BACKGROUNDAlzheimer illness (AD) is a progressive dysfunction that impacts cognitive operate. There is growing assist for the function of neuroinflammation and aberrant immune regulation in the pathophysiology of AD. The immunoregulatory human leukocyte antigen (HLA) advanced has been linked to susceptibility for a quantity of neurodegenerative ailments, together with AD; nonetheless, research thus far have did not constantly determine a risk HLA haplotype for AD.
Contributing to this issue are the advanced genetic group of the HLA area, variations in sequencing and allelic imputation strategies, and variety throughout ethnic populations.RESULTSBuilding on prior work linking the HLA to AD, we used a sturdy imputation methodology on two separate case-control cohorts to look at the relationship between HLA haplotypes and AD risk in 309 people (191 AD, 118 cognitively regular [CN] controls) from the San Francisco-based University of California, San Francisco (UCSF) Memory and Aging Center (collected between 1999-2015) and 11,381 people (5,728 AD, 5,653 CN controls) from the Alzheimer’s Disease Genetics Consortium (ADGC), a National Institute on Aging (NIA)-funded nationwide information repository (reflecting samples collected between 1984-2012).
We additionally examined cerebrospinal fluid (CSF) biomarker measures for sufferers seen between 2005-2007 and longitudinal cognitive information from the Alzheimer’s Disease Neuroimaging Initiative (n = 346, imply follow-up 3.15 ± 2.04 y in AD people) to evaluate the medical relevance of recognized risk haplotypes. The strongest affiliation with AD risk occurred with main histocompatibility advanced (MHC) haplotype A*03:01~B*07:02~DRB1*15:01~DQA1*01:02~DQB1*06:02 (p = 9.6 x 10-4, odds ratio [OR] [95% confidence interval] = 1.21 [1.08-1.37]) in the mixed UCSF + ADGC cohort. Secondary evaluation prompt that this impact could also be pushed primarily by people who’re damaging for the established AD genetic risk factor, apolipoprotein E (APOE) É›4.
Separate analyses of class I and II haplotypes additional supported the function of class I haplotype A*03:01~B*07:02 (p = 0.03, OR = 1.11 [1.01-1.23]) and sophistication II haplotype DRB1*15:01- DQA1*01:02- DQB1*06:02 (DR15) (p = 0.03, OR = 1.08 [1.01-1.15]) as risk components for AD. We adopted up these findings in the medical dataset representing the spectrum of cognitively regular controls, people with delicate cognitive impairment, and people with AD to evaluate their relevance to illness.
Carrying A*03:01~B*07:02 was related to increased CSF amyloid ranges (p = 0.03, β ± commonplace error = 47.19 ± 21.78). We additionally discovered a dose-dependent affiliation between the DR15 haplotype and larger charges of cognitive decline (larger impairment on the 11-item Alzheimer’s Disease Assessment Scale cognitive subscale [ADAS11] over time [p = 0.03, β ± standard error = 0.7 ± 0.3]; worse forgetting rating on the Rey Auditory Verbal Learning Test (RAVLT) over time [p = 0.02, β ± standard error = -0.2 ± 0.06]). In a subset of the similar cohort, dose of DR15 was additionally related to increased baseline ranges of chemokine CC-4, a biomarker of irritation (p = 0.005, β ± commonplace error = 0.08 ± 0.03). The predominant research limitations are that the outcomes symbolize solely people of European-ancestry and clinically identified people, and that our research used imputed genotypes for a subset of HLA genes.

CONCLUSIONSWe present proof that variation in the HLA locus-including risk haplotype DR15-contributes to AD risk. DR15 has additionally been related to a number of sclerosis, and its part alleles have been implicated in Parkinson illness and narcolepsy. Our findings thus elevate the chance that DR15-associated mechanisms could contribute to pan-neuronal illness vulnerability.
