Cells Commons^™

Cellular Bioenergetics Regulates Cell Proliferation During Mammalian Regeneration, Sandeep Saxena

Theses and Dissertations--Biology

Mammalian system consists of stress-sensing molecules that regulates their cellular response against damage, injury and oncogenic stress. During vertebrate regeneration, cells responding to injury re-enter the cell cycle and proliferate to form new tissue. Cell cycle re-entry or arrest is at least partly regulated by cellular senescence which negatively impacts the proliferative pool of cells during regeneration. What remains unclear is whether cells in regenerating systems possess an increased propensity to proliferate and are refractory to signals that induce senescence. My thesis work has focused on how fibroblasts from the ear pinna differentially regulate healing in highly regenerative mammals (e.g., …

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 …

The Role Of Reactive Oxygen Species In The Immunity Induced By Nano-Pulse Stimulation, Siqi Guo, Niculina I. Burcus, Megan Scott, Yu Jing, Iurii Semenov

Bioelectrics Publications

Reactive oxygen species (ROS) are byproducts of tumor cells treated with Nano-Pulse Stimulation (NPS). Recently, ROS have been suggested as a contributing factor in immunogenic cell death and T cell-mediated immunity. This research further investigated the role of NPS induced ROS in antitumor immunity. ROS production in 4T1-luc breast cancer cells was characterized using three detection reagents, namely, Amplex Red, MitoSox Red, and Dihydroethidium. The efficiency of ROS quenching was evaluated in the presence or absence of ROS scavengers and/or antioxidants. The immunogenicity of NPS treated tumor cells was assessed by ex vivo dendritic cell activation, in vivo vaccination assay …

Picosecond Pulsed Electric Fields And Promise In Neurodegeneration Research, Martina Zamponi, Ross Petrella, Peter A. Mollica

Medical Diagnostics & Translational Sciences Faculty Publications

The delivery of pulsed electric fields to biological cells for regenerative research and therapeutic applications is a field that has been widely explored. Picosecond pulsed electric fields have been shown to induce intracellular effects and directly target cell membrane proteins as well as being able to induce cell permeabilization and death by apoptosis. Additionally, ultrashort pulses can be focused and delivered in a noncontact manner for possible targeting of deep and inaccessible tissues. The unique characteristics of picosecond pulses make them a possible approach for treatment of Huntington's and Alzheimer's diseases, both characterized by progressive neuronal degeneration and death, and …

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 …

Peculiarities Of Neurostimulation By Intense Nanosecond Pulsed Electric Fields: How To Avoid Firing In Peripheral Nerve Fibers, Vitalii Kim, Emily Gudvangen, Oleg Kondratiev, Luis Redondo, Shu Xiao, Andrei G. Pakhomov

Bioelectrics Publications

Intense pulsed electric fields (PEF) are a novel modality for the efficient and targeted ablation of tumors by electroporation. The major adverse side effects of PEF therapies are strong involuntary muscle contractions and pain. Nanosecond-range PEF (nsPEF) are less efficient at neurostimulation and can be employed to minimize such side effects. We quantified the impact of the electrode configuration, PEF strength (up to 20 kV/cm), repetition rate (up to 3 MHz), bi- and triphasic pulse shapes, and pulse duration (down to 10 ns) on eliciting compound action potentials (CAPs) in nerve fibers. The excitation thresholds for single unipolar but not …

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 …

Site Tolerance Of The Rada Intein, Chase Taul, Christopher Lennon Dr

Honors College Theses

Inteins (intervening proteins) invade genes at the DNA level and splice out at the protein level. Once thought of as only a parasitic type of a mobile genetic element, recent work suggests a mutualistic relationship has formed in some cases within bacterial and archaeal hosts. After translation, a precursor protein is formed with the intein between two exteins. The intein is catalytic and can excise itself out through protein splicing. Intein insertion is biased towards the active site of the protein and is thought to cause inactivation of the host protein prior to splicing. Intein splicing is responsive to a …

Sexually Dimorphic Oxytocin Receptor-Expressing Neurons In The Anteroventral Periventricular Nucleus Regulates Maternal Behavior, Kaustubh Sharma

LSU Doctoral Dissertations

The neurohypophysial hormone oxytocin is involved in the regulation of social behaviors, including social recognition, pair bonding, and sex-specific parental behaviors in a variety of species. Oxytocin triggers these social behaviors by binding to oxytocin receptors (OXTR) in various parts of the brain. Oxytocin-induced sex-typical behavior, therefore, suggests a sexual dimorphic distribution of OXTR in the brain. In recent years, the oxytocin system in the brain received tremendous attention as a potential pharmacological target for treatment of many psychiatric disorders, such as anxiety, autism spectrum disorders, and even sex-specific psychiatric disorder like postpartum depression (PPD). An important problem and a …

On The Expanding Roles Of Trna Fragments In Modulating Cell Behavior, Rogan Magee, Isidore Rigoutsos

