CA2519476A1

CA2519476A1 - Genetic polymorphisms associated with rheumatoid arthritis, methods of detection and uses thereof

Genetic polymorphisms associated with rheumatoid arthritis, methods of detection and uses thereof Download PDF

Info

Publication number: CA2519476A1
Authority: CA; Canada
Prior art keywords: snp; nucleic acid; snps; protein; allele
Prior art date: 2003-03-18
Legal status : Abandoned

Application number

CA002519476A

Other languages

English (en)

French (fr)

Inventor

Michele Cargill

Ann B. Begovich

Heather C. Alexander

Current Assignee

Celera Corp

Original Assignee

Individual

Priority date

2003-03-18

Filing date

2004-03-18

Publication date

2004-09-30

2004-03-18 Application filed by Individual filed Critical Individual

2004-09-30 Publication of CA2519476A1 publication Critical patent/CA2519476A1/en

Status Abandoned legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims abstract description 188
206010039073 rheumatoid arthritis Diseases 0.000 title claims abstract description 150
238000001514 detection method Methods 0.000 title claims abstract description 100
206010071602 Genetic polymorphism Diseases 0.000 title abstract description 5
150000007523 nucleic acids Chemical class 0.000 claims abstract description 289
102000039446 nucleic acids Human genes 0.000 claims abstract description 272
108020004707 nucleic acids Proteins 0.000 claims abstract description 272
239000003153 chemical reaction reagent Substances 0.000 claims abstract description 80
108700028369 Alleles Proteins 0.000 claims description 231
125000003729 nucleotide group Chemical group 0.000 claims description 187
239000002773 nucleotide Substances 0.000 claims description 184
239000000523 sample Substances 0.000 claims description 166
108090000765 processed proteins & peptides Proteins 0.000 claims description 91
239000012634 fragment Substances 0.000 claims description 72
102000004196 processed proteins & peptides Human genes 0.000 claims description 68
238000003556 assay Methods 0.000 claims description 66
238000012360 testing method Methods 0.000 claims description 55
125000003275 alpha amino acid group Chemical group 0.000 claims description 53
230000027455 binding Effects 0.000 claims description 50
229920001184 polypeptide Polymers 0.000 claims description 47
102000040430 polynucleotide Human genes 0.000 claims description 45
108091033319 polynucleotide Proteins 0.000 claims description 45
239000002157 polynucleotide Substances 0.000 claims description 45
238000004458 analytical method Methods 0.000 claims description 38
108091028043 Nucleic acid sequence Proteins 0.000 claims description 37
238000003199 nucleic acid amplification method Methods 0.000 claims description 35
239000003795 chemical substances by application Substances 0.000 claims description 34
230000003321 amplification Effects 0.000 claims description 33
238000009396 hybridization Methods 0.000 claims description 32
230000001965 increasing effect Effects 0.000 claims description 30
108091034117 Oligonucleotide Proteins 0.000 claims description 29
208000023275 Autoimmune disease Diseases 0.000 claims description 28
230000000295 complement effect Effects 0.000 claims description 27
238000012163 sequencing technique Methods 0.000 claims description 19
230000015572 biosynthetic process Effects 0.000 claims description 18
230000003247 decreasing effect Effects 0.000 claims description 18
102000004190 Enzymes Human genes 0.000 claims description 12
108090000790 Enzymes Proteins 0.000 claims description 12
230000008569 process Effects 0.000 claims description 12
101710163270 Nuclease Proteins 0.000 claims description 7
239000000427 antigen Substances 0.000 claims description 6
108091007433 antigens Proteins 0.000 claims description 6
102000036639 antigens Human genes 0.000 claims description 6
208000023328 Basedow disease Diseases 0.000 claims description 5
208000015943 Coeliac disease Diseases 0.000 claims description 5
206010018364 Glomerulonephritis Diseases 0.000 claims description 5
208000015023 Graves' disease Diseases 0.000 claims description 5
208000022559 Inflammatory bowel disease Diseases 0.000 claims description 5
208000009525 Myocarditis Diseases 0.000 claims description 5
208000031845 Pernicious anaemia Diseases 0.000 claims description 5
201000004681 Psoriasis Diseases 0.000 claims description 5
208000021386 Sjogren Syndrome Diseases 0.000 claims description 5
208000004732 Systemic Vasculitis Diseases 0.000 claims description 5
206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 5
206010047115 Vasculitis Diseases 0.000 claims description 5
206010047642 Vitiligo Diseases 0.000 claims description 5
208000006673 asthma Diseases 0.000 claims description 5
201000006417 multiple sclerosis Diseases 0.000 claims description 5
201000000596 systemic lupus erythematosus Diseases 0.000 claims description 5
206010043778 thyroiditis Diseases 0.000 claims description 5
239000000872 buffer Substances 0.000 claims description 4
230000002596 correlated effect Effects 0.000 claims description 3
230000029087 digestion Effects 0.000 claims description 3
108090000623 proteins and genes Proteins 0.000 abstract description 526
102000004169 proteins and genes Human genes 0.000 abstract description 388
102000054765 polymorphisms of proteins Human genes 0.000 abstract description 37
108091005461 Nucleic proteins Proteins 0.000 abstract description 2
235000018102 proteins Nutrition 0.000 description 381
210000004027 cell Anatomy 0.000 description 126
239000013615 primer Substances 0.000 description 125
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 100
230000014509 gene expression Effects 0.000 description 97
150000001875 compounds Chemical class 0.000 description 85
201000010099 disease Diseases 0.000 description 85
239000003814 drug Substances 0.000 description 80
108020004414 DNA Proteins 0.000 description 67
241000282414 Homo sapiens Species 0.000 description 67
239000000047 product Substances 0.000 description 64
235000001014 amino acid Nutrition 0.000 description 54
241001465754 Metazoa Species 0.000 description 53
239000013598 vector Substances 0.000 description 53
150000001413 amino acids Chemical class 0.000 description 45
230000001225 therapeutic effect Effects 0.000 description 44
230000002068 genetic effect Effects 0.000 description 43
229940079593 drug Drugs 0.000 description 41
238000011282 treatment Methods 0.000 description 41
230000000694 effects Effects 0.000 description 40
238000003205 genotyping method Methods 0.000 description 40
230000009261 transgenic effect Effects 0.000 description 39
230000000875 corresponding effect Effects 0.000 description 35
108020004705 Codon Proteins 0.000 description 34
108020004999 messenger RNA Proteins 0.000 description 34
102000054766 genetic haplotypes Human genes 0.000 description 33
230000002974 pharmacogenomic effect Effects 0.000 description 30
229940124597 therapeutic agent Drugs 0.000 description 30
230000001105 regulatory effect Effects 0.000 description 28
230000010076 replication Effects 0.000 description 27
210000001519 tissue Anatomy 0.000 description 27
238000003752 polymerase chain reaction Methods 0.000 description 26
230000006870 function Effects 0.000 description 25
108091032973 (ribonucleotides)n+m Proteins 0.000 description 24
230000000692 anti-sense effect Effects 0.000 description 24
239000013604 expression vector Substances 0.000 description 24
239000002609 medium Substances 0.000 description 24
239000002987 primer (paints) Substances 0.000 description 24
238000006243 chemical reaction Methods 0.000 description 23
238000006467 substitution reaction Methods 0.000 description 23
