Considering A New Paradigm For Alzheimer’S Disease Research,
2014
Animal Studies Repository
Considering A New Paradigm For Alzheimer’S Disease Research, Gillian R. Langley
Experimentation Collection
Using Alzheimer’s disease as a case study, this review argues that it might be time to consider a new paradigm in medical research and drug discovery. The existing framework is overly dependent on often unvalidated animal models, particularly transgenic mice. Translational success remains elusive and costly late-stage drug failure is common. The conventional paradigm tends to overlook species differences and assumes that animal-based findings are generally applicable to humans. Could pathways-based research using advanced human-specific models probed with new tools, including those of systems biology, take centre stage? The current transition in chemical toxicology to a 21st-century paradigm could be …
Chitosan-Cellulose Composite For Wound Dressing Material. Part 2. Antimicrobial Activity, Blood Absorption Ability, And Biocompatibility,
2014
Marquette University
Chitosan-Cellulose Composite For Wound Dressing Material. Part 2. Antimicrobial Activity, Blood Absorption Ability, And Biocompatibility, April L. Harkins, Simon Duri, Luther C. Kloth, Chieu D. Tran
Clinical Lab Sciences Faculty Research and Publications
Chitosan (CS), a polysaccharide derived from chitin, the second most abundant polysaccharide, is widely used in the medical world because of its natural and nontoxic properties and its innate ability for antibacterial and hemostasis effects. In this study, the novel composites containing CS and cellulose (CEL) (i.e., [CEL + CS]), which we have previously synthesized using a green and totally recyclable method, were investigated for their antimicrobial activity, absorption of anticoagulated whole blood, anti-inflammatory activity through the reduction of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and the biocompatibility with human fibroblasts. The [CEL + CS] composites were found to …
Strategies To Sensitize Bladder Cancer Cells To Small Molecule Inhibitors Targeting The Pi3k Pathway,
2014
The University of Texas Graduate School of Biomedical Sciences at Houston
Strategies To Sensitize Bladder Cancer Cells To Small Molecule Inhibitors Targeting The Pi3k Pathway, Giovanni Nitti
Dissertations and Theses (Open Access)
After many years of cancer research, it is well accepted by the scientific community that the future cure for this disease lies in a personalized therapeutic approach. Anticipating therapeutic outcome based on the genetic signature of a tumor has become the new paradigm. The PI3K pathway represents an ideal target for bladder cancer, as many of the key proteins of this pathway are altered or mutated in this particular type of cancer. Several small molecule inhibitors have been developed to target this pathway, but their efficacy has been shown to be heterogeneous among different cell lines and mostly cytostatic but …
Pi3k- And Mtor-Dependent Mechanisms Of Lapatinib Resistance And Resulting Therapeutic Opportunities,
2014
The University of Texas Graduate School of Biomedical Sciences at Houston
Pi3k- And Mtor-Dependent Mechanisms Of Lapatinib Resistance And Resulting Therapeutic Opportunities, Samuel Brady
Dissertations and Theses (Open Access)
Breast cancers with HER2 amplification represent 20-25% of breast cancer cases and are frequently responsive to the HER2 kinase inhibitor lapatinib, but generally for only short duration. We aimed to understand how breast cancers with HER2 amplification become resistant to lapatinib, in order to identify potential therapies that can overcome lapatinib resistance. To establish lapatinib resistance models we treated three HER2+ breast cancer cell lines with lapatinib for several months until they became lapatinib-resistant. We then compared lapatinib-sensitive (parental) cells with their lapatinib-resistant (LapR) counterparts to identify changes conferring lapatinib resistance. We found that activation of PI3K, specifically the p110α …
Reactive Oxygen Species And P21 Waf1/Cip1 Are Both Essential For,
2014
The University of Texas Graduate School of Biomedical Sciences at Houston
Reactive Oxygen Species And P21 Waf1/Cip1 Are Both Essential For, Alison Fitzgerald
Dissertations and Theses (Open Access)
Treatment of Head and Neck Squamous Cell Carcinoma, HNSCC, often requires multimodal therapy, including radiation therapy. The efficacy of radiotherapy in controlling locoregional recurrence, the most frequent cause of death from HNSCC, is critically important for patient survival. One potential biomarker to determine radioresistance is TP53, whose alterations are predictive of poor radiation response. The following work shows that the p53 transcriptional target, p21, is crucial in initiating and maintaining senescence in HNSCC, through its ability to regulate reactive oxygen species (ROS). With the use of a novel system to evaluate the impact of the TP53 missense mutations, we …
