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Pulmonary Surfactant Fortified With Cath-2 As A Novel Therapy For Bacterial Pneumonia, Brandon J. Baer 2017 University of Western Ontario

Pulmonary Surfactant Fortified With Cath-2 As A Novel Therapy For Bacterial Pneumonia, Brandon J. Baer

Western Research Forum

Background: Bacterial pneumonia is a leading cause of death worldwide, with high mortality rates persisting even after antibiotic treatment. Current treatments for pneumonia involve administration of antibiotics, however after the bacteria are killed they release toxic substances that induce inflammation and lung dysfunction. Host defense peptides represent a potential solution to this problem through their ability to down regulate inflammation. However, effective delivery to the lung is difficult because of the complex branching structure of the airways. My study addresses this delivery problem by using exogenous surfactant, a pulmonary delivery vehicle capable of improving spreading of these peptides throughout the ...


Transferrin Receptor Targeted Delivery Of Sirna For Gene Therapy, Yuran Xie 2017 Wayne State University

Transferrin Receptor Targeted Delivery Of Sirna For Gene Therapy, Yuran Xie

Wayne State University Dissertations

Gene therapy is thought to be a solution for various difficult to treat diseases such as cancer. Small interfering RNA (siRNA) as a promising anti-sense molecule can specifically silence disease related gene have been exploit in different diseases. However, lack of safe and efficient siRNA delivery systems limits the application of siRNA therapy in clinic. Transferrin receptor (TfR) is an essential transmembrane receptor involved in iron uptake. TfR universally express in most cells/ tissues but upregulated in certain cells, for example, many cancer cells and activated T cells (ATCs). To overcome the biological barriers and increase siRNA delivery efficiency, in ...


Network Inference Driven Drug Discovery, Gergely Zahoránszky-Kőhalmi, Tudor I. Oprea MD, PhD, Cristian G. Bologa PhD, Subramani Mani MD, PhD, Oleg Ursu PhD 2016 University of New Mexico School of Medicine

Network Inference Driven Drug Discovery, Gergely Zahoránszky-Kőhalmi, Tudor I. Oprea Md, Phd, Cristian G. Bologa Phd, Subramani Mani Md, Phd, Oleg Ursu Phd

Biomedical Sciences ETDs

The application of rational drug design principles in the era of network-pharmacology requires the investigation of drug-target and target-target interactions in order to design new drugs. The presented research was aimed at developing novel computational methods that enable the efficient analysis of complex biomedical data and to promote the hypothesis generation in the context of translational research. The three chapters of the Dissertation relate to various segments of drug discovery and development process.

The first chapter introduces the integrated predictive drug discovery platform „SmartGraph”. The novel collaborative-filtering based algorithm „Target Based Recommender (TBR)” was developed in the framework of this ...


Implementation Of Universal Hplc Analysis For Counterfeit Medication: A Partnership Of Purdue University And The Kilimanjaro School Of Pharmacy, Jordyn McCord, Michael Mavity, David Wintczak 2016 Purdue University

Implementation Of Universal Hplc Analysis For Counterfeit Medication: A Partnership Of Purdue University And The Kilimanjaro School Of Pharmacy, Jordyn Mccord, Michael Mavity, David Wintczak

Purdue Journal of Service-Learning and International Engagement

Jordyn McCord and Michael Mavity are 2016 graduates of both biological engineering and pharmaceutical sciences. David Wintczak is a third-year pharmacy doctoral candidate. Here, in their second article published in PJSL, they describe a weeklong study abroad course at the Kilimanjaro School of Pharmacy in Tanzania, designed to engage students in the implementation of methods for detecting counterfeit medications.


Synthetic And Biological Exploration Of (+)-Boldine - Identification Of Potential Cns Receptor Ligands, Sujay Joseph 2016 CUNY Hunter College

Synthetic And Biological Exploration Of (+)-Boldine - Identification Of Potential Cns Receptor Ligands, Sujay Joseph

School of Arts & Sciences Theses

(+)-Boldine, an aporphine alkaloid, is reported to be biologically active at various Central Nervous System(CNS) receptors. However, only a few Structure Activity Relationship(SAR) studies have been conducted using boldine’s aporphine scaffold. A library of novel analogs was synthesized from boldine to understand the effect of bisbenzylation at C2 and C9 positions on the affinity and selectivity at the serotonin receptors.


