192 research outputs found
Early response to impact knee injury in genetic strains of mice reveals similarity in cartilage but differences in synovium
Spinor Field Realizations of Non-critical Strings
In this paper, we construct the nilpotent Becchi-Rouet-Stora-Tyutin()
charges of spinor non-critical strings. The cases of are
discussed in detail, and spinor realization for is given explicitly. The
charges are graded.Comment: 9 pages, no figure
Molecular cytogenetic aberrations in patients with multiple myeloma studied by interphase fluorescence in situ hybridization
Background: Multiple myeloma (MM) is an incurable hematological disorder characterized by the accumulation of malignant plasma cells within the bone marrow (BM). The clinical heterogeneity of MM is dictated by the cytogenetic aberrations present in the clonal plasma cells (PCs). Cytogenetic studies in MM are hampered by the hypoproliferative nature of plasma cells in MM. Therefore, fluorescence in situ hybridization (FISH) analysis combined with magnetic-activated cell sorting (MACS) is an attractive alternative for evaluation of numerical and structural chromosomal changes in MM. Methods: Interphase FISH studies with three different specific probes for the regions containing 13q14.3 (D13S319), 14q32 (IGHC/IGHV) and 1q12(CEP1 ) were performed in 48 MM patients. Interphase FISH studies with LSI IGH/CCND1, LSI IGH/FGFR3, and LSI IGH/MAF probes were used to detect t(11;14)(q13;q32), t(4;14)(p16;q32), and t(14;16)(q32;q23) in patients with 14q32 rearrangement. Results: Molecular cytogenetic aberrations were found in 40 (83.3%) of the 48 MM patients. 13 patients (27.1%) simultaneously had 13q deletion/monosomy 13 [del(13q14)], illegitimate IGH rearrangement and chromosome 1 abnormality. Del(13q14) was detected in 21 cases (43.7%), and illegitimate IGH rearrangements in 29 (60.4%) including 6 with t(11;14) and 5 with t(4;14). None of 9 patients with illegitimate IGH rearrangements and without t(11;14) or t(4;14) we detected had t(14;16) (q32;q23). 24 of the 48 MM patients (50%) had chromosome 1 abnormalities. Among 21 patients with del(13q14), 15 patients had Amp1q12;16 had IgH rearrangements. Whereas, among 27 cases without del(13q14), 8 had Amp1q12; 13 had IgH rearrangements. There was a strong association between del(13q14) and Amp1q12(c2 = 8.26, Ρ < 0.01), and between del(13q14) and IgH rearrangement(c2 = 3.88, p < 0.05). Conclusion: 13q deletion/monosomy 13, IGH rearrangement and chromosome 1 abnormality are frequent in MM. They are not randomly distributed, but strongly interconnected. Interphase FISH technique combined with MACS using CD138-specific antibody is a highly sensitive technique at detecting molecular cytogenetic aberrations in MM.ΠΠ±ΠΎΡΠ½ΠΎΠ²Π°Π½ΠΈΠ΅: ΠΌΠ½ΠΎΠΆΠ΅ΡΡΠ²Π΅Π½Π½Π°Ρ ΠΌΠΈΠ΅Π»ΠΎΠΌΠ° (MM) β Π½Π΅ΠΈΠ·Π»Π΅ΡΠΈΠΌΠΎΠ΅ Π³Π΅ΠΌΠ°ΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ΅ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠ΅, Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΠΈΡΡΡΡΠ΅Π΅ΡΡ
