Akt Disruption Leads To Non-Canonical Apical Constriction In Drosophila Embryos,
2024
University of Denver
Akt Disruption Leads To Non-Canonical Apical Constriction In Drosophila Embryos, Vincent Brown
Electronic Theses and Dissertations
The Akt/mTOR pathway (Akt pathway) has largely been examined in terms of its role as the primary nutrient sensing pathway due to its ability to recognize nutrient availability within a cell, particularly amino acids and glucose. Among its nutrient sensing characteristics, this pathway also contributes to a large variety of other cell functions such as cell growth, proliferation, protein synthesis, and cell survival via anti-apoptotic signaling. Although many aspects of this pathway have been carefully studied, the extent to which it regulates embryonic development remains unclear. Here, I examine Akt function in the early Drosophila embryo and demonstrate that Akt …
Structural Basis For Substrate Binding And Selection By Human Mitochondrial Rna Polymerase,
2024
Thomas Jefferson University
Structural Basis For Substrate Binding And Selection By Human Mitochondrial Rna Polymerase, Karl Herbine, Ashok Nayak, Dmitry Temiakov
Department of Biochemistry and Molecular Biology Faculty Papers
The mechanism by which RNAP selects cognate substrates and discriminates between deoxy and ribonucleotides is of fundamental importance to the fidelity of transcription. Here, we present cryo-EM structures of human mitochondrial transcription elongation complexes that reveal substrate ATP bound in Entry and Insertion Sites. In the Entry Site, the substrate binds along the O helix of the fingers domain of mtRNAP but does not interact with the templating DNA base. Interactions between RNAP and the triphosphate moiety of the NTP in the Entry Site ensure discrimination against nucleosides and their diphosphate and monophosphate derivatives but not against non-cognate rNTPs and …
Absolute Quantification Of Human Myosin And Titin Isoforms In Disease By A Mass Spectrometry Approach,
2024
Loyola University of Chicago Graduate School
Absolute Quantification Of Human Myosin And Titin Isoforms In Disease By A Mass Spectrometry Approach, Nitha Aima Muntu
Master's Theses
Heart failure (HF) is the leading cause of death worldwide and produces an immense economic burden. Dilated cardiomyopathy (DCM), characterized by contractile weakness and chamber dilation, is a significant cause of HF. The sarcomeric proteins play a crucial role in regulating the contractile properties of the heart. As the primary motor protein, the expression of cardiac myosin isoforms (α-MHC and β-MHC) dictates the performance and cardiac energy utilization of the sarcomere. Titin is the giant spring protein in the sarcomere, and titin isoform expression impacts the passive stiffness of the myocardium. Small changes in the α-MHC/β-MHC and titin isoform ratios …
Role Of Pycr2 In Colorectal Cancer,
2024
University of Nebraska Medical Center
Role Of Pycr2 In Colorectal Cancer, Raju Lama Tamang
Theses & Dissertations
Despite significant progress in clinical management, colorectal cancer (CRC) remains the 3rd most common cause of cancer-related deaths. A positive association of PYCR2 (Pyrroline-5-carboxylate reductase-2), a terminal enzyme of proline metabolism, with CRC aggressiveness was recently reported including by us. However, how PYCR2 promotes colon carcinogenesis remains ill understood. In our studies, comprehensive in-silico and biochemical evaluations were performed along with genetic manipulations and in-vivo tumor growth assays to gain mechanistic understanding. Results showed that PYCR2 expression was significantly upregulated in CRC and associated with poor patient survival specifically among PYCR isoforms (PYCR-1, -2 and -3). Genetic inhibition of PYCR2 …
Determining If Cx45 Acts As An Arrythmogenic Substrate In The Diseased Myocardium,