239000000758 substrate Substances 0.000 description 23
230000035772 mutation Effects 0.000 description 22
125000000539 amino acid group Chemical group 0.000 description 21
239000000975 dye Substances 0.000 description 21
239000003550 marker Substances 0.000 description 21
239000000203 mixture Substances 0.000 description 21
238000012228 RNA interference-mediated gene silencing Methods 0.000 description 20
238000005516 engineering process Methods 0.000 description 20
230000009368 gene silencing by RNA Effects 0.000 description 20
239000003446 ligand Substances 0.000 description 20
238000012216 screening Methods 0.000 description 20
238000003491 array Methods 0.000 description 19
238000013461 design Methods 0.000 description 19
238000011161 development Methods 0.000 description 19
108091093037 Peptide nucleic acid Proteins 0.000 description 17
230000004927 fusion Effects 0.000 description 17
-1 small molecule compounds Chemical class 0.000 description 17
108091023040 Transcription factor Proteins 0.000 description 16
230000008901 benefit Effects 0.000 description 16
239000000126 substance Substances 0.000 description 16
210000000349 chromosome Anatomy 0.000 description 15
208000035475 disorder Diseases 0.000 description 15
238000004519 manufacturing process Methods 0.000 description 15
206010003246 arthritis Diseases 0.000 description 14
230000008859 change Effects 0.000 description 14
230000006378 damage Effects 0.000 description 14
230000007170 pathology Effects 0.000 description 14
230000004853 protein function Effects 0.000 description 14
238000003860 storage Methods 0.000 description 14
238000013518 transcription Methods 0.000 description 14
230000035897 transcription Effects 0.000 description 14
241000219061 Rheum Species 0.000 description 13
108700019146 Transgenes Proteins 0.000 description 13
238000003745 diagnosis Methods 0.000 description 13
102000037865 fusion proteins Human genes 0.000 description 13
108020001507 fusion proteins Proteins 0.000 description 13
239000000463 material Substances 0.000 description 13
102000040945 Transcription factor Human genes 0.000 description 12
238000004949 mass spectrometry Methods 0.000 description 12
230000004952 protein activity Effects 0.000 description 12
238000002560 therapeutic procedure Methods 0.000 description 12
108091026890 Coding region Proteins 0.000 description 11
239000012472 biological sample Substances 0.000 description 11
238000012217 deletion Methods 0.000 description 11
230000037430 deletion Effects 0.000 description 11
229940088598 enzyme Drugs 0.000 description 11
238000000338 in vitro Methods 0.000 description 11
238000001727 in vivo Methods 0.000 description 11
238000003780 insertion Methods 0.000 description 11
230000037431 insertion Effects 0.000 description 11
230000003993 interaction Effects 0.000 description 11
238000002360 preparation method Methods 0.000 description 11
JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 10
230000002950 deficient Effects 0.000 description 10
238000005755 formation reaction Methods 0.000 description 10
238000002493 microarray Methods 0.000 description 10
238000010369 molecular cloning Methods 0.000 description 10
230000001575 pathological effect Effects 0.000 description 10
230000004044 response Effects 0.000 description 10
239000007787 solid Substances 0.000 description 10
239000000243 solution Substances 0.000 description 10
230000014616 translation Effects 0.000 description 10
206010028980 Neoplasm Diseases 0.000 description 9
201000011510 cancer Diseases 0.000 description 9
239000012707 chemical precursor Substances 0.000 description 9
239000002299 complementary DNA Substances 0.000 description 9
239000011159 matrix material Substances 0.000 description 9
230000001404 mediated effect Effects 0.000 description 9
238000012545 processing Methods 0.000 description 9
YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 8
238000009015 Human TaqMan MicroRNA Assay kit Methods 0.000 description 8
102000007056 Recombinant Fusion Proteins Human genes 0.000 description 8
108010008281 Recombinant Fusion Proteins Proteins 0.000 description 8
230000004913 activation Effects 0.000 description 8
230000004075 alteration Effects 0.000 description 8
238000012093 association test Methods 0.000 description 8
239000011324 bead Substances 0.000 description 8
238000013500 data storage Methods 0.000 description 8
239000003623 enhancer Substances 0.000 description 8
230000007613 environmental effect Effects 0.000 description 8
238000003499 nucleic acid array Methods 0.000 description 8
239000008194 pharmaceutical composition Substances 0.000 description 8
239000000546 pharmaceutical excipient Substances 0.000 description 8
238000000746 purification Methods 0.000 description 8
102000040650 (ribonucleotides)n+m Human genes 0.000 description 7
108020005187 Oligonucleotide Probes Proteins 0.000 description 7
240000004808 Saccharomyces cerevisiae Species 0.000 description 7
239000000074 antisense oligonucleotide Substances 0.000 description 7
238000012230 antisense oligonucleotides Methods 0.000 description 7
238000004422 calculation algorithm Methods 0.000 description 7
238000003776 cleavage reaction Methods 0.000 description 7
238000009826 distribution Methods 0.000 description 7
239000003596 drug target Substances 0.000 description 7
238000009472 formulation Methods 0.000 description 7
238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 7
230000007246 mechanism Effects 0.000 description 7
238000012544 monitoring process Methods 0.000 description 7
239000002751 oligonucleotide probe Substances 0.000 description 7
230000007017 scission Effects 0.000 description 7
230000019491 signal transduction Effects 0.000 description 7
238000003786 synthesis reaction Methods 0.000 description 7
108020004459 Small interfering RNA Proteins 0.000 description 6
230000000890 antigenic effect Effects 0.000 description 6
238000005251 capillar electrophoresis Methods 0.000 description 6
230000001419 dependent effect Effects 0.000 description 6
238000007876 drug discovery Methods 0.000 description 6
239000000499 gel Substances 0.000 description 6
210000001503 joint Anatomy 0.000 description 6
239000007788 liquid Substances 0.000 description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
230000002441 reversible effect Effects 0.000 description 6
238000007619 statistical method Methods 0.000 description 6
238000013517 stratification Methods 0.000 description 6
238000013519 translation Methods 0.000 description 6
238000011144 upstream manufacturing Methods 0.000 description 6
108020000948 Antisense Oligonucleotides Proteins 0.000 description 5
238000000018 DNA microarray Methods 0.000 description 5
108020004485 Nonsense Codon Proteins 0.000 description 5
108700026244 Open Reading Frames Proteins 0.000 description 5
238000012408 PCR amplification Methods 0.000 description 5
230000002159 abnormal effect Effects 0.000 description 5
210000004369 blood Anatomy 0.000 description 5
239000008280 blood Substances 0.000 description 5
230000001413 cellular effect Effects 0.000 description 5
230000002163 immunogen Effects 0.000 description 5
230000001939 inductive effect Effects 0.000 description 5
230000004048 modification Effects 0.000 description 5
238000012986 modification Methods 0.000 description 5
230000001681 protective effect Effects 0.000 description 5
238000002331 protein detection Methods 0.000 description 5
230000008439 repair process Effects 0.000 description 5
229940124598 therapeutic candidate Drugs 0.000 description 5
241001515965 unidentified phage Species 0.000 description 5
108091023037 Aptamer Proteins 0.000 description 4
108090000994 Catalytic RNA Proteins 0.000 description 4
