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Effect Of An Arginine-To-Isoleucine Active Site Mutation On Escherichia Coli Malate Dehydrogenase Enzymatic Activity, Jon Zatorski, Bruce J. Heyen 2018 Olivet Nazarene University

Effect Of An Arginine-To-Isoleucine Active Site Mutation On Escherichia Coli Malate Dehydrogenase Enzymatic Activity, Jon Zatorski, Bruce J. Heyen

Scholar Week 2016 - present

Citric acid cycle enzymes function in an environment with numerous substrate analogues and therefore contain active site residue organizations that confer high substrate specificity. Extensive research into the catalytic mechanism of Escherichia coli malate dehydrogenase (eMDH) has identified arginine81 as being crucial to catalysis. In this investigation, an engineered eMDH having an Ile81 rather than an Arg81 (R81I) was isolated using a hexahistadine (His6) tag. Enzymatic activity of the R81I mutant with respect to malate, lactate, and pyruvate was explored. The R81I mutant did show significant activity toward malate, but did not show significant activity toward lactate or pyruvate. Investigations ...


History Of The 3rs In Toxicity Testing: From Russell And Burch To 21st Century Toxicology, Martin L. Stephens, Nina S. Mak 2018 Johns Hopkins University

History Of The 3rs In Toxicity Testing: From Russell And Burch To 21st Century Toxicology, Martin L. Stephens, Nina S. Mak

Martin Stephens, Ph.D.

Toxicity testing is a key part of the process of assessing the hazards, safety, or risk that chemicals and other substances pose to humans, animals, or the environment. Standardized methods for such testing, typically involving animals, began to emerge during the first half of the 20th century. In 1959, British scientists William Russell and Rex Burch proposed a framework for reducing, refining, or replacing animal use in toxicology and other forms of biomedical experimentation. This “3Rs” or “alternatives” approach emerged at a time of growing sensitivity to the use of animals in experimentation, and progress in its implementation has been ...


Studies Of Amino Acid Mutations In Drug Resistance Of The Smo Protein, Eunice Wintona 2018 University of Nebraska at Omaha

Studies Of Amino Acid Mutations In Drug Resistance Of The Smo Protein, Eunice Wintona

Student Research and Creative Activity Fair

Smoothened receptor (SMO) is a protein that in humans, is encoded by the SMO gene. A systemic mutation in its binding pocket helps predict the sensitivity of mutant proteins to different drugs. Known as a GPCR-like receptor, it is a component of the hedgehog signaling pathway; a pathway involved in body patterning and the regulation of adult stem cells. An uncontrolled or inappropriate activation of the Hedgehog pathway drives tumor progression in cancers and a number of birth defects. To achieve these goals, the molecular modeling software MOE was used to build small molecules and drug molecules like Vismodegib and ...


Dna Base Excision Repair And Double Strand Break Repair In Human Fibroblast, Mingyang Li 2017 Louisiana State University and Agricultural and Mechanical College

Dna Base Excision Repair And Double Strand Break Repair In Human Fibroblast, Mingyang Li

LSU Doctoral Dissertations

In eukaryotes, DNA repair mechanisms detect and repair damaged DNA. DNA damage is primarily caused by a variety of exogenous and endogenous sources. Several types of damage to DNA are repaired by different kinds of DNA repair pathways. This dissertation focused on repair of N-methylpurines (NMPs) and double-strand breaks (DSBs) in human fibroblasts.

NMPs, including N7-methylguanine (7MeG) and N3-methyladenine (3MeA), can be induced by environmental methylating agents (e.g. the soil fumigant methyl bromide), chemotherapeutics (e.g. nitrogen mustards), and natural cellular methyl donors like S-adenosylmethionine. In human cells, NMPs are repaired by the multi-step ...


Zinc Chloride Activates Phospho-Akt And Promotes Chondrocyte Maturation In The Atdc5 Chondrogenic Cell Line, Donya T. Burgess 2017 Seton Hall University

Zinc Chloride Activates Phospho-Akt And Promotes Chondrocyte Maturation In The Atdc5 Chondrogenic Cell Line, Donya T. Burgess

Seton Hall University Dissertations and Theses (ETDs)

Fracture healing is characterized by inflammation, cartilage formation, bone deposition, and remodeling. Endochondral ossification is an important part of callus formation that relies on the maturation of chondrocytes. Early in their maturation these cells express collagen type II alpha 1 chain (COL2A1) and express collagen type X alpha 1 chain (COL10A1) as they mature further and become hypertrophic chondrocytes. Activation of the insulin pathway is considered a primary factor involved in the initiation of chondrogenesis and its progression during bone healing. Insulin mimetics like zinc chloride (ZnCl2) have been shown to improve bone healing outcomes and enhance bone healing ...


