Genetic Analysis of Human Chymotrypsin-Like
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1 Evidence for Gliadin Antibodies As Causative Agents in Schizophrenia
1 Evidence for gliadin antibodies as causative agents in schizophrenia. C.J.Carter PolygenicPathways, 20 Upper Maze Hill, Saint-Leonard’s on Sea, East Sussex, TN37 0LG [email protected] Tel: 0044 (0)1424 422201 I have no fax Abstract Antibodies to gliadin, a component of gluten, have frequently been reported in schizophrenia patients, and in some cases remission has been noted following the instigation of a gluten free diet. Gliadin is a highly immunogenic protein, and B cell epitopes along its entire immunogenic length are homologous to the products of numerous proteins relevant to schizophrenia (p = 0.012 to 3e-25). These include members of the DISC1 interactome, of glutamate, dopamine and neuregulin signalling networks, and of pathways involved in plasticity, dendritic growth or myelination. Antibodies to gliadin are likely to cross react with these key proteins, as has already been observed with synapsin 1 and calreticulin. Gliadin may thus be a causative agent in schizophrenia, under certain genetic and immunological conditions, producing its effects via antibody mediated knockdown of multiple proteins relevant to the disease process. Because of such homology, an autoimmune response may be sustained by the human antigens that resemble gliadin itself, a scenario supported by many reports of immune activation both in the brain and in lymphocytes in schizophrenia. Gluten free diets and removal of such antibodies may be of therapeutic benefit in certain cases of schizophrenia. 2 Introduction A number of studies from China, Norway, and the USA have reported the presence of gliadin antibodies in schizophrenia 1-5. Gliadin is a component of gluten, intolerance to which is implicated in coeliac disease 6. -
Purification and Identification of a Binding Protein for Pancreatic
Biochem. J. (2003) 372, 227–233 (Printed in Great Britain) 227 Purification and identification of a binding protein for pancreatic secretory trypsin inhibitor: a novel role of the inhibitor as an anti-granzyme A Satoshi TSUZUKI*1,2,Yoshimasa KOKADO*1, Shigeki SATOMI*, Yoshie YAMASAKI*, Hirofumi HIRAYASU*, Toshihiko IWANAGA† and Tohru FUSHIKI* *Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan, and †Laboratory of Anatomy, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18-Nishi 9, Kita-ku, Sapporo 060-0818, Japan Pancreatic secretory trypsin inhibitor (PSTI) is a potent trypsin of GzmA-expressing intraepithelial lymphocytes in the rat small inhibitor that is mainly found in pancreatic juice. PSTI has been intestine. We concluded that the PSTI-binding protein isolated shown to bind specifically to a protein, distinct from trypsin, on from the dispersed cells is GzmA that is produced in the the surface of dispersed cells obtained from tissues such as small lymphocytes of the tissue. The rGzmA hydrolysed the N-α- intestine. In the present study, we affinity-purified the binding benzyloxycarbonyl-L-lysine thiobenzyl ester (BLT), and the BLT protein from the 2 % (w/v) Triton X-100-soluble fraction of hydrolysis was inhibited by PSTI. Sulphated glycosaminoglycans, dispersed rat small-intestinal cells using recombinant rat PSTI. such as fucoidan or heparin, showed almost no effect on the Partial N-terminal sequencing of the purified protein gave a inhibition of rGzmA by PSTI, whereas they decreased the inhi- sequence that was identical with the sequence of mouse granzyme bition by antithrombin III. -
Propranolol-Mediated Attenuation of MMP-9 Excretion in Infants with Hemangiomas
