Cell and Developmental Biology Commons^™

Cyclophilin D Is A Sensor Of Nano-Pulse Stimulation, Brittney Ruedlinger, Bani Hani Maisoun, Lucas Potter, Nicola Lai, Stephen J. Beebe

The Graduate School Posters

Nano-Pulse Stimulation (NPS), a pulsed power-derived technology, stimulates structural and functional changes in plasma membranes and cellular organelles. NPS induces a Ca²⁺ influx and opening of the mitochondrial permeability transition pore (mPTP) that dissipates the mitochondrial membrane potential (ΔΨ_m) and, when sustained, induces regulated cell death. Here we show that in rat cardiomyoblasts (H9C2) cyclophilin D (CypD) is a mitochondrial sensor for NPS as defined by observations that loss of ΔΨ_m is Ca²⁺ and mitochondrial reactive oxygen species (mROS) dependent and cyclosporin A (CsA)-sensitive, which are diagnostic qualities for effects on CypD and the mPTP. …

Trials And Tribulations Of Humanizing Mice For Cancer Research, Brittney Ruedlinger, Steven Warsof, Eric Feliberti, Mary Beth Hughes, Ayobami ‘Edwin’ Oshin, Chunqi Jiang, Brittany P. Lassiter, Siqi Guo, Stephen J. Beebe

The Graduate School Posters

Cancers are aggressive, evasive, and ruthless killers, claiming millions of lives every year. Cancers are heterogeneous and there is often no single, clearly defined problem as they harness and manipulate a multitude of fundamental mechanisms at the very essence of life. To investigate these mechanisms and vet potential interventive therapies, humanized mice offer a unique model as a prelude to the use of nanosecond pulse stimulation (NPS), a pulse power technology applying nanosecond duration, high electric field pulses, to ablate human tumors. Immunodeficient mouse strains, NSG and NSG-SGM3, were engrafted with human immune cells and human tumors, which would allow …

Influence Of Monovalent And Divalent Ions In The Conformational Change Of Caspase-Cleaved Par-4 (Cl-Par-4) Tumor Suppressor Protein, Krishna K. Raut, Komala Ponniah, Steven M. Pascal

College of Sciences Posters

Prostate apoptosis response-4 (Par-4) is a pro-apoptotic tumor suppressor protein. We have shown that this 38 kDa full-length Par-4 (Fl-Par-4) protein is predominantly intrinsically disordered in vitro. In vivo, Par-4 is cleaved by caspase-3 at Asp-131 to generate a 24 kDa functionally active cleaved Par-4 (cl-Par-4) fragment. The cl-Par-4 protein inhibits the NF-κB-mediated cell survival pathway and causes selective apoptosis in various tumor cells. Our laboratory is interested in how the disorder-order balance within Fl-Par-4 and cl-Par-4 may be related to the balance between cell survival and cell death. Currently, we are using biophysical techniques such as circular …

Stobe Photography Mapping Of Cell Membrane Potential With Nanosecond Resolution, Allen S. Kiester, Bennett L. Ibey, Zachary N. Coker, Andrei G. Pakhomov, Joel N. Bixler

Bioelectrics Publications

The ability to directly observe membrane potential charging dynamics across a full microscopic field of view is vital for understanding interactions between a biological system and a given electrical stimulus. Accurate empirical knowledge of cell membrane electrodynamics will enable validation of fundamental hypotheses posited by the single shell model, which includes the degree of voltage change across a membrane and cellular sensitivity to external electric field non-uniformity and directionality. To this end, we have developed a high-speed strobe microscopy system with a time resolution of ~ 6 ns that allows us to acquire time-sequential data for temporally repeatable events (non-injurious …

Connexin Hemichannel Activation By S-Nitrosoglutathione Synergizes Strongly With Photodynamic Therapy Potentiating Anti-Tumor Bystander Killing, Chiara Nardin, Chiara Peres, Sabrina Putti, Tiziana Orsini, Claudia Colussi, Flavia Mazzarda, Marcello Raspa, Ferdinando Scavizzi, Anna Maria Salvatore, Francesco Chiani, Abraham Tettey-Matey, Yuanyuan Kuang, Guang Yang, Mauricio A. Retamal, Fabio Mammano

