Medicine and Health Sciences Commons^™

The Finite Size Effects And Two-State Paradigm Of Protein Folding, Artem Badasyan, Matjaz Valant, Jože Grdadolnik, Vladimir N. Uversky

Molecular Medicine Faculty Publications

The coil to globule transition of the polypeptide chain is the physical phenomenon behind the folding of globular proteins. Globular proteins with a single domain usually consist of about 30 to 100 amino acid residues, and this finite size extends the transition interval of the coil-globule phase transition. Based on the pedantic derivation of the two-state model, we introduce the number of amino acid residues of a polypeptide chain as a parameter in the expressions for two cooperativity measures and reveal their physical significance. We conclude that the 𝑘2 measure, defined as the ratio of van ’t Hoff and calorimetric …

On The Roles Of Intrinsically Disordered Proteins And Regions In Cell Communication And Signaling, Sarah E. Bondos, A. Keith Dunker, Vladimir N. Uversky

Molecular Medicine Faculty Publications

For proteins, the sequence → structure → function paradigm applies primarily to enzymes, transmembrane proteins, and signaling domains. This paradigm is not universal, but rather, in addition to structured proteins, intrinsically disordered proteins and regions (IDPs and IDRs) also carry out crucial biological functions. For these proteins, the sequence → IDP/IDR ensemble → function paradigm applies primarily to signaling and regulatory proteins and regions. Often, in order to carry out function, IDPs or IDRs cooperatively interact, either intra- or inter-molecularly, with structured proteins or other IDPs or intermolecularly with nucleic acids. In this IDP/IDR thematic collection published in Cell Communication …

Predicting Associations Of Mirnas And Candidate Gastric Cancer Genes For Nanomedicine, Aigul Akimniyazova, Anna Pyrkova, Vladimir N. Uversky, Anatoliy Ivashchenko

Molecular Medicine Faculty Publications

Nanoscale miRNAs regulate the synthesis of most human proteins involved in differentiation, proliferation, cell cycle, apoptosis, and other processes associated with the growth and the development of an organism. miRNAs also play a number of important roles in the development of gastric cancer. In this work, we studied the quantitative characteristics of miRNA interactions with 69 candidate gastric cancer genes using bioinformatics approaches. To this end, the MirTarget program was used, which determines the characteristics of miRNA binding to mRNA in the 5′UTR, CDS, and 3′UTR. Associations of miRNAs with alternative target genes and associations of genes with alternative miRNAs …

Serotonin Promotes Serum Albumin Interaction With The Monomeric Amyloid Β Peptide, Ekaterina A. Litus, Alexei S. Kazakov, Eugenia I. Deryusheva, Ekaterina L. Nemashkalova, Marina P. Shevelyova, Aliya A. Nazipova, Maria E. Permyakova, Elena V. Raznikova, Vladimir N. Uversky, Sergei E. Permyakov

Molecular Medicine Faculty Publications

Prevention of amyloid β peptide (Aβ) deposition via facilitation of Aβ binding to its natural depot, human serum albumin (HSA), is a promising approach to preclude Alzheimer’s disease (AD) onset and progression. Previously, we demonstrated the ability of natural HSA ligands, fatty acids, to improve the affinity of this protein to monomeric Aβ by a factor of 3 (BBRC, 510(2), 248–253). Using plasmon resonance spectroscopy, we show here that another HSA ligand related to AD pathogenesis, serotonin (SRO), increases the affinity of the Aβ monomer to HSA by a factor of 7/17 for Aβ40/Aβ42, respectively. Meanwhile, the structurally homologous SRO …

The Role Of Non-Specific Interactions In Canonical And Alt-Associated Pml-Bodies Formation And Dynamics, Alexander V. Fonin, Sergey A. Silonov, Olesya G. Shpironok, Iuliia A. Antifeeva, Alexey V. Petukhov, Anna E. Romanovich, Irina M. Kuznetsova, Vladimir N. Uversky, Konstantin K. Turoverov

