Laboratory and Basic Science Research Commons^™

Can Acute Dermal Systemic Toxicity Tests Be Replaced With Oral Tests? A Comparison Of Route-Specific Systemic Toxicity And Hazard Classifications Under The Globally Harmonized System Of Classification And Labelling Of Chemicals (Ghs), Nigel P. Moore, David J. Andrew, Donald L. Bjerke, Stuart Creton, David Dreher, Thomas Holmes, Pilar Prieto, Troy Seidle, Tim G. Rowan

Experimentation Collection

Acute systemic toxicity data (LD50 values) and hazard classifications derived in the rat following oral administration and dermal application have been analysed to examine whether or not orally-derived hazard classification or LD50 values can be used to determine dermal hazard classification. Comparing the oral and dermal classifications for 335 substances derived from oral and dermal LD50 values respectively revealed 17% concordance, and indicated that 7% of substances would be classified less severely while 76% would be classified more severely if oral classifications were applied directly to the dermal route. In contrast, applying the oral LD50 values within the dermal classification …

Diabetes Mellitus And Hypercholesterolemia Are Risk Factors For Alzheimer’S Disease And Appear To Affect The Integrity Of The Blood Brain Barrier, Jacqueline Dash

Graduate School of Biomedical Sciences Theses and Dissertations

Studies have shown that the vascular risk factors common to diabetes mellitus and hypercholesterolemia are also risk factors for Alzheimer’s disease (AD). It is currently unknown how these diseases are associated with AD, but they may cause a leak in the blood brain barrier (BBB), which is one of the hallmarks of AD. In this preliminary study, over 150 pig brain slides were tested for the expression levels of tight junction proteins occludin and claudin V in the BBB microvasculature. There were three groups of pig brains used in this study namely, control pigs, pigs with diabetes mellitus and hypercholesterolemia …

A Mechanistic Hypothesis Of The Factors That Enhance Vulnerability To Nicotine Use In Females, Laura O'Dell

Laura Elena O'Dell

Women are particularly more vulnerable to tobacco use than men. This review proposes a unifying hypothesis that females experience greater rewarding effects of nicotine and more intense stress produced by withdrawal than males. We also provide a neural framework whereby estrogen promotes greater rewarding effects of nicotine in females via enhanced dopamine release in the nucleus accumbens (NAcc). During withdrawal, we suggest that corticotropin-releasing factor (CRF) stress systems are sensitized and promote a greater suppression of dopamine release in the NAcc of females versus males. Taken together, females display enhanced nicotine reward via estrogen and amplified effects of withdrawal via …

Purification And Characterization Of Oxidation-Resistant Ribonuclease Inhibitor Variants, Alec W. Uebersohn

Lawrence University Honors Projects

Ribonuclease inhibitor (RI) is an intracellular mammalian protein which binds vertebrate-specific ribonucleases; this interaction is one of the tightest non-covalent interactions yet discovered. The biological activity of RI is poorly understood, but it is thought to regulate the biological functions of ribonucleases, which include initiating blood vessel growth, maintaining neuron viability, attacking pathogens, and mediating cell stress responses. RI is also involved in pathways unrelated to ribonucleases, including interactions with Drosha and PTEN, an anti-tumor protein.

One of the defining characteristics of RI is its oxidation sensitivity, a result of its unusually high cysteine content. The oxidation of RI is …

Validation Of Antibodies Used To Study Hypoxia Inducible Factors In Two Species Of Fundulus, Jenna D. Hill

University of New Orleans Theses and Dissertations

Hypoxia inducible factors (HIFs) are transcription factors and the master regulators of oxygen-dependent gene expression in animals. The focus of this thesis is the distribution of HIF protein in tissues of the fish Fundulus heteroclitus and F. grandis, two widespread species that occur in naturally hypoxic waters. Polyclonal antibodies against HIF-1α, HIF-2α, and HIF-3α were tested on proteins made in vitro and on extracts made from several tissues of normoxic and hypoxic fish. Antibodies against HIF-1α and 3α bound specifically to full length protein made in vitro, and produced bands on western blots of nuclear extracts of near …

Metronidazole Effects On Hindgut Microflora Residing Within The Subterranean Termite Reticulitermes Flavipes, Alexandra Gjevre

Morehead State Theses and Dissertations

A thesis presented to the faculty of the College of Science and Technology at Morehead State University in partial fulfillment of the requirements for the Degree of Master of Science by Alexandra Gjevre on May 1, 2013.

