Laboratory and Basic Science Research Commons^™

Cyclin C Regulated Oxidative Stress Responsive Transcriptome In Mus Musculus Embryonic Fibroblasts, David C Stieg, Kai-Ti Chang, Katrina F Cooper, Randy Strich

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The transcriptional changes that occur in response to oxidative stress help direct the decision to maintain cell viability or enter a cell death pathway. Cyclin C-Cdk8 is a conserved kinase that associates with the RNA polymerase II Mediator complex that stimulates or represses transcription depending on the locus. In response to oxidative stress, cyclin C, but not Cdk8, displays partial translocation into the cytoplasm. These findings open the possibility that cyclin C relocalization is a regulatory mechanism governing oxidative stress-induced transcriptional changes. In the present study, the cyclin C-dependent transcriptome was determined and compared to transcriptional changes occurring in oxidatively …

Crystal Structure Of Zymonic Acid And A Redetermination Of Its Precursor, Pyruvic Acid, Dominik Heger, Alexis J. Eugene, Sean R. Parkin, Marcelo I. Guzman

Chemistry Faculty Publications

The structure of zymonic acid (systematic name: 4-hy­droxy-2-methyl-5-oxo-2,5-di­hydro­furan-2-carb­oxy­lic acid), C₆H₆O₅, which had previously eluded crystallographic determination, is presented here for the first time. It forms by intra­molecular condensation of parapyruvic acid, which is the product of aldol condensation of pyruvic acid. A redetermination of the crystal structure of pyruvic acid (systematic name: 2-oxo­propanoic acid), C₃H₄O₃, at low temperature (90 K) and with increased precision, is also presented [for the previous structure, see: Harata et al. (1977). Acta Cryst. B33, 210–212]. In zymonic acid, the hy­droxy­lactone ring …

A Discrepancy Between The Human Reference Genome (Grch37) And Transcriptome (Refseq) Results In The Incorrect Annotation Of A Clinically-Relevant Sequence Variant In Recql4, Lisa A. Lansdon

Research Days

No abstract provided.

Acute Promyelocytic Leukemia: A Case Study Correlating Cytogenetic Abnormality With Prognosis, Alyssa Lamond, Theresa Tellier-Castellone

Senior Honors Projects

Advancements in medical technology today have positively impacted the diagnosis, treatment, and prognosis of cancers. Particularly acute promyelocytic leukemia (APL) has completely improved from having the poorest prognosis to one of the best. Acute promyelocytic leukemia is a malignant disease of hematopoietic tissue classified by WHO as leukemia with >20% blasts from the myeloid lineage, specifically promyelocytes. Determined in 1976, FAB classified AML subtypes M1-M7, with APL being M3. Specific characteristics classify the subtype of AML, with each resulting from a different genetic abnormality. The focus of APL diagnosis, treatment, and prognosis occurs around the known PML-RARα fusion gene. Flow …

A Dedicated Chaperone Mediates The Safe Transfer Of Mitoribosomal Proteins To Their Site Of Assembly, Gabrielle Ashley Hillman

Graduate School of Biomedical Sciences Theses and Dissertations

Mitochondrial ribosomes are functionally specialized for the synthesis of several essential inner membrane proteins of the respiratory chain. While remarkable progress has recently been made towards understanding the structure of mitoribosomes, the unique pathways and factors that facilitate their biogenesis remain largely unknown. This dissertation defines the physiological role of an evolutionarily conserved yeast protein called Mam33 in mitochondrial ribosome assembly. The biomedical relevance of this finding stems from the fact that mutations or changes in its expression of the human ortholog p32 result in mitochondrial dysfunction. In human patients, bi-allelic mutations cause severe multisystemic defects in mitochondrial energy metabolism, …

Detection Of Genetic Thrombophilia (Fa V Leiden & Pt20210 Mutation) Using Genexpert Technology With Iqcp Implementation, Mariegrace Saquilayan

Natural Sciences and Mathematics | Clinical Laboratory Sciences

Abstract

Individuals having Genetic Thrombophilia pose a higher risk of having a thrombotic event. It is crucial to determine these gene variants to prevent a possible episode of thromboembolism. With the current PCR method, it involves individual processing of DNA isolation, amplification, and detection using three (3) different instruments resulting to an increased turnaround time of 5 to 7 days and additional staff utilization. It is performed by repetitive manual sample pipetting and preparation of reagent master mixes in small vials. Results interpretations are entered manually to a worklist built initially for final verification. These processes increase the risk of …

