Cell and Developmental Biology Commons^™

Visual Arts Enhance Instruction In Observation And Analysis Of Microscopic Forms In Developmental And Cell Biology, Max Ezin, Christina Noravian, Amira Mahomed, Adam Lyle, Aveleen Gill, Tamira Elul

The Transdisciplinary STEAM+ Journal

Two important skills for scientists in developmental and cell biology, as well as in fields such as neurobiology, histology and pathology, are: 1) observation of features and details in microscopic images of cells, and 2) quantification of cellular features observed in microscopic images. However, current training in developmental and cell biology does not emphasize observation and quantitative analysis of microscopic images, and it is unclear how best to teach students these skills. Here, we describe our experiences applying visual artistic approaches to instruct undergraduate and graduate students in how to observe and analyze cellular forms in microscopic images. At Loyola …

Epidemiology Of Non-Alcoholic Fatty Liver Disease And Risk Of Hepatocellular Carcinoma Progression, Krishna Chaitanya Thandra, Adam Barsouk, Kalyan Saginala, John Sukumar Aluru, Prashanth Rawla, Alexander Barsouk

Kimmel Cancer Center Faculty Papers

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. Its incidence has grown alongside the increasing global prevalence of type 2 diabetes, obesity, and metabolic syndrome. The risk of progression to hepatocellular carcinoma for nonalcoholic steatohepatitis patients over 5 years is 8%, and despite targeted and immunotherapy treatment advances, HCC maintains a bleak 5-year survival of 19%. NAFLD’s primary risk factors are components of metabolic syndrome as well as possible sleep disturbances. NAFLD is most common among men 50-60 years of age, though incidence in women catches up after menopause. In the US, Hispanics are …

Molecular Signatures Of Sexual Communication In The Phlebotomine Sand Flies, Paul V. Hickner, Nataliya Timoshevskaya, Ronald J. Nowling, Frédéric Labbé, Andrew D. Nguyen, Mary Ann Mcdowell, Carolina N. Spiegel, Zainulabeuddin Syed

Biology Faculty Publications

Phlebotomine sand flies employ an elaborate system of pheromone communication wherein males produce pheromones that attract other males to leks (thus acting as an aggregation pheromone) and females to the lekking males (sex pheromone). In addition, the type of pheromone produced varies among populations. Despite the numerous studies on sand fly chemical communication, little is known of their chemosensory genome. Chemoreceptors interact with chemicals in an organism’s environment to elicit essential behaviors such as the identification of suitable mates and food sources. Thus, they play important roles during adaptation and speciation. Major chemoreceptor gene families, odorant receptors (ORs), gustatory receptors …

Modeling By Disruption And A Selected-For Partner For The Nude Locus, Jian Li, Yun-Kyoung Lee, Wenyu Fu, Anne M. Whalen, Mario C. Estable, Laurel A. Raftery, Kristin White, Lorin Weiner, Janice L. Brissette

Life Sciences Faculty Research

A long‐standing problem in biology is how to dissect traits for which no tractable model exists. Here, we screen for genes like the nude locus (Foxn1)—genes central to mammalian hair and thymus development—using animals that never evolved hair, thymi, or Foxn1. Fruit flies are morphologically disrupted by the FOXN1 transcription factor and rescued by weak reductions in fly gene function, revealing molecules that potently synergize with FOXN1 to effect dramatic, chaotic change. Strong synergy/effectivity in flies is expected to reflect strong selection/functionality (purpose) in mammals; the more disruptive a molecular interaction is in alien contexts (flies), the more beneficial it …

Arp2/3-Independent Wave/Scar Pathway And Class Xi Myosin Control Sperm Nuclear Migration In Flowering Plants, Mohammad F. Ali, Umma Fatema, Xiongbo Peng, Samuel W. Hacker, Daisuke Maruyama, Meng-Xiang Sun, Tomokazu Kawashima

