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Full-Text Articles in Medicine and Health Sciences

On The Potential Therapeutic Roles Of Taurine In Autism Spectrum Disorder, Alberto Rubio-Casillas, Elrashdy M. Redwan, Vladimir N. Uversky Jan 2023

On The Potential Therapeutic Roles Of Taurine In Autism Spectrum Disorder, Alberto Rubio-Casillas, Elrashdy M. Redwan, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Contemporary research has found that people with autism spectrum disorder (ASD) exhibit aberrant immunological function, with a shift toward increased cytokine production and unusual cell function. Microglia and astroglia were found to be significantly activated in immuno-cytochemical studies, and cytokine analysis revealed that the macrophage chemoattractant protein-1 (MCP-1), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and transforming growth factor β-1 (TGFB-1), all generated in the neuroglia, constituted the most predominant cytokines in the brain. Taurine (2-aminoethanesulfonic acid) is a promising therapeutic molecule able to increase the activity of antioxidant enzymes and ATPase, which may be protective against aluminum-induced neurotoxicity. …

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Can Covid-19 Vaccines Induce Premature Non-Communicable Diseases: Where Are We Heading To?, Altijana Hromić-Jahjefendić, Debmalya Barh, Vladimir N. Uversky, Alaa A. A. Aljabali, Murtaza M. Tambuwala, Fuad M. Alzahrani, Saleh Alshammeri, Kenneth Lundstrom Jan 2023

Can Covid-19 Vaccines Induce Premature Non-Communicable Diseases: Where Are We Heading To?, Altijana Hromić-Jahjefendić, Debmalya Barh, Vladimir N. Uversky, Alaa A. A. Aljabali, Murtaza M. Tambuwala, Fuad M. Alzahrani, Saleh Alshammeri, Kenneth Lundstrom

Molecular Medicine Faculty Publications

According to the WHO, as of January 2023, more than 850 million cases and over 6.6 million deaths from COVID-19 have been reported worldwide. Currently, the death rate has been reduced due to the decreased pathogenicity of new SARS-CoV-2 variants, but the major factor in the reduced death rates is the administration of more than 12.8 billion vaccine doses globally. While the COVID-19 vaccines are saving lives, serious side effects have been reported after vaccinations for several premature non-communicable diseases (NCDs). However, the reported adverse events are low in number. The scientific community must investigate the entire spectrum of COVID-19-vaccine-induced …

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Pre-Molten, Wet, And Dry Molten Globules En Route To The Functional State Of Proteins, Munishwar Nath Gupta, Vladimir N. Uversky Jan 2023

Pre-Molten, Wet, And Dry Molten Globules En Route To The Functional State Of Proteins, Munishwar Nath Gupta, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Transitions between the unfolded and native states of the ordered globular proteins are accompanied by the accumulation of several intermediates, such as pre-molten globules, wet molten globules, and dry molten globules. Structurally equivalent conformations can serve as native functional states of intrinsically disordered proteins. This overview captures the characteristics and importance of these molten globules in both structured and intrinsically disordered proteins. It also discusses examples of engineered molten globules. The formation of these intermediates under conditions of macromolecular crowding and their interactions with nanomaterials are also reviewed.

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Limosilactobacillus Fermentum 3872 That Produces Class Iii Bacteriocin Forms Co-Aggregates With The Antibiotic-Resistant Staphylococcus Aureus Strains And Induces Their Lethal Damage, Vyacheslav M. Abramov, Igor V. Kosarev, Andrey V. Machulin, Tatiana V. Priputnevich, Eugenia I. Deryusheva, Ekaterina L. Nemashkalova, Irina O. Chikileva, Tatiana N. Abashina, Alexander N. Panin, Vyacheslav G. Melnikov, Natalia E. Suzina, Ilya N. Nikonov, Marina V. Selina, Valentin S. Khlebnikov, Vadim K. Sakulin, Vladimir A. Samoilenko, Alexey B. Gordeev, Gennady T. Sukhikh, Vladimir N. Uversky, Andrey V. Karlyshev Jan 2023

Limosilactobacillus Fermentum 3872 That Produces Class Iii Bacteriocin Forms Co-Aggregates With The Antibiotic-Resistant Staphylococcus Aureus Strains And Induces Their Lethal Damage, Vyacheslav M. Abramov, Igor V. Kosarev, Andrey V. Machulin, Tatiana V. Priputnevich, Eugenia I. Deryusheva, Ekaterina L. Nemashkalova, Irina O. Chikileva, Tatiana N. Abashina, Alexander N. Panin, Vyacheslav G. Melnikov, Natalia E. Suzina, Ilya N. Nikonov, Marina V. Selina, Valentin S. Khlebnikov, Vadim K. Sakulin, Vladimir A. Samoilenko, Alexey B. Gordeev, Gennady T. Sukhikh, Vladimir N. Uversky, Andrey V. Karlyshev

