DOCSLIB.ORG

Supplementary Figure 3. Hepatic Gene Expression Profiles of Drug-Treated Db/Db and Untreated Db/+ Compared to Untreated Db/Db

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Supplementary Figure 3. Hepatic gene expression profiles of drug-treated db/db and untreated db/+ compared to untreated db/db fold changes estimate fold changes estimate affy ID#genbank ID# symbol gene name RWT + RWT + db/db affy ID#genbank ID# symbol gene name RWT + RWT + db/db 145 Cellular Processes 4 chemotaxis 16 apoptosis 102938_atAB009687 Lect2 leukocyte cell-derived chemotaxin 2 -1,7-2,1 -1,5 -1,0 374 102016_atM61737 Fsp27 fat specific gene 27 5,43,1 3,6 -1,3 20 103448_atM83218 S100a8 S100 calcium binding protein A8 (calgranulin 1,1-1,0 1,8 -1,1 17 103029_atD86344 Pdcd4 programmed cell death 4 1,2-1,1 -1,4 1,6 174 97360_atAI841689 Cklfsf3 chemokine-like factor super family 3 1,11,1 1,6 1,0 11 93968_atAA870917 Pdcd5 programmed cell death 5 -1,01,5 1,0 -1,1 241 103240_f_atAF017258 Ear2 eosinophil-associated, ribonuclease, RNase A 1,2-1,0 1,9 1,0 35 93766_atU32170 Rgn regucalcin -1,2-1,3 -1,6 -1,0 1356 38 cytoskeleton 93869_s_atU23781 Bcl2a1d Bcl-2-related protein A1 (BFL-1 protein) 1,01,1 1,6 1,0 24 160065_s_atAI837625 Csrp1 cysteine and glycine-rich protein 1 1,21,2 1,7 1,0 21 161500_i_atAV102186 Bad Bcl-associated death promoter -1,1-1,1 -1,1 1,5 50 96298_f_atAF020185 Dnclc1 dynein, cytoplasmic, light chain 1 -1,6-1,1 1,2 -1,1 315 161980_f_atAV373612 Bag3 Bcl2-associated athanogene 3 1,1-1,3 1,7 1,2 30 99441_atAW123852 Gphn gephyrin 1,01,0 -1,5 1,5 85 93536_atL22472 Bax Bcl2-associated X protein 1,21,3 2,0 -1,1 64 93571_atM74773 Spnb2 spectrin beta 2 1,11,2 1,5 1,1 148 93697_atU63387 Cbx4 chromobox homolog 4 (Drosophila Pc class) -1,5-1,7 -1,9 -1,2 62 102043_atAF047704 Tuft1 tuftelin 1 -1,01,1 1,9 1,7 54 93093_atU35623 Mcl1 myeloid cell leukemia sequence 1 1,2-1,0 1,6 1,4 66 162379_r_atAV245272 Vim vimentin 1,1-1,0 1,0 1,6 20 97825_atAI854029 Perp-pen p53 apoptosis effector related to Pmp22 1,21,7 1,3 -1,3 196 160150_f_atAW125626 Cnn3 calponin 3, acidic -1,1-1,6 -1,2 1,2 261 99994_atAF041376 Cidea cell death-inducing DNA fragmentation factor, 5,49,5 2,0 1,0 28 101578_f_atM12481 Actb actin, beta, cytoplasmic 2,21,0 1,6 1,5 119 102114_f_atAI326963 Angptl4 angiopoietin-like 4 -1,11,5 -1,0 -1,3 108 96573_atM21495 Actg actin, gamma, cytoplasmic -1,21,1 1,6 -1,1 573 96119_s_atAA797604 Angptl4 angiopoietin-like 4 1,11,6 1,1 -1,5 156 103574_atAI841606 AbLIM1 actin-binding LIM protein 1 1,31,5 1,5 1,2 27 97890_atAW046181 Sgk serum/glucocorticoid regulated kinase -1,11,2 1,5 1,0 34 104578_f_atAI195392 Actn1 actinin, alpha 1 1,11,4 1,6 1,7 66 101521_atAB013819 Birc5 baculoviral IAP repeat-containing 5 -1,11,2 1,5 -1,1 16 93364_atX59990 Catna1 catenin alpha 1 1,11,1 1,6 1,1 102 40 cell adhesion 98107_atAW123801 Coro1c coronin, actin binding protein 1C 1,21,3 1,7 1,1 71 161996_f_atAV328452 Bcan brevican -1,6-1,2 -1,8 -1,6 25 96865_atM60474 Marcks myristoylated alanine rich protein