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2022

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Monitoring Drug Concentration In Emergency Medicine, Andrew Woods Jan 2022

Monitoring Drug Concentration In Emergency Medicine, Andrew Woods

Undergraduate Journal of Mathematical Modeling: One + Two

The careful monitoring of a drug’s concentration in the body of a patient is of the utmost importance in modern medicine. Many of the lifesaving medications that are administered in an emergency medicine environment have a narrow window of efficacy. This effective concentration is in an ever-changing state, as the body processes and eliminates exogenous compounds that are introduced to maintain homeostasis. To ensure the proper treatment and/or management of ailments, special attention must be given to the concentration of a given drug in the body as time progresses. These changing concentrations can be evaluated and tracked using the mathematical …

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Exploring The Functionality Of Putative Bop3 Post-Translational Modifications, Liliya Tkachuk, Rebecca Adams Phd Jan 2022

Exploring The Functionality Of Putative Bop3 Post-Translational Modifications, Liliya Tkachuk, Rebecca Adams Phd

[Archive] Belmont University Research Symposium (BURS)

All eukaryotic cells require that transcribed mRNAs undergo export form the nucleus to the cytoplasm where they can be translated into proteins. This process requires a host of proteins which are conserved between the unicellular budding yeast, S. cerevisiae, and humans. During this process, Mex67 and other associated proteins facilitate the mRNA to travel across the nuclear pore complex (NPC), doorways embedded in the nuclear envelope. Upon the exit of mRNA, Mex67 is released and recycled back into the nucleus to provide the export of more mRNA. This release occurs through the action of Dbp5, whose activity is regulated …

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2021 Kentucky River Watershed Watch: Annual Report, Malissa Mcalister, Steven Evans Jan 2022

2021 Kentucky River Watershed Watch: Annual Report, Malissa Mcalister, Steven Evans

Kentucky River Watershed Watch

No abstract provided.

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Isolation And Characterization Of Novel B. Subtilis Bacteriophages, Johnson Phung, Rebecca Adams Jan 2022

Isolation And Characterization Of Novel B. Subtilis Bacteriophages, Johnson Phung, Rebecca Adams

Science University Research Symposium (SURS)

Bacteriophages are viruses that infect bacteria cells. Bacteria, being the most abundant form of life on the planet, have an estimated ten to a hundred different types of bacteriophages that infect each species. Bacteriophages are everywhere on Earth, but the number of phages that have been identified is only a fraction of what are thought to exist. This project focuses on isolating and identifying phages that infect the bacterium Bacillus subtilis. B subtilis is a decomposition microbe commonly found in the soil. Our first goal was to determine whether the 3 samples of Bacillus subtilis phages that were previously …

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Establishing A Biochemical System For The Purification And Atpase Activity Of Gst-Dbp5, Sarah R. Utley, Rachel E. Rigsby Phd, Rebecca L. Adams Phd Jan 2022

Establishing A Biochemical System For The Purification And Atpase Activity Of Gst-Dbp5, Sarah R. Utley, Rachel E. Rigsby Phd, Rebecca L. Adams Phd

Science University Research Symposium (SURS)

The export of mRNA out of the nucleus is a crucial step for eukaryotic gene expression. The export of mRNA transcripts is aided by Mex67, which allows export through the nuclear pore complex doorways in the nuclear envelope. Once out of the nucleus, a protein known as Dbp5, bound to ATP, Gle1, and Nup42 aids in the directionality of mRNA export by helping remove Mex67 from the mRNA strand. Following interaction with RNA, Dbp5 then hydrolyzes ATP so that it unbinds the mRNA, allowing for enzyme recycling. Previous efforts worked towards the purification of Dbp5, but the attempts were unsuccessful …

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Identifying Adaptor Proteins For Selective Mrna Export In S. Cerevisiae, Chloe Baker, Rebecca Adams Jan 2022

Identifying Adaptor Proteins For Selective Mrna Export In S. Cerevisiae, Chloe Baker, Rebecca Adams

Science University Research Symposium (SURS)

The export of mature mRNA from the nucleus of the cell to the cytoplasm is crucial for a cell’s survival, as this process is necessary to produce proteins encoded by these transcripts. In S. cerevisiae (yeast) cells, a protein known as Mex67 must bind to the mRNA while it’s in the nucleus so it can cross through the nuclear pore complex (NPC). Mex67 cannot bind to the mRNA directly, instead it needs to be accompanied by adaptor proteins to aid it in getting across the NPC. Stress conditions such as heat shock interferes with the function of these adaptor …

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Addressing Choice Of Law Challenges In Multi-State Precision Medicine Research: Experts' Assessment Key Factors, Leslie E. Wolf, Erin Fuse Brown, Roxanne Greeson, Catherine Hammack-Aviran, James W. Hazel, William Rencher, Laura M. Beskow Jan 2022

