Coagulopathy In Severe Covid-19 Patients: Causes, Concerns And Current Treatment Regimen,
2024
SSN College of Engineering, Kalavakkam
Coagulopathy In Severe Covid-19 Patients: Causes, Concerns And Current Treatment Regimen, Tanusree Sengupta, Arun Luiz, Chennakesavan Suganthi, Samarpan Majumder
School of Graduate Studies Faculty Publications
Elevated D-dimer and fibrinogen level, mild thrombocytopenia, modest prolongation of prothrombin time, and activated partial thromboplastin time, are key indicators of coagulopathy, and have been consistently reported in severely ill COVID-19 patients. Coronavirus disease 2019 (COVID-19)-induced coagulopathy can develop serious venous and arterial thromboembolic complications. Endothelial dysfunction and hypercoagulability, triggered mostly by overproduction of inflammatory cytokines as an immune response to the infection, are the pivotal factors responsible for the above-mentioned coagulation disorder. Thus, low-molecular-weight heparin (LMWH), which has both anticoagulant and anti-inflammatory properties, has been reported to improve disease prognosis. However, there have been increasing reports of venous thromboembolic …
Structural Basis For Nuclear Import Of Hepatitis B Virus (Hbv) Nucleocapsid Core,
2024
Thomas Jefferson University
Structural Basis For Nuclear Import Of Hepatitis B Virus (Hbv) Nucleocapsid Core, Ruoyu Yang, Ying-Hui Ko, Fenglin Li, Ravi K. Lokareddy, Chun-Feng David Hou, Christine Kim, Shelby Klein, Santiago Antolínez, Juan F. Marín, Carolina Pérez-Segura, Martin F. Jarrold, Adam Zlotnick, Jodi A. Hadden-Perilla, Gino Cingolani
Student Papers, Posters & Projects
Nuclear import of the hepatitis B virus (HBV) nucleocapsid is essential for replication that occurs in the nucleus. The ~360-angstrom HBV capsid translocates to the nuclear pore complex (NPC) as an intact particle, hijacking human importins in a reaction stimulated by host kinases. This paper describes the mechanisms of HBV capsid recognition by importins. We found that importin α1 binds a nuclear localization signal (NLS) at the far end of the HBV coat protein Cp183 carboxyl-terminal domain (CTD). This NLS is exposed to the capsid surface through a pore at the icosahedral quasi-sixfold vertex. Phosphorylation at serine-155, serine-162, and serine-170 …
Exploring The Metabolic And Mitogenic Potential Of A Hyper-Stable Variant Of Fgf1,
2024
University of Arkansas, Fayetteville
Exploring The Metabolic And Mitogenic Potential Of A Hyper-Stable Variant Of Fgf1, Emma Starr, Oshadi Edirisinghe, Thallapuranam Krishnaswamy Suresh Kumar
Inquiry: The University of Arkansas Undergraduate Research Journal
Fibroblast growth factors (FGFs) are a family of 22 human cytokines involved in critical cellular processes, such as proliferation, differentiation, metabolism, angiogenesis, tumor metastasis, and wound healing. Among these, fibroblast growth factor 1 (FGF1) possesses a powerful mitogenic potential as it can nonspecifically bind to all four FGF receptors. However, the therapeutic applications of FGF1 are hindered by its inherent thermal and proteolytic instability, especially at physiological temperatures. This is believed to be attributed to the heparin-binding pocket at the C-terminus, which contains numerous positively charged residues that repel each other. To combat this instability, FGF1 binds to a negatively …
The Complex Protein Analysis Of Purified Extracellular Vesicles In The Study Of Colorectal Cancer,
2024
Belmont University
The Complex Protein Analysis Of Purified Extracellular Vesicles In The Study Of Colorectal Cancer, Renee Boone, Cecilia Osthoff
Science University Research Symposium (SURS)
Proteomics, the study of complex protein mixtures in which liquid chromatography-mass spectrometry (LC-MS) is used to analyze peptide sequences, is commonly utilized to study the double membrane, cell-derived vesicles known as exosomes. Exosomes are double membrane, cell-derived vesicles that contain cell components such as DNA, lipids, and proteins. They function to transport proteins and cellular materials between cells and are involved in the progression and metastasis of cancer. The impact of these extracellular vesicles on cancer spread can be analyzed using proteomics, through the purification of the proteins isolated from the vesicles. The purpose of our research is to analyze …
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 …
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 …
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 …
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 …
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 …
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 …
The Expression Of The Claudin Family Of Proteins In Colorectal Cancer,
2024
University of California - San Diego
The Expression Of The Claudin Family Of Proteins In Colorectal Cancer, Kristin E. Cox, Shanglei Liu, Robert M. Hoffman, Surinder K. Batra, Punita Dhawan, Michael Bouvet
Journal Articles: Biochemistry & Molecular Biology
Claudins (CLDN1-CLDN24) are a family of tight junction proteins whose dysregulation has been implicated in tumorigeneses of many cancer types. In colorectal cancer (CRC), CLDN1, CLDN2, CLDN4, and CLDN18 have been shown to either be upregulated or aberrantly expressed. In the normal colon, CLDN1 and CLDN3-7 are expressed. Although a few claudins, such as CLDN6 and CLDN7, are expressed in CRC their levels are reduced compared to the normal colon. The present review outlines the expression profiles of claudin proteins in CRC and those that are potential biomarkers for prognostication.
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 …
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 …
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 …
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 …
