Exploring Molecular Mechanisms Of Paradoxical Activation In The Braf Kinase Dimers: Atomistic Simulations Of Conformational Dynamics And Modeling Of Allosteric Communication Networks And Signaling Pathways, 2016 Chapman University
Exploring Molecular Mechanisms Of Paradoxical Activation In The Braf Kinase Dimers: Atomistic Simulations Of Conformational Dynamics And Modeling Of Allosteric Communication Networks And Signaling Pathways, Amanda Tse, Gennady M. Verkhivker
Mathematics, Physics, and Computer Science Faculty Articles and Research
The recent studies have revealed that most BRAF inhibitors can paradoxically induce kinase activation by promoting dimerization and enzyme transactivation. Despite rapidly growing number of structural and functional studies about the BRAF dimer complexes, the molecular basis of paradoxical activation phenomenon is poorly understood and remains largely hypothetical. In this work, we have explored the relationships between inhibitor binding, protein dynamics and allosteric signaling in the BRAF dimers using a network-centric approach. Using this theoretical framework, we have combined molecular dynamics simulations with coevolutionary analysis and modeling of the residue interaction networks to determine molecular determinants of paradoxical activation. We ...
Diagnostic Utility Of Anti-Citrullinated Protein Antibody And Its Comparison With Rheumatoid Factor In Rheumatoid Arthritis, Aysha Habib Khan, Lena Jafri, M Ahraz Hussain, Saliha Ishaq
To assess the diagnostic utility of anti-citrullinated protein antibody (anti-CCP) in rheumatoid arthritis (RA) and compare it with rheumatoid factor (RF).
Place and Duration of Study:
Section of Chemical Pathology, Department of Pathology and Microbiology and Medicine, the Aga Khan University, Karachi, from January to May 2010.
A review of medical records of patients presenting to the clinics with complaints of muscular or joint pains and who were tested for their serum anti-CCP was done. Inclusion criteria were presence of clinical synovitis in at least one joint and an absence of alternative diagnosis. Patients ...
Novel Ph-Sensitive Cyclic Peptides, 2016 University of Rhode Island
Novel Ph-Sensitive Cyclic Peptides, Dhammika Weerakkody, Anna Moshnikova, Naglaa Salem El-Sayed, Ramona-Cosima Adochite, Gregory Slaybaugh, Jovana Golijanin, Rakesh Tiwari, Oleg A. Andreev, Keykavous Parang, Yana K. Reshetnyak
Pharmacy Faculty Articles and Research
A series of cyclic peptides containing a number of tryptophan (W) and glutamic acid (E) residues were synthesized and evaluated as pH-sensitive agents for targeting of acidic tissue and pH-dependent cytoplasmic delivery of molecules. Biophysical studies revealed the molecular mechanism of peptides action and localization within the lipid bilayer of the membrane at high and low pHs. The symmetric, c[(WE)4WC], and asymmetric, c[E4W5C], cyclic peptides translocated amanitin, a polar cargo molecule of similar size, across the lipid bilayer and induced cell death in a pH- and concentration-dependent manner. Fluorescently-labelled peptides were evaluated for targeting of acidic 4T1 ...
Assembly Of Nucleic Acid-Based Nanoparticles By Gas-Liquid Segmented Flow Microfluidics, 2016 Purdue University
Assembly Of Nucleic Acid-Based Nanoparticles By Gas-Liquid Segmented Flow Microfluidics, Matthew L. Capek, Ross Verheul, David H. Thompson
The Summer Undergraduate Research Fellowship (SURF) Symposium
The development of novel and efficient mixing methods is important for optimizing the efficiency of many biological and chemical processes. Tuning the physical and performance properties of nucleic acid-based nanoparticles is one such example known to be strongly affected by mixing efficiency. The characteristics of DNA nanoparticles (such as size, polydispersity, ζ-potential, and gel shift) are important to ensure their therapeutic potency, and new methods to optimize these characteristics are of significant importance to achieve the highest efficacy. In the present study, a simple segmented flow microfluidics system has been developed to augment mixing of pDNA/bPEI nanoparticles. This DNA ...
Conformational Dynamics And Stability Associated With Magnesium Or Calcium Binding To Dream In The Regulation Of Interactions Between Dream And Dna Or Presenilins, 2016 Florida International University
Conformational Dynamics And Stability Associated With Magnesium Or Calcium Binding To Dream In The Regulation Of Interactions Between Dream And Dna Or Presenilins, Khoa Ngoc Pham
FIU Electronic Theses and Dissertations
Downstream regulatory element antagonist modulator (DREAM) is involved in various interactions with targets both inside and outside of the nucleus. In the cytoplasm, DREAM interacts with the C-terminal fragments of presenilins to facilitate the production of β-amyloid plaques in Alzheimer’s disease. In the nucleus, Ca2+ free DREAM directly binds to specific downstream regulatory elements of prodynorphin/c-fos gene to repress the gene transcription in pain modulation. These interactions are regulated by Ca2+ and/or Mg2+ association at the EF-hands in DREAM. Therefore, understanding the conformational dynamics and stability associated with Ca2+ and/or Mg ...
