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101.
The association of a SNP upstream of INSIG2 with body mass index is reproduced in several but not all cohorts 总被引:1,自引:0,他引:1 下载免费PDF全文
Lyon HN Emilsson V Hinney A Heid IM Lasky-Su J Zhu X Thorleifsson G Gunnarsdottir S Walters GB Thorsteinsdottir U Kong A Gulcher J Nguyen TT Scherag A Pfeufer A Meitinger T Brönner G Rief W Soto-Quiros ME Avila L Klanderman B Raby BA Silverman EK Weiss ST Laird N Ding X Groop L Tuomi T Isomaa B Bengtsson K Butler JL Cooper RS Fox CS O'Donnell CJ Vollmert C Celedón JC Wichmann HE Hebebrand J Stefansson K Lange C Hirschhorn JN 《PLoS genetics》2007,3(4):e61
A SNP upstream of the INSIG2 gene, rs7566605, was recently found to be associated with obesity as measured by body mass index (BMI) by Herbert and colleagues. The association between increased BMI and homozygosity for the minor allele was first observed in data from a genome-wide association scan of 86,604 SNPs in 923 related individuals from the Framingham Heart Study offspring cohort. The association was reproduced in four additional cohorts, but was not seen in a fifth cohort. To further assess the general reproducibility of this association, we genotyped rs7566605 in nine large cohorts from eight populations across multiple ethnicities (total n = 16,969). We tested this variant for association with BMI in each sample under a recessive model using family-based, population-based, and case-control designs. We observed a significant (p < 0.05) association in five cohorts but saw no association in three other cohorts. There was variability in the strength of association evidence across examination cycles in longitudinal data from unrelated individuals in the Framingham Heart Study Offspring cohort. A combined analysis revealed significant independent validation of this association in both unrelated (p = 0.046) and family-based (p = 0.004) samples. The estimated risk conferred by this allele is small, and could easily be masked by small sample size, population stratification, or other confounders. These validation studies suggest that the original association is less likely to be spurious, but the failure to observe an association in every data set suggests that the effect of SNP rs7566605 on BMI may be heterogeneous across population samples. 相似文献
102.
Bengtsson L 《The FEBS journal》2007,274(6):1374-1382
The inner nuclear membrane protein MAN1 has been identified as an important factor in transforming growth factor beta/bone morphogenic protein (TGFbeta/BMP) signaling. Loss of MAN1 results in three autosomal dominant diseases in humans; all three characterized by increased bone density. Xenopus embryos lacking MAN1 develop severe morphological defects. Both in humans and in Xenopus embryos the defects originate from deregulation of TGFbeta/BMP signaling. Several independent studies have shown that MAN1 is antagonizing TGFbeta/BMP signaling through binding to regulatory Smads. Here, recent progress in understanding MAN1 functions is summarized and a model for MAN1-dependent regulation of TGFbeta/BMP signaling is proposed. 相似文献
103.
Zhang Q Bengtsson M Partridge C Salehi A Braun M Cox R Eliasson L Johnson PR Renström E Schneider T Berggren PO Göpel S Ashcroft FM Rorsman P 《Nature cell biology》2007,9(4):453-460
Pancreatic islets have a central role in blood glucose homeostasis. In addition to insulin-producing beta-cells and glucagon-secreting alpha-cells, the islets contain somatostatin-releasing delta-cells. Somatostatin is a powerful inhibitor of insulin and glucagon secretion. It is normally secreted in response to glucose and there is evidence suggesting its release becomes perturbed in diabetes. Little is known about the control of somatostatin release. Closure of ATP-regulated K(+)-channels (K(ATP)-channels) and a depolarization-evoked increase in cytoplasmic free Ca(2+) concentration ([Ca(2+)](i)) have been proposed to be essential. Here, we report that somatostatin release evoked by high glucose (>or=10 mM) is unaffected by the K(ATP)-channel activator diazoxide and proceeds normally in K(ATP)-channel-deficient islets. Glucose-induced somatostatin secretion is instead primarily dependent on Ca(2+)-induced Ca(2+)-release (CICR). This constitutes a novel mechanism for K(ATP)-channel-independent metabolic control of pancreatic hormone secretion. 相似文献
104.