Addressing Choice Of Law Challenges In Multi-State Precision Medicine Research: Experts' Assessment Key Factors, Leslie E. Wolf, Erin Fuse Brown, Roxanne Greeson, Catherine Hammack-Aviran, James W. Hazel, William Rencher, Laura M. Beskow

Law Faculty Scholarship

This article explores potential frameworks for resolving choice-of-law challenges in multi-state precision medicine research. Through expert workshops involving legal scholars and research ethics specialists, the study identifies key factors relevant to determining which state laws should apply when research spans multiple jurisdictions. Participants emphasized the importance of considering the location of research institutions, participant residence, and the site of potential harm. The discussion also examined potential solutions including federal legislation, model state laws, and centralized databases of relevant statutes. The findings highlight the complexity of legal governance in large-scale biomedical research and propose strategies to improve clarity and consistency in …

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Randomized Controlled Trial Of A Prenatal Focused Coparenting Consultation For Unmarried African American Families: One-Year Infant And Family Outcomes, James P. Mchale, Carla Smith Stover, Chad Dube, Yana Sirotkin, Serina Lewis, Katherine Mckay Jan 2022

Randomized Controlled Trial Of A Prenatal Focused Coparenting Consultation For Unmarried African American Families: One-Year Infant And Family Outcomes, James P. Mchale, Carla Smith Stover, Chad Dube, Yana Sirotkin, Serina Lewis, Katherine Mckay

USF St. Petersburg Campus Faculty Publications

Despite a nonmarital birth rate of 70% for non-Hispanic Black women in the United States, there is a dearth of research on culturally grounded coparenting interventions for unmarried Black families with infants. Accordingly, this randomized controlled trial investigated one-year post-partum child and family outcomes of a novel modest dosage (6 session) Focused Coparenting Consultation (FCC) offered prenatally. One-hundred-thirty-eight families led by unmarried Black coparents were randomized to an intervention (N=70) or Treatment-As-Usual (TAU; control) condition (N=68). TAU families received navigational support in accessing existing community services for pregnant and parenting families. Intervention families also received TAU along with 6 dyadic …

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America To Me – A Public Nuisance Reparations Framework Through The Lens Of The Tulsa Massacre, 55 Uic L. Rev. 681 (2022), Kerri Gefeke Jan 2022

America To Me – A Public Nuisance Reparations Framework Through The Lens Of The Tulsa Massacre, 55 Uic L. Rev. 681 (2022), Kerri Gefeke

UIC Law Review

No abstract provided.

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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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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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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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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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Msh3 Homology And Potential Recombination Link To Sars-Cov-2 Furin Cleavage Site, Balamurali K. Ambati, Akhil Varshney, Kenneth Lundstrom, Giorgio Palù, Bruce D. Uhal, Vladimir N. Uversky, Adam M. Brufsky Jan 2022

Msh3 Homology And Potential Recombination Link To Sars-Cov-2 Furin Cleavage Site, Balamurali K. Ambati, Akhil Varshney, Kenneth Lundstrom, Giorgio Palù, Bruce D. Uhal, Vladimir N. Uversky, Adam M. Brufsky

Molecular Medicine Faculty Publications

Among numerous point mutation differences between the SARS-CoV-2 and the bat RaTG13 coronavirus, only the 12-nucleotide furin cleavage site (FCS) exceeds 3 nucleotides. A BLAST search revealed that a 19 nucleotide portion of the SARS-CoV-2 genome encompassing the furin cleavage site is a 100% complementary match to a codon-optimized proprietary sequence that is the reverse complement of the human mutS homolog (MSH3). The reverse complement sequence present in SARS-CoV-2 may occur randomly but other possibilities must be considered. Recombination in an intermediate host is an unlikely explanation. Single stranded RNA viruses such as SARS-CoV-2 utilize negative strand RNA templates in …

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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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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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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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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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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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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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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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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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Ferritinophagy And Α-Synuclein: Pharmacological Targeting Of Autophagy To Restore Iron Regulation In Parkinson’S Disease, Matthew K. Boag, Angus Roberts, Vladimir N. Uversky, Linlin Ma, Des R. Richardson, Dean L. Pountney Jan 2022

Ferritinophagy And Α-Synuclein: Pharmacological Targeting Of Autophagy To Restore Iron Regulation In Parkinson’S Disease, Matthew K. Boag, Angus Roberts, Vladimir N. Uversky, Linlin Ma, Des R. Richardson, Dean L. Pountney

