Interaction And Regulation Between Lipid Mediator Phosphatidic Acid And Circadian Clock Regulators,
2019
University of Missouri–St. Louis
Interaction And Regulation Between Lipid Mediator Phosphatidic Acid And Circadian Clock Regulators, Sang-Chul Kim, Sang-Chul Kim, Dmitri Nusinow, Maria Sorkin, Maria Sorkin, Jose Pruneda-Paz, Xuemin Wang, Xuemin Wang
Biology Department Faculty Works
Circadian clocks play important roles in regulating cellular metabolism, but the reciprocal effect that metabolism has on the clock is largely unknown in plants. Here we show that the central glycerolipid metabolite and lipid mediator phosphatidic acid (PA) interacts with and modulates the function of the core clock regulators LATE ELONGATED HYPOCOTYL (LHY) and CIRCADIAN CLOCK ASSOCIATED1 (CCA1) in Arabidopsis thaliana. PA reduced the ability of LHY and CCA1 to bind the promoter of their target gene TIMING OF CAB EXPRESSION1. Increased PA accumulation and inhibition of PA-producing enzymes had opposite effects on circadian clock outputs. Diurnal change in levels …
Composition Of The Survival Motor Neuron (Smn) Complex In Drosophila Melanogaster,
2019
University of North Carolina at Chapel Hill
Composition Of The Survival Motor Neuron (Smn) Complex In Drosophila Melanogaster, A. Gregory Matera, Amanda C. Raimer, Casey A. Schmidt, Jo A. Kelly, Gaith N. Droby, David Baillat, Sara Ten Have, Angus I. Lamond, Eric J. Wagner, Kelsey M. Gray
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Spinal Muscular Atrophy (SMA) is caused by homozygous mutations in the human survival motor neuron 1 (SMN1) gene. SMN protein has a well-characterized role in the biogenesis of small nuclear ribonucleoproteins (snRNPs), core components of the spliceosome. SMN is part of an oligomeric complex with core binding partners, collectively called Gemins. Biochemical and cell biological studies demonstrate that certain Gemins are required for proper snRNP assembly and transport. However, the precise functions of most Gemins are unknown. To gain a deeper understanding of the SMN complex in the context of metazoan evolution, we investigated its composition in Drosophila …
Exploring The Ipf Lung Through The Lens Of Single Cell Rna Sequencing,
2019
Yale School of Medicine
Exploring The Ipf Lung Through The Lens Of Single Cell Rna Sequencing, Taylor Adams, Jonas Schupp
Yale Day of Data
This poster illustrates the differences between the IPF disease-specific variety of lung macrophages and the two varieties of macrophages known to reside in the normal human lung.
Deletion Of Mgr2p Affects The Gating Behavior Of The Tim23 Complex,
2019
CUNY Bernard M Baruch College
Deletion Of Mgr2p Affects The Gating Behavior Of The Tim23 Complex, Oygul Mirzalieva, Shinhye Jeon, Kevin Damri, Ruth Hartke, Layla Drwesh, Keren Demishtein-Zohary, Abdussalam Azem, Cory D. Dunn, Pablo M. Peixoto
Publications and Research
The TIM23 complex is a hub for translocation of preproteins into or across the mitochondrial inner membrane. This dual sorting mechanism is currently being investigated, and in yeast appears to be regulated by a recently discovered subunit, the Mgr2 protein. Deletion of Mgr2p has been found to delay protein translocation into the matrix and accumulation in the inner membrane. This result and other findings suggested that Mgr2p controls the lateral release of inner membrane proteins harboring a stop-transfer signal that follows an N-terminal amino acid signal. However, the mechanism of lateral release is unknown. Here, we used patch clamp electrophysiology …
Molecular Switch Model For Cardiomyocyte Proliferation,
2019
Aga Khan University
Molecular Switch Model For Cardiomyocyte Proliferation, Satwat Hashmi, H R. Ahmad
Department of Biological & Biomedical Sciences