kinase C 1,31,5 1,8 1,1 27 104083_atAI853217 Cdh5 cadherin 5 1,31,2 1,6 1,2 33 94991_atAW046661 Synpo synaptopodin 1,42,1 1,6 -1,0 16 92835_atAI840501 Cml1 camello-like 1 -2,4-3,1 -3,1 1,1 588 96426_atU38967 Tmsb4x thymosin, beta 4, X chromosome 1,31,0 2,7 1,3 109 95016_atD50086 Nrp neuropilin 1,01,7 1,1 2,0 74 93100_atX13297 Acta2 actin, alpha 2, smooth muscle, aorta 1,11,0 1,8 1,3 24 100120_atL17324 Nid1 nidogen 1 1,41,3 1,7 1,1 11 92608_atD88793 Csrp1 cysteine and glycine-rich protein 1 1,01,1 1,5 1,0 29 93318_atU91513 Ninj1 ninjurin 1 -1,2-1,5 -1,3 -1,2 203 103330_atAI838709 Strbp spermatid perinuclear RNA binding protein 1,11,6 1,4 1,1 30 96774_atAW047139 Plekhc1 pleckstrin homology domain containing, family -1,2-1,3 -1,5 1,8 78 100446_r_atX91825 Sprr1b small proline-rich protein 1B -1,11,1 1,6 -1,1 1204 92558_atM84487 Vcam1 vascular cell adhesion molecule 1 1,2-1,0 1,9 1,2 18 100554_atAF053367 Pdlim1 PDZ and LIM domain 1 (elfin) 1,01,0 1,8 1,2 109 161188_f_atAV238648 Lamb3 laminin, beta 3 1,12,2 -1,0 -1,1 51 160417_atU86090 Kif5b kinesin family member 5B -1,21,0 -1,0 1,6 25 92759_atU43298 Lamb3 laminin, beta 3 1,57,2 1,1 -1,3 39 98462_s_atAI322968 Klc8 kinesin-like protein 8 -1,3-1,3 -1,2 -1,6 41 102805_atM77196 Ceacam1 CEA-related cell adhesion molecule 1 -1,6-1,8 -2,1 -1,5 278 99458_i_atX70764 Mark2 MAP/microtubule affinity-regulating kinase 2 -1,21,1 1,5 1,1 104 102806_g_atM77196 Ceacam1 CEA-related cell adhesion molecule 1 -1,7-1,8 -2,1 -1,5 130 97447_atAI836718 Map1lc3a microtubule-associated protein 1 light chain 3 1,91,5 1,4 -1,1 106 101908_s_atAF101164 Ceacam2 CEA-related cell adhesion molecule 2 -1,4-1,5 -1,7 -1,5 135 100915_atAW125698 Myh9 myosin heavy chain IX 1,11,1 1,7 -1,0 155 93063_atU82624 App amyloid beta (A4) precursor protein 1,21,3 1,8 1,1 155 98409_atL00923 Myo1b myosin IB -1,4-2,9 -2,0 1,2 220 92593_atD13664 Osf2-pen osteoblast specific factor 2 (fasciclin I-like) 1,71,2 2,0 -1,2 20 92254_atM55253 Myo5b myosin Vb 1,31,6 1,5 -1,3 77 93353_atAF013262 Lum lumican -1,1-1,1 1,7 1,4 22 160532_atM22479 Tpm1 tropomyosin 1, alpha 1,31,4 2,5 1,1 75 160583_atAA880988 Xlkd1 extra cellular link domain-containing 1 1,41,3 1,9 -1,2 18 94270_atM22832 Krt1-18 keratin complex 1, acidic, gene 18 -1,01,3 2,7 1,0 209 104337_f_atAW208938 Pkp2 plakophilin 2 1,71,4 1,4 -1,1 116 101009_atX15662 Krt2-8 keratin complex 2, basic, gene 8 1,21,5 3,1 -1,1 377 102852_atM31131 Cdh2 cadherin 2 -1,2-1,1 -1,3 2,1 64 100342_i_atM28729 Tuba1 tubulin, alpha 1 1,21,0 1,6 1,2 82 98549_atM77123 Vtn vitronectin -1,5-2,0 -1,6 1,1 2239 100343_f_atM28729 Tuba1 tubulin, alpha 1 1,1-1,0 1,6 1,0 301 100990_g_atAJ001373 Itgb1bp1 integrin beta 1 binding protein 1 -1,2-1,1 1,6 -1,1 38 98759_f_atM28727 Tuba2 tubulin, alpha 2 1,11,1 1,7 1,1 540 94963_atAI462105 Vcl vinculin 1,11,6 1,6 1,3 63 94835_f_atM28739 Tubb2 tubulin, beta 2 4,22,8 6,4 -1,8 395 104257_g_atAI120844 Pscdbp pleckstrin homology, Sec7 and coiled-coil 1,21,1 1,3 1,5 24 160462_f_atAW050256 Tubb3 tubulin, beta 3 2,42,0 