Microfilariae Of Brugia Malayi Inhibit The Mtor Pathway And Induce Autophagy In Human Dendritic Cells, 2019 Cedarville University
Microfilariae Of Brugia Malayi Inhibit The Mtor Pathway And Induce Autophagy In Human Dendritic Cells, Prakash Babu Narasimhan, Sasisekhar Bennuru, Zhaojing Meng, Rachel N Cotton, Kathleen R Elliott, Sundar Ganesan, Renee Mcdonald-Fleming, Timothy Veenstra, Thomas B Nutman, Roshanak Tolouei Semnani
Timothy Veenstra, Ph.D.
Immune modulation is a hallmark of patent filarial infection, including suppression of antigen-presenting cell function and downmodulation of filarial antigen-specific T cell responses. The mammalian target of rapamycin (mTOR) signaling pathway has been implicated in immune regulation, not only by suppressing T cell responses but also by regulating autophagy (through mTOR sensing amino acid availability). Global proteomic analysis (liquid chromatography-tandem mass spectrometry) of microfilaria (mf)-exposed monocyte-derived dendritic cells (DC) indicated that multiple components of the mTOR signaling pathway, including mTOR, eIF4A, and eIF4E, are downregulated by mf, suggesting that mf target this pathway for immune modulation in DC. Utilizing ...
Mechanism For Apobec3g Catalytic Exclusion Of Rna And Non-Substrate Dna, 2019 University of Minnesota
Mechanism For Apobec3g Catalytic Exclusion Of Rna And Non-Substrate Dna, William C. Solomon, Wazo Myint, Shurong Hou, Tapan Kanai, Rashmi Tripathi, Nese Kurt Yilmaz, Celia A. Schiffer, Hiroshi Matsuo
Schiffer Lab Publications
The potent antiretroviral protein APOBEC3G (A3G) specifically targets and deaminates deoxycytidine nucleotides, generating deoxyuridine, in single stranded DNA (ssDNA) intermediates produced during HIV replication. A non-catalytic domain in A3G binds strongly to RNA, an interaction crucial for recruitment of A3G to the virion; yet, A3G displays no deamination activity for cytidines in viral RNA. Here, we report NMR and molecular dynamics (MD) simulation analysis for interactions between A3Gctd and multiple substrate or non-substrate DNA and RNA, in combination with deamination assays. NMR ssDNA-binding experiments revealed that the interaction with residues in helix1 and loop1 (T201-L220) distinguishes the binding mode of ...
Development Of A Screening Method For Drugs Of Abuse By Direct Analysis Of Dried Urine Spots Coupled To Mass Spectrometry, 2019 John Jay College of Criminal Justice
Development Of A Screening Method For Drugs Of Abuse By Direct Analysis Of Dried Urine Spots Coupled To Mass Spectrometry, Melanie Goldstein
Fast and easy screening procedures are essential in any forensic toxicology laboratory to differentiate negative samples from presumptive positive cases. Immunoassay techniques, such as enzyme multiplied immunoassay technique (EMIT), are routinely employed as screening procedures. However, these techniques lack specificity (only differentiate group of drugs and not individual compounds) and it is difficult to add new compounds to the panel. Direct analysis of dried urine spots (DUS) by mass spectrometry (MS) offers a novel strategy to overcome these issues. DUS offer an improved storage alternative for biological samples, reducing costs and space requirements. In this work, an original method to ...
Molecular And Structural Mechanism Of Pan-Genotypic Hcv Ns3/4a Protease Inhibition By Glecaprevir, 2019 University of Massachusetts Medical School
Molecular And Structural Mechanism Of Pan-Genotypic Hcv Ns3/4a Protease Inhibition By Glecaprevir, Jennifer Timm, Klajdi Kosovrasti, Mina Henes, Florian Leidner, Shurong Hou, Akbar Ali, Nese Kurt Yilmaz, Celia A. Schiffer
University of Massachusetts Medical School Faculty Publications
Hepatitis C virus (HCV), causative agent of chronic viral hepatitis, infects 71 million people worldwide and is divided into seven genotypes and multiple subtypes with sequence identities between 68 to 82%. While older generation direct-acting antivirals (DAAs) had varying effectiveness against different genotypes, the newest NS3/4A protease inhibitors including glecaprevir (GLE) have pan-genotypic activity. The structural basis for pan-genotypic inhibition and effects of polymorphisms on inhibitor potency were not well known due to lack of crystal structures of GLE-bound NS3/4A or genotypes other than 1. In this study, we determined the crystal structures of NS3/4A from genotypes ...
