The Bach1/Nrf2 Axis In Brain In Down Syndrome And Transition To Alzheimer Disease-Like Neuropathology And Dementia,
2020
Sapienza University of Rome, Italy
The Bach1/Nrf2 Axis In Brain In Down Syndrome And Transition To Alzheimer Disease-Like Neuropathology And Dementia, Marzia Perluigi, Antonella Tramutola, Sara Pagnotta, Eugenio Barone, D. Allan Butterfield
Chemistry Faculty Publications
Down syndrome (DS) is the most common genetic cause of intellectual disability that is associated with an increased risk to develop early-onset Alzheimer-like dementia (AD). The brain neuropathological features include alteration of redox homeostasis, mitochondrial deficits, inflammation, accumulation of both amyloid beta-peptide oligomers and senile plaques, as well as aggregated hyperphosphorylated tau protein-containing neurofibrillary tangles, among others. It is worth mentioning that some of the triplicated genes encoded are likely to cause increased oxidative stress (OS) conditions that are also associated with reduced cellular responses. Published studies from our laboratories propose that increased oxidative damage occurs early in life in …
Alcohol And Smoking Mediated Modulations In Adaptive Immunity In Pancreatitis,
2020
University of Nebraska Medical Center
Alcohol And Smoking Mediated Modulations In Adaptive Immunity In Pancreatitis, Rakesh Bhatia, Christopher Thompson, Koelina Ganguly, Shailender K. Singh, Surinder K. Batra, Sushil Kumar
Journal Articles: Biochemistry & Molecular Biology
Pancreatitis is a condition of pancreatic inflammation driven by injury to the pancreatic parenchyma. The extent of acinar insult, intensity, and type of immune response determines the severity of the disease. Smoking, alcohol and autoimmune pancreatitis are some of the predominant risk factors that increase the risk of pancreatitis by differentially influencing the adaptive immune system. The overall decrease in peripheral lymphocyte (T-, B- and (natural killer T-) NKT-cell) count and increased infiltration into the damaged pancreatic tissue highlight the contribution of adaptive immunity in the disease pathology. Smoking and alcohol modulate the responsiveness and apoptosis of T- and B-cells …
Mg2+-Dependent Methyl Transfer By A Knotted Protein: A Molecular Dynamics Simulation And Quantum Mechanics Study,
2020
University of Warsaw
Mg2+-Dependent Methyl Transfer By A Knotted Protein: A Molecular Dynamics Simulation And Quantum Mechanics Study, Agata P Perlinska, Marcin Kalek, Thomas Christian, Ya-Ming Hou, Joanna I Sulkowska
Department of Biochemistry and Molecular Biology Faculty Papers
Mg2+ is required for the catalytic activity of TrmD, a bacteria-specific methyltransferase that is made up of a protein topological knot-fold, to synthesize methylated m1G37-tRNA to support life. However, neither the location of Mg2+ in the structure of TrmD nor its role in the catalytic mechanism is known. Using molecular dynamics (MD) simulations, we identify a plausible Mg2+ binding pocket within the active site of the enzyme, wherein the ion is coordinated by two aspartates and a glutamate. In this position, Mg2+ additionally interacts with the carboxylate of a methyl donor cofactor S-adenosylmethionine (SAM). The computational results are validated by …
Lyssavirus Vaccine With A Chimeric Glycoprotein Protects Across Phylogroups,
2020
Thomas Jefferson University
Lyssavirus Vaccine With A Chimeric Glycoprotein Protects Across Phylogroups, Christine R Fisher, David E Lowe, Todd G Smith, Yong Yang, Christina L Hutson, Christoph Wirblich, Gino Cingolani, Matthias J. Schnell
Department of Biochemistry and Molecular Biology Faculty Papers