Plant and Soil Sciences Faculty Publications

After eukaryotic fertilization, gamete nuclei migrate to fuse parental genomes in order to initiate development of the next generation. In most animals, microtubules control female and male pronuclear migration in the zygote. Flowering plants, on the other hand, have evolved actin filament (F-actin)-based sperm nuclear migration systems for karyogamy. Flowering plants have also evolved a unique double-fertilization process: two female gametophytic cells, the egg and central cells, are each fertilized by a sperm cell. The molecular and cellular mechanisms of how flowering plants utilize and control F-actin for double-fertilization events are largely unknown. Using confocal microscopy live-cell imaging with a …

A Molecular Toolset For The In Vivo Detection Of A Sulfolobus Islandicus Leucyl Trna Synthetase Paralog, Nicholas Michael Bretz

Theses and Dissertations

An ancient and ubiquitous set of enzymes known as the aminoacyl-tRNA synthetases are required for the viability of all organisms. The aminoacyl-tRNA synthetases catalyze the attachment of amino acids onto tRNA molecules. The aminoacylated, or charged, tRNA is then transported and utilized at the ribosome for the synthesis of proteins. The genome of the hyperthermophilic microorganism Sulfolobus islandicus (S. islandicus) harbors a unique leucyl-tRNA synthetase paralog, LeuRS-I, of unknown function. While its duplicate, LeuRS-F, carries out all the classical functions of LeuRS-family enzymes, LeuRS-I fails to charge leucine onto tRNALeu, despite its ability to activate this amino acid and bind …

Biological Pretreatment Of Biomass For Enhanced Biogas Production, Skylar F. Van Horne

Undergraduate Honors Theses

The biogas output efficiency of controlled anaerobic digestion (AD) can be enhanced by several different pretreatment methods to produce renewable energy. According to the literature, there are pros and cons to each pretreatment method. Biological pretreatment provides environmentally safe and renewable means for enhancing biodegradability and net energy output. Current research has yet to reliably demonstrate the ability of bacterial strains, such as Caldicellulosiruptor bescii (C. bescii), to digest common waste substrates in efficient ways. Novel methods in key intermediate molecular quantification and alkalinity tracking are used here to explore C. bescii’s ability to digest lignocellulosic material in …

Targeted Therapies In Select Gastrointestinal Cancers And Cancer Cachexia, Scott Mulder

Theses & Dissertations

Hepatocellular carcinomas exhibit metabolic alterations to support their proliferative and biosynthetic needs. We identified that elevated expression of the mitochondrial oxidative carboxylase, malic enzyme 2 (ME2), correlates with poorer hepatocellular carcinoma patient survival. Hepatocellular carcinoma patient tumors with high ME2 expression exhibit transcriptomic alterations indicative of PI3K/AKT/mTOR and c-Myc signaling as well as elevated central carbon, fatty acid, and redox metabolism pathways. Depletion of ME2 in the hepatocellular carcinoma cell line PLC or in the livers of mice treated with diethylnitrosamine to chemically induce hepatocellular carcinomas, results in impaired proliferation and reduced tumor formation. Additionally, the loss of …

The Cellular Origin And Molecular Drivers Of Claudin-Low Mammary Cancer, Patrick D. Raedler

Theses & Dissertations

Breast cancers of the claudin-low subtype make up a substantial portion of triple-negative breast cancers and have stem cell-like and mesenchymal features. Although it has been recognized for some time that this breast cancer subtype is highly aggressive and difficult to treat, the molecular drivers and cellular origin of claudin-low breast cancer have been poorly defined. The lack of suitable in vivo models has prohibited the study of tumor initiation and progression of this subtype. In this work, we report two novel mouse models that, upon expression of oncogenic RAS in the mammary epithelium, develop highly metastatic triple-negative mammary tumors …

Mechanisms By Which Mnte-2-Pyp Suppresses Prostate Cancer Cell Growth, Yuxiang Zhu

Theses & Dissertations

Prostate cancer patients are often treated with radiotherapy. MnTE-2-PyP, is a superoxide dismutase (SOD) mimic and a known radioprotector of normal tissues. Our recent work demonstrates that MnTE-2-PyP also inhibits prostate cancer progression with radiotherapy; however, the mechanisms remain unclear. In this thesis, we identified that MnTE-2-PyP-induced intracellular H2O2 levels are critical in inhibiting growth of prostate cancer cells. We found that MnTE-2-PyP induced protein oxidations in PC3 cells and one major group of oxidized protein targets were involved in energy metabolism. The oxidative phosphorylation rates were significantly enhanced in both PC3 and LNCaP cells with MnTE-2-PyP treatment, but mitochondrial …