Bioelectrics Publications

In this study, we used B16-F10 cells grown in the dorsal skinfold chamber (DSC) preparation that allowed us to gain optical access to the processes triggered by photodynamic therapy (PDT). Partial irradiation of a photosensitized melanoma triggered cell death in non-irradiated tumor cells. Multiphoton intravital microscopy with genetically encoded fluorescence indicators revealed that bystander cell death was mediated by paracrine signaling due to adenosine triphosphate (ATP) release from connexin (Cx) hemichannels (HCs). Intercellular calcium (Ca²⁺) waves propagated from irradiated to bystander cells promoting intracellular Ca²⁺ transfer from the endoplasmic reticulum (ER) to mitochondria and rapid activation of …

Effect Of He Plasma Jet Versus Surface Plasma On The Metabolites Of Acute Myeloid Leukemia Cells, Dehui Xu, Ning Ning, Yujing Xu, Wenjie Xia, Hai-Lan Chen, Michael G. Kong

Bioelectrics Publications

Cold atmospheric plasma, including plasma jet and surface plasma, can promote the apoptosis of cancer cells without causing significant damage to surrounding normal cells, which was hopeful to be applied to the clinical cancer therapy. However, experimental plasma devices used directly to clinical experiments has challenges in technology and methods, especially the difference in killing tumor cells efficiency of these two common plasma sources. Therefore, it is great necessity to explore the differences in treating tumors between different plasma sources. This paper achieved good killing efficiency by using two kinds of cold atmospheric plasma generating devices, namely plasma jet and …

Photodynamic Therapy Of Inorganic Complexes For The Treatment Of Cancer, Chloe B. Smith, Lindsay C. Days, Duaa R. Alajroush, Khadija Faye, Yara Khodour, Stephen J. Beebe, Alvin Holder

Chemistry & Biochemistry Faculty Publications

Photodynamic therapy (PDT) is a medicinal tool that uses a photosensitiser and a light source to treat several conditions, including cancer. PDT uses reactive oxygen species (ROS) such as cytotoxic singlet oxygen ¹O₂ to induce cell death in cancer cells. Chemotherapy has historically utilized the cytotoxic effects of many metals, especially transition-metal complexes. However, chemotherapy is a systemic treatment so all cells in a patient's body are exposed to the same cytotoxic effects. Transition metal complexes have also shown high cytotoxicity as PDT agents. PDT is a potential localized method for treating several cancer types by using inorganic …

Tetraspanins As Potential Therapeutic Candidates For Targeting Flaviviruses, Waqas Ahmed, Girish Neelakanta, Hameeda Sultana

Biological Sciences Faculty Publications

Tetraspanin family of proteins participates in numerous fundamental signaling pathways involved in viral transmission, virus-specific immunity, and virus-mediated vesicular trafficking. Studies in the identification of novel therapeutic candidates and strategies to target West Nile virus, dengue and Zika viruses are highly warranted due to the failure in development of vaccines. Recent evidences have shown that the widely distributed tetraspanin proteins may provide a platform for the development of novel therapeutic approaches. In this review, we discuss the diversified and important functions of tetraspanins in exosome/extracellular vesicle biology, virus-host interactions, virus-mediated vesicular trafficking, modulation of immune mechanism(s), and their possible role(s) …

Self And Microbiota-Derived Epitopes Induce Cd4⁺ T Cell Anergy And Conversion Into Cd4⁺Foxp3⁺ Regulatory Cells, Michal P. Kuczma, Edyta A. Szurek, Anna Cebula, Vu L. Ngo, Maciej Pietrzak, Piotr Kraj, Timothy L. Denning, Leszek Ignatowicz