Π½Π°ΠΊΠΎΠΏΠ»Π΅Π½ΠΈΠ΅ΠΌ Π·Π»ΠΎΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΡ
ΠΏΠ»Π°Π·ΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΊΠ»Π΅ΡΠΎΠΊ Π² ΠΊΠΎΡΡΠ½ΠΎΠΌ ΠΌΠΎΠ·Π³Π΅ (ΠM). ΠΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠ°Ρ Π³Π΅ΡΠ΅ΡΠΎΠ³Π΅Π½Π½ΠΎΡΡΡ MM ΠΎΠΏΡΠ΅Π΄Π΅Π»ΡΠ΅ΡΡΡ
ΡΠΈΡΠΎΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ Π°Π±Π΅ΡΡΠ°ΡΠΈΡΠΌΠΈ, ΠΏΡΠΈΡΡΡΡΡΠ²ΡΡΡΠΈΠΌΠΈ Π² ΠΊΠ»ΠΎΠ½Π΅ ΠΏΠ»Π°Π·ΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΊΠ»Π΅ΡΠΎΠΊ (ΠΠ). Π¦ΠΈΡΠΎΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ
MM ΠΎΡΠ»ΠΎΠΆΠ½Π΅Π½Ρ Π³ΠΈΠΏΠΎΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΠ²Π½ΡΠΌΠΈ ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΡΠΌΠΈ ΠΠ. Π ΡΠ²ΡΠ·ΠΈ Ρ ΡΡΠΈΠΌ ΡΠ»ΡΠΎΡΠ΅ΡΡΠ΅Π½ΡΠ½Π°Ρ Π³ΠΈΠ±ΡΠΈΠ΄ΠΈΠ·Π°ΡΠΈΡ in situ (FISH)
Π² ΠΊΠΎΠΌΠ±ΠΈΠ½Π°ΡΠΈΠΈ Ρ ΡΠΎΡΡΠΈΡΠΎΠ²ΠΊΠΎΠΉ ΠΊΠ»Π΅ΡΠΎΠΊ, Π°ΠΊΡΠΈΠ²ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΠΌΠ°Π³Π½ΠΈΡΠ½ΡΠΌΠΈ ΠΏΠΎΠ»ΡΠΌΠΈ (MACS) ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»ΡΠ΅ΡΡΡ Π΄ΠΎΡΡΠΎΠΉΠ½ΠΎΠΉ Π°Π»ΡΡΠ΅ΡΠ½Π°ΡΠΈΠ²ΠΎΠΉ
ΠΌΠ΅ΡΠΎΠ΄Π°ΠΌ ΠΎΡΠ΅Π½ΠΊΠΈ ΡΠΎΡΠ΅ΡΠ½ΡΡ
ΠΈ ΡΡΡΡΠΊΡΡΡΠ½ΡΡ
ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠΉ Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌ ΠΏΡΠΈ MM. ΠΠ΅ΡΠΎΠ΄Ρ: ΠΈΠ½ΡΠ΅ΡΡΠ°Π·Π½ΡΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ
FISH Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΡΡΠ΅Ρ
ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΈΡ
Π·ΠΎΠ½Π΄ΠΎΠ² Π΄Π»Ρ ΡΡΠ°ΡΡΠΊΠΎΠ², ΡΠΎΠ΄Π΅ΡΠΆΠ°ΡΠΈΡ
13q14.3 (D13S319), 14q32
(IGHC/IGHV) ΠΈ 1q12(CEP1), ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΈ Ρ 48 Π±ΠΎΠ»ΡΠ½ΡΡ
Ρ MM. ΠΠ½ΡΠ΅ΡΡΠ°Π·Π½ΡΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ FISH Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ
Π·ΠΎΠ½Π΄ΠΎΠ² LSI IGH/CCND1, LSI IGH/FGFR3 ΠΈ LSI IGH/MAF ΠΏΡΠΈΠΌΠ΅Π½ΡΠ»ΠΈ Π΄Π»Ρ Π΄Π΅ΡΠ΅ΠΊΡΠΈΠΈ t(11;14)(q13;q32), t(4;14)(p16;q32), ΠΈ
t(14;16)(q32;q23) Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΠΏΠ΅ΡΠ΅ΡΡΡΠΎΠΉΠΊΠΎΠΉ 14q32. Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ: ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΠ΅ ΡΠΈΡΠΎΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ Π°Π±Π΅ΡΡΠ°ΡΠΈΠΈ Π²ΡΡΠ²Π»ΡΠ»ΠΈ Ρ
40 (83,3%) ΠΈΠ· 48 Π±ΠΎΠ»ΡΠ½ΡΡ
Ρ MM. Π£ 13 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² (27,1%) ΠΎΠ΄Π½ΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΠΎ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½Ρ 13q Π΄Π΅Π»Π΅ΡΠΈΡ/ΠΌΠΎΠ½ΠΎΡΠΎΠΌΠΈΡ 13 [del(13q14)],