Correction: Moxley, R.A., Et Al. Intimate Attachment Of Escherichia Coli O157:H7 To Urinary Bladder Epithelium In The Gnotobiotic Piglet Model. Microorganisms 2020, 8, 263, Rodney A. Moxley, Tom W. Bargar, Stephen D. Kachman, Diane R. Baker, David Francis

School of Veterinary and Biomedical Sciences: Faculty Publications

The authors wish to make the following corrections to this paper [1]: On page 2, the sentence that reads, “Hence, EHEC is a rare but established cause of HUS in children and adults.” should read, “Hence, EHEC is a rare but established cause of UTI-associated HUS in children and adults.” On page 4, the sentence that reads, “As noted previously, 14 of 126 (13.3%) piglets orally inoculated with EHEC O157:H7 strains developed mild to moderate purulent cystitis within 8 d PI [25] (Table 1).” should read, “As noted previously, 14 of 105 (13.3%) piglets orally inoculated with EHEC O157:H7 strains …

Single-Fluorophore Sensors For Mechanical Force In Living Cells, Sarah Kricheff

Honors Scholar Theses

Mechanotransduction is the process by which a mechanical stimulus is converted to a cellular signal. This process is heavily influential of cell morphology, differentiation, and behavior. However, altered levels of mechanical stimuli are also found in many pathological contexts. For example, cancerous cells have stiffer surrounding tissue than healthy cells, and research suggests that this alters cell behavior and promotes metastasis. Despite these findings, the cellular processes behind these signaling alterations remain widely unknown. Understanding these cascades is critical, as involved proteins can give us a deeper understanding of the role of mechanotransduction, and certain proteins can potentially be targeted …

K2p2.1 (Trek-1) Potassium Channel Activation Protects Against Hyperoxia-Induced Lung Injury, Tatiana Zyrianova, Benjamin Lopez, Riccardo Olcese, John Belperio, Christopher M. Waters, Leanne Wong, Victoria Nguyen, Sriharsha Talapaneni, Andreas Schwingshackl

Physiology Faculty Publications

No targeted therapies exist to counteract Hyperoxia (HO)-induced Acute Lung Injury (HALI). We previously found that HO downregulates alveolar K_2P2.1 (TREK-1) K⁺ channels, which results in worsening lung injury. This decrease in TREK-1 levels leaves a subset of channels amendable to pharmacological intervention. Therefore, we hypothesized that TREK-1 activation protects against HALI. We treated HO-exposed mice and primary alveolar epithelial cells (AECs) with the novel TREK-1 activators ML335 and BL1249, and quantified physiological, histological, and biochemical lung injury markers. We determined the effects of these drugs on epithelial TREK-1 currents, plasma membrane potential (Em), and intracellular Ca …

Translating Evidence-Based Guidelines Into Practice—Are We Getting It Right? A Multi-Centre Prospective International Audit Of Nutrition Care In Patients With Foregut Tumors (Inform), Merran Findlay, Judith D. Bauer, Rupinder Dhaliwal, Marian De Van Der Schueren, Alessandro Laviano, Adrianne Widaman, Lisa Martin, Andrew G. Day, Leah M. Gramlich

Faculty Research, Scholarly, and Creative Activity

Malnutrition is highly prevalent in patients with foregut tumors comprising head and neck (HNC) and esophageal (EC) cancers, negatively impacting outcomes. International evidence-based guidelines (EBGs) for nutrition care exist; however, translation of research evidence into practice commonly presents considerable challenges and consequently lags. This study aimed to describe and evaluate current international nutrition care practices compared with the best-available evidence for patients with foregut tumors who are at high risk of malnutrition. A multi-centre prospective cohort study enrolled 170 patients commencing treatment of curative intent for HNC (n = 119) or EC (n = 51) in 11 cancer …

Pd-L1 Expression On Circulating Tumor Cells May Be Predictive Of Response To Pembrolizumab In Advanced Melanoma: Results From A Pilot Study, Muhammad K. Khattak, Anna L. Reid, James Freeman, Michelle Pereira, Ashleigh Mcevoy, Johnny Lo, Markus Frank, Tarek Meniawy, Ali Didan, Isaac Spencer, Benhur Amanuel, Michael Millward, Mel Ziman, Elin Gray

Research outputs 2014 to 2021

BACKGROUND: PD-1 inhibitors are routinely used for the treatment of advanced melanoma. This study sought to determine whether PD-L1 expression on circulating tumor cells (CTCs) can serve as a predictive biomarker of clinical benefit and response to treatment with the PD-1 inhibitor pembrolizumab.

