gebhart/patrepeval huggingface dataset:
Mechanisms of processing and presentation of the antigens of Listeria monocytogenes. (1993)

Antigen processing is the series of events through which protein antigens become degraded and are sent to the cell surface for recognition by T cells. These events within the cell have been studied extensively using the model system of infection with Listeria monocytogenes. This bacteria resides primarily intracellularly; immunity to it is mediated by cellular responses. Upon phagocytosis by a macrophage, engulfed Listeria express a hemolytic molecule, listeriolysin O (LLO), and can disrupt the membrane of the endosome and escape into the cellular cytoplasm. This allows the organism to escape the hostile environment of the endosome and also gives it access to the processing machinery of the cytoplasm. Therefore, Listeria monocytogenes can be processed within an endosome and be presented by class II MHC, or can escape into the cytoplasm and be processed there and presented by class I MHC. This LLO molecule is not only an important virulence factor, it is also a dominant antigen in the cellular immune response to Listeria. The outcome of antigen processing and presentation can be influenced by the expression of LLO, by the state of activation of the macrophage, and by the cytokines involved in the immune response.
New insights into PGC‐1 coactivators: redefining their role in the regulation of mitochondrial function and beyond (2014)

Members of the PGC-1 family of coactivators have been revealed as key players in the regulation of energy metabolism. Early gain- and loss-of-function studies led to the conclusion that all members of the PGC-1 family (PGC-1α, PGC-1β and PRC) play redundant roles in the control of mitochondrial biogenesis by regulating overlapping gene expression programs. Regardless of this, all PGC-1 coactivators also appeared to differ in the stimuli to which they respond to promote mitochondrial gene expression. Although PGC-1α was found to be induced by different physiological or pharmacological cues, PGC-1β appeared to be unresponsive to such stimuli. Consequently, it has long been widely accepted that PGC-1α acts as a mediator of mitochondrial biogenesis induced by cues that signal high-energy needs, whereas the role of PGC-1β is restricted to the maintenance of basal mitochondrial function. By contrast, the function of PRC appears to be restricted to the regulation of gene expression in proliferating cells. However, recent studies using tissue-specific mouse models that lack or overexpress different PGC-1 coactivators have provided emerging evidence not only supporting new roles for PGC-1s, but also redefining some of the paradigms related to the precise function and mode of action of PGC-1 coactivators in mitochondrial biogenesis. The present review discusses some of the new findings regarding the control of mitochondrial gene expression by PGC-1 coactivators in a tissue-specific context, as well as newly-uncovered functions of PGC-1s beyond mitochondrial biogenesis, and their link to pathologies, such as diabetes, muscular dystrophies, neurodegenerative diseases or cancer.
Molecular Characteristics of Clostridium perfringens TpeL Toxin and Consequences of Mono-O-GlcNAcylation of Ras in Living Cells (2012)

TpeL is a member of the family of clostridial glucosylating toxins produced by Clostridium perfringens type A, B, and C strains. In contrast to other members of this toxin family, it lacks a C-terminal polypeptide repeat domain, which is suggested to be involved in target cell binding. It was shown that the glucosyltransferase domain of TpeL modifies Ras in vitro by mono-O-glucosylation or mono-O-GlcNAcylation (Nagahama, M., Ohkubo, A., Oda, M., Kobayashi, K., Amimoto, K., Miyamoto, K., and Sakurai, J. (2011) Infect. Immun. 79, 905-910). Here we show that TpeL preferably utilizes UDP-N-acetylglucosamine (UDP-GlcNAc) as a sugar donor. Change of alanine 383 of TpeL to isoleucine turns the sugar donor preference from UDP-GlcNAc to UDP-glucose. In contrast to previous studies, we show that Rac is a poor substrate in vitro and in vivo and requires 1-2 magnitudes higher toxin concentrations for modification by TpeL. The toxin is autoproteolytically processed in the presence of inositol hexakisphosphate (InsP(6)) by an intrinsic cysteine protease domain, located next to the glucosyltransferase domain. A C-terminally extended TpeL full-length variant (TpeL1-1779) induces apoptosis in HeLa cells (most likely by mono-O-GlcNAcylation of Ras), and inhibits Ras signaling including Ras-Raf interaction and ERK activation. In addition, TpeL blocks Ras signaling in rat pheochromocytoma PC12 cells. TpeL is a glucosylating toxin, which modifies Ras and induces apoptosis in target cells without having a typical C-terminal polypeptide repeat domain.
Stabilization of Wired Glucose Oxidase Anodes Rotating at 1000 rpm at 37°C (1999)