Determination Of Isotopic Abundance Of 13c/12c Or 2h/1h And 18o/16o In Biofield Energy Treated 1-Chloro-3-Nitrobenzene (3-Cnb) Using Gas Chromatography-Mass Spectrometry, Mahendra Kumar Trivedi 2016 Selected Works

Determination Of Isotopic Abundance Of 13c/12c Or 2h/1h And 18o/16o In Biofield Energy Treated 1-Chloro-3-Nitrobenzene (3-Cnb) Using Gas Chromatography-Mass Spectrometry, Mahendra Kumar Trivedi

Mahendra Kumar Trivedi

1-Chloro-3-nitrobenzene (3-CNB) is an aromatic halo-amine compound used as chemical intermediate for the production of several fine chemicals like pharmaceuticals, dyes, agricultural chemicals, etc. The stable isotope ratio analysis has drawn attention in numerous fields such as agricultural, food authenticity, biochemistry, etc. The objective of the current research was to investigate the impact of the biofield energy treatment on the isotopic abundance ratios of PM+1/PM, PM+2/PM and PM+3/PM in 3-CNB using gas chromatography - mass spectrometry (GC-MS). The sample, 3-CNB was divided into two parts - one part was denoted as control and another part was ...


Gas Chromatography-Mass Spectrometric Analysis Of Isotopic Abundance Of 13c, 2h, And 18o In Biofield Energy Treated P-Tertiary Butylphenol (Ptbp), Mahendra Kumar Trivedi 2016 Selected Works

Gas Chromatography-Mass Spectrometric Analysis Of Isotopic Abundance Of 13c, 2h, And 18o In Biofield Energy Treated P-Tertiary Butylphenol (Ptbp), Mahendra Kumar Trivedi

Mahendra Kumar Trivedi

p-tert-Butyphenol (PTBP) is a phenolic monomer used in the synthesis of numerous industrially useful chemicals. The current research work aimed to evaluate the effect of the biofield energy treatment on the isotopic abundance ratios of PM+1/PM and PM+2/PM in PTBP using gas chromatography - mass spectrometry (GC-MS). The sample, PTBP was distributed into two parts - one part was designated as control PTBP and another part was considered as biofield energy treated PTBP. The biofield energy treatment was achieved through unique biofield energy transmission process by Mr. Trivedi (also known as The Trivedi Effect®). T1, T2, T3, and ...


Structural Activity Relationship Study On Dual Plk1 /Brd4 Inhibitor, Bi- 2536, Hailemichael Yosief, Shuai Liu, Dennis L. Buckley, Justin M. Roberts, Alex M. Muthengi, Francesca M. Corsini, James E. Bradner, Wei Zhang 2016 University of Massachusetts Boston

Structural Activity Relationship Study On Dual Plk1 /Brd4 Inhibitor, Bi- 2536, Hailemichael Yosief, Shuai Liu, Dennis L. Buckley, Justin M. Roberts, Alex M. Muthengi, Francesca M. Corsini, James E. Bradner, Wei Zhang

UMass Center for Clinical and Translational Science Research Retreat

Polo-like kinase 1 (PLK1) and BRD4 are two different therapeutic targets in cancer drug discovery. Recently it has been reported that PLK1 inhibitor, BI-2536, is also a potent inhibitor of BRD4. The simultaneous inhibition of PLK1 and BRD4 by a single drug molecule is interesting because this could lead to the development of effective therapeutic strategy for different types of disease conditions in which PLK1 and BRD4 are implicated. Structural activity relationship studies has been carried out on BI-2536 to generate analogs with enhanced dual inhibitory activity against BRD4 and PLK1 as well as to render the molecule selective to ...


Anthelminthic Screening For Parasitic Nematodes, Elfawal A. Mostafa, Dan Lawler, Dirk Albrecht, Raffi V. Aroian 2016 University of Massachusetts Medical School

Anthelminthic Screening For Parasitic Nematodes, Elfawal A. Mostafa, Dan Lawler, Dirk Albrecht, Raffi V. Aroian

UMass Center for Clinical and Translational Science Research Retreat

For many parasitic diseases, high-throughput phenotypic screening is an important tool in finding new drugs. Some of the most important parasitic diseases are caused by nematodes. However, these parasitic nematodes are not typically amenable to high throughput screening. Due to the ease of its maintenance and suitability for high throughput assay, the nematode Caenorhabditis elegans is instead used. To address whether C. elegans is a good model for nematode drug discovery, we compared the drug susceptibility of C. elegans relative to the human hookworm nematode parasite Ancylostoma ceylanicum at several developmental stages using a library of FDA approved drugs. I ...