Characterization Of Notch1 And Pi3k-Pten-Akt/Mtor Pathway Interaction In Head And Neck Squamous Cell Carcinoma, Kyriante' Henry 2017 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Characterization Of Notch1 And Pi3k-Pten-Akt/Mtor Pathway Interaction In Head And Neck Squamous Cell Carcinoma, Kyriante' Henry

UT GSBS Dissertations and Theses (Open Access)

Head and neck squamous cell carcinoma (HNSCC) affects various mucosal sites of the upper aerodigestive tract, including the nasal and oral cavities, the nasopharynx, and the oropharynx. More than five hundred thousand new cases of HNSCC occurred in 2011 alone, with 50,000 reported cases in the United States. This trend made HNSCC the seventh most common non-skin cancer worldwide (Ferlay et al., 2015). Although significant epidemiological and pathological advancements have been made, survival rates have not improved much over the last 40 years, leaving a mortality rate that remains at approximately 50%. An unbiased drug screen demonstrated that HNSCC ...


Intracellular Signaling And Trafficking In Cancer: Role Of Rab5-Gtpase In Migration And Invasion Of Breast Cells, Nicole Porther 2017 Biological Sciences

Intracellular Signaling And Trafficking In Cancer: Role Of Rab5-Gtpase In Migration And Invasion Of Breast Cells, Nicole Porther

Nicole Porther

Metastasis is characterized pathologically by uncontrolled cell invasion, proliferation, migration and angiogenesis. Steroid hormones, such as estrogen, and growth factors, which include insulin growth factor I/II (IGF-1/IGF-2) therapy has been associated with most if not all of the features of metastasis. It has been determined that IGF-1 increases cell survival of cancer cells and potentiate the effect of E2 and other ligand growth factors on breast cancer cells. However not much information is available that comprehensively expounds on the roles of insulin growth factor receptor (IGFR) and Rab GTPases may play in breast cancer. The latter, Rab GTPases ...


Neuronal Degeneration And Short-Term Memory Impairment After Tbi, Obiamaraije Igwe 2017 University of Louisville

Neuronal Degeneration And Short-Term Memory Impairment After Tbi, Obiamaraije Igwe

Posters-at-the-Capitol

Traumatic brain injury (TBI) was associated with impaired short-term memory with causes of vehicle accidents and falls. Protein plaques containing fibrinogen (Fg), are associated with memory loss. After TBI, Fg in blood was higher than normal (>~2 mg/ml), which resulted in increased Fg in extravascular space. Therefore, Fg bonded to its endothelial receptor intercellular adhesion molecule-1 (ICAM-1). Fg then interacted with cellular prion protein (PrPC), which had a strong effect on the loss of memory and cognition. Mechanisms of Fg and PrPC complex formation and its functional implication are not known. This present study tested the level of Fg-PrPC ...


A Brief Guide To Striped Bass Ecology & Management In Chesapeake Bay, Mary C. Fabrizio, Troy D. Tuckey, Susanna Musick 2017 Virginia Institute of Marine Science

A Brief Guide To Striped Bass Ecology & Management In Chesapeake Bay, Mary C. Fabrizio, Troy D. Tuckey, Susanna Musick

Reports

Chesapeake Bay striped bass support important recreational fisheries along the US Atlantic coast; in the late 1970s, the population of striped bass collapsed as a result of overfishing and poor water quality in rivers used for spawning and rear-ing of young. Informed by stock assessments, strict management regulations were enacted in the mid-1980s and early 1990s; these highly effective regulations resulted in the recovery of the population in 1995. A key to the successful recov-ery of the Atlantic coast striped bass was the wide range of ages of spawning females and the associated differences in spawning behavior among ages. Age ...


E,E-Farnesol Inhibits Swarming Motility In Burkholderia Cepacia Through Rhamnolipid Production, Stephanie E. Nicholls, Alayna N. Sanderson, Andrea P. Schwartz, Lauren E. Ward, Jessica N. Weisensee, Molly Yandrofski, Tracy L. Collins 2017 Cedarville University

E,E-Farnesol Inhibits Swarming Motility In Burkholderia Cepacia Through Rhamnolipid Production, Stephanie E. Nicholls, Alayna N. Sanderson, Andrea P. Schwartz, Lauren E. Ward, Jessica N. Weisensee, Molly Yandrofski, Tracy L. Collins

Tracy Collins, Ph.D.

Burkholderia cepacia and Candida albicans both exhibit cell-to-cell communication through the use of quorum-sensing molecules (QSM) known as autoinducers. E,E-farnesol is a QSM produced by C. albicans which regulates its conversion from yeast to mycelium. Because there is a positive correlation between the presence of B. cepacia and C. albicans in the lungs of individuals with cystic fibrosis (CF), we examined whether E,E-farnesol had an effect on swarming motility in B. cepacia. Swarming motility was inhibited when B. cepacia was exposed to 250 µM of E,E-farnesol. In addition, there was a 26.8% decrease in rhamnolipid production ...


