The Role Of Proton Transport In Gating Current In A Voltage Gated Ion Channel, As Shown By Quantum Calculations,
2018
CUNY City College
The Role Of Proton Transport In Gating Current In A Voltage Gated Ion Channel, As Shown By Quantum Calculations, Alisher M. Kariev, Michael E. Green
Publications and Research
Over two-thirds of a century ago, Hodgkin and Huxley proposed the existence of voltage gated ion channels (VGIC) to carry Na+ and K+ ions across the cell membrane to create the nerve impulse, in response to depolarization of the membrane. The channels have multiple physiological roles, and play a central role in a wide variety of diseases when they malfunction. The first channel structure was found by MacKinnon and coworkers in 1998. Subsequently the structure of a number of VGIC was determined in the open (ion conducting) state. This type of channel consists of four voltage sensing domains …
Iron-Dependent Cleavage Of Ribosomal Rna During Oxidative Stress In The Yeast Saccharomyces Cerevisiae,
2018
Rowan University
Iron-Dependent Cleavage Of Ribosomal Rna During Oxidative Stress In The Yeast Saccharomyces Cerevisiae, Jessica A Zinskie, Arnab Ghosh, Brandon M Trainor, Daniel Shedlovskiy, Dimitri G Pestov, Natalia Shcherbik
Rowan-Virtua School of Osteopathic Medicine Departmental Research
Stress-induced strand breaks in rRNA have been observed in many organisms, but the mechanisms by which they originate are not well-understood. Here we show that a chemical rather than an enzymatic mechanism initiates rRNA cleavages during oxidative stress in yeast (Saccharomyces cerevisiae). We used cells lacking the mitochondrial glutaredoxin Grx5 to demonstrate that oxidant-induced cleavage formation in 25S rRNA correlates with intracellular iron levels. Sequestering free iron by chemical or genetic means decreased the extent of rRNA degradation and relieved the hypersensitivity of grx5Δ cells to the oxidants. Importantly, subjecting purified ribosomes to an in vitro iron/ascorbate …
Glutathione De Novo Synthesis But Not Recycling Process Coordinates With Glutamine Catabolism To Control Redox Homeostasis And Directs Murine T Cell Differentiation,
2018
The Ohio State University
Glutathione De Novo Synthesis But Not Recycling Process Coordinates With Glutamine Catabolism To Control Redox Homeostasis And Directs Murine T Cell Differentiation, Gaojian Lian, J. N. Rashida Gnanaprakasam, Tingting Wang, Ruohan Wu, Xuyong Chen, Lingling Liu, Yuqing Shen, Mao Yang, Jun Yang, Ying Chen, Vasilis Vasiliou, Teresa A. Cassel, Douglas R. Green, Yusen Liu, Teresa W. -M. Fan, Ruoning Wang
Toxicology and Cancer Biology Faculty Publications
Upon antigen stimulation, T lymphocytes undergo dramatic changes in metabolism to fulfill the bioenergetic, biosynthetic and redox demands of proliferation and differentiation. Glutathione (GSH) plays an essential role in controlling redox balance and cell fate. While GSH can be recycled from Glutathione disulfide (GSSG), the inhibition of this recycling pathway does not impact GSH content and murine T cell fate. By contrast, the inhibition of the de novo synthesis of GSH, by deleting either the catalytic (Gclc) or the modifier (Gclm) subunit of glutamate–cysteine ligase (Gcl), dampens intracellular GSH, increases ROS, and impact T cell differentiation. Moreover, the inhibition of …
Susceptibility Genes To Plant Viruses,
2018
University of Nebraska-Lincoln
Susceptibility Genes To Plant Viruses, Hernan Garcia-Ruiz
Nebraska Center for Virology: Faculty Publications
Plant viruses use cellular factors and resources to replicate and move. Plants respond to viral infection by several mechanisms, including innate immunity, autophagy, and gene silencing, that viruses must evade or suppress. Thus, the establishment of infection is genetically determined by the availability of host factors necessary for virus replication and movement and by the balance between plant defense and viral suppression of defense responses. Host factors may have antiviral or proviral activities. Proviral factors condition susceptibility to viruses by participating in processes essential to the virus. Here, we review current advances in the identification and characterization of host factors …
Membrane Expression Of Thymidine Kinase 1 And Potential Clinical Relevance In Lung, Breast, And Colorectal Malignancies,