Hydrogen Peroxide Assay Kit |
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NAT1002 | National Diagnostics | 1KIT | EUR 308.4 |
ProtoBlock System |
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NAT1004 | National Diagnostics | 1KIT | EUR 122.4 |
450ML PBS 10X |
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NAT1006 | National Diagnostics | 450ML | EUR 96 |
4L PBS 10X |
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NAT1008 | National Diagnostics | 4L | EUR 238.8 |
ProtoGlow ECL 200ml Kit |
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NAT1010 | National Diagnostics | EACH | EUR 354 |
ProtoGlow ECL 500ml Kit |
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NAT1012 | National Diagnostics | EACH | EUR 627.6 |
100G Acrylamide |
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NAT1014 | National Diagnostics | 100G | EUR 120 |
500G Acrylamide |
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NAT1016 | National Diagnostics | 500G | EUR 261.6 |
1KG Acrylamide |
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NAT1018 | National Diagnostics | 1KG | EUR 412.8 |
25G AquaPor LE |
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NAT1020 | National Diagnostics | 25G | EUR 132 |
100G AquaPor LE GTAC |
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NAT1022 | National Diagnostics | 100G | EUR 250.8 |
500G AquaPor LE GTAC |
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NAT1024 | National Diagnostics | 500G | EUR 878.4 |
25G AquaPor ES |
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NAT1026 | National Diagnostics | 25G | EUR 152.4 |
100G AquaPor ES |
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NAT1028 | National Diagnostics | 100G | EUR 350.4 |
25G AquaPor LM |
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NAT1030 | National Diagnostics | 25G | EUR 288 |
100G AquaPor LM |
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NAT1032 | National Diagnostics | 100G | EUR 860.4 |
25G AquaPor HR |
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NAT1034 | National Diagnostics | 25G | EUR 236.4 |
100G AquaPor HR |
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NAT1036 | National Diagnostics | 100G | EUR 592.8 |
25G AquaPor 3:1 |
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NAT1038 | National Diagnostics | 25G | EUR 250.8 |
100G AquaPor 3:1 |
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NAT1040 | National Diagnostics | 100G | EUR 570 |
25G Bis (Methylene Bis-Acrylamide) |
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NAT1042 | National Diagnostics | 25G | EUR 100.8 |
25G DATD Ultrapure |
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NAT1044 | National Diagnostics | 25G | EUR 168 |
250G Glycine |
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NAT1046 | National Diagnostics | 250G | EUR 94.8 |
1KG Glycine Ultrapure |
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NAT1048 | National Diagnostics | 1KG | EUR 128.4 |
250G Tris |
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NAT1050 | National Diagnostics | 250G | EUR 102 |
1KG Tris Ultrapure |
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NAT1052 | National Diagnostics | 1KG | EUR 177.6 |
100G Tricine |
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NAT1054 | National Diagnostics | 100G | EUR 120 |
100G Ion Exchange Resin (mixed bed) |
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NAT1056 | National Diagnostics | 100G | EUR 96 |
25G Riboflavin |
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NAT1058 | National Diagnostics | 25G | EUR 96 |
25ML TEMED |
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NAT1060 | National Diagnostics | 25ML | EUR 99.6 |
25G Ammonium Persulfate |
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NAT1062 | National Diagnostics | 25G | EUR 96 |
100G Ammonium Persulfate |
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NAT1064 | National Diagnostics | 100G | EUR 118.8 |
1G Dithiothreitol (DTT) |
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NAT1066 | National Diagnostics | 1G | EUR 103.2 |
5G Dithiothreitol (DTT) |
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NAT1068 | National Diagnostics | 5G | EUR 183.6 |
50ML 2-Mercaptoethanol |
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NAT1070 | National Diagnostics | 50ML | EUR 112.8 |
100G SDS Ultrapure |
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NAT1072 | National Diagnostics | 100G | EUR 111.6 |
1KG SDS Ultrapure |
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NAT1074 | National Diagnostics | 1KG | EUR 457.2 |
250G Urea |
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NAT1076 | National Diagnostics | 250G | EUR 98.4 |
1KG Urea |
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NAT1078 | National Diagnostics | 1KG | EUR 138 |
450ML Glycerol Ultrapure |
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NAT1080 | National Diagnostics | 450ML | EUR 132 |
200ML Tween 20 Ultrapure |
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NAT1082 | National Diagnostics | 200ML | EUR 132 |
