and industrial sectors use a wide variety of technological platforms available to achieve protection against SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), including vaccines. However, the virus evolves continually into new highly virulent variants, which might overcome the protection provided by vaccines and may re-expose the population to infections. Mass vaccinations should be continued in combination with more or less mandatory non-pharmaceutical interventions. Therefore, the key questions to be answered are: (i) How to identify the primary and secondary infections of SARS-CoV-2? (ii) Why are neutralizing antibodies not long-lasting in both cases of natural infections and post-vaccinations? …
Structural And Functional Insights Into Cp2c Transcription Factor Complexes, Seung Han Son, Min Young Kim, Eunbi Jo, Vladimir N. Uversky, Chul Geun Kim
Structural And Functional Insights Into Cp2c Transcription Factor Complexes, Seung Han Son, Min Young Kim, Eunbi Jo, Vladimir N. Uversky, Chul Geun Kim
Molecular Medicine Faculty Publications
CP2c, also known as TFCP2, α-CP2, LSF, and LBP-1c, is a prototypic member of the transcription factor (TF) CP2 subfamily involved in diverse ubiquitous and tissue/stage-specific cellular processes and in human malignancies including cancer. Despite its importance, many fundamental regulatory mechanisms of CP2c are still unclear. Here, we uncover unprecedented structural and functional aspects of CP2c using DSP crosslinking and Western blot in addition to conventional methods. We found that a monomeric form of a CP2c homotetramer (tCP2c; [C4]) binds to the known CP2c-binding DNA motif (CNRG-N(5~6)-CNRG), whereas a dimeric form of a CP2c, CP2b, and PIAS1 heterohexamer ([C2B2P2]2) binds …
Small Heat Shock Protein 22 Improves Cognition And Learning In The Tauopathic Brain, Santiago Rodriguez Ospina, Danielle M. Blazier, Marangelie Criado-Marrero, Lauren A. Gould, Niad T. Gebru, David Beaulieu-Abdelahad, Xinming Wang, Elizabeth Remily-Wood, Dale Chaput, Stanley Stevens Jr., Vladimir N. Uversky, Paula C. Bickford, Chad Anthony Dickey, Laura J. Blair
Small Heat Shock Protein 22 Improves Cognition And Learning In The Tauopathic Brain, Santiago Rodriguez Ospina, Danielle M. Blazier, Marangelie Criado-Marrero, Lauren A. Gould, Niad T. Gebru, David Beaulieu-Abdelahad, Xinming Wang, Elizabeth Remily-Wood, Dale Chaput, Stanley Stevens Jr., Vladimir N. Uversky, Paula C. Bickford, Chad Anthony Dickey, Laura J. Blair
Molecular Medicine Faculty Publications
The microtubule-associated protein tau pathologically accumulates and aggregates in Alzheimer’s disease (AD) and other tauopathies, leading to cognitive dysfunction and neuronal loss. Molecular chaperones, like small heat-shock proteins (sHsps), can help deter the accumulation of misfolded proteins, such as tau. Here, we tested the hypothesis that the overexpression of wild-type Hsp22 (wtHsp22) and its phosphomimetic (S24,57D) Hsp22 mutant (mtHsp22) could slow tau accumulation and preserve memory in a murine model of tauopathy, rTg4510. Our results show that Hsp22 protected against deficits in synaptic plasticity and cognition in the tauopathic brain. However, we did not detect a significant change in tau …
Early Taurine Administration As A Means For Halting The Cytokine Storm Progression In Covid-19 Patients, Alberto Rubio-Casillas, Ramesh C. Gupta, Elrashdy M. Redwan, Vladimir N. Uversky, Raied A. Badierah
Early Taurine Administration As A Means For Halting The Cytokine Storm Progression In Covid-19 Patients, Alberto Rubio-Casillas, Ramesh C. Gupta, Elrashdy M. Redwan, Vladimir N. Uversky, Raied A. Badierah