2018
Brigham Young University
Membrane Expression Of Thymidine Kinase 1 And Potential Clinical Relevance In Lung, Breast, And Colorectal Malignancies, Evita G. Weagel, Weston Burrup, Roman Kovtun, Edwin J. Valazquez, Abigail M. Felsted, Michelle H. Townsend, Zachary E. Ence, Erica Suh, Stephen Piccolo, K. Scott Weber, Richard A. Robison, Kim Oneill
Faculty Publications
Background: Lung, breast, and colorectal malignancies are the leading cause of cancer-related deaths in the world causing over 2.8 million cancer-related deaths yearly. Despite efforts to improve prevention methods, early detection, and treatments, survival rates for advanced stage lung, breast, and colon cancer remain low, indicating a critical need to identify cancer-specific biomarkers for early detection and treatment. Thymidine kinase 1 (TK1) is a nucleotide salvage pathway enzyme involved in cellular proliferation and considered an important tumor proliferation biomarker in the serum. In this study, we further characterized TK1’s potential as a tumor biomarker and immunotherapeutic target and clinical relevance. …
Escherichia Coli Itat Is A Type Ii Toxin That Inhibits Translation By Acetylating Isoleucyl-Trnaile,
2018
Skolkovo Institute of Science and Technology
Escherichia Coli Itat Is A Type Ii Toxin That Inhibits Translation By Acetylating Isoleucyl-Trnaile, Brendan Wilcox, Ilya Osterman, Marina Serebryakova, Dmitry Lukyanov, Ekaterina Komarova, Bridget Gollan, Natalia Morozova, Yuri I Wolf, Kira S Makarova, Sophie Helaine, Petr Sergiev, Svetlana Dubiley, Sergei Borukhov, Konstantin Severinov
Rowan-Virtua School of Osteopathic Medicine Departmental Research
Prokaryotic toxin-antitoxin (TA) modules are highly abundant and are involved in stress response and drug tolerance. The most common type II TA modules consist of two interacting proteins. The type II toxins are diverse enzymes targeting various essential intracellular targets. The antitoxin binds to cognate toxin and inhibits its function. Recently, TA modules whose toxins are GNAT-family acetyltransferases were described. For two such systems, the target of acetylation was shown to be aminoacyl-tRNA: the TacT toxin targets aminoacylated elongator tRNAs, while AtaT targets the amino acid moiety of initiating tRNAMet. We show that the itaRT gene pair from Escherichia coli …
Characterization Of The Protective Role Of Th17 Cells In An Fc Receptor-Targeted Vaccine Strategy Against Fracisella Tularensis Infection,
2018
Seton Hall University
Characterization Of The Protective Role Of Th17 Cells In An Fc Receptor-Targeted Vaccine Strategy Against Fracisella Tularensis Infection, Kyle Devenney
Seton Hall University Dissertations and Theses (ETDs)
Using a murine model, we have previously showed that targeting an inactivated form of F.tularensis (iFt) bacteria to Fcg receptors by utilizing an IgG2a, anti-LPS monoclonal antibody (mAb) provides 100% protection against a lethal dose with the live vaccine strain (LVS). The binding of anti-LPS monoclonal antibodies and iFt create an immune complex (mAb-iFt) allowing the Fc-region of the antibody to target Fc receptors expressed on antigen presenting cells, leading to a more robust and effective processing and presentation of the bacterial antigens. Although the resulting protective response generated relies on both humoral and cell-mediated immunity, in our study we …
Comparative Proteomic Analyses Of Human Adipose Extracellular Matrices Decellularized Using Alternative Procedures,
2018
Biomedical Science Program, Tulane University School of Medicine & Center for Stem Cell Research & Regenerative Medicine, Tulane University School of Medicine
Comparative Proteomic Analyses Of Human Adipose Extracellular Matrices Decellularized Using Alternative Procedures, Caasy Porch-Thomas, Jie Li, Fabiana Zanata, Elizabeth C. Martin, Nicholas Pashos, Kaylynn Genemaras, Nicholas J. Poche, Nicholas P. Totaro, Melyssa R. Bratton, Dina Gaupp, Trivia Frazier, Xiying Wu, Lydia Masako Ferreira, Weidong Tian, Guangdi Wang, Bruce A. Bunnell, Lauren Flynn, Daniel Hayes, Jeffrey M. Gimble
Anatomy and Cell Biology Publications