Zn(Ii), Cu(Ii), Sn(Ii), And Ni(Ii) And Other Metal Cations Do Not Prevent The Aggregation Of Hiapp, 2016 Loyola Marymount University and Loyola Law School
Zn(Ii), Cu(Ii), Sn(Ii), And Ni(Ii) And Other Metal Cations Do Not Prevent The Aggregation Of Hiapp, Charles Hoying
The Zn(II) metal ion has been shown to interact with Islet Amyloid Polypeptide (IAPP), a protein implicated in the progression of Type II Diabetes Mellitus, in such a way as to prevent the protein from aggregating into toxic fibers. We set out to find whether other metal ions might similarly prevent IAPP aggregation. Using Thioflavin T (ThT) spectroscopic assays, which measure fluorescence of ThT upon binding to aggregated IAPP, we observed a decrease in aggregation when incubated with Zn(II), Cu(II), Ni(II), and Sn(II). Atomic Force Microscopy (AFM), which can visualize fibril formation, revealed that the ...
Engineering A Mutation In The Heparin Binding Pocket Of The Human Fibroblast Growth Factor, 2016 University of Arkansas, Fayetteville
Engineering A Mutation In The Heparin Binding Pocket Of The Human Fibroblast Growth Factor, Roshni Patel
Chemistry & Biochemistry Undergraduate Honors Theses
Fibroblast growth factors (FGFs) are family of proteins that belong to a group of growth factors that are found in mammals and play an important role in angiogenesis, differentiation, organogenesis, and tissue repair. In summary, their main functionality is involved in cell division and proliferation. Because FGFs plays such a vital role in cell proliferation, they are mainly involved in the process of wound healing and injuries. FGF binds to its ligand, heparin—a heavily sulfated glycosaminoglycan. The binding of heparin to FGF occurs through electrostatic interactions, specifically between the negatively charged sulfate groups on heparin and positively charged residues ...
Protein Studies: The Function Of Constitutive Androstane Receptor (Car) And Its Associated Ligands, 2016 University of Tennessee, Knoxville
Protein Studies: The Function Of Constitutive Androstane Receptor (Car) And Its Associated Ligands, Jacob M. Amburn
University of Tennessee Honors Thesis Projects
No abstract provided.
Exploring The Mechanisms Of Action Of Antifungal Peptides Using Saccharomyces Cerevisiae., 2016 University of Arkansas, Fayetteville
Exploring The Mechanisms Of Action Of Antifungal Peptides Using Saccharomyces Cerevisiae., Michelle L. Mason
Biological Sciences Undergraduate Honors Theses
Candida albicans is a normal inhabitant of the skin and mucosal membranes of humans, however, in individuals with depressed immune systems or disrupted cutaneous flora, Candida can overgrow and cause serious infection. Candida infection is the fourth leading cause of nosocomial infection in the United States. These infections are often associated with longer hospital stays and higher mortality. Current drug therapies for this infection are largely ineffective due to the increased drug resistance of Candida species, and for some therapeutics, high levels of drug toxicity to humans. Histatin 5 is a naturally occurring salivary peptide that has strong antifungal properties ...
Analysis Of Mammalian Carboxypeptidase O Expression Patterns, 2016 Andrews University
Analysis Of Mammalian Carboxypeptidase O Expression Patterns, Christian Bardan
Carboxypeptidase 0 (CPO) is a protease that cuts acidic amino acids from the carboxy termini of substrate proteins. This study aims to describe the expression patterns of CPO in small mammals. We have sampled tissue from four different species: thirteen-lined ground squirrel, eastern chipmunk, eastern mole, and northern short-tailed shrew. Samples were analyzed via Western blot using two CPO antibodies. Immunoreactive bands likely to be CPO, with molecular weights approximately 42 kDa, were seen predominantly in kidney, liver, and intestinal tissue samples. This suggests CPO could play a specific physiological function in these organs.
