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Articles 1 - 15 of 15
Full-Text Articles in Biological Factors
Escherichia Coli Itat Is A Type Ii Toxin That Inhibits Translation By Acetylating Isoleucyl-Trnaile, Brendan Wilcox, Ilya Osterman, Marina Serebryakova, Dmitry Lukyanov, Ekaterina Komarova, Bridget Gollan, Natalia Morozova, Yuri I Wolf, Kira S Makarova, Sophie Helaine, Petr Sergiev, Svetlana Dubiley, Sergei Borukhov, Konstantin Severinov
Escherichia Coli Itat Is A Type Ii Toxin That Inhibits Translation By Acetylating Isoleucyl-Trnaile, Brendan Wilcox, Ilya Osterman, Marina Serebryakova, Dmitry Lukyanov, Ekaterina Komarova, Bridget Gollan, Natalia Morozova, Yuri I Wolf, Kira S Makarova, Sophie Helaine, Petr Sergiev, Svetlana Dubiley, Sergei Borukhov, Konstantin Severinov
Rowan-Virtua School of Osteopathic Medicine Departmental Research
Prokaryotic toxin-antitoxin (TA) modules are highly abundant and are involved in stress response and drug tolerance. The most common type II TA modules consist of two interacting proteins. The type II toxins are diverse enzymes targeting various essential intracellular targets. The antitoxin binds to cognate toxin and inhibits its function. Recently, TA modules whose toxins are GNAT-family acetyltransferases were described. For two such systems, the target of acetylation was shown to be aminoacyl-tRNA: the TacT toxin targets aminoacylated elongator tRNAs, while AtaT targets the amino acid moiety of initiating tRNAMet. We show that the itaRT gene pair from Escherichia coli …
Recombinant Human Proteoglycan-4 Reduces Phagocytosis Of Urate Crystals And Downstream Nuclear Factor Kappa B And Inflammasome Activation And Production Of Cytokines And Chemokines In Human And Murine Macrophages, Marwa Qadri, Gregory D. Jay, Ling X. Zhang, Wendy Wong, Anthony M. Reginato, Changqi Sun, Tannin A. Schmidt
Recombinant Human Proteoglycan-4 Reduces Phagocytosis Of Urate Crystals And Downstream Nuclear Factor Kappa B And Inflammasome Activation And Production Of Cytokines And Chemokines In Human And Murine Macrophages, Marwa Qadri, Gregory D. Jay, Ling X. Zhang, Wendy Wong, Anthony M. Reginato, Changqi Sun, Tannin A. Schmidt
Pharmacy Faculty Articles and Research
Microbial biofilms are organized communities of cells that are associated with a wide spectrum of resistant and chronic infections that lead to the treatment failure. Accordingly, there is an urgent demand to create novel effective therapeutic drugs that can inhibit biofilm formation with new mechanisms of action to surmount the current escalating resistance. In this study, in silico hybrid model was utilized to develop three novel short linear peptides (4, 5, and 6) with potential biofilm inhibiting activities (scores > 1.0). The peptides were composed of cationic and hydrophobic residues. They were synthesized using solid-phase strategy. Synthesized peptides were purified and …
Polyrotaxane Variants And Their Effects On The Cholesterol Efflux In Patients Suffering From Niemann Pick Type C, Sydney Smith, Zach Struzik, David Thompson
Polyrotaxane Variants And Their Effects On The Cholesterol Efflux In Patients Suffering From Niemann Pick Type C, Sydney Smith, Zach Struzik, David Thompson
The Summer Undergraduate Research Fellowship (SURF) Symposium
Niemann Pick type C disease (NPC) is a rare lysosomal storage disorder characterized by a progressive accumulation of cholesterol in the late endosomal/lysosomes compartment leading to cellular dysfunction and organ failure. Symptoms include ataxia, dysarthria, cognitive dysfunction, and seizures. Although average life expectancy is below 20, there are no FDA approved treatment available making it a serious unmet medical need. Clinical trials with 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) has shown promise in cholesterol normalization within NPC cells. However, HP-beta-CD treatment has been shown to cause ototoxicity in NPC patients at high dosages. Supramolecular complexes known as polyrotaxanes have been synthesized in hopes of …
Alpha-Amino Methylation And Acetylation Are Novel Regulators Of Myl9 Function., Christopher David Nevitt
Alpha-Amino Methylation And Acetylation Are Novel Regulators Of Myl9 Function., Christopher David Nevitt
Electronic Theses and Dissertations
Dysregulation of alpha-amino post-translational modifications (Nα-PTMs) is found in multiple cancers and developmental disorders. However, the exact roles Nα-PTMs play in regulating protein function remain poorly understood. I sought to clarify the role of Nα-methylation and Nα-acetylation in the regulation of Myosin Regulatory Light Chain 9 (MYL9). MYL9 is a key cytoskeletal regulator and transcription factor and is the first protein confirmed to undergo both Nα-methylation and Nα-acetylation. Through this work I revealed novel regulatory features of MYL9, while also presenting a framework by which to understand the coordinated regulation of proteins by Nα-methylation and Nα-acetylation. Nα-PTM selective mutants of …
A V-To-F Substitution In Sk2 Channels Causes Ca2+ Hypersensitivity And Improves Locomotion In A C. Elegans Als Model, Young-Woo Nam, Sabia N. Baskoylu, Dimitris Gazgalis, Razan Orfali, Meng Cui, Anne C. Hart, Miao Zhang