Supplementary Online Content Thaivalappil S, Bauman N, Saieg A, Movius E, Brown KJ, Preciado D. Propranolol-mediated attenuation of MMP-9 excretion in infants with hemangiomas. JAMA Otolaryngol Head Neck Surg. doi:10.1001/jamaoto.2013.4773 eTable. List of All of the Proteins Identified by Proteomics This supplementary material has been provided by the authors to give readers additional information about their work. © 2013 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 eTable. List of All of the Proteins Identified by Proteomics Protein Name Prop 12 mo/4 Pred 12 mo/4 Δ Prop to Pred mo mo Myeloperoxidase OS=Homo sapiens GN=MPO 26.00 143.00 ‐117.00 Lactotransferrin OS=Homo sapiens GN=LTF 114.00 205.50 ‐91.50 Matrix metalloproteinase‐9 OS=Homo sapiens GN=MMP9 5.00 36.00 ‐31.00 Neutrophil elastase OS=Homo sapiens GN=ELANE 24.00 48.00 ‐24.00 Bleomycin hydrolase OS=Homo sapiens GN=BLMH 3.00 25.00 ‐22.00 CAP7_HUMAN Azurocidin OS=Homo sapiens GN=AZU1 PE=1 SV=3 4.00 26.00 ‐22.00 S10A8_HUMAN Protein S100‐A8 OS=Homo sapiens GN=S100A8 PE=1 14.67 30.50 ‐15.83 SV=1 IL1F9_HUMAN Interleukin‐1 family member 9 OS=Homo sapiens 1.00 15.00 ‐14.00 GN=IL1F9 PE=1 SV=1 MUC5B_HUMAN Mucin‐5B OS=Homo sapiens GN=MUC5B PE=1 SV=3 2.00 14.00 ‐12.00 MUC4_HUMAN Mucin‐4 OS=Homo sapiens GN=MUC4 PE=1 SV=3 1.00 12.00 ‐11.00 HRG_HUMAN Histidine‐rich glycoprotein OS=Homo sapiens GN=HRG 1.00 12.00 ‐11.00 PE=1 SV=1 TKT_HUMAN Transketolase OS=Homo sapiens GN=TKT PE=1 SV=3 17.00 28.00 ‐11.00 CATG_HUMAN Cathepsin G OS=Homo -
Natural Single-Nucleotide Deletion in Chymotrypsinogen C Gene Increases Severity of Secretagogue-Induced Pancreatitis in C57BL/6 Mice
Natural single-nucleotide deletion in chymotrypsinogen C gene increases severity of secretagogue-induced pancreatitis in C57BL/6 mice Andrea Geisz, … , Eszter Hegyi, Miklós Sahin-Tóth JCI Insight. 2019;4(14):e129717. https://doi.org/10.1172/jci.insight.129717. Research Article Gastroenterology Inflammation Genetic susceptibility to chronic pancreatitis in humans is frequently associated with mutations that increase activation of the digestive protease trypsin. Intrapancreatic trypsin activation is an early event in experimental acute pancreatitis in rodents, suggesting that trypsin is a key driver of pathology. In contrast with trypsin, the pancreatic protease chymotrypsin serves a protective function by mitigating trypsin activation through degradation. In humans, loss-of-function mutations in chymotrypsin C (CTRC) are common risk factors for chronic pancreatitis; however, the pathogenic effect of CTRC deficiency has not been corroborated in animal models yet. Here we report that C57BL/6 mice that are widely used for genetic manipulations do not express functional CTRC because of a single-nucleotide deletion in exon 2 of the Ctrc gene. We restored a functional Ctrc locus in C57BL/6N mice and demonstrated that in the Ctrc+ strain, the severity of cerulein- induced experimental acute and chronic pancreatitis was significantly ameliorated. Improved disease parameters were associated with reduced intrapancreatic trypsin activation, suggesting a causal link between CTRC-mediated trypsinogen degradation and protection against pancreatitis. -
Mouse CELA3B ORF Mammalian Expression Plasmid, C-His Tag
Mouse CELA3B ORF mammalian expression plasmid, C-His tag Catalog Number: MG53134-CH General Information Plasmid Resuspension protocol Gene : chymotrypsin-like elastase family, 1. Centrifuge at 5,000×g for 5 min. member 3B 2. Carefully open the tube and add 100 l of sterile water to Official Symbol : CELA3B dissolve the DNA. Synonym : Ela3; Ela3b; AI504000; 0910001F22Rik; 2310074F01Rik 3. Close the tube and incubate for 10 minutes at room Source : Mouse temperature. cDNA Size: 810bp 4. Briefly vortex the tube and then do a quick spin to RefSeq : NM_026419.2 concentrate the liquid at the bottom. Speed is less than Description 5000×g. Lot : Please refer to the label on the tube 5. Store the plasmid at -20 ℃. Vector : pCMV3-C-His Shipping carrier : The plasmid is ready for: Each tube contains approximately 10 μg of lyophilized plasmid. • Restriction enzyme digestion Storage : • PCR amplification The lyophilized plasmid can be stored at ambient temperature for three months. • E. coli transformation Quality control : • DNA sequencing The plasmid is confirmed by full-length sequencing with primers in the sequencing primer list. E.coli strains for transformation (recommended Sequencing primer list : but not limited) pCMV3-F: 5’ CAGGTGTCCACTCCCAGGTCCAAG 3’ Most commercially available competent cells are appropriate for pcDNA3-R : 5’ GGCAACTAGAAGGCACAGTCGAGG 3’ the plasmid, e.g. TOP10, DH5α and TOP10F´. Or Forward T7 : 5’ TAATACGACTCACTATAGGG 3’ ReverseBGH : 5’ TAGAAGGCACAGTCGAGG 3’ pCMV3-F and pcDNA3-R are designed by Sino Biological Inc. Customers can order the primer pair from any oligonucleotide supplier. Manufactured By Sino Biological Inc., FOR RESEARCH USE ONLY. NOT FOR USE IN HUMANS. -
