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Full-Text Articles in Medicine and Health Sciences

Editorial: Emerging And Re-Emerging Viral Zoonoses, Naveen Kumar, Vladimir N. Uversky, Shailly Tomar, Kenneth S. M. Li, Keith Chappell, Susanna K. P. Lau Jan 2022

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.


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 Jan 2022

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 …


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 Jan 2022

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 …


Structural And Functional Insights Into Cp2c Transcription Factor Complexes, Seung Han Son, Min Young Kim, Eunbi Jo, Vladimir N. Uversky, Chul Geun Kim Jan 2022

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 …


Arrow Of Time, Entropy, And Protein Folding: Holistic View On Biochirality, Victor V. Dyakin, Vladimir N. Uversky Jan 2022

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 …


Effect Of Protein–Protein Interactions On Translational Diffusion Of Spheroidal Proteins, Aleksandra M. Kusova, Aleksandr E. Sitnitsky, Vladimir N. Uversky, Yuriy F. Zuev Jan 2022

Effect Of Protein–Protein Interactions On Translational Diffusion Of Spheroidal Proteins, Aleksandra M. Kusova, Aleksandr E. Sitnitsky, Vladimir N. Uversky, Yuriy F. Zuev

Molecular Medicine Faculty Publications

One of the commonly accepted approaches to estimate protein–protein interactions (PPI) in aqueous solutions is the analysis of their translational diffusion. The present review article observes a phenomenological approach to analyze PPI effects via concentration dependencies of self- and collective translational diffusion coefficient for several spheroidal proteins derived from the pulsed field gradient NMR (PFG NMR) and dynamic light scattering (DLS), respectively. These proteins are rigid globular α-chymotrypsin (ChTr) and human serum albumin (HSA), and partly disordered α-casein (α-CN) and β-lactoglobulin (β-Lg). The PPI analysis enabled us to reveal the dominance of intermolecular repulsion at low ionic strength of solution …


Peptidoglycan-Free Bacterial Ghosts Confer Enhanced Protection Against Yersinia Pestis Infection, Svetlana V. Dentovskaya, Anastasia S. Vagaiskaya, Mikhail E. Platonov, Alexandra S. Trunyakova, Sergey A. Kotov, Ekaterina A. Krasil’Nikova, Galina M. Titareva, Elizaveta M. Mazurina, Tat’Yana V. Gapel’Chenkova, Rima Z. Shaikhutdinova, Sergey A. Ivanov, Tat’Yana I. Kombarova, Vladimir N. Gerasimov, Vladimir N. Uversky, Andrey P. Anisimov Jan 2022

Peptidoglycan-Free Bacterial Ghosts Confer Enhanced Protection Against Yersinia Pestis Infection, Svetlana V. Dentovskaya, Anastasia S. Vagaiskaya, Mikhail E. Platonov, Alexandra S. Trunyakova, Sergey A. Kotov, Ekaterina A. Krasil’Nikova, Galina M. Titareva, Elizaveta M. Mazurina, Tat’Yana V. Gapel’Chenkova, Rima Z. Shaikhutdinova, Sergey A. Ivanov, Tat’Yana I. Kombarova, Vladimir N. Gerasimov, Vladimir N. Uversky, Andrey P. Anisimov

Molecular Medicine Faculty Publications

To develop a modern plague vaccine, we used hypo-endotoxic Yersinia pestis bacterial ghosts (BGs) with combinations of genes encoding the bacteriophage ɸX174 lysis-mediating protein E and/or holin-endolysin systems from λ or L-413C phages. Expression of the protein E gene resulted in the BGs that retained the shape of the original bacterium. Co-expression of this gene with genes coding for holin-endolysin system of the phage L-413C caused formation of structures resembling collapsed sacs. Such structures, which have lost their rigidity, were also formed as a result of the expression of only the L-413C holin-endolysin genes. A similar holin-endolysin system from phage …


Associations And Disease–Disease Interactions Of Covid-19 With Congenital And Genetic Disorders: A Comprehensive Review, Altijana Hromić-Jahjefendić, Debmalya Barh, Cecília Horta Ramalho Pinto, Lucas Gabriel Rodrigues Gomes, Jéssica Lígia Picanço Machado, Oladapo Olawale Afolabi, Sandeep Tiwari, Alaa A.A. Aljabali, Murtaza M. Tambuwala, Ángel Serrano-Aroca, Elrashdy M. Redwan, Vladimir N. Uversky, Kenneth Lundstrom Jan 2022

Associations And Disease–Disease Interactions Of Covid-19 With Congenital And Genetic Disorders: A Comprehensive Review, Altijana Hromić-Jahjefendić, Debmalya Barh, Cecília Horta Ramalho Pinto, Lucas Gabriel Rodrigues Gomes, Jéssica Lígia Picanço Machado, Oladapo Olawale Afolabi, Sandeep Tiwari, Alaa A.A. Aljabali, Murtaza M. Tambuwala, Ángel Serrano-Aroca, Elrashdy M. Redwan, Vladimir N. Uversky, Kenneth Lundstrom