Kvist AJ Johnson AE Mörgelin M Gustafsson E Bengtsson E Lindblom K Aszódi A Fässler R Sasaki T Timpl R Aspberg A 《The Journal of biological chemistry》2006,281(44):33127-33139
Inactivation of the perlecan gene leads to perinatal lethal chondrodysplasia. The similarity to the phenotypes of the Col2A1 knock-out and the disproportionate micromelia mutation suggests perlecan involvement in cartilage collagen matrix assembly. We now present a mechanism for the defect in collagen type II fibril assembly by perlecan-null chondrocytes. Cartilage perlecan is a heparin sulfate or a mixed heparan sulfate/chondroitin sulfate proteoglycan. The latter form binds collagen and accelerates fibril formation in vitro, with more defined fibril morphology and increased fibril diameters produced in the presence of perlecan. Interestingly, the enhancement of collagen fibril formation is independent on the core protein and is mimicked by chondroitin sulfate E but neither by chondroitin sulfate D nor dextran sulfate. Furthermore, perlecan chondroitin sulfate contains the 4,6-disulfated disaccharides typical for chondroitin sulfate E. Indeed, purified glycosaminoglycans from perlecan-enriched fractions of cartilage extracts contain elevated levels of 4,6-disulfated chondroitin sulfate disaccharides and enhance collagen fibril formation. The effect on collagen assembly is proportional to the content of the 4,6-disulfated disaccharide in the different cartilage extracts, with growth plate cartilage glycosaminoglycan being the most efficient enhancer. These findings demonstrate a role for perlecan chondroitin sulfate side chains in cartilage extracellular matrix assembly and provide an explanation for the perlecan-null chondrodysplasia. 相似文献
105.
Jeppsson M Bengtsson O Franke K Lee H Hahn-Hägerdal B Gorwa-Grauslund MF 《Biotechnology and bioengineering》2006,93(4):665-673
Xylose fermentation by Saccharomyces cerevisiae requires the introduction of a xylose pathway, either similar to that found in the natural xylose-utilizing yeasts Pichia stipitis and Candida shehatae or similar to the bacterial pathway. The use of NAD(P)H-dependent XR and NAD(+)-dependent XDH from P. stipitis creates a cofactor imbalance resulting in xylitol formation. The effect of replacing the native P. stipitis XR with a mutated XR with increased K(M) for NADPH was investigated for xylose fermentation to ethanol by recombinant S. cerevisiae strains. Enhanced ethanol yields accompanied by decreased xylitol yields were obtained in strains carrying the mutated XR. Flux analysis showed that strains harboring the mutated XR utilized a larger fraction of NADH for xylose reduction. The overproduction of the mutated XR resulted in an ethanol yield of 0.40 g per gram of sugar and a xylose consumption rate of 0.16 g per gram of biomass per hour in chemostat culture (0.06/h) with 10 g/L glucose and 10 g/L xylose as carbon source. 相似文献
106.
Patterns of stable isotope signatures in willow warbler Phylloscopus trochilus feathers collected in Africa 总被引:2,自引:0,他引:2
We conducted stable isotope analyses of nitrogen and carbon on feathers obtained from willow warblers in Africa to find an explanation for a previously observed pattern of different δ15 N and δ13 C values across a migratory divide in central Scandinavia. A new data set confirms that north Scandinavian birds of the subspecies P. t. acredula have higher δ15 N values than south Scandinavian birds of the subspecies P. t. trochilus . In Africa, we found significant differences for both δ15 N and δ13 C values among feathers collected from major geographical regions as well as between countries within regions. Isotope signatures of δ15 N and δ13 C in Scandinavian acredula matched well with those of willow warblers sampled in southern parts of Africa, but differed from samples obtained in East and West Africa. Isotope signatures in Scandinavian trochilus did not agree with the pattern in any of the three African regions (West, East or South). However, a more detailed analysis of the isotopic data in feathers from countries within West Africa, which is the wintering region of Swedish trochilus based on ringing recoveries, revealed a correspondence with samples from Liberia, the Ivory Coast and Nigeria. 相似文献
107.
