Critical Role Of The Sulfiredoxin-Peroxiredoxin Iv Axis In Urethane-Induced Non-Small Cell Lung Cancer,
2023
University of Kentucky
Critical Role Of The Sulfiredoxin-Peroxiredoxin Iv Axis In Urethane-Induced Non-Small Cell Lung Cancer, Yanning Hao, Hong Jiang, Pratik Thapa, Na Ding, Aziza Alshahrani, Junichi Fujii, Michel B. Toledano, Qiou Wei
Markey Cancer Center Faculty Publications
Non-small cell lung cancer (NSCLC), the most common type of lung cancer, etiologically associates with tobacco smoking which mechanistically contributes to oxidative stress to facilitate the occurrence of mutations, oncogenic transformation and aberrantly activated signaling pathways. Our previous reports suggested an essential role of Sulfiredoxin (Srx) in promoting the development of lung cancer in humans, and was causally related to Peroxiredoxin IV (Prx4), the major downstream substrate and mediator of Srx-enhanced signaling. To further explore the role of the Srx-Prx4 axis in de novo lung tumorigenesis, we established Prx4−/− and Srx−/−/Prx4−/− mice in pure FVB/N background. Together with wild-type litter …
Production And Characterization Of Monoclonal Antibodies To Xenopus Proteins,
2023
University of Massachusetts Amherst
Production And Characterization Of Monoclonal Antibodies To Xenopus Proteins, Brett Horr, Ryan Kurtz, Ankit Pandey, Benjamin G. Hoffstrom, Elizabeth Schock, Carole Labonne, Dominique Alfandari
Markey Cancer Center Faculty Publications
Monoclonal antibodies are powerful and versatile tools that enable the study of proteins in diverse contexts. They are often utilized to assist with identification of subcellular localization and characterization of the function of target proteins of interest. However, because there can be considerable sequence diversity between orthologous proteins in Xenopus and mammals, antibodies produced against mouse or human proteins often do not recognize Xenopus counterparts. To address this issue, we refined existing mouse monoclonal antibody production protocols to generate antibodies against Xenopus proteins of interest. Here, we describe several approaches for the generation of useful mouse anti-Xenopus antibodies to multiple …
Low Molecular Weight Cyclin E Deregulates Dna Replication And Damage Repair To Promote Genomic Instability In Breast Cancer,
2023
The Texas Medical Center Library
Low Molecular Weight Cyclin E Deregulates Dna Replication And Damage Repair To Promote Genomic Instability In Breast Cancer, Mi Li
Dissertations and Theses (Open Access)
Low molecular weight cyclin E (LMW-E) are oncogenic forms of cyclin E that are post translationally generated by neutrophil elastase (NE) mediated cleavage of the 50 KDa full-length cyclin E1 (FL-cycE, encoded by CCNE1gene). The resultant N-terminus deleted (40 amino acids) form of LMW-E is detected in breast cancer cells and tumor tissues, but not in normal mammary epithelial cells or adjacent normal tissues. Unlike FL-cycE, LMW-E drives mammary epithelial cell transformation in human cells and spontaneous mammary tumor formation in transgenic mouse models, but the oncogenic mechanisms of LMW-E and its unique function(s) independent of FL-cycE are not …
A Brief Overview Of Triple A Syndrome,
2023
Nova Southeastern University
A Brief Overview Of Triple A Syndrome, Jamaal Khan
Mako: NSU Undergraduate Student Journal
Triple A Syndrome, also known as AAA Syndrome, is a rare autosomal recessive disorder caused by any mutation in the AAAS gene on chromosome 12q13, whose main function is to code for the WD-repeat family regulatory protein, ALADIN. It typically occurs as a group of diseases that are characterized by alacrima, Addison's disease, and achalasia. Alacrima can be defined by a decrease in the amount of tears produced while achalasia is nerve damage in the esophagus that can cause difficulty swallowing. Lastly, Addison's disease is the insufficient production of cortisol and aldosterone produced by the adrenal cortex. There is no …
Displaying And Delivering Viral Membrane Antigens Via
Ww Domain–Activated Extracellular Vesicles,
2023
Harvard T.H. Chan School of Public Health