The stability of glucose electro‐oxidizing anodes rotating at 1000 rpm at 37°C was investigated. The anodes were made by coating 3 mm diam vitreous carbon disks with a cross‐linked, electron conducting redox hydrogel, which electrically connected reaction centers of glucose oxidase to the electrode. The endurance of the hydrogel films under the shear stress resulting from the rotation depended on their cross‐linking. Periodate oxidation of enzyme oligosaccharides, thereby forming multiple Schiff bases which cross‐linked the enzyme and the redox polymer, combined with additional cross‐linking by a diepoxide, resulted in toughened electrocatalytic films that survived the shearing caused by the rotation. The main residual cause of damage to the toughened films waschemical attack by , an undesired by‐product. Overcoating the "wired" enzyme film with a layer of immobilized catalasereduced such damage. The current density of glucose electro‐oxidation of the stabilized rotating electrodes was at 50 mM concentration, , decaying in the 11 h test period by . © 1999 The Electrochemical Society. All rights reserved.
Role of Lipopolysaccharides in Antibiotic Resistance and Bacteriophage Adsorption of Escherichia coli K-12 (1971)

Novobiocin-supersensitive (NS) mutants which could not grow on plates containing 40 mug or less of novobiocin per ml were isolated from Escherichia coli strain JE1011 (derived from E. coli K-12). Most of these NS mutants were found to have incomplete lipopolysaccharides (LPS), and they lack phosphate diester bridges in their backbone structure, with or without total loss of heptose, to which the phosphate diester is linked, and consequently lack external outer-core oligosaccharides. The phosphate diester bridges in the LPS backbone are apparently very important in forming a cell surface structure resistant to the penetration of antibiotics such as novobiocin, spiramycin, and actinomycin D. NS mutants, with incomplete LPS, lacking phosphates in their backbone structure were found to be resistant to phage T4, and those which also lacked heptose were resistant to phages T4 and T7. In contrast to the generally accepted idea that resistances to phages T3, T4, and T7 are linked genetically, no NS mutant was found to be resistant to T3. The possible structures of the receptors for T4 and T7 are discussed. The positions of novobiocin-supersensitive genes on the chromosome of several of the NS mutants defective in LPS were mapped. The genes were designated lpcA (between ara and lac) and lpcB (between 55 min and 60 min). The latter seemed to be a group of several related genes.
A topological model for the general aromatic amino acid permease, AroP, of Escherichia coli (1997)

The general aromatic amino acid permease, AroP, of Escherichia coli is responsible for the active transport of phenylalanine, tyrosine, and tryptophan. A proposed topological model for the AroP permease, consisting of 12 hydrophobic transmembrane spans connected by hydrophilic loops, is very similar to that of the closely related phenylalanine-specific permease. The validity of this model and its similarity to that of the PheP permease were investigated by studying fusion proteins of AroP permease and alkaline phosphatase. Based on the results obtained from the AroP-alkaline phosphatase sandwich fusions, we have significantly revised the proposed topological model for AroP in two regions. In this modified AroP topological model, the three charged residues E151, E153, and K160 are repositioned within the membrane in span 5. These three residues are conserved in a large family of amino acid transport proteins, and site-directed mutagenesis identifies them as being essential for transport activity. It is postulated that these residues together with E110 in transmembrane span 3 may be involved in a proton relay system.
Determination and Use of Stability Constants (1992)