3,4 -1,3 150 92880_atM38337 Mfge8 milk fat globule-EGF factor 8 protein 1,11,6 1,7 1,1 170 94788_f_atX04663 Tubb5 tubulin, beta 5 1,71,8 2,5 1,0 256 95706_atX16834 Lgals3 lectin, galactose binding, soluble 3 1,11,2 5,3 1,0 22 160461_f_atAW215736 Tubb6 tubulin, beta 6 1,31,6 2,4 -1,2 67 160099_atAF026799 Lgals4 lectin, galactose binding, soluble 4 1,11,7 -1,1 -1,3 54 5 peroxisome organization and biogenesis 99669_atX15986 Lgals1 lectin, galactose binding, soluble 1 3,92,9 4,5 -2,0 107 98965_atAC002397 Grcc3f, gene rich cluster, C3f gene 1,33,0 1,9 -1,4 141 95566_atAF050666 Gpld1 glycosylphosphatidylinositol specific -1,4-4,6 -2,5 1,3 288 95074_atAW125309 Pxf peroxisomal farnesylated protein 1,51,5 1,2 -1,4 96 160179_atAW124122 Col12a1 collagen, type XII, alpha1 -1,11,0 -1,1 1,6 54 104098_atL28835 Pxmp2 peroxisomal membrane protein 2 -1,0-1,3 -1,7 -1,1 1281 103709_atAA763466 Col1a1 procollagen, type I, alpha 1 1,11,2 1,8 1,1 58 94491_atAW123194 Pex13 peroxisomal biogenesis factor 13 1,21,6 -1,1 1,0 35 94305_atU03419 Col1a1 procollagen, type I, alpha 1 1,41,8 6,1 1,1 39 99469_atAW121865 Pex6 peroxisomal biogenesis factor 6 1,51,1 -1,1 1,2 127 101130_atX58251 Col1a2 procollagen, type I, alpha 2 1,11,2 2,4 1,1 45 299 Environmental Information Processing 161984_f_atAV234303 Col3a1 procollagen, type III, alpha 1 1,01,1 1,5 -1,0 10 3 angiogenesis 98331_atX52046 Col3a1 procollagen, type III, alpha 1 -1,01,3 3,0 -1,1 34 94392_f_atU22516 Ang angiogenin -1,8-1,4 -1,4 2,6 348 101093_atM15832 Col4a1 procollagen, type IV, alpha 1 1,61,5 2,6 1,2 47 101735_f_atU22519 Ang2 angiogenin, ribonuclease A family, member 2 -1,3-1,2 -1,1 1,8 50 101039_atX04647 Col4a2 procollagen, type IV, alpha 2 1,21,6 1,8 1,1 93 160484_atAI840118 Rtn4 reticulon 4 1,52,3 1,3 -2,0 185 92567_atL02918 Col5a2 procollagen, type V, alpha 2 1,21,2 2,3 1,1 17 17 blood coagulation 101110_atAF064749 Col6a3 procollagen, type VI, alpha 3 1,11,2 1,8 1,2 57 99638_atD17546 Col18a1 procollagen, type XVIII, alpha 1 -1,2-1,3 -1,6 -1,1 878 102291_atM23109 F9 coagulation factor IX -1,2-1,4 -1,8 1,1 335 93934_atAF072128 Cldn2 claudin 2 -1,2-1,3 -1,1 -1,6 195 97435_atD10071 F13b coagulation factor XIII, beta subunit -1,4-1,7 -1,7 -1,1 197 96868_atAI196896 Fgb fibrinogen, B beta polypeptide -1,3-1,4 -1,5 1,3 672 25 cell cycle 93096_atAA986050 FGG fibrinogen, gamma polypeptide -1,3-1,8 -1,6 1,4 1362 96146_atD83745 Btg3 B-cell translocation gene 3 -1,11,2 1,6 1,6 16 161458_atAV298640 F7 coagulation factor VII -1,4-1,5 -1,4 1,2 534 101906_atAA032310 Smc4l1 SMC4 structural maintenance of 1,01,8 1,6 1,0 23 92918_atU66079 F7 coagulation factor VII , serum prothrombin -1,5-2,6 -1,9 1,2 201 160623_atAI847045 Cdkl2 cyclin-dependent kinase-like 2 (CDC2-related 1,21,5 1,5 1,1 21 102748_atU52925 F5 coagulation factor V -1,7-2,0 -1,7 1,1 317 96319_atAW061324 Cdc20 cell division cycle 20 homolog (S.
Recommended publications
  • Proteomic Analyses Reveal a Role of Cytoplasmic Droplets As an Energy Source During Sperm Epididymal Maturation