A V-To-F Substitution In Sk2 Channels Causes Ca2+ Hypersensitivity And Improves Locomotion In A C. Elegans Als Model, Young-Woo Nam, Sabia N. Baskoylu, Dimitris Gazgalis, Razan Orfali, Meng Cui, Anne C. Hart, Miao Zhang
Pharmacy Faculty Articles and Research
Small-conductance Ca2+-activated K+ (SK) channels mediate medium afterhyperpolarization in the neurons and play a key role in the regulation of neuronal excitability. SK channels are potential drug targets for ataxia and Amyotrophic Lateral Sclerosis (ALS). SK channels are activated exclusively by the Ca2+-bound calmodulin. Previously, we identified an intrinsically disordered fragment that is essential for the mechanical coupling between Ca2+/calmodulin binding and channel opening. Here, we report that substitution of a valine to phenylalanine (V407F) in the intrinsically disordered fragment caused a ~6 fold increase in the Ca2+ sensitivity of SK2-a channels. This substitution resulted in a novel interaction between …
Radical Social Ecology As Deep Pragmatism: A Call To The Abolition Of Systemic Dissonance And The Minimization Of Entropic Chaos, Arielle Brender
Radical Social Ecology As Deep Pragmatism: A Call To The Abolition Of Systemic Dissonance And The Minimization Of Entropic Chaos, Arielle Brender
Student Theses 2015-Present
This paper aims to shed light on the dissonance caused by the superimposition of Dominant Human Systems on Natural Systems. I highlight the synthetic nature of Dominant Human Systems as egoic and linguistic phenomenon manufactured by a mere portion of the human population, which renders them inherently oppressive unto peoples and landscapes whose wisdom were barred from the design process. In pursuing a radical pragmatic approach to mending the simultaneous oppression and destruction of the human being and the earth, I highlight the necessity of minimizing entropic chaos caused by excess energy expenditure, an essential feature of systems that aim …
Transplantation Of Thioredoxin-1 Exosomes In A Murine Model Of Hind-Limb Ischemia: A Novel Therapeutic Approach, Shubham Kanake
Transplantation Of Thioredoxin-1 Exosomes In A Murine Model Of Hind-Limb Ischemia: A Novel Therapeutic Approach, Shubham Kanake
Honors Scholar Theses
Peripheral artery disease is one of the most prevalent cardiovascular diseases in the United States and worldwide. It is estimated that over 8 million people in the United States are affected with peripheral artery disease, and up to 40% of people over 80 years old may have some degree of the disease. Peripheral artery disease can increase one’s chances for having other cardiovascular co-morbidities such as coronary artery disease, among others. Current interventional strategies are endovascular treatments such as transluminal angioplasty and stenting, or in more advanced cases peripheral artery bypass grafting. Medical interventions focus on managing symptoms and treating …
The Regulation Of Dna Methylation In Mammalian Development And Cancer, Nicolas Veland
The Regulation Of Dna Methylation In Mammalian Development And Cancer, Nicolas Veland
Dissertations and Theses (Open Access)
DNA methylation is an essential epigenetic modification in mammals, as it plays important regulatory roles in multiple biological processes, such as gene transcription, maintenance of chromosomal structure and genomic stability, genomic imprinting, retrotransposon silencing, and X-chromosome inactivation. Dysregulation of DNA methylation is associated with various human diseases. For example, cancer cells usually show global hypomethylation and regional hypermenthylation, which have been implicated in genomic instability and tumor suppressor silencing, respectively. Although great progress has been made in elucidating the biological functions of DNA methylation over the last several decades, how DNA methylation patterns and levels are regulated and dysregulated is …
The Biologics Price Competition And Innovation Act: Is A Generic Market For Biologics Attainable?, Kasey E. Koballa
The Biologics Price Competition And Innovation Act: Is A Generic Market For Biologics Attainable?, Kasey E. Koballa
William & Mary Business Law Review
The Biologics Price Competition and Innovation Act of 2009 (BPCIA) provides an abbreviated approval pathway for biological therapeutic products shown to be biosimilar to an FDA-approved biological reference product. The BPCIA purported to reduce the price of biologics while promoting innovation. In two recent cases, the Federal Circuit interpreted a key provision of the BPCIA requiring an applicant to provide the reference product sponsor with notice 180 days before marketing the product. The Federal Circuit’s interpretation extends the exclusivity period already provided for the reference product sponsor, deterring innovation and price reduction. Thus, the Supreme Court granted certiorari in one …
Simian Virus 40 Large T Antigen As A Model To Test The Efficacy Of Flouroquinolones Against Viral Helicases, Sammer Siddiqui, Muhammad F. Anwar, Sadaf Naeem, Syed Hani Abidi, Shamshad Zarina, Syed Ali