Development Of Chimeric Type Iv Secretion Systems For Transfer Of Heterologous Substrates Across The Gram-Negative Cell Envelope,
2014
The University of Texas Graduate School of Biomedical Sciences at Houston
Development Of Chimeric Type Iv Secretion Systems For Transfer Of Heterologous Substrates Across The Gram-Negative Cell Envelope, Trista M. Berry
Dissertations and Theses (Open Access)
Many bacteria use Type IV Secretion Systems (T4SSs) to aid in pathogenesis by translocating virulence factors across the cell envelope and into eukaryotic cells. These systems are structurally and functionally diverse, but are often compared to the archetypal VirB/VirD4 T4SS of Agrobacterium tumefaciens. This system is composed of the VirD4 type IV coupling protein (T4CP) and 11 VirB subunits (VirB1-11) that assemble as the secretion channel and an extracellular pilus. The T4CP is an inner membrane ATPase that interacts with T4SS substrates and the secretion channel, and is thought to link substrates with the secretion channel and possibly energize …
Pancreatic Ribonuclease Functions As An Epidermal Growth Factor Receptor Ligand Independently Of Its Enzyme Activity And Contributes To Cetuximab Resistance,
2014
The University of Texas Graduate School of Biomedical Sciences at Houston
Pancreatic Ribonuclease Functions As An Epidermal Growth Factor Receptor Ligand Independently Of Its Enzyme Activity And Contributes To Cetuximab Resistance, Heng-Huan Lee
Dissertations and Theses (Open Access)
Ribonuclease (RNase) with its catalytic enzyme activity to degrade RNAs has been shown as a diagnostic serum marker for pancreatic cancer and has also been suspected to have an unidentified cell surface receptor. Epidermal growth factor receptor (EGFR), a well-characterized receptor tyrosine kinase is an effective therapeutic target in multiple cancer types. However, clinical trials targeting EGFR have not demonstrated improved therapeutic efficacy in pancreatic cancer. Here, we show that both bovine pancreatic RNase A (bRNaseA) and human RNase 5 (hRNase5) act as EGFR ligands and directly activate EGFR to promote epithelial-mesenchymal transition. This ligand-like activity is independent of RNases’ …
Targeting The Mdm2-P53 Axis For The Treatment Of Dedifferentiated Liposarcoma,
2014
The University of Texas Graduate School of Biomedical Sciences at Houston
Targeting The Mdm2-P53 Axis For The Treatment Of Dedifferentiated Liposarcoma, Katelynn Bill
Dissertations and Theses (Open Access)
Dedifferentiated liposarcoma (DDLPS) is an aggressive malignancy characterized by a high rate of recurrence and dismal patient outcome. Minimal improvement in patient survival has been made in the last several decades, highlighting the crucial need for improved therapeutic strategies. A better understanding of the molecular deregulations underlying DDLPS would facilitate the discovery of improved therapeutic approaches. MDM2 is a well characterized oncoprotein and the most known negative regulator of p53. MDM2 amplification is considered the “hallmark” of DDLPS. Additionally, these tumors are known to harbor wild-type p53. We sought to take advantage of this knowledge and evaluate the role of …
Energy Stress Causes Chaperones To Assemble Into Cytoplasmic Complexes,
2014
The University of Texas Graduate School of Biomedical Sciences at Houston
Energy Stress Causes Chaperones To Assemble Into Cytoplasmic Complexes, Kimberly J. Cope
Dissertations and Theses (Open Access)
The majority of proteins require molecular chaperones to assist their folding into tertiary and quaternary structures. Certain stresses can compromise the weak hydrophobic forces responsible for these structures and lead to protein unfolding, misfolding, and aggregation. Aggregates of proteins are hallmarks of devastating diseases such as Alzheimer’s, Parkinson’s, and Huntington’s diseases. Fortunately, bacteria, plants, and fungi have a potent disaggregase, named Hsp104 in Saccharomyces cerevisiae. Recently, heat-induced aggregates, termed Q-bodies, were found to contain three molecular chaperones: Hsp70, Hsp104, and Hsp42. Their coalescence from small puncta into larger inclusions required Hsp104. During glucose deprivation, a stress that isn’t known to …
A Comparison Of Fatigue During Cardiocerebral Resuscitation With Different Compression Rates Among Layperson And Professional Rescuers,
2014
California Polytechnic State University, San Luis Obispo
A Comparison Of Fatigue During Cardiocerebral Resuscitation With Different Compression Rates Among Layperson And Professional Rescuers, Christopher Cassidy
Master's Theses