Development Of A Cellular Model For Morquio A Syndrome, Virgen Guadalupe Sierra

Dissertations, Masters Theses, Capstones, and Culminating Projects

Mucopolysaccharidosis IVA (MPS IVA; Morquio A), is a lysosomal storage disorder characterized by the deficiency of N-acetylgalactosamine-6-sulfatase (GALNS), resulting in the accumulation of glycosaminoglycans (GAGs) such as keratan sulfate (KS) (Northover et al., 1996) and chondroitin-6-sulfate. There is no applicable animal model or appropriate cell lines currently available for the study of MPS IVA. Furthermore, patient-specific material is limited and difficult to obtain, rendering the study of MPSIVA pathogenesis challenging. Thus, the generation of an induced pluripotent stem cell (iPSC) line from patient-specific somatic cells shows potential for further examining the pathogenesis of MPS IVA. With this technology, differentiation protocols …

Characterization Of Tcl1-Tg:P53-/- Mice That Resemble Human Chronic Lymphocytic Leukemia With 17p-Deletion, Jinyun Liu

Dissertations & Theses (Open Access)

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the United Statesand Europe. CLL patients with deletion of chromosome 17p, where the tumor suppressor p53 gene is located, often develop a more aggressive disease with poor clinical outcomes. However, the underlying mechanism remains unclear. In order to understand the underneath mechanism in vivo, I have recently generated mice with E_u-TCL1-Tg:p53^-/- genotype and showed that these mice develop aggressive leukemia that resembles human CLL with 17p deletion. The E_u-TCL1-Tg:p53^-/- mice developed CLL disease at 3-4 months, …

Dual Mtor/Hdac Inhibition: Preclinical Development Of A Novel Breast Cancer Therapy, Mariya Alexandra Yevtushenko

Dissertations, Masters Theses, Capstones, and Culminating Projects

HER2 (human epidermal growth factor receptor-2) and/or estrogen receptor (ER) are overexpressed in ~80% of human breast cancers. Although modern therapeutics (e.g. Trastuzumab, Tamoxifen) target the HER2 and ER receptors, clinical resistance often develops due to activation of downstream signaling pathways, including phosphoinositide 3 kinase-AKT/protein kinase Bmammalian target of rapamycin (PI3K/AKT/mTOR), despite effective upstream receptor inhibition. Activation of this pathway increases ribosome biogenesis and translation of oncogenic mRNAs, which are controlled by intracellular histone deacetylase (HDAC) activity as well. In fact, HDAC inhibitors that have been implemented into clinical practice are capable of overcoming resistance to HER2 and ER targeted …

The Effects Of Chronic Cadmium Exposure On Breast Cancer Progression, Esmeralda Ponce

Dissertations, Masters Theses, Capstones, and Culminating Projects

Cadmium is an environmental contaminant that enters the body usually through diet or cigarette smoke. Exposure to cadmium has been associated with the development of breast cancer. Recent studies have suggested that cadmium functions as an endocrine disruptor and mimics the actions of estrogen in breast cancer cells by activating the receptor (ER) to promote breast cancer cell growth. Although acute cadmium exposure is known to promote estrogen receptor-mediated gene expression associated with growth, the consequence of chronic cadmium exposure has been unclear. Since heavy metals are known to bioaccumulate, it is necessary to understand and elucidate the effects of …

Enzyme Kinetics Of Recombinant Human Arylsulfatase B (Rhasb), Katherine Marie Cunico

Dissertations, Masters Theses, Capstones, and Culminating Projects

This project seeks to explain the enzyme kinetics of recombinant human Arylsulfate sulfatase B (rhASB) by using an in vitro bioassay and direct hydrolysis substrate assay to approach the problem of substrate limitation in establishing a representative kcat for rhASB. The project also explores the makeup of a possible ASB complex within the cell. Previous published studies have sought to establish a turnover rate for rhASB, but have run into the problem of substrate limitation. Using a direct monosaccharide hydrolysis assay in conjunction with the same natural substrate bioassay, this project will attempt to provide insight to the kcat, the …

Mutations In Parkin (Pdr-1) Results In Increased Reproductive Fitness In C. Elegans, Tracy Ann Barhydt

Dissertations, Masters Theses, Capstones, and Culminating Projects

Parkinson’s disease (PD) is largely an idiopathic disease that includes contributions from both genetic and environmental factors, with aging itself being the largest risk factor. These combined susceptibility factors are believed to accumulatively contribute to initiation and progression of Parkinson’s disease. Although most cases of PD are idiopathic, rare genetic forms of the disease do exist. In these cases, an important unanswered question is why mutations that cause the disease have come to be maintained within the human population? One possibility is based on what is known as the Antagonist Pleiotropic Theory (APT) of Aging, a theory that states that …

Moderate Intensity Cycling Following Eccentric Contractions Does Not Attenuate Indirect Markers Of Muscle Damage., Brendan P. Major