Molecular Medicine Faculty Publications
Around the world, more than 6.2 million individuals have died as a result of coronavirus disease 2019 (COVID-19). According to a recent survey conducted among immunologists, epidemiologists, and virologists, this disease is expected to become endemic. This implies that the disease could have a continuous presence and/or normal frequency in the population. Pharmacological interventions to prevent infection, as well as to treat the patients at an early phase of illness to avoid hospitalization are essential additions to the vaccines. Taurine is known to inhibit the generation of all inflammatory mediators linked to the cytokine storm. It can also protect against …
Interferon-Β Activity Is Affected By S100b Protein, Alexey S. Kazakov, Alexander D. Sofin, Nadezhda V. Avkhacheva, Eugenia I. Deryusheva, Victoria A. Rastrygina, Maria E. Permyakova, Vladimir N. Uversky, Eugene A. Permyakov, Sergei E. Permyakov
Interferon-Β Activity Is Affected By S100b Protein, Alexey S. Kazakov, Alexander D. Sofin, Nadezhda V. Avkhacheva, Eugenia I. Deryusheva, Victoria A. Rastrygina, Maria E. Permyakova, Vladimir N. Uversky, Eugene A. Permyakov, Sergei E. Permyakov
Molecular Medicine Faculty Publications
Interferon-β (IFN-β) is a pleiotropic cytokine secreted in response to various pathological conditions and is clinically used for therapy of multiple sclerosis. Its application for treatment of cancer, infections and pulmonary diseases is limited by incomplete understanding of regulatory mechanisms of its functioning. Recently, we reported that IFN-β activity is affected by interactions with S100A1, S100A4, S100A6, and S100P proteins, which are members of the S100 protein family of multifunctional Ca2+-binding proteins possessing cytokine-like activities (Int J Mol Sci. 2020;21(24):9473). Here we show that IFN-β interacts with one more representative of the S100 protein family, the S100B protein, involved in …
Intrinsic Disorder In Bap1 And Its Association With Uveal Melanoma, Mak B. Djulbegovic, David J. Taylor, Vladimir N. Uversky, Anat Galor, Carol L. Shields, Carol L. Karp
Intrinsic Disorder In Bap1 And Its Association With Uveal Melanoma, Mak B. Djulbegovic, David J. Taylor, Vladimir N. Uversky, Anat Galor, Carol L. Shields, Carol L. Karp
Molecular Medicine Faculty Publications
Background: Specific subvariants of uveal melanoma (UM) are associated with increased rates of metastasis compared to other subvariants. BRCA1 (BReast CAncer gene 1)-associated protein-1 (BAP1) is encoded by a gene that has been linked to aggressive behavior in UM. Methods: We evaluated BAP1 for the presence of intrinsically disordered protein regions (IDPRs) and its protein–protein interactions (PPI). We evaluated specific sequence-based features of the BAP1 protein using a set of bioinformatic databases, predictors, and algorithms. Results: We show that BAP1’s structure contains extensive IDPRs as it is highly enriched in proline residues (the most disordered amino acid; p-value < 0.05), the average percent of predicted disordered residues (PPDR) was 57.34%, and contains 9 disorder-based binding sites (ie. molecular recognition features (MoRFs)). BAP1’s intrinsic disorder allows it to engage in a complex PPI network with at least 49 partners (p-value < 1.0 × 10−16). Conclusion: These findings show that BAP1 contains IDPRs and an intricate PPI network. Mutations in UM that are associated with the BAP1 gene may alter the function of the IDPRs embedded into its structure. These findings develop the understanding of UM and may provide a target for potential novel therapies to treat this aggressive neoplasm.