Part 1 Introduction: stability constants - early work recent developments historical evolution of computational methods purpose of this book. Part 2 Equilibrium constants, protonation constants, formation constants: concentration constants and activity constants conventions employment for expressing equilibrium constants equilibrium constants and stability constants for EDTA species distribution curves. Part 3 Experimental methods for measuring equilibrium constants: methods available potentiometric pH measurements displacement methods pH and p[H]measurement of metal complex equilibria: materials, the reaction mixture calibration of the potentiometric apparatus the experimental runs computation of stability constants.Part 4 Common errors and their elimination or minimization: measurements errors calibration and electrode care reagents equilibrium measurements calculations selection of the model. Part 5 Examples of stability constant determination: iminodiacetic acid (IDA) procedure for IDA C-BISTREN procedure for C-BISTREN. Part 6 Macroscopic and microscopic constants: some definitions and concepts ionization of tyrosine microscopic protonation equilibria of DOPA general comments and conclusions. Determination of stability constants and species concentrations of complex systems: a mixed-ligand binuclear dioxygen system non-aqueous solvents complex multicomponent systems equilibrium with solid phases equilibrium involving hydrolytic species species distributions of hydroxo and fluoro complexes of AI(III). Part 7 Critical stability constants and their selection: general criteria examples of critical data selection need for additional critical constants. Part 8 Development of a complete metal complex data base: introduction linear stability. constant correlations estimation of estability constants not measured experimentally metal speciation in sea water with and without added ligands.
Characterization of Adsorption Enthalpy of Novel Water-Stable Zeolites and Metal-Organic Frameworks (2016)

Water adsorption is becoming increasingly important for many applications including thermal energy storage, desalination, and water harvesting. To develop such applications, it is essential to understand both adsorbent-adsorbate and adsorbate-adsorbate interactions, and also the energy required for adsorption/desorption processes of porous material-adsorbate systems, such as zeolites and metal-organic frameworks (MOFs). In this study, we present a technique to characterize the enthalpy of adsorption/desorption of zeolites and MOF-801 with water as an adsorbate by conducting desorption experiments with conventional differential scanning calorimetry (DSC) and thermogravimetric analyzer (TGA). With this method, the enthalpies of adsorption of previously uncharacterized adsorbents were estimated as a function of both uptake and temperature. Our characterizations indicate that the adsorption enthalpies of type I zeolites can increase to greater than twice the latent heat whereas adsorption enthalpies of MOF-801 are nearly constant for a wide range of vapor uptakes.
Direct Gene Transfer into Mouse Muscle in Vivo (1990)

RNA and DNA expression vectors containing genes for chloramphenicol acetyltransferase, luciferase, and beta-galactosidase were separately injected into mouse skeletal muscle in vivo. Protein expression was readily detected in all cases, and no special delivery system was required for these effects. The extent of expression from both the RNA and DNA constructs was comparable to that obtained from fibroblasts transfected in vitro under optimal conditions. In situ cytochemical staining for beta-galactosidase activity was localized to muscle cells following injection of the beta-galactosidase DNA vector. After injection of the DNA luciferase expression vector, luciferase activity was present in the muscle for at least 2 months.
STUDIES ON THE SOLUBILITY OF CYSTINE UNDER VARIOUS CONDITIONS, AND ON A NEW METHOD OF CYSTINE PREPARATION (1928)

Journal Article STUDIES ON THE SOLUBILITY OF CYSTINE UNDER VARIOUS CONDITIONS, AND ON A NEW METHOD OF CYSTINE PREPARATION Get access LEN OKABE LEN OKABE Biochemical Laboratory, Kitasato InstituteTokyo Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Biochemistry, Volume 8, Issue 2, January 1928, Pages 441–457, https://doi.org/10.1093/oxfordjournals.jbchem.a133434 Published: 01 January 1928 Article history Received: 17 December 1927 Published: 01 January 1928
Multimodal Image-Guided Enzyme/Prodrug Cancer Therapy (2006)

The conjugate of bacterial cytosine deaminase (bCD) and poly-l-lysine (PLL) that was functionalized with biotin, rhodamine, and Gd3+-DOTA was synthesized and characterized. It demonstrated high relaxivity, improved enzymatic specificity to prodrug 5-fluorocytosine, low cytotoxicity, efficient cell uptake, and high enzymatic stability in fresh mouse serum and human breast cancer cell culture.
Presentation and immunogenicity of the hepatitis B surface antigen and a poliovirus neutralization antigen on mixed empty envelope particles (1988)

