Digital Commons Network^™

Inhibition Of Src-3 As A Potential Therapeutic Strategy For Aggressive Mantle Cell Lymphoma, Imani Bijou, Yang Liu, Dong Lu, Jianwei Chen, Shelby Sloan, Lapo Alinari, David M Lonard, Bert W O'Malley, Michael Wang, Jin Wang

Faculty, Staff and Students Publications

Mantle cell lymphoma (MCL) has a poor prognosis and high relapse rates despite current therapies, necessitating novel treatment regimens. Inhibition of SRC-3 show effectiveness in vivo and in vitro in other B cell lymphomas. Additionally, previous studies have shown that SRC-3 is highly expressed in the lymph nodes of B cell non-Hodgkin's lymphoma patients, suggesting SRC-3 may play a role in the progression of B cell lymphoma. This study aimed to investigate novel SRC-3 inhibitors, SI-10 and SI-12, in mantle cell lymphoma. The cytotoxic effects of SI-10 and SI-12 were evaluated in vitro and demonstrated dose-dependent cytotoxicity in a panel …

Female Titin Mutant Mice Outperform Young And Old Males, Reese Ger

Scripps Senior Theses

Exercise performance is widely believed to generally be maximal among young males. However, little research has been conducted to investigate the impact of sex or age on muscle performance. This study investigated the effects of sex and age on forelimb and all limb grip strength performance in wildtype and titin mutant mice. Titin is the largest known protein, with known involvement in muscle function. The mice in this study were Ttn∆112-158 with a 75% deletion to the PEVK region of titin. Based on limited existing research, we hypothesized that wildtype mice would outperform all Ttn∆112-158 mice, males would outperform females …

Preliminary New Study Indicates Possible Dramatic Decline In The Diversity Of Insects Visiting Flowers Of Jarrah (Eucalyptus Marginata) In Kings Park Over 26 Years, Ashley R. Jenkin, Siegfried L. Krauss, Eddie Van Etten

Research outputs 2022 to 2026

The recent decline of terrestrial insects in many parts of the world is of growing concern due to the fundamental ecosystem services they perform. Pollination is a vital ecosystem service predominantly performed by insects, with inestimable environmental and economic benefits. Accurate assessment and management of insect pollinator declines, and of other ecosystem impacts are hindered by a lack of long-term monitoring data and notably an absence of Southern Hemisphere studies. This preliminary study aims to address some of these gaps by determining if the diversity of insect floral visitors and potential pollinators of the canopy tree species Jarrah (Eucalyptus marginata) …

A Review Of Dielectric Barrier Discharge Cold Atmospheric Plasma For Surface Sterilization And Decontamination, Kolawole Adesina, Ta Chun Lin, Yue-Wern Huang, Marek Locmelis, Daoru Frank Han

Biological Sciences Faculty Research & Creative Works

Numerous investigations have shown that non-equilibrium discharges at atmospheric pressure, also known as "cold atmospheric plasma" (CAP) are efficient to remove biological contaminants from surfaces of a variety of materials. Recently, CAP has quickly advanced as a technique for microbial cleaning, wound healing, and cancer therapy due to the chemical and biologically active radicals it produces, known collectively as reactive oxygen and nitrogen species (RONS). This article reviews studies pertaining to one of the atmospheric plasma sources known as Dielectric Barrier Discharge (DBD) which has been widely used to treat materials with microbes for sterilization, disinfection, and decontamination purposes. To …

Β2-Glycoprotein I Promotes The Clearance Of Circulating Mitochondria, Swapan Kumar Dasgupta, Jahnavi Gollamudi, Stefanie Rivera, Ross A Poche, Rolando E Rumbaut, Perumal Thiagarajan

Faculty, Staff and Students Publications

β2-glycoprotein I (β2-Gp1) is a cardiolipin-binding plasma glycoprotein. It is evolutionarily conserved from invertebrates, and cardiolipin-bound β2-Gp1 is a major target of antiphospholipid antibodies seen in autoimmune disorders. Cardiolipin is almost exclusively present in mitochondria, and mitochondria are present in circulating blood. We show that β2-Gp1 binds to cell-free mitochondria (CFM) in the circulation and promotes its phagocytosis by macrophages at physiological plasma concentrations. Exogenous CFM had a short circulation time of less than 10 minutes in mice. Following infusion of CFM, β2-Gp1-deficient mice had significantly higher levels of transfused mitochondria at 5 minutes (9.9 ± 6.4 pg/ml versus 4.0 …