New Evidence Of The Importance Of Weak Interactions In The Formation Of Pml-Bodies, Alexander V. Fonin, Sergey A. Silonov, Anna S. Fefilova, Olesya V. Stepanenko, Anastasia A. Gavrilova, Alexey V. Petukhov, Anna E. Romanovich, Anna L. Modina, Tatiana S. Zueva, Evgeniy M. Nedelyaev, Nadejda M. Pleskach, Irina M. Kuznetsova, Vladimir N. Uversky, Konstantin K. Turoverov, Mirya L. Kuranova
New Evidence Of The Importance Of Weak Interactions In The Formation Of Pml-Bodies, Alexander V. Fonin, Sergey A. Silonov, Anna S. Fefilova, Olesya V. Stepanenko, Anastasia A. Gavrilova, Alexey V. Petukhov, Anna E. Romanovich, Anna L. Modina, Tatiana S. Zueva, Evgeniy M. Nedelyaev, Nadejda M. Pleskach, Irina M. Kuznetsova, Vladimir N. Uversky, Konstantin K. Turoverov, Mirya L. Kuranova
Molecular Medicine Faculty Publications
In this work, we performed a comparative study of the formation of PML bodies by full-length PML isoforms and their C-terminal domains in the presence and absence of endogenous PML. Based on the analysis of the distribution of intrinsic disorder predisposition in the amino acid sequences of PML isoforms, regions starting from the amino acid residue 395 (i.e., sequences encoded by exons 4–6) were assigned as the C-terminal domains of these proteins. We demonstrate that each of the full-sized nuclear isoforms of PML is capable of forming nuclear liquid-droplet compartments in the absence of other PML isoforms. These droplets possess …
Bioactive Peptides: Synthesis, Sources, Applications, And Proposed Mechanisms Of Action, Mohsen Akbarian, Ali Khani, Sara Eghbalpour, Vladimir N. Uversky
Bioactive Peptides: Synthesis, Sources, Applications, And Proposed Mechanisms Of Action, Mohsen Akbarian, Ali Khani, Sara Eghbalpour, Vladimir N. Uversky
Molecular Medicine Faculty Publications
Bioactive peptides are a group of biological molecules that are normally buried in the structure of parent proteins and become active after the cleavage of the proteins. Another group of peptides is actively produced and found in many microorganisms and the body of organisms. Today, many groups of bioactive peptides have been marketed chemically or recombinantly. This article reviews the various production methods and sources of these important/ubiquitous and useful biomolecules. Their applications, such as antimicrobial, antihypertensive, antioxidant activities, blood-lipid-lowering effect, opioid role, antiobesity, ability to bind minerals, antidiabetic, and antiaging effects, will be explored. The types of pathways proposed …
Limosilactobacillus Fermentum Strain 3872: Antibacterial And Immunoregulatory Properties And Synergy With Prebiotics Against Socially Significant Antibiotic-Resistant Infections Of Animals And Humans, Vyacheslav M. Abramov, Igor V. Kosarev, Andrey V. Machulin, Tatiana V. Priputnevich, Irina O. Chikileva, Eugenia I. Deryusheva, Tatiana N. Abashina, Almira D. Donetskova, Alexander N. Panin, Vyacheslav G. Melnikov, Natalia E. Suzina, Ilya N. Nikonov, Marina V. Selina, Valentin S. Khlebnikov, Vadim K. Sakulin, Raisa N. Vasilenko, Vladimir A. Samoilenko, Vladimir N. Uversky, Andrey V. Karlyshev
Limosilactobacillus Fermentum Strain 3872: Antibacterial And Immunoregulatory Properties And Synergy With Prebiotics Against Socially Significant Antibiotic-Resistant Infections Of Animals And Humans, Vyacheslav M. Abramov, Igor V. Kosarev, Andrey V. Machulin, Tatiana V. Priputnevich, Irina O. Chikileva, Eugenia I. Deryusheva, Tatiana N. Abashina, Almira D. Donetskova, Alexander N. Panin, Vyacheslav G. Melnikov, Natalia E. Suzina, Ilya N. Nikonov, Marina V. Selina, Valentin S. Khlebnikov, Vadim K. Sakulin, Raisa N. Vasilenko, Vladimir A. Samoilenko, Vladimir N. Uversky, Andrey V. Karlyshev
Molecular Medicine Faculty Publications
Limosilactobacillus fermentum strain 3872 (LF3872) was originally isolated from the breast milk of a healthy woman during lactation and the breastfeeding of a child. The high-quality genome sequencing of LF3872 was performed, and a gene encoding a unique bacteriocin was discovered. It was established that the bacteriocin produced by LF3872 (BLF3872) belongs to the family of cell-wall-degrading proteins that cause cell lysis. The antibacterial properties of LF3872 were studied using test cultures of antibiotic-resistant Gram-positive and Gram-negative pathogens. Gram-positive pathogens (Staphylococcus aureus strain 8325-4 and S. aureus strain IIE CI-SA 1246) were highly sensitive to the bacteriolytic action of LF3872. …