Insertion of a synthetic DNA fragment encoding a poliovirus neutralization epitope into the S gene encoding the major envelope protein of hepatitis B virus has yielded hybrid (HBsPolioAg) particles closely resembling authentic 22-nm antigen (HBsAg) particles by expression of the modified gene in mammalian cells. In mice, these hybrid particles induce neutralizing antibodies against poliovirus but only weak immune response to HBsAg (F. Delpeyroux, N. Chenciner, A. Lim, Y. Malpièce, B. Blondel, R. Crainic, S. Van der Werf, and R. E. Streeck, Science 233:472-474, 1986). By cotransfection with different plasmids carrying either modified or unmodified S genes, we have now obtained mixed particles presenting both HBsAg and HBsPolioAg. When such particles were inoculated into rabbits, antibodies to both poliovirus and to HBsAg were induced. Moreover, the titers of neutralizing antibodies to poliovirus induced by HBsPolioAg were much higher than those previously obtained in mice. The design of multivalent particles carrying various peptide sequences or presenting several heterologous epitopes may therefore be possible.
Profound Methyl Effects in Drug Discovery and a Call for New CH Methylation Reactions (2013)

The methyl group is one of the most commonly occurring carbon fragments in small-molecule drugs. This simplest alkyl fragment appears in more than 67 % of the top-selling drugs of 2011 and can modulate both the biological and physical properties of a molecule. This Review focuses on so-called magic methyl effects on binding potency, where the seemingly mundane change of CH to CMe improves the IC50 value of a drug candidate more than 100-fold. This discussion is followed by a survey of recent advances in synthetic chemistry that allow the direct methylation of C(sp(2) )H and C(sp(3) )H bonds. It is our hope that the relevance of the meager methyl group to drug discovery as presented herein will inspire reports on new CH methylation reactions.
ChemInform Abstract: NOVEL REAGENT SYSTEM FOR CONVERTING A HYDROXY GROUP INTO AN IODO GROUP IN CARBOHYDRATES WITH INVERSION OF CONFIGURATION (1980)

Abstract Hydroxylgruppen in (I) und (IIIa) lasse sich mit Triphenylphosphin/2,4,5‐Triiod‐imidazol oder Triphenylphosphin/Iod/Imi azol unter Bildung der Iodide (II) und (IIIb) austauschen.
Effect of the Interferon Inducer, Dextran Phosphate, on Influenza Virus Infection in Mice (1975)

Intraperitoneal administration of dextran phosphate (MW 40,000) or DP 40, an interferon inducer, was shown to increase the survival rate of mice infected with 10 LD50 dose of influenza A2 virus (H2N2). In the treated mice, a 1-day delay was evident in the virus growth in lung, and production of HAI antibody, when compared to the nontreated or dextran-treated controls. More significant was the 2-day delay in the development of lung consolidation, which leads to 40% survival of the treated mice. Mediation of the protection by the interferon induced by DP 40 was indicated.
Synergistic Polymorphism at Two Positions Distal to the Ligand-Binding Site Makes KIR2DL2 a Stronger Receptor for HLA-C Than KIR2DL3 (2008)

Interactions between HLA-C ligands and inhibitory killer cell Ig-like receptors (KIR) control the development and response of human NK cells. This regulatory mechanism is usually described by mutually exclusive interactions of KIR2DL1 with C2 having lysine 80, and KIR2DL2/3 with C1 having asparagine 80. Consistent with this simple rule, we found from functional analysis and binding assays to 93 HLA-A, HLA-B, and HLA-C isoforms that KIR2DL1*003 bound all C2, and only C2, allotypes. The allotypically related KIR2DL2*001 and KIR2DL3*001 interacted with all C1, but they violated the simple rule through interactions with several C2 allotypes, notably Cw*0501 and Cw*0202, and two HLA-B allotypes (B*4601 and B*7301) that share polymorphisms with HLA-C. Although the specificities of the "cross-reactions" were similar for KIR2DL2*001 and KIR2DL3*001, they were stronger for KIR2DL2*001, as were the reactions with C1. Mutagenesis explored the avidity difference between KIR2DL2*001 and KIR2DL3*001. Recombinant mutants mapped the difference to the Ig-like domains, where site-directed mutagenesis showed that the combination, but not the individual substitutions, of arginine for proline 16 in D1 and cysteine for arginine 148 in D2 made KIR2DL2*001 a stronger receptor than KIR2DL3*001. Neither residue 16 or 148 is part of, or near to, the ligand-binding site. Instead, their juxtaposition near the flexible hinge between D1 and D2 suggests that their polymorphisms affect the ligand-binding site by changing the hinge angle and the relative orientation of the two domains. This study demonstrates how allelic polymorphism at sites distal to the ligand-binding site of KIR2DL2/3 has diversified this receptor's interactions with HLA-C.
Hypothesis: Persistent Expression of Fetal Phenotypic Characteristics by Fibroblasts Is Associated with an Increased Susceptibility to Neoplastic Disease (1987)