Shifting Soil Fungal Communities In Response To Fire And Weed Management In Urban Banksia Woodlands, Aaron Justin Brace

Theses: Doctorates and Masters

This research aims to fill the knowledge gap in soil fungi in the Banksia woodland and emphasizes considering holistic ecosystem dynamics in invasive species management strategies. This is accomplished by surveying soil fungi under different fire regime across the Swan Coastal Plain, and within both in and ex situ herbicide application trials. This is the first such study to investigate the fungal component of the Banksia woodland so thoroughly. Chapter 2 quantified and analysed changes in soil fungal community composition and functional groups over a 50-year fire chronosequence in fire-prone Banksia woodland in southwestern Australia. Effects were variable, but fungal …

Trends In Monitoring Of Australia’S Threatened Birds (1990–2020): Much Improved But Still Inadequate, Simon J. Verdon, Robert A. Davis, Ayesha Tulloch, Sarah M. Legge, David M. Watson, John C. Z. Woinarski, G. Barry Baker, Joris Driessen, Hayley M. Geyle, Hugh Possingham, Stephen T. Garnett

Research outputs 2022 to 2026

Monitoring is vital to conservation, enabling conservation scientists to detect population declines, identify threats and measure the effectiveness of interventions. However, not all threatened taxa are monitored, monitoring quality is variable, and the various components of monitoring are likely to differ in their rates of improvement over time. We assessed the presence of monitoring and monitoring quality, using a range of metrics, for all Australia’s threatened bird taxa from 1990 to 2020 (four assessments spanning 30 years). We used our assessments to understand decadal trends in the number of taxa monitored; monitoring quality; and the groups that conduct monitoring. The …

Characterization Of The Disease-Causing Mechanism Of Kif3b Mutations From Ciliopathy Patients, Jessica M. Adams, Caleb Sawe, Skye Rogers, Jordyn Reid, Ronith Dasari, Martin F. Engelke

Faculty Publications – Biological Sciences

The heterodimeric kinesin-2 motor (KIF3A/KIF3B with accessory protein KAP3) drives intraflagellar transport, essential for ciliogenesis and ciliary function. Three point mutations in the KIF3B subunit have recently been linked to disease in humans (E250Q and L523P) and Bengal cats (A334T) (Cogné et al., Am. J. Hum. Genet., 2020, 106, 893–904). Patients display retinal atrophy and, in some cases, other ciliopathy phenotypes. However, the molecular mechanism leading to disease is currently unknown. Here, we used Kif3a−/−;Kif3b−/− (knockout) 3T3 cells, which cannot make cilia, to characterize these mutations. While reexpression of KIF3B(E250Q) and KIF3B(L523P) did not rescue ciliogenesis, reexpression …

The Role Of Semaphorins In Response To Injury In C. Elegans Neurons, Maria Belen Harreguy Alfonso

Dissertations

When neural tissue is injured by trauma, delicate neuronal processes such as axons and dendrites are prone to lesion damage and often disconnect. The molecular, cellular, and circuit mechanisms that underlie the regrowth and reconnection of these processes and the recovery of behavior are major challenges in the fields of neuroscience, regeneration, and resilience. At the molecular and cellular levels, signaling pathways that mediate neuronal growth cone guidance during development can play a role in neuronal regeneration and recovery from injury. One family of signaling proteins involved in this process comprises the highly conserved semaphorins and their receptors, the plexins. …

Konsep Diagnosis Dan Penatalaksanaan Fraktur Osteoporosis Terkini, I Gusti Ngurah Wien Aryana, Febyan Febyan

