Open Access. Powered by Scholars. Published by Universities.®

Cell and Developmental Biology Commons™

Open Access. Powered by Scholars. Published by Universities.®

2023

Discipline
Institution
Keyword
Publication
Publication Type
File Type

Articles 361 - 390 of 490

Full-Text Articles in Cell and Developmental Biology

Comparison Of Two Diagnostic Assays For The Detection Of Serum Neutralizing Antibody To Porcine Epidemic Diarrhea Virus, Justin Brown, Korakrit Poonsuk, Ting-Yu Cheng, Chris Rademacher, Erin Kalkwarf, Liying Tian, Lauren A. Mckeen, Chong Wang, Luis Gimenez-Lirola, David Baum, Locke A. Karriker Feb 2023

Comparison Of Two Diagnostic Assays For The Detection Of Serum Neutralizing Antibody To Porcine Epidemic Diarrhea Virus, Justin Brown, Korakrit Poonsuk, Ting-Yu Cheng, Chris Rademacher, Erin Kalkwarf, Liying Tian, Lauren A. Mckeen, Chong Wang, Luis Gimenez-Lirola, David Baum, Locke A. Karriker

School of Veterinary and Biomedical Sciences: Faculty Publications

Lactogenic immunity is important for the protection of piglets against many pathogens including porcine epidemic diarrhea virus. Circulating neutralizing antibodies levels in sow sera may help determine if a detectable immune response could confer protection to piglets. Neutralizing antibodies can be detected through various diagnostic assays. This study evaluated the diagnostic characteristics of two neutralizing antibody assays for porcine epidemic diarrhea virus neutralizing antibodies in serum of challenged gilts. Four treatment groups, control, non-vaccinated, vaccinated prior to challenge, and vaccinated following challenge, were comprised of 20 gilts. Serum sample were collected from each gilt prior to and following challenge with …

Go to article

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 Feb 2023

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 …

Go to article

Production And Characterization Of Monoclonal Antibodies To Xenopus Proteins, Brett Horr, Ryan Kurtz, Ankit Pandey, Benjamin G. Hoffstrom, Elizabeth Schock, Carole Labonne, Dominique Alfandari Feb 2023

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 …

Go to article

Low Molecular Weight Cyclin E Deregulates Dna Replication And Damage Repair To Promote Genomic Instability In Breast Cancer, Mi Li Feb 2023

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 …

Go to article

A Brief Overview Of Triple A Syndrome, Jamaal Khan Jan 2023

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 …

Go to article

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 Jan 2023

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 …

Go to article

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 Jan 2023

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 …

Go to article

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 Jan 2023

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 …

Go to article

Vaccines Against Group B Coxsackieviruses And Their Importance, Kiruthiga Mone, Ninaad Lasrado, Meghna Sur, Jay Reddy Jan 2023

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.

Go to article

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 Jan 2023

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 = …

Go to article

Methylene Blue Inhibits Cromakalim-Activated K+ Currents In Follicle-Enclosed Oocytes, Dmytro Isaev, Keun-Hang Susan Yang, Georg Petroianu, Dietrich Ernst Lorke, Murat Oz Jan 2023

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 …

Go to article

Investigating The Absence Of A Dietary Response At The Neuromuscular Junction In Larval Drosophila Melanogaster, Suzanna Louise Marbach Jan 2023

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 …

Go to article

Comparison Of In-Vitro 3d Human Embryoids With Current Models For Gastrulation, Jin Park Jan 2023

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 …

Go to article

Quantification Of Nuclear Dynamics During Epithelial Remodeling, Noah De Leeuw Jan 2023

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 …

Go to article

Dna Damage Response Activates The Electron Transport Chain And Oxidative Metabolism By Two Parallel Mechanisms, Shreya Nagar Jan 2023

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), …

Go to article

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 Jan 2023

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 …

Go to article

Developing Red Fluorescent Zn2+ Sensors And Characterizing Zn2+ Homeostasis In Mucolipidosis Type Iv Disease, Anna M. Dischler Jan 2023

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 …

Go to article

Identifying The Role Of Phospholipase D1 And Phosphatidic Acid In Exocytosis, Broderick L. Bills Jan 2023

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. …

Go to article

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. Jan 2023

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 …

Go to article

Molecular And Systemic Epigenetic Inheritance: Integrating Development, Genetics, And Evolution, Robert Lickliter, David S. Moore Jan 2023

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. …

Go to article

Analysis Of A Cathepsin Protease In Normal Development And Tumor Metastasis In Drosophila Melanogaster, Lindsey Fannin Jan 2023

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 …

Go to article

Creating An In-Vitro Co-Culture Model Of Human Megakaryocytic-Erythroid Progenitors And Endothelial Cells, Clerin John Jan 2023