102000053642 Catalytic RNA Human genes 0.000 description 4
108010014303 DNA-directed DNA polymerase Proteins 0.000 description 4
102000016928 DNA-directed DNA polymerase Human genes 0.000 description 4
241000588724 Escherichia coli Species 0.000 description 4
108010070675 Glutathione transferase Proteins 0.000 description 4
102100029100 Hematopoietic prostaglandin D synthase Human genes 0.000 description 4
241000238631 Hexapoda Species 0.000 description 4
241000282412 Homo Species 0.000 description 4
108091092878 Microsatellite Proteins 0.000 description 4
108010076504 Protein Sorting Signals Proteins 0.000 description 4
108010091086 Recombinases Proteins 0.000 description 4
102000018120 Recombinases Human genes 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 4
238000007844 allele-specific PCR Methods 0.000 description 4
238000013459 approach Methods 0.000 description 4
238000012098 association analyses Methods 0.000 description 4
239000011230 binding agent Substances 0.000 description 4
229960002685 biotin Drugs 0.000 description 4
235000020958 biotin Nutrition 0.000 description 4
239000011616 biotin Substances 0.000 description 4
238000000423 cell based assay Methods 0.000 description 4
238000010367 cloning Methods 0.000 description 4
OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 4
238000009509 drug development Methods 0.000 description 4
238000007878 drug screening assay Methods 0.000 description 4
238000003366 endpoint assay Methods 0.000 description 4
210000003527 eukaryotic cell Anatomy 0.000 description 4
239000000284 extract Substances 0.000 description 4
239000011521 glass Substances 0.000 description 4
RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 4
UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 4
239000003112 inhibitor Substances 0.000 description 4
230000002401 inhibitory effect Effects 0.000 description 4
150000002500 ions Chemical class 0.000 description 4
238000002032 lab-on-a-chip Methods 0.000 description 4
238000007477 logistic regression Methods 0.000 description 4
230000037230 mobility Effects 0.000 description 4
230000037434 nonsense mutation Effects 0.000 description 4
210000000287 oocyte Anatomy 0.000 description 4
239000008177 pharmaceutical agent Substances 0.000 description 4
239000004033 plastic Substances 0.000 description 4
229920003023 plastic Polymers 0.000 description 4
230000008488 polyadenylation Effects 0.000 description 4
108091008146 restriction endonucleases Proteins 0.000 description 4
108091092562 ribozyme Proteins 0.000 description 4
230000028327 secretion Effects 0.000 description 4
241000894007 species Species 0.000 description 4
RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 4
231100000331 toxic Toxicity 0.000 description 4
230000002588 toxic effect Effects 0.000 description 4
231100000419 toxicity Toxicity 0.000 description 4
230000001988 toxicity Effects 0.000 description 4
241000701161 unidentified adenovirus Species 0.000 description 4
239000013603 viral vector Substances 0.000 description 4
108020005345 3' Untranslated Regions Proteins 0.000 description 3
108020003589 5' Untranslated Regions Proteins 0.000 description 3
206010067484 Adverse reaction Diseases 0.000 description 3
208000024827 Alzheimer disease Diseases 0.000 description 3
108020005544 Antisense RNA Proteins 0.000 description 3
102100029470 Apolipoprotein E Human genes 0.000 description 3
108020004635 Complementary DNA Proteins 0.000 description 3
230000004568 DNA-binding Effects 0.000 description 3
206010061818 Disease progression Diseases 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
238000000729 Fisher's exact test Methods 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
108060001084 Luciferase Proteins 0.000 description 3
239000005089 Luciferase Substances 0.000 description 3
241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 3
241000699666 Mus <mouse, genus> Species 0.000 description 3
108010033276 Peptide Fragments Proteins 0.000 description 3
102000007079 Peptide Fragments Human genes 0.000 description 3
239000002202 Polyethylene glycol Substances 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 3
238000001604 Rao's score test Methods 0.000 description 3
108020004511 Recombinant DNA Proteins 0.000 description 3
108700008625 Reporter Genes Proteins 0.000 description 3
108010090804 Streptavidin Proteins 0.000 description 3
241000700605 Viruses Species 0.000 description 3
239000002253 acid Substances 0.000 description 3
230000006838 adverse reaction Effects 0.000 description 3
239000000443 aerosol Substances 0.000 description 3
230000001093 anti-cancer Effects 0.000 description 3
230000005784 autoimmunity Effects 0.000 description 3
230000001580 bacterial effect Effects 0.000 description 3
230000004071 biological effect Effects 0.000 description 3
210000001124 body fluid Anatomy 0.000 description 3
230000003197 catalytic effect Effects 0.000 description 3
210000004671 cell-free system Anatomy 0.000 description 3
238000000546 chi-square test Methods 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
239000003184 complementary RNA Substances 0.000 description 3
230000021615 conjugation Effects 0.000 description 3
230000001276 controlling effect Effects 0.000 description 3
230000007423 decrease Effects 0.000 description 3
238000003935 denaturing gradient gel electrophoresis Methods 0.000 description 3
235000005911 diet Nutrition 0.000 description 3
230000037213 diet Effects 0.000 description 3
230000005750 disease progression Effects 0.000 description 3
238000012362 drug development process Methods 0.000 description 3
238000007877 drug screening Methods 0.000 description 3
238000001962 electrophoresis Methods 0.000 description 3
230000002255 enzymatic effect Effects 0.000 description 3
GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 3
238000002866 fluorescence resonance energy transfer Methods 0.000 description 3
230000030279 gene silencing Effects 0.000 description 3
238000012226 gene silencing method Methods 0.000 description 3
230000009395 genetic defect Effects 0.000 description 3
230000007614 genetic variation Effects 0.000 description 3
230000013595 glycosylation Effects 0.000 description 3
238000006206 glycosylation reaction Methods 0.000 description 3
239000001963 growth medium Substances 0.000 description 3
210000004209 hair Anatomy 0.000 description 3
238000011065 in-situ storage Methods 0.000 description 3
208000015181 infectious disease Diseases 0.000 description 3
230000000977 initiatory effect Effects 0.000 description 3
230000003834 intracellular effect Effects 0.000 description 3
230000002427 irreversible effect Effects 0.000 description 3
150000002632 lipids Chemical class 0.000 description 3
210000004962 mammalian cell Anatomy 0.000 description 3
239000003607 modifier Substances 0.000 description 3
239000003921 oil Substances 0.000 description 3
235000019198 oils Nutrition 0.000 description 3
239000002245 particle Substances 0.000 description 3
229940124531 pharmaceutical excipient Drugs 0.000 description 3
239000013612 plasmid Substances 0.000 description 3
229920002401 polyacrylamide Polymers 0.000 description 3
229920001223 polyethylene glycol Polymers 0.000 description 3
230000002028 premature Effects 0.000 description 3
238000004393 prognosis Methods 0.000 description 3
230000009145 protein modification Effects 0.000 description 3
230000002829 reductive effect Effects 0.000 description 3
238000011160 research Methods 0.000 description 3
238000012552 review Methods 0.000 description 3
230000003248 secreting effect Effects 0.000 description 3
230000035945 sensitivity Effects 0.000 description 3
238000000926 separation method Methods 0.000 description 3