Jurnal Penyakit Dalam Indonesia

Osteoporosis is a metabolic bone disease that is caused by a decreased amount of bone mass, and microarchitectural damage to bone tissue that affects the bone to break easily. Osteoporosis can be divided into primary and secondary etiologies. Vertebral, hip, distal radius, and proximal humerus are the most common predilection of fracture complication due to osteoporosis. The diagnosis of osteoporotic fractures is established based on the identification of risk factors, general clinical manifestations, specific manifestation from each fracture predilection, and advanced examinations, including radiology imaging and dual-energy x-ray absorptiometry. The purpose of osteoporotic fractures management in elderly is a stable …

Svm-Do: Identification Of Tumor-Discriminating Mrna Signatures Via Support Vectormachines Supported By Disease Ontology, Mustafa Erhan Özer, Pemra Özbek Sarica, Kazim Yalçin Arğa

Turkish Journal of Biology

Background/aim: The complicated nature of tumor formation makes it difficult to identify discriminatory genes. Recently, transcriptome-based supervised classification methods using support vector machines (SVMs) have become popular in this field. However, the inclusion of less significant variables in the construction of classification models can lead to misclassification. To improve model performance, feature selection methods such as enrichment analysis can be used to extract useful variable sets. The detection of genes that can discriminate between normal and tumor samples in the association of cancer and disease remains an area of limited information. We therefore aimed to discover novel and practical sets …

Physicochemical Differences Between Camelid Single-Domain Antibodies And Mammalian Antibodies, Nazli Eda Eski̇er, Doğa Eski̇er, Esi̇n Fi̇ruzan, Si̇bel Kalyoncu

Turkish Journal of Biology

Background/aim: In recent years, single-domain antibodies, also known as nanobodies, have emerged as an alternative to full immunoglobulin Gs (IgGs), due to their various advantages including increased solubility, faster clearance, and cheaper production. Nanobodies are generally derived from the variable domain of the camelid heavy-chain-only immunoglobulin Gs (hcIgGs). Due to the high sequence homology between variable heavy chains of camelids (VHHs) and humans (VHs), hcIgGs are ideal candidates for nanobody development. However, further examination is needed to understand the structural differences between VHs and VHHs. This analysis is essential for nanobody engineering to mitigate potential immunogenicity while preserving stability, functionality, …

Investigation Of The Deubiquitinating Enzyme Usp7 In The Brain, Hao Chen

Arts & Sciences Graduate Student Theses and Dissertations

The development of the nervous system relies on precise control of protein ubiquitination and degradation. Consequently, imbalance in the ubiquitin signaling network is believed to have significant implications for neurological disorders. Recent research has not only detailed the various functions of different ubiquitin ligases in neural development, but has also disclosed the role of deubiquitinating enzyme as an additional regulatory dimension in the ubiquitin signaling network. Specifically, deletion or mutation of the deubiquitinating enzyme USP7 causes the Hao-Fountain syndrome, characterized by developmental delay, intellectual disability, autism, and aggressive behavior. Although USP7 has been studied in proliferating cells in the context …

Tfeb Degradation Is Regulated By An Ikk/Β-Trcp2 Phosphorylation-Ubiquitination Cascade, Yan Xiong

Arts & Sciences Graduate Student Theses and Dissertations

Transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and autophagy that plays a key role in the regulation of cellular clearance pathways. TFEB is regulated via a complex array of post-translational modifications (PTMs), but the exact molecular mechanism that regulates TFEB stability has remained elusive. Here, we show that TFEB levels are critically regulated by a defined phosphorylation-ubiquitination cascade. A human kinome screen identifies IKK (inhibitor of κB kinase) as a TFEB modifier, and a combination of phosphorylation assays, mass spectrometry analyses, and site-specific mutagenesis unveils a previously unrecognized TFEB phospho-degron (423SPFPSLS429) as the target of IKK. …

Discerning The Roles Of Novel Glycosyltransferases In The Pathogenic Yeast Cryptococcus Neoformans, Liza Loza

Arts & Sciences Graduate Student Theses and Dissertations

Cryptococcus neoformans (Cn) is an opportunistic fungal pathogen responsible for over 112,000 deaths each year. This yeast is ubiquitous in the environment, where it is particularly associated with soil, trees, and bird excreta. When a susceptible host inhales infectious particles, Cn can proliferate in the lungs before disseminating to the brain to cause an often-fatal meningoencephalitis. Cryptococcosis primarily afflicts those living with uncontrolled HIV/AIDS, accounting for ~15% of AIDS-related mortality. The antifungals available to treat this devastating disease are few in number, toxic to patients, and largely inaccessible in resource-limited settings. The major virulence factor of Cn is its complex …