Molecular Medicine Faculty Publications

Since December 2019, the COVID-19 pandemic, which originated in Wuhan, China, has resulted in over six million deaths worldwide. Millions of people who survived this SARS-CoV-2 infection show a number of post-COVID complications. Although, the comorbid conditions and post-COVID complexities are to some extent well reviewed and known, the impact of COVID-19 on pre-existing congenital anomalies and genetic diseases are only documented in isolated case reports and case series, so far. In the present review, we analyzed the PubMed indexed literature published between December 2019 and January 2022 to understand this relationship from various points of view, such as susceptibility, …


Biapss: A Comprehensive Physicochemical Analyzer Of Proteins Undergoing Liquid–Liquid Phase Separation, Aleksandra E. Badaczewska-Dawid, Vladimir N. Uversky, Davit A. Potoyan Jan 2022

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.


Ibuprofen Favors Binding Of Amyloid-Β Peptide To Its Depot, Serum Albumin, Ekaterina A. Litus, Alexei S. Kazakov, Eugenia I. Deryusheva, Ekaterina L. Nemashkalova, Marina P. Shevelyova, Andrey V. Machulin, Aliya A. Nazipova, Maria E. Permyakova, Vladimir N. Uversky, Sergei E. Permyakov Jan 2022

Ibuprofen Favors Binding Of Amyloid-Β Peptide To Its Depot, Serum Albumin, Ekaterina A. Litus, Alexei S. Kazakov, Eugenia I. Deryusheva, Ekaterina L. Nemashkalova, Marina P. Shevelyova, Andrey V. Machulin, Aliya A. Nazipova, Maria E. Permyakova, Vladimir N. Uversky, Sergei E. Permyakov

Molecular Medicine Faculty Publications

The deposition of amyloid-β peptide (Aβ) in the brain is a critical event in the progression of Alzheimer’s disease (AD). This Aβ deposition could be prevented by directed enhancement of Aβ binding to its natural depot, human serum albumin (HSA). Previously, we revealed that specific endogenous ligands of HSA improve its affinity to monomeric Aβ. We show here that an exogenous HSA ligand, ibuprofen (IBU), exerts the analogous effect. Plasmon resonance spectroscopy data evidence that a therapeutic IBU level increases HSA affinity to monomeric Aβ40/Aβ42 by a factor of 3–5. Using thioflavin T fluorescence assay and transmission electron microcopy, we …


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 Jan 2022

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 …


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 Jan 2022

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 …


An Issue Of Concern: Unique Truncated Orf8 Protein Variants Of Sars-Cov-2, Sk. Sarif Hassan, Vaishnavi Kodakandla, Elrashdy M. Redwan, Kenneth Lundstrom, Pabitra Pal Choudhury, Tarek Mohamed El-Aziz, Kazuo Takayama, Ramesh Kandimalla, Amos Lal, Ángel Serrano-Aroca, Gajendra Kumar Azad, Alaa A.A. Aljabali, Giorgio Palù, Gaurav Chauhan, Parise Adadi, Murtaza Tambuwala, Adam M. Brufsky, Wagner Baetas-Da-Cruz, Debmalya Barh, Vasco Azevedo, Nikolas G. Bazan, Bruno Silva Andrade, Raner José Silva, Vladimir N. Uversky Jan 2022

An Issue Of Concern: Unique Truncated Orf8 Protein Variants Of Sars-Cov-2, Sk. Sarif Hassan, Vaishnavi Kodakandla, Elrashdy M. Redwan, Kenneth Lundstrom, Pabitra Pal Choudhury, Tarek Mohamed El-Aziz, Kazuo Takayama, Ramesh Kandimalla, Amos Lal, Ángel Serrano-Aroca, Gajendra Kumar Azad, Alaa A.A. Aljabali, Giorgio Palù, Gaurav Chauhan, Parise Adadi, Murtaza Tambuwala, Adam M. Brufsky, Wagner Baetas-Da-Cruz, Debmalya Barh, Vasco Azevedo, Nikolas G. Bazan, Bruno Silva Andrade, Raner José Silva, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Open reading frame 8 (ORF8) shows one of the highest levels of variability among accessory proteins in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19). It was previously reported that the ORF8 protein inhibits the presentation of viral antigens by the major histocompatibility complex class I (MHC-I), which interacts with host factors involved in pulmonary inflammation. The ORF8 protein assists SARS-CoV-2 in evading immunity and plays a role in SARS-CoV-2 replication. Among many contributing mutations, Q27STOP, a mutation in the ORF8 protein, defines the B.1.1.7 lineage of SARS-CoV-2, engendering the second wave of …


