Life Sciences Commons^™

A Novel Non‑Selective Atypical Pkc Agonist Could Protect Neuronal Cell Line From A Β ‑Oligomer Induced Toxicity By Suppressing A Β Generation, Dongmei Zou, Qian Li, Wenyang Pan, Peng Chen, Miao Sun, Xiaofeng Bao

Publications and Research

Atypical protein kinase C (aPKCs) serve key functions in embryonic development by regulating apical-basal polarity. Previous studies have shed light on their roles during adulthood, especially in the development of Alzheimer's disease (AD). Although the crystal structure of PKCι has been resolved, an agonist of aPKCs remains to be discovered. In the present study, by using the Discovery Studio program and LibDock methodology, a small molecule library (K66-X4436 KINA Set) of compounds were screened for potential binding to PKCι. Subsequently, the computational docking results were validated using affinity selection-mass spectrometry, before in vitro kinase activity was used to determine the …

Botanicals As Prospective Agents Against Sars-Cov-2 Virus, Vyacheslav Dushenkov, Anna Dushenkov

Publications and Research

The COVID-19 high morbidity and mortality resulted in a worldwide healthcare emergency that triggered accelerated and amplified efforts in the relevant areas of health sciences research and practice. Purpose: To assess the potential role of botanicals as therapeutic agents against the SARS-CoV-2 virus. Methods: This narrative review examined the potential role of botanicals as therapeutic agents against the SARS-CoV-2 virus based on the references limited to the English language and published up to February 2022 and retrieved from common academic search engines using multiple keywords and their combinations. The scientific names of plant species were confirmed using World Flora Online …

Insights Into Using Plants In Management Of Viral Diseases., Vyacheslav Dushenkov, Anna Dushenkov

Publications and Research

Botanical therapeutics possess a unique potential in the treatment of viral diseases. The pharmacological base and clinical use of botanical therapeutics have been extensively reviewed. The mode of action(s) may be built either on the direct interference with the virus's ability to enter human cells, virus replication, or exerting immune-modulatory and anti-inflammatory effects. The adjuvant treatment with botanical therapeutics has the potential to result in advances in symptom resolution, decrease in disease burden and shortening its duration.

Type Vi Secretion System Mutations Reduced Competitive Fitness Of Classical Vibrio Cholerae Biotype, Benjamin Kostiuk, Francis J. Santoriello, Laura Diaz-Satizabal, Fabiana Bisaro, Kyung-Jo Lee, Anna N. Dhody, Daniele Provenzano, Daniel Unterweger, Stefan Pukatzki

Publications and Research

The gram-negative bacterium Vibrio cholerae is the causative agent of the diarrhoeal disease cholera and is responsible for seven recorded pandemics. Several factors are postulated to have led to the decline of 6th pandemic classical strains and the rise of El Tor biotype V. cholerae, establishing the current 7th pandemic. We investigated the ability of classical V. cholerae of the 2nd and 6th pandemics to engage their type six secretion system (T6SS) in microbial competition against non-pandemic and 7th pandemic strains. We report that classical V. cholerae underwent sequential mutations in T6SS genetic determinants that initially exposed 2nd pandemic strains …

The Temperature-Dependent Conformational Ensemble Of Sars-Cov-2 Main Protease (Mpro), Ali Ebrahim, Blake T. Riley, Desigan Kumaran, Babak Andi, Martin R. Fuchs, Sean Mcsweeney, Daniel A. Keedy

Publications and Research

The COVID-19 pandemic, instigated by the SARS-CoV-2 coronavirus, continues to plague the globe. The SARS-CoV-2 main protease, or M^pro, is a promising target for development of novel antiviral therapeutics. Previous X-ray crystal structures of M^pro were obtained at cryogenic temperature or room temperature only. Here we report a series of high-resolution crystal structures of unliganded M^pro across multiple temperatures from cryogenic to physiological, and another at high humidity. We interrogate these datasets with parsimonious multiconformer models, multi-copy ensemble models, and isomorphous difference density maps. Our analysis reveals a temperature-dependent conformational landscape for M^pro, including …