Following The Paper Trail: An Ethnoecology Of Hand Papermaking Traditions, James Ojascastro

Arts & Sciences Graduate Student Theses and Dissertations

Plants and their fibers have served as simple yet incredibly versatile raw materials for innovation for as long as humans have been on the planet. As the principal structural building blocks of plant cell walls, these hollow, cellulosic fibers have been co-opted by cultures around the world to meet diverse structural, absorptive, motile, and thermoregulatory needs—especially as textiles and paper. Despite (or because of!) this versatility, fibers vary considerably in physiology, and ethnographic records show that very few plant species have been chosen by tradition for use in fiber products. Surprisingly, no fiber ethnobotany study to date has attempted to …

The Potential Of Stem Cell Therapy In Multiple Sclerosis Treatment: A Review, Sorina Amarculesei, Ava O'Meara Cushen, Cathy Brougham

SURE Journal: Science Undergraduate Research Experience Journal

Multiple Sclerosis is an autoimmune and neurodegenerative disease of the central nervous system. There are currently 2.8 million people living with Multiple Sclerosis worldwide, including 9000 people in Ireland, with a prevalence of 193 per 100,000 people. Symptoms of Multiple Sclerosis include sensory loss, fatigue, cognitive dysfunction, spasticity, depression, optic neuritis, gait ataxia, diplopia, and loss of bladder control. Currently, there is no standardised treatment or cure for Multiple Sclerosis with many strategies focusing on symptoms. Stem cells have emerged as promising approaches for Multiple Sclerosis therapeutics. Clinical trials primarily focus on mesenchymal stem cell-based therapies for Multiple Sclerosis. Furthermore, …

Feminist Biology: Towards Gender Equity In The Biology Curriculum, Nicole Danos, Carla Y. Bonilla, Sofia Leung

Feminist Pedagogy

The current curriculum in STEM is a product of historically unequal representation of genders in the science community. As a result, most attention has been given to male biology, creating a knowledge gap that has affected our social and political perspectives, such as an underinvestment in women’s health research. Feminist biology seeks to provide equal time and weight to the impact of sex as a biological factor, using inclusive definitions of biological sex that go beyond the male/female binary. Feminist pedagogy is a method of teaching that involves engaged learning and reflection in order to create a community of learners …

Regulation Of Mrna And Circrna As A Cause And Consequence Of Aging In Caenorhabditis Elegans, Rebekah Napier-Jameson

Biological Sciences Theses and Dissertations

A role for RNA binding proteins in regulating lifespan has emerged. We identified a pair of neuronal RBPs, exc-7 and mbl-1, which display synthetic lifespan defects. Such a strong synthetic phenotype represented an opportunity to use transcriptomics to search for potential causative targets that are synthetically regulated. We identified a small handful of genes synthetically dysregulated in double mutants and systematically tested each candidate gene for functional contribution to the exc-7; mbl-1 lifespan phenotype. We identified one such gene, the ion transporter nhx-6, which is highly upregulated in double mutants. Overexpression of nhx-6 causes reduced lifespan, and deletion …

Isolation And Characterization Of Bacteriophages From Fish Tank Samples, Oluwaseyi Oluwagbeminiyi Oladele-Ajose

Electronic Theses and Dissertations

Bacteriophages (phages) are viral obligate intracellular parasites that infect bacteria. Research has been carried out on alternative treatment plans for bacterial infections due to the increase in antibiotic resistance. Phages have been proposed as an alternative to antibiotics. This research focused on the isolation and characterization of bacteria from small aquariums. A total of 42 bacterial isolates were isolated from seven different fish tank water samples and were tested to determine if they possessed phages. Spot plaque assay revealed presence of lytic phage for only one of the isolated bacterial strains, which was determined to belong to Enterobacteriaceae family based …