Katarina Månsson Per Bengtson Ursula Falkengren‐Grerup Göran Bengtsson 《Oikos》2009,118(12):1908-1916
A green house experiment was designed to test the idea that competition for inorganic nitrogen (N) between plants and heterotrophic microorganisms occurs in soils with high C:N ratios, qualifying for N limited microbial activity, but not at low C:N ratios. The short‐term (24 h) 15N uptake by the grass Festuca gigantea and microorganisms in planted and unplanted soils was determined, and the bacterial activity was measured by the 3H‐thymidine incorporation technique. Two deciduous forest soils, with C:N‐ratios of 20 and 31, and the 20 soil amended with litter to a C:N ratio of 34, were used. A novel and important part of the experimental design was the preparation of the unplanted reference soil with plants present until the competition assay started by the addition of 15N labelled ammonium ( ) or nitrate ). The results suggested that plants and soil microorganisms competed for mineral N but under influence of other factors than the soil C:N ratio. The plants reduced the microbial uptake of and in the soil with low C:N ratio, which also had the lowest bacterial activity. The plants had a larger N uptake than microorganisms in the two natural soils but smaller in the litter‐amended, and their presence enhanced the bacterial activity, especially in the latter soil. The litter‐amended soil with its high C:N ratio and easily decomposable C was the soil that best fulfilled the criteria for competition, including a net consumption of mineral N during the assay, the lowest plant uptake of mineral N due to the high N immobilization by microorganisms, and a reduced microbial 15N uptake‐to‐bacterial activity in the presence of plants. Thus, other factors, such as the decomposability of the soil C and the bacterial activity, were more important than the soil C:N ratio to the outcome of plant–microbial competition for N. 相似文献
108.
Maria Kahlert Raino-Lars Albert Eeva-Leena Anttila Roland Bengtsson Christian Bigler Tiina Eskola Veronika Gälman Steffi Gottschalk Eva Herlitz Amelie Jarlman Jurate Kasperoviciene Mikołaj Kokociński Helen Luup Juha Miettinen Ieva Paunksnyte Kai Piirsoo Isabel Quintana Janne Raunio Bernt Sandell Heikki Simola Irene Sundberg Sirje Vilbaste Jan Weckström 《Journal of applied phycology》2009,21(4):471-482
The goal of this study was a harmonization of diatom identification and counting among diatomists from the Scandinavian and
Baltic countries to improve the comparison of diatom studies in this geographical area. An analysis of the results of 25 diatomists
following the European standard EN 14407 during an intercalibration exercise showed that a high similarity was achieved by
harmonization and not because of a long experience with diatoms. Sources of error were wrong calibration scales, overlooking
of small taxa, especially small Navicula s.l., misidentifications (Eunotia rhomboidea was mistaken for Eunotia incisa) and unclear separation between certain taxa in the identification literature. The latter was discussed during a workshop
with focus on the Achnanthes minutissima group, the separation of Fragilaria capucina var. gracilis from F. capucina var. rumpens, and Nitzschia palea var. palea from N. palea var. debilis. The exercise showed also that the Swedish standard diatom method tested here worked fine with acceptable error for the indices
IPS (Indice de Polluo-sensibilité Spécifique) and ACID (ACidity Index for Diatoms) when diatomists with a low similarity (Bray–Curtis
<60%) with the auditor in at least one of the samples are excluded. 相似文献
109.
Potato late blight disease caused by the zoospore-producing pathogen Phytophthora infestans (Mont.) de Bary is one of the most destructive plant diseases world-wide and currently its management mainly relies on the frequent use of fungicides. This study investigated the possibility of reducing potato late blight by biocontrol with the biosurfactant-producing strain Pseudomonas koreensis 2.74. Significant disease reduction with the biosurfactant-producing strain and its biosurfactant was observed in greenhouse trials using a detached-leaf assay. A direct effect of the biosurfactant on zoospores of P. infestans was also observed, whereas the biosurfactant only caused a minor reduction in mycelial growth rate and had no effect on the rate of sporangia production in pure culture. 相似文献
110.