Intangible Cultural Heritage: A Benefit To Climate-Displaced And Host Communities, Gül Aktürk, Martha B. Lerski

Publications and Research

Climate change is borderless, and its impacts are not shared equally by all communities. It causes an imbalance between people by creating a more desirable living environment for some societies while erasing settlements and shelters of some others. Due to floods, sea level rise, destructive storms, drought, and slow-onset factors such as salinization of water and soil, people lose their lands, homes, and natural resources. Catastrophic events force people to move voluntarily or involuntarily. The relocation of communities is a debatable climate adaptation measure which requires utmost care with human rights, ethics, and psychological well-being of individuals upon the issues …

When The Pandemic Opts For The Lockdown: Secretion System Evolution In The Cholera Bacterium, Francis J. Santoriello, Stefan Pukatzki

Publications and Research

Vibrio cholerae, the causative agent of the diarrheal disease cholera, is a microbe capable of inhabiting two different ecosystems: chitinous surfaces in brackish, estuarine waters and the epithelial lining of the human gastrointestinal tract. V. cholerae defends against competitive microorganisms with a contact-dependent, contractile killing machine called the type VI secretion system (T6SS) in each of these niches. The T6SS resembles an inverted T4 bacteriophage tail and is used to deliver toxic effector proteins into neighboring cells. Pandemic strains of V. cholerae encode a unique set of T6SS effector proteins, which may play a role in pathogenesis or pandemic …

Pandemic Vibrio Cholerae Shuts Down Site-Specific Recombination To Retain An Interbacterial Defence Mechanism, Francis J. Santoriello, Lina Michel, Daniel Unterweger, Stefan Pukatzki

Publications and Research

Vibrio cholerae is an aquatic microbe that can be divided into three subtypes: harmless environmental strains, localised pathogenic strains, and pandemic strains causing global cholera outbreaks. Each type has a contact-dependent type VI secretion system (T6SS) that kills neighbouring competitors by translocating unique toxic effector proteins. Pandemic isolates possess identical effectors, indicating that T6SS effectors may affect pandemicity. Here, we show that one of the T6SS gene clusters (Aux3) exists in two states: a mobile, prophage-like element in a small subset of environmental strains, and a truncated Aux3 unique to and conserved in pandemic isolates. Environmental Aux3 can be readily …

Understanding Of Aerosol Transmission Of Covid 19 In Indoor Environments, Adama Barro, Cathal O'Toole, Jacob S. Lopez, Matthew Quinones, Sherene Moore

Publications and Research

Our reason for discussing severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) or 2019 novel corona virus (Covid-19), is to understand its aerosol transmission characteristics in indoor spaces and to mitigate further spread of this disease by designing a new HVAC system. The problem that we are tackling is the spread of covid-19 droplets through aerosol transmission by looking at potential engineering solutions to the existing HVAC systems. The purpose is to eradicate the spread of the COVID-19 by testing indoor spaces in an effort to understand the effectiveness of ventilation controls. We believe that scientists and engineers have not …

Antibacterial, Antifungal, Antioxidant Activity And Polyphenol Content Of Aerial Parts And Bulbs Of Allium Schugnanicum., Saidbeg Satorov, F. Mirzoeva, Sh. Kurbonbekova, Sh. Satorov, M. Vakhidova, Vyacheslav Dushenkov

Publications and Research

Objective: То study of antibacterial, antifungal and antioxidant activity, and content of polyphenols in the bulb and aerial parts of an endemic species of onion A. schugnanicum. Methods: An ethanol-based extract was prepared from fresh plants. Total polyphenolic content (Folin) and ABTS antioxidant capacity assays were used to characterized extracts. Extracts obtained from bulbs, peduncle, and seeds demonstrated antibacterial activity against the reference Staphylococcus aureus (ATCC 4929), Pseudomonas aeruginosa (ATCC 4930) and Klebsiella pneumoniae (ATCC 4927) strains, as well as against the hospital strains of the same types of bacteria, i.e. strains isolated from inpatient surgical patients. Results: The study …