2024
University of Nebraska Medical Center
Determining If Cx45 Acts As An Arrythmogenic Substrate In The Diseased Myocardium, Stephen R. Sobota
Theses & Dissertations
Proper contraction of the heart relies on gap junction channels (GJCs) composed of Cx40 and Cx43 in the atrial and ventricular tissues which mediate electrical conductance in the working myocardium. Also expressed is Cx45, which is limited to the pacemaker system. Studies in diseased human hypertrophic cardiac tissue have shown expression of Cx45 and decrease of Cx43 in the myocardium. Cx43 and Cx45 in vitro form heterometric GJCs, where the channel characteristics (metabolite transfer, electrical conductance, etc.) resemble those of Cx45. There is little-to-no data showing whether GJCs composed of Cx43 and Cx45 in cardiac hypertrophy result in altered conductance. …
Enpp1 Enzyme Replacement Therapy Improves Ectopic Calcification But Does Not Rescue Skeletal Phenotype In A Mouse Model For Craniometaphyseal Dysplasia,
2024
Thomas Jefferson University
Enpp1 Enzyme Replacement Therapy Improves Ectopic Calcification But Does Not Rescue Skeletal Phenotype In A Mouse Model For Craniometaphyseal Dysplasia, Ernst Reichenberger, Kevin O'Brien, Ayano Hatori, Thomas Carpenter, Koen Van De Wetering, Lisa Flaman, Jennifer Howe, Daniel Ortiz, Yves Sabbagh, I-Ping Chen
Jefferson Institute of Molecular Medicine Papers and Presentations
Craniometaphyseal dysplasia (CMD) is a rare genetic bone disorder, characterized by progressive thickening of craniofacial bones and flared metaphyses of long bones. Craniofacial hyperostosis leads to the obstruction of neural foramina and neurological symptoms such as facial palsy, blindness, deafness, or severe headache. Mutations in ANKH (mouse ortholog ANK), a transporter of small molecules such as citrate and ATP, are responsible for autosomal dominant CMD. Knock-in (KI) mice carrying an ANKF377del mutation (AnkKI/KI) replicate many features of human CMD. Pyrophosphate (PPi) levels in plasma are significantly reduced in AnkKI/KI mice. PPi is a potent inhibitor of …
Stem-Loop And Circle-Loop Tads Generated By Directional Pairing Of Boundary Elements Have Distinct Physical And Regulatory Properties,
2024
Thomas Jefferson University
Stem-Loop And Circle-Loop Tads Generated By Directional Pairing Of Boundary Elements Have Distinct Physical And Regulatory Properties, Wenfan Ke, Miki Fujioka, Paul Schedl, James Jaynes
Department of Biochemistry and Molecular Biology Faculty Papers
The chromosomes in multicellular eukaryotes are organized into a series of topologically independent loops called TADs. In flies, TADs are formed by physical interactions between neighboring boundaries. Fly boundaries exhibit distinct partner preferences, and pairing interactions between boundaries are typically orientation-dependent. Pairing can be head-to-tail or head-to-head. The former generates a stem-loop TAD, while the latter gives a circle-loop TAD. The TAD that encompasses the Drosophila even skipped (eve) gene is formed by the head-to-tail pairing of the nhomie and homie boundaries. To explore the relationship between loop topology and the physical and regulatory landscape, we flanked the nhomie boundary …
Assessment Of Tripeptides Self-Assembly & Er Stress On Cell Viability And Exosome Secretion In Mda-Mb231,
2024
CUNY Hunter College
Assessment Of Tripeptides Self-Assembly & Er Stress On Cell Viability And Exosome Secretion In Mda-Mb231, Azmat Parveen
Theses and Dissertations
This study delves into the effects of tripeptides KYpF and WYpK(NBD) on MDA-MB-231 cells, uncovering KYpF's ability to reduce cell proliferation and exosome secretion in peptide treated cells. Conversely, WYpK(NBD) demonstrated significant toxicity at 10 μM. These insights pave the way for optimizing peptide-based cellular treatments for exosome secretion purposes.