Biological Sciences Faculty Publications

The physiological role of T cell anergy induction as a key mechanism supporting self-tolerance remains undefined, and natural antigens that induce anergy are largely unknown. In this report, we used TCR sequencing to show that the recruitment of CD4⁺CD44⁺Foxp3⁻CD73⁺FR4⁺ anergic (Tan) cells expands the CD4⁺Foxp3⁺ (Tregs) repertoire. Next, we report that blockade in peripherally-induced Tregs (pTregs) formation due to mutation in CNS1 region of Foxp3 or chronic exposure to a selecting self-peptide result in an accumulation of Tan cells. Finally, we show that microbial antigens from Akkermansia muciniphila …

The Resistive Barrier Discharge: A Brief Review Of The Device And Its Biomedical Applications, Mounir Laroussi

Electrical & Computer Engineering Faculty Publications

This paper reviews the principles behind the design and operation of the resistive barrier discharge, a low temperature plasma source that operates at atmospheric pressure. One of the advantages of this plasma source is that it can be operated using either DC or AC high voltages. Plasma generated by the resistive barrier discharge has been used to efficiently inactivate pathogenic microorganisms and to destroy cancer cells. These biomedical applications of low temperature plasma are of great interest because in recent times bacteria developed increased resistance to antibiotics and because present cancer therapies often are accompanied by serious side effects. Low …

Plasma-Treated Solutions (Pts) In Cancer Therapy, Hiromasa Tanaka, Sander Bekeschus, Dayun Yan, Masaru Hori, Michael Keidar, Mounir Laroussi

Electrical & Computer Engineering Faculty Publications

Cold physical plasma is a partially ionized gas generating various reactive oxygen and nitrogen species (ROS/RNS) simultaneously. ROS/RNS have therapeutic effects when applied to cells and tissues either directly from the plasma or via exposure to solutions that have been treated beforehand using plasma processes. This review addresses the challenges and opportunities of plasma-treated solutions (PTSs) for cancer treatment. These PTSs include plasma-treated cell culture media in experimental research as well as clinically approved solutions such as saline and Ringer’s lactate, which, in principle, already qualify for testing in therapeutic settings. Several types of cancers were found to succumb to …

Tick Extracellular Vesicles Enable Arthropod Feeding And Promote Distinct Outcomes Of Bacterial Infection, Adela S. Oliva Chávez, Xiaowei Wang, Liron Marnin, Nathan K. Archer, Holly L. Hammond, Erin E. Mcclure Carroll, Dana K. Shaw, Brenden G. Tully, Amanda D. Buskirk, Shelby L. Ford, L. Rainer Butler, Preeti Shahi, Kateryna Morozova, Cristina C. Clement, Lauren Lawres, Anya J. O'Neal, Choukri Ben Mamoun, Kathleen L. Mason, Brandi E. Hobbs, Glen A. Scoles, Eileen M. Barry, Daniel E. Sonenshine, Utpal Pal, Jesus G. Valenzuela, Marcelo B. Sztein, Marcela F. Pasetti, Michael L. Levin, Michail Kotsyfakis, Steven M. Jay, Jason F. Huntley, Lloyd S. Miller, Laura Santambrogio, Joao H.F. Pedra

Biological Sciences Faculty Publications

Extracellular vesicles are thought to facilitate pathogen transmission from arthropods to humans and other animals. Here, we reveal that pathogen spreading from arthropods to the mammalian host is multifaceted. Extracellular vesicles from Ixodes scapularis enable tick feeding and promote infection of the mildly virulent rickettsial agent Anaplasma phagocytophilum through the SNARE proteins Vamp33 and Synaptobrevin 2 and dendritic epidermal T cells. However, extracellular vesicles from the tick Dermacentor andersoni mitigate microbial spreading caused by the lethal pathogen Francisella tularensis. Collectively, we establish that tick extracellular vesicles foster distinct outcomes of bacterial infection and assist in vector feeding by acting …

Modulation Of Ros In Nanosecond-Pulsed Plasma-Activated Media For Dosage-Dependent Cancer Cell Inactivation In Vitro, Chunqi Jiang, Esin Bengisu Sozer, Shutong Song, Nicola Lai, P. Thomas Vernier, Sigi Guo