Displaying And Delivering Viral Membrane Antigens Via Ww Domain–Activated Extracellular Vesicles, Sengjin Choi, Zhiping Yang, Qiyu Wang, Zhi Qiao, Maoyun Sun, Joshua Wiggins, Shi-Hua Xiang, Quan Lu
Nebraska Center for Virology: Faculty Publications
Membrane proteins expressed on the surface of enveloped viruses are conformational antigens readily recognized by B cells of the immune system. An effective vaccine would require the synthesis and delivery of these native conformational antigens in lipid membranes that preserve specific epitope structures. We have created an extracellular vesicle–based technology that allows viral membrane antigens to be selectively recruited onto the surface of WW domain–activated extracellular vesicles (WAEVs). Budding of WAEVs requires secretory carrier-associated membrane protein 3, which through its proline-proline-alanine-tyrosine motif interacts with WW domains to recruit fused viral membrane antigens onto WAEVs. Immunization with influenza and HIV viral …
Displaying And Delivering Viral Membrane Antigens Via
Ww Domain–Activated Extracellular Vesicles,
2023
Harvard T.H. Chan School of Public Health
Displaying And Delivering Viral Membrane Antigens Via Ww Domain–Activated Extracellular Vesicles, Sengjin Choi, Zhiping Yang, Qiyu Wang, Zhi Qiao, Maoyun Sun, Joshua Wiggins, Shi-Hua Xiang, Quan Lu
Nebraska Center for Virology: Faculty Publications
Membrane proteins expressed on the surface of enveloped viruses are conformational antigens readily recognized by B cells of the immune system. An effective vaccine would require the synthesis and delivery of these native conformational antigens in lipid membranes that preserve specific epitope structures. We have created an extracellular vesicle–based technology that allows viral membrane antigens to be selectively recruited onto the surface of WW domain–activated extracellular vesicles (WAEVs). Budding of WAEVs requires secretory carrier-associated membrane protein 3, which through its proline-proline-alanine-tyrosine motif interacts with WW domains to recruit fused viral membrane antigens onto WAEVs. Immunization with influenza and HIV viral …
Displaying And Delivering Viral Membrane Antigens Via
Ww Domain–Activated Extracellular Vesicles,
2023
Harvard T.H. Chan School of Public Health
Displaying And Delivering Viral Membrane Antigens Via Ww Domain–Activated Extracellular Vesicles, Sengjin Choi, Zhiping Yang, Qiyu Wang, Zhi Qiao, Maoyun Sun, Joshua Wiggins, Shi-Hua Xiang, Quan Lu
School of Veterinary and Biomedical Sciences: Faculty Publications
Membrane proteins expressed on the surface of enveloped viruses are conformational antigens readily recognized by B cells of the immune system. An effective vaccine would require the synthesis and delivery of these native conformational antigens in lipid membranes that preserve specific epitope structures. We have created an extracellular vesicle–based technology that allows viral membrane antigens to be selectively recruited onto the surface of WW domain–activated extracellular vesicles (WAEVs). Budding of WAEVs requires secretory carrier-associated membrane protein 3, which through its proline-proline-alanine-tyrosine motif interacts with WW domains to recruit fused viral membrane antigens onto WAEVs. Immunization with influenza and HIV viral …
Vaccines Against Group B Coxsackieviruses And Their Importance,
2023
University of Nebraska-Lincoln
Vaccines Against Group B Coxsackieviruses And Their Importance, Kiruthiga Mone, Ninaad Lasrado, Meghna Sur, Jay Reddy
School of Veterinary and Biomedical Sciences: Faculty Publications
The group B coxsackieviruses (CVBs) exist in six serotypes (CVB1 to CVB6). Disease associations have been reported for most serotypes, and multiple serotypes can cause similar diseases. For example, CVB1, CVB3, and CVB5 are generally implicated in the causation of myocarditis, whereas CVB1 and CVB4 could accelerate the development of type 1 diabetes (T1D). Yet, no vaccines against these viruses are currently available. In this review, we have analyzed the attributes of experimentally tested vaccines and discussed their merits and demerits or limitations, as well as their impact in preventing infections, most importantly myocarditis and T1D.