Computational Medicine Center Faculty Papers

The fragments that derive from transfer RNAs (tRNAs) are an emerging category of regulatory RNAs. Known as tRFs, these fragments were reported for the first time only a decade ago, making them a relatively recent addition to the ever-expanding pantheon of non-coding RNAs. tRFs are short, 16-35 nucleotides (nts) in length, and produced through cleavage of mature and precursor tRNAs at various positions. Both cleavage positions and relative tRF abundance depend strongly on context, including the tissue type, tissue state, and disease, as well as the sex, population of origin, and race/ethnicity of an individual. These dependencies increase the urgency …

Quantification Of Lactoyl-Coa (Lactyl-Coa) By Liquid Chromatography Mass Spectrometry In Mammalian Cells And Tissues., Erika L Varner, Sophie Trefely, David Bartee, Eliana Von Krusenstiern, Luke Izzo, Carmen Bekeova, Roddy S O'Connor, Erin L Seifert, Kathryn E Wellen, Jordan L Meier, Nathaniel W Snyder

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Lysine lactoylation is a recently described protein post-translational modification (PTM). However, the biochemical pathways responsible for this acylation remain unclear. Two metabolite-dependent mechanisms have been proposed: enzymatic histone lysine lactoylation derived from lactoyl-coenzyme A (lactoyl-CoA, also termed lactyl-CoA), and non-enzymatic lysine lactoylation resulting from acyl-transfer via lactoyl-glutathione. While the former has precedent in the form of enzyme-catalysed lysine acylation, the lactoyl-CoA metabolite has not been previously quantified in mammalian systems. Here, we use liquid chromatography-high-resolution mass spectrometry (LC-HRMS) together with a synthetic standard to detect and validate the presence of lactoyl-CoA in cell and tissue samples. Conducting a retrospective analysis …

Regulation Of Microrna-497-Targeting Akt2 Influences Tumor Growth And Chemoresistance To Cisplatin In Lung Cancer., Lin Wang, Xiang-Bo Ji, Li-Hong Wang, Jian-Ge Qiu, Feng-Mei Zhou, Wen-Jing Liu, Di-Di Wan, Marie Chai-Mi Lin, Ling-Zhi Liu, Jian-Ying Zhang, Bing-Hua Jiang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: MicroRNA-497 (miR-497) has been implicated in several cancers. Increasing studies demonstrate the role of AKT2 in cancers as an oncogene which is closely associated with tumor aggressiveness by enhancing cancer cell survival, migration and invasion However, miR-497/AKT2 axis in non-small cell lung cancer (NSCLC) remains unclear.

Methods: Quantitative real-time PCR (qRT-PCR) was used to quantify the expression of miR-497 and its target gene. The function of miR-497 in lung cancer was investigated through in vitro and in vivo assays (cell proliferation assay, cell migration assay, colony formation assay, flow cytometry assay, immunoblotting and tumorigenesis assay). Luciferase reporter assay was …

Cd4 Deficiency Causes Poliomyelitis And Axonal Blebbing In Murine Coronavirus-Induced Neuroinflammation., Debanjana Chakravarty, Fareeha Saadi, Soumya Kundu, Abhishek Bose, Reas Khan, Kimberly Dine, Lawrence C Kenyon, Kenneth S Shindler, Jayasri Das Sarma

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Mouse hepatitis virus (MHV) is a murine betacoronavirus (m-CoV) that causes a wide range of diseases in mice and rats, including hepatitis, enteritis, respiratory diseases, and encephalomyelitis in the central nervous system (CNS). MHV infection in mice provides an efficient cause-effect experimental model to understand the mechanisms of direct virus-induced neural-cell damage leading to demyelination and axonal loss, which are pathological features of multiple sclerosis (MS), the most common disabling neurological disease in young adults. Infiltration of T lymphocytes, activation of microglia, and their interplay are the primary pathophysiological events leading to disruption of the myelin sheath in MS. However, …

The Current Neuroscientific Understanding Of Alzheimer's Disease, Rachel A. Brandes

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Alzheimer’s disease is a degenerative neurological illness characterized by the deterioration of brain regions implicated in memory and cognitive function. While researchers have yet to find a cure or effective treatment, they have gained a better understanding of its pathology and development. Through years of neuroscience research, scientists have discovered much of what happens in the brain during Alzheimer’s disease onset and how this causes its symptoms; many hypotheses regarding this aspect of the illness involve temporal lobe atrophy, neurofibrillary tangles, and amyloid plaques. Although Alzheimer’s disease affects millions of people every day, it seems that most are unaware of …

Effects Of Alternative Chemotherapeutic Agents On Thyroid Cancer Cell Line Ml-1, Husref Rizvanovic