This review deals with the human adult cardiomyocyte proliferation as a potential source for heart repair after injury. The mechanism to regain the proliferative capacity of adult cardiomyocytes is a challenge. However, recent studies are promising in showing that the 'locked' cell cycle of adult cardiomyocytes could be released through modulation of cell cycle checkpoints. In support of this are the signaling pathways of Notch, Hippo, Wnt, Akt and Jak/Stat that facilitate or inhibit the transition at cell cycle checkpoints. Cyclins and cyclin dependant kinases (CDKs) facilitate this transition which in turn is regulated by inhibitory action of pocket protein …
Cyclin C: The Story Of A Non-Cycling Cyclin,
2019
Rowan University
Cyclin C: The Story Of A Non-Cycling Cyclin, Jan Jezek, Daniel G J Smethurst, David C Stieg, Z A C Kiss, Sara E Hanley, Vidyaramanan Ganesan, Kai-Ti Chang, Katrina F Cooper, Randy Strich
Rowan-Virtua School of Osteopathic Medicine Departmental Research
The class I cyclin family is a well-studied group of structurally conserved proteins that interact with their associated cyclin-dependent kinases (Cdks) to regulate different stages of cell cycle progression depending on their oscillating expression levels. However, the role of class II cyclins, which primarily act as transcription factors and whose expression remains constant throughout the cell cycle, is less well understood. As a classic example of a transcriptional cyclin, cyclin C forms a regulatory sub-complex with its partner kinase Cdk8 and two accessory subunits Med12 and Med13 called the Cdk8-dependent kinase module (CKM). The CKM reversibly associates with the multi-subunit …
The Phytoremediative Effects Of Cilantro (Coriandrum Sativum) In Lead Contaminated Soil,
2019
Southern Adventist University
The Phytoremediative Effects Of Cilantro (Coriandrum Sativum) In Lead Contaminated Soil, Sierra D. Garrett, Timothy D. Trott
Research in Biology
Environmental exposure to heavy metals such as lead pose a significant health threat. The goal of this project was to evaluate the effectiveness of Coriandrum sativum (Cilantro) as a potential lead (II), Pb2+, phytoremediator. C. sativumplants were allowed to grow for 43 days while exposed to with different amounts of lead nitrate, Pb(NO3)2. Lead exposure was accomplished by regular watering with a concentration series of lead nitrate solutions. The roots and shoots of these plants were separated and dried. Ground plant material was liquefied by nitric acid digestion. The amount of lead absorbed …
Insights Into The Ribosomal, Extra-Ribosomal And Developmental Role Of Rp L13a In Mammalian Model,
2019
Cleveland State University
Insights Into The Ribosomal, Extra-Ribosomal And Developmental Role Of Rp L13a In Mammalian Model, Ravinder Kour
ETD Archive
Ribosomal protein L13a plays an extra-ribosomal function in translational silencing of GAIT (IFN-gamma-activated inhibitor of translation) element bearing mRNAs encoding inflammatory proteins but the underlying molecular mechanism of translational silencing and ribosomal incorporation of L13a remains poorly understood. Also, our laboratory showed that L13a acts as a physiological defense against uncontrolled inflammation in macrophage-specific knockout (KO) mice. However, the consequence of a total knockout of L13a in mammals remains unexplored. Therefore, our current study is focused on (i) identifying the amino acid residue(s) of L13a essential for incorporation and translational silencing of target mRNAs and (ii) studying the consequences of …
Systemic Inhibition Of Tissue-Nonspecific Alkaline Phosphatase Alters The Brain-Immune Axis In Experimental Sepsis,
2019
West Virginia University
Systemic Inhibition Of Tissue-Nonspecific Alkaline Phosphatase Alters The Brain-Immune Axis In Experimental Sepsis, Allison L. Brichacek, Stanely A. Benkovic, Sreeparna Chakraborty, Divine C. Nwafor, Wei Wang, Sujung Jun, Duaa Dakhlallah, Werner Geldenhuys, Anthony B. Pinkerton, José Luis Millán, Candice M. Brown
Faculty & Staff Scholarship