G12/13 Signaling In Asthma,
2024
Thomas Jefferson University
G12/13 Signaling In Asthma, Elizabeth L. Mcduffie, Reynold A Panettieri, Charles P. Scott
Department of Biochemistry and Molecular Biology Faculty Papers
Shortening of airway smooth muscle and bronchoconstriction are pathognomonic for asthma. Airway shortening occurs through calcium-dependent activation of myosin light chain kinase, and RhoA-dependent calcium sensitization, which inhibits myosin light chain phosphatase. The mechanism through which pro-contractile stimuli activate calcium sensitization is poorly understood. Our review of the literature suggests that pro-contractile G protein coupled receptors likely signal through G12/13 to activate RhoA and mediate calcium sensitization. This hypothesis is consistent with the effects of pro-contractile agonists on RhoA and Rho kinase activation, actin polymerization and myosin light chain phosphorylation. Recognizing the likely role of G12/13 signaling in the pathophysiology …
Detection Of Cryptosporidium Spp. In Surface Water And Tissues Of Bivalves In Waterways Of Coney Island, New York (Usa),
2024
Pace University
Detection Of Cryptosporidium Spp. In Surface Water And Tissues Of Bivalves In Waterways Of Coney Island, New York (Usa), Manasvi Patel
Biochemistry and Molecular Biology
Combined sewer overflows (CSOs) are major sources of pollutants such as microbial pathogens, total suspended solids (TSS), oxygen depleting substances, toxicants, and nutrients. Untreated wastewater contains parasites like Giardia, Cryptosporidium and Entamoeba which impact human health. Cryptosporidium is the leading cause of diarrheal diseases which spreads through contaminated water supplies. Our research on Coney Island in Brooklyn investigated the amount of Cryptosporidium oocysts found in the water and bivalves/shellfish tissue and to supports a parallel study examining both people's use of waterways around Coney Island (for religious ceremonies, fishing, foraging, swimming, etc.) and their perceptions of how polluted the …
Furthering Ascidian Taxonomy Using Molecular Biology,
2024
Coastal Carolina University
Furthering Ascidian Taxonomy Using Molecular Biology, Nicholas Gulnick
Electronic Theses and Dissertations
Ascidians are our closest invertebrate relatives and comprise nearly 3,000 species separated into three orders: Aplousobranchia (most speciose), Stolidobranchia, and Phlebobranchia (least speciose). Ascidians can be classified as either solitary or colonial organisms. Species delimitation using morphological characters alone has had varied results. Well known, widely distributed, morphological species have turned out to be catch all species comprised of several cryptic species. Molecular markers can help mitigate some of the issues presented by strictly using morphological observations, including resolving the status of cryptic species, and accessing the expert knowledge required to identify a species. By incorporating molecular markers and pairing …
Deciphering The Wheat Seed Core Mycobiome Of Two Egyptian Cultivars (Giza 171 And Sids 14) By Using High Throughput Amplicon Sequencing Of The Its2 Region,
2024
Faculty of Agriculture
Deciphering The Wheat Seed Core Mycobiome Of Two Egyptian Cultivars (Giza 171 And Sids 14) By Using High Throughput Amplicon Sequencing Of The Its2 Region, Sobhy S.H. Abdelsalam, Muziri Mugwanya, Ahmed G. Gad, Ayman B.A. Basyony
Faculty Journal Articles
Wheat (Triticum aestivum L.) is an important food crop throughout the world. The seed mycobiome is the primary inoculum affecting the overall health and productivity of wheat plants. Seed-borne fungi can have an impact on the production of wheat and cause health complications upon consumption. Therefore, for durable and sustainable wheat production, it is imperative to characterise the wheat mycobiome. The rationale of this study was to investigate the wheat seed mycobiome of two Egyptian wheat cultivars (Sids 14 and Giza 171) using a culture-independent technique. The fungal community in 6 wheat seed samples was identified by high-throughput amplicon sequencing …
Developing A Comprehensive Genome-Scale Metabolic Model For The Arabidopsis Thaliana Root System,
