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Articles 1 - 20 of 20
Full-Text Articles in Amino Acids, Peptides, and Proteins
Enhancement Of Tki Sensitivity In Lung Adenocarcinoma Through M6a-Dependent Translational Repression Of Wnt Signaling By Circ-Fbxw7, Kai Li, Zi Yang Peng, Rui Wang, Xiang Li, Ning Du, Da Peng Liu, Jia Zhang, Yun Feng Zhang, Lei Ma, Ye Sun, Shou Ching Tang, Hong Ren, Yi Ping Yang, Xin Sun
Enhancement Of Tki Sensitivity In Lung Adenocarcinoma Through M6a-Dependent Translational Repression Of Wnt Signaling By Circ-Fbxw7, Kai Li, Zi Yang Peng, Rui Wang, Xiang Li, Ning Du, Da Peng Liu, Jia Zhang, Yun Feng Zhang, Lei Ma, Ye Sun, Shou Ching Tang, Hong Ren, Yi Ping Yang, Xin Sun
School of Medicine Faculty Publications
Background: Tyrosine kinase inhibitors (TKIs) that specifically target mutational points in the EGFR gene have significantly reduced suffering and provided greater relief to patients with lung adenocarcinoma (LUAD). The third-generation EGFR-TKI, Osimertinib, has been successfully employed in clinical treatments to overcome resistance to both original and acquired T790M and L858R mutational points. Nevertheless, the issue of treatment failure response has emerged as an insurmountable problem. Methods: By employing a combination of multiple and integrated approaches, we successfully identified a distinct population within the tumor group that plays a significant role in carcinogenesis, resistance, and recurrence. Our research suggests that addressing …
Targeting Cgas/Sting Signaling-Mediated Myeloid Immune Cell Dysfunction In Time, Vijay Kumar, Caitlin Bauer, John H. Stewart
Targeting Cgas/Sting Signaling-Mediated Myeloid Immune Cell Dysfunction In Time, Vijay Kumar, Caitlin Bauer, John H. Stewart
School of Graduate Studies Faculty Publications
Myeloid immune cells (MICs) are potent innate immune cells serving as first responders to invading pathogens and internal changes to cellular homeostasis. Cancer is a stage of altered cellular homeostasis that can originate in response to different pathogens, chemical carcinogens, and internal genetic/epigenetic changes. MICs express several pattern recognition receptors (PRRs) on their membranes, cytosol, and organelles, recognizing systemic, tissue, and organ-specific altered homeostasis. cGAS/STING signaling is a cytosolic PRR system for identifying cytosolic double-stranded DNA (dsDNA) in a sequence-independent but size-dependent manner. The longer the cytosolic dsDNA size, the stronger the cGAS/STING signaling activation with increased type 1 interferon …
Determining The Genomic Localization And Binding Partners Of Zinc Finger Protein 410, Mariko Locke
Determining The Genomic Localization And Binding Partners Of Zinc Finger Protein 410, Mariko Locke
Senior Honors Theses
The results of a folate deficiency study affecting cognition in mice suggested the altered genes may be controlled by a transcription factor known as Zinc Finger Protein 410 (Zfp410). Due to a lack of literature on Zfp410’s interacting proteins and DNA-binding location, our study aims to further elucidate the role Zfp410 plays in affecting cognition. A custom antibody was used to determine the Zfp410 isoforms present in mouse and rat brains. Moreover, the antibody was used to determine the binding partners of Zfp410 in the brain and locate specific genomic regions/sequences with which it associates in vivo. These results may …
Control Of Antiviral Innate Immune Response By Protein Geranylgeranylation, Shigao Yang, Zhaozhao Jiang, Katherine A. Fitzgerald, Donghai Wang
Control Of Antiviral Innate Immune Response By Protein Geranylgeranylation, Shigao Yang, Zhaozhao Jiang, Katherine A. Fitzgerald, Donghai Wang
Katherine A. Fitzgerald
The mitochondrial antiviral signaling protein (MAVS) orchestrates host antiviral innate immune response to RNA virus infection. However, how MAVS signaling is controlled to eradicate virus while preventing self-destructive inflammation remains obscure. Here, we show that protein geranylgeranylation, a posttranslational lipid modification of proteins, limits MAVS-mediated immune signaling by targeting Rho family small guanosine triphosphatase Rac1 into the mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) at the mitochondria-ER junction. Protein geranylgeranylation and subsequent palmitoylation promote Rac1 translocation into MAMs upon viral infection. MAM-localized Rac1 limits MAVS' interaction with E3 ligase Trim31 and hence inhibits MAVS ubiquitination, aggregation, and activation. Rac1 also facilitates …
Assessment Of Physical Fitness After Bariatric Surgery And Its Association With Protein Intake And Type Of Cholecalciferol Supplementation, Hendrika J M Smelt, Sjaak Pouwels, Alper Celik, Adarsh Gupta, Johannes F Smulders
Assessment Of Physical Fitness After Bariatric Surgery And Its Association With Protein Intake And Type Of Cholecalciferol Supplementation, Hendrika J M Smelt, Sjaak Pouwels, Alper Celik, Adarsh Gupta, Johannes F Smulders
Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship
Background: Several studies showed that there is a relationship between vitamin and mineral status and muscle strength. In particular this is the case for handgrip strength (HS) and vitamin D deficiency. In bariatric surgery there is a risk of decrease in muscle strength after surgery and also vitamin and mineral deficiencies are not uncommon. The aim of this study is to assess the effect of low vitamin 25 (OH) cholecalciferol levels, high dose cholecalciferol supplementation regime and protein intake on physical fitness, measured using handgrip strength (HS) and the shuttle walk run test (SWRT). Methods: For this retrospective …
The Pharmabiotic For Phenylketonuria: Development Of A Novel Therapeutic, Chloé Elizabeth Lebegue
The Pharmabiotic For Phenylketonuria: Development Of A Novel Therapeutic, Chloé Elizabeth Lebegue
Senior Theses
Phenylketonuria, now known as phenylalanine hydroxylase (PAH) deficiency, is a genetic disorder of metabolism affecting approximately one in every 15,000 infants born in the United States. Patients have nonfunctional PAH enzyme secondary to one or more genetic mutations. The enzyme deficit results in destructive supraphysiologic blood phenylalanine levels upon consumption of the essential dietary amino acid phenylalanine. Current standards of care mitigate signs and symptoms of the disorder, but do not approach a cure. The methods for creating a prototype pharmabiotic as an innovative treatment strategy for PAH deficiency are described herein.
DNA molecular cloning techniques were utilized to engineer …
Toward An Enzyme-Coupled, Bioorthogonal Platform For Methyltransferases: Probing The Specificity Of Methionine Adenosyltransferases, Tyler D. Huber
Toward An Enzyme-Coupled, Bioorthogonal Platform For Methyltransferases: Probing The Specificity Of Methionine Adenosyltransferases, Tyler D. Huber
Theses and Dissertations--Pharmacy
Methyl group transfer from S-adenosyl-l-methionine (AdoMet) to various substrates including DNA, proteins, and natural products (NPs), is accomplished by methyltransferases (MTs). Analogs of AdoMet, bearing an alternative S-alkyl group can be exploited, in the context of an array of wild-type MT-catalyzed reactions, to differentially alkylate DNA, proteins, and NPs. This technology provides a means to elucidate MT targets by the MT-mediated installation of chemoselective handles from AdoMet analogs to biologically relevant molecules and affords researchers a fresh route to diversify NP scaffolds by permitting the differential alkylation of chemical sites vulnerable to NP MTs that are unreactive to …
Leucine Supplementation In Cuprizone-Induced Oligodendrocyte Toxicity, Michael Ley
Leucine Supplementation In Cuprizone-Induced Oligodendrocyte Toxicity, Michael Ley
Williams Honors College, Honors Research Projects
Cuprizone is a copper chelator that induces demyelination in the central nervous system when fed to mice. This compound is thought to target Complex IV and disrupt mitochondrial metabolism leading to loss of myelin-producing oligodendrocytes. In this proposal, we further examine the chemical and toxicological properties of cuprizone. Immunofluorescence imaging and microarray data on MO3.13 cells treated with cuprizone revealed the possibility of alterations in lysosomal function, as well as mitochondrial disruption via mTOR and Electron Transport Chain (ETC) related pathways. Cell viability assays conducted suggest that addition of Branched-Chain Amino Acids, most commonly used from literature, leucine, can increase …
Alpha-Amino Methylation And Acetylation Are Novel Regulators Of Myl9 Function., Christopher David Nevitt
Alpha-Amino Methylation And Acetylation Are Novel Regulators Of Myl9 Function., Christopher David Nevitt
Electronic Theses and Dissertations
Dysregulation of alpha-amino post-translational modifications (Nα-PTMs) is found in multiple cancers and developmental disorders. However, the exact roles Nα-PTMs play in regulating protein function remain poorly understood. I sought to clarify the role of Nα-methylation and Nα-acetylation in the regulation of Myosin Regulatory Light Chain 9 (MYL9). MYL9 is a key cytoskeletal regulator and transcription factor and is the first protein confirmed to undergo both Nα-methylation and Nα-acetylation. Through this work I revealed novel regulatory features of MYL9, while also presenting a framework by which to understand the coordinated regulation of proteins by Nα-methylation and Nα-acetylation. Nα-PTM selective mutants of …
Age Drives Distortion Of Brain Metabolic, Vascular And Cognitive Functions, And The Gut Microbiome, Jared D. Hoffman, Ishita Parikh, Stefan J. Green, George Chlipala, Robert P. Mohney, Mignon Keaton, Bjoern Bauer, Anika M. S. Hartz, Ai-Ling Lin
Age Drives Distortion Of Brain Metabolic, Vascular And Cognitive Functions, And The Gut Microbiome, Jared D. Hoffman, Ishita Parikh, Stefan J. Green, George Chlipala, Robert P. Mohney, Mignon Keaton, Bjoern Bauer, Anika M. S. Hartz, Ai-Ling Lin
Sanders-Brown Center on Aging Faculty Publications
Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer’s disease (AD). However, the contribution of aging processes to AD etiology remains unclear. Emerging evidence shows that reduced brain metabolic and vascular functions occur decades before the onset of cognitive impairments, and these reductions are highly associated with low-grade, chronic inflammation developed in the brain over time. Interestingly, recent findings suggest that the gut microbiota may also play a critical role in modulating immune responses in the brain via the brain-gut axis. In this study, our goal was to identify associations between deleterious changes in …
Zn(Ii), Cu(Ii), Sn(Ii), And Ni(Ii) And Other Metal Cations Do Not Prevent The Aggregation Of Hiapp, Charles Hoying
Zn(Ii), Cu(Ii), Sn(Ii), And Ni(Ii) And Other Metal Cations Do Not Prevent The Aggregation Of Hiapp, Charles Hoying
Honors Thesis
The Zn(II) metal ion has been shown to interact with Islet Amyloid Polypeptide (IAPP), a protein implicated in the progression of Type II Diabetes Mellitus, in such a way as to prevent the protein from aggregating into toxic fibers. We set out to find whether other metal ions might similarly prevent IAPP aggregation. Using Thioflavin T (ThT) spectroscopic assays, which measure fluorescence of ThT upon binding to aggregated IAPP, we observed a decrease in aggregation when incubated with Zn(II), Cu(II), Ni(II), and Sn(II). Atomic Force Microscopy (AFM), which can visualize fibril formation, revealed that the metals were not inhibiting IAPP …
Protein Studies: The Function Of Constitutive Androstane Receptor (Car) And Its Associated Ligands, Jacob M. Amburn
Protein Studies: The Function Of Constitutive Androstane Receptor (Car) And Its Associated Ligands, Jacob M. Amburn
Chancellor’s Honors Program Projects
No abstract provided.
Characterization Of Ghrelin O-Acyltransferase Active Site, Leslie Patton
Characterization Of Ghrelin O-Acyltransferase Active Site, Leslie Patton
Honors Capstone Projects - All
Ghrelin, first discovered in 1999, is a 28-amino acid peptide hormone involved in the regulation of appetite, insulin secretion and sensitivity, and many neurological effects such as learning, memory, and depression.1-6 Ghrelin has been identified to have a unique posttranslational octanoylation carried out by the enzyme ghrelin O-acyltransferase (GOAT). This distinctive modification is a point of interest in studying GOAT whereby blocking the acylation of the ghrelin could potentially halt the activity of the peptide hormone and provide a means of treating obesity, diabetes, and other diseases affected by ghrelin levels. The duration of my project involved working …
Biochemical Assay Optimization And Computational Screening Efforts To Identify Potential Luxs Inhibitors, Keeshia Q. Wang
Biochemical Assay Optimization And Computational Screening Efforts To Identify Potential Luxs Inhibitors, Keeshia Q. Wang
Master's Theses
Quorum sensing (QS) is a process of coordination of bacterial gene expression in response to cell population. System two QS is regulated by the small signaling molecule autoinducer-2 (AI-2) and is implicated in the infectious behaviors of various bacterial species. AI-2 is biosynthesized from S-ribosylhomocysteine (SRH) by the enzyme LuxS and induces interspecies cell-to-cell communication. Inhibition of LuxS would therefore inhibit interspecies QS. Herein, a search for novel molecular species that will competitively bind with SRH in the LuxS binding site is performed in silico. Computational screening results are then validated in vitro using an optimized LuxS inhibition …
Radiation-Induced Glutamate Transport Alterations In Neuron-Astrocyte Coupling, Martha Celia Sanchez
Radiation-Induced Glutamate Transport Alterations In Neuron-Astrocyte Coupling, Martha Celia Sanchez
Loma Linda University Electronic Theses, Dissertations & Projects
Exposure of the central nervous system (CNS) to ionizing radiation is known to result in behavioral, cognitive, and motor deficits - effects similar to those seen in many neurodegenerative disorders. Neurons and astrocytes, two principal cell types in the brain, coexist as an interdependent metabolic unit via the neurotransmitter glutamate. Disruption of this metabolic coupling would have widespread effects within the CNS, therefore it is hypothesized that ionizing radiation impairs glutamate transport and metabolism, and increases oxidative stress, ultimately impairing neuron-astrocyte coupling. We propose to investigate the mechanism and determine the impetus for radiation-induced neurotoxicity by measuring the temporal sequence …
Effect Of Monounsaturated Fat Rich Almonds On Hemostatic And Inflammatory Factors In Healthy Adults, Kristianne M. Connell
Effect Of Monounsaturated Fat Rich Almonds On Hemostatic And Inflammatory Factors In Healthy Adults, Kristianne M. Connell
Loma Linda University Electronic Theses, Dissertations & Projects
Background: The frequent consumption of nuts is inversely associated with the incidence of cardiovascular disease. Nuts are known to decrease the risk of cardiovascular disease by reducing serum total and low-density lipoprotein (LDL) cholesterol. Markers of inflammation including C-reactive protein, E-selectin and interleukin-6 have been proposed to be newer risk factors for cardiovascular disease. However, the influence of nuts such as almonds on markers of inflammation and hemostasis that influence cardiovascular disease risk is not currently known.