Genetic Determinants Of Telomere Length In African American Youth, Andrew M. Zeiger, Marquitta J. White, Celeste Eng, Sam S. Oh, Jonathan Witonsky, Pagé C. Goddard, Maria G. Contreras, Jennifer R. Elhawary, Donglei Hu, Angel C. Y. Mak, Eunice Y. Lee, Kevin L. Keys, Lesly-Anne Samedy, Oona Risse Adams, Joaquín Magaña, Scott Huntsman, Sandra Salazar, Adam Davis, Kelley Meade, Emerita Brigino-Buenaventura, Michael A. Lenoir, Harold J. Farber, Kirsten Bibbins-Domingo, Luisa N. Borrell, Esteban G. Burchard

Publications and Research

Telomere length (TL) is associated with numerous disease states and is affected by genetic and environmental factors. However, TL has been mostly studied in adult populations of European or Asian ancestry. These studies have identified 34 TL-associated genetic variants recently used as genetic proxies for TL. The generalizability of these associations to pediatric populations and racially diverse populations, specifically of African ancestry, remains unclear. Furthermore, six novel variants associated with TL in a population of European children have been identified but not validated. We measured TL from whole blood samples of 492 healthy African American youth (children and adolescents between …

Plasmid Diversity And Phylogenetic Consistency In The Lyme Disease Agent Borrelia Burgdorferi, Sherwood R. Casjens, Eddie B. Gilcrease, Marija Vujadinovic, Emmanuel F. Mongodin, Benjamin J. Luft, Steven E. Schutzer, Claire M. Fraser, Wei-Gang Qiu

Publications and Research

Background: Bacteria from the genus Borrelia are known to harbor numerous linear and circular plasmids. We report here a comparative analysis of the nucleotide sequences of 236 plasmids present in fourteen independent isolates of the Lyme disease agent B. burgdorferi.

Results: We have sequenced the genomes of 14 B. burgdorferi sensu stricto isolates that carry a total of 236 plasmids. These individual isolates carry between seven and 23 plasmids. Their chromosomes, the cp26 and cp32 circular plasmids, as well as the lp54 linear plasmid, are quite evolutionarily stable; however, the remaining plasmids have undergone numerous non-homologous and often duplicative recombination …

Electro-Chemotactic Fields Induce Cooperative Movement Of Cns Cells, Shawn Mishra, Stephen Redenti, Maribel Vazquez

Publications and Research

Vision loss in adults with Age Related Macular Degeneration (AMD) is attributed to damage of retinal photoreceptor cells that initiate vision by absorbing light. Mouse models have suggested that transplantation of precursor cells may be a novel approach to restore vision. This project uses a combination of electrotactic and chemotactic stimuli to promote and guide CNS cell migration within a microdevice model.

Insights Into The Molecular Roles Of Heparan Sulfate Proteoglycans (Hspgs-Syndecans) In Autocrine And Paracrine Growth Factor Signaling In The Pathogenesis Of Hodgkin's Lymphoma, Rajendra Ghardbaran

Publications and Research

Syndecans (SDC, SYND) comprise a group of four structurally related type 1 transmembrane heparan sulfate proteoglycans (HSPGs) that play important roles in tumorigenic processes. SDCs exert signaling via their protein cores and their conserved transmembrane and cytoplasmic domains or by forming complexes with growth factors (GFs). In classical Hodgkin's lymphoma (cHL), a lymphoid neoplasm of predominantly B cell origin, SDC1 and SDC4 are the active SDCs, and a number of GF (vascular endothelial growth factor, fibroblast growth factor, etc.) signaling pathways have been studied. However, despite extensive pre-clinical and clinical research on SDC-mediated GF signaling in many cancer types, there …

Mechanism Of Action And Applications Of Interleukin 24 In Immunotherapy, Leah Persaud, Dayenny De Jesus, Oliver Brannigan, Maria Richiez-Paredes, Jeannette Huaman, Giselle Alvarado, Linda Riker, Gissete Mendez, Jordan Dejoie, Moira Sauane