Decellularized human adipose tissue has potential clinical utility as a processed biological scaffold for soft tissue cosmesis, grafting, and reconstruction. Adipose tissue decellularization has been accomplished using enzymatic-, detergent-, and/or solvent-based methods. To examine the hypothesis that distinct decellularization processes may yield scaffolds with differing compositions, the current study employed mass spectrometry to compare the proteomes of human adipose-derived matrices generated through three independent methods combining enzymatic-, detergent-, and/or solvent-based steps. In addition to protein content, bioscaffolds were evaluated for deoxyribose nucleic acid depletion, extracellular matrix composition, and physical structure using optical density, histochemical staining, and scanning electron microscopy. Mass …
Strategies Involving The Food-Derived Agent Curcumin To Eliminate Brain Cancer,
2018
CUNY Graduate Center
Strategies Involving The Food-Derived Agent Curcumin To Eliminate Brain Cancer, Sumit Mukherjee
Dissertations, Theses, and Capstone Projects
Glioblastoma (GBM) is one of the most deadly forms of cancer with a mean 5-year survival rate of ≤5%. We have used the non-invasive strategy of long-term intranasal (IN) delivery of a glioblastoma-directed adduct of curcumin (CC), CC-CD68Ab, into the brain of murine GBM cell line GL261-implanted mice to study the therapeutic effect of CC on GBM remission. The treatment caused GBM tumor remission in 50% of GL261-implanted GBM mice. A similar rescue rate (60%) was also achieved through long-term intraperitoneal (i.p) infusion of a highly bioavailable phosphotidylcholine (PC)-encapsulated formulation of CC, Curcumin Phytosome Meriva (CCP), into the GL261-implanted GBM …
Mechanisms Adopted By Dengue-2 Viruses To Induce Autophagy In Mammalian Cells,
2018
CUNY Graduate Center
Mechanisms Adopted By Dengue-2 Viruses To Induce Autophagy In Mammalian Cells, Sounak Ghosh Roy
Dissertations, Theses, and Capstone Projects
Dengue, the most rapidly spreading flavivirus, threatens to affect almost half of the human global population. We previously showed that dengue-2 protects canine kidney cells (MDCK) from cytotoxic chemicals. We showed, independently, that cell protection, as well as viral replication and maturation, are positively regulated by PI3K-dependent autophagy. However, we had not identified the specific pathway that induces autophagy in infected cells. The current study explores the role of a specific branch of the endoplasmic reticulum (ER) stress-mediated Unfolded Protein Response (UPR), the PERK/eIF2α/ATF4 pathway in the induction of autophagy by …
Renal Risk Variants Of Apolipoprotein L-1 Form Channels At The Plasma Membrane That Lead To A Cytotoxic Influx Of Calcium,
2018
CUNY Graduate Center
Renal Risk Variants Of Apolipoprotein L-1 Form Channels At The Plasma Membrane That Lead To A Cytotoxic Influx Of Calcium, Joseph A. Giovinazzo
Dissertations, Theses, and Capstone Projects
Apolipoprotein L-1 (APOL1) is a secreted protein that provides protection against several protozoan parasites due to its channel forming properties. Recently evolved variants, G1 and G2, increase kidney disease risk when present in two copies. In mammalian cells, overexpression of G1 and G2, but not wild-type G0, leads to swelling and eventual lysis. However, the mechanism of cell death remains elusive with multiple pathways being invoked, such as autophagic cell death mediated by a BH3 domain in APOL1, which we evaluated in this study. We hypothesized that the common trigger for these pathways is the APOL1 cation channel, which is …
Phospholipase D-Dependent Mtorc1 Activation By Glutamine,
2018
CUNY Graduate Center
Phospholipase D-Dependent Mtorc1 Activation By Glutamine, Elyssa Bernfeld
Dissertations, Theses, and Capstone Projects
Glutamine, the conditionally essential amino acid and most abundant amino acid in human sera, is a key nutrient required for sustaining cell proliferation. Glutamine is essential for nucleotide, protein, and lipid synthesis, all of which are essential for cell proliferation. The mammalian target of rapamycin complex 1 (mTORC1) is a highly conserved protein complex that acts as a sensor of nutrients, relaying signals for the shift from catabolic to anabolic metabolism. While glutamine plays an important role in activating mTORC1, the mechanism is not completely clear. Here we describe a Rag-independent mechanism of mTORC1 activation by glutamine that is dependent …
