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2024

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Articles 31 - 60 of 223

Full-Text Articles in Cell Biology

Dysfunction Of Polyamine Metabolism In Down Syndrome Related To Cellular Senescence And Β-Amyloid Production, Andres D. Sola Nov 2024

Dysfunction Of Polyamine Metabolism In Down Syndrome Related To Cellular Senescence And Β-Amyloid Production, Andres D. Sola

Electronic Theses and Dissertations

Polyamines (PA) are ubiquitous in cells and highly involved in several important cellular functions and thus the dysregulation of their biosynthetic pathway is potentially associated with the progression of age-related diseases like Alzheimer’s’ disease (AD). Though there is research describing how PA content changes in organisms as they age or in those experiencing rapid aging from increased rates of senescence, as in Down syndrome (DS), it is not clear how this connection occurs and whether modulating this pathway may reveal downstream effects on related disease progression. This study examines how the modulation of the PA biosynthetic pathway by inhibition of …


Phagolysosomes Break Down The Membrane Of A Non-Apoptotic Corpse Independent Of Macroautophagy, Shruti Kolli, Cassidy J. Kline, Kimya M. Rad, Ann M. Wehman Nov 2024

Phagolysosomes Break Down The Membrane Of A Non-Apoptotic Corpse Independent Of Macroautophagy, Shruti Kolli, Cassidy J. Kline, Kimya M. Rad, Ann M. Wehman

Biological Sciences: Faculty Scholarship

Cell corpses must be cleared in an efficient manner to maintain tissue homeostasis and regulate immune responses. Ubiquitin-like Atg8/LC3 family proteins promote the degradation of membranes and internal cargo during both macroautophagy and corpse clearance, raising the question how macroautophagy contributes to corpse clearance. Studying the clearance of non-apoptotic dying polar bodies in Caenorhabditis elegans embryos, we show that the LC3 ortholog LGG-2 is enriched inside the polar body phagolysosome independent of autophagosome formation. We demonstrate that ATG-16.1 and ATG-16.2, which promote membrane association of lipidated Atg8/LC3 proteins, redundantly promote polar body membrane breakdown in phagolysosomes independent of their role …


Mechanisms Of Extracellular Vesicle Uptake And Implications For The Design Of Cancer Therapeutics, Stephanie R Jackson Cullison, Joseph P Flemming, Kubra Karagoz, Peter J Wermuth, Mỹ G Mahoney Nov 2024

Mechanisms Of Extracellular Vesicle Uptake And Implications For The Design Of Cancer Therapeutics, Stephanie R Jackson Cullison, Joseph P Flemming, Kubra Karagoz, Peter J Wermuth, Mỹ G Mahoney

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The translation of pre-clinical anti-cancer therapies to regulatory approval has been promising, but slower than hoped. While innovative and effective treatments continue to achieve or seek approval, setbacks are often attributed to a lack of efficacy, failure to achieve clinical endpoints, and dose-limiting toxicities. Successful efforts have been characterized by the development of therapeutics designed to specifically deliver optimal and effective dosing to tumour cells while minimizing off-target toxicity. Much effort has been devoted to the rational design and application of synthetic nanoparticles to serve as targeted therapeutic delivery vehicles. Several challenges to the successful application of this modality as …


Srebp Versus Nrf1 Behavior Based On Cholesterol Sensing In Niemann-Pick Type C Using A Cos-7 Model, Christine Tran, Jacob Mcintyre, Felicity Sterling Phd Nov 2024

Srebp Versus Nrf1 Behavior Based On Cholesterol Sensing In Niemann-Pick Type C Using A Cos-7 Model, Christine Tran, Jacob Mcintyre, Felicity Sterling Phd

Science University Research Symposium (SURS)

Niemann-Pick disease type C (NPC) is a rare genetic disorder where cholesterol and lipid transport are blocked leading to accumulation in the lysosomes (National Organization of Rare Diseases (NORD), 2024; Boston Children’s Hospital). This accumulation can lead to neurological issues, such as developmental delay, ataxia, seizures, and early onset of dementia (Patterson, 2000). To study this disease more in depth, scientists have identified a drug called U18666A that induces NPC in the cells it is administered to (Lu, et al., 2015) which allows for the study of other structures and biomolecules in the sterol sensing and transport pathways.