Bioelectrics Publications

Dosage control of reactive oxygen and nitrogen species (RONS) is critical to low-temperature plasma applications in cancer therapy. Production of RONS by atmospheric pressure, nonequilibrium plasmas in contact with liquid may be modulated via plasma conditions including plasma treatment time and pulse voltage and repetition frequency. In this study, a terephthalic acid-based probe was used to measure hydroxyl radicals [OH_aq] in water exposed to plasma and to demonstrate that the OH_ag concentration increases linearly with treatment time. Fluorometric measurements of hydrogen peroxide concentration in plasma-activated water show a linear relationship between the H₂O₂ production …

Biomechanical And Biophysical Properties Of Breast Cancer Cells Under Varying Glycemic Regimens, Diganta Dutta, Xavier-Lewis Palmer, Jose Ortega-Rodas, Vasundhara Balraj, Indrani Ghosh Dastider, Surabhi Chandra

Electrical & Computer Engineering Faculty Publications

Diabetes accelerates cancer cell proliferation and metastasis, particularly for cancers of the pancreas, liver, breast, colon, and skin. While pathways linking the 2 disease conditions have been explored extensively, there is a lack of information on whether there could be cytoarchitectural changes induced by glucose which predispose cancer cells to aggressive phenotypes. It was thus hypothesized that exposure to diabetes/high glucose alters the biomechanical and biophysical properties of cancer cells more than the normal cells, which aids in advancing the cancer. For this study, atomic force microscopy indentation was used through microscale probing of multiple human breast cancer cells (MCF-7, …

Aging, Gait Variability, And Adaptability, Collin Douglas Bowersock

Health Services Research Dissertations

The purpose of this work was to study the relationships between age, measures of gait variability, and locomotor adaptability. Measures of gait variability are used to identify maladapted locomotor behavior, motor disease, and risk of falls. The first aim was to determine the relationships between age and measures of gait variability. Thirty-four participants (23-71 years old) walked on a treadmill for 6 minutes at their preferred speed. Variability of stride times and lengths was computed via linear measures (standard deviation and coefficient of variation) and nonlinear measures (sample entropy and detrended fluctuation analysis). Movement trajectory variability of the dominant knee …

Secretion Of Proteins And Antibody Fragments From Transiently Transfected Endothelial Progenitor Cells, Loree Heller, Reynald Thinard, Melanie Chevalier, Sezgi Arpag, Yu Jing, Ruth Greferath, Richard Heller, Claude Nicolau

Bioelectrics Publications

In neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis and amyotrophic lateral sclerosis, neuroinflammation can lead to blood-brain barrier (BBB) breakdown. After intravenous or intra-arterial injection into mice, endothelial progenitor cells (EPCs) home to the damaged BBB to promote neurovascular repair. Autologous EPCs transfected to express specific therapeutic proteins offer an innovative therapeutic option. Here, we demonstrate that EPC transfection by electroporation with plasmids encoding the reporter protein GFP or an anti-beta-amyloid antibody fragment (Fab) leads to secretion of each protein. We also demonstrate the secreted anti-beta-amyloid Fab protein functions in beta-amyloid aggregate solubilization.

Protonic Capacitor: Elucidating The Biological Significance Of Mitochondrial Cristae Formation, James Weifu Lee

Chemistry & Biochemistry Faculty Publications

For decades, it was not entirely clear why mitochondria develop cristae? The work employing the transmembrane-electrostatic proton localization theory reported here has now provided a clear answer to this fundamental question. Surprisingly, the transmembrane-electrostatically localized proton concentration at a curved mitochondrial crista tip can be significantly higher than that at the relatively flat membrane plane regions where the proton-pumping respiratory supercomplexes are situated. The biological significance for mitochondrial cristae has now, for the first time, been elucidated at a protonic bioenergetics level: 1) The formation of cristae creates more mitochondrial inner membrane surface area and thus more protonic capacitance for …