Molecular Medicine Faculty Publications

LF3872 was isolated from the milk of a healthy lactating and breastfeeding woman. Earlier, the genome of LF3872 was sequenced, and a gene encoding unique bacteriocin was discovered. We have shown here that the LF3872 strain produces a novel thermolabile class III bacteriolysin (BLF3872), exhibiting antimicrobial activity against antibiotic-resistant Staphylococcus aureus strains. Sequence analysis revealed the two-domain structural (lysozyme-like domain and peptidase M23 domain) organization of BLF3872. At least 25% residues of this protein are expected to be intrinsically disordered. Furthermore, BLF3872 is predicted to have a very high liquid-liquid phase separation. According to the electron microscopy data, the bacterial …

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Exploring The Mechanisms By Which Camel Lactoferrin Can Kill Salmonella Enterica Serovar Typhimurium And Shigella Sonnei, Hussein A. Almehdar, Nawal Abd El-Baky, Ehab H. Mattar, Raed S. Albiheyri, Atif Bamagoos, Abdullah A. Aljaddawi, Vladimir N. Uversky, Elrashdy M. Redwan Jan 2023

Exploring The Mechanisms By Which Camel Lactoferrin Can Kill Salmonella Enterica Serovar Typhimurium And Shigella Sonnei, Hussein A. Almehdar, Nawal Abd El-Baky, Ehab H. Mattar, Raed S. Albiheyri, Atif Bamagoos, Abdullah A. Aljaddawi, Vladimir N. Uversky, Elrashdy M. Redwan

Molecular Medicine Faculty Publications

There is a continuously increasing pressure associated with the appearance of Salmonella enterica Serovar typhimurium (S. typhimurium) and Shigella sonnei (S. sonnei) that have developed pathogenic multiple antibiotic resistance and the cost of cure and control of these enterobacteriaceae infections increases annually. The current report for first time demonstrated the distinguished antimicrobial action of camel lactoferrin (cLf) obtained from the milk of different clans of camel in Saudi Arabia against S. typhimurium and S. sonnei. These cLf subtypes showed comparable antimicrobial potential when tested against the two bacterial strains but were superior to either bovine (bLf) …

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Liaisons Dangereuses: Intrinsic Disorder In Cellular Proteins Recruited To Viral Infection-Related Biocondensates, Greta Bianchi, Stefania Brocca, Sonia Longhi, Vladimir N. Uversky Jan 2023

Liaisons Dangereuses: Intrinsic Disorder In Cellular Proteins Recruited To Viral Infection-Related Biocondensates, Greta Bianchi, Stefania Brocca, Sonia Longhi, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Liquid–liquid phase separation (LLPS) is responsible for the formation of so-called membrane-less organelles (MLOs) that are essential for the spatio-temporal organization of the cell. Intrinsically disordered proteins (IDPs) or regions (IDRs), either alone or in conjunction with nucleic acids, are involved in the formation of these intracellular condensates. Notably, viruses exploit LLPS at their own benefit to form viral replication compartments. Beyond giving rise to biomolecular condensates, viral proteins are also known to partition into cellular MLOs, thus raising the question as to whether these cellular phase-separating proteins are drivers of LLPS or behave as clients/regulators. Here, we focus on …

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Yield And Composition Variations Of The Milk From Different Camel Breeds In Saudi Arabia, Amr A. El-Hanafy, Yasser M. Saad, Saleh A. Alkarim, Hussein A. Almehdar, Fuad M. Alzahrani, Mohammed A. Almatry, Vladimir N. Uversky, Elrashdy M. Redwan Jan 2023

Yield And Composition Variations Of The Milk From Different Camel Breeds In Saudi Arabia, Amr A. El-Hanafy, Yasser M. Saad, Saleh A. Alkarim, Hussein A. Almehdar, Fuad M. Alzahrani, Mohammed A. Almatry, Vladimir N. Uversky, Elrashdy M. Redwan

Molecular Medicine Faculty Publications

With the increasing interest in the identification of differences between camel breeds over the last decade, this study was conducted to estimate the variability of milk production and composition of four Saudi camel breeds during different seasons. Milk records were taken two days per week from females of Majahem, Safra, Wadha, and Hamra breeds distributed over Saudi Arabia. The milk yield during winter indicated that the weekly average of the Wadha breed was significantly lower (27.13 kg/week) than Majahem and Hamra breeds. The Safra breed had the lowest milk yield (30.7 kg/week) during summer. During winter, the Hamra breed had …

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From The Hydrophobic Core To The Globular-Disorder Interface: New Challenges And Insights Into Protein Design, Sankar Basu, Devlina Chakravarty, Qingzhen Hou, Vladimir N. Uversky Jan 2023

From The Hydrophobic Core To The Globular-Disorder Interface: New Challenges And Insights Into Protein Design, Sankar Basu, Devlina Chakravarty, Qingzhen Hou, Vladimir N. Uversky

Molecular Medicine Faculty Publications

No abstract provided.