Tissue-nonspecific alkaline phosphatase (TNAP) is a ubiquitous enzyme present in many cells and tissues, including the central nervous system. Yet its functions at the brain-immune axis remain unclear. The goal of this study was to use a novel small molecular inhibitor of TNAP, SBI-425, to interrogate the function of TNAP in neuroimmune disorders. Following intraperitoneal (IP) administration of SBI-425, mass spectrometry analysis revealed that the SBI-425 does not cross the blood-brain barrier (BBB) in healthy mice. To elucidate the role of TNAP at the brain-immune axis, mice were subjected to experimental sepsis and received either vehicle or SBI-425 (25 mg/kg, …
Enhancement Of Immune Response Against Bordetella Spp. By Disrupting Immunomodulation,
2019
University of Georgia
Enhancement Of Immune Response Against Bordetella Spp. By Disrupting Immunomodulation, Monica C. Gestal, Laura K. Howard, Kalyan Dewan, Hannah M. Johnson, Mariette Barbier, Clare Bryant, Illiassou Hamidou Soumana, Israel Rivera, Bodo Lina, Uriel Blas-Machado, Eric T. Harvill
Faculty & Staff Scholarship
Well-adapted pathogens must evade clearance by the host immune system and the study of how they do this has revealed myriad complex strategies and mechanisms. Classical bordetellae are very closely related subspecies that are known to modulate adaptive immunity in a variety of ways, permitting them to either persist for life or repeatedly infect the same host. Exploring the hypothesis that exposure to immune cells would cause bordetellae to induce expression of important immunomodulatory mechanisms, we identified a putative regulator of an immunomodulatory pathway. The deletion of btrS in B. bronchiseptica did not affect colonization or initial growth in the …
The Role Of The Cell-Surface Protease Tmprss13 In Colorectal Cancer,
2019
Wayne State University
The Role Of The Cell-Surface Protease Tmprss13 In Colorectal Cancer, Fausto Alexander Varela
Wayne State University Dissertations
Colorectal cancer (CRC) is one of the most common and deadly cancers in both men and women in the United States. Extracellular proteolysis is often dysregulated in cancer including (CRC), resulting in degradation of extracellular matrix, as well as cleavage, processing, or shedding of cell adhesion molecules, growth factors, and cytokines. Several members of the type II transmembrane serine protease (TTSP) family have been shown to play critical roles in cancer progression; however, many family members have not yet been characterized in malignancy. We identified TMPRSS13 transcript to be upregulated in CRC compared to normal colon. This increase was confirmed …
Cornus Officinalis Significantly Improves Oxidative Capacity And Promotes The Calcium-Dependent Transcription Factor, Nfatc2, In Human 1.1b4 Pancreatic Cell Line,
2019
University of South Florida
Cornus Officinalis Significantly Improves Oxidative Capacity And Promotes The Calcium-Dependent Transcription Factor, Nfatc2, In Human 1.1b4 Pancreatic Cell Line, Arielle Sharp, Alexis Coiner, Brant Burkhardt
Molecular Biosciences Faculty Publications
Type 1 diabetes (T1D) is an autoimmune disease resulting in the destruction of pancreatic β cells (β-cells) and subsequent loss of insulin production. The only treatment for T1D is using exogenous insulin coupled with continual glucose monitoring following significant autoimmune destruction of β-cells. Novel interventional therapies are needed that can preserve and protect existing pancreatic β cells in individuals with early identified T1D autoimmunity. Our initial in-vitro evidence indicates Cornus officinalis (CO) may be able to serve in this function. What sets ethnopharmacology apart from conventional medicine is the simultaneous targeting of multiple mechanisms using a single herb due to …
Structural Basis Of Phosphatidylcholine Recognition By The C2–Domain Of Cytosolic Phospholipase A,2Α,
2019
Nara Institute of Science and Technology
Structural Basis Of Phosphatidylcholine Recognition By The C2–Domain Of Cytosolic Phospholipase A,2Α, Yoshinori Hirano, Yong-Guang Gao, Daniel J. Stephenson, Ngoc T. Vu, Lucy Malinina, Dhirendra K. Simanshu, Charles E. Chalfant, Dinshaw J. Patel, Rhoderick E. Brown