Electronic Thesis and Dissertation Repository

Unaccustomed eccentric muscle contraction causes prolonged changes to indirect markers of muscle damage (Clarkson & Hubal, 2002). It has been proposed that active recovery therapy (ART) consisting of non-eccentric based movements may aid in the recovery process uts of moderate intensity cycling in the followin(Sayers et al., 2000). The purpose of this investigation was to compare the effect of ART on changes in one repetition maximum (1RM), dynamic muscle function, swelling, delayed onset muscle soreness (DOMS), and changes in MRI T2 relaxation times post exercise induced muscle damage (EIMD). Ten previously trained participants (at least 1 lower body resistance training …

Histological And Biochemical Changes In Aegle Marmelos Corr. Before And After Acclimatization, Rajesh Pati

Rajesh Pati

Maximum mortality of micropropagated plants occur during acclimatization phase because plantlets undergo rapid and extreme changes in physiological functioning, histological and biochemical changes. In order to investigate the actual reason of this limitation, test samples were collected at different stages of micropropagation of Aegle marmelos Corr. (In vitro stage, acclimation stage). The biochemical result showed that micropropagated plantlets produced significantly low total chlorophyll (0.042 mg/g fresh weight), reducing sugar (3.227%), NR activity (1.353 NO2/h/g fresh weight) and but higher protein (0.048 μg/g) during in vitro phase. The in vitro raised plants showed abnormal histological features like altered leaf mesophyll, absence …

Flash4 Dark Reference Images, George Mcnamara

George McNamara

Hamamatsu FLASH4.0 dark reference images, acquired with 10 second exposure times, no light to camera. Camera offset (set by Hamamatsu( is ~100 (the average intensity of the first image is always ~1 intensity level higher - an odd feature, but trivial in practice for a 16-bit camera).

George McNamara, Ph.D.

Single Cells Analyst at L.J.N. Cooper Lab

University of Texas M.D. Anderson Cancer Center

Inflammatory Findings On Species Extrapolations: Humans Are Definitely No 70-Kg Mice, Marcel Leist, Thomas Hartung

Validation of Alternative Methods Collection

Modern toxicology has embraced in vitro methods, and major hopes are based on the Omics technologies and systems biology approaches they bring along (Hartung and McBride in ALTEX 28(2):83–93, 2011; Hartung et al. in ALTEX 29(2):119–28, 2012). A culture of stringent validation has been developed for such approaches (Leist et al. in ALTEX 27(4):309–317, 2010; ALTEX 29(4):373–88, 2012a; Toxicol Res 1:8–22, 2012b), while the quality and usefulness of animal experiments have been little scrutinized. A new study (Seok et al. 2013) now shows the low predictivity of animal responses in the field of inflammation. These findings corroborate earlier findings from …

The Effects Of Blocking Hippocampal Acetylcholine On Meal Onset In Male Rats, Jasmine Nicole Gentry

Georgia State Undergraduate Research Conference

No abstract provided.

Video Codec Performance (Excel Spreadsheet), George Mcnamara

George McNamara

Video codec performance (Excel spreadsheet). Movie was made in 2005-2006 when I worked at City of Hope National Medical Center. VTLF refers to Video Timelapse Light Facility. Videos were outputted from MetaMorph as AVI files. Personally, I always recommend uncompressed video files fro scientific uses. I also encourage posting the original scientific data format (ex. .lsm, .zvi, .lif, .stk).

Pubspectra Tattletales, George Mcnamara

George McNamara

Tattletales for Multiplex Fluorescent Reporters in Single Cells for Metabolomics

George McNamara

As of April 2013: L.J.N. Cooper & D.A. Lee Cellular Immunotherapy Lab, University of Texas M.D. Anderson Cancer Center, Houston, TX

Email: gtmcnamara@mdanderson.org, geomcnamara@earthlink.net

Tattletales is my concept for spatial multiplexing many fluorescent protein (FP) biosensors in the same live cell. For example, there are excellent FP biosensors to Ca++ ions, pH, glucose, ribose, glutamine, glutamate, ATP, redox, ROS, pyruvate, cAMP, cGMP, IP3, PI(3,4,5)P3, cell cycle indicators (Fucci2), PKA, PKC, photsphatases, caspase(s) [1, 2]. However, these are typically used one biosensor per experiment, due in part to flooding …

The Problem Of Too Many Statistical Tests: Subgroup Analyses In A Study Comparing The Effectiveness Of Online And Live Lectures, David M. Lane

Numeracy

The more statistical analyses performed in the analysis of research data, the more likely it is that one or more of the conclusions will be in error. Multiple statistical analyses can occur when the sample contains several subgroups and the researchers perform separate analyses for each subgroup. For example, separate analyses may be done for different ethnic groups, different levels of education, and/or for both genders. Media reports of research frequently omit information on the number of subgroup analyses performed thus leaving the reader with insufficient information to assess the validity of the conclusions. This article discusses the problems with …