Molecular Medicine Faculty Publications

In this work, we put forward a hypothesis about the decisive role of multivalent nonspecific interactions in the early stages of PML body formation. Our analysis of the PML isoform sequences showed that some of the PML isoforms, primarily PML-II, are prone to phase separation due to their polyampholytic properties and the disordered structure of their C-terminal domains. The similarity of the charge properties of the C-terminal domains of PML-II and PML-VI isoforms made it possible for the first time to detect migration of PML-VI from PML bodies to the periphery of the cell nucleus, similar to the migration of …

Association Analysis Of Genetic Variants Of Sodium Taurocholate Co-Transporting Polypeptide Ntcp Gene (Slc10a1) And Hbv Infection Status In A Cohort Of Egyptian Patients, Maissa El Said El Raziky, Naglaa Ali Zayed, Yasmin Saad Ibrahim, Fatma Elrashdy, Rasha Mohamad Hosny Shahin, Mohamed Hassany, Magdy El Serafy, Wahid Doss, Vladimir N. Uversky, Ayman Yosry, Hadeel Gamal Eldeen

Molecular Medicine Faculty Publications

Background: Single nucleotide polymorphisms (SNPs) in the SLC10A1 gene, coding for a functional receptor of hepatitis B virus (HBV), sodium taurocholate co-transporting polypeptide (NTCP), may influence the susceptibility, outcome, and disease course of HBV infection in some populations. Aim: to determine the prevalence of SNPs of the NTCP gene, rs2296651 and rs943277, and their relationship with chronic HBV infection in a group of Egyptian patients. Methods: One hundred and thirty seven patients with HBV and 65 healthy controls were enrolled, and the patients were divided into two groups; group I chronic HBV infection (68 patients with normal ALT and minimal …

Potential Molecular Mechanisms Of Rare Anti-Tumor Immune Response By Sars-Cov-2 In Isolated Cases Of Lymphomas, Debmalya Barh, Sandeep Tiwary, Lucas Gabriel Rodrigues Gomes, Marianna E. Weener, Khalid J. Alzahrani, Khalaf F. Alsharif, Alaa A. A. Aljabali, Murtaza M. Tambuwala, Kenneth Lundstrom, Sk. Sarif Hassan, Ángel Serrano-Aroca, Kazuo Takayama, Preetam Ghosh, Elrashdy M. Redwan, Bruno Silva Andrade, Siomar De Castro Soares, Vasco Azevedo, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Recently, two cases of complete remission of classical Hodgkin lymphoma (cHL) and follicular lymphoma (FL) after SARS-CoV-2 infection were reported. However, the precise molecular mechanism of this rare event is yet to be understood. Here, we hypothesize a potential anti-tumor immune response of SARS-CoV-2 and based on a computational approach show that: (i) SARS-CoV-2 Spike-RBD may bind to the extracellular domains of CD15, CD27, CD45, and CD152 receptors of cHL or FL and may directly inhibit cell proliferation. (ii) Alternately, upon internalization after binding to these CD molecules, the SARS-CoV-2 membrane (M) protein and ORF3a may bind to gamma-tubulin complex …

The Participation Of The Intrinsically Disordered Regions Of The Bhlh-Pas Transcription Factors In Disease Development, Marta Kolonko-Adamska, Vladimir N. Uversky, Beata Greb-Markiewicz

Molecular Medicine Faculty Publications

The basic helix–loop–helix/Per-ARNT-SIM (bHLH-PAS) proteins are a family of transcription factors regulating expression of a wide range of genes involved in different functions, ranging from differentiation and development control by oxygen and toxins sensing to circadian clock setting. In addition to the well-preserved DNA-binding bHLH and PAS domains, bHLH-PAS proteins contain long intrinsically disordered C-terminal regions, responsible for regulation of their activity. Our aim was to analyze the potential connection between disordered regions of the bHLH-PAS transcription factors, post-transcriptional modifications and liquid-liquid phase separation, in the context of disease-associated missense mutations. Highly flexible disordered regions, enriched in short motives which …

