Laboratory and Basic Science Research Commons^™

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 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 …

Enhancing Communication Between Scientists, Government Officials, And The Lay Public: Advancing Science And Protecting The Public's Welfare Through Better Multi-Stakeholder Interfacing, Clark J. Lee, Patrick P. Rose, Earl Stoddard Iii

Homeland Security Publications

No abstract provided.

Generation And Characterization Of Peptide Fusion Proteins, Brianna L. Probasco

Graduate School of Biomedical Sciences Theses and Dissertations

Pathogenic Th17 cells drive progression of many autoimmune diseases. Th17 cells develop from naïve T cells in the immune system after antigen-driven stimulation in a specific cytokine environment. Normally, T cells act to fight off infection, but when not properly controlled, they can cause disease. The cytokine interleukin-23 (IL-23) plays an essential role in the expansion of pathogenic Th17 cells. IL-23 is a heterodimeric protein, composed of a p19 alpha chain and a p40 beta chain. The p40 is also part of IL-12 and binds to the IL-12 receptor beta 1 (IL-12Rβ1) subunit. Thus, it follows that the IL-23 receptor …

Humane Society International’S Global Campaign To End Animal Testing, Troy Seidle

Experimentation Collection

The Research & Toxicology Department of Humane Society International (HSI) operates a multifaceted and science-driven global programme aimed at ending the use of animals in toxicity testing and research. The key strategic objectives include: a) ending cosmetics animal testing worldwide, via the multinational Be Cruelty-Free campaign; b) achieving near-term reductions in animal testing requirements through revision of product sector regulations; and c) advancing humane science by exposing failing animal models of human disease and shifting science funding toward human biology-based research and testing tools fit for the 21st century. HSI was instrumental in ensuring the implementation of the March 2013 …

A Vision Becoming Reality, Gill Langley

Laboratory Experiments Collection

Non-animal science in toxicology and health research has been progressing for decades, but only now is it being seen widely as advanced science. The emergence of novel human biology-based tools and models, combined with legislative and regulatory change, a 21st century concept for toxicology, continuing failures in the drug pipeline, and systematic critiques of animal models, have created a pivotal moment of change. The leading edge is starting to become the norm. Humans and other animals are likely to benefit as a result.

Food For Thought … Mechanistic Validation, Thomas Hartung, Sebastian Hoffman, Martin Stephens

Experimentation Collection

Validation of new approaches in regulatory toxicology is commonly defined as the independent assessment of the reproducibility and relevance (the scientific basis and predictive capacity) of a test for a particular purpose. In large ring trials, the emphasis to date has been mainly on reproducibility and predictive capacity (comparison to the traditional test) with less attention given to the scientific or mechanistic basis. Assessing predictive capacity is difficult for novel approaches (which are based on mechanism), such as pathways of toxicity or the complex networks within the organism (systems toxicology). This is highly relevant for implementing Toxicology for the 21st …

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

Humane Science Movement Collection

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 …

White Bass Assessment In Regards To Changes In Water Level On Lake Traverse, Aaron Wilson

Journal of Earth and Life Science

Until recently the white bass Morone chrysops has been somewhat ignored by anglers, more so in Minnesota than other states; most likely due to their limited distribution throughout the state. However, with more anglers becoming aware of the sporting and culinary potentials of white bass, interests have risen. With this rise in angler interest, there should be a rise in white bass assessments. Knowing what factors may be influencing white bass population dynamics will allow fisheries professionals to better manage and protect white bass fisheries. White bass are often found in rivers and impoundments were dams are present and water …

The Effect Of Visual Wulst Lesions And Trigeminal Nerve Sectioning On The Discrimination Of Magnetic Inclination In The Homing Pigeon (Columba Livia), Merissa Acerbi

Honors Projects

The ability of homing pigeons to return to their loft from unknown places has fascinated scientists for centuries. It is well established that homing pigeons, like migratory birds, posses an innate magnetic inclination compass to determine direction by measuring the angle between the magnetic field vector and the Earth's surface. Recent work has indicated that the avian magnetic compass is light mediated and appears to mediate magnetic information to the brain. This occurs via a visual pathway with processing in the visual Wulst area of the forebrain. There is, however, also evidence from other avian species that magnetic direction may …

Brown Trout Spawning Location And Relationship To Suitable Winter Habitat, Matthew L. Skoog