Cholesterol has …


Advancing Crispr-Based Solutions For Covid-19 Diagnosis And Therapeutics, Roaa Hadi, Abhishek Poddar, Shivakuma Sonnaila, Venkata Suryanarayana Murthy Bhavaraju, Shilpi Agrawal Nov 2024

Advancing Crispr-Based Solutions For Covid-19 Diagnosis And Therapeutics, Roaa Hadi, Abhishek Poddar, Shivakuma Sonnaila, Venkata Suryanarayana Murthy Bhavaraju, Shilpi Agrawal

Chemistry & Biochemistry Faculty Publications and Presentations

Since the onset of the COVID-19 pandemic, a variety of diagnostic approaches, including RT-qPCR, RAPID, and LFA, have been adopted, with RT-qPCR emerging as the gold standard. However, a significant challenge in COVID-19 diagnostics is the wide range of symptoms presented by patients, necessitating early and accurate diagnosis for effective management. Although RT-qPCR is a precise molecular technique, it is not immune to false-negative results. In contrast, CRISPR-based detection methods for SARS-CoV-2 offer several advantages: they are cost-effective, time-efficient, highly sensitive, and specific, and they do not require sophisticated instruments. These methods also show promise for scalability, enabling diagnostic tests. …


The Role Of Siamese In G2 Checkpoint Regulation In Arabidopsis Thaliana, Martha A. Schwall Oct 2024

The Role Of Siamese In G2 Checkpoint Regulation In Arabidopsis Thaliana, Martha A. Schwall

LSU Doctoral Dissertations

Cyclin-cyclin dependent kinase (Cyclin-CDK) pairs regulate progression through the checkpoints of the cell cycle. They bind with some specificity and must be bound to for their regulative properties to be active. The presence of cyclin-CDKs is conserved throughout eukaryotes, while differences in specifics exist between yeast, animals, and plants. In Arabidopsis, SIAMESE (SIM) is a CDK inhibitor that restricts progression through mitosis. Overexpression of SIM is required for endoreplication in Arabidopsis trichomes, and overexpression of SIM results in increased endoreplication in leaf epidermal cells. SIM is expressed at high levels in the root elongation zone, where it plays a …


Selective Pericyte Recruitment To Ec-Lined Tubes, Vessel Assembly Enhancement Through Pericyte Timp-3 Induction, And Pericyte Tbx2 In Capillary Formation And Maturation, Ksenia Marilyn Yrigoin Kaluguina Oct 2024

Selective Pericyte Recruitment To Ec-Lined Tubes, Vessel Assembly Enhancement Through Pericyte Timp-3 Induction, And Pericyte Tbx2 In Capillary Formation And Maturation, Ksenia Marilyn Yrigoin Kaluguina

USF Tampa Graduate Theses and Dissertations

Capillaries, the smallest blood vascular networks, are formed by narrow and elongated endothelial cell (EC)-lined tubes with associated pericytes anchored to the abluminal tube surface. Our laboratory demonstrated that dynamic interactions between ECs and pericytes during capillary tube network assembly are required for basement membrane matrix deposition and maturation. We have also shown that key EC-derived factors promote pericyte recruitment, proliferation, and pericyte-induced basement membrane formation during capillary assembly. In the first section, we aim to identify if vascular smooth muscle cells (VSMCs) respond to the same factors and have the same invasive ability as pericytes since they are both …


Ferroptotic Cardiomyocytes Regulate Angiogenesis In The Regenerative Mouse Heart After Myocardial Infarction Through Direct And Indirect Mechanisms, Rebecca Ashley Stairley Oct 2024

Ferroptotic Cardiomyocytes Regulate Angiogenesis In The Regenerative Mouse Heart After Myocardial Infarction Through Direct And Indirect Mechanisms, Rebecca Ashley Stairley

MUSC Theses and Dissertations

Cardiovascular diseases (CVDs) are the leading cause of death in the United States, and heart attack occurs every 40 seconds in the US. A myocardial infarction (MI), or heart attack, results in ischemic injury and cardiomyocyte (CM) death. Mature mammalian CM renewal in the heart is insufficient to repopulate the lost tissue. However, the neonatal mouse heart retains its regenerative capacity through the first week of life, providing a valuable model to identifying regenerative factors.