Identification Of Potential Drug Targets In Cancer Signaling Pathways Using Stochastic Logical Models, 2016 Northwestern Polytechnical University
Identification Of Potential Drug Targets In Cancer Signaling Pathways Using Stochastic Logical Models, Peican Zhu, Hamidreza Montazeri Aliabadi, Hasan Uludag, Jie Han
Pharmacy Faculty Articles and Research
The investigation of vulnerable components in a signaling pathway can contribute to development of drug therapy addressing aberrations in that pathway. Here, an original signaling pathway is derived from the published literature on breast cancer models. New stochastic logical models are then developed to analyze the vulnerability of the components in multiple signalling sub-pathways involved in this signaling cascade. The computational results are consistent with the experimental results, where the selected proteins were silenced using specific siRNAs and the viability of the cells were analyzed 72 hours after silencing. The genes elF4E and NFkB are found to have nearly no ...
Theoretical Investigation Of Interaction Between The Set Of Ligands And Α7 Nicotinic Acetylcholine Receptor, 2016 Saratov State University
Theoretical Investigation Of Interaction Between The Set Of Ligands And Α7 Nicotinic Acetylcholine Receptor, O. E. Glukhova, Tatiana Prytkova, D. S. Shmygin
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Nicotinic acetylcholine receptors (nAChRs) are neuron receptor proteins that provide a transmission of nerve impulse through the synapses. They are composed of a pentametric assembly of five homologous subunits (5 α7 subunits for α7nAChR, for example), oriented around the central pore. These receptors might be found in the chemical synapses of central and peripheral nervous system, and also in the neuromuscular synapses. Transmembrane domain of the one of such receptors constitutes ion channel. The conductive properties of ion channel strongly depend on the receptor conformation changes in the response of binding with some molecule, f.e. acetylcholine. Investigation of interaction ...
Clinical Study Of Canine Tear Lacritin As A Treatment For Dry Eye, 2016 James Madison University
Clinical Study Of Canine Tear Lacritin As A Treatment For Dry Eye, Katherine E. Kelly
Senior Honors Projects
Keratoconjunctivitis sicca (KCS), the deficiency of tears also known as dry eye, is a prevalent disease that affects both humans and canines. The current treatment for dye eye, cyclosporine (Restatis®), only provides temporary relief, is often associated with discomfort and is inconsistently effective. Lacritin is a naturally occurring tear glycoprotein secreted from the human and canine lacrimal glands. It has been shown that lacritin stimulates basal tearing in rabbits when applied topically. This study characterized the amount and form of lacritin found in the tears of dogs with healthy and dry eyes—information which may be applied to the development ...
Circulating Fibroblast Growth Factor-2, Hiv-Tat, And Vascular Endothelial Cell Growth Factor-A In Hiv-Infected Children With Renal Disease Activate Rho-A And Src In Cultured Renal Endothelial Cells., 2016 George Washington University
Circulating Fibroblast Growth Factor-2, Hiv-Tat, And Vascular Endothelial Cell Growth Factor-A In Hiv-Infected Children With Renal Disease Activate Rho-A And Src In Cultured Renal Endothelial Cells., Jharna R Das, J Silvio Gutkind, Patricio E. Ray
Pediatrics Faculty Publications
Renal endothelial cells (REc) are the first target of HIV-1 in the kidney. The integrity of REc is maintained at least partially by heparin binding growth factors that bind to heparan sulfate proteoglycans located on their cell surface. However, previous studies showed that the accumulation of two heparin-binding growth factors, Vascular Endothelial Cell Growth Factor-A (VEGF-A) and Fibroblast Growth Factor-2 (FGF-2), in combination with the viral protein Tat, can precipitate the progression of HIV-renal diseases. Nonetheless, very little is known about how these factors affect the behavior of REc in HIV+ children. We carried out this study to determine how ...
Human Anatomy And Physiology Preparatory Course (Interactive), 2016 CUNY Bronx Community College
Human Anatomy And Physiology Preparatory Course (Interactive), Carlos Liachovitzky
Open Educational Resources
The overall purpose of these preparatory course set of learning objectives is to help students familiarize with some terms and some basic concepts they will find later in the Human Anatomy and Physiology I course.
These 40+ learning objectives to prepare for Human Anatomy and Physiology can be downloaded and played in a desktop, or laptop (windows exe file).
The entire course has four parts (A, B, C, and D). Each learning objective is followed by a set of multiple choice question similar to those found later in a Human Anatomy and Physiology course.
The organization and functioning of the ...