Effects of Glycosylation on the Enzymatic Activity and Mechanisms of Proteases
International Journal of Molecular Sciences Review Effects of Glycosylation on the Enzymatic Activity and Mechanisms of Proteases Peter Goettig Structural Biology Group, Faculty of Molecular Biology, University of Salzburg, Billrothstrasse 11, 5020 Salzburg, Austria; [email protected]; Tel.: +43-662-8044-7283; Fax: +43-662-8044-7209 Academic Editor: Cheorl-Ho Kim Received: 30 July 2016; Accepted: 10 November 2016; Published: 25 November 2016 Abstract: Posttranslational modifications are an important feature of most proteases in higher organisms, such as the conversion of inactive zymogens into active proteases. To date, little information is available on the role of glycosylation and functional implications for secreted proteases. Besides a stabilizing effect and protection against proteolysis, several proteases show a significant influence of glycosylation on the catalytic activity. Glycans can alter the substrate recognition, the specificity and binding affinity, as well as the turnover rates. However, there is currently no known general pattern, since glycosylation can have both stimulating and inhibiting effects on activity. Thus, a comparative analysis of individual cases with sufficient enzyme kinetic and structural data is a first approach to describe mechanistic principles that govern the effects of glycosylation on the function of proteases. The understanding of glycan functions becomes highly significant in proteomic and glycomic studies, which demonstrated that cancer-associated proteases, such as kallikrein-related peptidase 3, exhibit strongly altered glycosylation patterns in pathological cases. Such findings can contribute to a variety of future biomedical applications. Keywords: secreted protease; sequon; N-glycosylation; O-glycosylation; core glycan; enzyme kinetics; substrate recognition; flexible loops; Michaelis constant; turnover number 1. -
The Role of High Density Lipoprotein Compositional and Functional Heterogeneity in Metabolic Disease
The role of high density lipoprotein compositional and functional heterogeneity in metabolic disease By Scott M. Gordon B.S. State University of New York College at Brockport October, 2012 A Dissertation Presented to the Faculty of The University of Cincinnati College of Medicine in partial fulfillment of the requirements for the Degree of Doctor of Philosophy from the Pathobiology and Molecular Medicine graduate program W. Sean Davidson Ph.D. (Chair) David Askew Ph.D. Professor and Thesis Chair Professor Department of Pathology Department of Pathology University of Cincinnati University of Cincinnati Francis McCormack M.D. Gangani Silva Ph.D. Professor Assistant Professor Department of Pathology Department of Pathology University of Cincinnati University of Cincinnati Jason Lu Ph.D. Assistant Professor Division of Bioinformatics Cincinnati Children’s Hospital i Abstract High density lipoproteins (HDL) are complexes of phospholipid, cholesterol and protein that circulate in the blood. Epidemiological studies have demonstrated a strong inverse correlation between plasma levels of HDL associated cholesterol (HDL-C) and the incidence of cardiovascular disease (CVD). Clinically, HDL-C is often measured and used in combination with low density lipoprotein cholesterol (LDL-C) to assess overall cardiovascular health. HDL have been shown to possess a wide variety of functional attributes which likely contribute to this protection including anti-inflammatory and anti- oxidative properties and the ability to remove excess cholesterol from peripheral tissues and deliver it to the liver for excretion, a process known as reverse cholesterol transport. This functional diversity might be explained by the complexity of HDL composition. Recent studies have taken advantage of advances in mass spectrometry technologies to characterize the proteome of total HDL finding that over 50 different proteins can associate with these particles. -
Cellular and Molecular Signatures in the Disease Tissue of Early