Quality chest compressions during Cardiopulmonary Resuscitation (CPR) are vital to maintaining adequate perfusion of oxygenated blood to the organs of the body to sustain life. Over the years, the compression rate recommended in Basic Life Support (BLS)/ Advanced Cardiac Life Support (ACLS) protocols for the best possible outcome has risen, and with that increase there are questions regarding rescuer fatigue and the effectiveness of compressions. Layperson and professional rescuers, answering to an emergency, both maintain continuous chest compressions until advanced life support arrives. Depending on the location, this arrival time would most likely be longer than the two minute standard …
The Effect Of Attentional Focus Instructions On Golf Swing Performance In Recreational Golfers,
2014
Boise State University
The Effect Of Attentional Focus Instructions On Golf Swing Performance In Recreational Golfers, Jeffrey D. Eggleston
Boise State University Theses and Dissertations
Previous research has addressed the effectiveness of attentional focus instructions in improving golf performance with a single training session. The purpose of the current study was to investigate the effect of external (EF) attentional focus instructions on recreational golfers’ performance over a distributed training period and extended retention interval. Performance was measured by club head velocity (CHV) and X-factor as both have been correlated with greater performance. The current study extends the work of An, Wulf, and Kim (2013), by increasing the training period and retention interval. It was hypothesized EF group would have greater CHV and X-factor measurements during …
Strategic Focus On 3r Principles Reveals Major Reductions In The Use Of Animals In Pharmaceutical Toxicity Testing,
2014
Karolinska Institutet
Strategic Focus On 3r Principles Reveals Major Reductions In The Use Of Animals In Pharmaceutical Toxicity Testing, Elin Törnqvist, Anita Annas, Britta Granath, Elisabeth Jalkesten, Ian Cotgreave, Mattias Öberg
Application of Alternative Methods Collection
The principles of the 3Rs, Replacement, Reduction and Refinement, are being increasingly incorporated into legislations, guidelines and practice of animal experiments in order to safeguard animal welfare. In the present study we have studied the systematic application of 3R principles to toxicological research in the pharmaceutical industry, with particular focus on achieving reductions in animal numbers used in regulatory and investigatory in vivo studies. The work also details major factors influencing these reductions including the conception of ideas, cross-departmental working and acceptance into the work process. Data from 36 reduction projects were collected retrospectively from work between 2006 and 2010. …
Blood-Based Biomarkers For Traumatic Brain Injury: Evaluation Of Research Approaches, Available Methods And Potential Utility From The Clinician And Clinical Laboratory Perspectives,
2014
ARUP Institute for Clinical and Experimental Pathology, ARUP Laboratories
Blood-Based Biomarkers For Traumatic Brain Injury: Evaluation Of Research Approaches, Available Methods And Potential Utility From The Clinician And Clinical Laboratory Perspectives, Frederick G. Strathmann, Stefanie Podlog (Nee Schulte), Kyle Goerl, David J. Petron
Athletic Training Collection
Blood-based biomarkers for traumatic brain injury (TBI) have been investigated and proposed for decades, yet the current clinical assessment of TBI is largely based on clinical symptoms that can vary widely amongst patients, and have significant overlap with unrelated disease states. A careful review of current treatment guidelines for TBI further highlights the potential utility of a blood-based TBI biomarker panel in augmenting clinical decision making. Numerous expert reviews on blood-based TBI biomarkers have been published but a close look at the methods used and the astonishing paucity of validation and quality control data has not been undertaken from the …
Regulation Of Strand-Specific Processing In Human Pre-Mir-371 And Its Mouse Homologs,
2014
Rowan University
Regulation Of Strand-Specific Processing In Human Pre-Mir-371 And Its Mouse Homologs, Jianting Shi
Graduate School of Biomedical Sciences Theses and Dissertations
MicroRNAs (miRNAs) are small noncoding RNAs, known to regulate genes by inducing target mRNA degradation or translational repression. This regulatory function has been shown to assist developmental timing control and increasingly more evidence reveals some of the miRNAs may have tissue/cell type-specific function, showing the potential to assist cell differentiation. Mouse miR-290-295 cluster is embryonic stem cell (ESCs)-specific miRNA cluster and human miR-371-373 cluster has been verified to be its functional homolog. We have previously demonstrated that human pre-miR-371 is processed into multiple miRNA species, which represent the seeds of the mouse of miR-290-5p, miR-292-5p, miR-292-3p-iso2 and miR-293-3p. Deep sequencing …
Technique For Staining The Myelin-Like Sheath In Earthworms,
2014
Bemidji State University
Technique For Staining The Myelin-Like Sheath In Earthworms, Kayla Brown
Honors Capstones
Capstone submitted as a graduation requirement for the BSU Honors Program.