Molecular Medicine Faculty Publications

A major hallmark of Parkinson’s disease (PD) is the fatal destruction of dopaminergic neurons within the substantia nigra pars compacta. This event is preceded by the formation of Lewy bodies, which are cytoplasmic inclusions composed of α-synuclein protein aggregates. A triad contribution of α-synuclein aggregation, iron accumulation, and mitochondrial dysfunction plague nigral neurons, yet the events underlying iron accumulation are poorly understood. Elevated intracellular iron concentrations up-regulate ferritin expression, an iron storage protein that provides cytoprotection against redox stress. The lysosomal degradation pathway, autophagy, can release iron from ferritin stores to facilitate its trafficking in a process termed ferritinophagy. Aggregated …

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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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Would New Sars-Cov-2 Variants Change The War Against Covid-19?, Elrashdy M. Redwan, Fatma Elrashdy, Alaa A.A. Aljabali, Wagner Baetas-Da-Cruz, Debmalya Barh, Adam M. Brufsky, Sk. Sarif Hassan, Kenneth Lundstrom, Ángel Serrano-Aroca, Kazuo Takayama, Murtaza M. Tambuwala, Bruce D. Uhal, Vladimir N. Uversky Jan 2022

Would New Sars-Cov-2 Variants Change The War Against Covid-19?, Elrashdy M. Redwan, Fatma Elrashdy, Alaa A.A. Aljabali, Wagner Baetas-Da-Cruz, Debmalya Barh, Adam M. Brufsky, Sk. Sarif Hassan, Kenneth Lundstrom, Ángel Serrano-Aroca, Kazuo Takayama, Murtaza M. Tambuwala, Bruce D. Uhal, Vladimir N. Uversky

Molecular Medicine Faculty Publications

The scientific, private, and industrial sectors use a wide variety of technological platforms available to achieve protection against SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), including vaccines. However, the virus evolves continually into new highly virulent variants, which might overcome the protection provided by vaccines and may re-expose the population to infections. Mass vaccinations should be continued in combination with more or less mandatory non-pharmaceutical interventions. Therefore, the key questions to be answered are: (i) How to identify the primary and secondary infections of SARS-CoV-2? (ii) Why are neutralizing antibodies not long-lasting in both cases of natural infections and post-vaccinations? …

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Intrinsic Disorder In Bap1 And Its Association With Uveal Melanoma, Mak B. Djulbegovic, David J. Taylor, Vladimir N. Uversky, Anat Galor, Carol L. Shields, Carol L. Karp Jan 2022

Intrinsic Disorder In Bap1 And Its Association With Uveal Melanoma, Mak B. Djulbegovic, David J. Taylor, Vladimir N. Uversky, Anat Galor, Carol L. Shields, Carol L. Karp

Molecular Medicine Faculty Publications

Background: Specific subvariants of uveal melanoma (UM) are associated with increased rates of metastasis compared to other subvariants. BRCA1 (BReast CAncer gene 1)-associated protein-1 (BAP1) is encoded by a gene that has been linked to aggressive behavior in UM. Methods: We evaluated BAP1 for the presence of intrinsically disordered protein regions (IDPRs) and its protein–protein interactions (PPI). We evaluated specific sequence-based features of the BAP1 protein using a set of bioinformatic databases, predictors, and algorithms. Results: We show that BAP1’s structure contains extensive IDPRs as it is highly enriched in proline residues (the most disordered amino acid; p-value < 0.05), the average percent of predicted disordered residues (PPDR) was 57.34%, and contains 9 disorder-based binding sites (ie. molecular recognition features (MoRFs)). BAP1’s intrinsic disorder allows it to engage in a complex PPI network with at least 49 partners (p-value < 1.0 × 10−16). Conclusion: These findings show that BAP1 contains IDPRs and an intricate PPI network. Mutations in UM that are associated with the BAP1 gene may alter the function of the IDPRs embedded into its structure. These findings develop the understanding of UM and may provide a target for potential novel therapies to treat this aggressive neoplasm.

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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. …

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A Study On The Nature Of Sars-Cov-2 Using The Shell Disorder Models: Reproducibility, Evolution, Spread, And Attenuation, Gerard Kian-Meng Goh, A. Keith Dunker, James A. Foster, Vladimir N. Uversky Jan 2022

A Study On The Nature Of Sars-Cov-2 Using The Shell Disorder Models: Reproducibility, Evolution, Spread, And Attenuation, Gerard Kian-Meng Goh, A. Keith Dunker, James A. Foster, Vladimir N. Uversky

Molecular Medicine Faculty Publications

The basic tenets of the shell disorder model (SDM) as applied to COVID-19 are that the harder outer shell of the virus shell (lower PID—percentage of intrinsic disorder—of the membrane protein M, PIDM) and higher flexibility of the inner shell (higher PID of the nucleocapsid protein N, PIDN) are correlated with the contagiousness and virulence, respectively. M protects the virion from the anti-microbial enzymes in the saliva and mucus. N disorder is associated with the rapid replication of the virus. SDM predictions are supported by two experimental observations. The first observation demonstrated lesser and greater presence of the Omicron particles …

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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.

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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.

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