Personalized Matched Targeted Therapy In Advanced Pancreatic
Cancer: A Pilot Cohort Analysis,
2023
University of California San Diego Moores Cancer Center
Personalized Matched Targeted Therapy In Advanced Pancreatic Cancer: A Pilot Cohort Analysis, Justin Shaya, Shumei Kato, Jacob J. Adashek, Hitendra Patel, Paul T. Fanta, Gregory P. Botta, Jason K. Sicklick, Razelle Kurzrock
School of Veterinary and Biomedical Sciences: Faculty Publications
Despite progress, 2-year pancreatic cancer survival remains dismal. We evaluated a biomarker-driven, combination/N-of-one strategy in 18 patients (advanced/metastatic pancreatic cancer) (from Molecular Tumor Board). Targeted agents administered/ patient = 2.5 (median) (range, 1–4); first-line therapy (N = 5); second line, (N = 13). Comparing patients (high versus low degrees of matching) (matching score ≥50% versus <50%; reflecting number of alterations matched to targeted agents divided by number of pathogenic alterations), survival was significantly longer (hazard ratio [HR] 0.24 (95% confidence interval [CI], 0.078–0.76, P = 0.016); clinical benefit rates (CBR) (stable disease ≥6 months/partial/complete response) trended higher (45.5 vs 0.0%, P = 0.10); progression-free survival, HR, 95% CI, 0.36 (0.12–1.10) (p = 0.075). First versus ≥2nd-line therapy had higher CBRs (80.0 vs 7.7%, P = …50%;>
Methylene Blue Inhibits Cromakalim-Activated K+ Currents In Follicle-Enclosed Oocytes,
2023
Bogomoletz Institute of Physiology
Methylene Blue Inhibits Cromakalim-Activated K+ Currents In Follicle-Enclosed Oocytes, Dmytro Isaev, Keun-Hang Susan Yang, Georg Petroianu, Dietrich Ernst Lorke, Murat Oz
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
The effects of methylene blue (MB) on cromakalim-induced K+ currents were investigated in follicle-enclosed Xenopus oocytes. In concentrations ranging from 3–300 μM, MB inhibited K+ currents (IC50: 22.4 μM) activated by cromakalim, which activates KATP channels. MB inhibited cromakalim-activated K+ currents in a noncompetitive and voltage-independent manner. The respective EC50 and slope values for cromakalim-activation of K+ currents were 194 ± 21 µM and 0.91 for controls, and 206 ± 24 µM and 0.87 in the presence of 30 μM MB. The inhibition of cromakalim-induced K+ currents by MB was not …
Investigating The Absence Of A Dietary Response At The Neuromuscular Junction In Larval Drosophila Melanogaster,
2023
St. Mary's University
Investigating The Absence Of A Dietary Response At The Neuromuscular Junction In Larval Drosophila Melanogaster, Suzanna Louise Marbach
Honors Program Theses and Research Projects
Research in Drosophila melanogaster (D. melanogaster) has been growing in order to identify the fundamental processes of human disorders of the central nervous system such as Alzheimer’s disease, diabetes, and other neurological disorders at a molecular level. Altered insulin signaling itself has been linked to widespread nervous system dysfunction including cognitive dysfunction, neuropathies, and susceptibility to neurodegenerative disease. However, knowledge of the cellular mechanisms underlying the effects of insulin on nervous system function is still incomplete. The focus behind investigating the insulin signaling pathway is derived from our observations in the adult D. melanogaster neuromuscular junction (NMJ) to changes in …
Comparison Of In-Vitro 3d Human Embryoids With Current Models For Gastrulation,
2023
Washington University in St. Louis
Comparison Of In-Vitro 3d Human Embryoids With Current Models For Gastrulation, Jin Park
McKelvey School of Engineering Graduate Student Theses & Dissertations
Gastrulation is an early morphogenetic process that is conserved across most metazoans and lays out the future body plan through the formation and shaping of the three germ layers: endoderm, mesoderm, and ectoderm. Despite its importance, not much is known about the events surrounding human gastrulation that occurs in utero due to ethical and technical limitations on studying human embryos. Therefore, many researchers have devised protocols for creating in vitro models of gastrulation using embryonic stem cells. Initially starting with mouse embryonic stem cells, the field of in vitro embryo models has advanced rapidly, with protocols using human embryonic stem …