Publications and Research

Interleukin 24 (IL-24) is an important pleiotropic immunoregulatory cytokine, whose gene is located in human chromosome 1q32-33. IL-24’s signaling pathways have diverse biological functions related to cell differentiation, proliferation, development, apoptosis, and inflammation, placing it at the center of an active area of research. IL-24 is well known for its apoptotic effect in cancer cells while having no such effect on normal cells. IL-24 can also be secreted by both immune and non-immune cells. Downstream effects of IL-24, after binding to the IL-20 receptor, can occur dependently or independently of the JAK/STAT signal transduction pathway, which is classically involved in …

Pvt1 Exon 9: A Potential Biomarker Of Aggressive Prostate Cancer?, Adeodat Ilboudo, Jyoti Chouhan, Brian K. Mcneil, Joseph R. Osborne, Olorunseun O. Ogunwobi

Publications and Research

Prostate cancer (PCa) is the most commonly diagnosed cancer as well as the greatest source of cancer-related mortality in males of African ancestry (MoAA). Interestingly, this has been shown to be associated with single nucleotide polymorphisms around regions 2 and 3 of the 8q24 human chromosomal region. The non-protein coding gene locus Plasmacytoma Variant Translocation 1 (PVT1) is located at 8q24 and is overexpressed in PCa and, therefore, is also a candidate biomarker to explain the well-known disparity in this group. PVT1 has at least 12 exons that make separate transcripts which may have different functions, all of which are …

Common Cell Shape Evolution Of Two Nasopharyngeal Pathogens, Frédéric J. Veyrier, Nicolas Biais, Pablo Morales, Nouria Belkacem, Cyril Guilhen, Sylvia Ranjeva, Odile Sismeiro, Gérard Péhau-Arnaudet, Eduardo P. Rocha, Catherine Werts, Muhamed-Kheir Taha, Ivo G. Boneca

Publications and Research

Respiratory infectious diseases are the third cause of worldwide death. The nasopharynx is the portal of entry and the ecological niche of many microorganisms, of which some are pathogenic to humans, such as Neisseria meningitidis and Moraxella catarrhalis. These microbes possess several surface structures that interact with the actors of the innate immune system. In our attempt to understand the past evolution of these bacteria and their adaption to the nasopharynx, we first studied differences in cell wall structure, one of the strongest immune-modulators. We were able to show that a modification of peptidoglycan (PG) composition (increased proportion of pentapeptides) …

Lesion-Specific Immune Response In Granulomas Of Patients With Pulmonary Tuberculosis: A Pilot Study, Selvakumar Subbian, Liana Tsenova, Mi-Jeong Kim, Helen C. Wainwright, Annalie Visser, Nirmalya Bandyopadhyay, Joel S. Bader, Petros C. Karakousis, Gabriele B. Murrmann, Linda-Gail Bekker, David G. Russell, Gilla Kaplan

Publications and Research

The formation and maintenance of granulomas is central to the host response to Mycobacterium tuberculosis (Mtb) infection. It is widely accepted that the lungs of patients with tuberculosis (TB) usually contain multiple infection foci, and that the granulomas evolve and differentiate independently, resulting in considerable heterogeneity. Although gene expression profiles of human blood cells have been proposed as biomarkers of Mtb infection and/or active disease, the immune profiles of discrete lesion types has not been studied extensively. Using histology, immunopathology and genome-wide transcriptome analysis, we explored the immunological profile of human lung TB granulomas. We show that although the different …

Atypical Multisensory Integration In Niemann-Pick Type C Disease – Towards Potential Biomarkers, Gizely N. Andrade, Sophie Molholm, John S. Butler, Alice Brown Brandwein, Steven U. Walkley, John J. Foxe

