Response To Replication Stress And Maintenance Of Genome Stability By Wrn, The Werner Syndrome Protein,
2024
University of Kentucky
Response To Replication Stress And Maintenance Of Genome Stability By Wrn, The Werner Syndrome Protein, David K. Orren, Amrita Machwe
Markey Cancer Center Faculty Publications
Werner syndrome (WS) is an autosomal recessive disease caused by loss of function of WRN. WS is a segmental progeroid disease and shows early onset or increased frequency of many characteristics of normal aging. WRN possesses helicase, annealing, strand exchange, and exonuclease activities and acts on a variety of DNA substrates, even complex replication and re- combination intermediates. Here, we review the genetics, biochemistry, and probably physiological functions of the WRN protein. Although its precise role is unclear, evidence suggests WRN plays a role in pathways that respond to replication stress and maintain genome stability particularly in telomeric regions.
Carbon-Based Nanocomposite Membranes For Membrane Distillation: Progress, Problems And Future Prospects,
2024
University of Arkansas, Fayetteville
Carbon-Based Nanocomposite Membranes For Membrane Distillation: Progress, Problems And Future Prospects, Chhabilal Regmi, Yuwaraj K. Kshetri, S. Ranil Wickramasinghe
Chemical Engineering Faculty Publications and Presentations
The development of an ideal membrane for membrane distillation (MD) is of the utmost importance. Enhancing the efficiency of MD by adding nanoparticles to or onto a membrane’s surface has drawn considerable attention from the scientific community. It is crucial to thoroughly examine state-of-the-art nanomaterials-enabled MD membranes with desirable properties, as they greatly enhance the efficiency and reliability of the MD process. This, in turn, opens up opportunities for achieving a sustainable water–energy–environment nexus. By introducing carbon-based nanomaterials into the membrane’s structure, the membrane gains excellent separation abilities, resistance to various feed waters, and a longer lifespan. Additionally, the use …
Decisions, Decisions: Dna Damage Induced Modification Of P53 And The Effect Of Modifications On P53 Differential Binding To The Dna,
2024
University of South Carolina
Decisions, Decisions: Dna Damage Induced Modification Of P53 And The Effect Of Modifications On P53 Differential Binding To The Dna, Savannah Gabrielle Keating
Theses and Dissertations
p53 is the most frequently mutated tumor suppressor protein in cancer. It is highly regulated, most often via post-translational modifications (PTMs). Different pathways and target genes are differentially activated by p53 and there is much left to understand how this occurs. The regulation of p53 at the post-translational level is incredibly important to its DNA damage response, and, therefore, it is understood that PTMs are often involved in the differential activation of pathways by p53. This project aimed to identify some of the types and locations of post-translational modifications on p53 in response to different modes of DNA damage with …
Identifying And Training Deep Learning Neural Networks On Biomedical-Related Datasets,
2024
University of Arkansas, Fayetteville
Identifying And Training Deep Learning Neural Networks On Biomedical-Related Datasets, Alan E. Woessner, Usman Anjum, Hadi Salman, Jacob Lear, Jeffrey T. Turner, Ross Campbell, Laura Beaudry, Justin Zhan, Lawrence E. Cornett, Susan Gauch, Kyle P. Quinn
Computer Science and Computer Engineering Faculty Publications and Presentations
This manuscript describes the development of a resources module that is part of a learning platform named 'NIGMS Sandbox for Cloud-based Learning' https://github.com/NIGMS/NIGMS-Sandbox. The overall genesis of the Sandbox is described in the editorial NIGMS Sandbox at the beginning of this Supplement. This module delivers learning materials on implementing deep learning algorithms for biomedical image data in an interactive format that uses appropriate cloud resources for data access and analyses. Biomedical-related datasets are widely used in both research and clinical settings, but the ability for professionally trained clinicians and researchers to interpret datasets becomes difficult as the size and …