Experimental In-Vivo Models Used In Fat Grafting Research For Volume Augmentation In Soft Tissue Reconstruction, Jorge Lujan-Hernandez, Raghu Appasani, Kylee Sullivan, Leah Siegel-Reamer, Janice F. Lalikos 2017 University of Massachusetts Medical School

Experimental In-Vivo Models Used In Fat Grafting Research For Volume Augmentation In Soft Tissue Reconstruction, Jorge Lujan-Hernandez, Raghu Appasani, Kylee Sullivan, Leah Siegel-Reamer, Janice F. Lalikos

Open Access Articles

As the popularity of fat grafting research increases, animal models are being used as the source of pre-clinical experimental information for discovery and to enhance techniques. To date, animal models used in this research have not been compared to provide a standardized model. We analyzed publications from 1968-2015 to compare published accounts of animal models in fat grafting research. Data collected included: species used, graft characteristics (donor tissue, recipient area, amount injected, injection technique), time of sacrifice and quantification methods. Mice were most commonly used (56% of studies), with the "athymic nude" strain utilized most frequently (44%). Autologous fat was ...


Identification Of Stiffness-Induced Signalling Mechanisms In Cells From Patent And Fused Sutures Associated With Craniosynostosis., Sara Barreto, Arlyng Gonzalez Vazquez, Andrew R. Cameron, Fergal J. O'Brien, Dylan J Murray 2017 Royal College of Surgeons in Ireland

Identification Of Stiffness-Induced Signalling Mechanisms In Cells From Patent And Fused Sutures Associated With Craniosynostosis., Sara Barreto, Arlyng Gonzalez Vazquez, Andrew R. Cameron, Fergal J. O'Brien, Dylan J Murray

Anatomy Articles

Craniosynostosis is a bone developmental disease where premature ossification of the cranial sutures occurs leading to fused sutures. While biomechanical forces have been implicated in craniosynostosis, evidence of the effect of microenvironmental stiffness changes in the osteogenic commitment of cells from the sutures is lacking. Our aim was to identify the differential genetic expression and osteogenic capability between cells from patent and fused sutures of children with craniosynostosis and whether these differences are driven by changes in the stiffness of the microenvironment. Cells from both sutures demonstrated enhanced mineralisation with increasing substrate stiffness showing that stiffness is a stimulus capable ...


Intracellular Signalling Crosstalk In The Differentiation Of F9 Cells Into Extraembryonic Endoderm, Tina Nicole Cuthbert 2017 The University of Western Ontario

Intracellular Signalling Crosstalk In The Differentiation Of F9 Cells Into Extraembryonic Endoderm, Tina Nicole Cuthbert

Electronic Thesis and Dissertation Repository

Mouse F9 cells differentiate into primitive extraembryonic endoderm (PrE) with retinoic acid (RA) treatment, resulting in up-regulation of Gata6, which when translated directly activates Wnt6. Canonical Wnt signalling is required for PrE differentiation, and this, like most developmental processes, requires input from one or more additional pathways, including hedgehog (Hh). The Hh pathway is regulated by GATA6, and crosstalks positively/negatively with Wnt signalling. Ihh up-regulation in F9 cells accompanies PrE induction, but a role for GATA6 or Hh pathway activation in obligatory Wnt/ß-catenin signalling is not known. To address this, I show that RA induces Ihh and altered ...


Fs2 Equipment List And Closure Plan, Framingham State Food Study 2017 Framingham State University

Fs2 Equipment List And Closure Plan, Framingham State Food Study

(FS)2 Closure Plan

Framingham State Food Study Equipment List and Closure Plan


The Effect Of Hemodynamic Force On The Maturation Of Blood Vessels During Embryogenesis, Rachel Lee Padget 2017 Missouri State University

The Effect Of Hemodynamic Force On The Maturation Of Blood Vessels During Embryogenesis, Rachel Lee Padget

MSU Graduate Theses

Throughout embryonic development, blood vessels are derived from endothelial cells by way of vasculogenesis. During angiogenesis, vessels remodel to form a hierarchy of large-diameter arteries that branch into small-diameter capillaries. In this maturation, vessels respond to unidentified signaling events to become surrounded with an outer layer of vascular smooth muscle cells (vSMCs). This results in arteries that have a thick vSMC layer, veins that have a thin vSMC layer, and capillaries that have a very thin or absent vSMC layer. What remains to be determined is the cause of the thicker layer of vSMCs around proximal arteries. Previous studies have ...