Recent work by our lab revealed that the main mechanism of CM death in the heart post-MI is ferroptosis. In this study, we investigate the …


Effects Of Cadherin Mediated Contact Normalization On Oncogenic Src Kinase Mediated Gene Expression And Protein Phosphorylation, Rachel E Nicoletto, Cayla J Holdcraft, Ariel C Yin, Edward P Retzbach, Stephanie A Sheehan, Amanda A Greenspan, Christopher M Laugier, Jason Trama, Caifeng Zhao, Haiyan Zheng, Gary S Goldberg Oct 2024

Effects Of Cadherin Mediated Contact Normalization On Oncogenic Src Kinase Mediated Gene Expression And Protein Phosphorylation, Rachel E Nicoletto, Cayla J Holdcraft, Ariel C Yin, Edward P Retzbach, Stephanie A Sheehan, Amanda A Greenspan, Christopher M Laugier, Jason Trama, Caifeng Zhao, Haiyan Zheng, Gary S Goldberg

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Nontransformed cells form heterotypic cadherin junctions with adjacent transformed cells to inhibit tumor cell growth and motility. Transformed cells must override this form of growth control, called "contact normalization", to invade and metastasize during cancer progression. Heterocellular cadherin junctions between transformed and nontransformed cells are needed for this process. However, specific mechanisms downstream of cadherin signaling have not been clearly elucidated. Here, we utilized a β-catenin reporter construct to determine if contact normalization affects Wnt signaling in transformed cells. β-catenin driven GFP expression in Src transformed mouse embryonic cells was decreased when cultured with cadherin competent nontransformed cells compared to …


Hepatic Targets To Control Blood Glucose And Potentially Aid In The Treatment Of Diabetes, Rena A. Velissarios Oct 2024

Hepatic Targets To Control Blood Glucose And Potentially Aid In The Treatment Of Diabetes, Rena A. Velissarios

PANDION: The Osprey Journal of Research and Ideas

Maintaining glucose homeostasis is extremely important to remain in good health and prevent disease. This homeostasis is achieved via the regulation of hepatic metabolic pathways like gluconeogenesis and glycogenesis by insulin, which is expressed during high blood glucose. Insulin is responsible for facilitating the uptake of glucose into other tissues from the blood, as well as signaling whether to stimulate or slow glucose metabolism in the liver. Hyperglycemia is one of the main effects of diabetes, a disease characterized by the body’s inability to produce or respond to insulin. Without insulin, hepatic glucose output continues and blood glucose accumulates, causing …


Denaturation Station: The Effect Of Guanidinium Chloride On Yeast Flocculation, Taylor Pulley, Jade Riddle, Angelina Scotece Oct 2024

Denaturation Station: The Effect Of Guanidinium Chloride On Yeast Flocculation, Taylor Pulley, Jade Riddle, Angelina Scotece

Fall Showcase for Research and Creative Inquiry

Flocculation is a phenomenon found in yeast such as Saccharomyces cerevisiae in which cells aggregate in response to stressful environmental conditions. This occurs as the result of the interaction of flocculin proteins on the plasma membrane with mannose residues on the surface of other yeast cells which is often exploited in the brewing process to avoid expensive filtration steps. Guanidine is a chaotropic agent which reduces the stability of proteins by weakening the hydrophobic effect. Since it is believed that flocculation is dependent on protein-mannose binding interactions, if the structure of the flocculin proteins is altered by guanidine, their functionality …


Conditional Deletion Of Ceacam1 In Hepatic Stellate Cells Causes Their Activation, Harrison T. Muturi, Hilda E. Ghadieh, Suman Asalla, Sumona G. Lester, Getachew D. Belew, Sobia Zaidi, Raziyeh Abdolahipour, Abhishek P. Shrestha, Agnes O. Portuphy, Hannah L. Stankus, Raghd Abu Helal, Stefaan Verhulst, Sergio Duarte, Ali Zarrinpar, Leo A. Van Grunsven, Scott L. Friedman, Robert F. Schwabe, Terry D. Hinds, Jr., Sivarajan Kumarasamy, Sonia M. Najjar Oct 2024