    Proteomic Analyses Reveal a Role of Cytoplasmic Droplets As an Energy Source During Sperm Epididymal Maturation

    Proteomic analyses reveal a role of cytoplasmic droplets as an energy source during sperm epididymal maturation Shuiqiao Yuana,b, Huili Zhenga, Zhihong Zhengb, Wei Yana,1 aDepartment of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, 89557; and bDepartment of Laboratory Animal Medicine, China Medical University, Shenyang, 110001, China Corresponding author. Email: [email protected] Supplemental Information contains one Figure (Figure S1), three Tables (Tables S1-S3) and two Videos (Videos S1 and S2) files. Figure S1. Scanning electron microscopic images of purified murine cytoplasmic droplets. Arrows point to indentations resembling the resealed defects at the detaching points when CDs come off the sperm flagella. Scale bar = 1µm Table S1 Mass spectrometry-based identifiaction of proteins highly enriched in murine cytoplasmic droplets. # MS/MS View:Identified Proteins (105) Accession Number Molecular Weight Protein Grouping Ambiguity Dot_1_1 Dot_2_1 Dot_3_1 Dot_4_1Dot_5_1 Dot_1_2 Dot_2_2 Dot_3_2 Dot_4_2 Dot_5_2 1 IPI:IPI00467457.3 Tax_Id=10090 Gene_Symbol=Ldhc L-lactate dehydrogenase C chain IPI00467457 36 kDa TRUE 91% 100% 100% 100% 100% 100% 100% 100% 100% 2 IPI:IPI00473320.2 Tax_Id=10090 Gene_Symbol=Actb Putative uncharacterized protein IPI00473320 42 kDa TRUE 75% 100% 100% 100% 100% 89% 76% 100% 100% 100% 3 IPI:IPI00224181.7 Tax_Id=10090 Gene_Symbol=Akr1b7 Aldose reductase-related protein 1 IPI00224181 36 kDa TRUE 100% 100% 76% 100% 100% 4 IPI:IPI00228633.7 Tax_Id=10090 Gene_Symbol=Gpi1 Glucose-6-phosphate
  • 1 Metabolic Dysfunction Is Restricted to the Sciatic Nerve in Experimental

    1 Metabolic Dysfunction Is Restricted to the Sciatic Nerve in Experimental

    Page 1 of 255 Diabetes Metabolic dysfunction is restricted to the sciatic nerve in experimental diabetic neuropathy Oliver J. Freeman1,2, Richard D. Unwin2,3, Andrew W. Dowsey2,3, Paul Begley2,3, Sumia Ali1, Katherine A. Hollywood2,3, Nitin Rustogi2,3, Rasmus S. Petersen1, Warwick B. Dunn2,3†, Garth J.S. Cooper2,3,4,5* & Natalie J. Gardiner1* 1 Faculty of Life Sciences, University of Manchester, UK 2 Centre for Advanced Discovery and Experimental Therapeutics (CADET), Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester, UK 3 Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, UK 4 School of Biological Sciences, University of Auckland, New Zealand 5 Department of Pharmacology, Medical Sciences Division, University of Oxford, UK † Present address: School of Biosciences, University of Birmingham, UK *Joint corresponding authors: Natalie J. Gardiner and Garth J.S. Cooper Email: [email protected]; [email protected] Address: University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, United Kingdom Telephone: +44 161 275 5768; +44 161 701 0240 Word count: 4,490 Number of tables: 1, Number of figures: 6 Running title: Metabolic dysfunction in diabetic neuropathy 1 Diabetes Publish Ahead of Print, published online October 15, 2015 Diabetes Page 2 of 255 Abstract High glucose levels in the peripheral nervous system (PNS) have been implicated in the pathogenesis of diabetic neuropathy (DN). However our understanding of the molecular mechanisms which cause the marked distal pathology is incomplete. Here we performed a comprehensive, system-wide analysis of the PNS of a rodent model of DN.
  • Supplementary Table S4. FGA Co-Expressed Gene List in LUAD

