Understanding The Function Of Pax5 In Development Of Docetaxel-Resistant Neuroendocrine-Like Prostate Cancers,
2024
University of Nebraska Medical Center
Understanding The Function Of Pax5 In Development Of Docetaxel-Resistant Neuroendocrine-Like Prostate Cancers, Sreyashi Bhattacharya, Hannah Harris, Ridwan Islam, Sanika Bodas, Navatha S. Polavaram, Juhi Mishra, Dipanwita Das, Parthasarathy Seshacharyulu, Achyuth Kalluchi, Anirban Pal, Manish Kohli, Subodh M. Lele, Michael Muders, Surinder K. Batra, Paramita M. Ghosh, Kaustubh Datta, M. Jordan Rowley, Samikshan Dutta
Journal Articles: Biochemistry & Molecular Biology
Resistance to the current Androgen Receptor Signaling Inhibitor (ARSI) therapies has led to higher incidences of therapy-induced neuroendocrine-like prostate cancer (t-NEPC). This highly aggressive subtype with predominant small-cell-like characteristics is resistant to taxane chemotherapies and has a dismal overall survival. t-NEPCs are mostly treated with platinum-based drugs with a combination of etoposide or taxane and have less selectivity and high systemic toxicity, which often limit their clinical potential. During t-NEPC transformation, adenocarcinomas lose their luminal features and adopt neuro-basal characteristics. Whether the adaptive neuronal characteristics of t-NEPC are responsible for such taxane resistance remains unknown. Pathway analysis from patient gene-expression …
Enhancing Translation: A Need To Leverage Complex Preclinical Models Of Addictive Drugs To Accelerate Substance Use Treatment Options,
2024
University of Kentucky
Enhancing Translation: A Need To Leverage Complex Preclinical Models Of Addictive Drugs To Accelerate Substance Use Treatment Options, Christa Corley, Ashley Craig, Safiyah M. Sadek, Julie A. Marusich, Samar N. Chehimi, Ashley M. White, Lexi J. Holdiness, Benjamin C. Reiner, Cassandra D. Gipson
Markey Cancer Center Faculty Publications
Preclinical models of addictive drugs have been developed for decades to model aspects of the clinical experience in substance use disorders (SUDs). These include passive exposure as well as volitional intake models across addictive drugs and have been utilized to also measure withdrawal symptomatology and potential neuro- behavioral mechanisms underlying relapse to drug seeking or taking. There are a number of Food and Drug Administration (FDA)-approved medications for SUDs, however, many demonstrate low clinical efficacy as well as potential sex differences, and we also note gaps in the continuum of care for certain aspects of clinical ex- periences in individuals …
Ftsk Regulates The Assembly Of The Division Machinery In The Ftsz-Less Chlamydia Trachomatis,
2024
University of Tennessee Health Science Center
Ftsk Regulates The Assembly Of The Division Machinery In The Ftsz-Less Chlamydia Trachomatis, Mckenna Katherine Harpring
Theses and Dissertations (ETD)
In evolving to obligate intracellular dependence, Chlamydia trachomatis serovar L2 (Ct), has eliminated several gene products essential for cell division in most other bacteria, including FtsZ, the central coordinator of divisome assembly. In the absence of FtsZ, we show that divisome assembly in Ct is initiated by FtsK, a chromosomal translocase. Chlamydial FtsK forms discrete foci at the septum and at the base of the progenitor mother cell, and our data indicate that FtsK foci at the base of the mother cell mark the location of nascent divisome complexes that form at the site where a daughter cell will emerge …
The Role Of Uric Acid In Metabolic Abnormalities Of Obesity,
2024
West Virginia University School of Medicine
The Role Of Uric Acid In Metabolic Abnormalities Of Obesity, Andrew P. Giromini
Graduate Theses, Dissertations, and Problem Reports (ETD)
Uric acid (UA) is the single most tightly associated metabolite for obesity and type 2 diabetes. While the field varies on whether UA is causative or correlative of the metabolic dysfunction allied to obesity, these studies use different diets and animal models to make these claims. It is the goal of this dissertation to compare different diets commonly used in this research to delve deeper into the data and determine which diets induce elevated circulating UA levels as well as which diets also induce metabolic dysfunction. Early chapters of this dissertation examine the comparison of high fructose consumption, both in …