Disphscan: A Multi-Sequence Web Tool For Predicting Protein Disorder As A Function Of Ph, Carlos Pintado-Grima, Valentín Iglesias, Jaime Santos, Vladimir N. Uversky, Salvador Ventura

Molecular Medicine Faculty Publications

Proteins are exposed to fluctuating environmental conditions in their cellular context and during their biotechnological production. Disordered regions are susceptible to these fluctuations and may experience solvent-dependent conformational switches that affect their local dynamism and activity. In a recent study, we modeled the influence of pH in the conformational state of IDPs by exploiting a charge–hydrophobicity diagram that considered the effect of solution pH on both variables. However, it was not possible to predict context-dependent transitions for multiple sequences, precluding proteome-wide analysis or the screening of collections of mutants. In this article, we present DispHScan, the first computational tool dedicated …

Structural Protein Analysis Of Driver Gene Mutations In Conjunctival Melanoma, Mak B. Djulbegovic, Vladimir N. Uversky, J. William Harbour, Anat Galor, Carol L. Karp

Molecular Medicine Faculty Publications

In recent years, there has been tremendous enthusiasm with respect to detailing the genetic basis of many neoplasms, including conjunctival melanoma (CM). We aim to analyze five proteins associated with CM, namely BRAF, NRAS, c-KIT, NF1, and PTEN. We evaluated each protein for its intrinsically disordered protein regions (IDPRs) and its protein-protein interactions (PPI) with the Predictor of Natural Disordered Protein Regions (PONDR®) and the Search Tool for the Retrieval of Interacting Genes (STRING®). Our PONDR® analysis found high levels of IDPRs in all five proteins with mutations linked to CM. The highest levels of IDPRs were in BRAF (45.95%), …

Covid-19 Vaccines And Thrombosis—Roadblock Or Dead-End Street?, Kenneth Lundstrom, Debmalya Barh, Bruce D. Uhal, Kazuo Takayama, Alaa A. A. Aljabali, Tarek Mohamed Abd El-Aziz, Amos Lal, Elrashdy M. Redwan, Parise Adadi, Gaurav Chauhan, Samendra P. Sherchan, Gajendra Kumar Azad, Nima Rezaei, Ángel Serrano-Aroca, Nicolas G. Bazan, Sk. Sarif Hassan, Pritam Kumar Panda, Pabitra Pal Choudhury, Damiano Pizzol, Ramesh Kandimalla, Wagner Baetas-Da-Cruz, Yogendra Kumar Mishra, Giorgio Palù, Adam M. Brufsky, Murtaza M. Tambuwala, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Two adenovirus-based vaccines, ChAdOx1 nCoV-19 and Ad26.COV2.S, and two mRNA-based vaccines, BNT162b2 and mRNA.1273, have been approved by the European Medicines Agency (EMA), and are invaluable in preventing and reducing the incidence of coronavirus disease-2019 (COVID-19). Recent reports have pointed to thrombosis with associated thrombocytopenia as an adverse effect occurring at a low frequency in some individuals after vaccination. The causes of such events may be related to SARS-CoV-2 spike protein interactions with different C-type lectin receptors, heparan sulfate proteoglycans (HSPGs) and the CD147 receptor, or to different soluble splice variants of the spike protein, adenovirus vector interactions with the …

Analysis Of The Dark Proteome Of Chandipura Virus Reveals Maximum Propensity For Intrinsic Disorder In Phosphoprotein, Nishi R. Sharma, Kundlik Gadhave, Prateek Kumar, Mohammad Saif, Md. M. Khan, Debi P. Sarkar, Vladimir N. Uversky, Rajanish Giri

