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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 2018 Chapman University

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 ...


Allostatic Load Biomarker Associations With Depressive Symptoms Vary Among Us Black And White Women And Men, Ganga Bey, William M. Jesdale, Christine M. Ulbricht, Eric O. Mick, Sharina D. Person 2018 University of Massachusetts Medical School

Allostatic Load Biomarker Associations With Depressive Symptoms Vary Among Us Black And White Women And Men, Ganga Bey, William M. Jesdale, Christine M. Ulbricht, Eric O. Mick, Sharina D. Person

Open Access Articles

The prevalence and severity of depression differ in women and men and across racial groups. Psychosocial factors such as chronic stress have been proposed as contributors, but causes of this variation are not fully understood. Allostatic load, a measure of the physiological burden of chronic stress, is known to be associated with depression. Using data from the National Health and Nutrition Examination Survey 2005(-)2010, we examined the associations of nine allostatic load biomarkers with depression among US black and white adults aged 18(-)64 years (n = 6431). Depressive symptoms were assessed using the Patient Health Questionaire-9; logistic models estimated ...


Polyrotaxane Variants And Their Effects On The Cholesterol Efflux In Patients Suffering From Niemann Pick Type C, Sydney Smith, Zach Struzik, David Thompson 2018 Purdue University

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 ...


Alpha-Amino Methylation And Acetylation Are Novel Regulators Of Myl9 Function., Christopher David Nevitt 2018 University of Louisville

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 ...


Investigation Of Hnf-1b As A Diagnostic Biomarker For Pancreatic Ductal Adenocarcinoma, Michelle X. Yang, Ryan F. Coates, Abiy Ambaye, Juli-Anne Gardner, Richard Zubarick, Yuan Gao, Joan Skelly, James G. Liu, Mari Mino-Kenudson 2018 University of Massachusetts Medical School

Investigation Of Hnf-1b As A Diagnostic Biomarker For Pancreatic Ductal Adenocarcinoma, Michelle X. Yang, Ryan F. Coates, Abiy Ambaye, Juli-Anne Gardner, Richard Zubarick, Yuan Gao, Joan Skelly, James G. Liu, Mari Mino-Kenudson

Open Access Articles

Background: Diagnosing pancreatic ductal adenocarcinoma (PDAC) in the setting of metastasis with an unknown primary remains very challenging due to the lack of specific biomarkers. HNF-1B has been characterized as an important transcription factor for pancreatic development and was reported as a biomarker for clear cell subtype of PDAC.

Methods: To investigate the diagnostic role of HNF-1B for PDAC, we used tissue microarray (TMA) and immunohistochemistry (IHC) to characterize HNF-1B expression in a large cohort of carcinomas, including 127 primary PDACs, 47 biliary adenocarcinomas, 17 metastatic PDACs, and 231 non-pancreaticobiliary carcinomas.

Results: HNF-1B was expressed in 107 of 127 (84 ...


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 2018 Chapman University

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 ...


The N-Terminal Region Of Photocleavable Peptides That Bind Hla-Dr1 Determines The Kinetics Of Fragment Release, Maria P. Negroni, Lawrence J. Stern 2018 University of Massachusetts Medical School

The N-Terminal Region Of Photocleavable Peptides That Bind Hla-Dr1 Determines The Kinetics Of Fragment Release, Maria P. Negroni, Lawrence J. Stern

Open Access Articles

Major Histocompatibility Complex class II (MHC-II) molecules bind peptides and present them to receptors on CD4+ T cells as part of the immune system's surveillance of pathogens and malignancy. In the absence of peptide, MHC-II equilibrates between peptide-receptive and peptide-averse conformations. The conversion between these forms has been postulated to be important in regulating cellular antigen presentation but has been difficult to study. In order to generate the MHC-II molecule HLA-DR1 in the peptide-receptive form, we designed and tested a series of photocleavable peptides that included the UV-sensitive 3-amino-3-(2-nitrophenyl)-propionate amino acid analog. They were intended to bind ...


Radical Social Ecology As Deep Pragmatism: A Call To The Abolition Of Systemic Dissonance And The Minimization Of Entropic Chaos, Arielle Brender 2018 Fordham University

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 ...


The Regulation Of Dna Methylation In Mammalian Development And Cancer, Nicolas Veland 2018 The University of Texas M D Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

The Regulation Of Dna Methylation In Mammalian Development And Cancer, Nicolas Veland

UT GSBS 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 ...