Rabies is nearly 100% lethal in the absence of treatment, killing an estimated 59,000 people annually. Vaccines and biologics are highly efficacious when administered properly. Sixteen rabies-related viruses (lyssaviruses) are similarly lethal, but some are divergent enough to evade protection from current vaccines and biologics, which are based only on the classical rabies virus (RABV). Here we present the development and characterization of LyssaVax, a vaccine featuring a structurally designed, functional chimeric glycoprotein (G) containing immunologically important domains from both RABV G and the highly divergent Mokola virus (MOKV) G. LyssaVax elicits high titers of antibodies specific to both RABV …
Thrombospondin-1 Plays An Essential Role In Yes-Associated Protein Nuclear Translocation During The Early Phase Of Trypanosoma Cruzi Infection In Heart Endothelial Cells,
2020
Meharry Medical College
Thrombospondin-1 Plays An Essential Role In Yes-Associated Protein Nuclear Translocation During The Early Phase Of Trypanosoma Cruzi Infection In Heart Endothelial Cells, Ashutosh Arun, Kayla J. Rayford, Ayorinde Cooley, Girish Rachakonda, Fernando Villalta, Siddharth Pratap, Maria F. Lima, Nader Sheibani, Pius N. Nde
Publications and Research
The protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease. This neglected tropical disease causes severe morbidity and mortality in endemic regions. About 30% of T. cruzi infected individuals will present with cardiac complications. Invasive trypomastigotes released from infected cells can be carried in the vascular endothelial system to infect neighboring and distant cells. During the process of cellular infection, the parasite induces host cells, to increase the levels of host thrombospondin-1 (TSP-1), to facilitate the process of infection. TSP-1 plays important roles in the functioning of vascular cells, including vascular endothelial cells with important implications in cardiovascular …
Sleep-Wake Disturbances In Mild Traumatic Brain Injury: Meta Analysis Of Literature And Modeling Of Cerebral Tissue Vulnerability,
2020
CUNY New York City College of Technology
Sleep-Wake Disturbances In Mild Traumatic Brain Injury: Meta Analysis Of Literature And Modeling Of Cerebral Tissue Vulnerability, Xiangfu Zhang, Subhendra Sarkar, Mary A. Browne
Publications and Research
Sleep disturbance is a frequent complaint for patients with mild traumatic brain injury (mTBI), it can prolong recovery, and the oxidative stress from lack of sleep could worsen other secondary damages of mTBI. The common types of sleep disturbance of mTBI include insomnia, daytime sleepiness, and obstructive sleep apnea. Conventional imaging often fails to detect any abnormalities in mTBI, and the etiology of sleep disturbance is still unclear. Based on the analysis of current published neurobiological and imaging literature, multiple factors could play a role leading to sleep disturbance in mTBI, however, we have focused on the diencephalon, melatonin and …
Molecular Mechanisms Of Manganese Porphyrin Compounds In The Prevention Of Radiation-Induced Fibrosis,
2020
University of Nebraska Medical Center
Molecular Mechanisms Of Manganese Porphyrin Compounds In The Prevention Of Radiation-Induced Fibrosis, Shashank Shrishrimal
Theses & Dissertations
Radiation therapy is frequently used as a treatment strategy for prostate cancer patients, which leads to several side effects due to damage to health tissue around the tumor and the development of radiation-induced fibrosis (RIF). Manganese (III) meso-tetrakis (N-ethylpyridinium-2-yl) porphyrin (MnTE-2-PyP or T2E or BMX-010) and other similar manganese porphyrin compounds that scavenge superoxide molecules have been demonstrated to be effective radioprotectors and prevent the development of RIF. However, understanding of the radioprotective molecular pathway associated with these compounds remains limited. Recent RNA-sequencing data from our laboratory revealed that MnTE-2-PyP treatment may activate the nuclear factor erythroid 2-related factor 2 …