METHODS: Blood samples were collected from patients with metastatic melanoma receiving pembrolizumab, prior to treatment and 6-12 weeks after initiation of therapy. Multiparametric flow cytometry was used to identify CTCs and evaluate the expression of PD-L1.

RESULTS: CTCs were detected in 25 of 40 patients (63%). Patients with detectable PD-L1

CONCLUSION: Our results reveal the potential of …

Structural Characterization And In Vitro Lipid Binding Studies Of Non-Specific Lipid Transfer Protein 1 (Nsltp1) From Fennel (Foeniculum Vulgare) Seeds, Mekdes Megeressa, Bushra Siraj, Shamshad Zarina, Aftab Ahmed

Pharmacy Faculty Articles and Research

Non-specific lipid transfer proteins (nsLTPs) are cationic proteins involved in intracellular lipid shuttling in growth and reproduction, as well as in defense against pathogenic microbes. Even though the primary and spatial structures of some nsLTPs from different plants indicate their similar features, they exhibit distinct lipid-binding specificities signifying their various biological roles that dictate further structural study. The present study determined the complete amino acid sequence, in silico 3D structure modeling, and the antiproliferative activity of nsLTP1 from fennel (Foeniculum vulgare) seeds. Fennel is a member of the family Umbelliferae (Apiaceae) native to southern Europe and the Mediterranean …

Tunel Apoptotic Cell Detection In Stony Coral Tissue Loss Disease (Sctld): Evaluation Of Potential And Improvements, E. Murphy Mcdonald

All HCAS Student Capstones, Theses, and Dissertations

Stony coral tissue loss disease (SCTLD) is a highly lethal coral disease that has caused a dramatic loss of coral tissue along the Florida Reef Tract and throughout the Wider Caribbean. This study seeks to understand whether programmed cell death (apoptosis) is involved in the pathology of the highly virulent SCTLD tissue loss lesion. Tissues from diseased colonies of Pseudodiploria strigosa collected in 2018 and 2020 were stained using the terminal deoxyribonucleotidyltransferase (TdT) mediated dUTP-biotin nick end labeling (TUNEL) assay to visualize areas of programmed cell death. The archived tissue samples collected in 2018 exhibited a significantly higher degree of …

Unconventional Constituents And Shared Molecular Architecture Of The Melanized Cell Wall Of C. Neoformans And Spore Wall Of S. Cerevisiae, Christine Chrissian, Coney Pei-Chin Lin, Emma Camacho, Arturo Casadevall, Aaron M. Neiman, Ruth E. Stark

Publications and Research

The fungal cell wall serves as the interface between the cell and the environment. Fungal cell walls are composed largely of polysaccharides, primarily glucans and chitin, though in many fungi stress-resistant cell types elaborate additional cell wall structures. Here, we use solid-state nuclear magnetic resonance spectroscopy to compare the architecture of cell wall fractions isolated from Saccharomyces cerevisiae spores and Cryptococcus neoformans melanized cells. The specialized cell walls of these two divergent fungi are highly similar in composition. Both use chitosan, the deacetylated derivative of chitin, as a scaffold on which a polyaromatic polymer, dityrosine and melanin, respectively, is assembled. …

Technology Aiding In Neonatal Lung Developmental Care, Megan Kirk

Undergraduate Honors Theses

In this paper, old as well as new technological findings to decrease premature infant mortality are reviewed. This paper discusses fetal development throughout pregnancy from conception to full-term status as well as fetal lung development specifically from conception until full-term status. Several ideas to rapidly develop and mature fetal lungs are discussed such as mothers ingesting artificial surfactant supplements, either independently or coupled with antenatal corticosteroids, as well as intra-amniotic instillation prior to 28 weeks gestational. Drawbacks regarding these two are mentioned as well such as the fetus’s lungs not being mature enough to use the artificial surfactant leading into …