Micro Rnas From Dna Viruses Are Found Widely In Plasma In A Large Observational Human Population, Milka Koupenova-Zamor, Eric O. Mick, Heather A. Corkrey, Tianxiao Huan, Lauren Clancy, Ravi Shah, Emelia J. Benjamin, Daniel Levy, Evelyn A. Kurt-Jones, Kahraman Tanriverdi, Jane E. Freedman 2018 University of Massachusetts Medical School

Micro Rnas From Dna Viruses Are Found Widely In Plasma In A Large Observational Human Population, Milka Koupenova-Zamor, Eric O. Mick, Heather A. Corkrey, Tianxiao Huan, Lauren Clancy, Ravi Shah, Emelia J. Benjamin, Daniel Levy, Evelyn A. Kurt-Jones, Kahraman Tanriverdi, Jane E. Freedman

Open Access Articles

Viral infections associate with disease risk and select families of viruses encode miRNAs that control an efficient viral cycle. The association of viral miRNA expression with disease in a large human population has not been previously explored. We sequenced plasma RNA from 40 participants of the Framingham Heart Study (FHS, Offspring Cohort, Visit 8) and identified 3 viral miRNAs from 3 different human Herpesviridae. These miRNAs were mostly related to viral latency and have not been previously detected in human plasma. Viral miRNA expression was then screened in the plasma of 2763 participants of the remaining cohort utilizing high-throughput RT-qPCR ...


Antibiotic Residues In Milk From Three Popular Kenyan Milk Vending Machines, Amos Kosgey, Anakalo Shitandi, Jason W. Marion 2018 Eastern Kentucky University

Antibiotic Residues In Milk From Three Popular Kenyan Milk Vending Machines, Amos Kosgey, Anakalo Shitandi, Jason W. Marion

EKU Faculty and Staff Scholarship

Milk vending machines (MVMs) are growing in popularity in Kenya and worldwide. Milk vending machines dispense varying quantities of locally sourced, pasteurized milk. The Kenya Dairy Board has a regulatory framework, but surveillance is weak because of several factors. Milk vending machines’ milk is not routinely screened for antibiotics, thereby increasing potential for antibiotic misuse. To investigate, a total of 80 milk samples from four commercial providers (N = 25), street vendors (N = 21), and three MVMs (N = 34) were collected and screened in Eldoret, Kenya. Antibiotic residue surveillance occurred during December 2016 and January 2017 using Idexx SNAP tests for ...


The Biologics Price Competition And Innovation Act: Is A Generic Market For Biologics Attainable?, Kasey E. Koballa 2018 College of William & Mary Law School

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 ...


Prognostic Role Of Elevated Mir-24-3p In Breast Cancer And Its Association With The Metastatic Process, Alireza Khodadadi-Jamayran, Betul Akgol-Oksuz, Yelena Afanasyeva, Adriana Heguy, Marae Thompson, Karina Ray, Ariadna Giro-Perafita, Irma Sanchez, Xifeng Wu, Debu Tripathy, Anne Zeleniuch-Jacquotte, Aristotelis Tsirigos, Francisco J. Esteva 2018 New York University

Prognostic Role Of Elevated Mir-24-3p In Breast Cancer And Its Association With The Metastatic Process, Alireza Khodadadi-Jamayran, Betul Akgol-Oksuz, Yelena Afanasyeva, Adriana Heguy, Marae Thompson, Karina Ray, Ariadna Giro-Perafita, Irma Sanchez, Xifeng Wu, Debu Tripathy, Anne Zeleniuch-Jacquotte, Aristotelis Tsirigos, Francisco J. Esteva

Open Access Articles

MicroRNAs have been shown to play important roles in breast cancer progression and can serve as biomarkers. To assess the prognostic role of a panel of miRNAs in breast cancer, we collected plasma prospectively at the time of initial diagnosis from 1,780 patients with stage I-III breast cancer prior to definitive treatment. We identified plasma from 115 patients who subsequently developed distant metastases and 115 patients without metastatic disease. Both groups were matched by: age at blood collection, year of blood collection, breast cancer subtype, and stage. The median follow up was 3.4 years (range, 1-9 years). We ...


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 2018 Tulane University, New Orleans, LA, USA

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 ...