    Supplementary Table S4. FGA Co-Expressed Gene List in LUAD

    Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase
  • The Metabolic Serine Hydrolases and Their Functions in Mammalian Physiology and Disease Jonathan Z

    The Metabolic Serine Hydrolases and Their Functions in Mammalian Physiology and Disease Jonathan Z

    REVIEW pubs.acs.org/CR The Metabolic Serine Hydrolases and Their Functions in Mammalian Physiology and Disease Jonathan Z. Long* and Benjamin F. Cravatt* The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States CONTENTS 2.4. Other Phospholipases 6034 1. Introduction 6023 2.4.1. LIPG (Endothelial Lipase) 6034 2. Small-Molecule Hydrolases 6023 2.4.2. PLA1A (Phosphatidylserine-Specific 2.1. Intracellular Neutral Lipases 6023 PLA1) 6035 2.1.1. LIPE (Hormone-Sensitive Lipase) 6024 2.4.3. LIPH and LIPI (Phosphatidic Acid-Specific 2.1.2. PNPLA2 (Adipose Triglyceride Lipase) 6024 PLA1R and β) 6035 2.1.3. MGLL (Monoacylglycerol Lipase) 6025 2.4.4. PLB1 (Phospholipase B) 6035 2.1.4. DAGLA and DAGLB (Diacylglycerol Lipase 2.4.5. DDHD1 and DDHD2 (DDHD Domain R and β) 6026 Containing 1 and 2) 6035 2.1.5. CES3 (Carboxylesterase 3) 6026 2.4.6. ABHD4 (Alpha/Beta Hydrolase Domain 2.1.6. AADACL1 (Arylacetamide Deacetylase-like 1) 6026 Containing 4) 6036 2.1.7. ABHD6 (Alpha/Beta Hydrolase Domain 2.5. Small-Molecule Amidases 6036 Containing 6) 6027 2.5.1. FAAH and FAAH2 (Fatty Acid Amide 2.1.8. ABHD12 (Alpha/Beta Hydrolase Domain Hydrolase and FAAH2) 6036 Containing 12) 6027 2.5.2. AFMID (Arylformamidase) 6037 2.2. Extracellular Neutral Lipases 6027 2.6. Acyl-CoA Hydrolases 6037 2.2.1. PNLIP (Pancreatic Lipase) 6028 2.6.1. FASN (Fatty Acid Synthase) 6037 2.2.2. PNLIPRP1 and PNLIPR2 (Pancreatic 2.6.2.
  • ESID Registry – Working Definitions for Clinical Diagnosis of PID

    ESID Registry – Working Definitions for Clinical Diagnosis of PID

    ESID Registry – Working Definitions for Clinical Diagnosis of PID These criteria are only for patients with no genetic diagnosis*. *Exceptions: Atypical SCID, DiGeorge syndrome – a known genetic defect and confirmation of criteria is mandatory. Available entries (Please click on an entry to see the criteria.) Page Acquired angioedema .................................................................................................................................................................. 4 Agammaglobulinemia .................................................................................................................................................................. 4 Asplenia syndrome (Ivemark syndrome) ................................................................................................................................... 4 Ataxia telangiectasia (ATM) ......................................................................................................................................................... 4 Atypical Severe Combined Immunodeficiency (Atypical SCID) ............................................................................................... 5 Autoimmune lymphoproliferative syndrome (ALPS) ................................................................................................................ 5 APECED / APS1 with CMC - Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) .................. 5 Barth syndrome ...........................................................................................................................................................................
  • Comprehensive Genetic Analysis of Complement and Coagulation Genes in Atypical Hemolytic Uremic Syndrome

    Comprehensive Genetic Analysis of Complement and Coagulation Genes in Atypical Hemolytic Uremic Syndrome