Wee1 And Cell Size Control In Fission Yeast By The Protein Kinase Cdr2,
2024
Dartmouth College
Wee1 And Cell Size Control In Fission Yeast By The Protein Kinase Cdr2, Rachel Berg-Murante
Dartmouth College Ph.D Dissertations
The mechanisms that govern cell size have long been topics of study in the field of cell biology. In eukaryotic cells this size control is tied to checkpoints, a set threshold of minimum necessary growth linked to cyclin dependent kinase activity regulation. In the fission yeast Schizosaccharomyces pombe, the Cdk1 regulatory network is conserved, and G2/M represents the major size checkpoint. Prior to mitosis, Cdk1 is inhibited by phosphorylation applied by Wee1 during G2 phase. Once S. pombe cells have satisfied the size checkpoint, Cdk1 is activated through dephosphorylation by Cdc25. Wee1 is a dose-dependent regulator of mitotic entry …
Optimizing The Expression Of Polyethylene Terephtalate Hydrolase-Encoding Synthetic Gene In Escherichia Coli Arctic Express (De3),
2024
Department of Biology, University of Indonesia, Depok 16424, West Java
Optimizing The Expression Of Polyethylene Terephtalate Hydrolase-Encoding Synthetic Gene In Escherichia Coli Arctic Express (De3), Jocelyn Nataniel, Maria Ulfah, Dini Achnafani, Niknik Nurhayati, Gabriela Christy Sabbathini, Sri Rezeki Wulandari, Abinawanto Abinawanto, Is Helianti
Makara Journal of Science
The waste of polyethylene terephthalate (PET) plastic waste in Indonesia is a pressing concern due to its slow degradation and potential environmental damage. One promising solution is to utilize polyethylene terephthalate hydrolase from Ideonella sakaiensis (IsPETase), an enzyme that specifically degrades PET. However, inducing the expression of IsPETase synthetic gene in Escherichia coli BL21 (DE3) has been challenging because much of it remains insoluble. This study aimed to express IsPETase in E. coli Arctic Express (DE3) and optimize the conditions to enhance its production. First, pET22b(+)pelB-IsPETase was inserted into E. coli Arctic Express (DE3). The …
Roles Of Mitochondrial Chchd2 And Gpcr-Associated Β-Arrestin2 In The Pathogenesis Of Lewy Body Disorders,
2024
University of South Florida
Roles Of Mitochondrial Chchd2 And Gpcr-Associated Β-Arrestin2 In The Pathogenesis Of Lewy Body Disorders, Teresa R. Kee
USF Tampa Graduate Theses and Dissertations
Coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) is a mitochondrial protein that plays important roles in cristae structure, oxidative phosphorylation, and apoptosis. Multiple mutations in CHCHD2 have been associated with Lewy body disorders (LBDs), such as Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), with the CHCHD2T61I mutation being the most widely studied. We generated the first transgenic mouse models expressing human CHCHD2WT and the PD-linked CHCHD2T61I mutation driven by the mPrP promoter. CHCHD2T61I Tg, but not CHCHD2WT Tg mice exhibit perinuclear mitochondrial aggregates, neuroinflammation, and have impaired long-term synaptic plasticity associated with synaptic dysfunction. Dopaminergic neurodegeneration, a hallmark of PD, …
Functional Studies Of Dcaf14 In Replication Fork Stability And Genome Integrity,
2024
University of South Florida
Functional Studies Of Dcaf14 In Replication Fork Stability And Genome Integrity, Neysha Tirado-Class
USF Tampa Graduate Theses and Dissertations
The response to replication stress is critical for ensuring the stability of replication forks and preserving genome integrity. To aid this response, several factors are recruited to stalled replication forks to prevent irreversible collapse of the replication machinery. Replication fork proteomic analyses of stalled forks reveal enrichment of DCAF14, a component of the Cullin4-RING (CRL4) E3 ubiquitin ligase complex, that mediates replication fork protection by blocking nuclease-mediated digestion of nascent DNA. However, little is known about the molecular mechanism by which DCAF14 functions in the context of replication stress. Notably, loss of function mutations in DCAF14 are associated with a …