Published data from our own and other laboratories have indicated that fibroblasts obtained from patients with different types of epithelial cancers commonly display aberrant (i.e. fetal-like or transformed) phenotypic characteristics. Previous interpretations of these results have tended to regard the study of fibroblasts as a convenient means to demonstrate genetic abnormalities also expressed in the target epithelial cell population and did not ascribe a particular causative role to fibroblast abnormalities in the genesis of neoplastic lesions. In this communication we present an alternative, but not mutually exclusive, hypothesis suggesting that aberrations expressed solely by fibroblasts may lead to the development of an epithelial tumour by virtue of a dysfunction in normal epithelial-mesenchymal interactions.
Molecular profiling of cervical neoplasia (2006)

Cervical cancer, a potentially preventable disease, remains the second most common malignancy in women worldwide. Human papillomavirus is the single most important etiological agent in cervical cancer, contributing to neoplastic progression through the action of viral oncoproteins, mainly E6 and E7, which interfere with critical cell cycle pathways, p53 and retinoblastoma. However, evidence suggests that human papillomavirus infection alone is insufficient to induce malignant changes and that other host genetic variations are important in the development of cervical cancer. This article will discuss the latest molecular profiling techniques available and review the published literature relating to their role in the diagnosis and management of cervical dysplasia and cancer. It is hoped that these techniques will allow the detection of novel biomarkers at DNA, RNA, microRNA and protein levels, which may ultimately play a role in facilitating early disease diagnosis and in predicting response to therapies, thus allowing the development of personalized treatment strategies.
Identification of a cyclic peptide inhibitor of platelet‐derived growth factor–BB receptor‐binding and mitogen‐induced DNA synthesis in human fibroblasts (1997)

Peptides corresponding to residues from Loops I and III of platelet-derived growth factor-BB (PDGF-BB) were examined for their potential to act as PDGF antagonists. We have identified two peptides which directly stimulated DNA synthesis in human dermal fibroblasts and a cyclic peptide which inhibited PDGF-induced DNA synthesis. The inhibitory action of cyclic PDGF-BB(73-81), on DNA synthesis was shown to be restricted to cells which express PDGF receptors. Also cyclic PDGF-BB(73-81) specifically competed for 125I-labelled PDGF-BB but not for 125I-labelled EGF binding to their respective cellular receptors. The cyclic peptide therefore provides a minimum structure to investigate PDGF/receptor interactions and our findings confirm the importance of the loop configuration of PDGF-BB(73-81) in the native molecule. The cyclic peptide may constitute a basis for developing more potent inhibitors of PDGF action.
Mineralization of the s-triazine ring of atrazine by stable bacterial mixed cultures (1993)

Enrichment cultures containing atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine) at a concentration of 100 ppm (0.46 mM) as a sole nitrogen source were obtained from soils exposed to repeated spills of atrazine, alachlor, and metolachlor. Bacterial growth occurred concomitantly with formation of metabolites from atrazine and subsequent biosynthesis of protein. When ring-labeled [14C]atrazine was used, 80% or more of the s-triazine ring carbon atoms were liberated as 14CO2. Hydroxyatrazine may be an intermediate in the atrazine mineralization pathway. More than 200 pure cultures isolated from the enrichment cultures failed to utilize atrazine as a nitrogen source. Mixing pure cultures restored atrazine-mineralizing activity. Repeated transfer of the mixed cultures led to increased rates of atrazine metabolism. The rate of atrazine degradation, even at the elevated concentrations used, far exceeded the rates previously reported in soils, waters, and mixed and pure cultures of bacteria.