229940126586 small molecule drug Drugs 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
238000010561 standard procedure Methods 0.000 description 3
238000001890 transfection Methods 0.000 description 3
238000011277 treatment modality Methods 0.000 description 3
238000011269 treatment regimen Methods 0.000 description 3
239000001226 triphosphate Substances 0.000 description 3
235000011178 triphosphate Nutrition 0.000 description 3
125000002264 triphosphate group Chemical class [H]OP(=O)(O[H])OP(=O)(O[H])OP(=O)(O[H])O* 0.000 description 3
241000701447 unidentified baculovirus Species 0.000 description 3
241001430294 unidentified retrovirus Species 0.000 description 3
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
230000005730 ADP ribosylation Effects 0.000 description 2
101150037123 APOE gene Proteins 0.000 description 2
GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 2
229930024421 Adenine Natural products 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
241000894006 Bacteria Species 0.000 description 2
241000283690 Bos taurus Species 0.000 description 2
241000283707 Capra Species 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
208000024172 Cardiovascular disease Diseases 0.000 description 2
108091033380 Coding strand Proteins 0.000 description 2
108020004394 Complementary RNA Proteins 0.000 description 2
102000004127 Cytokines Human genes 0.000 description 2
108090000695 Cytokines Proteins 0.000 description 2
230000004544 DNA amplification Effects 0.000 description 2
239000003155 DNA primer Substances 0.000 description 2
238000001712 DNA sequencing Methods 0.000 description 2
229920002307 Dextran Polymers 0.000 description 2
238000002965 ELISA Methods 0.000 description 2
102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 2
108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 2
240000005702 Galium aparine Species 0.000 description 2
235000014820 Galium aparine Nutrition 0.000 description 2
206010064571 Gene mutation Diseases 0.000 description 2
208000034826 Genetic Predisposition to Disease Diseases 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
108010024636 Glutathione Proteins 0.000 description 2
208000026350 Inborn Genetic disease Diseases 0.000 description 2
206010061218 Inflammation Diseases 0.000 description 2
108091029795 Intergenic region Proteins 0.000 description 2
108091092195 Intron Proteins 0.000 description 2
102000003960 Ligases Human genes 0.000 description 2
108090000364 Ligases Proteins 0.000 description 2
108010001441 Phosphopeptides Proteins 0.000 description 2
208000025747 Rheumatic disease Diseases 0.000 description 2
208000009921 Rheumatoid Nodule Diseases 0.000 description 2
238000012300 Sequence Analysis Methods 0.000 description 2
208000003028 Stuttering Diseases 0.000 description 2
238000009825 accumulation Methods 0.000 description 2
DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
230000009471 action Effects 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
239000008186 active pharmaceutical agent Substances 0.000 description 2
238000007792 addition Methods 0.000 description 2
239000000654 additive Substances 0.000 description 2
230000000996 additive effect Effects 0.000 description 2
229960000643 adenine Drugs 0.000 description 2
230000002411 adverse Effects 0.000 description 2
238000001042 affinity chromatography Methods 0.000 description 2
210000004507 artificial chromosome Anatomy 0.000 description 2
238000002820 assay format Methods 0.000 description 2
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 2
239000013060 biological fluid Substances 0.000 description 2
238000001574 biopsy Methods 0.000 description 2
239000002775 capsule Substances 0.000 description 2
239000013592 cell lysate Substances 0.000 description 2
238000012512 characterization method Methods 0.000 description 2
238000007385 chemical modification Methods 0.000 description 2
230000002759 chromosomal effect Effects 0.000 description 2
238000004590 computer program Methods 0.000 description 2
239000013068 control sample Substances 0.000 description 2
238000012937 correction Methods 0.000 description 2
229940104302 cytosine Drugs 0.000 description 2
239000002254 cytotoxic agent Substances 0.000 description 2
229940127089 cytotoxic agent Drugs 0.000 description 2
231100000599 cytotoxic agent Toxicity 0.000 description 2
230000034994 death Effects 0.000 description 2
231100000517 death Toxicity 0.000 description 2
238000002405 diagnostic procedure Methods 0.000 description 2
230000000857 drug effect Effects 0.000 description 2
229940088679 drug related substance Drugs 0.000 description 2
238000006911 enzymatic reaction Methods 0.000 description 2
238000001976 enzyme digestion Methods 0.000 description 2
230000003628 erosive effect Effects 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
239000012530 fluid Substances 0.000 description 2
238000001917 fluorescence detection Methods 0.000 description 2
230000006251 gamma-carboxylation Effects 0.000 description 2
238000004817 gas chromatography Methods 0.000 description 2
238000003197 gene knockdown Methods 0.000 description 2
238000003209 gene knockout Methods 0.000 description 2
208000016361 genetic disease Diseases 0.000 description 2
229960003180 glutathione Drugs 0.000 description 2
210000002478 hand joint Anatomy 0.000 description 2
230000036541 health Effects 0.000 description 2
229940088597 hormone Drugs 0.000 description 2
239000005556 hormone Substances 0.000 description 2
210000004408 hybridoma Anatomy 0.000 description 2
230000033444 hydroxylation Effects 0.000 description 2
238000005805 hydroxylation reaction Methods 0.000 description 2
238000003018 immunoassay Methods 0.000 description 2
238000001114 immunoprecipitation Methods 0.000 description 2
238000007901 in situ hybridization Methods 0.000 description 2
238000010348 incorporation Methods 0.000 description 2
238000011534 incubation Methods 0.000 description 2
230000004054 inflammatory process Effects 0.000 description 2
238000001499 laser induced fluorescence spectroscopy Methods 0.000 description 2
238000007834 ligase chain reaction Methods 0.000 description 2
230000033001 locomotion Effects 0.000 description 2
210000004698 lymphocyte Anatomy 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
210000001161 mammalian embryo Anatomy 0.000 description 2
238000013507 mapping Methods 0.000 description 2
238000002844 melting Methods 0.000 description 2
230000008018 melting Effects 0.000 description 2
239000012528 membrane Substances 0.000 description 2
230000004060 metabolic process Effects 0.000 description 2
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
238000000520 microinjection Methods 0.000 description 2
230000005012 migration Effects 0.000 description 2
238000013508 migration Methods 0.000 description 2
238000002703 mutagenesis Methods 0.000 description 2
231100000350 mutagenesis Toxicity 0.000 description 2
208000015122 neurodegenerative disease Diseases 0.000 description 2
230000003287 optical effect Effects 0.000 description 2
239000000123 paper Substances 0.000 description 2
230000037361 pathway Effects 0.000 description 2
238000000059 patterning Methods 0.000 description 2
238000001558 permutation test Methods 0.000 description 2
230000002085 persistent effect Effects 0.000 description 2
230000026731 phosphorylation Effects 0.000 description 2
238000006366 phosphorylation reaction Methods 0.000 description 2
239000006187 pill Substances 0.000 description 2
238000011176 pooling Methods 0.000 description 2
230000004481 post-translational protein modification Effects 0.000 description 2
210000001236 prokaryotic cell Anatomy 0.000 description 2