Size-Dependent Inhibitory Effects Of Antibiotic Nanocarriers On Filamentation Of E. Coli, Preeyaporn Songkiatisak, Feng Ding, Pavan Kumar Cherukuri, Xiao-Hong Nancy Xu

Chemistry & Biochemistry Faculty Publications

Multidrug membrane transporters exist in both prokaryotic and eukaryotic cells and cause multidrug resistance (MDR), which results in an urgent need for new and more effective therapeutic agents. In this study, we used three different sized antibiotic nanocarriers to study their mode of action and their size-dependent inhibitory effects against Escherichia coli (E. coli). Antibiotic nanocarriers (AgMUNH–Oflx NPs) with 8.6 × 10², 9.4 × 10³ and 6.5 × 10⁵ Oflx molecules per nanoparticle (NP) were prepared by functionalizing Ag NPs (2.4 ± 0.7, 13.0 ± 3.1 and 92.6 ± 4.4 nm) with a monolayer …

Npgreat: Hybrid Assembly Of Human Subtelomeres With The Use Of Nanopore And Linked-Read Datasets, Eleni Adam, Desh Ranjan, Harold Riethman

College of Sciences Posters

The telomeres are vitally important regions that are located at the tips of the chromosomes. Their dysfunction, caused by length shortening can lead to senescent cells, which in turn cause age-related diseases, including cancer. The subtelomeres, located next to the telomeres, possess the critical role of regulating the adjacent telomere lengths. Even after many years of research, human subtelomeres have proven to be very hard to assemble due to their morphology. In order to overcome these problems, the hybrid assembly method we develop utilizes two of the latest available types of data, which complement each other: Linked-Reads and ultralong Nanopore …

Pthr1/Sox9 And Idh1/Idh2 Relative Expression In Primary Chondrocyte And Chondrosarcoma Cells Under The Synergistic Influence Of Inducible Hypoxia And Extracellular Acidosis, Kostika Vangjeli

Biological Sciences Theses & Dissertations

Cartilage cells (Chondrocytes) grow in rather unique environmental conditions in the human body. Cartilage is avascular tissue and lacks innervation. Its main source of nutrients is derived from the synovial fluid and/or perichondrium. Consequently, these cells must survive and thrive under hypoxic and acidic stressors. Published data suggests that there are a multitude of genes affected from either one of these two stressors or both. However, these factors are frequently overlooked in cartilage research, and results are reported in either normoxia/pH=7.0 conditions, or they only account for one of the conditions. The scope of this study is to examine how …

Essential Role Of The Crk Family-Dosage In Digeorge-Like Anomaly And Metabolic Homeostasis, Akira Imamoto, Sewon Ki, Leiming Li, Kazunari Iwamoto, Venkat Maruthamuthu, John Devany, Ocean Lu, Suxiang Zhang, Takuji Yamada, Akiyoshi Hirayama, Shinji Fukuda, Yutaka Suzuki, Mariko Okada

Mechanical & Aerospace Engineering Faculty Publications

CRK and CRKL (CRK-like) encode adapter proteins with similar biochemical properties. Here, we show that a 50% reduction of the family-combined dosage generates developmental defects, including aspects of DiGeorge/del22q11 syndrome in mice. Like the mouse homologs of two 22q11.21 genes CRKL and TBX1, Crk and Tbx1 also genetically interact, thus suggesting that pathways shared by the three genes participate in organogenesis affected in the syndrome. We also show that Crk and Crkl are required during mesoderm development, and Crk/Crkl deficiency results in small cell size and abnormal mesenchyme behavior in primary embryonic fibroblasts. Our systems-wide analyses reveal impaired …

Bone Morphogenic Proteins Are Immunoregulatory Cytokines Controlling Foxp3+ TReg Cells, Lauren M. Browning, Caroline Miller, Michal Kuczma, Maciej Pietrzak, Yu Jing, Grzegorz Rempala, Pawel Muranski, Leszek Ignatowicz, Piotr Kraj