Creating An In-Vitro Co-Culture Model Of Human Megakaryocytic-Erythroid Progenitors And Endothelial Cells, Clerin John

Holster Scholar Projects

Previous studies have suggested that endothelial cells promote red blood cell (RBC) production in human bone marrow, which has implications for improved treatments for anemia, cancer, and reproduction. However, investigation of this phenomenon is hindered by a dearth of studies that have successfully isolated primary endothelial cells from human bone marrow. Using flow cytometry, magnetic cell separation, and primary cell culture techniques we tested the hypothesis that adult bone marrow-derived endothelial cells can be isolated from previously frozen bone marrow samples by selecting for CD144+ expressing cells and culturing them in vitro. Magnetic cell separation utilizing the marker CD144 to …

Go to article

Investigating The Effects Of Paraquat On Kidney Disease Biomarkers In Hek293 Cells, Zounaira Shahzad Jan 2023

Investigating The Effects Of Paraquat On Kidney Disease Biomarkers In Hek293 Cells, Zounaira Shahzad

Honors Undergraduate Theses

Farmworkers in Apopka, FL, have been subjected to overhead pesticide exposure since the 1940s. Pesticides including Paraquat (PQ), Metribuzin and Aldicarb were sprayed onto the field while farmworkers worked. In "Fed Up: The High Cost of Cheap Food," farmworkers recalled the physical toll these conditions took on their bodies, blaming pesticides for their diseases, such as chronic kidney disease (CKD). While established that pesticides, specifically PQ, may be involved in some forms of Parkinson's disease, no explicit connection has been identified for SLE, CKD, and other diseases experienced by farm workers. This study evaluated whether pesticides could contribute to kidney …

Go to article

Dcaf14 Regulates Cdt2 To Promote Set8-Dependent Replication Fork Protection, Neysha Tirado-Class, Caitlin Hathaway, Anthony Nelligan, Huzefa Dungrawala Jan 2023

Dcaf14 Regulates Cdt2 To Promote Set8-Dependent Replication Fork Protection, Neysha Tirado-Class, Caitlin Hathaway, Anthony Nelligan, Huzefa Dungrawala

Molecular Biosciences Faculty Publications

DDB1- and CUL4-associated factors (DCAFs) CDT2 and DCAF14 are substrate receptors for Cullin4–RING E3 ubiquitin ligase (CRL4) complexes. CDT2 is responsible for PCNA-coupled proteolysis of substrates CDT1, p21, and SET8 during S-phase of cell cycle. DCAF14 functions at stalled replication forks to promote genome stability, but the mechanism is unknown. We find that DCAF14 mediates replication fork protection by regulating CRL4CDT2 activity. Absence of DCAF14 causes increased proteasomal degradation of CDT2 substrates. When forks are challenged with replication stress, increased CDT2 function causes stalled fork collapse and impairs fork recovery in DCAF14-deficient conditions. We further show that stalled fork protection …

Go to article

Otud5 Limits Replication Fork Instability By Organizing Chromatin Remodelers, Angelo De Vivo, Hongseon Song, Yujin Lee, Neysha Tirado-Class, Anthony Sanchez, Sandy D. Westerheide, Huzefa Dungrawala, Younghoon Kee Jan 2023

Otud5 Limits Replication Fork Instability By Organizing Chromatin Remodelers, Angelo De Vivo, Hongseon Song, Yujin Lee, Neysha Tirado-Class, Anthony Sanchez, Sandy D. Westerheide, Huzefa Dungrawala, Younghoon Kee

Molecular Biosciences Faculty Publications

Proper regulation of replication fork progression is important for genomic maintenance. Subverting the transcription-induced conflicts is crucial in preserving the integrity of replication forks. Various chromatin remodelers, such as histone chaperone and histone deacetylases are known to modulate replication stress, but how these factors are organized or collaborate are not well understood. Here we found a new role of the OTUD5 deubiquitinase in limiting replication stress. We found that OTUD5 is recruited to replication forks, and its depletion causes replication fork stress. Through its C-terminal disordered tail, OTUD5 assembles a complex containing FACT, HDAC1 and HDAC2 at replication forks. A …

Go to article

The Identification Of Two M20b Family Peptidases Required For Full Virulence In Staphylococcus Aureus, Nathanial James Torres, Devon Rizzo, Maria A. Reinberg, Mary-Elizabeth Jobson, Brendan C. Totzke, Jessica K. Jackson, Wenqi Yu, Lindsey Neil Shaw Jan 2023