The Role Of The Epithelial-To-Mesenchymal Transition (Emt) In Lung Cancer Progression, David H. Peng 2017 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

The Role Of The Epithelial-To-Mesenchymal Transition (Emt) In Lung Cancer Progression, David H. Peng

UT GSBS Dissertations and Theses (Open Access)

Lung cancer is the leading cause of cancer-related deaths due to conventional therapy resistance and metastatic disease, therefore understanding the mechanisms governing these biological functions is vital for improving patient survival. Approximately 30% of patients with the adenocarcinoma histologic subset of lung cancer possess an activating KRAS mutation, characterized by a lack of response to chemotherapies with a poor overall 5-year survival rate. Despite the mutational frequency, KRAS remains a challenge to pharmacologically inhibit and current drugs undergoing clinical trials that target specific downstream effector proteins of KRAS, such as MEK inhibitors, have failed to produce significant clinical benefits. Previous ...


Characterizing Reactive Glutamines In Fibrinogen And Elucidating Factor Xiii Substrate Specificity., Kelly Njine Mouapi 2017 University of Louisville

Characterizing Reactive Glutamines In Fibrinogen And Elucidating Factor Xiii Substrate Specificity., Kelly Njine Mouapi

Electronic Theses and Dissertations

Fibrinogen is the most abundant protein involved in blood coagulation and has been associated with many pathological implications in cardiovascular disease. At the final stages of blood clot formation, the transglutaminase Factor XIIIa introduces γ-glutamyl-ε-lysinyl covalent bonds between reactive glutamines and lysines in fibrin, which results in a tighter clot network that is resistant to fibrinolysis. Factor XIIIa crosslinks specific reactive glutamines on fibrinogen, selecting more reactive glutamines in the αC region of fibrinogen than any other chain. Although crosslinking pairs in the αC region have been identified, little is known about the extent of crosslinking and the role played ...


Characterization Of An 18f-Growth Hormone Secretagogue Probe For Positron Emission Tomography Imaging Of The Growth Hormone Secretagogue Receptor, Ahmed Abbas 2017 The University of Western Ontario

Characterization Of An 18f-Growth Hormone Secretagogue Probe For Positron Emission Tomography Imaging Of The Growth Hormone Secretagogue Receptor, Ahmed Abbas

Electronic Thesis and Dissertation Repository

Cardiovascular disease affects 1.6 million Canadians, of whom one-third have heart failure (HF). HF is diagnosed by imaging investigations and detection of circulating biomarkers. Most of the current imaging strategies study morphologic and gross functional changes, but fall short of imaging molecular abnormalities associated with HF. Biomarkers offer molecular targets; however, clinical biomarkers circulate systemically and are not cardiac-specific. Thus, there is critical need for a biomarker that is endogenous to myocardial tissues. The growth hormone secretagogue receptor 1a (GHSR1a), which binds the hormone ghrelin, is expressed by cardiomyocytes and is elevated in HF patients. This study characterized the ...


The Effect Of Insulin Treatment And Exercise Modality On Skeletal Muscle Fiber Size In Streptozotocin-Induced Type 1 Diabetic Rats, John Z. Nickels 2017 The University of Western Ontario

The Effect Of Insulin Treatment And Exercise Modality On Skeletal Muscle Fiber Size In Streptozotocin-Induced Type 1 Diabetic Rats, John Z. Nickels

Electronic Thesis and Dissertation Repository

Severe Type 1 Diabetes Mellitus (T1DM) is known to have several negative effects on skeletal muscle mass, a condition known as diabetic myopathy. One of these effects is the atrophy of the glycolytic muscle fibers. However, the role of intensity of insulin treatment and exercise modality in attenuating this loss in fiber cross-sectional area (CSA) specifically has yet to be determined. The purpose of this investigation was to determine the effects of 12 weeks of differing intensity of insulin therapy and exercise modality on the CSA of plantaris muscle fibers, identified by myosin heavy chain (MHC) of STZ-induced T1DM rats ...


Characterization Of Zic2 As An Oncoprotein In Prostate Cancer, Keira C. Davis 2017 Clark Atlanta University

Characterization Of Zic2 As An Oncoprotein In Prostate Cancer, Keira C. Davis

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

The field of prostate cancer research is in need of biological markers that predict which cancers do not need treatment, those that can be treated successfully with a localized treatment and more specific cases in which patients are likely to have an aggressive form of cancer that will require more aggressive surgical and chemotherapeutic treatments. ZIC2 is one of five members of a family of proteins that play critical roles in neural crest and mesoderm growth in normal embryonic brain development and in the adult cerebellum of vertebrates. Found throughout the animal kingdom, ZIC1-5 genes encode five distinct ZIC proteins ...


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