Poly(Ethylene Glycol)-Based Peptidomimetic "Pegtide" Of Oligo-Arginine Allows For Efficient Sirna Transfection And Gene Inhibition., 2019 Royal College of Surgeons in Ireland
Poly(Ethylene Glycol)-Based Peptidomimetic "Pegtide" Of Oligo-Arginine Allows For Efficient Sirna Transfection And Gene Inhibition., Alan Hibbitts, Aoife M O'Connor, Joanna Mccarthy, Éanna B Forde, Gary Hessman, Caitriona M O'Driscoll, Sally-Ann Cryan, Marc Devocelle
While a wide range of experimental and commercial transfection reagents are currently available, persistent problems remain regarding their suitability for continued development. These include the transfection efficiency for difficult-to-transfect cell types and the risks of decreased cell viability that may arise from any transfection that does occur. Therefore, research is now turning toward alternative molecules that improve the toxicity profile of the gene delivery vector (GDV), while maintaining the transfection efficiency. Among them, cell-penetrating peptides, such as octa-arginine, have shown significant potential as GDVs. Their pharmacokinetic and pharmacodynamic properties can be enhanced through peptidomimetic conversion, whereby a peptide is modified ...
Integration Of Random Forest Classifiers And Deep Convolutional Neural Networks For Classification And Biomolecular Modeling Of Cancer Driver Mutations, Steve Agajanian, Odeyemi Oluyemi, Gennady M. Verkhivker
Mathematics, Physics, and Computer Science Faculty Articles and Research
Development of machine learning solutions for prediction of functional and clinical significance of cancer driver genes and mutations are paramount in modern biomedical research and have gained a significant momentum in a recent decade. In this work, we integrate different machine learning approaches, including tree based methods, random forest and gradient boosted tree (GBT) classifiers along with deep convolutional neural networks (CNN) for prediction of cancer driver mutations in the genomic datasets. The feasibility of CNN in using raw nucleotide sequences for classification of cancer driver mutations was initially explored by employing label encoding, one hot encoding, and embedding to ...
Determination Of Anxiolytic And Antidepressant Medicines In New York City Wastewater Samples, 2019 CUNY John Jay College
Determination Of Anxiolytic And Antidepressant Medicines In New York City Wastewater Samples, Jasmine J. Gayle
Wastewater-based epidemiology (WBE) provides information about a population’s exposure to certain chemical agents, such as drugs of abuse and medicines, by the analysis of human biomarkers, also known as excretion products, in wastewater samples. Although this is a growing field worldwide, mainly in Europe, Oceania, and Asia, limited data from the US are currently available. We developed and validated an analytical method to quantitatively and qualitatively determine the presence of commonly prescribed drugs to treat anxiety (alprazolam, buspirone, clonazepam, lorazepam, and propranolol) and depression (bupropion, citalopram, clomipramine, duloxetine, fluoxetine, imipramine, paroxetine, sertraline, and venlafaxine) in wastewater using liquid chromatography ...
Rapid Characterization Of Formulated Pharmaceuticals Using Fast Mas 1h Solid-State Nmr Spectroscopy, 2019 Iowa State University
Rapid Characterization Of Formulated Pharmaceuticals Using Fast Mas 1h Solid-State Nmr Spectroscopy, David A. Hirsh, Anuradha V. Wijesekara, Scott L. Carnahan, Ivan Hung, Joseph W. Lubach, Karthik Nagapudi, Aaron J. Rossini
Active pharmaceutical ingredients (APIs) can be prepared in many different solid forms and phases that affect their physicochemical properties and suitability for oral dosage forms. The development and commercialization of dosage forms require analytical techniques that can determine and quantify the API phase in the final drug product. 13C solid-state NMR (SSNMR) spectroscopy is widely employed to characterize pure and formulated solid APIs; however, 13C SSNMR experiments on dosage forms with low API loading are often challenging due to low sensitivity and interference from excipients. Here, fast MAS 1H SSNMR experiments are shown to be applicable for the rapid characterization ...
The Characterization Of A New Metabolite From A Trichodesmium Bloom, 2019 University of Rhode Island
The Characterization Of A New Metabolite From A Trichodesmium Bloom, Kelly M. Mcmanus
Senior Honors Projects
Our laboratory has been investigating blooms of Trichodesmium, a genus of ecologically important, nitrogen-fixing cyanobacteria, collected from Padre Island in the Gulf of Mexico. Trichodesmium species are an underexplored biological source of cyanobacteria – a taxa that has been shown to produce chemically diverse secondary metabolites. With our focus on the isolation and structure characterization of new bioactive marine natural products, our research group has discovered over 25 new-to-science compounds over the past three years from these blooms. UV and mass spectrometry-guided isolation of Trichodesmium chromatography fractions were utilized to isolate a new metabolite. Isolation of this metabolite was carried out ...