Molecular Medicine Faculty Publications

Chandipura virus (CHPV, a member of the Rhabdoviridae family) is an emerging pathogen that causes rapidly progressing influenza-like illness and acute encephalitis often leading to coma and death of the human host. Given several CHPV outbreaks in Indian sub-continent, recurring sporadic cases, neurological manifestation, and high mortality rate of this infection, CHPV is gaining global attention. The ‘dark proteome’ includes the whole proteome with special emphasis on intrinsically disordered proteins (IDP) and IDP regions (IDPR), which are proteins or protein regions that lack unique (or ordered) three-dimensional structures within the cellular milieu. These proteins/regions, however, play a number of vital …

Hydrogen Bond Arrangement Is Shown To Differ In Coexisting Phases Of Aqueous Two-Phase Systems, Pedro P. Madeira, Amber R. Titus, 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

Analysis by attenuated total reflection–Fourier transform infrared spectroscopy shows that each coexisting phase in aqueous two-phase systems has a different arrangement of hydrogen bonds. Specific arrangements vary for systems formed by different solutes. The hydrogen bond arrangement is shown to correlate with differences in hydrophobic and electrostatic properties of the different phases of five specific systems, four formed by two polymers and one by a single polymer and salt. The results presented here suggest that the arrangement of hydrogen bonds may be an important factor in phase separation.

Understanding Structural Malleability Of The Sars-Cov-2 Proteins And Their Relation To The Comorbidities, Sagnik Sen, Ashmita Dey, Sanghamitra Bandyopadhyay, Ujjwal Maulik, Vladimir Uversky

Molecular Medicine Faculty Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a causative agent of the coronavirus disease (CoVID-19), is a part of the β-coronaviridae family. In comparison with two other members of this family of coronaviruses infecting humans (SARS-CoV and Middle East Respiratory Syndrome (MERS) CoV), SARS-CoV-2 showed the most severe effects on the entire Earth population causing world-wide CoVID-19 pandemic. SARS-CoV-2 contains five major protein classes, such as four structural proteins (Nucleocapsid (N), Membrane (M), Envelop (E), and Spike Glycoprotein (S)) and Replicase polyproteins (R), which are synthesized as two polyproteins (ORF1a and ORF1ab) that are subsequently processed into 12 nonstructural proteins …

Chemical Synthesis Of Peptidoglycan Mimetic–Disaccharide-Tetrapeptide Conjugate And Its Hydrolysis By Bacteriophage T5, Rb43 And Rb49 L-Alanyl-D-Glutamate Peptidases, Viatcheslav Azev, Alexey Chulin, Maxim Molchanov, Dmitry Prokhorov, Galina Mikoulinskaia, Vladimir N. Uversky, Viktor Kutyshenko

Molecular Medicine Faculty Publications

Endolysins of a number of bacteriophages, including coliphages T5, RB43, and RB49, target the peptidoglycans of the bacterial cell wall. The backbone of these bacterial peptidoglycans consist of alternating N-acetylglucosamine and N-acetylmuramic acid residues that is further “reinforced” by the peptide subunits. Because of the mesh-like structure and insolubility of peptidoglycans, the processes of the peptidoglycan binding and hydrolysis by enzymes cannot be studied by spectral methods. To overcome these issues we synthesized and analyzed here one of the simplest water soluble peptidoglycan mimetics.