Quantification Of Nuclear Dynamics During Epithelial Remodeling,
2023
University of Denver
Quantification Of Nuclear Dynamics During Epithelial Remodeling, Noah De Leeuw
Electronic Theses and Dissertations
The morphogenesis of developing tissues is contingent on an extensive array of rearrangements in cellular shape, position and identity at large and small scales. One commonly used process to reshape tissues is the cell intercalation-driven elongation of a tissue in a common axis, in which rows of epithelial cells undergo oriented intercalation in a directional fashion. In most models of intercalation, cells are treated as homogeneous objects directed in their shape changes by cortical forces localized along cell-cell interfaces or tricellular junctions. However, less attention has been paid to how inhomogeneities in mechanical resistance of their own internal structures affects …
Dna Damage Response Activates The Electron Transport Chain And Oxidative Metabolism By Two Parallel Mechanisms,
2023
Saint John's University, Jamaica New York
Dna Damage Response Activates The Electron Transport Chain And Oxidative Metabolism By Two Parallel Mechanisms, Shreya Nagar
Theses and Dissertations
The DNA damage response (DDR) is an evolutionarily conserved process essential for cell survival. Major part of DDR is coordinated by DNA damage checkpoint (DDC). In addition to DDC, eukaryotic cells also have DNA replication checkpoint (DRC) that is distinct from the DDC and specifically signals slowly progressing or arrested replication forks. DDR involves stalling or arrest of the cell cycle, initiation of DNA repair, and altered regulation of transcription, translation, and the ubiquitin-proteasome system. DDR also triggers transcription shut-off of histone genes. One of the key outcomes of DDC/DRC activation is the increased synthesis of the deoxyribonucleoside triphosphates (dNTPs), …
Molecular Regulation Of The Salicylic Acid Hormone Pathway In Plants Under Changing Environmental Conditions,
2023
Wilfrid Laurier University
Molecular Regulation Of The Salicylic Acid Hormone Pathway In Plants Under Changing Environmental Conditions, Christina A. M. Rossi, Eric J. R. Marchetta, Jong Hum Kim, Christian Castroverde
Biology Faculty Publications
Salicylic acid (SA) is a central plant hormone mediating immunity, growth, and development. Recently, studies have highlighted the sensitivity of the SA pathway to changing climatic factors and the plant microbiome. Here we summarize organizing principles and themes in the regulation of SA biosynthesis, signaling, and metabolism by changing abiotic/biotic environments, focusing on molecular nodes governing SA pathway vulnerability or resilience. We especially highlight advances in the thermosensitive mechanisms underpinning SA-mediated immunity, including differential regulation of key transcription factors (e.g., CAMTAs, CBP60g, SARD1, bHLH059), selective protein–protein interactions of the SA receptor NPR1, and dynamic phase separation of the recently identified …
Developing Red Fluorescent Zn2+ Sensors And Characterizing Zn2+ Homeostasis In Mucolipidosis Type Iv Disease,
2023
University of Denver
Developing Red Fluorescent Zn2+ Sensors And Characterizing Zn2+ Homeostasis In Mucolipidosis Type Iv Disease, Anna M. Dischler
Electronic Theses and Dissertations
Zinc (Zn2+) is a divalent, redox-inert metal that plays a vital role in many cellular processes either by acting as a catalytic cofactor or a labile signaling molecule in the cytoplasm. Cytosolic Zn2+ levels are tightly regulated to stay within a narrow window of concentrations, but fluctuations in Zn2+ signals have been detected in a variety of cells. We developed a genetically encoded, single red fluorescent protein (RFP) based Zn2+ sensor, RZnP1, that can be used alongside green-wavelength sensors for the simultaneous detection of different signaling molecules within the same cells or among different subcellular …