Bioelectrics Publications

Bone morphogenic proteins (BMPs) are members of the transforming growth factor β (TGF-β) cytokine family promoting differentiation, homeostasis, and self-renewal of multiple tissues. We show that signaling through the bone morphogenic protein receptor 1α (BMPR1α) sustains expression of FOXP3 in T_reg cells in peripheral lymphoid tissues. BMPR1α signaling promotes molecular circuits supporting acquisition and preservation of T_reg cell phenotype and inhibiting differentiation of pro-inflammatory effector Th1/Th17 CD4+ T cell. Mechanistically, increased expression of KDM6B (JMJD3) histone demethylase, an antagonist of the polycomb repressive complex 2, underlies lineage-specific changes of T cell phenotypes associated with abrogation of BMPR1α signaling. …

Mitochondrial Utilization Of Competing Fuels Is Altered In Insulin Resistant Skeletal Muscle Of Non-Obese Rats (Goto-Kakizaki), Nicola Lai, Ciarán E. Fealy, Chinna M. Kummitha, Silvia Cabras, John P. Kirwan, Charles L. Hoppel

Electrical & Computer Engineering Faculty Publications

Aim: Insulin-resistant skeletal muscle is characterized by metabolic inflexibility with associated alterations in substrate selection, mediated by peroxisome-proliferator activated receptor 𝜹 (PPAR𝜹). Although it is established that PPAR𝜹 contributes to the alteration of energy metabolism, it is not clear whether it plays a role in mitochondrial fuel competition. While nutrient overload may impair metabolic flexibility by fuel congestion within mitochondria, in absence of obesity defects at a mitochondrial level have not yet been excluded. We sought to determine whether reduced PPAR𝜹 content in insulin-resistant rat skeletal muscle of a non-obese rat model of T2DM (Goto-Kakizaki, GK) ameliorate the inhibitory effect …

Granulosa Cell Proliferation Is Inhibited By Pge2 In The Primate Ovulatory Follicle, Patric S. Lundberg, Gil J. Moskowitz, Carmel Bellacose, Esra Demirel, Heidi A. Trau, Diane M. Duffy

Computer Science Faculty Publications

Prostaglandin E2 (PGE2) is a key paracrine mediator of ovulation. Few specific PGE2-regulated gene products have been identified, so we hypothesized that PGE2 may regulate the expression and/or activity of a network of proteins to promote ovulation. To test this concept, Ingenuity Pathway Analysis (IPA) was used to predict PGE2-regulated functionalities in the primate ovulatory follicle. Cynomolgus macaques underwent ovarian stimulation. Follicular granulosa cells were obtained before (0 h) or 36 h after an ovulatory dose of human chorionic gonadotropin (hCG), with ovulation anticipated 37-40 h after hCG. Granulosa cells were obtained from additional monkeys 36 h after treatment with …

Dynamics Of Trophoblast Differentiation In Peri-Implantation–Stage Human Embryos, Rachel C. West, Hao Ming, Deirdre M. Logsdon, Jiangwen Sun, Sandeep K. Rajput, Rebecca A. Kile, William B. Schoolcraft, R. Michael Roberts, Rebecca L. Krisher, Zongliang Jiang, Ye Yuan

Computer Science Faculty Publications

Single-cell RNA sequencing of cells from cultured human blastocysts has enabled us to define the transcriptomic landscape of placental trophoblast (TB) that surrounds the epiblast and associated embryonic tissues during the enigmatic day 8 (D8) to D12 peri-implantation period before the villous placenta forms. We analyzed the transcriptomes of 3 early placental cell types, cytoTB (CTB), syncytioTB (STB), and migratoryTB (MTB), picked manually from cultured embryos dissociated with trypsin and were able to follow sublineages that emerged from proliferating CTB at the periphery of the conceptus. A unique form of CTB with some features of STB was detectable at D8, …

Dormant Pathogenic Cd4(+) T Cells Are Prevalent In The Peripheral Repertoire Of Healthy Mice, Anna Cebula, Michal Kuczma, Edyta Szurek, Maciej Pietrzak, Natasha Savage, Wessam R. Elhefnawy, Grzegorz Rempala, Piotr Kraj, Leszek Ignatowicz

