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101.
Deelen J Beekman M Uh HW Helmer Q Kuningas M Christiansen L Kremer D van der Breggen R Suchiman HE Lakenberg N van den Akker EB Passtoors WM Tiemeier H van Heemst D de Craen AJ Rivadeneira F de Geus EJ Perola M van der Ouderaa FJ Gunn DA Boomsma DI Uitterlinden AG Christensen K van Duijn CM Heijmans BT Houwing-Duistermaat JJ Westendorp RG Slagboom PE 《Aging cell》2011,10(4):686-698
By studying the loci that contribute to human longevity, we aim to identify mechanisms that contribute to healthy aging. To identify such loci, we performed a genome-wide association study (GWAS) comparing 403 unrelated nonagenarians from long-living families included in the Leiden Longevity Study (LLS) and 1670 younger population controls. The strongest candidate SNPs from this GWAS have been analyzed in a meta-analysis of nonagenarian cases from the Rotterdam Study, Leiden 85-plus study, and Danish 1905 cohort. Only one of the 62 prioritized SNPs from the GWAS analysis (P<1×10(-4) ) showed genome-wide significance with survival into old age in the meta-analysis of 4149 nonagenarian cases and 7582 younger controls [OR=0.71 (95% CI 0.65-0.77), P=3.39 × 10(-17) ]. This SNP, rs2075650, is located in TOMM40 at chromosome 19q13.32 close to the apolipoprotein E (APOE) gene. Although there was only moderate linkage disequilibrium between rs2075650 and the ApoE ε4 defining SNP rs429358, we could not find an APOE-independent effect of rs2075650 on longevity, either in cross-sectional or in longitudinal analyses. As expected, rs429358 associated with metabolic phenotypes in the offspring of the nonagenarian cases from the LLS and their partners. In addition, we observed a novel association between this locus and serum levels of IGF-1 in women (P=0.005). In conclusion, the major locus determining familial longevity up to high age as detected by GWAS was marked by rs2075650, which tags the deleterious effects of the ApoE ε4 allele. No other major longevity locus was found. 相似文献
102.
Mirjafari H Farragher TM Verstappen SM Yates A Bunn D Marshall T Lunt M Symmons DP Bruce IN 《Arthritis research & therapy》2011,13(5):R159
Introduction
Cardiovascular disease (CVD) is the leading cause of death in patients with inflammatory polyarthritis (IP), especially in seropositive disease. In established rheumatoid arthritis (RA), insulin resistance (IR) is increased and associated with CVD. We investigated factors associated with IR in an inception cohort of patients with early IP. 相似文献103.
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Jarom Heijmans Jooske F. van Lidth de Jeude Bon-Kyoung Koo Sanne L. Rosekrans Mattheus C.B. Wielenga Marc van de Wetering Marc Ferrante Amy S. Lee Jos J.M. Onderwater James C. Paton Adrienne W. Paton A. Mieke Mommaas Liudmila L. Kodach James C. Hardwick Daniël W. Hommes Hans Clevers Vanesa Muncan Gijs R. van den Brink 《Cell reports》2013,3(4):1128-1139
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Laurence Dedeken Rudy Chapusette Phu Quoc Lê Catherine Heijmans Christine Devalck Sophie Huybrechts France Ziereisen Laurence Hanssens Laurence Rozen Denis Noubouossie Malou Ngalula Mujinga Alina Ferster 《PloS one》2014,9(10)
Background
The 6-minute walk test (6MWT) is used in adults and children affected by a wide range of chronic diseases to evaluate their sub-maximal exercise capacity. It reflects the global response of various physiological systems in a situation simulating a daily life activity.Methods
We analyzed factors affecting the 6MWT in 46 Sickle Cell Disease children. Forty-two were treated with hydroxyurea (HU). Patients with normal test (>80% of the age-standardized predicted value) were compared to patients with abnormal test (≤80%). Baseline hematological values, clinical events, cerebrovascular disease, cardio-pulmonary parameters and disease-modifying treatment were compared according to the performance of the test.Results
Among the 46 patients, 14 had an abnormal 6MWT. In univariate analysis, both groups were similar for biological and clinical data. Six of the 14 patients with an abnormal 6MWT had silent infarct (SI) compared to 6/32 with a normal test (P = 0.09). When excluding chronically transfused patients, 4 of the 11 patients with an abnormal 6MWT had SI compared to 1/26 (P = 0.02). Baseline pulse oximetry was normal in both groups but slightly lower in patients with abnormal 6MWT (P = 0.02). No patient presented exercise-induced desaturation. In multivariate analysis, the only factor associated with abnormal 6MWT was the presence of SI (P = 0.045).Conclusions
In our cohort of 46 patients characterized by high exposure rate to HU and by the absence of severe cardiopulmonary disease, the sole factor independently associated with 6MWT was the presence of SI. The lower exercise capacity of children with SI may reflect some subclinical neurological impairment as they do not differ by hemoglobin level or cardiopulmonary parameters. 相似文献107.
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Climate warming is likely to increase nutrient mineralization rates in bog ecosystems which may change the plant species composition.
We examined the competitive relationships between two graminoid species, Eriophorum vaginatum and Rhynchospora alba, and two ericoid species, Calluna vulgaris and Vaccinium oxycoccus, at different nutrient supply rates. In a greenhouse, the plants were grown in monocultures and mixtures at four nutrient
treatments: control, high N, high P, and high N + P. The results show that the ericoids responded more strongly to the nutrient
treatments than the graminoids. The dwarf shrubs showed higher growth rates and reduced root:shoot ratio at high N + P supply.
When grown in mixture the ericoids increased their growth, while graminoids decreased in biomass or showed signs of nutrient
limitation compared to their monoculture plants. This suggests that under increased nutrient availability, bogs are more likely
to turn into dwarf shrub dominated ecosystems and not grassland. 相似文献