Exploring The Skin Microbiome Of Alopecic Cynomolgus Macaques (Macaca Fascicularis) Based On Oxford Nanopore Technologies,
2024
Faculty of Medicine
Exploring The Skin Microbiome Of Alopecic Cynomolgus Macaques (Macaca Fascicularis) Based On Oxford Nanopore Technologies, Natthanit Phokkhasub
Chulalongkorn University Theses and Dissertations (Chula ETD)
Alopecia or hair loss in captive non-human primates (NHPs) such as cynomolgus macaques is a major concern of animal welfare in many primate facilities. The purpose of this study is to investigate the association between alopecic and healthy skin microbiome in cynomolgus macaques. This study included skin swab samples (head, arm, leg, ventral, and dorsal areas) collected from 33 healthy and 50 alopecic macaques housed at the NPRCT-CU. LEfSe analysis revealed the significant bacteria found in multiple areas of the alopecic group, including P. copri and L. animalis. The significant fungi found in double areas (arm-dorsal, dorsal-head, and leg-ventral) of …
Roles Of Mtor Complex 2 Signaling In The Sphingolipid Production Of Brain Cancer Cell Lines,
2024
Faculty of Medicine
Roles Of Mtor Complex 2 Signaling In The Sphingolipid Production Of Brain Cancer Cell Lines, Nuanwan Songcharoen
Chulalongkorn University Theses and Dissertations (Chula ETD)
Gliomas, which include low- and high-grade types, represent a particularly aggressive form of primary brain tumor, especially glioblastoma (GBM). Metabolic reprogramming in lipid metabolism supports cell proliferation; alterations in the sphingolipid pathway, elevated glucosylceramide (GlcCer) levels through glucosylceramide synthase (GCS), promote the production of glycosphingolipids, which serve as building blocks for cancer cells. Furthermore, mTORC2, which is a kinase protein, contributes to lipid metabolism. Thus, the study aims to investigate the roles of mTORC2 signaling in lipid metabolism through lipid accumulation, which was reduced with AZD8055 treatment as the mTORC2 inhibitor. Additionally, p-AKT (S473), which is downstream of mTORC2, was …
Immunotherapeutic Properties Of Virus Like Particles Displaying Allergens In A Mouse Model Of House Dust Mite Allergy,
2024
Faculty of Medicine
Immunotherapeutic Properties Of Virus Like Particles Displaying Allergens In A Mouse Model Of House Dust Mite Allergy, Piyachat Patniboon
Chulalongkorn University Theses and Dissertations (Chula ETD)
House dust mite (HDM) represents one of the most prominent sources of allergens. The rising prevalence of HDM-induced allergic diseases such as allergic rhinitis, allergic asthma or atopic dermatitis is a major global health challenge. Allergen immunotherapy (AIT), by frequent administrations of HDM allergen extracts, is the unique treatment capable of alleviating the Th2-biased allergic response through the induction of immune tolerance. However, AIT faces limitations in terms of duration, efficacy and safety, explaining the poor patient adherence. Clinical efficacy of HDM extract-based AIT was shown to be dependent on the selection of patients sensitized to the two major HDM …
Depletion Of Oxalate In High-Oxalate Beverages By Positively Charged Particles,
2024
Faculty of Medicine
Depletion Of Oxalate In High-Oxalate Beverages By Positively Charged Particles, Sukrita Aungsuthan
Chulalongkorn University Theses and Dissertations (Chula ETD)
Excessive dietary intake of oxalate is a key risk factor of calcium oxalate (CaOx) nephrolithiasis. Therefore, limiting daily oxalate intake is recommended to prevent CaOx stone formation. Black tea and coffee are commonly consumed beverages that are rich in oxalate, and avoidance of tea and coffee consumption is relatively hard. In this study, therefore, we aimed to develop a novel tool for depleting oxalate in black tea and coffee. Since oxalate is negatively charged, we hypothesized that positively charged particles would be an effective tool for capturing and removing oxalate. Hydroxyapatite (HA) and calcium alginate (Ca-Alg) beads were fabricated and …