Π°Π½ΠΎΠΌΠ°Π»ΡΠ½Π°Ρ ΠΏΠ΅ΡΠ΅ΡΡΡΠΎΠΉΠΊΠ° IGH ΠΈ Π°Π½ΠΎΠΌΠ°Π»ΠΈΡ Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌΡ 1. Del(13q14) Π΄Π΅ΡΠ΅ΠΊΡΠΈΡΠΎΠ²Π°Π»ΠΈ Π² 21 ΡΠ»ΡΡΠ°Π΅ (43,7%), Π° Π°Π½ΠΎΠΌΠ°Π»ΡΠ½ΡΠ΅
ΠΏΠ΅ΡΠ΅ΡΡΡΠΎΠΉΠΊΠΈ IGH β Π² 29 (60,4%), Π² ΡΠΎΠΌ ΡΠΈΡΠ»Π΅ Ρ 6 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ t(11;14) ΠΈ 5 Ρ t(4;14). ΠΠΈ Ρ ΠΎΠ΄Π½ΠΎΠ³ΠΎ ΠΈΠ· 9 Π±ΠΎΠ»ΡΠ½ΡΡ
Ρ Π°Π½ΠΎΠΌΠ°Π»ΡΠ½ΡΠΌΠΈ
ΠΏΠ΅ΡΠ΅ΡΡΡΠΎΠΉΠΊΠ°ΠΌΠΈ IGH ΠΈ Π±Π΅Π· t(11;14) ΠΈΠ»ΠΈ t(4;14) Π½Π΅ Π²ΡΡΠ²Π»ΡΠ»ΠΈ ΡΡΠ°Π½ΡΠ»ΠΎΠΊΠ°ΡΠΈΡ t(14;16) (q32;q23). Π£ 24 ΠΈΠ· 48 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ MM
(50%) ΠΎΠΏΡΠ΅Π΄Π΅Π»ΡΠ»ΠΈ Π°Π½ΠΎΠΌΠ°Π»ΠΈΠΈ Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌΡ 1. Π Π³ΡΡΠΏΠΏΠ΅ ΠΈΠ· 21 Π±ΠΎΠ»ΡΠ½ΡΡ
Ρ del(13q14) Π² 15 ΡΠ»ΡΡΠ°ΡΡ
ΠΈΠΌΠ΅Π»ΠΈΡΡ ΠΏΠ΅ΡΠ΅ΡΡΡΠΎΠΉΠΊΠΈ IgH
Amp1q12;16. Π ΡΠΎ ΠΆΠ΅ Π²ΡΠ΅ΠΌΡ ΠΈΠ· 27 ΡΠ»ΡΡΠ°Π΅Π² Π±Π΅Π· del(13q14) Ρ 8 ΡΠΎΠ΄Π΅ΡΠΆΠ°Π»ΠΈΡΡ Amp1q12; Π² 13 ΡΠ»ΡΡΠ°ΡΡ
ΠΎΡΠΌΠ΅ΡΠ°Π»ΠΈ ΠΏΠ΅ΡΠ΅ΡΡΡΠΎΠΉΠΊΠΈ
IgH. ΠΡΡΠ²Π»Π΅Π½Π° Π²Π·Π°ΠΈΠΌΠΎΡΠ²ΡΠ·Ρ ΠΌΠ΅ΠΆΠ΄Ρ del(13q14) ΠΈ Amp1q12(Ο2
= 8,26, p < 0,01) ΠΈ ΠΌΠ΅ΠΆΠ΄Ρ del(13q14) ΠΈ ΠΏΠ΅ΡΠ΅ΡΡΡΠΎΠΉΠΊΠ°ΠΌΠΈ IgH
(Ο2 = 3,88, p < 0,05). ΠΡΠ²ΠΎΠ΄Ρ: 13q Π΄Π΅Π»Π΅ΡΠΈΡ/ΠΌΠΎΠ½ΠΎΡΠΎΠΌΠΈΡ 13, ΠΏΠ΅ΡΠ΅ΡΡΡΠΎΠΉΠΊΡ IGH ΠΈ Π°Π½ΠΎΠΌΠ°Π»ΠΈΡ Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌΡ 1 ΡΠ°ΡΡΠΎ ΠΎΡΠΌΠ΅ΡΠ°ΡΡ
ΠΏΡΠΈ MM, ΠΏΡΠΈΡΠ΅ΠΌ ΠΈΡ
ΡΠ°ΡΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ Π½Π΅ ΡΠ»ΡΡΠ°ΠΉΠ½ΠΎ ΠΈ ΡΠ΅ΡΠ½ΠΎ Π²Π·Π°ΠΈΠΌΠΎΡΠ²ΡΠ·Π°Π½ΠΎ. ΠΠ½ΡΠ΅ΡΡΠ°Π·Π½ΡΠΉ Π°Π½Π°Π»ΠΈΠ· FISH Π² ΠΊΠΎΠΌΠ±ΠΈΠ½Π°ΡΠΈΠΈ Ρ
MACS Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ CD138-ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ½ΡΡ
Π°Π½ΡΠΈΡΠ΅Π» ΡΠ²Π»ΡΠ΅ΡΡΡ Π²ΡΡΠΎΠΊΠΎΡΡΠ²ΡΡΠ²ΠΈΡΠ΅Π»ΡΠ½ΡΠΌ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ Π΄Π΅ΡΠ΅ΠΊΡΠΈΠΈ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΡ
ΡΠΈΡΠΎΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
Π°Π±Π΅ΡΡΠ°ΡΠΈΠΉ ΠΏΡΠΈ MM
Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group
Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71β857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conducted a pharmacogenomic genome-wide association study of sulfonylurea use and three ECG phenotypes: QT, JT and QRS intervals. In ancestry-specific meta-analyses, eight novel pharmacogenomic loci met the threshold for genome-wide significance (P<5 Γ 10β8), and a pharmacokinetic variant in CYP2C9 (rs1057910) that has been associated with sulfonylurea-related treatment effects and other adverse drug reactions in previous studies was replicated. Additional research is needed to replicate the novel findings and to understand their biological basis
Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels
Background So far, more than 170 loci have been associated with circulating lipid levels through genomewide association studies (GWAS). These associations are largely driven by common variants, their function is often not known, and many are likely to be markers for the causal variants. In this study we aimed to identify more new rare and low-frequency functional variants associated with circulating lipid levels. Methods We used the 1000 Genomes Project as a reference panel for the imputations of GWAS data from ~60 000 individuals in the discovery stage and ~90 000 samples in the replication stage. Results Our study resu
Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function
Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of l
Serum magnesium and calcium levels in relation to ischemic stroke : Mendelian randomization study
ObjectiveTo determine whether serum magnesium and calcium concentrations are causally associated with ischemic stroke or any of its subtypes using the mendelian randomization approach.MethodsAnalyses were conducted using summary statistics data for 13 single-nucleotide polymorphisms robustly associated with serum magnesium (n = 6) or serum calcium (n = 7) concentrations. The corresponding data for ischemic stroke were obtained from the MEGASTROKE consortium (34,217 cases and 404,630 noncases).ResultsIn standard mendelian randomization analysis, the odds ratios for each 0.1 mmol/L (about 1 SD) increase in genetically predicted serum magnesium concentrations were 0.78 (95% confidence interval [CI] 0.69-0.89; p = 1.3
7 10-4) for all ischemic stroke, 0.63 (95% CI 0.50-0.80; p = 1.6
7 10-4) for cardioembolic stroke, and 0.60 (95% CI 0.44-0.82; p = 0.001) for large artery stroke; there was no association with small vessel stroke (odds ratio 0.90, 95% CI 0.67-1.20; p = 0.46). Only the association with cardioembolic stroke was robust in sensitivity analyses. There was no association of genetically predicted serum calcium concentrations with all ischemic stroke (per 0.5 mg/dL [about 1 SD] increase in serum calcium: odds ratio 1.03, 95% CI 0.88-1.21) or with any subtype.ConclusionsThis study found that genetically higher serum magnesium concentrations are associated with a reduced risk of cardioembolic stroke but found no significant association of genetically higher serum calcium concentrations with any ischemic stroke subtype
Age at first birth in women is genetically associated with increased risk of schizophrenia
Prof. Paunio on PGC:n jΓ€senPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe
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