Protocol To Build A Drug-Testing Pipeline Using Large Populations Of Drosophila Melanogaster, Jay Deloriea, Cassandra Millet-Boureima, Chiara Gamberi

Biology

As a small animal that recapitulates many fundamental aspects of human disease, Drosophila lends itself to probing the biological activity of molecules and drug candidates. Here, we present a protocol to build a drug-testing pipeline in Drosophila. We describe steps for generating synchronous populations of Bicaudal C mutants by genetic crossing and wild-type fly culturing for controlled compound administration and exemplary phenotypic assays. For complete details on the use and execution of this protocol, please refer to Millet-Boureima et al.,¹ Millet-Boureima et al.,² and Gamberi et al.³

Characterization Of Trafficking And Metabolic Functions Of The Endocytic Regulator Ehd1 In Ewing Sarcoma, Sukanya Chakraborty

Theses & Dissertations

Ewing sarcoma (EWS) is the second most common bone malignancy in children and adolescents. Despite improvement in survival due to advances in multimodality treatment strategies, patients with metastatic or recurrent disease have very poor outcomes. Overexpression of the EPS15 Homology Domain containing 1 (EHD1) protein has been linked to tumorigenesis but whether its core function as a regulator of intracellular traffic of cell surface receptors plays a role in oncogenesis remains unknown.

Studies presented in this dissertation establish that EHD1 overexpression is a feature of nearly 90% EWS patient tumors with high EHD1 expression specifying shorter patient survival. ShRNA-knockdown and …

Targeting Eif4a Triggers An Interferon Response To Synergize With Chemotherapy And Suppress Triple-Negative Breast Cancer, Na Zhao, Elena B Kabotyanski, Alexander B Saltzman, Anna Malovannaya, Xueying Yuan, Lucas C Reineke, Nadia Lieu, Yang Gao, Diego A Pedroza, Sebastian J Calderon, Alex J Smith, Clark Hamor, Kazem Safari, Sara Savage, Bing Zhang, Jianling Zhou, Luisa M Solis, Susan G Hilsenbeck, Cheng Fan, Charles M Perou, Jeffrey M Rosen

Faculty, Staff and Students Publications

Protein synthesis is frequently dysregulated in cancer and selective inhibition of mRNA translation represents an attractive cancer therapy. Here, we show that therapeutically targeting the RNA helicase eIF4A with zotatifin, the first-in-class eIF4A inhibitor, exerts pleiotropic effects on both tumor cells and the tumor immune microenvironment in a diverse cohort of syngeneic triple-negative breast cancer (TNBC) mouse models. Zotatifin not only suppresses tumor cell proliferation but also directly repolarizes macrophages toward an M1-like phenotype and inhibits neutrophil infiltration, which sensitizes tumors to immune checkpoint blockade. Mechanistic studies revealed that zotatifin reprograms the tumor translational landscape, inhibits the translation of Sox4 …

Habitat And Demography Of The Ozark Chinquapin (Castanea Ozarkensis) At Roaring River State Park In Barry County, Missouri, Danielle Evilsizor

Electronic Theses & Dissertations

The Ozark chinquapin, Castanea ozarkensis Ashe, is a chestnut tree with a range concentrated in the Interior Highlands of North America. Like other North American members of Castanea, it was reduced from an overstory tree to an understory shrub by the invasive chestnut blight fungus (Cryphonectria parasitica [Murrill] M.E. Barr) during the early 20^th century. However, relatively little is known about the habitat of this species or its health and reproductive capability post chestnut blight. Chapter one of this study analyzed the habitat of this species through a random forest species distribution model (SDM) to predict where …

Monitoring Time Domain Characteristics Of Parkinson's Disease Using 3d Memristive Neuromorphic System, Md Abu Bakr Siddique, Yan Zhang, Hongyu An

Michigan Tech Publications

INTRODUCTION: Parkinson's disease (PD) is a neurodegenerative disorder affecting millions of patients. Closed-Loop Deep Brain Stimulation (CL-DBS) is a therapy that can alleviate the symptoms of PD. The CL-DBS system consists of an electrode sending electrical stimulation signals to a specific region of the brain and a battery-powered stimulator implanted in the chest. The electrical stimuli in CL-DBS systems need to be adjusted in real-time in accordance with the state of PD symptoms. Therefore, fast and precise monitoring of PD symptoms is a critical function for CL-DBS systems. However, the current CL-DBS techniques suffer from high computational demands for real-time …