A compound has been synthesized that mimics the peptidoglycan fragment of the bacterial cell wall, N-acetylglucosaminyl-β(1-4)-N-acetylmuramoyl-l-alanyl-γ-d-glutamyl-l-alanyl-d-alanine. …

Natural Resources To Control Covid-19: Could Lactoferrin Amend Sars-Cov-2 Infectivity?, Ehab H. Mattar, Fatma Elrashdy, Hussein A. Almehdar, Vladimir N. Uversky, Elrashdy M. Redwan

Molecular Medicine Faculty Publications

The world population is still facing the second wave of the COVID-19 pandemic. Such a challenge requires complicated tools to control, namely vaccines, effective cures, and complementary agents. Here we present one candidate for the role of an effective cure and/or complementary agent: lactoferrin. It is the cross-talking mediator between many organs/cellular systems in the body. It serves as a physiological, immunological, and anti-microbial barrier, and acts as a regulator molecule. Furthermore, lactoferrin has receptors on most tissues cells, and is a rich source for bioactive peptides, particularly in the digestive system. In the past months, in vitro and in …

Networks Of Networks: An Essay On Multi-Level Biological Organization, Vladimir N. Uversky, Alessandro Giuliani

Molecular Medicine Faculty Publications

The multi-level organization of nature is self-evident: proteins do interact among them to give rise to an organized metabolism, while in the same time each protein (a single node of such interaction network) is itself a network of interacting amino-acid residues allowing coordinated motion of the macromolecule and systemic effect as allosteric behavior. Similar pictures can be drawn for structure and function of cells, organs, tissues, and ecological systems. The majority of biologists are used to think that causally relevant events originate from the lower level (the molecular one) in the form of perturbations, that “climb up” the hierarchy reaching …

Biomolecules From Different Angles, Vladimir N. Uversky

Molecular Medicine Faculty Publications

No abstract provided.

On The Prevalence And Potential Functionality Of An Intrinsic Disorder In The Mers-Cov Proteome, Manal A. Alshehri, Manee M. Manee, Fahad H. Alqahtani, Badr M. Al-Shomrani, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Middle East respiratory syndrome is a severe respiratory illness caused by an infectious coronavirus. This virus is associated with a high mortality rate, but there is as of yet no effective vaccine or antibody available for human immunity/treatment. Drug design relies on understanding the 3D structures of viral proteins; however, arriving at such understanding is difficult for intrinsically disordered proteins, whose disorder-dependent functions are key to the virus’s biology. Disorder is suggested to provide viral proteins with highly flexible structures and diverse functions that are utilized when invading host organisms and adjusting to new habitats. To date, the functional roles …

Baicalein Inhibits Heparin-Induced Tau Aggregation By Initializing Non-Toxic Tau Oligomer Formation, Shweta Kishor Sonawane, Vladimir N. Uversky, Subashchandrabose Chinnathambi

Molecular Medicine Faculty Publications

Background: Amyloid aggregate deposition is the key feature of Alzheimer’s disease. The proteinaceous aggregates found in the afflicted brain are the intra-neuronal neurofibrillary tangles formed by the microtubule-associated protein Tau and extracellular deposits, senile plaques, of amyloid beta (Aβ) peptide proteolytically derived from the amyloid precursor protein. Accumulation of these aggregates has manifestations in the later stages of the disease, such as memory loss and cognitive inabilities originating from the neuronal dysfunction, neurodegeneration, and brain atrophy. Treatment of this disease at the late stages is difficult, and many clinical trials have failed. Hence, the goal is to find means capable …

Effects Of Different Solutes On The Physical Chemical Properties Of Aqueous Solutions Via Rearrangement Of Hydrogen Bonds In Water, Nuno Da Silva, Luisa A. Ferreira, Alexander I. Belgovskiy, Pedro P. Madeira, José A. Teixeira, Elizabeth K. Mann, J. Adin Mann, William V. Meyer, Anthony E. Smart, Vladimir Y. Chernyak, Vladimir N. Uversky, Boris Y. Zaslavsky

Molecular Medicine Faculty Publications

The Attenuated Total Reflection – Fourier Transform Infrared (ATR-FTIR) spectra of the OH-stretch band in aqueous solutions of inorganic salts and organic materials; Na₂SO₄, NaCl, NaClO₄, NaSCN, trimethylamine N-oxide, urea, poly(ethylene glycol), polyvinylpyrrolidone, and copolymer of ethylene glycol and propylene glycol (Ucon) were studied at various concentrations. The decomposition of the band into four Gaussian components peaking at 3080, 3230, 3400, and 3550 cm⁻¹ fits every compound examined here with essentially flat residuals. These components were viewed as representing four different subpopulations of water with different H-bond arrangements. The experimentally estimated relative contributions …