2024
University of Nebraska-Lincoln
Developing A Comprehensive Genome-Scale Metabolic Model For The Arabidopsis Thaliana Root System, Lohani Esterhuizen
Department of Chemical and Biomolecular Engineering: Dissertations, Theses, and Student Research
Arabidopsis thaliana (Arabidopsis) is the most well-established model plant to date. Being the first plant to have its genome mapped, studies on Arabidopsis have provided insurmountable insights into the physiological and biochemical nature of plants. Methods that allow us to computationally study the metabolism of organisms include the use of genome-scale metabolic models (GEMs). Despite its popularity, no GEM currently maps the metabolic activity in the root system of Arabidopsis, which is the first organ to face and respond to stress conditions in the soil. This work aims to develop and implement a comprehensive GEM of the Arabidopsis root system …
Elucidating The Roles Of Septin Proteins In Thermotolerance And Cell Wall Integrity In Cryptococcus Neoformans,
2024
Clemson University
Elucidating The Roles Of Septin Proteins In Thermotolerance And Cell Wall Integrity In Cryptococcus Neoformans, Stephani S. Martinez Barrera
All Dissertations
Cryptococcus neoformans is a globally distributed fungal pathogen responsible for causing cryptococcal meningitis in immunocompromised individuals. This pathogenic yeast must adapt to changes in temperature upon entering the human host. Septin proteins are conserved filament-forming GTPases that assemble as higher-order complexes at the cell cortex to support cytokinesis and morphogenesis in fungal and animal cells. In C. neoformans, four septin homologs (Cdc3, Cdc10, Cdc11, and Cdc12) assemble at the mother-bud neck, contributing to cytokinesis through poorly understood mechanisms. C. neoformans strains lacking the septins Cdc3 or Cdc12 are viable at 25°C, but fail to proliferate at 37°C, and are …
Investigation Of The Microbiome Of A Recirculating Aquaculture System (Ras) For Crassostrea Virginica Larvae,
2024
The University of Southern Mississippi
Investigation Of The Microbiome Of A Recirculating Aquaculture System (Ras) For Crassostrea Virginica Larvae, Isabelle Townsend
Master's Theses
Recirculating Aquaculture Systems (RAS) offer control over physicochemical and biological factors impacting aquaculture success. One understudied facet of RASs is the water microbiome. Oyster larval microbiomes are shaped by their aquatic microbiomes. Understanding the dynamics of and the factors shaping RAS microbiome may provide insights to how the microbiome can be a tool for optimizing larval production. This study’s goals were to investigate the microbiome stability of a RAS rearing oyster larvae across time and space, determine impacts of larval presence on the microbiome, and examine connections between larvae production outcomes and microbiome stability. Water samples were collected weekly from …
Cigarette Smoke-Induced Epithelial-To-Mesenchymal Transition: Insights Into Cellular Mechanisms And Signaling Pathways,
2024
University of Kentucky
Cigarette Smoke-Induced Epithelial-To-Mesenchymal Transition: Insights Into Cellular Mechanisms And Signaling Pathways, Sarah Mohammed Alqithami, Amrita Machwe, David K. Orren
Markey Cancer Center Faculty Publications
This review delves into the molecular complexities underpinning the epithelial-to-mesenchymal transition (EMT) induced by cigarette smoke (CS) in human bronchial epithelial cells (HBECs). The complex interplay of pathways, including those related to WNT//β-catenin, TGF-β/SMAD, hypoxia, oxidative stress, PI3K/Akt, and NF-κB, plays a central role in mediating this transition. While these findings significantly broaden our understanding of CS-induced EMT, the research reviewed herein leans heavily on 2D cell cultures, highlighting a research gap. Furthermore, the review identifies a stark omission of genetic and epigenetic factors in recent studies. Despite these shortcomings, the findings furnish a consolidated foundation not only for the …
Nsd3::Nutm1 Fusion Sarcoma Mimicking Malignant Peripheral Nerve Sheath Tumor With Prolonged Survival,