Conditional Deletion Of Ceacam1 In Hepatic Stellate Cells Causes Their Activation, Harrison T. Muturi, Hilda E. Ghadieh, Suman Asalla, Sumona G. Lester, Getachew D. Belew, Sobia Zaidi, Raziyeh Abdolahipour, Abhishek P. Shrestha, Agnes O. Portuphy, Hannah L. Stankus, Raghd Abu Helal, Stefaan Verhulst, Sergio Duarte, Ali Zarrinpar, Leo A. Van Grunsven, Scott L. Friedman, Robert F. Schwabe, Terry D. Hinds, Jr., Sivarajan Kumarasamy, Sonia M. Najjar

Markey Cancer Center Faculty Publications

Objectives: Hepatic CEACAM1 expression declines with advanced hepatic fibrosis stage in patients with metabolic dysfunction-associated steatohepatitis (MASH). Global and hepatocyte-specific deletions of Ceacam1 impair insulin clearance to cause hepatic insulin resistance and steatosis. They also cause hepatic inflammation and fibrosis, a condition characterized by excessive collagen production from activated hepatic stellate cells (HSCs). Given the positive effect of PPARg on CEACAM1 transcription and on HSCs quiescence, the current studies investigated whether CEACAM1 loss from HSCs causes their activation.

Methods: We examined whether lentiviral shRNA-mediated CEACAM1 donwregulation (KD-LX2) activates cultured human LX2 stellate cells. We also generated LratCre þ Cc1fl/fl mutants …


Development And Quantification Of An Attachment Assay For Epidermal Cells To Varying Extracellular Matrix Dilutions, Julian Vargas '26, Colleen L. Doçi Oct 2024

Development And Quantification Of An Attachment Assay For Epidermal Cells To Varying Extracellular Matrix Dilutions, Julian Vargas '26, Colleen L. Doçi

Annual Student Research Poster Session

The concept of cellular attachment is cells interacting with the extracellular matrices surrounding it. Extracellular matrices are made of various components, and it has been shown that the interactions differ between different classes of extracellular matrices. The basement membrane plays a critical role in the structure and function of the epidermis, the outermost layer of the skin. It is composed of key extracellular matrix components, which are crucial for structural stability of the skin and for maintaining the integrity of the epidermis. Through components like collagen, laminin, and proteoglycans, the BM facilitates communication between the epidermal cells and the connective …


The Effects Of Cannabinoids On Migration-Related Protein Expression In Ewing’S Sarcoma, Allison Lashall Oct 2024

The Effects Of Cannabinoids On Migration-Related Protein Expression In Ewing’S Sarcoma, Allison Lashall

Theses

Ewing’s sarcoma is an aggressive pediatric bone cancer that has low five-year survival rates, primarily due to metastatic disease and resistance of recurring tumors to traditional treatment options; therefore, novel treatment options are needed. The compound cannabidiol (CBD) has been shown to reduce cell viability, migration, and invasion in several tumor types, though the cellular mechanism of action is not well understood. Our lab has demonstrated the ability of CBD to reduce viability, migration, and invasion of Ewing’s sarcoma cells in vitro and is investigating differential protein and cytokine expression of known mediators of migration, such as intercellular adhesion molecule …


Identification Of Inflammatory Factors Contributing To Foaming In Atherosclerosis, Kavya Podila Oct 2024

Identification Of Inflammatory Factors Contributing To Foaming In Atherosclerosis, Kavya Podila

Holster Scholar Projects

According to the National Institute of Health (NIH), atherosclerosis is attributed to the majority of cardiovascular disease (CVD) cases and is the leading cause of mortality in the US and worldwide. Despite significant medical advancements, the risk of cardiovascular events remains, warranting further mechanistic and pathogenic investigation. Advances in high-resolution omics profiling and the development of novel data-analytic bioinformatic tools previously enabled the novel discovery of two distinct programs in foaming, the central process in atherogenesis. The programs are pathogenic and homeostatic foaming, with the pathogenic foaming program being positively associated with disease. Using single-cell RNA sequencing (scRNA-seq) data from …