Identification Of Anaerobes In Clinical Specimens Comparison Between The Rapid Ana Ii System And The Bruker Maldi-Tof Ms System Utilized In The Clinical Laboratory, Raymond Chow

Natural Sciences and Mathematics | Clinical Laboratory Sciences

Matrix-Assisted Laser Desorption and Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) has been revealed as an invaluable platform for identifying anaerobic bacteria in the clinical laboratory over traditional methods such as the RapID ANA II System.

A qualitative comparison is made, through the analysis of methodologies and specifications, to determine whether the RapID ANA II system or Bruker MALDI-TOF MS is more suitable for identifying anaerobic organism in the clinical laboratory. Based on the data reviewed, the MALDI-TOF MS is a more intuitive platform within the clinical laboratory due to its increased specificity, cost-effectiveness, and shorten turnaround time for the identification …

The Acute Effects Of Citrulline Malate And Bonded Arginine Silicate Supplementation On Vasodilation Of Young Adults, Jeffrey Rogers

Health, Human Performance and Recreation Undergraduate Honors Theses

Abstract

Background

Clinicians, professional athletes, and recreational athletes are interested in supplementation that up-regulates nitric oxide (NO) production in blood vessel endothelium, increasing arterial vasodilation. Benefits from these supplements include improvements in blood pressure, muscle hyperemia, and exercise performance. Citrulline Malate (CM) is a pre-workout ingredient, popular for its ability to increase exercise performance and blood serum concentrations of L-arginine, resulting in NO production. Recently, Inositol-Stabilized Arginine Silicate (ASI, Nitrosigine) has been added to many of the most popular pre-workout blends, following a group of studies showing ASI increases serum arginine and reduces post-workout muscle damage. Research has yet to …

2018 Guide Summer Research - Breast Cancer, Qur'annah Jones, Delawnia Comer-Hagans

Research Days

This research poster details the relationship between cancer treatments and alternative approaches, such as mindfulness. The purpose of this study was to determine the methodology used by doctors to treat breast cancer and their willingness to try a holistic approach. This study was conducted on site at the UIC Cancer Center as well as remotely within hospitals around the Chicagoland area. We determined that mindfulness is in fact a worthwhile asset to breast cancer patients and that the field of oncology could support further research.

Publication Reform To Safeguard Wildlife From Researcher Harm, Kate A. Field, Paul C. Paquet, Kyle A. Artelle, Gilbert Proulx, Ryan K. Brook, Chris T. Darimont

Professional Science Research Ethics Collection

Despite abundant focus on responsible care of laboratory animals, we argue that inattention to the maltreatment of wildlife constitutes an ethical blind spot in contemporary animal research. We begin by reviewing significant shortcomings in legal and institutional oversight, arguing for the relatively rapid and transformational potential of editorial oversight at journals in preventing harm to vertebrates studied in the field and outside the direct supervision of institutions. Straightforward changes to animal care policies in journals, which our analysis of 206 journals suggests are either absent (34%), weak, incoherent, or neglected by researchers, could provide a practical, effective, and rapidly imposed …

Characterizing Aft1/2-Grx3/4 Interaction And The Role Of Bol2 During Iron Regulation In Saccharomyces Cerevisiae, William Rivers

Senior Theses

Iron dysregulation has been linked to a variety of human diseases, such as anemia, Friedreich’s ataxia, X-linked sideroblastic anemia, sideroblastic-like microcytic anemia, and myopathy. Thus, it is vitally important to understand the mechanisms for regulating intracellular iron. Here, we use fluorescence microscopy techniques in live cells to study interactions of the yeast proteins Grx3/4, Aft1/2, and Bol2, which have been shown to be involved in turning off iron import when the cell has adequate iron. Modified versions of genes encoding these proteins have been incorporated into several yeast backgrounds to use fluorescence to monitor interactions under varying iron levels.