The Identification Of Two M20b Family Peptidases Required For Full Virulence In Staphylococcus Aureus, Nathanial James Torres, Devon Rizzo, Maria A. Reinberg, Mary-Elizabeth Jobson, Brendan C. Totzke, Jessica K. Jackson, Wenqi Yu, Lindsey Neil Shaw

Molecular Biosciences Faculty Publications

We have previously demonstrated that deletion of an intracellular leucine aminopeptidase results in attenuated virulence of S. aureus. Herein we explore the role of 10 other aminopeptidases in S. aureus pathogenesis. Using a human blood survival assay we identified mutations in two enzymes from the M20B family (PepT1 and PepT2) as having markedly decreased survival compared to the parent. We further reveal that pepT1, pepT2 and pepT1/2 mutant strains are impaired in their ability to resist phagocytosis by, and engender survival within, human macrophages. Using a co-infection model of murine sepsis, we demonstrate impairment of dissemination and survival …

Go to article

S-Acylation Is A Key Regulator Of Orai1/Stim1-Mediated Store-Operated Calcium Entry In T Cells, Savannah J. West Diaz Jan 2023

S-Acylation Is A Key Regulator Of Orai1/Stim1-Mediated Store-Operated Calcium Entry In T Cells, Savannah J. West Diaz

Dissertations and Theses (Open Access)

Orai1 and STIM1 proteins are the essential components of the Ca2+ release activated Ca2+ (CRAC) channel which is required for store-operated Ca2+ entry (SOCE) in T cells and subsequent signaling events leading to T cell activation, proliferation, and differentiation. Plasma membrane (PM)-localized Orai1 is the pore-forming subunit of the CRAC channel, and STIM1 is the Ca2+ sensor localized to the endoplasmic reticulum (ER) membrane in quiescent T cells. T cell receptor (TCR) stimulation leads to depletion of ER Ca2+ stores resulting in Ca2+ no longer being bound to STIM1. This activates STIM1 by triggering …

Go to article

Investigating Smooth Muscle Myosin Dynamics And Assembly In Physiology And Pathology, Maggie Bennett Jan 2023

Investigating Smooth Muscle Myosin Dynamics And Assembly In Physiology And Pathology, Maggie Bennett

Dissertations

Vascular smooth muscle cells (SMCs) surround many blood vessels throughout the body,where they dynamically alter vessel diameter to regulate blood pressure, provide structural integrity, and absorb shock on a beat-to-beat timescale. As smooth muscle function fails, profound vascular disease ensues, often with tragic results- even death. Smooth muscle myosin 2 (SM2) is the dominant motor protein that actuates contractility and allows SMCs to perform these vital functions. To function, SM2 monomers dynamically assemble into filaments, which upon SMC activation, associate with filamentous actin to drive contractility. Despite the critical contribution of SM2 to SMC function, foundational aspects of SM2 assembly …

Go to article

Assessing The Roles Of Myc And Egr1 In Endoderm Differentiation, Sadaf R. Shahebrahimi, Joseph Nguyen, Kyra Skye Thomas, Erick Spears Jan 2023

Assessing The Roles Of Myc And Egr1 In Endoderm Differentiation, Sadaf R. Shahebrahimi, Joseph Nguyen, Kyra Skye Thomas, Erick Spears

Science University Research Symposium (SURS)

The Wnt signaling pathway is evolutionarily conserved from fruit flies to humans. Strongly associated with development and embryonic morphogenesis, it is known to be required for early endoderm and later hindgut development in mammals. In adults, the Wnt signaling pathway is required for the proper maintenance of the intestinal epithelium and mutations in critical Wnt signaling pathway components are initiating events in the development of essentially all colorectal cancers. An important target gene whose expression is upregulated by Wnt signaling pathway activation is the oncogene MYC. This gene produces a transcription factor whose typical cellular role is to stimulate …

Go to article

Testing Ssa4:Ade3 Reporters For Mcs Screening, Karah Edmonds, Rebecca Adams Jan 2023

Testing Ssa4:Ade3 Reporters For Mcs Screening, Karah Edmonds, Rebecca Adams

Science University Research Symposium (SURS)

In eukaryotic cells, after transcription, mRNA is escorted from the nucleus to the cytoplasm to be translated. This process, called mRNA export, is essential for gene expression. However, when the cell exists in stressful conditions, mRNA export becomes regulated, and only select transcripts, including the stress-responsive SSA4 mRNA, can be exported. This project aims to uncover the mechanism of selective SSA4 mRNA export by generating a reporter that enables phenotypically visible expression under stressful conditions. Specifically, the ADE3 ORF was placed under the regulatory sequence of SSA4, which was anticipated to induce a red color for colonies only following stress. …

Go to article

First Prev Next Last