Arrangement Of Hydrogen Bonds In Aqueous Solutions Of Different Globular Proteins, Amber R. Titus, Pedro P. Madeira, Luisa A. Ferreira, Alexander I. Belgovskiy, Elizabeth K. Mann, Jay Adin Mann Jr., William V. Meyer, Anthony E. Smart, Vladimir N. Uversky, Boris Zaslavsky
Arrangement Of Hydrogen Bonds In Aqueous Solutions Of Different Globular Proteins, Amber R. Titus, Pedro P. Madeira, Luisa A. Ferreira, Alexander I. Belgovskiy, Elizabeth K. Mann, Jay Adin Mann Jr., William V. Meyer, Anthony E. Smart, Vladimir N. Uversky, Boris Zaslavsky
Molecular Medicine Faculty Publications
This work presents the first evidence that dissolved globular proteins change the arrangement of hydrogen bonds in water, with different proteins showing quantitatively different effects. Using ATR-FTIR (attenuated total reflection—Fourier transform infrared) spectroscopic analysis of OH-stretch bands, we obtain quantitative estimates of the relative amounts of the previously reported four subpopulations of water structures coexisting in a variety of aqueous solutions. Where solvatochromic dyes can measure the properties of solutions of non-ionic polymers, the results correlate well with ATR-FTIR measurements. In protein solutions to which solvatochromic dye probes cannot be applied, NMR (nuclear magnetic resonance) spectroscopy was used for the …
Nanoparticles For Coronavirus Control, Maryam Kianpour, Mohsen Akbarian, Vladimir N. Uversky
Nanoparticles For Coronavirus Control, Maryam Kianpour, Mohsen Akbarian, Vladimir N. Uversky
Molecular Medicine Faculty Publications
More than 2 years have passed since the SARS-CoV-2 outbreak began, and many challenges that existed at the beginning of this pandemic have been solved. Some countries have been able to overcome this global challenge by relying on vaccines against the virus, and vaccination has begun in many countries. Many of the proposed vaccines have nanoparticles as carriers, and there are different nano-based diagnostic approaches for rapid detection of the virus. In this review article, we briefly examine the biology of SARS-CoV-2, including the structure of the virus and what makes it pathogenic, as well as describe biotechnological methods of …
The Aqueous Humor Proteome Is Intrinsically Disordered, Mak B. Djulbegovic, Vladimir N. Uversky
The Aqueous Humor Proteome Is Intrinsically Disordered, Mak B. Djulbegovic, Vladimir N. Uversky
Molecular Medicine Faculty Publications
No abstract provided.
Bayesian Molecular Dating Analyses Combined With Mutational Profiling Suggest An Independent Origin And Evolution Of Sars-Cov-2 Omicron Ba.1 And Ba.2 Sub-Lineages, Naveen Kumar, Rahul Kaushik, Ashutosh Singh, Vladimir N. Uversky, Kam Y. J. Zhang, Upasana Sahu, Sandeep Bhatia, Aniket Sanyal
Bayesian Molecular Dating Analyses Combined With Mutational Profiling Suggest An Independent Origin And Evolution Of Sars-Cov-2 Omicron Ba.1 And Ba.2 Sub-Lineages, Naveen Kumar, Rahul Kaushik, Ashutosh Singh, Vladimir N. Uversky, Kam Y. J. Zhang, Upasana Sahu, Sandeep Bhatia, Aniket Sanyal
Molecular Medicine Faculty Publications
The ongoing evolution of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has resulted in the recent emergence of a highly divergent variant of concern (VOC) defined as Omicron or B.1.1.529. This VOC is of particular concern because it has the potential to evade most therapeutic antibodies and has undergone a sustained genetic evolution, resulting in the emergence of five distinct sub-lineages. However, the evolutionary dynamics of the initially identified Omicron BA.1 and BA.2 sub-lineages remain poorly understood. Herein, we combined Bayesian phylogenetic analysis, mutational profiling, and selection pressure analysis to track the virus’s genetic changes that drive the early evolutionary dynamics of …
Insights Into The Structural Properties Of Sars-Cov-2 Main Protease, Ibrahim Y. Akbaryak, Sule I. Caglayan, Lukasz Kurgan, Vladimir N. Uversky, Orkid Coskuner-Weber