Hiv Vaccines: Progress, Limitations And A Crispr/Cas9 Vaccine, Omar A. Garcia Martinez 2016 Augustana College, Rock Island Illinois

Hiv Vaccines: Progress, Limitations And A Crispr/Cas9 Vaccine, Omar A. Garcia Martinez

Biology: Student Scholarship & Creative Works

ABSTRACT: The HIV-1 pandemic continues to thrive due to ineffective HIV-1 vaccines. Historically, the world’s most infectious diseases, such as polio and smallpox, have been eradicated or have come close to eradication due to the advent of effective vaccines. Highly active antiretroviral therapy is able to delay the onset of AIDS but can neither rid the body of HIV-1 proviral DNA nor prevent further transmission. A prophylactic vaccine that prevents the various mechanisms HIV-1 has to evade and attack our immune system is needed to end the HIV-1 pandemic. Recent advances in engineered nuclease systems, like the CRISPR/Cas9 ...


Pioneering A Novel Class Of Tetrahydroimidazopyridines With Anti-Proliferative Property Study Against Prostate Cancer, Napoleon D'Cunha 2016 Clark Atlanta University

Pioneering A Novel Class Of Tetrahydroimidazopyridines With Anti-Proliferative Property Study Against Prostate Cancer, Napoleon D'Cunha

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

The synthesis of tetrahydroimidazo[1,5-a]pyridine (rIMP) through the transfer hydrogenation of imidazo[1,5-a]pyridine (IMP) was successfully developed. The simple two-step procedure is the most viable and efficient method that results in a unique conjugated system with pyridine at the 1-position and functionalized phenyl group at the 3-position.

In the synthesis of imidazo[1,5-a]pyridine, the reaction between di-2-pyridil ketone, substituted benzaldehyde and ammonium acetate in acetic acid under N2 was highly successful, resulting in yields ranging from 35-95%. Highest yields were obtained for compounds that had electron withdrawing group on them.

The transfer hydrogenation ...


Impacts From The Use Of Antibiotics In Livestock: Methods Of Transmission Of Antibiotic Resistance From Livestock To Humans, Kristin M. Walden 2016 Augustana College, Rock Island Illinois

Impacts From The Use Of Antibiotics In Livestock: Methods Of Transmission Of Antibiotic Resistance From Livestock To Humans, Kristin M. Walden

Biology: Student Scholarship & Creative Works

Antibiotic use in livestock production has been around since the 1950s. Antibiotic feed is used in livestock and other meat producing animals for three reasons: illness prevention, illness treatment, and growth promotion. Unfortunately, since the time that antibiotics were first invented, antibiotic resistant bacteria have become a threat to public health. There are many studies showing methods of transmission of antibiotic resistance from livestock to humans. Antibiotic resistance can spread from livestock to soil, water, insects, and food, which ultimately comes into contact with humans. A proposed study to measure antibiotic resistance when eliminating antibiotic feed will provide a hypothesis ...


Exploring The Effect Of Novel Small Molecules On Oligodendrocyte Precursor Proliferation, Sagune Sakya 2016 University of Connecticut - Storrs

Exploring The Effect Of Novel Small Molecules On Oligodendrocyte Precursor Proliferation, Sagune Sakya

University Scholar Projects

Gliomas, a type of brain tumor, can be difficult to treat and have a poor survival rate. One pathway that leads to glioma formation is excessive signaling by platelet derived growth factors (PDGF) through PDGF receptor α (PDGFRα). Through this research, I found that novel compounds that downregulate PDGFRα decrease proliferation of Oli-neu cells, an oligodendrocyte precursor cell model, and identified signaling pathways through which these compounds may exert their effect. Further investigation may identify targets for development of glioma treatments.