1L Tween 20 |
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NAT1084 | National Diagnostics | 1L | EUR 169.2 |
200ML Formamide |
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NAT1086 | National Diagnostics | 200ML | EUR 111.6 |
500ML Boric Acid |
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NAT1088 | National Diagnostics | 500ML | EUR 103.2 |
100G EDTA |
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NAT1090 | National Diagnostics | 100G | EUR 94.8 |
500G EDTA |
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NAT1092 | National Diagnostics | 500G | EUR 177.6 |
GelDry Film 11 X 12 cm |
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NAT1094 | National Diagnostics | PK50 | EUR 100.8 |
25ML Formamide CE |
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NAT1096 | National Diagnostics | 25ML | Ask for price |
25ML Glass Bond |
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NAT1098 | National Diagnostics | 25ML | EUR 158.4 |
450ML Glass Free |
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NAT1100 | National Diagnostics | 450ML | EUR 196.8 |
GelDry Film 22.5 X 22.5 cm |
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NAT1102 | National Diagnostics | PK50 | EUR 130.8 |
1L DEPC Treated Water |
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NAT1104 | National Diagnostics | 1L | EUR 120 |
Sterling Rapid Silver Stain Kit |
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NAT1106 | National Diagnostics | 1KIT | EUR 265.2 |
1L ProtoBlue Safe |
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NAT1108 | National Diagnostics | 1L | EUR 159.6 |
4L ProtoBlue Safe |
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NAT1110 | National Diagnostics | 4L | EUR 282 |
1L ProtoStain Blue |
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NAT1112 | National Diagnostics | 1L | EUR 164.4 |
25ML Nuclistain |
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NAT1114 | National Diagnostics | 25ML | EUR 128.4 |
450ML AcrylaGel 30% |
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NAT1116 | National Diagnostics | 450ML | EUR 128.4 |
1L AcrylaGel 30% |
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NAT1118 | National Diagnostics | 1L | EUR 177.6 |
450ML Bis-AcrylaGel 2% |
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NAT1120 | National Diagnostics | 450ML | EUR 98.4 |
1L Bis-AcrylaGel 2% |
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NAT1122 | National Diagnostics | 1L | EUR 111.6 |
450ML UreaGel 29:1 Concentrate |
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NAT1124 | National Diagnostics | 450ML | EUR 133.2 |
1L UreaGel 29:1 Concentrate |
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NAT1126 | National Diagnostics | 1L | EUR 183.6 |
UreaGel 29:1 System 1L Kit |
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NAT1128 | National Diagnostics | EACH | EUR 171.6 |
UreaGel 29:1 System 2.2L Kit |
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NAT1130 | National Diagnostics | EACH | EUR 253.2 |
450ML SequaGel UreaGel Concentrate |
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NAT1132 | National Diagnostics | 450ML | EUR 126 |
1L SequaGel UreaGel Concentrate |
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NAT1134 | National Diagnostics | 1L | EUR 160.8 |
SequaGel Sequencing System 1L Kit |
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NAT1136 | National Diagnostics | 1KIT | EUR 171.6 |
SequaGel Sequencing System 2.2L Kit |
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NAT1138 | National Diagnostics | EACH | EUR 253.2 |
100ML SequaGel Buffer |
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NAT1140 | National Diagnostics | 100ML | EUR 80.4 |
200ML SequaGel UreaGel Buffer |
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450ML SequaGel UreaGel-6 |
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1L SequaGel UreaGel-6 |
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450ML SequaGel UreaGel-8 |
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1L SequaGel UreaGel-8 |
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450ML SequaGel UreaGel Diluent |
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NAT1152 | National Diagnostics | 450ML | EUR 90 |
1L SequaGel UreaGel Diluent |
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NAT1154 | National Diagnostics | 1L | EUR 103.2 |
90ML SequaGel Complete Buffer |
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NAT1156 | National Diagnostics | 90ML | EUR 79.2 |
200ML SequaGel UreaGel Complete Buffer |
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NAT1158 | National Diagnostics | 200ML | EUR 85.2 |
450ML SequaGel XR |
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NAT1160 | National Diagnostics | 450ML | EUR 126 |
1L SequaGel XR |
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NAT1162 | National Diagnostics | 1L | EUR 165.6 |
100ML SequaGel XR Concentrate |
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NAT1164 | National Diagnostics | 100ML | EUR 128.4 |