    BASIC RESEARCH www.jasn.org Comprehensive Genetic Analysis of Complement and Coagulation Genes in Atypical Hemolytic Uremic Syndrome † † † ‡ † Fengxiao Bu,* Tara Maga,* Nicole C. Meyer, Kai Wang, Christie P. Thomas, § † † Carla M. Nester, § and Richard J. H. Smith* § *Interdisciplinary PhD Program in Genetics, †Molecular Otolaryngology and Renal Research Laboratories, ‡Department of Biostatistics, College of Public Health, and §Rare Renal Disease Clinic, Departments of Pediatrics and Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa ABSTRACT Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy caused by uncontrolled activation of the alternative pathway of complement at the cell surface level that leads to microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney failure. In approximately one half of affected patients, pathogenic loss-of-function variants in regulators of complement or gain-of-function variants in effectors of complement are identified, clearly implicating complement in aHUS. However, there are strong lines of evidence supporting the presence of additional genetic contributions to this disease. To identify novel aHUS-associated genes, we completed a comprehensive screen of the complement and coagulation pathways in 36 patients with sporadic aHUS using targeted genomic enrichment and mas- sively parallel sequencing. After variant calling, quality control, and hard filtering, we identified 84 reported or novel nonsynonymous variants, 22 of which have been previously associated with disease. Using computational prediction methods, 20 of the remaining 62 variants were predicted to be dele- terious. Consistent with published data, nearly one half of these 42 variants (19; 45%) were found in genes implicated in the pathogenesis of aHUS. Several genes in the coagulation pathway were also identified as important in the pathogenesis of aHUS.
  • Hypoxia Restrains the Expression of Complement Component 9 in Tumor

    Hypoxia Restrains the Expression of Complement Component 9 in Tumor

    Li et al. Cell Death Discovery (2018) 4:63 DOI 10.1038/s41420-018-0064-3 Cell Death Discovery ARTICLE Open Access Hypoxia restrains the expression of complement component 9 in tumor- associated macrophages promoting non- smallcelllungcancerprogression Lei Li1, Hong Yang1,2,3, Yan Li1, Xiao-Dong Li1,3, Ting-Ting Zeng1,Su-XiaLin4,Ying-HuiZhu1 and Xin-Yuan Guan 1,5 Abstract The tumor microenvironment, including stroma cells, signaling molecules, and the extracellular matrix, critically regulates the growth and survival of cancer cells. Dissecting the active molecules in tumor microenvironment may uncover the key factors that can impact cancer progression. Human NSCLC tumor tissue-conditioned medium (TCM) and adjacent nontumor tissue-conditioned medium (NCM) were used to treat two NSCLC cells LSC1 and LAC1, respectively. Cell growth and foci formation assays were applied to assess the effects of TCM and NCM on cancer cells. The active factors were identified by protein mass spectrometry. Cell growth and foci formation assays showed that 8 of 26 NCM and none of TCM could effectively lead to tumor cell lysis, which was known as tumoricidal activity. And then protein mass spectrometry analysis and functional verifications confirmed that complement component 9 (C9) played a crucial role in the complement-dependent cytotoxicity (CDC)-mediated tumoricidal activity in vitro. Furthermore, immunofluorescent staining revealed that C9 specifically expressed in most alveolar macrophages (AMs) 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; in adjacent lung tissues and a small fraction of tumor-associated macrophages (TAMs) in NSCLC tissues. Most importantly, the percentage of C9-positive cells in AMs or TAMs was responsible for the tumoricidal activity of NCM and TCM.
  • Synthesis, Molecular Docking, and Biological Evaluation of 3-Oxo-2