Chemotherapeutic Efficiency Of Drugs In Vitro: Comparison Of Doxorubicin Exposure In 3d And 2d Culture Matrices, Alan Casey, Mahmood Gargotti, Franck Bonnier, Hugh Byrne 2016 Dublin Institute of Technology

Chemotherapeutic Efficiency Of Drugs In Vitro: Comparison Of Doxorubicin Exposure In 3d And 2d Culture Matrices, Alan Casey, Mahmood Gargotti, Franck Bonnier, Hugh Byrne

Articles

The interest in the use of 3D matrices for in vitro analysis, with a view to increasing the relevance of in vitro studies and reducing the dependence on in vivo studies, has been growing in recent years. Cells grown in a 3D in vitro matrix environment have been reported to exhibit significantly different properties to those in a conventional 2D culture environment. However, comparison of 2D and 3D cell culture models have recently been noted to result in differing responses of cytotoxic assays, without any associated change in viability. The effect was attributed to differing conversion rates and effective concentrations ...


Chemical Investigation Of Antarctic Marine Organisms & Their Role In Modern Drug Discovery, Jacqueline Lee Fries 2016 University of South Florida

Chemical Investigation Of Antarctic Marine Organisms & Their Role In Modern Drug Discovery, Jacqueline Lee Fries

Graduate Theses and Dissertations

The chemicals produced by biological systems, whether proteins, peptides, or terpenes, will always provide an intriguing topic for researchers. Invisibly controlling every aspect of nature, these molecules are responsible for life, evolution, and death. Specifically, here is described the secondary metabolites produced by Antarctic marine organisms as well as others, and how they are used to defend or attract other animals while potentially providing health benefits to mankind. This is done through collection, extraction, and separation of individual specimens. The respective mixtures of compounds after isolation are then analyzed via spectroscopic methods such as nuclear magnetic resonance spectroscopy, mass spectrometry ...


The Ssdna Mutator Apobec3a Is Regulated By Cooperative Dimerization, Markus-Frederik Bohn, Shivender Shandilya, Tania Silvas, Ellen Nalivaika, Takahide Kouno, Brian Kelch, Sean Ryder, Nese Yilmaz, Mohan Somasundaran, Celia Schiffer 2016 University of Massachusetts Medical School

The Ssdna Mutator Apobec3a Is Regulated By Cooperative Dimerization, Markus-Frederik Bohn, Shivender Shandilya, Tania Silvas, Ellen Nalivaika, Takahide Kouno, Brian Kelch, Sean Ryder, Nese Yilmaz, Mohan Somasundaran, Celia Schiffer

Celia A. Schiffer

Deaminase activity mediated by the human APOBEC3 family of proteins contributes to genomic instability and cancer. APOBEC3A is by far the most active in this family and can cause rapid cell death when overexpressed, but in general how the activity of APOBEC3s is regulated on a molecular level is unclear. In this study, the biochemical and structural basis of APOBEC3A substrate binding and specificity is elucidated. We find that specific binding of single-stranded DNA is regulated by the cooperative dimerization of APOBEC3A. The crystal structure elucidates this homodimer as a symmetric domain swap of the N-terminal residues. This dimer interface ...


Structure Of The Vif-Binding Domain Of The Antiviral Enzyme Apobec3g, Takahide Kouno, Elizabeth Luengas, Megumi Shigematsu, Shivender Shandilya, JingYing Zhang, Luan Chen, Mayuko Hara, Celia Schiffer, Reuben Harris, Hiroshi Matsuo 2016 University of Massachusetts Medical School

Structure Of The Vif-Binding Domain Of The Antiviral Enzyme Apobec3g, Takahide Kouno, Elizabeth Luengas, Megumi Shigematsu, Shivender Shandilya, Jingying Zhang, Luan Chen, Mayuko Hara, Celia Schiffer, Reuben Harris, Hiroshi Matsuo

Celia A. Schiffer

The human APOBEC3G (A3G) DNA cytosine deaminase restricts and hypermutates DNA-based parasites including HIV-1. The viral infectivity factor (Vif) prevents restriction by triggering A3G degradation. Although the structure of the A3G catalytic domain is known, the structure of the N-terminal Vif-binding domain has proven more elusive. Here, we used evolution- and structure-guided mutagenesis to solubilize the Vif-binding domain of A3G, thus permitting structural determination by NMR spectroscopy. A smaller zinc-coordinating pocket and altered helical packing distinguish the structure from previous catalytic-domain structures and help to explain the reported inactivity of this domain. This soluble A3G N-terminal domain is bound by ...