Objective: The objective of this study was to determine the effect of almond consumption on markers of inflammation and hemostatic factors in healthy …
Glucocorticoid Regulation Of Insulin Like Growth Factor Binding Protein-5 Gene Transcription In Human Osteoblasts, Xiaoying Wang
Glucocorticoid Regulation Of Insulin Like Growth Factor Binding Protein-5 Gene Transcription In Human Osteoblasts, Xiaoying Wang
Loma Linda University Electronic Theses, Dissertations & Projects
Glucocorticoids (GCs) inhibit bone formation in vivo and inhibit osteoblast proliferation and collagen synthesis in vitro. These effects may be mediated by alterations in the insulin-like growth factor (IGF) system. In the present study of normal human osteoblast-like (HOB) cells, we tested the hypothesis that dexamethasone (Dex) inhibits the expression of IGF binding protein-5 (IGFBP-5). Dex decreased IGFBP-5 mRNA levels to 54% of control after 4 hr. Dex did not modify the decay of IGFBP-5 mRNA in transcriptionally arrested osteoblast cells. Dex decreased IGFBP-5 hnRNA levels to 67% of control after 2 hr, and the activity of the human IGFBP- …
Signal Transduction In Bacterial Chemotaxis, Edward Heath Rowsell
Signal Transduction In Bacterial Chemotaxis, Edward Heath Rowsell
Loma Linda University Electronic Theses, Dissertations & Projects
This study investigated the site of ATP utilization in the signal transduction pathway of bacterial chemotaxis and localized the point of convergence of a methylation-independent system of chemotaxis with the methylation-dependent system. The identity of the signal originating from the phosphotransferase system was investigated by substituting the fructose-inducible HPr-like protein FPr for HPr in transport and chemotaxis. In addition, a novel chemoattractant, glycerol, was identified for Salmonella typhimurium. Histidine-auxotrophic S. typhimurium strains ST23 (hisF) and ST171 (hisF cheB) were depleted for ATP. The times required for the bacteria to adapt to a step increase in serine, …
Muscle Catabolism During A Protein Sparing Modified Fast As Measured By Urinary 3-Methylhistidine, Judith D. Nielsen
Muscle Catabolism During A Protein Sparing Modified Fast As Measured By Urinary 3-Methylhistidine, Judith D. Nielsen
Loma Linda University Electronic Theses, Dissertations & Projects
The urinary excretion of 3-Methylhistidine was used as an index of muscle catabolism in four groups of obese persons receiving a Protein Sparing Modified Fast (PSMF). The composition of the supplements were as follows: Group I: 75 g protein, 25 g complex carbohydrate (starch) per day; Group II: 25 g protein, 75 g complex carbohydrate (starch) per day; Group III: 75 g protein, 25 g simple carbohydrate (glucose) per day; Group IV: 25 g protein, 75 g simple carbohydrate (glucose) per day. The PSMF lasted for seven days and a 24-hour urine sample was collected at the beginning of the …
The Effect Of Varying Protein Intake On Trichinella Spiralis Infection In Mice, Clare K. Kwan
The Effect Of Varying Protein Intake On Trichinella Spiralis Infection In Mice, Clare K. Kwan
Loma Linda University Electronic Theses, Dissertations & Projects
Three hundred Swiss Webster albino mice three weeks of age were placed on low (8%), medium (24%), high (48%) protein levels and a commercial laboratory animal feed, Purina Chow for various lengths of time: (1) simultaneously with infection, and four weeks thereafter, (2) three weeks before infection and throughout the four-week infection period, and (3) six weeks prior to infection and during the infection period. The protein source was casein. Sixty of the 300 mice used served as noninfected controls, and the other 240 were each infected with 400 washed, suspended Trichinella spiralis larvae obtained from a rat by the …