Questions Concerning The Proximal Origin Of Sars-Cov-2, Murat Seyran, Damiano Pizzol, Parise Adadi, Tarek M. El-Aziz, Sk. Sarif Hassan, Antonio Soares, Ramesh Kandimalla, Kenneth Lundstrom, Murtaza Tambuwala, Alaa A. Aljabali, Amos Lal, Gajendra K. Azad, Pabitra P. Choudhury, Vladimir N. Uversky, Samendra P. Sherchan, Bruce D. Uhal, Nima Rezaei, Adam M. Brufsky

Molecular Medicine Faculty Publications

No abstract provided.

Tudor Staphylococcal Nuclease Is A Docking Platform For Stress Granule Components And Is Essential For Snrk1 Activation In Arabidopsis, Emilio Gutierrez-Beltran, Pernilla H. Elander, Kerstin Dalman, Guy W. Dayhoff, Panagiotis N. Moschou, Vladimir N. Uversky, Jose L. Crespo, Peter V. Bozhkov

Molecular Medicine Faculty Publications

Tudor staphylococcal nuclease (TSN; also known as Tudor-SN, p100, or SND1) is a multifunctional, evolutionarily conserved regulator of gene expression, exhibiting cytoprotective activity in animals and plants and oncogenic activity in mammals. During stress, TSN stably associates with stress granules (SGs), in a poorly understood process. Here, we show that in the model plant Arabidopsis thaliana, TSN is an intrinsically disordered protein (IDP) acting as a scaffold for a large pool of other IDPs, enriched for conserved stress granule components as well as novel or plant-specific SG-localized proteins. While approximately 30% of TSN interactors are recruited to stress granules …

Targeting Autophagy In Ischemic Stroke: From Molecular Mechanisms To Clinical Therapeutics, Amir Ajoolabady, Shuyi Wang, Guido Kroemer, Josef M. Penninger, Vladimir N. Uversky, Domenico Pratico, Nils Henninger, Russel J. Reiter, Askiel Bruno, Kaumudi Joshipura, Hamid Aslkhodapasandhokmabad, Daniel J. Klionsky, Jun Ren

Molecular Medicine Faculty Publications

Stroke constitutes the second leading cause of death and a major cause of disability worldwide. Stroke is normally classified as either ischemic or hemorrhagic stroke (HS) although 87% of cases belong to ischemic nature. Approximately 700,000 individuals suffer an ischemic stroke (IS) in the US each year. Recent evidence has denoted a rather pivotal role for defective macroautophagy/autophagy in the pathogenesis of IS. Cellular response to stroke includes autophagy as an adaptive mechanism that alleviates cellular stresses by removing long-lived or damaged organelles, protein aggregates, and surplus cellular components via the autophagosome-lysosomal degradation process. In this context, autophagy functions as …

Simple And Efficient Protocol For Immunoglobulin Y Purification From Chicken Egg Yolk, Elrashdy M. Redwan, Abdullah A. Aljadawi, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Besides being a common food component broadly consumed worldwide, egg yolk immunoglobulin Y (IgY) has essential therapeutic potentials. In fact, in a time of ever-increasing risk of antibiotic resistance, it is crucial to find new ways to battle infection, and oral administration of preformed specific antibodies represents one of the most attractive approaches against infection. Infectious diseases of bacterial and viral origin in humans and animals can be controlled and passively cured by orally applied IgYs isolated from chicken egg yolks. Despite multiple obvious advantages of oral administration of IgY, harvesting IgY from egg yolk in a pure form is …