Simian Virus 40 Large T Antigen As A Model To Test The Efficacy Of Flouroquinolones Against Viral Helicases, Sammer Siddiqui, Muhammad F. Anwar, Sadaf Naeem, Syed Hani Abidi, Shamshad Zarina, Syed Ali
Department of Biological & Biomedical Sciences
Simian virus 40 large T-antigen (SV40 LT-Ag) is a 708 amino acid nuclear phosphoprotein. Among many functions of LT-Ag is its ability to perform as an ATPase-helicase, catalyzing the unwinding of viral genome during replication. The LT-Ag has been employed in the studies of helicase structure and function, and has served as a model helicase for the screening of antiviral drugs that target viral helicase. In this study, using in vitro enzyme assays and in silico computer modeling, we screened a batch of 18 fluoroquinolones to assess their potential as antivirals by virtue of their inhibition of the LT-Ag helicase. …
Microrna 1207-3p In Prostate Cancer, Dibash Das
Microrna 1207-3p In Prostate Cancer, Dibash Das
Dissertations, Theses, and Capstone Projects
Prostate cancer (PCa) is the most commonly diagnosed male cancer and the second leading cause of cancer-related death for men in the United States. Understanding the molecular mechanisms involved in progression from the asymptomatic androgen-dependent PCa to the lethal castration resistant prostate cancer (CRPC) is a major challenge. MicroRNAs (miRNAs), are known to be dysregulated in PCa. MicroRNA-1207-3p (miR-1207-3p) is encoded by the non-protein coding gene locus PVT1 on the 8q24 human chromosomal region, an established PCa susceptibility locus. However, the role of miR-1207-3p in PCa is unclear. We have discovered that miR-1207-3p is significantly underexpressed in PCa cell lines …
Elevated L-Lactate Drives Major Cellular Pathologies Associated With Neurodegeneration, Jessica Behnke
Elevated L-Lactate Drives Major Cellular Pathologies Associated With Neurodegeneration, Jessica Behnke
Dissertations, Master's Theses and Master's Reports
Within the past few decades, lactate research has expanded from initial findings deeming lactate as a dead-end metabolic product to recognition of lactate’s role as a potential energy substrate in the CNS. Due to the tight relationship between lactate and energy metabolism, interest in the scientific community has been mounting around associations among metabolic dysregulation, elevated lactate and neurodegenerative states such as Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis, ischemia/reperfusion (AD, PD, ALS, I/R injuries), and physiological aging, however underlying cellular mechanisms and/or facilitators for neuronal degeneration pathologies still remain unknown. Here, we tested several hypotheses that implicate L-lactate to various neurodegenerative …
Effect Of Energy Metabolism On Nf-Kb Activity In Ovarian Cancer, Simren K. Bagri
Effect Of Energy Metabolism On Nf-Kb Activity In Ovarian Cancer, Simren K. Bagri
UROP Posters
NF-kB is a transcription factor involved in cancer cell growth and survival. The activation of NF-kB can be assessed by monitoring phosphorylation of RelA p65 at Ser-536, which is a surrogate of the NF-kB transcription factor activation. The objective of this study was to determine if the loss of ATP leads to NF-kB deficiency and thus, apoptotic cell death of “bad” cells in ovarian cancer cells. The independent variables were metformin (Met), an anti-diabetic medicine, another compound MinB functionally similar to Met and a glucose transporter inhibitor BAY-876. The dependent variables were the resulting effect of Met and MinB on …
Clearance Concepts: Fundamentals And Application To Pharmacokinetic Behavior Of Drugs, Reza Mehvar
Clearance Concepts: Fundamentals And Application To Pharmacokinetic Behavior Of Drugs, Reza Mehvar
Pharmacy Faculty Articles and Research
Clearance concepts were introduced into the pharmacokinetics discipline in the 1970s and since then have played a major role in characterization of the pharmacokinetic behavior of drugs. These concepts are based on the relationship between organ extraction ratio or clearance and physiologic parameters such as the organ blood flow and the intrinsic capability of the eliminating organ to remove the free (unbound) drug from the body. Several theoretical models have been developed, which define these relationships and may be used to predict the effects of changes in the physiological parameters on various pharmacokinetic parameters of drugs, such as drug clearance. …
On The Efficacy Of High-Dose Ascorbic Acid As Anticancer Treatment: A Literature Survey, Florentin Smarandache, Victor Christianto
On The Efficacy Of High-Dose Ascorbic Acid As Anticancer Treatment: A Literature Survey, Florentin Smarandache, Victor Christianto
Branch Mathematics and Statistics Faculty and Staff Publications
Vitamin C (ascorbic acid, ascorbate) has a controversial history in cancer treatment. Emerging evidence indicates that ascorbate in cancer treatment deserves re-examination. As research results concerning ascorbate pharmacokinetics and its mechanisms of action against tumor cells have been published, and as evidence from case studies has continued to mount that ascorbate therapy could be effective if the right protocols were used, interest among physicians and scientists has increased.