Computer Science Faculty Publications

Thymic central tolerance eliminates most immature T cells with autoreactive T cell receptors (TCR) that recognize self MHC/peptide complexes. Regardless, an unknown number of autoreactive CD4+Foxp3⁻ T cells escape negative selection and in the periphery require continuous suppression by CD4+Foxp3⁺ regulatory cells (Tregs). Here, we compare immune repertoires of Treg-deficient and Treg-sufficient mice to find Tregs continuously constraining one-third of mature CD4⁺Foxp3⁻ cells from converting to pathogenic effectors in healthy mice. These dormant pathogenic clones frequently express TCRs activatable by ubiquitous autoantigens presented by class II MHCs on conventional dendritic cells, including selfpeptides that select …

Effect Of The Physical Micro-Environment On Cell Adhesion And Force Exertion, Mohamad Eftekharjoo

Mechanical & Aerospace Engineering Theses & Dissertations

Physical characteristics of the microenvironment, such as geometry and stiffness, influence cell adhesion and contractile forces. Here, we determined how these physical factors influenced cell force exertion and adhesion in two specific contexts that have broad relevance.

Fibroblasts are cells in connective tissues that interact with a fibrous extracellular matrix (ECM) that have a predominantly one-dimensional (1D) (fibrillar) geometry. However, it has been unclear as to how the 1D nature of the fibrillar ECM influences the forces exerted by fibroblasts. Here, we used fibroblast cells adherent on fibronectin lines on polyacrylamide (PAA) gels of stiffness 13 and 45 kPa to …

The Expression Of Connexin-43 By Cd11c+ Dendritic Cells Is Required To Maintain Cd4+ Foxp3+ Regulatory T Cell Population In Peripheral Lymphoid Organs, Caroline Titus Miller

Biological Sciences Theses & Dissertations

Foxp3⁺ regulatory T cells (T_R) are an immunosuppressive subset of CD4⁺ T cells that maintain homeostasis of the immune system. They are sustained by the interaction between the Major Histocompatibility Complex (MHC) molecules present on antigen presenting dendritic cells and the T Cell Receptor (TCR) expressed on T_R cells that is specific for the MHC loaded with an antigenic peptide. Here, we show that in addition to MHC/TCR interaction, Connexin-43 (Cx43) expression by dendritic cells is required to maintain the TR cell population. CD11c⁺ dendritic cells represent a major subset of antigen presenting cells. …

Endogenous Force Transmission Between Epithelial Cells And A Role For Α-Catenin, Sandeep Dumbali

Mechanical & Aerospace Engineering Theses & Dissertations

In epithelial tissues, epithelial cells adhere to each other as well as to the underlying extra-cellular matrix (ECM). E-cadherin-based intercellular junctions play an important role in tissue integrity. These junctions experience cell-generated mechanical forces via apparent adaptor proteins such as beta (β) catenin, alpha (α) catenin and vinculin. Abnormalities in these junctions may result in skin related diseases and cancers. Here, I devised methods to determine the endogenous intercellular force within cell pairs as well as in large epithelial islands. I further ascertained the factors that affect the level of inter-cellular tension.

Experiments with pairs of epithelial cells exogenously expressing …

Study Of The Effects Of Silver Ions And Silver Nanoparticles On Embryonic Development, Martha Sharisha Johnson

Biomedical Sciences Theses & Dissertations

This dissertation focuses on the study of the toxicity of metal nanoparticles (NPs) and their ions on the development of zebrafish embryos, aiming to understand unique biological effects of NPs and ions, and design new in vivo assays to characterize the toxicity of these metal NPs and metal ions. Currently, the underlying molecular mechanisms of biological effects of nanomaterials are partially understood. Some studies assume that the toxic effects of NPs can be attributed to the release of their ions. We investigate the effects of silver NPs (Ag NPs) and silver ions (Ag+ ions) on the embryonic development of zebrafish …