Effect Of Heat Stress On The Expression Of Circulating Cyto(Chemo)Kine And Inflammatory Markers In Broiler Chickens Selected For High- Or Low-Water Efficiency, Elizabeth S. Greene, Travis Tabler, Walter G. Bottje, Sara Orlowski, Sami Dridi Oct 2024

Effect Of Heat Stress On The Expression Of Circulating Cyto(Chemo)Kine And Inflammatory Markers In Broiler Chickens Selected For High- Or Low-Water Efficiency, Elizabeth S. Greene, Travis Tabler, Walter G. Bottje, Sara Orlowski, Sami Dridi

Poultry Science Faculty Publications and Presentations

Background:

Water scarcity is a current, significant global concern that will only increase under the pressure of climate change. Improving water efficiency of poultry is a new and promising area to help temper agriculture's future impact on fresh water availability. Here, we explored the effects of acute heat stress (HS) on circulating stress and inflammatory markers in 2 lines of broilers divergently selected for water efficiency. Methods:

Male chicks from low (LWE) and high water efficient (HWE) lines were raised in 12 environmental chambers (2 pens/chamber, 6 chambers/line, 20 birds/pen) under normal conditions until day 28. On day 29, birds …


Intercellular Mitochondrial Transfer Contributes To Microenvironmental Fate Redirection Of Mammary Cancer Cells, Julie Sofie Bjerring Oct 2024

Intercellular Mitochondrial Transfer Contributes To Microenvironmental Fate Redirection Of Mammary Cancer Cells, Julie Sofie Bjerring

Biomedical Sciences Theses & Dissertations

The dynamic cellular microenvironment, made up of resident cells and various macromolecules, differs markedly across tissues in the body. The multidirectional signals that cells receive from this microenvironment, along with the signaling they send back, heavily influence their physiology and behavior. Recent important findings have further validated this notion as the mammary microenvironment has been shown to suppress tumor progression by redirecting cancer cells to adopt a normal mammary epithelial progenitor fate in vivo. However, the mechanism(s) driving changes in metabolic reprogramming and cancer fate redirection is understudied. The work presented in this dissertation focuses on exploring the impact of …


Characterization Of Stealth Liposome-Based Nanoparticles Encapsulating Acat1/Soat1 Inhibitor F26: Potential Therapeutics For Niemann-Pick Type C And Other Neurodegenerative Diseases., Junghoon Lee Oct 2024

Characterization Of Stealth Liposome-Based Nanoparticles Encapsulating Acat1/Soat1 Inhibitor F26: Potential Therapeutics For Niemann-Pick Type C And Other Neurodegenerative Diseases., Junghoon Lee

Dartmouth College Ph.D Dissertations

Cholesterol dysregulation is implicated in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD) and Niemann-Pick type C disease (NPCD). This study focused on evaluating the potent ACAT1 inhibitor, F26, as a therapeutic strategy for NPCD. F26 demonstrated superior ACAT1 inhibition and efficacy compared to the previously studied inhibitor, F12511, both in vitro and in vivo. Notably, F26 exhibited enhanced pharmacokinetic properties, including prolonged duration of action and better brain retention, making it a more promising candidate for treating neurodegenerative diseases.

F26 was encapsulated in a liposome-based nanoparticle system, DSPE-PEG2000 with phosphatidylcholine (PC), for enhancing its …


Enhanced Bmp Signaling Via Alk2 In Osteoclasts Decreases Bone Density In Mice, Yolanda V. Gutierrez, Hiroyuki Yamaguchi, Yuji Mishina, Yoshihiro Komatsu Sep 2024

Enhanced Bmp Signaling Via Alk2 In Osteoclasts Decreases Bone Density In Mice, Yolanda V. Gutierrez, Hiroyuki Yamaguchi, Yuji Mishina, Yoshihiro Komatsu