The Effects Of Alpha-Tocopherol And Ascorbic Acid On Metastatic Breast Cancer Cells,
2020
University of Mississippi
The Effects Of Alpha-Tocopherol And Ascorbic Acid On Metastatic Breast Cancer Cells, Scout Treadwell
Honors Theses
Breast cancer is a multifaceted, complex disease that affects hundreds of thousands of patients every year. Although there has a been a decline in the mortality rate of this disease, it is still vital to investigate and discover new possible treatments. One area of research involves the generation of reactive oxygen species (ROS) in cancer cells and the possibility of ROS-induced apoptosis. Antioxidants such as Vitamin C and Vitamin E have been shown to serve as pro-oxidants. Instead of detoxifying the cell from damaging ROS, these compounds can stimulate ROS production, triggering an apoptotic cascade in the cell. In this …
Effects Of Nicotinamide Riboside And Beta-Hydroxybutyrate On C. Elegans Lifespan,
2020
East Tennessee State University
Effects Of Nicotinamide Riboside And Beta-Hydroxybutyrate On C. Elegans Lifespan, Jeffery Peters
Undergraduate Honors Theses
The nicotinamide riboside (NR) form of vitamin B3and the ketone body ß-hydroxybutyrate (BHB) are two of the most promising natural compounds yet identified for the treatment of aging and aging-related diseases. Forms of vitamin B3are precursors for the synthesis of the coenzymes nicotinamide adenine dinucleotide (NAD(H)) and nicotinamide adenine dinucleotide phosphate (NADP(H)). In aged cells levels of NAD+decline, decreasing metabolism and decreasing activity of protective sirtuin protein deacetylases. In aged cells NR, but not more common forms of vitamin B3, boost NAD+levels. BHB is naturally produced by the body when individuals fast …
Gut Pathophysiology In Mouse Models Of Social Behavior Deficits,
2020
East Tennessee State University
Gut Pathophysiology In Mouse Models Of Social Behavior Deficits, Kyla Scott
Undergraduate Honors Theses
Autism spectrum disorders (ASD) encompass neurodevelopment disorders characterized by atypical patterns of development that impact multiple areas of functioning beginning in early childhood. The etiology of ASD is unknown and there are currently no preventative treatment options. Gastrointestinal symptoms are commonly associated comorbidities. The microbiota-gut-brain axis is a multidirectional communication chain that connects the central and enteric nervous system that relates brain function to peripheral intestinal functions. Changes within this axis have been postulated in ASD. For example, the “leaky gut theory” proposes that chronic inflammation is linked to alterations in the bacterial profiles of the gut microbiome and subsequent …
The Determination Of Phosphorylation Of Nato3 By Pka,
2020
Grand Valley State University
The Determination Of Phosphorylation Of Nato3 By Pka, Miranda M. Regenold
Masters Theses
One of the leading regulators of neuronal cell differentiation in the CNS is the family of basic helix–loop–helix (bHLH) transcription factors. One of these proteins, Nato3, is associated with the formation of dopaminergic neurons. Transcription factors can be regulated by kinase activity, and in order to detect the associated change of phosphorylation of Nato3, we have generated Nato3 with specific epitope tags that allow for the detection and isolation of the Nato3 protein. Through subcloning techniques and a successful transformation of the Nato3 gene with the sequences of the 3X-Flag epitope and the Myc epitope into the pcDNA3.0 vector, we …
Alternative Polyadenylation Modulates Expression Of Pro-Fibrotic Proteins And Contributes To Lung Fibrosis,
2020
The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences
Alternative Polyadenylation Modulates Expression Of Pro-Fibrotic Proteins And Contributes To Lung Fibrosis, Junsuk Ko
Dissertations and Theses (Open Access)
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease which affects about 5 to 8 million individuals in the world. Despite the high prevalence, there is currently no cure for IPF, and the cause of this disease is still unclear. Our laboratory and collaborators have shown that nudix hydrolase 21 (NUDT21, which is also known as cleavage factor 25, CFIm25) is a key regulator of alternative polyadenylation (APA). NUDT21 depletion causes 3’UTR shortening via APA leading to enhanced mRNA stability and protein translation. This NUDT21 reduction promotes tumor growth in glioblastoma by enhancing expression of oncogenes. Cancer and IPF share …
Small Extracellular Vesicles Modulated By Αvβ3 Integrin Induce Neuroendocrine Differentiation In Recipient Cancer Cells,
2020
Thomas Jefferson University
Small Extracellular Vesicles Modulated By Αvβ3 Integrin Induce Neuroendocrine Differentiation In Recipient Cancer Cells, Fabio Quaglia, Shiv Ram Krishn, George G. Daaboul, Srawasti Sarker, Raffaella Pippad, Josep Domingo-Domenech, Gaurav Kumar, Paolo Fortina, Peter Mccuee, William K. Kelly, Himisha Beltran, Qin Liu, Lucia R. Languinoa
Department of Biochemistry and Molecular Biology Faculty Papers
The ability of small extracellular vesicles (sEVs) to reprogram cancer cells is well established. However, the specific sEV components able to mediate aberrant effects in cancer cells have not been characterized. Integrins are major players in mediating sEV functions. We have previously reported that the αVβ3 integrin is detected in sEVs of prostate cancer (PαVβ3rCa) cells and transferred into recipient cells. Here, we investigate whether sEVs from -expressing cells affect tumour growth differently than sEVs from control cells that do not express αVβ3. We compared the ability of sEVs to stimulate tumour growth, using sEVs isolated from PrCa C4-2B cells …
Lectin Properties Of Synthetically Produced Glucuronate, Alginate, And Related Boronates,
2020
Andrews University
Lectin Properties Of Synthetically Produced Glucuronate, Alginate, And Related Boronates, Vanessa Angel
Honors Theses
In the nineteenth century, researchers discovered that some proteins had the ability to agglutinate red blood cells (Goldstein, 1980). These proteins were found mainly in the seeds of leguminous plants and were named phytohemagglutinins or hemagglutinins. Particular hemagglutinins were able to agglutinate red blood cells (RBCs) of a specific blood type. Now a days, these proteins are more widely known as Lectins. Lectins are proteinaceous macromolecules of nonimmune origin, capable of interacting with carbohydrates to form complexes (Goldstein, 1980). Lectins sources derive mainly from leguminous plants, animals, fruiting bodies of fungi, and bacteria. This research focuses on identifying the lectin …
Potential Role Of The Large Protein Titin In The Development Of Heart Failure,
2020
University of South Carolina
Potential Role Of The Large Protein Titin In The Development Of Heart Failure, Mary M. Prickett
Senior Theses
I will be exploring the impact of the large protein Titin on heart failure with a preserved ejection fraction (HFpEF). It was hypothesized that myocardial Titin plays a significant role in the progression of HFpEF through isoform, N2BA and N2B, changes. It was hypothesized that an increase in the quantity of N2B Titin, less compliant, and a decrease in N2BA Titin, more compliant, will be observed as HF progresses, contributing to an increase in passive stiffness involved in heart contraction. I will cover a detailed report on the role of Titin in HFpEF and propose research methods to explore further.