Group B Streptococcus Intestinal Barrier Disruption And The Protective Role Of Butyrate,
2024
University of South Florida
Group B Streptococcus Intestinal Barrier Disruption And The Protective Role Of Butyrate, Kristen Dominguez
USF Tampa Graduate Theses and Dissertations
Group B Streptococcus (Streptococcus agalactiae; GBS) is a leading cause of neonatal sepsis worldwide. Intrapartum antibiotics in GBS-colonized mothers significantly reduced the incidence of early-onset sepsis occurring in the first week of life; however, there are currently no prophylactic interventions for late-onset sepsis, occurring within the first 3 months of life. GBS is a pathobiont that primarily colonizes the gastrointestinal tract and can cross the intestinal barrier via both the paracellular and transcellular routes, causing invasive disease. Neonatal susceptibility to GBS intestinal translocation is mediated by inadequate epithelial barrier function and microbiome immaturity; however, the mechanisms by which GBS exploits …
A Homogeneous Time-Resolved Fluorescence Screen To Identify Sirt2 Deacetylase And Defatty-Acylase Inhibitors,
2024
Rowan University
A Homogeneous Time-Resolved Fluorescence Screen To Identify Sirt2 Deacetylase And Defatty-Acylase Inhibitors, Jie Yang, Joel Cassel, Brian C Boyle, Daniel Oppong, Young-Hoon Ahn, Brian P Weiser
Rowan-Virtua School of Osteopathic Medicine Departmental Research
Human sirtuin-2 (SIRT2) has emerged as an attractive drug target for a variety of diseases. The enzyme is a deacylase that can remove chemically different acyl modifications from protein lysine residues. Here, we developed a high-throughput screen based on a homogeneous time-resolved fluorescence (HTRF) binding assay to identify inhibitors of SIRT2's demyristoylase activity, which is uncommon among many ligands that only affect its deacetylase activity. From a test screen of 9600 compounds, we identified a small molecule that inhibited SIRT2's deacetylase activity (IC50 = 7 μM) as well as its demyristoylase activity (IC50 = 37 μM). The inhibitor was composed …
Adipose-Derived Mesenchymal Stem Cells And Their Derived Epidermal Progenitor Cells Conditioned Media Ameliorate Skin Aging In Rats,
2024
The British University in Egypt
Adipose-Derived Mesenchymal Stem Cells And Their Derived Epidermal Progenitor Cells Conditioned Media Ameliorate Skin Aging In Rats, Mohamed M. Kamal, Omar Ibrahim Badr, Tasnim Mahmoud
Pharmacy
BACKGROUND: Skin alterations are among the most prominent signs of aging, and they arise from both intrinsic and extrinsic factors that interact and mutually influence one another. The use of D-galactose as an aging model in animals has been widely employed in anti-aging research. Adipose tissue-derived mesenchymal stem cells (Ad-MSCs) are particularly promising for skin anti-aging therapy due to their capacity for effective re-epithelization and secretion of various growth factors essential for skin regeneration. Accordingly, we aimed to examine the potential utility of Ad-MSCs as a therapy for skin anti-aging. METHODS: In this study, we isolated and characterized adipose-derived mesenchymal …
Cellular Energy Cycle Mediates An Advection-Like Forward Cell Flow To Support Collective Invasion,
2024
University of Arkansas, Fayetteville
Cellular Energy Cycle Mediates An Advection-Like Forward Cell Flow To Support Collective Invasion, Jian Zhang, Jenna Mosier, Yusheng Wu, Logan Waddle, Paul V. Taufelele, Wenjun Wang, Heng Sun, Cynthia A. Reinhart-King
Biomedical Engineering Faculty Publications and Presentations