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Advanced Phytochemical-Based Nanocarrier Systems For The Treatment Of Breast Cancer, Vivek P. Chavda, Lakshmi Vineela Nalla, Pankti Balar, Rajashri Bezbaruah, Vasso Apostolopoulos, Rajeev K. Singla, Avinash Khadela, Lalitkumar K. Vora, Vladimir N. Uversky Jan 2023

Advanced Phytochemical-Based Nanocarrier Systems For The Treatment Of Breast Cancer, Vivek P. Chavda, Lakshmi Vineela Nalla, Pankti Balar, Rajashri Bezbaruah, Vasso Apostolopoulos, Rajeev K. Singla, Avinash Khadela, Lalitkumar K. Vora, Vladimir N. Uversky

Molecular Medicine Faculty Publications

As the world’s most prevalent cancer, breast cancer imposes a significant societal health burden and is among the leading causes of cancer death in women worldwide. Despite the notable improvements in survival in countries with early detection programs, combined with different modes of treatment to eradicate invasive disease, the current chemotherapy regimen faces significant challenges associated with chemotherapy-induced side effects and the development of drug resistance. Therefore, serious concerns regarding current chemotherapeutics are pressuring researchers to develop alternative therapeutics with better efficacy and safety. Due to their extremely biocompatible nature and efficient destruction of cancer cells via numerous mechanisms, phytochemicals …

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Sumoylation-Mediated Psme3-20s Proteasomal Degradation Of Transcription Factor Cp2c Is Crucial For Cell Cycle Progression, Seung Han Son, Min Young Kim, Young Su Lim, Hyeon Cheol Jin, June Ho Shin, Jae Kyu Yi, Sungwoo Choi, Mi Ae Park, Ji Hyung Chae, Ho Chul Kang, Young Jin Lee, Vladimir N. Uversky, Chul Geun Kim Jan 2023

Sumoylation-Mediated Psme3-20s Proteasomal Degradation Of Transcription Factor Cp2c Is Crucial For Cell Cycle Progression, Seung Han Son, Min Young Kim, Young Su Lim, Hyeon Cheol Jin, June Ho Shin, Jae Kyu Yi, Sungwoo Choi, Mi Ae Park, Ji Hyung Chae, Ho Chul Kang, Young Jin Lee, Vladimir N. Uversky, Chul Geun Kim

Molecular Medicine Faculty Publications

Transcription factor CP2c (also known as TFCP2, α-CP2, LSF, and LBP-1c) is involved in diverse ubiquitous and tissue/stage-specific cellular processes and in human malignancies such as cancer. Despite its importance, many fundamental regulatory mechanisms of CP2c are still unclear. Here, we uncover an unprecedented mechanism of CP2c degradation via a previously unidentified SUMO1/PSME3/20S proteasome pathway and its biological meaning. CP2c is SUMOylated in a SUMO1-dependent way, and SUMOylated CP2c is degraded through the ubiquitin-independent PSME3 (also known as REGγ or PA28)/20S proteasome system. SUMOylated PSME3 could also interact with CP2c to degrade CP2c via the 20S proteasomal pathway. Moreover, precisely …

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Paving The Way For Synthetic Intrinsically Disordered Polymers For Soft Robotics, Orkid Coskuner-Weber, Elif Yuce-Erarslan, Vladimir N. Uversky Jan 2023

Paving The Way For Synthetic Intrinsically Disordered Polymers For Soft Robotics, Orkid Coskuner-Weber, Elif Yuce-Erarslan, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Nature is full of examples of processes that, through evolution, have been perfected over the ages to effectively use matter and sustain life. Here, we present our strategies for designing intrinsically disordered smart polymers for soft robotics applications that are bio-inspired by intrinsically disordered proteins. Bio-inspired intrinsically disordered smart and soft polymers designed using our deep understanding of intrinsically disordered proteins have the potential to open new avenues in soft robotics. Together with other desirable traits, such as robustness, dynamic self-organization, and self-healing abilities, these systems possess ideal characteristics that human-made formations strive for but often fail to achieve. Our …

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Biomolecular Condensates: Insights Into Early And Late Steps Of The Hiv-1 Replication Cycle, Francesca Di Nunzio, Vladimir N. Uversky, Andrew J. Mouland Jan 2023

Biomolecular Condensates: Insights Into Early And Late Steps Of The Hiv-1 Replication Cycle, Francesca Di Nunzio, Vladimir N. Uversky, Andrew J. Mouland

Molecular Medicine Faculty Publications

A rapidly evolving understanding of phase separation in the biological and physical sciences has led to the redefining of virus-engineered replication compartments in many viruses with RNA genomes. Condensation of viral, host and genomic and subgenomic RNAs can take place to evade the innate immunity response and to help viral replication. Divergent viruses prompt liquid–liquid phase separation (LLPS) to invade the host cell. During HIV replication there are several steps involving LLPS. In this review, we characterize the ability of individual viral and host partners that assemble into biomolecular condensates (BMCs). Of note, bioinformatic analyses predict models of phase separation …

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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.

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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 …

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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 …

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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 …

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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 …

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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 …

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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 …

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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, …

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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.

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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 …

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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 …

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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 …

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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 …

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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 …

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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 …

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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 …

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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 …

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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 …

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