Effect Of The Il-1 Receptor Antagonist Kineret® On Disease Phenotype In Mdx Mice., 2016 Children’s National Medical Center, Washington, DC
Effect Of The Il-1 Receptor Antagonist Kineret® On Disease Phenotype In Mdx Mice., Margaret E. Benny Klimek, Arpana Sali, Sree Rayavarapu, Jack Van Der Meulen, Kanneboyina Nagaraju
Integrative Systems Biology Faculty Publications
Duchenne muscular dystrophy (DMD) is an X-linked muscle disease caused by mutations in the dystrophin gene. The pathology of DMD manifests in patients with progressive muscle weakness, loss of ambulation and ultimately death. One of the characteristics of DMD is muscle inflammation, and dystrophin-deficient skeletal muscles produce higher levels of the pro-inflammatory cytokine interleukin 1β (IL-1β) in response to toll like receptor (TLR) stimulation compared to controls; therefore, blocking the IL-1β pathway could improve the disease phenotype in mdx mice, a mouse model of DMD. Kineret® or IL-1Ra is a recombinant IL-1 receptor antagonist approved by the FDA for treating ...
Single-Molecule Imaging Reveals That Argonaute Re-Shapes The Properties Of Its Nucleic Acid Guides: A Dissertation, 2015 University of Massachusetts Medical School
Single-Molecule Imaging Reveals That Argonaute Re-Shapes The Properties Of Its Nucleic Acid Guides: A Dissertation, William E. Salomon
GSBS Dissertations and Theses
Small RNA silencing pathways regulate development, viral defense, and genomic integrity in all kingdoms of life. An Argonaute (Ago) protein, guided by a tightly bound, small RNA or DNA, lies at the core of these pathways. Argonaute uses its small RNA or DNA to find its target sequences, which it either cleaves or stably binds, acting as a binding scaffold for other proteins. We used Co-localization Single-Molecule Spectroscopy (CoSMoS) to analyze target binding and cleavage by Ago and its guide. We find that both eukaryotic and prokaryotic Argonaute proteins re-shape the fundamental properties of RNA:RNA, RNA:DNA, and DNA ...
Dancing Through Life: Molecular Dynamics Simulations And Network-Centric Modeling Of Allosteric Mechanisms In Hsp70 And Hsp110 Chaperone Proteins, Gabrielle Stetz, Gennady M. Verkhivker
Mathematics, Physics, and Computer Science Faculty Articles and Research
Hsp70 and Hsp110 chaperones play an important role in regulating cellular processes that involve protein folding and stabilization, which are essential for the integrity of signaling networks. Although many aspects of allosteric regulatory mechanisms in Hsp70 and Hsp110 chaperones have been extensively studied and significantly advanced in recent experimental studies, the atomistic picture of signal propagation and energetics of dynamics-based communication still remain unresolved. In this work, we have combined molecular dynamics simulations and protein stability analysis of the chaperone structures with the network modeling of residue interaction networks to characterize molecular determinants of allosteric mechanisms. We have shown that ...
Identification Of Cisplatin-Binding Proteins Using Agarose Conjugates Of Platinum Compounds, 2015 Portland State University
Identification Of Cisplatin-Binding Proteins Using Agarose Conjugates Of Platinum Compounds, Takatoshi Karasawa, Martha Sibrian-Vazquez, Robert Strongin, Peter Steyger
Robert M. Strongin
Cisplatin is widely used as an antineoplastic drug, but its ototoxic and nephrotoxic side-effects, as well as the inherent or acquired resistance of some cancers to cisplatin, remain significant clinical problems. Cisplatin’s selectivity in killing rapidly proliferating cancer cells is largely dependent on covalent binding to DNA via cisplatin’s chloride sites that had been aquated. We hypothesized that cisplatin’s toxicity in slowly proliferating or terminally differentiated cells is primarily due to drug-protein interactions, instead of drug-DNA binding. To identify proteins that bind to cisplatin, we synthesized two different platinum-agarose conjugates, one with two amino groups and another ...
Real-Time Detection Of Breast Cancer Cells Using Peptidefunctionalized Microcantilever Arrays, 2015 University of Alberta
Real-Time Detection Of Breast Cancer Cells Using Peptidefunctionalized Microcantilever Arrays, Hashem Etayash, Keren Jiang, Sarfuddin Azmi, Thomas Thundat, Kamaljit Kaur
Pharmacy Faculty Articles and Research
Ligand-directed targeting and capturing of cancer cells is a new approach for detecting circulating tumor cells (CTCs). Ligands such as antibodies have been successfully used for capturing cancer cells and an antibody based system (CellSearch®) is currently used clinically to enumerate CTCs. Here we report the use of a peptide moiety in conjunction with a microcantilever array system to selectively detect CTCs resulting from cancer, specifically breast cancer. A sensing microcantilever, functionalized with a breast cancer specific peptide 18-4 (WxEAAYQrFL), showed significant deflection on cancer cell (MCF7 and MDA-MB-231) binding compared to when exposed to noncancerous (MCF10A and HUVEC) cells ...