Research Colloquium

Bone remodeling is a complex biological process that has been extensively studied. Bone Morphogenetic Proteins (BMPs) are recognized as one of the critical growth factors that coordinate bone remodeling. Previous studies have demonstrated that BMP signaling in osteoclasts has a positive effect on osteoclast function. However, little is known about how each BMP type I receptors control osteoclastogenesis. To investigate this question, we utilized the Cre-LoxP system to specifically activate BMP signaling through ALK2 in mice. We utilized Cathepsin K (Ctsk)-Cre driver to activate BMP signaling in osteoclasts in mice. Compared with aged- and gender-matched controls, gain-of-function of BMP mutant …


Keratin 17 Is A Prognostic And Predictive Biomarker In Pancreatic Ductal Adenocarcinoma, Lyanne Delgado-Coka, Lucia Roa-Peña, Sruthi Babu, Michael Horowitz, Emanuel Petricoin, Lynn Matrisian, Edik Blais, Natalia Marchenko, Felicia Allard, Ali Akalin, Wei Jiang, Md, Phd, Brent Larson, Andrew Hendifar, Vincent Picozzi, Minsig Choi, Kenneth Shroyer, Luisa Escobar-Hoyos Sep 2024

Keratin 17 Is A Prognostic And Predictive Biomarker In Pancreatic Ductal Adenocarcinoma, Lyanne Delgado-Coka, Lucia Roa-Peña, Sruthi Babu, Michael Horowitz, Emanuel Petricoin, Lynn Matrisian, Edik Blais, Natalia Marchenko, Felicia Allard, Ali Akalin, Wei Jiang, Md, Phd, Brent Larson, Andrew Hendifar, Vincent Picozzi, Minsig Choi, Kenneth Shroyer, Luisa Escobar-Hoyos

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

OBJECTIVES: To determine the role of keratin 17 (K17) as a predictive biomarker for response to chemotherapy by defining thresholds of K17 expression based on immunohistochemical tests that could be used to optimize therapeutic intervention for patients with pancreatic ductal adenocarcinoma (PDAC).

METHODS: We profiled K17 expression, a hallmark of the basal molecular subtype of PDAC, by immunohistochemistry in 2 cohorts of formalin-fixed, paraffin-embedded PDACs (n = 305). We determined a K17 threshold of expression to optimize prognostic stratification according to the lowest Akaike information criterion and explored the potential relationship between K17 and chemoresistance by multivariate predictive analyses.

RESULTS: …


Examination Of Oncogenic Effects Of Environmental Pollutants, Andrew Ackerman, Matthew Behling, Brock Earley, Janay Vacharasin Sep 2024

Examination Of Oncogenic Effects Of Environmental Pollutants, Andrew Ackerman, Matthew Behling, Brock Earley, Janay Vacharasin

Journal of the South Carolina Academy of Science

Chemical byproducts produced by surrounding industrial complexes have polluted the local estuaries of Georgetown, South Carolina for several decades1. Previous studies completed by the EPA and SCDNR showed that the estuaries contained carcinogenic pollutants released from the local manufacturing plants1. One of the mentioned pollutants was dioxins which are produced during the paper bleaching process2. Dioxins are highly toxic compounds that have various carcinogenic effects on the organisms that inhabit the area. These previous studies were conducted over thirty years ago. Therefore, a current study to determine if chemical byproducts are contaminating local estuaries …


Autophagy And Meiotic Fidelity In C. Elegans, Kaitlin E. Kosinski Sep 2024

Autophagy And Meiotic Fidelity In C. Elegans, Kaitlin E. Kosinski

Dissertations, Theses, and Capstone Projects

Autophagy is an evolutionarily conserved multi-step recycling process in which cellular material is enclosed in the double membrane-bound autophagosome, which fuses with the lysosome to degrade its contents. Autophagy is essential for development and cellular adaptation to environmental or intracellular stress and is an important regulator of germline stem cell homeostasis in the model nematode C. elegans. We sought to determine if autophagy is important for genome stability during meiosis and found that the core adult C. elegans autophagy genes bec-1, atg-7, unc-51, and atg-18 were all required for proper meiotic development of oocytes. Loss of these …