Effects Of Dimerization On The Deacylase Activities Of Human Sirt2.,
2023
Rowan University
Effects Of Dimerization On The Deacylase Activities Of Human Sirt2., Jie Yang, Nathan I Nicely, Brian P Weiser
Rowan-Virtua School of Osteopathic Medicine Departmental Research
Human sirtuin isoform 2 (SIRT2) is an NAD+-dependent enzyme that functions as a lysine deacetylase and defatty-acylase. Here, we report that SIRT2 readily dimerizes in solution and in cells and that dimerization affects its ability to remove different acyl modifications from substrates. Dimerization of recombinant SIRT2 was revealed with analytical size exclusion chromatography and chemical cross-linking. Dimerized SIRT2 dissociates into monomers upon binding long fatty acylated substrates (decanoyl-, dodecanoyl-, and myristoyl-lysine). However, we did not observe dissociation of dimeric SIRT2 in the presence of acetyl-lysine. Analysis of X-ray crystal structures led us to discover a SIRT2 double mutant (Q142A/E340A) that …
Hnf4Α Isoforms Regulate The Circadian Balance Between Carbohydrate And Lipid Metabolism In The Liver,
2023
The Texas Medical Center Library
Hnf4Α Isoforms Regulate The Circadian Balance Between Carbohydrate And Lipid Metabolism In The Liver, Jonathan R Deans, Poonamjot Deol, Nina Titova, Sarah H Radi, Linh M Vuong, Jane R Evans, Songqin Pan, Johannes Fahrmann, Jun Yang, Bruce D Hammock, Oliver Fiehn, Baharan Fekry, Kristin Eckel-Mahan, Frances M Sladek
Faculty, Staff and Student Publications
Hepatocyte Nuclear Factor 4α (HNF4α), a master regulator of hepatocyte differentiation, is regulated by two promoters (P1 and P2) which drive the expression of different isoforms. P1-HNF4α is the major isoform in the adult liver while P2-HNF4α is thought to be expressed only in fetal liver and liver cancer. Here, we show that P2-HNF4α is indeed expressed in the normal adult liver at Zeitgeber time (ZT)9 and ZT21. Using exon swap mice that express only P2-HNF4α we show that this isoform orchestrates a distinct transcriptome and metabolome via unique chromatin and protein-protein interactions, including with different clock proteins at different …
Investigating The Role Of Maternal Adiposity On Human Breast Milk And Preterm Infant Stool Short Chain Fatty Acid And Microbiome Profiles,
2023
East Tennessee State University
Investigating The Role Of Maternal Adiposity On Human Breast Milk And Preterm Infant Stool Short Chain Fatty Acid And Microbiome Profiles, Kristy L. Thomas
Electronic Theses and Dissertations
Preterm birth is the number one cause of death in neonates, accounting for 35% of neonatal mortality. The preterm birth rate in the U.S. in 2021 was 10.5%, disproportionally affected by race and ethnicity. Obese women have an increased risk of preterm pregnancy, and if delivered before 37 weeks of gestation, the offspring have higher rates of complications that extend from the neonatal period into life-long metabolic and immune adverse outcomes. In the early months after delivery, preterm infants have higher rates of adverse health outcomes than term infants, including infections, extrauterine growth restrictions, respiratory, metabolic, and neurological complications, necrotizing …
Design Of An Fgf-1-Fgf-2 Heterodimer Variant With Enhanced Stability And Cell Proliferation Activity,
2023
University of Arkansas, Fayetteville
Design Of An Fgf-1-Fgf-2 Heterodimer Variant With Enhanced Stability And Cell Proliferation Activity, Nicholas Alan Pohlman
Chemistry & Biochemistry Undergraduate Honors Theses
The FGF-1 subfamily, composed of FGF-1 and FGF-2, assists in broad health-related processes such as cell proliferation and angiogenesis respectively.1,2 The subfamily shows promising signs as a therapeutic, however, the inherent thermal instability leads to a low half-life in vivo.3 To assist in improving the stability, FGF-1 and FGF-2 were connected via a 12-residue glycine linker ultimately producing a heterodimer. This heterodimer was further examined to discover its novel properties. Inspiration for this project was drawn from previous research which performed five mutations on FGF-1 ultimately improving stability in the protein complex. In addition to these five …