The Use Of Heterocycles As Important Structures In Medicinal Chemistry, 2019 The University of Southern Mississippi
The Use Of Heterocycles As Important Structures In Medicinal Chemistry, Sayre Weast
Heterocycles have many applications in the discipline of medicinal chemistry. These structures are found in various natural products with relevant biological activity. Our research group, in collaboration with two others, is particularly interested in one heterocycle, quinoline, as a scaffold for HIV-1 integrase inhibitors. A synthetic route has been developed to produce a derivatized structure on small scale. One goal of this thesis was to expand the scale of this route to provide increased quantities of the quinoline scaffold. Procedures were adapted to accommodate the increase in scale to convert commercially available anthranilic acids to quinolines via the isatoic anhydride ...
Preparation Of Enantioenriched Alkyltin Species And Their Application In Stereospecific Transformations, 2019 The Graduate Center, City University of New York
Preparation Of Enantioenriched Alkyltin Species And Their Application In Stereospecific Transformations, Glenn O. Ralph
All Dissertations, Theses, and Capstone Projects
Organometallic reagents containing the tin-carbon bond are used extensively in modern synthetic chemistry for the formation of new bonds to carbon. Over recent decades, transition metal catalyzed cross coupling reactions between two C(sp2) centers have been widely developed. However, the introduction of a C(sp3) center complicates the catalytic cycle, and opens unproductive chemical pathways which lead to isomerization, elimination, and racemization. Our lab has developed a modified-Stille reaction to combat the deleterious effects of β-hydride elimination. Our protocol enables unactivated 2° alkyl organotin nucleophiles to undergo efficient cross coupling reactions with C(sp2) electrophiles, avoiding ...
Defining Cell Cluster Size By Dielectrophoretic Capture At An Array Of Wireless Electrodes Of Several Distinct Lengths, Joseph T. Banovetz, Min Li, Darshna Pagariya, Sungu Kim, Baskar Ganapathysubramanian, Robbyn Anand
Clusters of biological cells play an important role in normal and disease states, such as in the release of insulin from pancreatic islets and in the enhanced spread of cancer by clusters of circulating tumor cells. We report a method to pattern cells into clusters having sizes correlated to the dimensions of each electrode in an array of wireless bipolar electrodes (BPEs). The cells are captured by dielectrophoresis (DEP), which confers selectivity, and patterns cells without the need for physical barriers or adhesive interactions that can alter cell function. Our findings demonstrate that this approach readily achieves fine control of ...
The Effects Of Cannabidiol And Delta 9-Tetrahydrocannabinol Concentration On Breast Cancer Cells, 2019 University of Northern Colorado
The Effects Of Cannabidiol And Delta 9-Tetrahydrocannabinol Concentration On Breast Cancer Cells, Dorothy Agyemang
Ursidae: The Undergraduate Research Journal at the University of Northern Colorado
Delta 9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are phytocannabinoids that have a potential impact on cancer treatments. Studies have shown that certain cannabinoids cause cancer cells to die, but only with the right concentration, which has not been well documented. The purpose of this study is to determine the exact concentration of CBD and THC needed to kill MCF-7 breast cancer cells. In this experiment, the initial treatment group will be treated with CBD or THC at concentrations of 0.1, 1, 10 and 100 micromolar. These concentrations were arbitrarily chosen because there is not an established baseline. Cell metabolic activity ...
Analysis Of Drug-Protein Interactions During Diabetes By High-Performance Affinity Chromatography, 2019 University of Nebraska - Lincoln
Analysis Of Drug-Protein Interactions During Diabetes By High-Performance Affinity Chromatography, Pingyang Tao
Student Research Projects, Dissertations, and Theses - Chemistry Department
High-performance affinity chromatography (HPAC) is a type of liquid chromatography in which solutes are separated based on their binding to a stationary phase that is a biologically-related agent. Sulfonylurea drugs have significant binding to proteins in blood, with most of this binding is believed to occur with human serum albumin (HSA). HSA is known to be modified as a result of the high serum levels of glucose that is present during diabetes, which may also alter the function of HSA as a binding agent for many drugs in circulation. Some modifications of HSA that can occur during diabetes involves early ...