The Master Synaptic Regulator: Activity Regulated Cytoskeleton Associated Protein, Arc, In Normal Aging And Diseases With Cognitive Impairment, Amber Khan

Dissertations, Theses, and Capstone Projects

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with complex underlying pathogenic mechanisms. Epidemiological studies have forecasted that in the next 3 decades, the number of AD cases will rise to epidemic proportions with enormous medical, emotional and financial burdens impacting individuals affected and society. Among many risk factors for AD, advancing age is clearly essential and necessary. Revelation of molecular changes in synaptic activities leading to the prodromal, mild cognitive impairment (MCI) stage may help illuminate the course of pathogenic progression and its cause-effect relationship with various targets thereby enabling target-driven disease-modifying therapeutic agents for AD.

Activity-regulated cytoskeleton-associated (Arc) …

Refinement On The Way Towards Replacement: Are We Doing What We Can?, Kathrin Herrmann

Humane Science Movement Collection

No abstract provided.

Contesting Animal Experiments Through Ethics And Epistemology: In Defense Of A Political Critique Of Animal Experimentation, Arianna Ferrari

Professional Science Research Ethics Collection

Generally, an animal experiment can be defined as an intervention on an animal, which causes suffering, harm, and distress, for scientific purposes. In this definition, animal experiments differ from more general scientific investigations concerning animals, such as observational studies in the wild in the fields of ethology or conservation, in which animals are involved but may not be harmed. Nowadays, the use of the term vivisection, in the case of animal experiments, is very controversial. This term originally referred to the cutting of living bodies for scientific purposes and has a long conceptual history (Maehle, 1992). In ancient times, it …

How Can The Final Goal Of Completely Replacing Animal Procedures Successfully Be Achieved?, Christiane Baumgartl-Simons, Christiane Hohense

Validation of Alternative Methods Collection

Article 23 of European Union (EU) Directive 86/609/EEC required that Member States promote the development and validation of alternative technologies and stated that the European Commission (EC) “shall report before the end of 1987 on the possibility of modifying tests and guidelines” (European Parliament, 1986, Article 23). This Directive was replaced by Directive 2010/63/EU on the protection of animals used for scientific purposes, which now requires that Member States develop and validate alternative approaches much more precisely and specifies that the ultimate objective is the “full replacement of procedures on live animals for scientific and educational purposes, as soon as …

How To Evaluate The Science Of Non-Human Animal Use In Biomedical Research And Testing: A Proposed Format For Debate, Ray Greek, Lisa A. Kramer

Validation of Alternative Methods Collection

Over time, the interpretation of science has occasionally been corrupted by vested interest groups, be they financially motivated or ego driven. Scientific consensus and widespread public beliefs usually catch up with the evidence, but this can take a very long time and often costs lives. The use of non-human animals in biomedical research and testing is a scientific endeavor and, as such, can and should be evaluated in light of the best science currently available. But facts that have been accepted in all areas of science are routinely ignored or called into question by well-funded, vested interest groups, compromising the …

Rethinking The 3rs: From Whitewashing To Rights, Charlotte E. Blattner

Humane Science Movement Collection

Few other issues have prompted as many legislators to adopt legal instruction on the “proper” use of non-human animals (hereinafter referred to as animals) in medical and scientific research. Today, the 3Rs (replacement, reduction, and refinement of animals in scientific procedures) are globally accepted by a vast majority of states (Blattner, 2014); and prominent international organizations, such as the World Organisation for Animal Health (Terrestrial Animal Health Code, 2018, Article 7(8)(3)) and the Council of Europe (Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes, 1986, Articles 6(2), 7 and 8). Widespread acceptance of the …

Replacing Animal Tests To Improve Safety For Humans, Kathy Archibald, Robert Coleman, Tamara Drake

Application of Alternative Methods Collection

In this chapter, we propose a new, pragmatic approach that could accelerate the replacement of most, if not all, regulatory animal tests with superior tests based on human biology. We also propose that changes to the requirements for safety testing, issued by the us Food and Drug Administration (fda), must be made in order to enable the use of superior new tests, which are currently disadvantaged by the outdated language of the regulations. But first, it is imperative to establish some level of understanding of the efficacy of existing animal-based methods in order to know whether any possible replacement is …