450ML SequaGel XR Concentrate |
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NAT1166 | National Diagnostics | 450ML | EUR 361.2 |
200ML SequaGel MD Monomer Solution |
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NAT1168 | National Diagnostics | 200ML | EUR 220.8 |
SequaGel MD SSCP Kit |
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NAT1170 | National Diagnostics | 1KIT | EUR 253.2 |
SequaGel MD Heteroduplex Kit |
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NAT1172 | National Diagnostics | EACH | EUR 265.2 |
1.2ML SequaGel MD SSCP Stop Solution |
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NAT1174 | National Diagnostics | 1.2ML | EUR 85.2 |
450ML AccuGel 19:1 (30%) |
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NAT1176 | National Diagnostics | 450ML | EUR 126 |
1L AccuGel 19:1 (30%) |
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NAT1178 | National Diagnostics | 1L | EUR 165.6 |
450ML AccuGel 19:1 (40%) |
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NAT1180 | National Diagnostics | 450ML | EUR 130.8 |
1L AccuGel 19:1 (40%) |
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NAT1182 | National Diagnostics | 1L | EUR 168 |
450ML AccuGel 29:1 (30%) |
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NAT1184 | National Diagnostics | 450ML | EUR 126 |
1L AccuGel 29:1 (30%) |
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NAT1186 | National Diagnostics | 1L | EUR 165.6 |
450ML AccuGel 29:1 (40%) |
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NAT1188 | National Diagnostics | 450ML | EUR 130.8 |
1L AccuGel 29:1 (40%) |
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NAT1190 | National Diagnostics | 1L | EUR 168 |
1.2ML Triple Dye Loading Buffer (6X) |
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NAT1192 | National Diagnostics | 1.2ML | EUR 85.2 |
UreaGel Loading Buffer |
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NAT1194 | National Diagnostics | 10X1ML | EUR 222 |
1L TBE 10X |
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NAT1196 | National Diagnostics | 1L | EUR 98.4 |
4L TBE 10X |
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NAT1198 | National Diagnostics | 4L | EUR 145.2 |
1L TBE 5X |
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NAT1200 | National Diagnostics | 1L | EUR 92.4 |
4L TBE 5X |
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NAT1202 | National Diagnostics | 4L | EUR 111.6 |
25ML TE BUFFER 100X |
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NAT1204 | National Diagnostics | 25ML | EUR 98.4 |
25ML 10X CE Buffer |
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NAT1206 | National Diagnostics | 25ML | EUR 138 |
100ML 10X CE Buffer |
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NAT1208 | National Diagnostics | 100ML | EUR 196.8 |
450ML 20X Tris-MOPS SDS |
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NAT1210 | National Diagnostics | 450ML | EUR 130.8 |
450ML 20X Tris-MEPS SDS |
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NAT1212 | National Diagnostics | 450ML | EUR 130.8 |
1L Tris-Tricine-SDS PAGE Buffer (10X) |
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NAT1214 | National Diagnostics | 1L | EUR 217.2 |
1L Tris-Glycine-SDS PAGE Buffer (10X) |
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NAT1216 | National Diagnostics | 1L | EUR 105.6 |
4L Tris-Glycine-SDS PAGE Buffer (10X) |
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NAT1218 | National Diagnostics | 4L | EUR 148.8 |
1L TTE Glycerol Tolerant Buffer 20X |
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NAT1220 | National Diagnostics | 1L | EUR 160.8 |
1L TAE Buffer 50X |
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NAT1222 | National Diagnostics | 1L | EUR 148.8 |
1L SSC Buffer 20X |
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NAT1224 | National Diagnostics | 1L | EUR 98.4 |
4L SSC Buffer 20X |
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NAT1226 | National Diagnostics | 4L | EUR 174 |
100ML SDS Solution 20% |
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NAT1228 | National Diagnostics | 100ML | EUR 92.4 |
450ML SDS Solution 20% |
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NAT1230 | National Diagnostics | 450ML | EUR 138 |
1L Denaturation Solution |
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NAT1232 | National Diagnostics | 1L | EUR 102 |
1L Neutralization Solution |
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NAT1234 | National Diagnostics | 1L | EUR 102 |
50G Dextran Sulfate |
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NAT1236 | National Diagnostics | 50G | EUR 193.2 |
250G Dextran Sulfate |
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NAT1238 | National Diagnostics | 250G | EUR 524.4 |
1L Tris-Glycine Electroblotting Buffer 10X |
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NAT1240 | National Diagnostics | 1L | EUR 102 |
4L Tris-Glycine Electroblotting Buffer 10X |
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NAT1242 | National Diagnostics | 4L | EUR 145.2 |