Localization, Tissue Biology, And T Cell State — Implications For Cancer Immunotherapy,
2023
The Texas Medical Center Library
Localization, Tissue Biology, And T Cell State — Implications For Cancer Immunotherapy, Jason M Schenkel, Kristen E Pauken
Faculty, Staff and Student Publications
Tissue localization is a critical determinant of T cell immunity. CD8+ T cells are contact-dependent killers, which requires them to physically be within the tissue of interest to kill peptide-MHC class I-bearing target cells. Following their migration and extravasation into tissues, T cells receive many extrinsic cues from the local microenvironment, and these signals shape T cell differentiation, fate and function. Because major organ systems are variable in their functions and compositions, they apply disparate pressures on T cells to adapt to the local microenvironment. Additional complexity arises in the context of malignant lesions (either primary or metastatic), and this …
Loss Of The Methylarginine Reader Function Of Snd1 Confers Resistance To Hepatocellular Carcinoma,
2023
The Texas Medical Center Library
Loss Of The Methylarginine Reader Function Of Snd1 Confers Resistance To Hepatocellular Carcinoma, Tanner Wright, Yalong Wang, Sabrina A Stratton, Manu Sebastian, Bin Liu, David G Johnson, Mark T Bedford
Faculty, Staff and Student Publications
Staphylococcal nuclease Tudor domain containing 1 (SND1) protein is an oncogene that 'reads' methylarginine marks through its Tudor domain. Specifically, it recognizes methylation marks deposited by protein arginine methyltransferase 5 (PRMT5), which is also known to promote tumorigenesis. Although SND1 can drive hepatocellular carcinoma (HCC), it is unclear whether the SND1 Tudor domain is needed to promote HCC. We sought to identify the biological role of the SND1 Tudor domain in normal and tumorigenic settings by developing two genetically engineered SND1 mouse models, an Snd1 knockout (Snd1 KO) and an Snd1 Tudor domain-mutated (Snd1 KI) mouse, whose mutant SND1 can …
“Cost-Effective Markers To Identify Metabolically Healthy/Unhealthy Individuals And Their Future Risk For Cardiovascular Disorders”,
2023
JSS Medical College, JSSAHER, Mysuru
“Cost-Effective Markers To Identify Metabolically Healthy/Unhealthy Individuals And Their Future Risk For Cardiovascular Disorders”, Shobha C Ramachandra, Akila Prashant, Akshitha Shivanna, Ananth Koushik Bhujanga, Syeda Meherunnisa, Prashant Vishwanath
International Journal of Health and Allied Sciences
Background: With the rising prevalence of metabolically healthy obese, it becomes essential to identify markers to differentiate them from metabolically unhealthy obese and their future risk for cardiovascular disorders (CVD). The study aims to identify suitable markers for risk stratification of metabolically healthy/unhealthy individuals and their risk for CVD. Method: Total 84 individuals aged 18-60 years of age without any comorbidities were enrolled. Their demographic details along with anthropometric measurements were noted. The biochemical parameters like fasting glucose, insulin, lipid profile, and serum adipokines were estimated. Insulin resistance (IR) markers and atherogenic indices were calculated. The data were analyzed on …
Conformational Ensemble-Dependent Lipid Recognition And Segregation By Prenylated Intrinsically Disordered Regions In Small Gtpases,
2023
The Texas Medical Center Library
Conformational Ensemble-Dependent Lipid Recognition And Segregation By Prenylated Intrinsically Disordered Regions In Small Gtpases, Mussie K Araya, Alemayehu A Gorfe
Faculty, Staff and Student Publications
We studied diverse prenylated intrinsically disordered regions (PIDRs) of Ras and Rho family small GTPases using long timescale atomistic molecular dynamics simulations in an asymmetric model membrane of phosphatidylcholine (PC) and phosphatidylserine (PS) lipids. Here we show that conformational plasticity is a key determinant of lipid sorting by polybasic PIDRs and provide evidence for lipid sorting based on both headgroup and acyl chain structures. We further show that conformational ensemble-based lipid recognition is generalizable to all polybasic PIDRs, and that the sequence outside the polybasic domain (PBD) modulates the conformational plasticity, bilayer adsorption, and interactions of PIDRs with membrane lipids. …