The Changing Paradigm In Preclinical Toxicology: In Vitro And In Silico Methods In Liver Toxicity Evaluations, Fozia Noor

Application of Alternative Methods Collection

In vitro methods, based on human primary cells, cell lines, and genetically modified reporter cell lines, have greatly expanded the scope of in vitro toxicology. Other significant progress in the area of human-induced pluripotent stem cells (hiPSCs) (Asgari et al., 2010; Schwartz et al., 2014; Shinde et al., 2016; Shtrichman, Germanguz and Itskovitz-Eldor, 2013) is allowing the application of patient and disease-specific hiPSCs (Ghodsizadeh et al., 2010; McCracken et al., 2014; Siller et al., 2013). Moreover, the tools of precise genome editing with engineered nucleases, such as the zinc finger nucleases (zfns), the transcription activator-like effecter nucleases (talens) and, more …

The Potential Of Organ On Chip Technology For Replacing Animal Testing, Malcolm Wilkinson

Human Clinical Trials Collection

The term organ on a chip is used to describe the latest stage of development of in vitro cell culture technology. Figure 26.1 shows its steady development since the 1960s. Each step forward has improved our ability to model human-clinical response to new drugs or therapies and has enabled safety risk assessment of existing cosmetics, personal care products, or other chemicals in the environment. Scientific evidence that the predictive power of in vitro tests is superior to the use of animals will trigger a major shift in the way that medical research, in many areas, is carried out. In this …

Recent Developments In Alternatives To Animal Testing, Katy Taylor

Application of Alternative Methods Collection

Methods that replace techniques that use live animals, or methods of testing substances without live animal use, are known as alternatives, replacements or non-animal methods. Some prefer the term advanced technologies given the fact that they often rely on more sophisticated technology and are more human- relevant than the animal test they replace (see Langley et al., 2015). There have been efforts to replace animal tests since the 1960s. Significant progress initially came in replacing animals used to diagnose human disease; to produce biological drugs (such as vaccines); and to safety test batches of these drugs as they were produced. …

When Is An Alternative Not An Alternative? Supporting Progress For Absolute Replacement Of Animals In Science, Craig Redmond

Humane Science Movement Collection

This chapter addresses some of the areas in which animals are still used within “alternatives”-based research and calls on animal welfare and in vitro organizations to lead the debate and encourage absolute replacement of animal use in research. Without this, progress to end animal research will always remain limited, despite the paradigm shift seen in recent decades.

Research And Testing Without Animals: Where Are We Now And Where Are We Heading?, Thomas Hartung

Humane Science Movement Collection

Experiments involving non-human animals (hereinafter referred to as animals) were the predominant technology in the life sciences from the 1920s to the 1970s. Increasingly, animal-based procedures have been complemented and superseded by other approaches; yet, they still have an enormous reputation as an apparent definitive answer to many scientific and, especially, regulatory questions. They have been questioned first for ethical reasons: Can we justify making animals suffer for scientific inquiry? Simply said, people have different views on this question, but the general public views animal experimentation more and more critically. The animal research community has sought a compromise between those …

Mechanisms Of Trinucleotide Repeat Instability During Dna Synthesis, Kara Y. Chan

Theses and Dissertations--Toxicology and Cancer Biology

Genomic instability, in the form of gene mutations, insertions/deletions, and gene amplifications, is one of the hallmarks in many types of cancers and other inheritable genetic disorders. Trinucleotide repeat (TNR) disorders, such as Huntington’s disease (HD) and Myotonic dystrophy (DM) can be inherited and repeats may be extended through subsequent generations. However, it is not clear how the CAG repeats expand through generations in HD. Two possible repeat expansion mechanisms include: 1) polymerase mediated repeat extension; 2) persistent TNR hairpin structure formation persisting in the genome resulting in expansion after subsequent cell division. Recent in vitro studies suggested that a …

Chronic Low Intensity Continuous And Interval Training Prevent Heart Failure-Related Coronary Artery Stiffness, An Ouyang