Supersize It! Developing A "Supercytoplast" Through Platelet Fusion, Taulbee B. Gunter

Animal Science Undergraduate Honors Theses

Stem cell research opens a wide range of possibilities from lab-grown tissues for medical purposes to cloned animals for livestock production. The issue with one of the most popular forms of cell recombination into a stem cell, known as somatic cell nuclear transfer (SCNT), is that it requires an oocyte. The requirement of an oocyte is often the host of public scrutiny for its economic and ethical issues. Platelets may offer a less expensive and more accessible alternative to oocytes as sources of naturally enucleated cells. Thus, the objective of this explorative research project is to isolate and fuse platelets …

Conditional Distance Correlation Test For Gene Expression Level, Dna Methylation Level And Copy Number, Shanshan Zhang

Graduate Theses and Dissertations

Over the past years, efforts have been devoted to the genome-wide analysis of genetic and epigenetic profiles to better understand the underlying biological mechanisms of complex diseases such as cancer. It is of great importance to unravel the complex dependence structure between biological factors, and many conditional dependence tests have been developed to meet this need. The traditional partial correlation method can only capture the linear partial correlation, but not the nonlinear correlation. To overcome this limitation, we propose to use the innovative conditional distance correlation (CDC), which measures the conditional dependence between random vectors and detect nonlinear relations. In …

A Two-Clone Approach To Study Signaling Interactions Among Neuronal Cells In A Pre-Clinical Alzheimer’S Disease Model, Catherine J. Yeates, Ankita Sarkar, Prajakta Deshpande, Madhuri Kango-Singh, Amit Singh

Biology Faculty Publications

To understand the progression of Alzheimer's disease, studies often rely on ectopic expression of amyloid-beta 42 (Aβ42) throughout an entire tissue. Uniform ectopic expression of Aβ42 may obscure cell-cell interactions that contribute to the progression of the disease. We developed a two-clone system to study the signaling cross talk between GFP-labeled clones of Aβ42-expressing neurons and wild-type neurons simultaneously generated from the same progenitor cell by a single recombination event. Surprisingly, wild-type clones are reduced in size as compared with Aβ42-producing clones. We found that wild-type cells are eliminated by the induction of cell death. Furthermore, aberrant activation of c-Jun-N-terminal …

Does The Presence Of Multiple Β-Lactamases In Gram-Negative Bacilli Impact The Results Of Antimicrobial Susceptibility Tests And Extended-Spectrum Β-Lactamase And Carbapenemase Confirmation Methods?, Fred C. Tenover, Caitlin M. Dela Cruz, Scott Dewell, Victoria M. Le, Isabella A. Tickler

Biology Faculty Publications

Objectives: Many multidrug-resistant Gram-negative bacilli (MDR-GNB) harbour multiple β-lactamases. The aim of this study was to assess the impact of multiple β-lactamase carriage on the accuracy of susceptibility tests and extended-spectrum β-lactamase (ESBL) and carbapenemase confirmation methods.

Methods: A total of 50 MDR-GNB, of which 29 carried multiple β-lactamases, underwent broth microdilution (BMD) and disk diffusion (DD) testing as well as confirmation tests for ESBLs and carbapenemases. Whole-genome sequencing (WGS) was used for β-lactamase gene identification.

Results: Categorical agreement of BMD and DD testing results ranged from 86.5 to 97.7% for 10 β-lactam agents. BMD and DD algorithms for ESBL …

Role Of Β-Glucan Structure In Dectin-1 Homo- And Hetero-Oligomerization In Innate Anti-Fungal Immunity, Eduardo U. Anaya

Biomedical Sciences ETDs

Dectin-1A is a C-type Lectin innate immunoreceptor that recognizes β-(1,3)-glucan, a structural component of Candida species cell walls. Dectin-1 has eight alternative splice isoforms including, A and B. Innate immunocytes can express one or both isoforms, but neither their relative responsiveness to β-glucan nor the potential for inter-isoform signaling cross-talk is well understood. In this study, we determine how the different structures of soluble β-glucans affect both isoforms and unravel how differences in glucan structure impact the earliest events in Dectin-1 signaling. Using quantitative microscopy techniques, we explored the role of glucan structure on Dectin-1A oligomerization, which is thought to …