The Effect Of Heat-Moisture Treatment Changed The Binding Of Starch, Protein And Lipid In Rice Flour To Affect Its Hierarchical Structure And Physicochemical Properties,
2023
The Texas Medical Center Library
The Effect Of Heat-Moisture Treatment Changed The Binding Of Starch, Protein And Lipid In Rice Flour To Affect Its Hierarchical Structure And Physicochemical Properties, Seung Hee Yoo, Mi Jin Jue, Yu-Hee Kim, Sooyoung Cho, Won-Joong Kim, Kye-Min Kim, Jong In Han, Heeseung Lee
Faculty, Staff and Student Publications
Dexmedetomidine prevents postoperative cognitive dysfunction by inhibiting high-mobility group box 1 (HMGB1), which acts as an inflammatory marker. This study investigated the HMGB1 levels and the cognitive function using a Mini-Cog© score in elderly patients undergoing orthopedic surgery with dexmedetomidine infusion. In total, 128 patients aged ≥ 65 years were analyzed. The patients received saline in the control group and dexmedetomidine in the dexmedetomidine group until the end of surgery. Blood sampling and the Mini-Cog© test were performed before the surgery and on postoperative days 1 and 3. The primary outcomes were the effect of dexmedetomidine on the HMGB1 levels …
On A Sugar High: Role Of O-Glcnacylation In Cancer,
2023
Thomas Jefferson University
On A Sugar High: Role Of O-Glcnacylation In Cancer, Giang Le Minh, Emily M. Esquea, Riley G. Young, Jessie Huang, Mauricio J. Reginato
Kimmel Cancer Center Papers, Presentations, and Grand Rounds
Recent advances in the understanding of the molecular mechanisms underlying cancer progression have led to the development of novel therapeutic targeting strategies. Aberrant glycosylation patterns and their implication in cancer have gained increasing attention as potential targets due to the critical role of glycosylation in regulating tumor-specific pathways that contribute to cancer cell survival, proliferation, and progression. A special type of glycosylation that has been gaining momentum in cancer research is the modification of nuclear, cytoplasmic, and mitochondrial proteins, termed O-GlcNAcylation. This protein modification is catalyzed by an enzyme called O-GlcNAc transferase (OGT), which uses the final product of the …
Novel Therapy Targeting Mutant-Krasg12d And Galectin-1 In Pancreatic Cancer,
2023
The University of Texas Rio Grande Valley
Novel Therapy Targeting Mutant-Krasg12d And Galectin-1 In Pancreatic Cancer, Ana I. Martinez Bulnes, Nirnoy Dan, Poornima Devi Shaji, Swathi Holla, Murali M. Yallapu, Sheema Khan
Research Colloquium
Introduction: Although, surgical resection and chemotherapy are the gold standard for treating Pancreatic Ductal Adenocarcinoma (PDAC), low patient survival rate remains the problem. The activating point mutation of the KRAS on codon-12 is present in 70–95% of PDAC cases and so far, no success has been achieved to inhibit KRAS. KRASG12D regulates cell proliferation, differentiation, apoptosis. Recent preliminary and published studies show high Galectin-1 (Gal-1) levels in both pancreatic cancer and stromal cells, which modulate tumor microenvironment and metastasis. Additionally, genetic deletion of gal1 inhibits metastasis and improves survival in KRAS mouse model of PDAC (1). Therefore, our objective is …
Molecular And Biochemical Analysis Of Cytochrome P450 2c19 And 2d6,
2023
United Arab Emirates University
Molecular And Biochemical Analysis Of Cytochrome P450 2c19 And 2d6, Reema Saleous
Theses
Pharmacogenomics (PGx) is a relatively new field of study. It links genetics to pharmacology since it deals with the influence of the genetic makeup of the individual on their ability to respond to specific medications. Some of the most important genes in this field, dubbed very important pharmacogenes (VIPs), belong to the cytochrome P450 (CYP) superfamily of drug metabolizing enzymes. The two members of this family that are the main focus of this thesis are CYP2C19 and CYP2D6. They play major roles in the metabolism of numerous medications, and it is therefore imperative that variations within those genes in various …