102000021127 protein binding proteins Human genes 0.000 description 2
108091011138 protein binding proteins Proteins 0.000 description 2
230000002797 proteolythic effect Effects 0.000 description 2
239000002213 purine nucleotide Substances 0.000 description 2
150000003212 purines Chemical class 0.000 description 2
239000012857 radioactive material Substances 0.000 description 2
238000003127 radioimmunoassay Methods 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
230000004043 responsiveness Effects 0.000 description 2
238000003757 reverse transcription PCR Methods 0.000 description 2
PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 2
210000003296 saliva Anatomy 0.000 description 2
210000000582 semen Anatomy 0.000 description 2
210000002966 serum Anatomy 0.000 description 2
230000037432 silent mutation Effects 0.000 description 2
230000000391 smoking effect Effects 0.000 description 2
210000001082 somatic cell Anatomy 0.000 description 2
230000019635 sulfation Effects 0.000 description 2
238000005670 sulfation reaction Methods 0.000 description 2
239000006228 supernatant Substances 0.000 description 2
208000024891 symptom Diseases 0.000 description 2
230000009885 systemic effect Effects 0.000 description 2
239000003826 tablet Substances 0.000 description 2
229940113082 thymine Drugs 0.000 description 2
231100000027 toxicology Toxicity 0.000 description 2
238000010361 transduction Methods 0.000 description 2
230000026683 transduction Effects 0.000 description 2
238000012546 transfer Methods 0.000 description 2
230000007704 transition Effects 0.000 description 2
230000032258 transport Effects 0.000 description 2
DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 2
229940045145 uridine Drugs 0.000 description 2
238000010200 validation analysis Methods 0.000 description 2
239000003981 vehicle Substances 0.000 description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
ASWBNKHCZGQVJV-UHFFFAOYSA-N (3-hexadecanoyloxy-2-hydroxypropyl) 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(O)COP([O-])(=O)OCC[N+](C)(C)C ASWBNKHCZGQVJV-UHFFFAOYSA-N 0.000 description 1
UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
229930182837 (R)-adrenaline Natural products 0.000 description 1
OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
VGIRNWJSIRVFRT-UHFFFAOYSA-N 2',7'-difluorofluorescein Chemical compound OC(=O)C1=CC=CC=C1C1=C2C=C(F)C(=O)C=C2OC2=CC(O)=C(F)C=C21 VGIRNWJSIRVFRT-UHFFFAOYSA-N 0.000 description 1
UFBJCMHMOXMLKC-UHFFFAOYSA-N 2,4-dinitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O UFBJCMHMOXMLKC-UHFFFAOYSA-N 0.000 description 1
102100027962 2-5A-dependent ribonuclease Human genes 0.000 description 1
108010000834 2-5A-dependent ribonuclease Proteins 0.000 description 1
WCKQPPQRFNHPRJ-UHFFFAOYSA-N 4-[[4-(dimethylamino)phenyl]diazenyl]benzoic acid Chemical compound C1=CC(N(C)C)=CC=C1N=NC1=CC=C(C(O)=O)C=C1 WCKQPPQRFNHPRJ-UHFFFAOYSA-N 0.000 description 1
ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
CJIJXIFQYOPWTF-UHFFFAOYSA-N 7-hydroxycoumarin Natural products O1C(=O)C=CC2=CC(O)=CC=C21 CJIJXIFQYOPWTF-UHFFFAOYSA-N 0.000 description 1
102100033639 Acetylcholinesterase Human genes 0.000 description 1
108010022752 Acetylcholinesterase Proteins 0.000 description 1
108010000239 Aequorin Proteins 0.000 description 1
102000002260 Alkaline Phosphatase Human genes 0.000 description 1
108020004774 Alkaline Phosphatase Proteins 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
108091093088 Amplicon Proteins 0.000 description 1
101710095339 Apolipoprotein E Proteins 0.000 description 1
108090001008 Avidin Proteins 0.000 description 1
231100000699 Bacterial toxin Toxicity 0.000 description 1
102100026189 Beta-galactosidase Human genes 0.000 description 1
241000282472 Canis lupus familiaris Species 0.000 description 1
108010078791 Carrier Proteins Proteins 0.000 description 1
208000016216 Choristoma Diseases 0.000 description 1
208000017667 Chronic Disease Diseases 0.000 description 1
238000000959 Cochran–Mantel–Haenszel (CMH) test Methods 0.000 description 1
108700010070 Codon Usage Proteins 0.000 description 1
108010047041 Complementarity Determining Regions Proteins 0.000 description 1
108010051219 Cre recombinase Proteins 0.000 description 1
241000699800 Cricetinae Species 0.000 description 1
201000003883 Cystic fibrosis Diseases 0.000 description 1
241000701022 Cytomegalovirus Species 0.000 description 1
IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 1
XPDXVDYUQZHFPV-UHFFFAOYSA-N Dansyl Chloride Chemical compound C1=CC=C2C(N(C)C)=CC=CC2=C1S(Cl)(=O)=O XPDXVDYUQZHFPV-UHFFFAOYSA-N 0.000 description 1
CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 1
206010012289 Dementia Diseases 0.000 description 1
BVTJGGGYKAMDBN-UHFFFAOYSA-N Dioxetane Chemical group C1COO1 BVTJGGGYKAMDBN-UHFFFAOYSA-N 0.000 description 1
241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
241000196324 Embryophyta Species 0.000 description 1
108010013369 Enteropeptidase Proteins 0.000 description 1
102100029727 Enteropeptidase Human genes 0.000 description 1
108091029865 Exogenous DNA Proteins 0.000 description 1
108010046276 FLP recombinase Proteins 0.000 description 1
108010074860 Factor Xa Proteins 0.000 description 1
240000008168 Ficus benjamina Species 0.000 description 1
BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 1
108010001515 Galectin 4 Proteins 0.000 description 1
102100039556 Galectin-4 Human genes 0.000 description 1
241000287828 Gallus gallus Species 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
108700039691 Genetic Promoter Regions Proteins 0.000 description 1
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
101001033249 Homo sapiens Interleukin-1 beta Proteins 0.000 description 1
108010001336 Horseradish Peroxidase Proteins 0.000 description 1
108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
206010062717 Increased upper airway secretion Diseases 0.000 description 1
108020005350 Initiator Codon Proteins 0.000 description 1
229930010555 Inosine Natural products 0.000 description 1
UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
102100034343 Integrase Human genes 0.000 description 1
101710203526 Integrase Proteins 0.000 description 1
102100039065 Interleukin-1 beta Human genes 0.000 description 1
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
108090001090 Lectins Proteins 0.000 description 1
102000004856 Lectins Human genes 0.000 description 1
DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 1
206010058467 Lung neoplasm malignant Diseases 0.000 description 1
GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
238000000585 Mann–Whitney U test Methods 0.000 description 1
241000699660 Mus musculus Species 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
108010021466 Mutant Proteins Proteins 0.000 description 1
102000008300 Mutant Proteins Human genes 0.000 description 1
GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
238000005481 NMR spectroscopy Methods 0.000 description 1
229930193140 Neomycin Natural products 0.000 description 1
238000000636 Northern blotting Methods 0.000 description 1
239000004677 Nylon Substances 0.000 description 1
108700020796 Oncogene Proteins 0.000 description 1
241000283973 Oryctolagus cuniculus Species 0.000 description 1
240000007594 Oryza sativa Species 0.000 description 1
235000007164 Oryza sativa Nutrition 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
241001494479 Pecora Species 0.000 description 1
108091005804 Peptidases Proteins 0.000 description 1
102000035195 Peptidases Human genes 0.000 description 1
108010067902 Peptide Library Proteins 0.000 description 1
108010004729 Phycoerythrin Proteins 0.000 description 1