Collective cell migration is a model for nonequilibrium biological dynamics, which is important for morphogenesis, pattern formation, and cancer metastasis. The current understanding of cellular collective dynamics is based primarily on cells moving within a 2D epithelial monolayer. However, solid tumors often invade surrounding tissues in the form of a stream-like 3D structure, and how biophysical cues are integrated at the cellular level to give rise to this collective streaming remains unclear. Here, it is shown that cell cycle-mediated bioenergetics drive a forward advective flow of cells and energy to the front to support 3D collective invasion. The cell division …
Cornus Officinalis Extract Activates The Keap1/Nrf2 Pathway And Delays T1d Onset In The Nod Mouse,
2024
University of South Florida
Cornus Officinalis Extract Activates The Keap1/Nrf2 Pathway And Delays T1d Onset In The Nod Mouse, Justin D. Fletcher
USF Tampa Graduate Theses and Dissertations
Type 1 diabetes (T1D) is an autoimmune disorder that results in the destruction of the insulin producing pancreatic β cells. The only therapeutic option following T1D clinical onset is exogenous insulin supplementation. At present, there is no cure for T1D and attempted interventional therapy has been focused on modulating the immune system. Few attempts have been pursued at preserving β cell function and survival. Here we provide a novel approach using extract from the fruit of the Cornus officinalis (CO) tree to preserve β cell function through the prevention of β cell stress. CO has been used in traditional Chinese …
The Role Of Edc3 In Drosophila Melanogaster Neuronal Development,
2024
University of Denver
The Role Of Edc3 In Drosophila Melanogaster Neuronal Development, Keelan Zius
Electronic Theses and Dissertations
Enhancer of mRNA-decay 3 (Edc3) is a component of multiple decapping complexes that regulates the transcriptome by targeting a subset of transcripts for decapping for 5’-to-3’ messenger RNA (mRNA) decay. A missense mutation in the conserved Lsm domain of Edc3 has been reported in two siblings presenting with mild, non-syndromic intellectual disability (ID), however, the role of Edc3 is neuronal development has never been evaluated. Here, we use the Drosophila melanogaster model system to investigate the effects of Edc3 disruption on neuronal development. We found Edc3 reduction leads to significant hyperplasia at the larval neuromuscular junction (NMJ), providing the first …
Colocalization Of Odc And Amyloid Plaques In Patients With Alzheimer’S Disease And Down Syndrome,
2024
University of Denver
Colocalization Of Odc And Amyloid Plaques In Patients With Alzheimer’S Disease And Down Syndrome, Julia S. Gielczynski
Undergraduate Theses, Capstones, and Recitals
Polyamines, and their rate-limiting enzyme ornithine decarboxylase (ODC), are crucial for many functions in the central nervous system but levels decrease with age. In neurodegenerative diseases, like Alzheimer’s Disease (AD), polyamine levels begin to increase again. Yet, there are still many unanswered questions surrounding polyamine’s possible role in AD, especially in those with Down Syndrome (DS), who also have an extra copy of the amyloid precursor protein (APP) and tend to get AD far earlier than the general population. We aim to investigate if there is colocalization between amyloid plaques and Ornithine Decarboxylase (ODC) in patients with AD and AD/DS, …
Morphological Remodeling Of The Endoplasmic Reticulum During Mitosis And Its Influence On The Integrity Of The Spindle Apparatus,
2024
University of Denver
Morphological Remodeling Of The Endoplasmic Reticulum During Mitosis And Its Influence On The Integrity Of The Spindle Apparatus, Katie R. Rollins
Electronic Theses and Dissertations
The Endoplasmic Reticulum (ER) is the largest organelle in the cell by surface area and forms contacts with other organelles throughout the cell. In recent work, the ER has been implicated in numerous processes within the cell beyond its canonical roles of protein synthesis and calcium storage. The ER also undergoes a remarkable transition in morphology during cell division, with mitotic divisions requiring a massive remodeling of various membranous organelles such as the nuclear envelope and Golgi. However, whether changes in ER behaviors modulate mitotic events is less clear. The rapid cleavage divisions in the early Drosophila embryo are a …