Novel Psychoplastogen Dm506 Reduces Cue-Induced Heroin-Seeking And Inhibits Tonic Gaba Currents In The Prelimbic Cortex, Kassandra Looschen, Shailesh N. Khatri, Malabika Maulik, Colin Salisbury, Alaina F. Carman, Katilyn Corriveau, Colton Smith, Dina Manetti, Maria Novella Romanelli, Hugo R. Arias, Cassandra D. Gipson, Swarup Mitra Sep 2024

Novel Psychoplastogen Dm506 Reduces Cue-Induced Heroin-Seeking And Inhibits Tonic Gaba Currents In The Prelimbic Cortex, Kassandra Looschen, Shailesh N. Khatri, Malabika Maulik, Colin Salisbury, Alaina F. Carman, Katilyn Corriveau, Colton Smith, Dina Manetti, Maria Novella Romanelli, Hugo R. Arias, Cassandra D. Gipson, Swarup Mitra

Markey Cancer Center Faculty Publications

Opioid use disorder is a major public health crisis that is manifested by persistent drug-seeking behavior and high relapse frequency. Most of the available treatments rely on targeting opioid receptors using small molecules that do not provide sustained symptom alleviation. Psychoplastogens are a novel class of non-opioid drugs that produce rapid and sustained effects on neuronal plasticity, intended to produce therapeutic benefits. Ibogalogs are synthetic derivatives of iboga alkaloids that lack hallucinogenic or adverse side effects. In the current study, we examine the therapeutic potential of DM506, a novel ibogalog lacking any cardiotoxic or hallucinogenic effects, in cue-induced seeking behavior …


Identifying The Roles Of Mir-17 In Ciliogenesis And Cell Cycle, Ashwaq Alanazi, Ayan K. Barui, Ashraf M. Mohieldin, Ankan Gupta, Ramani Ramachandran, Surya M. Nauli Aug 2024

Identifying The Roles Of Mir-17 In Ciliogenesis And Cell Cycle, Ashwaq Alanazi, Ayan K. Barui, Ashraf M. Mohieldin, Ankan Gupta, Ramani Ramachandran, Surya M. Nauli

Pharmacy Faculty Articles and Research

Emerging evidence suggests a significant contribution of primary cilia to cell division and proliferation. MicroRNAs, especially miR-17, contribute to cell cycle regulation and proliferation. Recent investigations have highlighted the dysregulated expression of miR-17 in various malignancies, underlining its potential role in cancer. However, the correlation between primary cilia and miR-17 has yet to be fully elucidated. The present study examines the presence of miR-17 in primary cilia. The miR-17 expression is studied in selected ciliary protein knockdown cells. Using in situ hybridization (ISH), we identified the subcellular localization of miR-17 in both cilium and cell body. We confirmed the importance …


Unraveling The Role Of Hid-1: Insights Into Sgii Regulation, Breanna L. Sellers Aug 2024

Unraveling The Role Of Hid-1: Insights Into Sgii Regulation, Breanna L. Sellers

Electronic Theses and Dissertations

The regulated secretory pathway is important for the secretion of hormones and neuropeptides from large dense core vesicles (LDCVs). Dysregulation of the biogenesis of LDCVs can result in metabolic and neurological diseases. Recent studies have suggested that the peripheral membrane protein HID-1 plays a role in the sorting and storage of granins which contribute to LDCV biogenesis. To further understand how HID-1 influences the regulation of granins, we investigated potential HID-1 interactors. We determined that while HID-1 is likely functioning in the same pathway as USP25, a deubiquitinating enzyme (DUB), the cause of reduced cellular SgII levels is likely not …


Cpsf6'S Nuclear Localization Signal Mediates Hiv-1 Intranuclear Events Following Nuclear Import, Nick Rohlfes Aug 2024

Cpsf6'S Nuclear Localization Signal Mediates Hiv-1 Intranuclear Events Following Nuclear Import, Nick Rohlfes

Dissertations

The early stages of the HIV-1 lifecycle include the trafficking of the viral capsid into the nucleus of infected cells. The viral capsid, which encloses the viral genome and accessory proteins required for reverse transcription (RT) and integration, traffics towards the nucleus and enters through the nuclear pore complex (NPC). This process is mediated through interactions between the virus and several host proteins, including cleavage and polyadenylation specificity factor 6 (CPSF6). CPSF6 is an early HIV-1 host factor which assists HIV-1 nuclear localization and post-entry integration targeting. CPSF6 contains a function nuclear localization signal (NLS), and as a result, is …