Theses and Dissertations--Kinesiology and Health Promotion

Heart failure (HF) induced by aortic pressure over-load is associated with increased coronary artery stiffness. Perivascular adipose tissue (PVAT) and advanced glycation end products (AGE) both promote arterial stiffness. However, the mechanisms by which coronary PVAT promotes arterial stiffness and the efficacy of exercise to prevent coronary stiffness are unknown. The present study hypothesized both chronic continuous and interval exercise training would prevent coronary artery stiffness associated with inhibition of PVAT secreted AGE. Yucatan mininature swine were divided into four groups: control-sedentary (CON), aortic-banded sedentary heart failure (HF), aortic-banded HF continuous exercise trained (HF+CONT), and aortic-banded HF interval exercise trained …

Effects Of Acute Hypoxia On Danio Rerio, Karly Crail

Williams Honors College, Honors Research Projects

The purpose of this research experiment was to determine the effects of acute hypoxia on the embryonic zebrafish (Danio rerio) cardiovascular system and assess the critical oxygen level at which embryonic function is compromised. This goal was achieved by exposing embryos to decreasing oxygen concentrations, (6.0 mg/L-0 mg/L) and observing the heart under an inverted microscope. Data analysis was conducted to determine end systolic volume, end diastolic volume, stroke volume, heart rate, and cardiac output. It was hypothesized that hypoxia would stimulate cardiac activity, because in early developmental stages, tissues are supplied with oxygen through bulk diffusion, and …

The Role Of Tumor Suppressor Dear1 In The Acquisition Of Mammary Stem/Progenitor Cell Properties, Uyen Le

Dissertations and Theses (Open Access)

Breast cancer is the most commonly diagnosed cancer in women in America. Ductal carcinoma in situ (DCIS), one of the earliest pre-invasive forms of invasive ductal carcinoma (IDC), has a 30-50% risk of progressing to IDC. Understanding the mechanisms regulating progression from DCIS to IDC would help identify biomarkers to stratify patients at higher risk of progression or metastasis. Cumulative literature suggests the earliest phase of dissemination from the primary tumor is driven by the epithelial-mesenchymal transition (EMT) program. DEAR1 is a tumor suppressor gene which is mutated, undergoes loss of heterozygosity in breast cancer, and is downregulated in DCIS …

Behavioral Insights Into Nociceptor Function: A Systematic Approach To Understanding Postsurgical And Neuropathic Pain Mechanisms In Rats, Max Odem

Dissertations and Theses (Open Access)

Postsurgical and neuropathic pain are each clinically common, and often associated with ongoing pain. Ongoing pain has been linked to ongoing activity (OA) in human C-fiber nociceptors. Preclinical studies using rodent neuropathic models have concentrated on allodynia driven by OA generated in non-nociceptive Aβ fibers, but little attention has been paid to postsurgical pain in sham controls or to C-fiber nociceptor OA promoting ongoing pain.

Operant assays that reveal negative motivational and cognitive aspects of voluntary pain-related behavior may be particularly sensitive to pain-related alterations. In the mechanical conflict (MC) test, rodents can freely choose to escape from a brightly …

Comparisons Between Movement Onset Identification Methods Used In Isometric Mid-Thigh Pull Test, Junshi Liu

Electronic Theses and Dissertations

This dissertation aimed to explore the usefulness of using force derivatives for onset detection in the isometric mid-thigh pull test. First, we examined applications of three differential calculus principles, first and second derivative, and curvature using visual detection as a reference under different baseline conditions. Second, we compared the best derivative method to a threshold-based method using visual detection as a reference. Results of our first investigation showed trivial differences between many differential calculus methods and visual detection. However, statistical differences exceeding a trivial effect was observed when instantaneous force and rate of force develop were examined. Through the first …

Adapting Cell-Free Protein Synthesis As A Platform Technology For Education, Grace W. Chu, Max Z. Levine, Nicole E. Gregorio, Javin P. Oza

STAR Program Research Presentations

Cell-free protein synthesis (CFPS) has emerged as an enabling biotechnology for research and biomanufacturing as it allows for the production of protein without the need for a living cell. Applications of CFPS include the construction of libraries for functional genomics and structural biology, the production of personalized medicine, and the expression of virus-like particles. The absence of a cell wall provides an open platform for direct manipulation of the reaction conditions and biological machinery. This project focuses on adapting the CFPS biotechnology to the classroom, making a hands-on bioengineering approach to learning protein synthesis accessible to students grades K-16 through …