Simultaneously Targeting The Ns3 Protease And Helicase Activities For More Effective Hepatitis C Virus Therapy, Jean Ndjomou, M Corby, Noreena Sweeney, Alicia Hanson, Cihan Aydin, Akbar Ali, Celia Schiffer, Kelin Li, Kevin Frankowski, Frank Schoenen, David Frick 2016 University of Wisconsin—Milwaukee

Simultaneously Targeting The Ns3 Protease And Helicase Activities For More Effective Hepatitis C Virus Therapy, Jean Ndjomou, M Corby, Noreena Sweeney, Alicia Hanson, Cihan Aydin, Akbar Ali, Celia Schiffer, Kelin Li, Kevin Frankowski, Frank Schoenen, David Frick

Celia A. Schiffer

This study examines the specificity and mechanism of action of a recently reported hepatitis C virus (HCV) nonstructural protein 3 (NS3) helicase-protease inhibitor (HPI), and the interaction of HPI with the NS3 protease inhibitors telaprevir, boceprevir, danoprevir, and grazoprevir. HPI most effectively reduced cellular levels of subgenomic genotype 4a replicons, followed by genotypes 3a and 1b replicons. HPI had no effect on HCV genotype 2a or dengue virus replicon levels. Resistance evolved more slowly to HPI than telaprevir, and HPI inhibited telaprevir-resistant replicons. Molecular modeling and analysis of the ability of HPI to inhibit peptide hydrolysis catalyzed by a variety ...


Structural Basis For Mutation-Induced Destabilization Of Profilin 1 In Als, Sivakumar Boopathy, Tania Silvas, Maeve Tischbein, Silvia Jansen, Shivender Shandilya, Jill Zitzewitz, John Landers, Bruce Goode, Celia Schiffer, Daryl Bosco 2016 University of Massachusetts Medical School

Structural Basis For Mutation-Induced Destabilization Of Profilin 1 In Als, Sivakumar Boopathy, Tania Silvas, Maeve Tischbein, Silvia Jansen, Shivender Shandilya, Jill Zitzewitz, John Landers, Bruce Goode, Celia Schiffer, Daryl Bosco

Celia A. Schiffer

Mutations in profilin 1 (PFN1) are associated with amyotrophic lateral sclerosis (ALS); however, the pathological mechanism of PFN1 in this fatal disease is unknown. We demonstrate that ALS-linked mutations severely destabilize the native conformation of PFN1 in vitro and cause accelerated turnover of the PFN1 protein in cells. This mutation-induced destabilization can account for the high propensity of ALS-linked variants to aggregate and also provides rationale for their reported loss-of-function phenotypes in cell-based assays. The source of this destabilization is illuminated by the X-ray crystal structures of several PFN1 proteins, revealing an expanded cavity near the protein core of the ...


Inhibition Of Apobec3g Activity Impedes Double-Stranded Dna Repair, Ponnandy Prabhu, Shivender Shandilya, Elena Britan-Rosich, Adi Nagler, Celia Schiffer, Moshe Kotler 2016 The Hebrew University-Hadassah Medical School

Inhibition Of Apobec3g Activity Impedes Double-Stranded Dna Repair, Ponnandy Prabhu, Shivender Shandilya, Elena Britan-Rosich, Adi Nagler, Celia Schiffer, Moshe Kotler

Celia A. Schiffer

The cellular cytidine deaminase APOBEC3G (A3G) was first described as an anti-HIV-1 restriction factor, acting by directly deaminating reverse transcripts of the viral genome. HIV-1 Vif neutralizes the activity of A3G, primarily by mediating degradation of A3G to establish effective infection in host target cells. Lymphoma cells, which express high amounts of A3G, can restrict Vif-deficient HIV-1. Interestingly, these cells are more stable in the face of treatments that result in double-stranded DNA damage, such as ionizing radiation and chemotherapies. Previously, we showed that the Vif-derived peptide (Vif25-39) efficiently inhibits A3G deamination, and increases the sensitivity of lymphoma cells to ...


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