Cell-Based Medicinal Products: Progress And Perspectives, Lijian Hui, Xiang Yuan, Jingqi Wu Aug 2024

Cell-Based Medicinal Products: Progress And Perspectives, Lijian Hui, Xiang Yuan, Jingqi Wu

Bulletin of Chinese Academy of Sciences (Chinese Version)

Cell-based medicinal products are a breakthrough that has been proven to treat previously incurable diseases, making them a topic of global interest. This review delves into the current state and progress of cell therapy, highlighting the remarkable therapeutic effects of various types of cell-based medicinal products. We specifically explore the potential development of cell-based medicinal products in China, focusing on promoting clinical translation and commercialization. We propose necessary actions to achieve these goals, such as fostering cutting-edge basic research, innovative therapeutic approaches, scalable manufacturing processes, and policy changes.


Regulation Of Sterile Inflammatory Responses By Mitochondria-Associated Proteins, Meghana Venkatesan Aug 2024

Regulation Of Sterile Inflammatory Responses By Mitochondria-Associated Proteins, Meghana Venkatesan

Master's Theses

Inflammation is an important defense mechanism through which cells respond to pathogenic insults and damage/stress signals. Immune cells mediate extracellular inflammatory responses by synthesizing and releasing small proteins called cytokines, which play critical roles in modulating these responses. Specifically, key pro-inflammatory cytokines such as IL-1beta are released upon the assembly and activation of a multi-protein intracellular complex called the inflammasome, the most well-studied of which is the NLRP3 inflammasome. Several proteins have been identified as important regulators of cellular stress responses, including vacuole membrane protein 1 (VMP1). The present research shows that VMP1-depleted cells exhibit exacerbated cellular inflammation and are …


Design, Synthesis, And Evaluation Of Oleyl-Wrh Peptides For Sirna Delivery, Mrigank Shekhar Rai, Muhammad Imran Sajid, Jonathan Moreno, Keykavous Parang, Rakesh Kumar Tiwari Aug 2024

Design, Synthesis, And Evaluation Of Oleyl-Wrh Peptides For Sirna Delivery, Mrigank Shekhar Rai, Muhammad Imran Sajid, Jonathan Moreno, Keykavous Parang, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

Delivering nucleic acid therapeutics across cell membranes is a significant challenge. Cell-penetrating peptides (CPPs) containing arginine (R), tryptophan (W), and histidine (H) show promise for siRNA delivery. To improve siRNA delivery and silence a model STAT3 gene, we hypothesized that oleyl acylation to CPPs, specifically (WRH)n, would enhance STAT3 silencing efficiency in breast and ovarian cancer cells. Using Fmoc/tBu solid-phase peptide chemistry, we synthesized, purified, and characterized the oleyl-conjugated (WRH)n (n = 1–4) peptides. The peptide/siRNA complexes were non-cytotoxic at N/P 40 (~20 μM) against MDA-MB-231, MCF-7, SK-OV-3, and HEK-293 cells after 72 h incubation. All peptide/siRNA complexes showed serum …


A Comparison Of Diploid And Triploid Eastern Oysters For Aquaculture Production Under Extreme Temperatures And Salinities, Joshua H. Kim Aug 2024

A Comparison Of Diploid And Triploid Eastern Oysters For Aquaculture Production Under Extreme Temperatures And Salinities, Joshua H. Kim

LSU Master's Theses

Off-bottom aquaculture of Eastern oysters (Crassostrea virginica) is a nascent industry that is increasingly supported by the use of triploid oysters, which grow faster than diploids. Despite their growth advantage, elevated triploid mortality compared to diploids under high temperature, low salinity, or a combination of these conditions challenge consistent triploid production. Identifying the environmental thresholds at which differential triploid mortality occurs and predicting its economic impact are important to informing decision-making in oyster aquaculture. The goal of this thesis was to compare the biological and economic performance of diploid and triploid oysters under high temperature and low salinity conditions. …