Integration Of Bmp And Insulin/Igf-1 Signaling Regulates Multiple Homeostatic Functions In Caenorhabditis Elegans,
2018
CUNY Graduate Center
Integration Of Bmp And Insulin/Igf-1 Signaling Regulates Multiple Homeostatic Functions In Caenorhabditis Elegans, James F. Clark
Dissertations, Theses, and Capstone Projects
The maintenance of homeostatic functions is key to the survival and well-being of an organism. Regulation of homeostasis relies on varied inputs, both intrinsic and extrinsic, to potentiate a web of interconnected signaling relays. Insulin/IGF-1 signaling (IIS) is a well-known regulator of glucose and lipid metabolism, as well as having far reaching effects in other homeostatic mechanisms. On the other hand, bone morphogenetic protein (BMP), a member of the transforming growth factor beta signaling superfamily, is known for its role in differentiation and development, with only recent studies highlighting potential roles in metabolic homeostasis. Here we elucidate new functions for …
Small Noncoding Rna Profiles Along Alternative Developmental Trajectories In An Annual Killifish,
2018
Portland State University
Small Noncoding Rna Profiles Along Alternative Developmental Trajectories In An Annual Killifish, Amie L. Romney, Jason E. Podrabsky
Biology Faculty Publications and Presentations
Embryonic development of Austrofundulus limnaeus can occur along two phenotypic trajectories that are physiologically and biochemically distinct. Phenotype appears to be influenced by maternal provisioning based on the observation that young females produce predominately non-diapausing embryos and older females produce mostly diapausing embryos. Embryonic incubation temperature can override this pattern and alter trajectory. We hypothesized that temperature-induced phenotypic plasticity may be regulated by post-transcriptional modification via noncoding RNAs. As a first step to exploring this possibility, RNA-seq was used to generate transcriptomic profiles of small noncoding RNAs in embryos developing along the two alternative trajectories. We find distinct profiles of …
Crispr Knockouts Reveal An Endogenous Role For Ancient Neuropeptides In Regulating Developmental Timing In A Sea Anemone,
2018
University of Arkansas, Fayetteville
Crispr Knockouts Reveal An Endogenous Role For Ancient Neuropeptides In Regulating Developmental Timing In A Sea Anemone, Nagayasu Nakanishi, Mark Q. Martindale
Biological Sciences Faculty Publications and Presentations
Neuropeptides are evolutionarily ancient peptide hormones of the nervous and neuroendocrine systems, and are thought to have regulated metamorphosis in early animal ancestors. In particular, the deeply conserved Wamide family of neuropeptides—shared across Bilateria (e.g. insects and worms) and its sister group Cnidaria (e.g. jellyfishes and corals)—has been implicated in mediating life-cycle transitions, yet their endogenous roles remain poorly understood. By using CRISPR-Cas9-mediated reverse genetics, we show that cnidarian Wamide—referred to as GLWamide—regulates the timing of life cycle transition in the sea anemone cnidarian Nematostella vectensis. We find that mutant planula larvae lacking GLWamides transform into morphologically normal polyps …
Recombinant Human Proteoglycan-4 Reduces Phagocytosis Of Urate Crystals And Downstream Nuclear Factor Kappa B And Inflammasome Activation And Production Of Cytokines And Chemokines In Human And Murine Macrophages,
2018
Chapman University
Recombinant Human Proteoglycan-4 Reduces Phagocytosis Of Urate Crystals And Downstream Nuclear Factor Kappa B And Inflammasome Activation And Production Of Cytokines And Chemokines In Human And Murine Macrophages, Marwa Qadri, Gregory D. Jay, Ling X. Zhang, Wendy Wong, Anthony M. Reginato, Changqi Sun, Tannin A. Schmidt
Pharmacy Faculty Articles and Research
Microbial biofilms are organized communities of cells that are associated with a wide spectrum of resistant and chronic infections that lead to the treatment failure. Accordingly, there is an urgent demand to create novel effective therapeutic drugs that can inhibit biofilm formation with new mechanisms of action to surmount the current escalating resistance. In this study, in silico hybrid model was utilized to develop three novel short linear peptides (4, 5, and 6) with potential biofilm inhibiting activities (scores > 1.0). The peptides were composed of cationic and hydrophobic residues. They were synthesized using solid-phase strategy. Synthesized peptides were purified and …