Molecular Biosciences Faculty Publications
Ca2+-stimulated translocation of cytosolic phospholipase A2α (cPLA2α) to the Golgi induces arachidonic acid production, the rate-limiting step in pro-inflammatory eicosanoid synthesis. Structural insights into the cPLA2α preference for phosphatidylcholine (PC)-enriched membranes have remained elusive. Here, we report the structure of the cPLA2α C2-domain (at 2.2 Å resolution), which contains bound 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC) and Ca2+ ions. Two Ca2+ are complexed at previously reported locations in the lipid-free C2-domain. One of these Ca2+ions, along with a third Ca2+, bridges the C2-domain to the DHPC phosphate group, which also interacts with Asn65. Tyr96 plays a key role in lipid …
Conserved Glycines Control Disorder And Function In The Cold-Regulated Protein, Cor15a,
2019
University of South Florida
Conserved Glycines Control Disorder And Function In The Cold-Regulated Protein, Cor15a, Oluwakemi T. Sowemimo, Patrick Knox-Brown, Wade M. Borcherds, Tobias Rindfleisch, Anja Thalhammer, Gary W. Daughdrill
Molecular Biosciences Faculty Publications
Cold-regulated (COR) 15A is an intrinsically disordered protein (IDP) from Arabidopsis thaliana important for freezing tolerance. During freezing-induced cellular dehydration, COR15A transitions from a disordered to mostly α-helical structure. We tested whether mutations that increase the helicity of COR15A also increase its protective function. Conserved glycine residues were identified and mutated to alanine. Nuclear magnetic resonance (NMR) spectroscopy was used to identify residue-specific changes in helicity for wildtype (WT) COR15A and the mutants. Circular dichroism (CD) spectroscopy was used to monitor the coil–helix transition in response to increasing concentrations of trifluoroethanol (TFE) and ethylene glycol. The impact of the COR15A …
The Role Of Serum Histones In Canine Heat Stroke,
2019
Claremont Colleges
The Role Of Serum Histones In Canine Heat Stroke, Jenna Acutt
Scripps Senior Theses
Rising temperatures all over the world has correlated with more frequent heat stroke related injuries and death. This statistic not only applies to humans, but to canines as well, who have similar body temperature thresholds. Recent studies have demonstrated that serum histones, released after cell death from heat stroke, play a role in heat stroke related injuries and death. This proposal aims to determine the severity of the effects caused by serum histone release after heat stroke by exposing selected canine cell lines to cell lysate and purified histones H2A, H2B, H3, and H4, which have been found to be …
Functional Inhibition Of Acid Sphingomyelinase Disrupts Infection By Intracellular Bacterial Pathogens,
2019
University Medical Center
Functional Inhibition Of Acid Sphingomyelinase Disrupts Infection By Intracellular Bacterial Pathogens, Chelsea L. Cockburn, Ryan S. Green, Sheela R. Damle, Rebecca K. Martin, Naomi N. Ghahrai, Punsiri M. Colonne, Marissa S. Fullerton, Daniel H. Conrad, Charles E. Chalfant, Daniel E. Voth, Elizabeth A. Rucks, Stacey D. Gilk, Jason A. Carlyon
Molecular Biosciences Faculty Publications
Intracellular bacteria that live in host cell–derived vacuoles are significant causes of human disease. Parasitism of low-density lipoprotein (LDL) cholesterol is essential for many vacuole-adapted bacteria. Acid sphingomyelinase (ASM) influences LDL cholesterol egress from the lysosome. Using functional inhibitors of ASM (FIASMAs), we show that ASM activity is key for infection cycles of vacuole-adapted bacteria that target cholesterol trafficking—Anaplasma phagocytophilum, Coxiella burnetii, Chlamydia trachomatis, and Chlamydia pneumoniae. Vacuole maturation, replication, and infectious progeny generation by A. phagocytophilum, which exclusively hijacks LDL cholesterol, are halted and C. burnetii, for which lysosomal cholesterol accumulation is bactericidal, …
Functional Analysis Of The Replication Fork Proteome Identifies Bet Proteins As Pcna Regulators,