Identifying The Role Of Phospholipase D1 And Phosphatidic Acid In Exocytosis,
2023
University of Denver
Identifying The Role Of Phospholipase D1 And Phosphatidic Acid In Exocytosis, Broderick L. Bills
Electronic Theses and Dissertations
Exocytosis is an essential process for intercellular communication in eukaryotic cells. This process involves significant changes in membrane curvature, and lipids and curvature-sensing proteins can assist these processes. One protein in particular, phospholipase D1 (PLD1), and its product, the lipid phosphatidic acid (PA), are involved in multiple exocytic processes. However, PLD1 and PA’s role in this process has remained unclear. In this work, PLD1 and the production of PA were visualized during exocytosis, and PA localization to regions of membrane curvature was established. Together, these results support the hypothesis that PLD1 production of PA stabilizes negative curvature during membrane fusion. …
The Role Of Schwann Cells In Nerve Injury: Forskolin-Mediated Camp Activation Upregulates Tnfα Expression Despite Nf-Κb Downregulation In Lps-Treated Schwann Cells,
2023
Misericordia University
The Role Of Schwann Cells In Nerve Injury: Forskolin-Mediated Camp Activation Upregulates Tnfα Expression Despite Nf-Κb Downregulation In Lps-Treated Schwann Cells, Caitlyn E. Henry, Angela L. Asirvatham Ph.D.
Student Research Poster Presentations 2023
Although Schwann cells are known to play a role in axonal regeneration following nerve injury and inflammation, the exact mechanism is unknown. This study explores two potential mechanisms: the NF-κB and cAMP pathways. The NF-κB pathway produces cytokines, such as TNFα, to regulate inflammation, whereas the cAMP pathway is anti-inflammatory and regulates Schwann cell proliferation via AKAP95 and cyclin D3. Although it is well-known that NF-κB and cAMP are involved in inflammation, not much is known regarding the effects of forskolin-mediated cAMP activation on LPS-mediated NF-κB activation in Schwann cells. In this study, RT4-D6P2T immortalized rat Schwann cells were treated …
Molecular And Systemic Epigenetic Inheritance: Integrating Development, Genetics, And Evolution,
2023
Florida International University
Molecular And Systemic Epigenetic Inheritance: Integrating Development, Genetics, And Evolution, Robert Lickliter, David S. Moore
Pitzer Faculty Publications and Research
Currently, a central problem for theoretical biology is the integration of development with genetics and evolutionary theory. Through the late 20th century, biologists held that animals resemble their ancestors strictly because of the transgenerational transmission of DNA. This view effectively wrote development out of evolutionary biology. However, many molecular and developmental biologists now understand that phenotypes—anatomical, physiological, and behavioral traits—are not determined by genes (i.e., DNA segments) alone; instead, they emerge epigenetically from developmental processes involving co-acting genetic factors, environmental factors, molecular epigenetic factors, and other non-genetic factors within organisms’ bodies. This insight forces a rethinking of biological inheritance. …
Analysis Of A Cathepsin Protease In Normal Development And Tumor Metastasis In Drosophila Melanogaster,
2023
Western Kentucky University
Analysis Of A Cathepsin Protease In Normal Development And Tumor Metastasis In Drosophila Melanogaster, Lindsey Fannin
Mahurin Honors College Capstone Experience/Thesis Projects
Cysteine cathepsins are an important class of fifteen proteases with involvement in normal development and tumor progression. To better understand their contribution to these processes, the cathepsin L protease in Drosophila melanogaster was studied. In part one of this project, the role of this cathepsin in the normal development of Drosophila wings was analyzed. The GAL4/UAS-system and RNAi were used to downregulate this cathepsin in various regions of the wing and progeny were inspected for phenotypic irregularities. An abnormal phenotype of curved wings was found and hypothesized to be a result of apoptosis. Further experimentation will be required to prove …