Enniatin A Inhibits The Chaperone Hsp90 And Unleashes The Immune System Against Triple-Negative Breast Cancer, Nada H Eisa, Vincent M Crowley, Asif Elahi, Vamsi Krishna Kommalapati, Michael A Serwetnyk, Taoufik Llbiyi, Sumin Lu, Kashish Kainth, Yasmeen Jilani, Daniela Marasco, Abdeljabar El Andaloussi, Sukyeong Lee, Francis T F Tsai, Paulo C Rodriguez, David Munn, Esteban Celis, Hasan Korkaya, Abdessamad Debbab, Brian Blagg, Ahmed Chadli

Faculty, Staff and Students Publications

Low response rates and immune-related adverse events limit the remarkable impact of cancer immunotherapy. To improve clinical outcomes, preclinical studies have shown that combining immunotherapies with N-terminal Hsp90 inhibitors resulted in improved efficacy, even though induction of an extensive heat shock response (HSR) and less than optimal dosing of these inhibitors limited their clinical efficacy as monotherapies. We discovered that the natural product Enniatin A (EnnA) targets Hsp90 and destabilizes its client oncoproteins without inducing an HSR. EnnA triggers immunogenic cell death in triple-negative breast cancer (TNBC) syngeneic mouse models and exhibits superior antitumor activity compared to Hsp90 N-terminal inhibitors. …

Salamander Modeling: Bridging The Gaps In Environmental Science Accessibility, Grace Leopold

Honors Program Theses and Projects

In the realm of science education, ensuring inclusivity and accessibility for all students, especially those with Individualized Education Programs (IEPs), is an imperative goal. IEPs are customized plans designed to support students with diverse learning needs, which can encompass a broad spectrum of disabilities and learning differences (Shaw, 2021). Providing learners with an IEP is an integral part of Special Education, however, there are a host of overarching challenges faced by students with IEPs in science education, especially in environmental science classes. In this thesis, the development and application of clay salamander models are evaluated for their potential to provide …

Investigating The Role Of Bhlhe40 In Host Responses To Mycobacterium Tuberculosis Infection And Myeloid Cell Development, Skyler Hendrix

Arts & Sciences Graduate Student Theses and Dissertations

Infections with Mycobacterium tuberculosis (Mtb), the causative agent of the disease tuberculosis (TB), remain a prominent global health threat that affects millions of people annually. While antibiotic treatments for Mtb infections are available, the increased prevalence of drug-resistant Mtb cases has highlighted the urgent need to develop additional therapeutic options such as host-directed therapies. Development of host-directed therapies, however, first requires a better understanding of the protective immune responses required to control Mtb infection. Such responses must strike a precise balance between pro-inflammatory and anti-inflammatory responses that promote bacterial clearance while also minimizing tissue damage. Here we show that the …

Tropicalization Fact Sheet, Linda Walters, Carla Perscky

CEELAB Outreach Materials

The goal of this 2-sided fact sheet is to introduce the topic of tropicalization along our coastlines to young audiences and their families. Tropicalization is defined as, "the transformation of ecosystems by tropical organisms that migrate towards the poles in response to warming minimum winter temperatures."

Understanding And Combating The Spread Of Antibiotic-Resistant Organisms, Bejan Mahmud

Arts & Sciences Graduate Student Theses and Dissertations

The introduction of antibiotics in the 20th century stands as one of our greatest scientific achievements, profoundly transforming human health and global well-being. Over the past century, antibiotics have ensured that infectious diseases are no longer the most common causes of death worldwide. In further enabling a vast array of invasive medical procedures (e.g., surgeries, organ transplants), antibiotics have effectively added decades to the average human lifespan. In agriculture, antibiotics have been heavily relied upon to meet the nutritional demands of the growing human population. Thus, ever since the introduction of penicillin, antibiotics have been the “miracle drugs” they were …