Journal of Earth and Life Science

Brown trout are a popular game fish throughout much of the world. Understanding habitat requirements is necessary for the successful management of brown trout. This study looks at the spawning habitat preferences and relationship of redd location to wintering habitat of brown trout in the Straight River, Minnesota. Brown trout in the Straight River were found to spawn in similar habitat to brown trout looked at in previous literature. All redds were located on gravel substrate. Seventy eight percent of redds were associated with some sort of cover. Water velocities at the redd sites. (mean=0.456 ms/cm), dissolved oxygen (mean=9.78 mg/L), …

Comparison Of A Length Size Limit Of Northern Pike Population On Two Lakes In North Central Minnesota, Ethan A. Puttonen

Journal of Earth and Life Science

Fisheries managers use length size limits on northern pike (Esox lucis) to improve the size structure in select lakes. The objective of this study was to compare two similar lakes, one with a length size limit and one without, to determine if a length size limit is improving the northern pike size structure. Blueberry Lake showed a higher abundance of larger fish than Stocking Lake. Of the fish caught, 25% in Blueberry Lake were over 600 mm (24 in), and were in the protected slot. Stocking Lake had a smaller portion of fish of this size with only …

Biology Department Newsletter, No. 3, Sacred Heart University

Biology Newsletter

No abstract provided.

Diagnosis Of Schistosoma Mansoni Without The Stool: Comparison Of Three Diagnostic Tests To Detect Schiostosoma Mansoni Infection From Filtered Urine In Zambia, Nilanjan Lodh, James C. L. Mwansa, Mabel M. Mutengo, Clive J. Shiff

Clinical Lab Sciences Faculty Research and Publications

Diagnosis for intestinal Schistosoma mansoni lacks sensitivity and is arduous to conduct. The standard diagnostic tests, Kato-Katz (KK) and circulating cathodic antigen (CCA) both lack sensitivity and with KK, require obtaining, transporting, and examining fresh stool. We compared diagnostic efficacy of KK, CCA, and polymerase chain reaction (PCR) to detect S. mansoni infection (species-specific DNA) from 89 filtered urine samples collected in Zambia. The PCR was the strongest indicator of positive cases with sensitivity and specificity of 100% in comparison to CCA (67% and 60%) and KK (50% and 100%). High positive and negative predictive values (100%) were also indicative …

Filtering Efficiency And Feeding Mechanisms Of Daphnia Pulex On Microcystis Aeruginosa And Nannochloropsis, Elizabeth Orlowicz

Honors Theses and Capstones

The filtering and feeding rate of Daphnia pulex from the Old Durham Reservoir, Durham, NH, were measured to determine the feeding efficiency on different concentrations of non-toxic Nannochloropsis (Class Eustigmatophyceae) and toxigenic cyanobacteria Microcystis aeruginosa. Direct observations of thoracic appendage beats and post-abdominal rejections were also measured at 5*10⁵ and 10⁶ cells mL^-1 concentrations of Nannochloropsis and M. aeruginosa to examine the feeding mechanisms of the D. pulex. In the presence of increasing Nannochloropsis concentrations, the filtering rates decreased and the feeding rates increased. When exposed to M. aeruginosa, both the filtering and feeding …

Brief Embryonic Strychnine Exposure In Zebrafish Causes Long-Term Adult Behavioral Impairment With Indications Of Embyronic Synaptic Changes, Nicole M. Roy, Brianna Arpie, Joseph Lugo, Elwood Linney, Edward D. Levin, Daniel Cerutti

Biology Faculty Publications

Zebrafish provide a powerful model of the impacts of embryonic toxicant exposure on neural development that may result in long-term behavioral dysfunction. In this study, zebrafish embryos were treated with 1.5mM strychnine for short embryonic time windows to induce transient changes in inhibitory neural signaling, and were subsequently raised in untreated water until adulthood. PCR analysis showed indications that strychnine exposure altered expression of some genes related to glycinergic, GABAergic and glutamatergic neuronal synapses during embryonic development. In adulthood, treated fish showed significant changes in swimming speed and tank diving behavior compared to controls. Taken together, these data show that …

Light Scattering Study Of Elongated Particles: From Inorganic Nanorice To Polypeptide Micelles, Philip Dee

Undergraduate Research Posters 2012

Utilizing the powerful experimental technique of Dynamic Light Scattering (DLS) for size characterization of anisotropic particles can be extremely misleading. Unfortunately, this point is often not realized by researchers who strive for particle sizing of nanoparticles in suspensions. We present a consistent analysis of DDLS results on FeOOH nanorice and outline the potential difficulties and challenges of DDLS application for polypeptide micelles.