Deconvolution Of Subcellular Protrusion Heterogeneity And The Underlying Actin Regulator Dynamics From Live Cell Imaging, Chuangqi Wang, Hee June Choi, Sung-Jin Kim, Aesha Desai, Namgyu Lee, Dohoon Kim, Yongho Bae, Kwonmoo Lee 2018 Worcester Polytechnic Institute

Deconvolution Of Subcellular Protrusion Heterogeneity And The Underlying Actin Regulator Dynamics From Live Cell Imaging, Chuangqi Wang, Hee June Choi, Sung-Jin Kim, Aesha Desai, Namgyu Lee, Dohoon Kim, Yongho Bae, Kwonmoo Lee

University of Massachusetts Medical School Faculty Publications

Cell protrusion is morphodynamically heterogeneous at the subcellular level. However, the mechanistic understanding of protrusion activities is usually based on the ensemble average of actin regulator dynamics at the cellular or population levels. Here, we establish a machine learning-based computational framework called HACKS (deconvolution of Heterogeneous Activity Coordination in cytosKeleton at a Subcellular level) to deconvolve the subcellular heterogeneity of lamellipodial protrusion in migrating cells. HACKS quantitatively identifies distinct subcellular protrusion phenotypes from highly heterogeneous protrusion activities and reveals their underlying actin regulator dynamics at the leading edge. Furthermore, it can identify specific subcellular protrusion phenotypes susceptible to pharmacological perturbation ...


Effect Of Energy Metabolism On Nf-Kb Activity In Ovarian Cancer, Simren K. Bagri 2018 Virginia Commonwealth University

Effect Of Energy Metabolism On Nf-Kb Activity In Ovarian Cancer, Simren K. Bagri

Undergraduate Research 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 2018 Chapman University

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 ...


Nicotine Administration And Withdrawal And Its Effect On Sleep Latency, Relevant Sleep Variables, And Endogenous Corticosterone Levels In Mice, Vishnu Iyer 2018 University of Colorado, Boulder

Nicotine Administration And Withdrawal And Its Effect On Sleep Latency, Relevant Sleep Variables, And Endogenous Corticosterone Levels In Mice, Vishnu Iyer

Undergraduate Honors Theses

NREM and REM sleep have shown an exceptional importance in controlling various cognitive functions (Brown et al, 2012), and disruption of such sleep states can cause mental and physical impairments (Christie et al, 2008). Disruptions in sleep stages (Wakefulness, REM, NREM) can be identified via EEG recordings in mice without much interference (Mckenna et al, 2008). Circadian Rhythm, hormonal markers, and stress all affect the duration, intensity and timing of these sleep stages (Brown et al, 2004; Veasey et al 2004; Christie et al, 2008). One cohort of mice (n=7) underwent a baseline condition (BL), a nicotine administration condition ...


Novel Therapeutic Strategies For Treatment Of Castration-Resistant Prostate Cancer, Matthew A. Ingersoll 2017 University of Nebraska Medical Center

Novel Therapeutic Strategies For Treatment Of Castration-Resistant Prostate Cancer, Matthew A. Ingersoll

Theses & Dissertations

Prostate cancer (PCa) remains the most commonly diagnosed solid tumor and is the third leading cause of cancer-related death in United States men. While androgen deprivation therapy is the current standard-of-care treatment for metastatic PCa, most patients eventually relapse and develop castration-resistant (CR) tumors, for which there is currently no effective treatment. Therefore, synthesis of novel therapeutic agents and identification of alternative target proteins are necessary to improve treatment. Herein, I investigate the efficacy of novel imidazopyridine and statin derivatives as alternative therapeutic compounds. These molecules not only inhibit androgen receptor signaling, but also block activation of the AKT axis ...


Habituation And Dishabituation In The Olfactory Bulb: From Neural Responses To Behavior, Mary Cameron Ogg 2017 University of Tennessee Health Science Center

Habituation And Dishabituation In The Olfactory Bulb: From Neural Responses To Behavior, Mary Cameron Ogg

Theses and Dissertations (ETD)

Habituation and dishabituation modulate the neural resources and behavioral significance allocated to incoming stimuli across the sensory systems. The purpose of the research presented in this dissertation was to characterize these processes in the mouse olfactory bulb (OB) and to determine if OB acetylcholine (ACh) has a role in physiological and behavioral olfactory dishabituation. Calcium imaging was used to determine the timecourse and magnitude of habituation in different parts of the OB during and after a prolonged odor presentation. Widefield imaging of the dendritic, or glomerular, response of OB output cells demonstrated that prolonged odor input habituates glomerular responses during ...


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