On The Safety Of The Covid-19 Convalescent Plasma Treatment: Thrombotic And Thromboembolic Concerns, Fatma Elrashdy, Elrashdy M. Redwan, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Recently, it was reported that near-sourced COVID-19 convalescent plasma (CP) is more efficient than distantly sourced CP. What was left behind in this analysis is the investigation of the possible causes of mortality associated with the CP transfusion itself. Knowing this information is important for determining whether not receiving CP of near source is the main cause of high rate of death in the group of patients who received distantly sourced CP. We argue that the thrombotic and thromboembolic events may act as risk factors for adverse complications and death associated with CP transfusion. Therefore, they have to be considered …

Protein Intrinsic Disorder And Evolvability Of Mers-Cov, Vladimir N. Uversky, Elrashdy M. Redwan, Abdullah A. Aljadawi

Molecular Medicine Faculty Publications

No abstract provided.

The Signal Peptide Of The Amyloid Precursor Protein Forms Amyloid-Like Aggregates And Enhances Aβ42 Aggregation, Kundlik Gadhave, Taniya Bhardwaj, Vladimir N. Uversky, Michele Vendruscolo, Rajanish Giri

Molecular Medicine Faculty Publications

Signal sequences are short peptides at the N terminus of proteins destined for the secretion pathway. Typically, after cleavage by peptidases, signal peptides are degraded by intra-membrane proteases. In some cases, however, signal peptides can be processed further and released into the endoplasmic reticulum, secretion pathways, or cytoplasm. The consequences of these processes remain unclear, in particular considering that dysregulated signal peptides could potentially aggregate and induce cytotoxicity. To investigate this problem, we study the signal peptide of the amyloid precursor protein (APP), which originates the Alzheimer’s β-amyloid (Aβ) peptide. Our results show that this signal peptide (residues 1–17 of …

Evolutionary Signatures Governing The Codon Usage Bias In Coronaviruses And Their Implications For Viruses Infecting Various Bat Species, Naveen Kumar, Rahul Kaushik, Chandana Tennakoon, Vladimir N. Uversky, Anamika Mishra, Richa Sood, Pratiksha Srivastava, Meghna Tripathi, Kam Y. J. Zhang, Sandeep Bhatia

Molecular Medicine Faculty Publications

Many viruses that cause serious diseases in humans and animals, including the betacoronaviruses (beta-CoVs), such as SARS-CoV, MERS-CoV, and the recently identified SARS-CoV-2, have natural reservoirs in bats. Because these viruses rely entirely on the host cellular machinery for survival, their evolution is likely to be guided by the link between the codon usage of the virus and that of its host. As a result, specific cellular microenvironments of the diverse hosts and/or host tissues imprint peculiar molecular signatures in virus genomes. Our study is aimed at deciphering some of these signatures. Using a variety of genetic methods we demonstrated …

Isolation And Characterization Of Human Colon Adenocarcinoma Stem-Like Cells Based On The Endogenous Expression Of The Stem Markers, Sergei A. Koshkin, Olga V. Anatskaya, Alexander E. Vinogradov, Vladimir N. Uversky, Guy W. Dayhoff Ii, Margarita A. Bystriakova, Valery A. Pospelov, Elena N. Tolkunova

Molecular Medicine Faculty Publications

Background: Cancer stem cells’ (CSCs) self-maintenance is regulated via the pluripotency pathways promoting the most aggressive tumor phenotype. This study aimed to use the activity of these pathways for the CSCs’ subpopulation enrichment and separating cells characterized by the OCT4 and SOX2 expression. Methods: To select and analyze CSCs, we used the SORE6x lentiviral reporter plasmid for viral transduction of colon adenocarcinoma cells. Additionally, we assessed cell chemoresistance, clonogenic, invasive and migratory activity and the data of mRNA-seq and intrinsic disorder predisposition protein analysis (IDPPA). Results: We obtained the line of CSC-like cells selected on the basis of the expression …