MSU Graduate Theses

Though differentiated thyroid carcinomas have decent prognosis when detected early, radioactive iodine (RAI) resistant and advanced thyroid cancers are still difficult to treat with existing therapies. Better therapeutic agents are needed. Studies have shown that aggressive thyroid cancers (ML-1) express the extracellular matrix protein, matrix metalloproteinase (MMP-2). MMP-2 has been linked to metastasis and aggressiveness of several cancers and has been shown to play a crucial role in tumor invasion. Chlorotoxin is a selective MMP-2 receptor agonist, and Saporin is a well-known ribosome-inactivating protein used for anti-cancer treatment; however, these two agents have never been studied when conjugated together. I …

A Closer Look At Muscle Breakdown: An Overview Of The Causes, Complications, And Diagnostics Of Rhabdomyolysis, Jamie Holchin

Senior Honors Theses

Rhabdomyolysis is the rapid breakdown of myocytes in skeletal muscle. This condition can be triggered by a variety of things including crush injury, drugs, prolonged exercise, and venom. Although the causes can vary, the general pathophysiology of rhabdomyolysis is similar. Increased intracellular calcium ion levels instigate the breakdown of cellular and certain organelle membranes of muscle cells. Reactive oxygen species form, ATP is depleted, and the sarcoplasmic reticulum, which regulates muscle contraction, is also damaged. Necrosis ensues, leading to toxic intracellular components spreading throughout the body. Rhabdomyolysis can then lead to several complications including acute renal injury and heart arrhythmias, …

The Effect Of Hypoxia On Brain Cell Proliferation In Weakly Electric Fish, Petrocephalus Degeni, Kaitlin Klovdahl

Senior Theses and Projects

Oxygen levels tend to remain at a steady state concentration in the Earth’s atmosphere, yet in some bodies of water, they can fluctuate and decrease drastically. Many organisms that inhabit the swamps, lakes, streams, and parts of the ocean where this occurs have evolved adaptations to manage this environmental uncertainty and continue normal oxygen consumption. The Lwamunda swamp in Uganda is chronically hypoxic, yet it is home to many species, including the electric fish Petrocephalus degeni. P. degeni are unusual by nature of their immense brain, and the Lwamunda swamp appears ill-suited for maintaining this large, metabolically active organ. To …

Abrogation Of Esophageal Carcinoma Development In Mir-31 Knockout Rats., Louise Y Fong, Cristian Taccioli, Alexey Palamarchuk, Guidantonio Malagoli Tagliazucchi, Ruiyan Jing, Karl J Smalley, Sili Fan, Joseph Altemus, Oliver Fiehn, Kay Huebner, John L Farber, Carlo M Croce

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

MicroRNA-31 (miR-31) is overexpressed in esophageal squamous cell carcinoma (ESCC), a deadly disease associated with dietary Zn deficiency and inflammation. In a Zn deficiency-promoted rat ESCC model with miR-31 up-regulation, cancer-associated inflammation, and a high ESCC burden following N-nitrosomethylbenzylamine (NMBA) exposure, systemic antimiR-31 delivery reduced ESCC incidence from 85 to 45% (P = 0.038) and miR-31 gene knockout abrogated development of ESCC (P = 1 × 10-6). Transcriptomics, genome sequencing, and metabolomics analyses in these Zn-deficient rats revealed the molecular basis of ESCC abrogation by miR-31 knockout. Our identification of EGLN3, a known negative regulator of nuclear …

Single-Molecule Analysis Of Subtelomeres And Telomeres In Alternative Lengthening Of Telomeres (Alt) Cells, Heba Z. Abid, Jennifer Mccaffrey, Kaitlin Raseley, Eleanor Young, Katy Lassahn, Dharma Varapula, Harold Riethman, Ming Xiao

Medical Diagnostics & Translational Sciences Faculty Publications

BACKGROUND: Telomeric DNA is typically comprised of G-rich tandem repeat motifs and maintained by telomerase (Greider CW, Blackburn EH; Cell 51:887-898; 1987). In eukaryotes lacking telomerase, a variety of DNA repair and DNA recombination based pathways for telomere maintenance have evolved in organisms normally dependent upon telomerase for telomere elongation (Webb CJ, Wu Y, Zakian VA; Cold Spring Harb Perspect Biol 5:a012666; 2013); collectively called Alternative Lengthening of Telomeres (ALT) pathways. By measuring (TTAGGG) n tract lengths from the same large DNA molecules that were optically mapped, we simultaneously analyzed telomere length dynamics and subtelomere-linked structural changes at a large …

Hsp90 Inhibitors For Ipf/Covid-19, Ruben Manuel Luciano Colunga Biancatelli, Pavel A. Solopov, John Catravas

Bioelectrics Publications

Heat shock protein 90 (HSP90) is an important chaperone that assists the late stage folding of several proteins involved in cell survival in response to environmental stressors. The inhibition of HSP90 is followed by a complex modulation of the proteome and the kinome, that has proved beneficial in cancer and various neurodegenerative diseases. Additionally, accumulating literature suggests that HSP90 may be a key target during the development of pulmonary fibrosis and that its inhibition could serve as a new and exciting therapeutic approach. We have summarized the current evidence about HSP90’s role in Idiopathic Pulmonary Fibrosis (IPF), the results from …