Method And System For Identification Of Metabolites Using Mass Spectra,
2020
University of Kentucky
Method And System For Identification Of Metabolites Using Mass Spectra, Hunter N. B. Moseley, William J. Carreer, Joshua Mitchell, Robert M. Flight
Molecular and Cellular Biochemistry Faculty Patents
A method and system is provided for mass spectrometry for identification of a specific elemental formula for an unknown compound which includes but is not limited to a metabolite. The method includes calculating a natural abundance probability (NAP) of a given isotopologue for isotopes of non-labelling elements of an unknown compound. Molecular fragments for a subset of isotopes identified using the NAP are created and sorted into a requisite cache data structure to be subsequently searched. Peaks from raw spectrum data from mass spectrometry for an unknown compound. Sample-specific peaks of the unknown com- pound from various spectral artifacts in …
Prostate Field Cancerization And Exosomes: Association Between Cd9, Early Growth Response 1 And Fatty Acid Synthase,
2020
Chapman University
Prostate Field Cancerization And Exosomes: Association Between Cd9, Early Growth Response 1 And Fatty Acid Synthase, Farideh Amirrad, Philip A. Pytak, Neda Sadeghiani-Pelar, Julie P. T. Nguyen, Emily L. Cauble, Anna C. Jones
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Intracapsular and well‑defined adenocarcinomas of the prostate are often surrounded by tissue areas that harbor molecular aberrations, including those of genetic, epigenetic and biochemical nature. This is known as field cancerization, or a field effect and denotes a state of pre‑malignancy. Such alterations in histologically normal tumor‑adjacent prostatic tissues have been recognized as clinically important and are potentially exploitable as biomarkers of disease and/or targets for preventative/therapeutic intervention. The authors have previously identified and validated two protein markers of field cancerization: The expressional upregulation of the transcription factor early growth response 1 (EGR‑1) and the lipogenic enzyme fatty acid synthase …
Development And Characterization Of A Wee1 Kinase Degrader,
2020
The Texas Medical Center Library
Development And Characterization Of A Wee1 Kinase Degrader, Zhengnian Li, Benika J Pinch, Calla M Olson, Katherine A Donovan, Radosław P Nowak, Caitlin E Mills, David A Scott, Zainab M Doctor, Nicholas A Eleuteri, Mirra Chung, Peter K Sorger, Eric S Fischer, Nathanael S Gray
Faculty, Staff and Students Publications
The G1/S cell cycle checkpoint is frequently dysregulated in cancer, leaving cancer cells reliant on a functional G2/M checkpoint to prevent excessive DNA damage. Wee1 regulates the G2/M checkpoint by phosphorylating CDK1 at Tyr15 to prevent mitotic entry. Previous drug development efforts targeting Wee1 resulted in the clinical-grade inhibitor, AZD1775. However, AZD1775 is burdened by dose-limiting adverse events, and has off-target PLK1 activity. In an attempt to overcome these limitations, we developed Wee1 degraders by conjugating AZD1775 to the cereblon (CRBN)-binding ligand, pomalidomide. The resulting lead compound, ZNL-02-096, degrades Wee1 while sparing PLK1, induces G2/M accumulation at 10-fold lower doses …
Targeting Potential Drivers Of Covid-19: Neutrophil Extracellular Traps.,
2020
Zucker School of Medicine at Hofstra/Northwell
Targeting Potential Drivers Of Covid-19: Neutrophil Extracellular Traps., Bj Barnes, Jm Adrover, A Baxter-Stoltzfus, A Borczuk, J Cools-Lartigue, Jm Crawford, J Daßler-Plenker, P Guerci, A Weber, M Egeblad, +13 Additional Authors
Journal Articles
No abstract provided.
Dysfunctional Mitochondrial Biogenesis: A Potential Underlying Cause For Metabolic Diseases,
2020
Marshall University
Dysfunctional Mitochondrial Biogenesis: A Potential Underlying Cause For Metabolic Diseases, Caroline Ann Hunter
Theses, Dissertations and Capstones
Mitochondria are essential organelles that play crucial roles in many aspects of cellular homeostasis. More importantly, the mitochondria are home to the majority of the metabolic pathways within the cell and are responsible for producing most of the cell’s useable energy in the form of adenine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). In mammals, the majority of OXPHOS complex subunits are encoded by nuclear deoxyribonucleic acid (DNA); however, 13 core subunits essential for the function of OXPHOS complexes I, III, IV, and V are encoded in the mitochondrial (mt) DNA (mtDNA) and are synthesized within the mitochondria by its own …