Cellular and Molecular Signatures in the Disease Tissue of Early Rheumatoid Arthritis Stratify Clinical Response to csDMARD-Therapy and Predict Radiographic Progression Frances Humby1,* Myles Lewis1,* Nandhini Ramamoorthi2, Jason Hackney3, Michael Barnes1, Michele Bombardieri1, Francesca Setiadi2, Stephen Kelly1, Fabiola Bene1, Maria di Cicco1, Sudeh Riahi1, Vidalba Rocher-Ros1, Nora Ng1, Ilias Lazorou1, Rebecca E. Hands1, Desiree van der Heijde4, Robert Landewé5, Annette van der Helm-van Mil4, Alberto Cauli6, Iain B. McInnes7, Christopher D. Buckley8, Ernest Choy9, Peter Taylor10, Michael J. Townsend2 & Costantino Pitzalis1 1Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. Departments of 2Biomarker Discovery OMNI, 3Bioinformatics and Computational Biology, Genentech Research and Early Development, South San Francisco, California 94080 USA 4Department of Rheumatology, Leiden University Medical Center, The Netherlands 5Department of Clinical Immunology & Rheumatology, Amsterdam Rheumatology & Immunology Center, Amsterdam, The Netherlands 6Rheumatology Unit, Department of Medical Sciences, Policlinico of the University of Cagliari, Cagliari, Italy 7Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, UK 8Rheumatology Research Group, Institute of Inflammation and Ageing (IIA), University of Birmingham, Birmingham B15 2WB, UK 9Institute of -
Serine Proteases with Altered Sensitivity to Activity-Modulating
(19) & (11) EP 2 045 321 A2 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 08.04.2009 Bulletin 2009/15 C12N 9/00 (2006.01) C12N 15/00 (2006.01) C12Q 1/37 (2006.01) (21) Application number: 09150549.5 (22) Date of filing: 26.05.2006 (84) Designated Contracting States: • Haupts, Ulrich AT BE BG CH CY CZ DE DK EE ES FI FR GB GR 51519 Odenthal (DE) HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI • Coco, Wayne SK TR 50737 Köln (DE) •Tebbe, Jan (30) Priority: 27.05.2005 EP 05104543 50733 Köln (DE) • Votsmeier, Christian (62) Document number(s) of the earlier application(s) in 50259 Pulheim (DE) accordance with Art. 76 EPC: • Scheidig, Andreas 06763303.2 / 1 883 696 50823 Köln (DE) (71) Applicant: Direvo Biotech AG (74) Representative: von Kreisler Selting Werner 50829 Köln (DE) Patentanwälte P.O. Box 10 22 41 (72) Inventors: 50462 Köln (DE) • Koltermann, André 82057 Icking (DE) Remarks: • Kettling, Ulrich This application was filed on 14-01-2009 as a 81477 München (DE) divisional application to the application mentioned under INID code 62. (54) Serine proteases with altered sensitivity to activity-modulating substances (57) The present invention provides variants of ser- screening of the library in the presence of one or several ine proteases of the S1 class with altered sensitivity to activity-modulating substances, selection of variants with one or more activity-modulating substances. A method altered sensitivity to one or several activity-modulating for the generation of such proteases is disclosed, com- substances and isolation of those polynucleotide se- prising the provision of a protease library encoding poly- quences that encode for the selected variants. -
System, Method and Software for Calculation of a Cannabis Drug Efficiency Index for the Reduction of Inflammation
International Journal of Molecular Sciences Article System, Method and Software for Calculation of a Cannabis Drug Efficiency Index for the Reduction of Inflammation Nicolas Borisov 1,† , Yaroslav Ilnytskyy 2,3,†, Boseon Byeon 2,3,4,†, Olga Kovalchuk 2,3 and Igor Kovalchuk 2,3,* 1 Moscow Institute of Physics and Technology, 9 Institutsky lane, Dolgoprudny, Moscow Region 141701, Russia; [email protected] 2 Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada; [email protected] (Y.I.); [email protected] (B.B.); [email protected] (O.K.) 3 Pathway Rx., 16 Sandstone Rd. S., Lethbridge, AB T1K 7X8, Canada 4 Biomedical and Health Informatics, Computer Science Department, State University of New York, 2 S Clinton St, Syracuse, NY 13202, USA * Correspondence: [email protected] † First three authors contributed equally to this research. Abstract: There are many varieties of Cannabis sativa that differ from each other by composition of cannabinoids, terpenes and other molecules. The medicinal properties of these cultivars are often very different, with some being more efficient than others. This report describes the development of a method and software for the analysis of the efficiency of various cannabis extracts to detect the anti-inflammatory properties of the various cannabis extracts. The method uses high-throughput gene expression profiling data but can potentially use other omics data as well. According to the signaling pathway topology, the gene expression profiles are convoluted into the signaling pathway activities using a signaling pathway impact analysis (SPIA) method. The method was tested by inducing inflammation in human 3D epithelial tissues, including intestine, oral and skin, and then exposing these tissues to various extracts and then performing transcriptome analysis. -