    Synthesis, Molecular Docking, and Biological Evaluation of 3-Oxo-2

    Bioorganic Chemistry 91 (2019) 103097 Contents lists available at ScienceDirect Bioorganic Chemistry journal homepage: www.elsevier.com/locate/bioorg Synthesis, molecular docking, and biological evaluation of 3-oxo-2- T tolylhydrazinylidene-4,4,4-trifluorobutanoates bearing higher and natural alcohol moieties as new selective carboxylesterase inhibitors Galina F. Makhaevaa, Natalia A. Elkinab, Evgeny V. Shchegolkovb, Natalia P. Boltnevaa, Sofya V. Lushchekinac, Olga G. Serebryakovaa, Elena V. Rudakovaa, Nadezhda V. Kovalevaa, Eugene V. Radchenkod, Vladimir A. Palyulind, Yanina V. Burgartb, Victor I. Saloutinb, ⁎ Sergey O. Bachurina, Rudy J. Richardsone,f, a Institute of Physiologically Active Compounds Russian Academy of Sciences, Chernogolovka 142432, Russia b Postovsky Institute of Organic Synthesis, Urals Branch of Russian Academy of Sciences, Yekaterinburg 620990, Russia c Emanuel Institute of Biochemical Physics Russian Academy of Sciences, Moscow 119334, Russia d Department of Chemistry, Lomonosov Moscow State University, Moscow 119991, Russia e Departments of Environmental Health Sciences and Neurology, University of Michigan, Ann Arbor, MI 48109, USA f Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA ARTICLE INFO ABSTRACT Keywords: To search for effective and selective inhibitors of carboxylesterase (CES), a series of 3-oxo-2-tolylhy- 3-oxo-2-tolylhydrazinylidene-4,4,4- drazinylidene-4,4,4-trifluorobutanoates bearing higher or natural alcohol moieties was synthesized viapre- trifluorobutanoates transesterification of ethyl trifluoroacetylacetate with alcohols to isolate transesterificated oxoesters aslithium Higher alcohols salts, which were then subjected to azo coupling with tolyldiazonium chloride. Inhibitory activity against por- Natural alcohols cine liver CES, along with two structurally related serine hydrolases, acetylcholinesterase and butyr- Transesterification ylcholinesterase, were investigated using enzyme kinetics and molecular docking.
  • The Effect of Bee Venom Peptides Melittin, Tertiapin, and Apamin On

    The Effect of Bee Venom Peptides Melittin, Tertiapin, and Apamin On

    H OH metabolites OH Article The Effect of Bee Venom Peptides Melittin, Tertiapin, and Apamin on the Human Erythrocytes Ghosts: A Preliminary Study 1, 2, 1 3 Agata Swiatły-Błaszkiewicz´ y, Lucyna Mrówczy ´nska y, Eliza Matuszewska , Jan Lubawy , Arkadiusz Urba ´nski 3 , Zenon J. Kokot 1, Grzegorz Rosi ´nski 3 and Jan Matysiak 1,* 1 Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, 60-780 Poznan, Poland; [email protected] (A.S.-B.);´ [email protected] (E.M.); [email protected] (Z.J.K.) 2 Department of Cell Biology, Faculty of Biology, Adam Mickiewicz University in Poznan, 61-614 Poznan, Poland; [email protected] 3 Department of Animal Physiology and Development, Faculty of Biology, Adam Mickiewicz University in Poznan, 61-614 Poznan, Poland; [email protected] (J.L.); [email protected] (A.U.); [email protected] (G.R.) * Correspondence: [email protected] These two authors contributed equally to this work. y Received: 11 April 2020; Accepted: 11 May 2020; Published: 13 May 2020 Abstract: Red blood cells (RBCs) are the most abundant cells in the human blood that have been extensively studied under morphology, ultrastructure, biochemical and molecular functions. Therefore, RBCs are excellent cell models in the study of biologically active compounds like drugs and toxins on the structure and function of the cell membrane. The aim of the present study was to explore erythrocyte ghost’s proteome to identify changes occurring under the influence of three bee venom peptides-melittin, tertiapin, and apamin. We conducted preliminary experiments on the erythrocyte ghosts incubated with these peptides at their non-hemolytic concentrations.
  • Aberrant Complement System Activation in Neurological Disorders

    Aberrant Complement System Activation in Neurological Disorders

    International Journal of Molecular Sciences Review Aberrant Complement System Activation in Neurological Disorders Karolina Ziabska , Malgorzata Ziemka-Nalecz, Paulina Pawelec, Joanna Sypecka and Teresa Zalewska * Mossakowski Medical Research Centre, NeuroRepair Department, Polish Academy of Sciences, 5 Pawinskiego Street, 02-106 Warsaw, Poland; [email protected] (K.Z.); [email protected] (M.Z.-N.); [email protected] (P.P.); [email protected] (J.S.) * Correspondence: [email protected]; Tel.: +48-(22)-608-65-29; Fax: +48-(22)-608-66-23 Abstract: The complement system is an assembly of proteins that collectively participate in the functions of the healthy and diseased brain. The complement system plays an important role in the maintenance of uninjured (healthy) brain homeostasis, contributing to the clearance of invading pathogens and apoptotic cells, and limiting the inflammatory immune response. However, overacti- vation or underregulation of the entire complement cascade within the brain may lead to neuronal damage and disturbances in brain function. During the last decade, there has been a growing interest in the role that this cascading pathway plays in the neuropathology of a diverse array of brain disorders (e.g., acute neurotraumatic insult, chronic neurodegenerative diseases, and psychiatric disturbances) in which interruption of neuronal homeostasis triggers complement activation. Dys- function of the complement promotes a disease-specific response that may have either beneficial or detrimental effects. Despite recent advances, the explicit link between complement component regulation and brain disorders remains unclear. Therefore, a comprehensible understanding of such relationships at different stages of diseases could provide new insight into potential therapeutic targets to ameliorate or slow progression of currently intractable disorders in the nervous system.
  • Carboxylesterases in Lipid Metabolism: from Mouse to Human