What Is Parvalbumin For?, Eugene A. Permyakov, Vladimir N. Uversky Jan 2022

What Is Parvalbumin For?, Eugene A. Permyakov, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Parvalbumin (PA) is a small, acidic, mostly cytosolic Ca2+-binding protein of the EF-hand superfamily. Structural and physical properties of PA are well studied but recently two highly conserved structural motifs consisting of three amino acids each (clusters I and II), which contribute to the hydrophobic core of the EF-hand domains, have been revealed. Despite several decades of studies, physiological functions of PA are still poorly known. Since no target proteins have been revealed for PA so far, it is believed that PA acts as a slow calcium buffer. Numerous experiments on various muscle systems have shown that PA accelerates the …


Α-Synuclein Fibrils As Penrose Machines: A Chameleon In The Gear, Francesca De Giorgi, Vladimir N. Uversky, François Ichas Jan 2022

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 …


Sars-Cov-2 Intermittent Virulence As A Result Of Natural Selection, Alberto Rubio-Casillas, Elrashdy M. Redwan, Vladimir N. Uversky Jan 2022

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 …


Intrinsically Disordered Proteins Play Diverse Roles In Cell Signaling, Sarah E. Bondos, A. Keith Dunker, Vladimir N. Uversky Jan 2022

Intrinsically Disordered Proteins Play Diverse Roles In Cell Signaling, Sarah E. Bondos, A. Keith Dunker, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Signaling pathways allow cells to detect and respond to a wide variety of chemical (e.g. Ca2+ or chemokine proteins) and physical stimuli (e.g., sheer stress, light). Together, these pathways form an extensive communication network that regulates basic cell activities and coordinates the function of multiple cells or tissues. The process of cell signaling imposes many demands on the proteins that comprise these pathways, including the abilities to form active and inactive states, and to engage in multiple protein interactions. Furthermore, successful signaling often requires amplifying the signal, regulating or tuning the response to the signal, combining information sourced from multiple …


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 Jan 2022

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 …


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 Jan 2022

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 …


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 Jan 2022

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. …


Bioactive Peptides: Synthesis, Sources, Applications, And Proposed Mechanisms Of Action, Mohsen Akbarian, Ali Khani, Sara Eghbalpour, Vladimir N. Uversky Jan 2022

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 …


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 Jan 2022

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 …


Are The Functions Of Milk Exosomes Restricted To Their Protein Cargoes?, Elrashdy M. Redwan, Vladimir N. Uversky Jan 2022

Are The Functions Of Milk Exosomes Restricted To Their Protein Cargoes?, Elrashdy M. Redwan, 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 Jan 2022

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 …


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 Jan 2022

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 …


Nanoparticles For Coronavirus Control, Maryam Kianpour, Mohsen Akbarian, Vladimir N. Uversky Jan 2022

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 …


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 Jan 2022

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, …


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 Jan 2022

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 …


The Aqueous Humor Proteome Is Intrinsically Disordered, Mak B. Djulbegovic, Vladimir N. Uversky Jan 2022

The Aqueous Humor Proteome Is Intrinsically Disordered, Mak B. Djulbegovic, Vladimir N. Uversky

Molecular Medicine Faculty Publications

No abstract provided.


Specific S100 Proteins Bind Tumor Necrosis Factor And Inhibit Its Activity, Alexey S. Kazakov, Marina Y. Zemskova, Gleb K. Rystsov, Alisa A. Vologzhannikova, Eugenia I. Deryusheva, Victoria A. Rastrygina, Andrey S. Sokolov, Maria E. Permyakova, Ekaterina A. Litus, Vladimir N. Uversky, Eugene A. Permyakov, Sergei E. Permyakov Jan 2022

Specific S100 Proteins Bind Tumor Necrosis Factor And Inhibit Its Activity, Alexey S. Kazakov, Marina Y. Zemskova, Gleb K. Rystsov, Alisa A. Vologzhannikova, Eugenia I. Deryusheva, Victoria A. Rastrygina, Andrey S. Sokolov, Maria E. Permyakova, Ekaterina A. Litus, Vladimir N. Uversky, Eugene A. Permyakov, Sergei E. Permyakov

Molecular Medicine Faculty Publications

Tumor necrosis factor (TNF) inhibitors (anti-TNFs) represent a cornerstone of the treatment of various immune-mediated inflammatory diseases and are among the most commercially successful therapeutic agents. Knowledge of TNF binding partners is critical for identification of the factors able to affect clinical efficacy of the anti-TNFs. Here, we report that among eighteen representatives of the multifunctional S100 protein family, only S100A11, S100A12 and S100A13 interact with the soluble form of TNF (sTNF) in vitro. The lowest equilibrium dissociation constants (Kd) for the complexes with monomeric sTNF determined using surface plasmon resonance spectroscopy range from 2 nM to 28 nM. The …