231100000742 Plant toxin Toxicity 0.000 description 1
241000276498 Pollachius virens Species 0.000 description 1
229920002873 Polyethylenimine Polymers 0.000 description 1
208000032236 Predisposition to disease Diseases 0.000 description 1
241000288906 Primates Species 0.000 description 1
102100037681 Protein FEV Human genes 0.000 description 1
101710198166 Protein FEV Proteins 0.000 description 1
241000700159 Rattus Species 0.000 description 1
108700005075 Regulator Genes Proteins 0.000 description 1
238000012952 Resampling Methods 0.000 description 1
206010038997 Retroviral infections Diseases 0.000 description 1
AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 1
108010083644 Ribonucleases Proteins 0.000 description 1
102000006382 Ribonucleases Human genes 0.000 description 1
108010039491 Ricin Proteins 0.000 description 1
241000283984 Rodentia Species 0.000 description 1
235000004789 Rosa xanthina Nutrition 0.000 description 1
241000109329 Rosa xanthina Species 0.000 description 1
241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 1
244000180577 Sambucus australis Species 0.000 description 1
235000018734 Sambucus australis Nutrition 0.000 description 1
108091081021 Sense strand Proteins 0.000 description 1
229920002684 Sepharose Polymers 0.000 description 1
238000002105 Southern blotting Methods 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
241000187747 Streptomyces Species 0.000 description 1
238000000692 Student's t-test Methods 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
241000701093 Suid alphaherpesvirus 1 Species 0.000 description 1
108020005038 Terminator Codon Proteins 0.000 description 1
239000004098 Tetracycline Substances 0.000 description 1
108091036066 Three prime untranslated region Proteins 0.000 description 1
108010022394 Threonine synthase Proteins 0.000 description 1
108090000190 Thrombin Proteins 0.000 description 1
240000007591 Tilia tomentosa Species 0.000 description 1
206010070863 Toxicity to various agents Diseases 0.000 description 1
GYDJEQRTZSCIOI-UHFFFAOYSA-N Tranexamic acid Chemical compound NCC1CCC(C(O)=O)CC1 GYDJEQRTZSCIOI-UHFFFAOYSA-N 0.000 description 1
108020004566 Transfer RNA Proteins 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
108091023045 Untranslated Region Proteins 0.000 description 1
241000700618 Vaccinia virus Species 0.000 description 1
210000001766 X chromosome Anatomy 0.000 description 1
210000002593 Y chromosome Anatomy 0.000 description 1
230000001594 aberrant effect Effects 0.000 description 1
230000005856 abnormality Effects 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
230000021736 acetylation Effects 0.000 description 1
238000006640 acetylation reaction Methods 0.000 description 1
229940022698 acetylcholinesterase Drugs 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000003213 activating effect Effects 0.000 description 1
239000011149 active material Substances 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
238000001261 affinity purification Methods 0.000 description 1
239000000556 agonist Substances 0.000 description 1
235000004279 alanine Nutrition 0.000 description 1
238000012867 alanine scanning Methods 0.000 description 1
WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
230000009435 amidation Effects 0.000 description 1
238000007112 amidation reaction Methods 0.000 description 1
150000001408 amides Chemical group 0.000 description 1
238000012870 ammonium sulfate precipitation Methods 0.000 description 1
210000004102 animal cell Anatomy 0.000 description 1
235000020244 animal milk Nutrition 0.000 description 1
125000000129 anionic group Chemical group 0.000 description 1
150000001450 anions Chemical group 0.000 description 1
238000000137 annealing Methods 0.000 description 1
230000003042 antagnostic effect Effects 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
238000009175 antibody therapy Methods 0.000 description 1
239000002246 antineoplastic agent Substances 0.000 description 1
230000010516 arginylation Effects 0.000 description 1
230000002917 arthritic effect Effects 0.000 description 1
238000013528 artificial neural network Methods 0.000 description 1
210000001106 artificial yeast chromosome Anatomy 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
230000001363 autoimmune Effects 0.000 description 1
208000037979 autoimmune inflammatory disease Diseases 0.000 description 1
239000000688 bacterial toxin Substances 0.000 description 1
239000013602 bacteriophage vector Substances 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
108010005774 beta-Galactosidase Proteins 0.000 description 1
102000023732 binding proteins Human genes 0.000 description 1
108091008324 binding proteins Proteins 0.000 description 1
210000002459 blastocyst Anatomy 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
210000004204 blood vessel Anatomy 0.000 description 1
230000037396 body weight Effects 0.000 description 1
210000000988 bone and bone Anatomy 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
238000004364 calculation method Methods 0.000 description 1
239000003560 cancer drug Substances 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
229910002092 carbon dioxide Inorganic materials 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
210000000748 cardiovascular system Anatomy 0.000 description 1
239000000969 carrier Substances 0.000 description 1
108020001778 catalytic domains Proteins 0.000 description 1
125000002091 cationic group Chemical group 0.000 description 1
238000004113 cell culture Methods 0.000 description 1
210000000170 cell membrane Anatomy 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
238000012412 chemical coupling Methods 0.000 description 1
238000001311 chemical methods and process Methods 0.000 description 1
238000002038 chemiluminescence detection Methods 0.000 description 1
235000013330 chicken meat Nutrition 0.000 description 1
210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
238000004140 cleaning Methods 0.000 description 1
230000002860 competitive effect Effects 0.000 description 1
230000009918 complex formation Effects 0.000 description 1
108091036078 conserved sequence Proteins 0.000 description 1
238000010276 construction Methods 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
208000029078 coronary artery disease Diseases 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
238000004132 cross linking Methods 0.000 description 1
239000013078 crystal Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
229960003067 cystine Drugs 0.000 description 1
238000007405 data analysis Methods 0.000 description 1
238000013502 data validation Methods 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
230000007547 defect Effects 0.000 description 1
230000003413 degradative effect Effects 0.000 description 1
230000002939 deleterious effect Effects 0.000 description 1
230000017858 demethylation Effects 0.000 description 1
238000010520 demethylation reaction Methods 0.000 description 1
239000003398 denaturant Substances 0.000 description 1
230000000368 destabilizing effect Effects 0.000 description 1
230000001627 detrimental effect Effects 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
238000012631 diagnostic technique Methods 0.000 description 1
238000010586 diagram Methods 0.000 description 1
239000005546 dideoxynucleotide Substances 0.000 description 1
230000004069 differentiation Effects 0.000 description 1
102000004419 dihydrofolate reductase Human genes 0.000 description 1
239000000539 dimer Substances 0.000 description 1
206010013023 diphtheria Diseases 0.000 description 1
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
238000011979 disease modifying therapy Methods 0.000 description 1