    Carboxylesterases in Lipid Metabolism: from Mouse to Human

    Protein Cell DOI 10.1007/s13238-017-0437-z Protein & Cell REVIEW Carboxylesterases in lipid metabolism: from mouse to human & Jihong Lian1,2 , Randal Nelson1,2, Richard Lehner1,2,3 1 Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada 2 Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada 3 Department of Cell Biology, University of Alberta, Edmonton, Alberta, Canada & Correspondence: [email protected] (J. Lian) Received March 2, 2017 Accepted May 31, 2017 Cell & ABSTRACT Hatfield et al., 2016; Fukami et al., 2015; Laizure et al., 2013; Staudinger et al., 2010; Sanghani et al., 2009; Imai, 2006). Mammalian carboxylesterases hydrolyze a wide range However, carboxylesterases have also been demonstrated of xenobiotic and endogenous compounds, including to hydrolyze endogenous esters and thioesters including lipid esters. Physiological functions of car- lipids and some of these enzymes have been shown to play Protein boxylesterases in lipid metabolism and energy home- important physiological functions in lipid metabolism and ostasis in vivo have been demonstrated by genetic energy homeostasis. Recent research endeavors have manipulations and chemical inhibition in mice, and provided more insight into the roles of human car- in vitro through (over)expression, knockdown of boxylesterases in metabolic diseases. expression, and chemical inhibition in a variety of cells. Genes encoding six human carboxylesterases and twenty Recent research advances have revealed the relevance mouse carboxylesterases have been classified. However, of carboxylesterases to metabolic diseases such as given the interspecies diversity of carboxylesterases both in obesity and fatty liver disease, suggesting these the number and primary amino acid sequences there is a enzymes might be potential targets for treatment of need to define functional mouse and human orthologs.
  • Identification of Genomic Biomarkers of Exposure to Ahr Ligands Bladimir J Ovando1, Corie a Ellison1, Chad M Vezina2, James R Olson1*

    Identification of Genomic Biomarkers of Exposure to Ahr Ligands Bladimir J Ovando1, Corie a Ellison1, Chad M Vezina2, James R Olson1*

    Ovando et al. BMC Genomics 2010, 11:583 http://www.biomedcentral.com/1471-2164/11/583 RESEARCH ARTICLE Open Access Toxicogenomic analysis of exposure to TCDD, PCB126 and PCB153: identification of genomic biomarkers of exposure to AhR ligands Bladimir J Ovando1, Corie A Ellison1, Chad M Vezina2, James R Olson1* Abstract Background: Two year cancer bioassays conducted by the National Toxicology Program have shown chronic exposure to dioxin-like compounds (DLCs) to lead to the development of both neoplastic and non-neoplastic lesions in the hepatic tissue of female Sprague Dawley rats. Most, if not all, of the hepatotoxic effects induced by DLC’s are believed to involve the binding and activation of the transcription factor, the aryl hydrocarbon receptor (AhR). Toxicogenomics was implemented to identify genomic responses that may be contributing to the development of hepatotoxicity in rats. Results: Through comparative analysis of time-course microarray data, unique hepatic gene expression signatures were identified for the DLCs, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (100 ng/kg/day) and 3,3’,4,4’,5-pentachlorobiphenyl (PCB126) (1000 ng/kg/day) and the non-DLC 2,2’,4,4’,5,5’,-hexachlorobiphenyl (PCB153) (1000 μg/kg/day). A common time independent signature of 41 AhR genomic biomarkers was identified which exhibited at least a 2-fold change in expression following subchronic (13-wk) and chronic (52-wk) p.o. exposure to TCDD and PCB126, but not the non DLC, PCB153. Real time qPCR analysis validated that 30 of these genes also exhibited at least a 2-fold change in hepatic expression at 24 hr following a single exposure to TCDD (5 μg/kg, po).