2019
Vanderbilt University
Functional Analysis Of The Replication Fork Proteome Identifies Bet Proteins As Pcna Regulators, Sarah R. Wessel, Kareem N. Mohni, Jessica W. Luzwick, Huzefa Dungrawala, David Cortez
Molecular Biosciences Faculty Publications
Identifying proteins that function at replication forks is essential to understanding DNA replication, chromatin assembly, and replication-coupled DNA repair mechanisms. Combining quantitative mass spectrometry in multiple cell types with stringent statistical cutoffs, we generated a high-confidence catalog of 593 proteins that are enriched at replication forks and nascent chromatin. Loss-of-function genetic analyses indicate that 85% yield phenotypes that are consistent with activities in DNA and chromatin replication or already have described functions in these processes. We illustrate the value of this resource by identifying activities of the BET family proteins BRD2, BRD3, and BRD4 in controlling DNA replication. These proteins …
P53 Phosphomimetics Preserve Transient Secondary Structure But Reduce Binding To Mdm2 And Mdmx,
2019
University of South Florida
P53 Phosphomimetics Preserve Transient Secondary Structure But Reduce Binding To Mdm2 And Mdmx, Robin Levy, Emily Gregory, Wade Borcherds, Gary W. Daughdrill
Molecular Biosciences Faculty Publications
The disordered p53 transactivation domain (p53TAD) contains specific levels of transient helical secondary structure that are necessary for its binding to the negative regulators, mouse double minute 2 (Mdm2) and MdmX. The interactions of p53 with Mdm2 and MdmX are also modulated by posttranslational modifications (PTMs) of p53TAD including phosphorylation at S15, T18 and S20 that inhibits p53-Mdm2 binding. It is unclear whether the levels of transient secondary structure in p53TAD are changed by phosphorylation or other PTMs. We used phosphomimetic mutants to determine if adding a negative charge at positions 15 and 18 has any effect on the transient …
Identification Of Proteins Interacting With Zebrafish Miro Orthologs In The Yeast Two-Hybrid System,
2019
Rollins College
Identification Of Proteins Interacting With Zebrafish Miro Orthologs In The Yeast Two-Hybrid System, Yiran Tao
Honors Program Theses
The motility of mitochondria is required for providing energy and maintaining basic cellular functions in neurons. Mitochondrial Rho GTPase (Miro) is an essential component of the mitochondrial trafficking machinery, a protein complex that anchors mitochondria to the microtubule motor protein for long-distance transport. As a protein localizing to the mitochondrial outer membrane, Miro regulates the morphology and the motility of mitochondria. Upon mitochondrial depolarization, the PINK1/Parkin pathway is activated to arrest mitochondrial movement by targeting Miro for phosphorylation and ubiquitination in a calcium-sensitive manner. However, it remains unclear what effects the PINK1-dependent phosphorylation has on the structure and binding properties …
The Otud5–Ubr5 Complex Regulates Fact-Mediated Transcription At Damaged Chromatin,
2019
University of South Florida
The Otud5–Ubr5 Complex Regulates Fact-Mediated Transcription At Damaged Chromatin, Angelo De Vivo, University Of South Florida, Jose Yegres, Jeonghyeon Kim, Sylvia Emly, Younghoon Kee
Molecular Biosciences Faculty Publications
Timely stalling and resumption of RNA polymerases at damaged chromatin are actively regulated processes. Prior work showed an importance of FACT histone chaperone in such process. Here we provide a new role of OTUD5 deubiquitinase in the FACT-dependent process. Through a DUB RNAi screen, we found OTUD5 as a specific stabilizer of the UBR5 E3 ligase. OTUD5 localizes to DNA double strand breaks (DSBs), interacts with UBR5 and represses the RNA Pol II elongation and RNA synthesis. OTUD5 co-localizes and interacts with the FACT component SPT16 and antagonizes the histone H2A deposition at DSB lesions. OTUD5 interacts with UBR5 and …