Disruption Of Dna Polymerase Zeta Promotes An Innate Immune Response, Sara Martin

Dissertations and Theses (Open Access)

DNA polymerase ζ (pol ζ) is a specialized polymerase that protects cells from the consequences of DNA damage and stress. Without pol ζ function mammalian cells and yeast are exquisitely sensitive to genotoxic stresses including ultraviolet irradiation and platinum compounds such as the chemotherapeutic agent cisplatin. This elevated sensitivity arises from the central role of pol ζ in lesion bypass. Pol ζ is also required to protect cells from endogenous genomic damage or stress. In primary mammalian cells, the function of pol ζ is required for genome protection and normal proliferation. Immortalized Rev3lknockout (KO) MEFs are under considerable constitutive …

Calcium Dyshomeostasis In Neurodegeneration, Nicholas Emanuel Karagas

Dissertations and Theses (Open Access)

Neurodegenerative diseases, despite constituting a major and growing cause of mortality globally, have few effective treatments. In order to develop novel therapeutics to combat neurodegeneration, a better understanding of the molecular mechanisms underlying these diseases is needed. Neurons rely on Ca²⁺ to mediate many of their unique functions, and aberrant Ca²⁺ signaling has been broadly implicated in neurodegeneration. The goal of this dissertation is to delineate specific examples of Ca²⁺ dyshomeostasis that I have uncovered in Drosophila models of neurodegeneration.

I first define the role a neurodegeneration-associated mutation plays in perturbing presynaptic [Ca²⁺], which is …

The Role Of Liver Sinusoidal Endothelial Cells In Liver Malady Homeostasis, Fatima Cabral

Department of Biochemistry: Dissertations, Theses, and Student Research

Current literature described techniques for the purification of liver cell types through text alone. The techniques described for the isolation of liver sinusoidal endothelial cells as well as hepatocytes described here are modified from a published article in the Journal of Visualized experiments. The video protocol allows for the user to successfully isolate cells as the most difficult parts of the procedure are demonstrated visually. The detection of liver maladies such as the non-alcoholic fatty liver disease, the stage if this disease and differentiation between non-alcoholic and alcoholic fatty liver disease is demonstrated in the development of a unique panel …

Assessment Of The Potential Anti-Tumour Effect Of Salvia Triloba And The Combination Of Salvia Triloba And Paclitaxel On Ovarian Cancer: Skov3 Cell Line, Naela Adel Mohammed

Archived Theses and Dissertations

No abstract provided.

Gap Junctions In Stem Cells Provide An Essential Conduit For Cell-Cell Communication, Jacob M. Gunn, David L. Geenen

Student Summer Scholars Manuscripts

Introduction: Myocardial infarction (MI) results from the death of cardiomyocytes (CM) following obstruction of blood flow and diminished oxygen supply to the tissue (hypoxia). Human adipose tissue-derived stem cells (hADSCs) used in pre-clinical models can replace damaged CM, however, this has not been replicated in human clinical trials due to early loss of hADSCs. We hypothesize that coupling of hADSCs to dying CMs may account for part of this loss. Furthermore, cell culturing is essential aspect of any in-vitro experiment. Through multiple trials we sought to maximize the efficiency of our culturing procedures in order to best facilitate the …

Impact Of Global Structure On Diffusive Exploration Of Organelle Networks, Aidan I. Brown, Laura M. Westrate, Elena F. Koslover

University Faculty Publications and Creative Works

We investigate diffusive search on planar networks, motivated by tubular organelle networks in cell biology that contain molecules searching for reaction partners and binding sites. Exact calculation of the diffusive mean first-passage time on a spatial network is used to characterize the typical search time as a function of network connectivity. We find that global structural properties — the total edge length and number of loops — are sufficient to largely determine network exploration times for a variety of both synthetic planar networks and organelle morphologies extracted from living cells. For synthetic networks on a lattice, we predict the search …