2024
University of Kentucky
Nsd3::Nutm1 Fusion Sarcoma Mimicking Malignant Peripheral Nerve Sheath Tumor With Prolonged Survival, Jing Di, Ali M. Alhaidary, Chi Wang, Jinge Liu, Sainan Wei, Joseph Valentino, Therese J. Bocklage
Markey Cancer Center Faculty Publications
Nuclear Protein in Testis (NUT)-rearranged tumors comprise predominantly NUT car- cinoma but also include certain lymphomas, leukemias, skin appendage tumors, and sarcomas. Although histologically diverse, all are genetically identified by oncogenic rearrangement in the NUTM1 gene. Many fusion partners occur, and NSD3 is NUT carcinoma’s third most common partner. Herein, we present a case of a 26-year-old man with an NSD3::NUTM1 fusion sarcoma. The patient presented at the age of 13 months with a scalp nodule. Over the next 24 years, he experienced five local recurrences and ultimately expired of a rapidly progressive recurrence. His treatment included surgical resections, radiation, …
Placental Co-Transcriptional Activator Vestigial-Like 1 (Vgll1) Drives Tumorigenesis Via Increasing Transcription Of Proliferation And Invasion Genes,
2024
The Texas Medical Center Library
Placental Co-Transcriptional Activator Vestigial-Like 1 (Vgll1) Drives Tumorigenesis Via Increasing Transcription Of Proliferation And Invasion Genes, Heather Sonnemann
Dissertations and Theses (Open Access)
Vestigial-like 1 (VGLL1) is a co-transcriptional activator that binds to TEA domain containing transcription factors (TEADs). Its expression is upregulated in a variety of aggressive cancer types, including pancreatic and basal-like breast cancer, and increased transcription of VGLL1 is strongly correlated with poor prognosis and decreased overall patient survival. In normal tissues, VGLL1 is most highly expressed within placental trophoblast cells, which share the common attributes of rapid cellular proliferation and invasion with tumor cells. The impact of VGLL1 in cancer has not been fully elucidated and no VGLL1-targeted therapy currently exists. The aim of this study was to evaluate …
Exploring Acetate Metabolism: Genetically Characterizing Acetate Production And Acetate Utilization In The Fungal Pathogen Cryptococcus Neoformans,
2024
Clemson University
Exploring Acetate Metabolism: Genetically Characterizing Acetate Production And Acetate Utilization In The Fungal Pathogen Cryptococcus Neoformans, Rodrigo Catalan-Hurtado
All Dissertations
The basidiomycete Cryptococcus neoformans is an invasive opportunistic fungal pathogen and the most frequent cause of fungal meningitis resulting in approximately 112,000 deaths per year worldwide. Recently, the World Health Organization systematically prioritized fungal pathogens in which C. neoformans was among four fungal pathogens deemed critically important. Current methods of treatment are inadequate for most of the infected population; therefore, it is imperative to find novel therapeutic targets. Previous studies have shown that acetate is a major metabolite found in biopsies of C. neoformans infected mouse brain and lung tissues. Two potential pathways for acetate production have been identified. …
Assessment Of Tce And Chiral Pcb Dechlorination Rate, Congener Diversity, And Enantioselectivity In Town Creek, Sc, Usa Sediment Microcosms,
2024
Clemson University
Assessment Of Tce And Chiral Pcb Dechlorination Rate, Congener Diversity, And Enantioselectivity In Town Creek, Sc, Usa Sediment Microcosms, Catherine P. Sumner
All Dissertations
Polychlorinated biphenyls (PCBs) and trichloroethene (TCE) are ubiquitous contaminants and are recognized as persistent organic pollutants due to their extreme chemical stability. PCBs were manufactured by chlorinating biphenyls that created 209 congeners with various structures, of which 19 are chiral and can exist as a pair of stable atropisomers. PCBs have been known to cause developmental and neurological toxicity in humans and wildlife; they can act as endocrine disrupters, carcinogens, and teratogens. Sangamo Weston Inc. was an industrial plant located near Town Creek in Pickens Country, South Carolina, that manufactured capacitors and used Aroclors 1016 and 1254 as dialectic fluids …