208000022602 disease susceptibility Diseases 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
230000003828 downregulation Effects 0.000 description 1
238000001647 drug administration Methods 0.000 description 1
229940000406 drug candidate Drugs 0.000 description 1
230000036267 drug metabolism Effects 0.000 description 1
238000013399 early diagnosis Methods 0.000 description 1
230000002526 effect on cardiovascular system Effects 0.000 description 1
238000004520 electroporation Methods 0.000 description 1
210000001671 embryonic stem cell Anatomy 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
230000002708 enhancing effect Effects 0.000 description 1
YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
229960005139 epinephrine Drugs 0.000 description 1
IINNWAYUJNWZRM-UHFFFAOYSA-L erythrosin B Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(I)C(=O)C(I)=C2OC2=C(I)C([O-])=C(I)C=C21 IINNWAYUJNWZRM-UHFFFAOYSA-L 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
230000029142 excretion Effects 0.000 description 1
238000011985 exploratory data analysis Methods 0.000 description 1
238000000605 extraction Methods 0.000 description 1
230000001815 facial effect Effects 0.000 description 1
210000003811 finger Anatomy 0.000 description 1
235000013312 flour Nutrition 0.000 description 1
MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
238000002875 fluorescence polarization Methods 0.000 description 1
239000007850 fluorescent dye Substances 0.000 description 1
230000022244 formylation Effects 0.000 description 1
238000006170 formylation reaction Methods 0.000 description 1
230000005714 functional activity Effects 0.000 description 1
239000007789 gas Substances 0.000 description 1
210000004051 gastric juice Anatomy 0.000 description 1
238000001502 gel electrophoresis Methods 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
238000001415 gene therapy Methods 0.000 description 1
239000008103 glucose Substances 0.000 description 1
125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
150000002334 glycols Chemical class 0.000 description 1
239000011544 gradient gel Substances 0.000 description 1
230000012010 growth Effects 0.000 description 1
150000003278 haem Chemical group 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
238000013537 high throughput screening Methods 0.000 description 1
238000012188 high-throughput screening assay Methods 0.000 description 1
238000002744 homologous recombination Methods 0.000 description 1
230000006801 homologous recombination Effects 0.000 description 1
210000003917 human chromosome Anatomy 0.000 description 1
238000004191 hydrophobic interaction chromatography Methods 0.000 description 1
230000002706 hydrostatic effect Effects 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
238000012872 hydroxylapatite chromatography Methods 0.000 description 1
238000003384 imaging method Methods 0.000 description 1
230000003100 immobilizing effect Effects 0.000 description 1
230000028993 immune response Effects 0.000 description 1
208000026278 immune system disease Diseases 0.000 description 1
230000003053 immunization Effects 0.000 description 1
238000002649 immunization Methods 0.000 description 1
229940127121 immunoconjugate Drugs 0.000 description 1
238000010166 immunofluorescence Methods 0.000 description 1
230000005847 immunogenicity Effects 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
230000006872 improvement Effects 0.000 description 1
230000002779 inactivation Effects 0.000 description 1
239000011261 inert gas Substances 0.000 description 1
230000008595 infiltration Effects 0.000 description 1
238000001764 infiltration Methods 0.000 description 1
208000027866 inflammatory disease Diseases 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
229960003786 inosine Drugs 0.000 description 1
238000007689 inspection Methods 0.000 description 1
230000010354 integration Effects 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
230000026045 iodination Effects 0.000 description 1
238000006192 iodination reaction Methods 0.000 description 1
238000011901 isothermal amplification Methods 0.000 description 1
108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 1
239000008101 lactose Substances 0.000 description 1
230000002045 lasting effect Effects 0.000 description 1
239000002523 lectin Substances 0.000 description 1
231100000518 lethal Toxicity 0.000 description 1
230000001665 lethal effect Effects 0.000 description 1
210000000265 leukocyte Anatomy 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
238000012417 linear regression Methods 0.000 description 1
238000001638 lipofection Methods 0.000 description 1
239000002502 liposome Substances 0.000 description 1
230000004807 localization Effects 0.000 description 1
238000000504 luminescence detection Methods 0.000 description 1
HWYHZTIRURJOHG-UHFFFAOYSA-N luminol Chemical compound O=C1NNC(=O)C2=C1C(N)=CC=C2 HWYHZTIRURJOHG-UHFFFAOYSA-N 0.000 description 1
201000005202 lung cancer Diseases 0.000 description 1
208000020816 lung neoplasm Diseases 0.000 description 1
230000002934 lysing effect Effects 0.000 description 1
229920002521 macromolecule Polymers 0.000 description 1
210000002540 macrophage Anatomy 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
238000012423 maintenance Methods 0.000 description 1
230000013011 mating Effects 0.000 description 1
238000005259 measurement Methods 0.000 description 1
238000002483 medication Methods 0.000 description 1
125000001360 methionine group Chemical class N[C@@H](CCSC)C(=O)* 0.000 description 1
230000011987 methylation Effects 0.000 description 1
238000007069 methylation reaction Methods 0.000 description 1
YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical class CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
238000004377 microelectronic Methods 0.000 description 1
239000011707 mineral Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
230000009456 molecular mechanism Effects 0.000 description 1
238000002625 monoclonal antibody therapy Methods 0.000 description 1
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
210000000472 morula Anatomy 0.000 description 1
230000007498 myristoylation Effects 0.000 description 1
ZTLGJPIZUOVDMT-UHFFFAOYSA-N n,n-dichlorotriazin-4-amine Chemical compound ClN(Cl)C1=CC=NN=N1 ZTLGJPIZUOVDMT-UHFFFAOYSA-N 0.000 description 1
239000002105 nanoparticle Substances 0.000 description 1
229930014626 natural product Natural products 0.000 description 1
229960004927 neomycin Drugs 0.000 description 1
230000004770 neurodegeneration Effects 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
229960002748 norepinephrine Drugs 0.000 description 1
SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
238000007899 nucleic acid hybridization Methods 0.000 description 1
238000001668 nucleic acid synthesis Methods 0.000 description 1
235000015097 nutrients Nutrition 0.000 description 1
229920001778 nylon Polymers 0.000 description 1
238000002966 oligonucleotide array Methods 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
238000004806 packaging method and process Methods 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
230000006320 pegylation Effects 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
238000002823 phage display Methods 0.000 description 1
208000026435 phlegm Diseases 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
239000002953 phosphate buffered saline Substances 0.000 description 1
125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
229940080469 phosphocellulose Drugs 0.000 description 1
150000004713 phosphodiesters Chemical class 0.000 description 1
238000005222 photoaffinity labeling Methods 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