Effect Of Plumbagin On Chemo-Resistant Metastatic Retinoblastoma,
2024
CUNY Lehman College
Effect Of Plumbagin On Chemo-Resistant Metastatic Retinoblastoma, John J. Soto
Theses and Dissertations
Retinoblastoma, which is an ocular malignancy, usually results in poor prognoses in pediatric patients worldwide. Retinoblastoma in some events, can develop metastatic phenotypes which can lead to secondary tumor formation, furthering deleterious patient outcomes. It is of paramount importance to identify and research potent novel compounds that can be used to increase the likelihood of remission. Plumbagin (PLB) is a plant-derived, neuroprotective agent, which exhibits significant anticancer activities during in vitro study. PLB has been shown to have a high therapeutic efficacy against chemoresistant sublines as well as their normal counterparts. We attempted to show that the chemoresistant ABCC1 could …
Frontotemporal Dementia-Like Disease Progression Elicited By Seeded Aggregation And Spread Of Fus,
2024
Thomas Jefferson University
Frontotemporal Dementia-Like Disease Progression Elicited By Seeded Aggregation And Spread Of Fus, Sonia Vazquez-Sanchez, Britt Tilkin, Fatima Gasset-Rosa, Sitao Zhang, Diana Piol, Melissa Mcalonis-Downes, Jonathan Artates, Noe Govea-Perez, Yana Verresen, Lin Guo, Don Cleveland, James Shorter, Sandrine Da Cruz
Department of Biochemistry and Molecular Biology Faculty Papers
RNA binding proteins have emerged as central players in the mechanisms of many neurodegenerative diseases. In particular, a proteinopathy of fused in sarcoma (FUS) is present in some instances of familial Amyotrophic lateral sclerosis (ALS) and about 10% of sporadic Frontotemporal lobar degeneration (FTLD). Here we establish that focal injection of sonicated human FUS fibrils into brains of mice in which ALS-linked mutant or wild-type human FUS replaces endogenous mouse FUS is sufficient to induce focal cytoplasmic mislocalization and aggregation of mutant and wild-type FUS which with time spreads to distal regions of the brain. Human FUS fibril-induced FUS aggregation …
Macrophage-Driven Car T Cell Resistance In B Cell Lymphoma,
2024
University of South Florida
Macrophage-Driven Car T Cell Resistance In B Cell Lymphoma, Sae Bom Lee
USF Tampa Graduate Theses and Dissertations
Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of patients with relapsed/ refractory large B cell lymphoma (LBCL). Despite its promising efficacy, a subset of patients experiences primary resistance or relapse. In Chapter 2, we explore the tumor microenvironment (TME)-induced resistance mechanisms in patients with LBCL. Analysis of the intratumoral immune infiltrates in pre-infusion tumor biopsies revealed that the levels of immunoregulatory macrophages were elevated in patients who responded poorly to axicabtagene ciloleucel (axi-cel). Using preclinical mouse B cell tumor models, we found that the CAR T-cell-produced interferon-gamma (IFN-γ) enhanced the expression of inducible nitric oxide synthase (iNOS, …
Establishment Of Bacteroides In The Gut And Its Role In The Cystic Fibrosis Gut-Lung Axis,
2024
Dartmouth College
Establishment Of Bacteroides In The Gut And Its Role In The Cystic Fibrosis Gut-Lung Axis, Rebecca A. Valls
Dartmouth College Ph.D Dissertations
In the quest to understand the complex interplay between the gut microbiota and cystic fibrosis (CF), a disease characterized by chronic upper respiratory complications and an exacerbated proinflammatory response, our lab engaged in a collaborative study with Dartmouth-Hitchcock Medical Center (DHMC) to characterize the gut microbiota of pediatric CF patients. Initial analyses established a connection between gut microbial composition and respiratory health, particularly highlighting a scarcity of Bacteroides species compared to healthy controls. In following investigations, we utilized random forest models to understand how stool microbiota may influence clinical outcomes of these pediatric CF patients, including: age, upper respiratory infections, …