Insights Into The Structural Properties Of Sars-Cov-2 Main Protease, Ibrahim Y. Akbaryak, Sule I. Caglayan, Lukasz Kurgan, Vladimir N. Uversky, Orkid Coskuner-Weber
Molecular Medicine Faculty Publications
SARS-CoV-2 is the infectious agent responsible for the coronavirus disease since 2019, which is the viral pneumonia pandemic worldwide. The structural knowledge on SARS-CoV-2 is rather limited. These limitations are also applicable to one of the most attractive drug targets of SARS-CoV-2 proteins – namely, main protease Mpro, also known as 3C-like protease (3CLpro). This protein is crucial for the processing of the viral polyproteins and plays crucial roles in interfering viral replication and transcription. In fact, although the crystal structure of this protein with an inhibitor was solved, Mpro conformational dynamics in aqueous solution is usually studied by molecular …
Hepatitis C Virus Infection And Intrinsic Disorder In The Signaling Pathways Induced By Toll-Like Receptors, Elrashdy M. Redwan, Abdullah A. Aljadawi, Vladimir N. Uversky
Hepatitis C Virus Infection And Intrinsic Disorder In The Signaling Pathways Induced By Toll-Like Receptors, Elrashdy M. Redwan, Abdullah A. Aljadawi, Vladimir N. Uversky
Molecular Medicine Faculty Publications
In this study, we examined the interplay between protein intrinsic disorder, hepatitis C virus (HCV) infection, and signaling pathways induced by Toll-like receptors (TLRs). To this end, 10 HCV proteins, 10 human TLRs, and 41 proteins from the TLR-induced downstream pathways were considered from the prevalence of intrinsic disorder. Mapping of the intrinsic disorder to the HCV-TLR interactome and to the TLR-based pathways of human innate immune response to the HCV infection demonstrates that substantial levels of intrinsic disorder are characteristic for proteins involved in the regulation and execution of these innate immunity pathways and in HCV-TLR interaction. Disordered regions, …
Fight Fire With Fire: The Need For A Vaccine Based On Intrinsic Disorder And Structural Flexibility, Vladimir N. Uversky
Fight Fire With Fire: The Need For A Vaccine Based On Intrinsic Disorder And Structural Flexibility, Vladimir N. Uversky
Molecular Medicine Faculty Publications
The absence of advancement in finding efficient vaccines for several human viruses, such as hepatitis C virus (HCV), human immunodeficiency virus type 1 (HIV-1), and herpes simplex viruses (HSVs) despite 30, 40, and even 60 years of research, respectively, is unnerving. Among objective reasons for such failure are the highly glycosylated nature of proteins used as primary vaccine targets against these viruses and the presence of neotopes and cryptotopes, as well as high mutation rates of the RNA viruses HCV and HIV-1 and the capability to establish latency by HSVs. However, the lack of success in utilization of the structure-based …
Bmi1 Silencing Induces Mitochondrial Dysfunction In Lung Epithelial Cells Exposed To Hyperoxia, Helena Hernández-Cuervo, Ramani Soundararajan, Sahebgowda Sidramagowda Patil, Mason T. Breitzig, Matthew Alleyn, Lakshmi Galam, Richard Lockey, Vladimir N. Uversky, Narasaiah Kolliputi
Bmi1 Silencing Induces Mitochondrial Dysfunction In Lung Epithelial Cells Exposed To Hyperoxia, Helena Hernández-Cuervo, Ramani Soundararajan, Sahebgowda Sidramagowda Patil, Mason T. Breitzig, Matthew Alleyn, Lakshmi Galam, Richard Lockey, Vladimir N. Uversky, Narasaiah Kolliputi
Molecular Medicine Faculty Publications
Acute Lung Injury (ALI), characterized by bilateral pulmonary infiltrates that restrict gas exchange, leads to respiratory failure. It is caused by an innate immune response with white blood cell infiltration of the lungs, release of cytokines, an increase in reactive oxygen species (ROS), oxidative stress, and changes in mitochondrial function. Mitochondrial alterations, changes in respiration, ATP production and the unbalancing fusion and fission processes are key events in ALI pathogenesis and increase mitophagy. Research indicates that BMI1 (B cell-specific Moloney murine leukemia virus integration site 1), a protein of the Polycomb repressive complex 1, is a cell cycle and survival …