App21 Transgenic Rats Develop Age-Dependent Cognitive Impairment And Microglia Accumulation Within White Matter Tracts,
2018
Vulnerable Brain Laboratory, Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario
App21 Transgenic Rats Develop Age-Dependent Cognitive Impairment And Microglia Accumulation Within White Matter Tracts, Nina Weishaupt, Qingfan Liu, Sheojung Shin, Ramandeep Singh, Yuksel Agca, Cansu Agca, Vladimir Hachinski, Shawn Narain Whitehead
Anatomy and Cell Biology Publications
Background: Most of the animal models commonly used for preclinical research into Alzheimer's disease (AD) largely fail to address the pathophysiology, including the impact of known risk factors, of the widely diagnosed sporadic form of the disease. Here, we use a transgenic rat (APP21) that does not develop AD-like pathology spontaneously with age, but does develop pathology following vascular stress. To further the potential of this novel rat model as a much-needed pre-clinical animal model of sporadic AD, we characterize APP21 transgenic rats behaviorally and histologically up to 19 months of age. Methods: The open field test was used as …
Ubiquitin Regulation: The Histone Modifying Enzyme's Story,
2018
University of Kentucky
Ubiquitin Regulation: The Histone Modifying Enzyme's Story, Jianlin Wang, Zhaoping Qiu, Yadi Wu
Pharmacology and Nutritional Sciences Faculty Publications
Histone post-translational modifications influence many fundamental cellular events by regulating chromatin structure and gene transcriptional activity. These modifications are highly dynamic and tightly controlled, with many enzymes devoted to the addition and removal of these modifications. Interestingly, these modifying enzymes are themselves fine-tuned and precisely regulated at the level of protein turnover by ubiquitin-proteasomal processing. Here, we focus on recent progress centered on the mechanisms regulating ubiquitination of histone modifying enzymes, including ubiquitin proteasomal degradation and the reverse process of deubiquitination. We will also discuss the potential pathophysiological significance of these processes.
Identification Of Three Required Positive Cis-Regulated Inputs Of The Sea Urchin Pigment Cell Gene Polyketide Synthase 1,
2018
Valdosta State University
Identification Of Three Required Positive Cis-Regulated Inputs Of The Sea Urchin Pigment Cell Gene Polyketide Synthase 1, Cristina Calestani, Preston Dean, Xiaoman Li
Georgia Journal of Science
Sea urchin pigment cells are single cells of mesodermal origin embedded in the aboral ectoderm. Strongylocentrotus purpuratus polyketide synthase 1 (Sp-PKS1) is required for the biosynthesis of the echinochrome pigment. Evidence suggests that pigment cells are immune cells. In order to reconstruct the gene regulatory network of pigment cells a bottom-up approach combined with comparative genomics has been used in this study. We compared the cis-regulatory regions of five pigment cell genes, Sp-Pks1, flavin monooxygenase 1, 2, and 3 (Sp-Fmo) and sulfotransferase (Sp-Sult), across three different species, Strongylocentrotus purpuratus, Mesocentrotus franciscanus …
Mobile Elements Shape Plastome Evolution In Ferns,
2018
Utah State University
Mobile Elements Shape Plastome Evolution In Ferns, Tanner A. Robison, Amanda L. Grusz, Paul G. Wolf, Jeffrey P. Mower, Blake D. Fauskee, Karla Sosa, Eric Schuettpelz
Biology Faculty Publications
Plastid genomes display remarkable organizational stability over evolutionary time. From green algae to angiosperms, most plastid genomes are largely collinear, with only a few cases of inversion, gene loss, or, in extremely rare cases, gene addition. These plastome insertions are mostly clade-specific and are typically of nuclear or mitochondrial origin. Here, we expand on these findings and present the first family-level survey of plastome evolution in ferns, revealing a novel suite of dynamic mobile elements. Comparative plastome analyses of the Pteridaceae expose several mobile open reading frames that vary in sequence length, insertion site, and configuration among sampled taxa. Even …