Diapause in the Mosquito Culex Pipiens Evokes a Metabolic Switch from Blood Feeding to Sugar Gluttony
Diapause in the mosquito Culex pipiens evokes a metabolic switch from blood feeding to sugar gluttony Rebecca M. Robich* and David L. Denlinger† Department of Entomology, Ohio State University, 318 West 12th Avenue, Columbus, OH 43210 Contributed by David L. Denlinger, September 12, 2005 A key characteristic of overwintering dormancy (diapause) in the Although the physiological and ecological aspects of blood and mosquito Culex pipiens is the switch in females from blood feeding sugar feeding in diapausing C. pipiens have been well described, the to sugar gluttony. We present evidence demonstrating that genes molecular events that contribute to this metabolic decision have not encoding enzymes needed to digest a blood meal (trypsin and a been explored. In this study, we used suppressive subtractive chymotrypsin-like protease) are down-regulated in diapause-des- hybridization (SSH) to isolate three clones linked to this metabolic tined females, and that concurrently, a gene associated with the decision: fatty acid synthase, trypsin, and chymotrypsin-like serine accumulation of lipid reserves (fatty acid synthase) is highly up- protease. We then used these clones to probe the metabolic path- regulated. As the females then enter diapause, fatty acid synthase ways associated with the mosquito’s metabolic decision to enter and is only sporadically expressed, and expression of trypsin and terminate diapause. Because both short day length and low tem- chymotrypsin-like remains undetectable. Late in diapause (2–3 perature program diapause in C. pipiens, we also distinguished months at 18°C), the genes encoding the digestive enzymes begin between temperature and photoperiodic effects. We concluded to be expressed as the female prepares to take a blood meal upon that the short-day programming of diapause results in the down- the termination of diapause. -
Wsn 40 (2016) 147-162 Eissn 2392-2192
Available online at www.worldscientificnews.com WSN 40 (2016) 147-162 EISSN 2392-2192 Utilization of mulberry leaves treated with seed powder cowpea, Vigna unguiculata (L) for feeding the fifth instar larvae of silkworm, Bombyx mori (L) (Race: PM x CSR2) Vitthalrao B. Khyade1,*, Atharv Atul Gosavi2 1Department of Zoology, Shardabai Pawar Mahila Mahavidyalaya, Shardanagar Tal. Baramati; Dist. Pune - 413115, India 2Agriculture Development Trust Agri Polytechnic, Sharadanagar, Malegaon Colony, Tal: Baramati, Dist: Pune. PIN: 413115 Maharashtra, India *E-mail address: [email protected] ABSTRACT The present attempt was to screen the changes in the cocoon parameters; silk filament parameters and activities of biochemical reactions catalyzed by the midgut enzymes fifth instsr larvae of silkworm fed with mulberry leaves treated with aqueous solution of seed powder of Cowpeas (Vigna unguiculata). The cowpea seed powder was dissolved in distilled water and diluted to 2.5%, 5%, 7.5%, and 10% concentrations. Fresh mulberry leaves were dipped in each concentration of aqueous solution of cowpea seed powder for half an hour. 1000 ml solution was used for 100 grams of mulberry leaves. Treated mulberry leaves were drained off completely and then used for feeding. The mulberry leaves were fed five times per day at the rate of 100 grams per 100 larvae for each time. Untreated group of larvae were feed with untreated mulberry leaves. Water treated group of larvae were feed with water treated mulberry leaves. The experimental groups of larvae were feed with feed separately with 2.5 percent cowpea treated; 5.00 percent cowpea treated; 7.5 percent cowpea treated and 10.00 percent cowpea treated mulberry leaves.