1L TBS (10X) Tris Buffered Saline |
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NAT1244 | National Diagnostics | 1L | EUR 126 |
1L TBST (10X) Tris Buffered Saline w/Tween 20 |
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NAT1246 | National Diagnostics | 1L | EUR 126 |
ProtoGel Sample Prep Kit |
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NAT1248 | National Diagnostics | EACH | EUR 223.2 |
Protein Loading Buffer Blue 2X |
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NAT1250 | National Diagnostics | 10X1ML | EUR 105.6 |
Protein Loading Buffer 5X |
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NAT1252 | National Diagnostics | 10X1ML | EUR 151.2 |
50ML Protein Precipitation Kit |
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NAT1254 | National Diagnostics | 50ML | EUR 270 |
100ML ProtoLift Western Strip Buffer |
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NAT1256 | National Diagnostics | 100ML | EUR 121.2 |
450ML ProtoGel (30%) |
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NAT1258 | National Diagnostics | 450ML | EUR 136.8 |
1L ProtoGel (30%) |
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NAT1260 | National Diagnostics | 1L | EUR 187.2 |
450ML ProtoGel (40%) |
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NAT1262 | National Diagnostics | 450ML | EUR 157.2 |
1L ProtoGel (40%) |
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NAT1264 | National Diagnostics | 1L | EUR 204 |
450ML ProtoGel Resolving Buffer 4X |
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NAT1266 | National Diagnostics | 450ML | EUR 100.8 |
1L ProtoGel Resolving Buffer |
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NAT1268 | National Diagnostics | 1L | EUR 128.4 |
200ML ProtoGel Stacking Buffer |
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NAT1270 | National Diagnostics | 200ML | EUR 92.4 |
100ML ProtoGel Quick-Cast 12% |
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NAT1272 | National Diagnostics | 100ML | EUR 105.6 |
450ML ProtoGel Quick-Cast 12% |
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NAT1274 | National Diagnostics | 450ML | EUR 223.2 |
0.5ML Insite Markers |
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NAT1276 | National Diagnostics | 0.5ML | EUR 238.8 |
0.5ML ProtoMarkers |
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NAT1278 | National Diagnostics | 0.5ML | EUR 236.4 |
ProtoMetrics |
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NAT1280 | National Diagnostics | EACH | EUR 242.4 |
1L EDTA 0.5M Solution |
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NAT1282 | National Diagnostics | 1L | EUR 183.6 |
1L Sodium Chloride 0.009 Solution |
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NAT1284 | National Diagnostics | 1L | EUR 140.4 |
1L Sodium Chloride 1M Solution |
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NAT1286 | National Diagnostics | 1L | EUR 140.4 |
1L Potassium Chloride 1M Solution |
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NAT1288 | National Diagnostics | 1L | EUR 140.4 |
1L Tris-HCL 1M pH 7.2 |
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NAT1290 | National Diagnostics | 1L | EUR 126 |
1L Tris-HCL 1M pH 7.4 |
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NAT1292 | National Diagnostics | 1L | EUR 126 |
1L Tris-HCL 1M pH 7.6 |
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NAT1294 | National Diagnostics | 1L | EUR 126 |
Histosol |
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Histosol |
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NAT1298 | National Diagnostics | EACH | EUR 270 |
Mirskys Fixative (ready-to-use) |
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NAT1300 | National Diagnostics | 1USGALLON | EUR 96 |
Mirskys Fixative (ready-to-use) |
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NAT1302 | National Diagnostics | EACH | EUR 228 |
200ML Mirskys Fixative |
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NAT1304 | National Diagnostics | 200ML | EUR 92.4 |
2L Mirskys Fixative |
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NAT1306 | National Diagnostics | 2L | EUR 134.4 |
100ML Histomount |
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NAT1308 | National Diagnostics | 100ML | EUR 86.4 |
450ML Histomount |
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NAT1310 | National Diagnostics | 450ML | EUR 111.6 |
Calci-Clear |
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NAT1312 | National Diagnostics | EACH | EUR 93.6 |
Calci-Clear |
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NAT1314 | National Diagnostics | EACH | EUR 153.6 |
Calci-Clear |
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NAT1316 | National Diagnostics | EACH | EUR 463.2 |
Calci-Clear Rapid |
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NAT1318 | National Diagnostics | EACH | EUR 90 |
Calci-Clear Rapid |
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NAT1320 | National Diagnostics | EACH | EUR 153.6 |