Earthworm Remyelination Gene Expression Analysis,
2014
Bemidji State University
Earthworm Remyelination Gene Expression Analysis, Shelby Shevik
Honors Capstones
Capstone submitted as a graduation requirement for the BSU Honors Program.
Apolipoprotein E4 And Sirt1 Interaction In Alzheimer’S Disease,
2014
Dominican University of California
Apolipoprotein E4 And Sirt1 Interaction In Alzheimer’S Disease, Brittany Ann Philpot
Dissertations, Masters Theses, Capstones, and Culminating Projects
Alzheimer’s disease (AD) is a neurodegenerative disorder whose exact cause(s) are still unknown. Εpsilon 4, an allele of apolipoprotein E (ApoE4), is currently the most important risk factor for Alzheimer’s disease. Individuals that inherit two copies of the ApoE ε4 allele have an approximately ten to thirty times increased risk of developing AD in comparison to persons not carrying this allele. This association may relate to ApoE4’s susceptibility to proteolysis and neurotoxicity. Amyloid precursor protein (APP) is involved with neurite extension and neurite retraction, and has been shown to function as a molecular switch with two separate cleavage patterns. Cleavage …
Effects Of Heregulin On Muscle: A Biochemical And Histological Analysis,
2014
Dominican University of California
Effects Of Heregulin On Muscle: A Biochemical And Histological Analysis, Nicole Justine Moss
Dissertations, Masters Theses, Capstones, and Culminating Projects
Duchenne Muscular Dystrophy, the most common inherited X-linked genetic disease affecting 1 in 5000 boys, results from a dysfunctional dystrophin protein encoded by the DMD gene. Dystrophin interacts with protein complexes linking the extracellular matrix to the cytoskeleton of muscle fibers. Without dystrophin functioning properly, sarcolemmal membrane stabilization is compromised during the mechanical rigors involved with muscle contraction leading to progressive muscular dystrophy. Heregulin/neuregulin-1 (HRG), a member of the epidermal growth factor family has been shown to induce neuromuscular junction (NMJ) gene expression in vitro and improve skeletal muscle function in dystrophic mice. However, it is unclear if the HRG …
Microrna Expression Signature Of Retinal Pigmented Epithelial Cells Associated With The Phenotype Of Age-Related Macular Degeneration,
2014
Dominican University of California
Microrna Expression Signature Of Retinal Pigmented Epithelial Cells Associated With The Phenotype Of Age-Related Macular Degeneration, Mark Anthony Gutierrez
Dissertations, Masters Theses, Capstones, and Culminating Projects
Age-related macular degeneration is a debilitating condition that manifests as a loss of the central portion of an individual’s field of vision, affecting 1 in 3 people over the age of 80. With regards to the retina, the organ primarily responsible for an individual’s sense of vision, this condition is associated with the degeneration of the central point in the retina, known as the macula, which contains the highest concentration of light-sensitive photoreceptors. It is currently known that the human retina exhibits a gradual decrease in protective detoxifying factors such as glutathione-S-transferase-1 and catalase as well as increased lipid peroxidation, …
Evaluation Of Select Publicly Available In Silico Methods For Predicting Functional Effects Of Missense Mutations In The Galns Gene,
2014
Dominican University of California
Evaluation Of Select Publicly Available In Silico Methods For Predicting Functional Effects Of Missense Mutations In The Galns Gene, Kathryn Davidson
Dissertations, Masters Theses, Capstones, and Culminating Projects
The ability to sequence patient DNA has led to an explosion in the reports of mutations for a number of diseases. Frequently, published reports include in silico predictions of the probability that the mutations are disease-associated. The question asked here is how well these in silico methods predict the effects of new mutations, i.e., mutations not included in the dataset(s) used for training and testing the in silico method. To address this question, we examined mutations associated, or potentially associated, with Morquio A (MPS IVA), a rare, autosomal recessive lysosomal storage disorder (LSD) caused by a deficiency of lysosomal enzyme …