Nonlinear Optical Measurements Of Bf2–Aza Dipyrromethene Fluorophores., 2019 Royal College of Surgeons in Ireland-Medical University of Bahrain
Nonlinear Optical Measurements Of Bf2–Aza Dipyrromethene Fluorophores., Fryad Z. Henari, Donal F. O'Shea, Dan Wu
Nonlinear absorption coefficient and the nonlinear refractive index of a series of BF2 aza dipyrromethene chromophores in tetrahydrofuran (THF) solutions were measured using the Z-scan technique with a low power continuous wave laser at 633 nm. Acquired data illustrated that the process involved in nonlinear absorption is reverse saturation absorption. The excited state absorption cross sections for all complexes were calculated and a pump and probe technique was used to record the triplet absorption spectrum. The band gap of the triplet state was estimated from this spectral data and the optical limiting behavior was demonstrated for each derivative.
Development Of Ruthenium Drugs As Anticancer Agents, 2019 Taylor University
Development Of Ruthenium Drugs As Anticancer Agents, Daniel Boy
Student Scholarship: Chemistry
An overview of literature that outlines the research methods of the development of proposed Ruthenium based anti-cancer agents.
Ligand-Protein Binding Of Cantharidin And Norcantharidin On Hsf1: A Docking Study, 2019 La Salle University
Ligand-Protein Binding Of Cantharidin And Norcantharidin On Hsf1: A Docking Study, Daniel Coyle
Previous research provides experimental evidence that cantharidin acts as an inhibitor of HSF1 in cancer cells whereas the similar norcantharidin exhibits no inhibitory activity on HSF1. This computational study utilized Autodock to suggest both binding site(s) and binding energies of cantharidin and norcantharidin on HSF1. This study found cantharidin to consistently bind stronger than norcantharidin in the same area on HSF1 when assuming a rigid protein structure.
Tracking Decitabine Incorporation Into Malignant Myeloid Cell Dna In Vitro And In Vivo By Lc-Ms/Ms With Enzymatic Digestion, 2019 Cleveland State University
Tracking Decitabine Incorporation Into Malignant Myeloid Cell Dna In Vitro And In Vivo By Lc-Ms/Ms With Enzymatic Digestion, Sujatha Chilakala, Ye Feng, Lan Li, Reda Mahfouz, Ebrahem Quteba, Yogen Saunthararajah, Yan Xu
Chemistry Faculty Publications
The DNA hypomethylating agents decitabine and 5-azacytidine are the only two drugs approved for treatment of all subtypes of the myeloid malignancy myelodysplastic syndromes (MDS). The key to drug activity is incorporation into target cell DNA, however, a practical method to measure this incorporation is un-available. Here, we report a sensitive and specific LC-MS/MS method to simultaneously measure decitabine incorporation and DNA hypomethylation. A stable heavy isotope of 2'-deoxycytidine was used as an internal standard and one-step multi-enzyme digestion was used to release the DNA bound drug. Enzyme-released decitabine along with other mononucleosides were separated by a reverse-phase ...
Purification And Characterization Of A Nonspecific Lipid Transfer Protein 1 (Nsltp1) From Ajwain (Trachyspermum Ammi) Seeds, Meshal Nazeer, Humera Waheed, Maria Saeed, Saman Yousuf Ali, M. Iqbal Choudhary, Zaheer Ul-Haq, Aftab Ahmed
Pharmacy Faculty Articles and Research
Ajwain (Trachyspermum ammi) belongs to the family Umbelliferae, is commonly used in traditional, and folk medicine due to its carminative, stimulant, antiseptic, diuretic, antihypertensive, and hepatoprotective activities. Non-specific lipid transfer proteins (nsLTPs) reported from various plants are known to be involved in transferring lipids between membranes and in plants defense response. Here, we describe the complete primary structure of a monomeric non-specific lipid transfer protein 1 (nsLTP1), with molecular weight of 9.66 kDa, from ajwain seeds. The nsLTP1 has been purified by combination of chromatographic techniques, and further characterized by mass spectrometry, and Edman degradation. The ajwain nsLTP1 is ...
Synthesis Of A Sulfur Variant For Treatment Of Trypanosomiasis, 2019 University of Nebraska at Omaha
Synthesis Of A Sulfur Variant For Treatment Of Trypanosomiasis, Carlos Vera-Esquivel
Student Research and Creative Activity Fair
Previous work in our lab has found diphenyl ether benzylamines showed a successful response with a micromolar concentration of our lead compound to treat the deadly Trypanosamiosis rhodesience. Furthermore, mammalian cell lines saw promising resistance towards damages. The goal of this study was to synthesize a diphenyl thio benzylamine variant. This variant was more active toward T. b. rhodesience but showed more toxicity to both rat 10 (IC50 mM) and human cell lines (HFF, HC-04, U-2 OS, and HEK293). The selectivity index (ratio of toxicity to activity in the same concentration units (SI)) varied from 55 ...