230000004962 physiological condition Effects 0.000 description 1
230000006461 physiological response Effects 0.000 description 1
239000003123 plant toxin Substances 0.000 description 1
210000002381 plasma Anatomy 0.000 description 1
229920001983 poloxamer Polymers 0.000 description 1
229920000447 polyanionic polymer Polymers 0.000 description 1
229920005862 polyol Polymers 0.000 description 1
150000003077 polyols Chemical class 0.000 description 1
239000013641 positive control Chemical group 0.000 description 1
231100000683 possible toxicity Toxicity 0.000 description 1
230000001323 posttranslational effect Effects 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000002243 precursor Substances 0.000 description 1
230000035935 pregnancy Effects 0.000 description 1
230000013823 prenylation Effects 0.000 description 1
230000002265 prevention Effects 0.000 description 1
230000003449 preventive effect Effects 0.000 description 1
230000002250 progressing effect Effects 0.000 description 1
208000037821 progressive disease Diseases 0.000 description 1
230000000750 progressive effect Effects 0.000 description 1
230000002062 proliferating effect Effects 0.000 description 1
230000000644 propagated effect Effects 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
238000003498 protein array Methods 0.000 description 1
238000000159 protein binding assay Methods 0.000 description 1
108020001580 protein domains Proteins 0.000 description 1
238000001742 protein purification Methods 0.000 description 1
238000001243 protein synthesis Methods 0.000 description 1
230000012743 protein tagging Effects 0.000 description 1
230000006337 proteolytic cleavage Effects 0.000 description 1
229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
238000005086 pumping Methods 0.000 description 1
229940043131 pyroglutamate Drugs 0.000 description 1
238000012175 pyrosequencing Methods 0.000 description 1
239000010453 quartz Substances 0.000 description 1
238000010791 quenching Methods 0.000 description 1
230000006340 racemization Effects 0.000 description 1
230000002285 radioactive effect Effects 0.000 description 1
230000008707 rearrangement Effects 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
238000003259 recombinant expression Methods 0.000 description 1
238000010188 recombinant method Methods 0.000 description 1
230000009467 reduction Effects 0.000 description 1
238000000611 regression analysis Methods 0.000 description 1
230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
230000003014 reinforcing effect Effects 0.000 description 1
238000005067 remediation Methods 0.000 description 1
230000001850 reproductive effect Effects 0.000 description 1
238000007894 restriction fragment length polymorphism technique Methods 0.000 description 1
210000001525 retina Anatomy 0.000 description 1
210000003705 ribosome Anatomy 0.000 description 1
235000009566 rice Nutrition 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
238000005096 rolling process Methods 0.000 description 1
150000003839 salts Chemical class 0.000 description 1
238000005464 sample preparation method Methods 0.000 description 1
238000005070 sampling Methods 0.000 description 1
238000010845 search algorithm Methods 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
231100000004 severe toxicity Toxicity 0.000 description 1
239000013605 shuttle vector Substances 0.000 description 1
208000007056 sickle cell anemia Diseases 0.000 description 1
230000011664 signaling Effects 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
239000010703 silicon Substances 0.000 description 1
229910052710 silicon Inorganic materials 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
238000003201 single nucleotide polymorphism genotyping Methods 0.000 description 1
238000002741 site-directed mutagenesis Methods 0.000 description 1
238000004513 sizing Methods 0.000 description 1
235000020183 skimmed milk Nutrition 0.000 description 1
210000003491 skin Anatomy 0.000 description 1
210000004927 skin cell Anatomy 0.000 description 1
239000004055 small Interfering RNA Substances 0.000 description 1
150000003384 small molecules Chemical group 0.000 description 1
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
230000000392 somatic effect Effects 0.000 description 1
238000000527 sonication Methods 0.000 description 1
239000003549 soybean oil Substances 0.000 description 1
235000012424 soybean oil Nutrition 0.000 description 1
230000009870 specific binding Effects 0.000 description 1
238000011895 specific detection Methods 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
238000000528 statistical test Methods 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
238000012916 structural analysis Methods 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
230000008093 supporting effect Effects 0.000 description 1
239000000829 suppository Substances 0.000 description 1
230000001629 suppression Effects 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
208000037369 susceptibility to malaria Diseases 0.000 description 1
239000000725 suspension Substances 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
210000004243 sweat Anatomy 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
238000012353 t test Methods 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
210000001138 tear Anatomy 0.000 description 1
229960002180 tetracycline Drugs 0.000 description 1
229930101283 tetracycline Natural products 0.000 description 1
235000019364 tetracycline Nutrition 0.000 description 1
150000003522 tetracyclines Chemical class 0.000 description 1
MPLHNVLQVRSVEE-UHFFFAOYSA-N texas red Chemical compound [O-]S(=O)(=O)C1=CC(S(Cl)(=O)=O)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 MPLHNVLQVRSVEE-UHFFFAOYSA-N 0.000 description 1
229940126585 therapeutic drug Drugs 0.000 description 1
238000003161 three-hybrid assay Methods 0.000 description 1
229960004072 thrombin Drugs 0.000 description 1
210000003813 thumb Anatomy 0.000 description 1
231100000041 toxicology testing Toxicity 0.000 description 1
230000005026 transcription initiation Effects 0.000 description 1
230000002103 transcriptional effect Effects 0.000 description 1
230000009466 transformation Effects 0.000 description 1
238000011830 transgenic mouse model Methods 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
239000013638 trimer Substances 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
230000007306 turnover Effects 0.000 description 1
238000003160 two-hybrid assay Methods 0.000 description 1
238000010396 two-hybrid screening Methods 0.000 description 1
238000010798 ubiquitination Methods 0.000 description 1
230000034512 ubiquitination Effects 0.000 description 1
ORHBXUUXSCNDEV-UHFFFAOYSA-N umbelliferone Chemical compound C1=CC(=O)OC2=CC(O)=CC=C21 ORHBXUUXSCNDEV-UHFFFAOYSA-N 0.000 description 1
HFTAFOQKODTIJY-UHFFFAOYSA-N umbelliferone Natural products Cc1cc2C=CC(=O)Oc2cc1OCC=CC(C)(C)O HFTAFOQKODTIJY-UHFFFAOYSA-N 0.000 description 1
230000003827 upregulation Effects 0.000 description 1
210000002700 urine Anatomy 0.000 description 1
229960005486 vaccine Drugs 0.000 description 1
235000013311 vegetables Nutrition 0.000 description 1
210000003462 vein Anatomy 0.000 description 1
238000012795 verification Methods 0.000 description 1
230000029812 viral genome replication Effects 0.000 description 1
230000004304 visual acuity Effects 0.000 description 1
239000006226 wash reagent Substances 0.000 description 1
238000005406 washing Methods 0.000 description 1
238000001262 western blot Methods 0.000 description 1
210000003857 wrist joint Anatomy 0.000 description 1
238000001086 yeast two-hybrid system Methods 0.000 description 1