Publications and Research

Background: Niemann-Pick type C (NPC) is an autosomal recessive disease in which cholesterol and glycosphingolipids accumulate in lysosomes due to aberrant cell-transport mechanisms. It is characterized by progressive and ultimately terminal neurological disease, but both pre-clinical studies and direct human trials are underway to test the safety and efficacy of cholesterol clearing compounds, with good success already observed in animal models. Key to assessing the effectiveness of interventions in patients, however, is the development of objective neurobiological outcome measures. Multisensory integration mechanisms present as an excellent candidate since they necessarily rely on the fidelity of long-range neural connections between the …

Chagas Disease In The 21st Century: A Public Health Success Or An Emerging Threat?, Kevin M. Bonney

Publications and Research

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a major public health burden in Latin America and a potentially serious emerging threat to a number of countries throughout the world. Although public health programs have significantly reduced the prevalence of Chagas disease in Latin America in recent decades, the number of infections in the United States and non-endemic countries in Europe and the Western Pacific Region continues to rise. Moreover, there is still no vaccine or highly effective cure available for the approximately 10 million people currently infected with T. cruzi, a third of which will develop potentially …

Candidatus Syngnamydia Venezia, A Novel Member Of The Phylum Chlamydiae From The Broad Nosed Pipefish, Syngnathustyphle Typhle, Alexander Fehr, Elisabeth Walther, Heike Schmidt-Posthaus, Lisbeth Nufer, Anthony B. Wilson, Miroslav Svercel, Denis Richter, Helmut Segner, Andreas Pospischil, Lloyd Vaughan

Publications and Research

Chlamydia are obligate intracellular bacteria and important pathogens of humans and animals. Chlamydia-related bacteria are also major fish pathogens, infecting epithelial cells of the gills and skin to cause the disease epitheliocystis. Given the wide distribution, ancient origins and spectacular diversity of bony fishes, this group offers a rich resource for the identification and isolation of novel Chlamydia. The broad-nosed pipefish (Syngnathus typhle) is a widely distributed and genetically diverse temperate fish species, susceptible to epitheliocystis across much of its range. We describe here a new bacterial species, Candidatus Syngnamydia venezia; epitheliocystis agent of S. typhle and close relative to …

Polyglutamine Toxicity Is Controlled By Prion Composition And Gene Dosage In Yeast, He Gong, Nina V. Romanova, Kim D. Allen, Pavithra Chandramowlishwaran, Kavita Gokhale, Gary P. Newnam, Piotr Miceczkowski, Michael Y. Sherman, Yury O. Chernoff

Publications and Research

Polyglutamine expansion causes diseases in humans and other mammals. One example is Huntington’s disease. Fragments of human huntingtin protein having an expanded polyglutamine stretch form aggregates and cause cytotoxicity in yeast cells bearing endogenous QN-rich proteins in the aggregated (prion) form. Attachment of the proline(P)-rich region targets polyglutamines to the large perinuclear deposit (aggresome). Aggresome formation ameliorates polyglutamine cytotoxicity in cells containing only the prion form of Rnq1 protein. Here we show that expanded polyglutamines both with (poly-QP) or without (poly-Q) a P-rich stretch remain toxic in the presence of the prion form of translation termination (release) factor Sup35 (eRF3). …

Meiotic And Mitotic Phenotypes Conferred By The Blm1-1 Mutation In Saccharomyces Cerevisiae And Msh4 Suppression Of The Bleomycin Hypersusceptibility, Georgia Anyatonwu, Ediberto Garcia, Ajay Pramanik, Marie Powell, Carol Wood Moore

Publications and Research

Oxidative damage can lead to a number of diseases, and can be fatal. The blm1-1 mutation of Saccharomyces cerevisiae confers hypersusceptibility to lethal effects of the oxidative, anticancer and antifungal agent, bleomycin. For the current report, additional defects conferred by the mutation in meiosis and mitosis were investigated. The viability of spores produced during meiosis by homozygous normal BLM1/BLM1, heterozygous BLM1/blm1-1, and homozygous mutant blm1-1/blm1-1 diploid strains was studied and compared. Approximately 88% of the tetrads derived from homozygous blm1-1/blm1-1 mutant diploid cells only produced one or two viable spores. In contrast, just one tetrad among all BLM1/BLM1 and BLM1/blm1-1 …