A Genetic Survey Of English Sole Populations In The Salish Sea, Elizabeth S. Gutierrez, Gary A. Winans, Jon Baker, Amanda Cope

STAR Program Research Presentations

This summer I interned at the Northwest Fisheries Science Center in Seattle, WA and participated in NOAA’s Salish Sea Project. The Salish Sea Project’s goal is to identify genetically distinctive groups of species in the Salish Sea that may have unique evolutionary and/or adaptive backgrounds. These findings will allow NOAA to promote and monitor the natural production of species in the Salish Sea, to select representative populations for experimental work regarding pollution, ocean acidification and climate change, to contribute to managing the ecosystem for intra- and inter-species diversity, and to help make informed decisions about adaptive management and marine protected …

Analyzing Environmental Microbes For Genomic Regions Promoting Ionic Liquid Tolerance In E. Coli, Ann Nguyen, Alison Richins, Thomas Rüegg, Steven Singer, Michael Thelen

STAR Program Research Presentations

Ionic liquids (ILs) are promising as solvents to increase the efficiency of biofuel production; however, ILs are toxic to microbes used in the fermentation of liquid fuels. To engineer IL resistant biofuel hosts, environmental bacteria were screened for tolerance, and these were used to create gene libraries to test in E. coli. Future characterization of these libraries using molecular techniques will be used to identify genes that contribute IL-tolerance to transformed microbes.

Targeting Akt/Mtor Signaling Pathways During Murine Skin Tumor Promotion And The Impact Of Dietary Energy Balance Manipulation, Laura A. Checkley

Dissertations and Theses (Open Access)

The prevalence of obesity has continued to rise over the last several decades in the United States lending to overall increases in risk for chronic diseases including many types of cancer. In contrast, reduction in energy consumption via calorie restriction (CR) has been shown to be a potent inhibitor of carcinogenesis across a broad range of species and tumor types. Previous data has demonstrated differential signaling through Akt and mTOR via the IGF-1R and other growth factor receptors across the diet-induced obesity (DIO)/CR spectrum. Furthermore, mTORC1 is known to be regulated directly via nutrient availability, supporting its role in the …

Characterization Of The Infectivity Of Non-Replicating Human Immunodeficiency Virus (Hiv)-Derived Viral Vectors., Vanessa E. Rodriguez, Manuel Llano, Luis Valdes

COURI Symposium Abstracts, Summer 2012

The ability of HIV-derived viral vectors to integrate genes of interest into the host genome causing permanent phenotypic modifications makes them excellent tools in gene therapy. However, integration also causes insertional mutagenesis and controlling integration site selection will increase the biosafety of these molecular tools. HIV DNA integration site selection is influenced by LEDGF/p75, a chromatin-bound cellular protein that interacts with the viral enzyme integrase through the integrase binding domain (IBD). Integrase catalyzes viral DNA integration and non-covalently associates with the HIV genome forming the pre-integration complex (PIC). Therefore, interaction of chromatin-bound LEDGF/p75 with the PIC-associated integrase tethers the HIV …

Studying Human Disease Genes In Caenorhabditis Elegans : A Molecular Genetics Laboratory Project, Elisabeth A. Cox-Paulson, Theresa M. Grana, Michelle A. Harris, Janet M. Batzli

Biological Sciences Research

Scientists routinely integrate information from various channels to explore topics under study. We designed a 4-wk undergraduate laboratory module that used a multifaceted approach to study a question in molecular genetics. Specifcally, students investigated whether Caenorhabditis elegans can be a useful model system for studying genes associated with human disease. In a large-enrollment, sophomore-level laboratory course, groups of three to four students were assigned a gene associated with either breast cancer (brc-1), Wilson disease (cua-1), ovarian dysgenesis (fshr-1), or colon cancer (mlh-1). Students compared observable phenotypes of wild-type C. elegans and C. elegans with a homozygous deletion in the assigned …

A Study Of Histone Deacetylase Inhibitors: Determination Of The Binding Energetics Of Suberoylanilide Hydroxamic Acid With Zinc And Cobalt And Preliminary Screening Of Nitric Oxide Donors, Erin Gallagher

College of Science and Health Theses and Dissertations

Inhibiting histone deacetylases (HDACs) can suppress tumor cell growth eventually leading to their death, makeing HDACs an important drug target. Therefore, understanding the mechanism behind inhibiting HDACs is imperative. To determine the thermodynamic parameters for the interaction of a known competitive HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA), with zinc(II), the metal ion in the HDAC active site, and cobalt(II), isothermal titration calorimetry (ITC) was used. The results showed that SAHA binds to zinc(II) more strongly than it does to cobalt(II) as the equilibrium binding constants were 4.3 ± 0.5 x 10² M^-1 and 2.0 ± 0.5 x 10 …

But What Is It That You Actually Do? (What It's Really Like Working In The Lab), Michael Reagan

Headwaters

No abstract provided.

Analysis Of Biodiesel Quality Using Reversed Phase High-Performance Liquid Chromatography, Kellyann M. Murphy

Pomona Senior Theses

The alternative fuel biodiesel is produced from the transesterification of vegetable oils or animal fat to fatty acid methyl esters. Pomona has a reactor on campus that can be used to run this reaction and produce biodiesel. The use of biodiesel has been found to lower air pollutant and greenhouse gas emissions, but can be potentially harmful to the engines if it contains impurities. This paper proposes a method using high-performance liquid chromatography to test the quality of biodiesel. This method utilizes instrumentation and materials that are available in Pomona College's Chemistry Department, requires very little sample preparation, and is …

Mutation And Complementation Of A Cellulose Synthase (Cesa) Gene, Ahmed Y. El-Araby

Senior Honors Projects

Cellulose is a carbohydrate polymer that is composed of repeating glucose subunits. Being the most abundant organic compound in the biosphere and comprising a large percentage of all plant biomass, cellulose is extremely plentiful and has a significant role in nature. Cellulose is present in plant cell walls, in commercial products such as those made from wood or cotton, and is of interest to the biofuel industry as a potential alternative fuel source. Although indigestible by humans, cellulose is nutritionally valuable, serving as a dietary fiber. Because of its ubiquity and importance in many areas, studying cellulose will prove to …

Perceptions Of The Aging Voice, Salem Vaught

Rehabilitation, Human Resources and Communication Disorders Undergraduate Honors Theses

The purpose of this study was to gauge whether the age and status of an individual could be discerned or perceived by voice alone. The participants of the study were 7 female and 1 male undergraduate students between the ages of 18-25. The materials for this study consisted of audio segments from different individuals at various ages that were assembled by the researcher into a randomized recording. The audio segments were played to the participants of the study and then were followed by a voice discrimination questionnaire developed from the literature. Procedures for data collection required participants to listen to …

Lmw-E Mediates Mammary Tumorigenesis By Deregulating Acinar Morphogenesis & Generating Cancer Stem Cells, Mylinh T. Duong

Dissertations and Theses (Open Access)

Cyclin E is the regulatory subunit of the cyclin E/CDK2 complex that

mediates the G1-S phase transition. N-terminal cleavage of cyclin E by elastase in

breast cancer generates two low molecular weight (LMW) isoforms that exhibit both

enhanced kinase activity and resistance to p21 and p27 inhibition compared to fulllength cyclin E. Clinically, approximately 27% of breast cancer patients overexpress

LMW-E and associate with poor survival. Therefore, we hypothesize that LMW-E

disrupts normal mammary acinar morphogenesis and serves as the initial route into

breast tumor development. We first demonstrate that LMW-E overexpression in

non-tumorigenic hMECs is sufficient to induce tumor …

Increased Geranylgeranylated K-Ras Contributes To Antineoplastic Effects Of Farnesyltransferase Inhibitors., Mandy A. Hall

Dissertations and Theses (Open Access)

The Ras family of small GTPases (N-, H-, and K-Ras) is a group of important signaling mediators. Ras is frequently activated in some cancers, while others maintain low level activity to achieve optimal cell growth. In cells with endogenously low levels of active Ras, increasing Ras signaling through the ERK and p38 MAPK pathways can cause growth arrest or cell death. Ras requires prenylation – the addition of a 15-carbon (farnesyl) or 20-carbon (geranylgeranyl) group – to keep the protein anchored into membranes for effective signaling. N- and K-Ras can be alternatively geranylgeranylated (GG’d) if farnesylation is inhibited but are …

Chemosensitization Of Hepatocellular Carcinoma To Gemcitabine By Non-Invasive Radiofrequency Field-Induced Hyperthermia, Mustafa Raoof

Dissertations and Theses (Open Access)

Gemcitabine is a potent nucleoside analogue against solid tumors however drug resistance rapidly emerges. Removal of gemcitabine incorporated in the DNA by repair mechanisms could potentially contribute to resistance in chemo-refractory solid tumors. In this study, we evaluated homologous recombination repair of gemcitabine-stalled replication forks as a potential mechanism contributing to resistance. We also studied the effect of hyperthermia on homologous recombination pathway to explain the previously reported synergy between gemcitabine and hyperthermia. We found that hyperthermia degrades and inhibits localization of Mre11 to gemcitabine-stalled replication forks. Furthermore, gemcitabine-treated cells that were also treated with hyperthermia demonstrate a prolonged passage …