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排序方式: 共有825条查询结果,搜索用时 15 毫秒
751.
Francesco Gianfagna Daniela Cugino Wolfgang Ahrens Mark E. S. Bailey Karin Bammann Diana Herrmann Anna C. Koni Yiannis Kourides Staffan Marild Dénes Molnár Luis A. Moreno Yannis P. Pitsiladis Paola Russo Alfonso Siani Sabina Sieri Isabelle Sioen Toomas Veidebaum Licia Iacoviello 《PloS one》2013,8(8)
Neuromedin U, encoded by the NMU gene, is a hypothalamic neuropeptide that regulates both energy metabolism and bone mass. The beta-2 adrenergic receptor, encoded by the ADRB2 gene, mediates several effects of catecholamine hormones and neurotransmitters in bone. We investigated whether NMU single nucleotide polymorphisms (SNPs) and haplotypes, as well as functional ADRB2 SNPs, are associated with bone stiffness in children from the IDEFICS cohort, also evaluating whether NMU and ADRB2 interact to affect this trait. A sample of 2,274 subjects (52.5% boys, age 6.2±1.8 years) from eight European countries, having data on calcaneus bone stiffness index (SI, mean of both feet) and genotyping (NMU gene: rs6827359, rs12500837, rs9999653; ADRB2 gene: rs1042713, rs1042714), was studied. After false discovery rate adjustment, SI was significantly associated with all NMU SNPs. rs6827359 CC homozygotes showed the strongest association (recessive model, Δ = −1.8, p = 0.006). Among the five retrieved haplotypes with frequencies higher than 1% (range 2.0–43.9%), the CCT haplotype (frequency = 39.7%) was associated with lower SI values (dominant model, Δ = −1.0, p = 0.04) as compared to the most prevalent haplotype. A non-significant decrease in SI was observed in in ADRB2 rs1042713 GG homozygotes, while subjects carrying SI-lowering genotypes at both SNPs (frequency = 8.4%) showed much lower SI than non-carriers (Δ = −3.9, p<0.0001; p for interaction = 0.025). The association was more evident in preschool girls, in whom SI showed a curvilinear trend across ages. In subgroup analyses, rs9999653 CC NMU or both GG ADRB2 genotypes were associated with either lower serum calcium or β-CrossLaps levels (p = 0.01). This study in European children shows, for the first time in humans, a role for NMU gene through interaction with ADRB2 gene in bone strength regulation, more evident in preschool girls. 相似文献
752.
Synapse elimination in the adult central nervous system can be modelled by axotomy of spinal motoneurons which triggers removal of synapses from the cell surface of lesioned motoneurons by processes that remain elusive. Proposed candidate mechanisms are removal of synapses by reactive microglia and astrocytes, based on the remarkable activation of these cell types in the vicinity of motoneurons following axon lesion, and/or decreased expression of synaptic adhesion molecules in lesioned motoneurons. In the present study, we investigated glia activation and adhesion molecule expression in motoneurons in two mouse strains with deviant patterns of synapse elimination following axotomy. Mice deficient in complement protein C3 display a markedly reduced loss of synapses from axotomized motoneurons, whereas mice with impaired function of major histocompatibility complex (MHC) class Ia display an augmented degree of stripping after axotomy. Activation of microglia and astrocytes was assessed by semiquantative immunohistochemistry for Iba 1 (microglia) and GFAP (astrocytes), while expression of synaptic adhesion molecules was determined by in situ hybridization. In spite of the fact that the two mouse strains display very different degrees of synapse elimination, no differences in terms of glial activation or in the downregulation of the studied adhesion molecules (SynCAM1, neuroligin-2,-3 and netrin G-2 ligand) could be detected. We conclude that neither glia activation nor downregulation of synaptic adhesion molecules are correlated to the different extent of the synaptic stripping in the two studied strains. Instead the magnitude of the stripping event is most likely a consequence of a precise molecular signaling, which at least in part is mediated by immune molecules. 相似文献
753.
Genotoxicity, inflammation and physico-chemical properties of fine particle samples from an incineration energy plant and urban air 总被引:1,自引:0,他引:1
Sharma AK Jensen KA Rank J White PA Lundstedt S Gagne R Jacobsen NR Kristiansen J Vogel U Wallin H 《Mutation research》2007,633(2):95-111
Airborne particulate matter (PM) was sampled by use of an electrostatic sampler in an oven hall and a receiving hall in a waste-incineration energy plant, and from urban air in a heavy-traffic street and from background air in Copenhagen. PM was sampled for 1-2 weeks, four samples at each site. The samples were extracted and examined for mutagenicity in Salmonella typhimurium strains TA98, YG1041 and YG5161, for content of inorganic elements and for the presence of eight polycyclic aromatic hydrocarbons. The induction of IL-6 and IL-8 mRNA expression and the presence of DNA damage - tested by the comet assay - were determined after 24-h incubations with human A549 lung epithelial cells. The PM(2.5) concentration was about twofold greater in the oven hall than in the receiving hall. The particle size distribution in the receiving hall was similar to that in street air (maximum mode at about 25nm), but the distribution was completely different in the oven hall (maximum mode at about 150nm). Also chemically, the samples from the oven hall were highly different from the other samples. PM extracts from the receiving hall, street and background air were more mutagenic than the PM extracts from the oven hall. PM from all four sites caused similar levels of DNA damage in A549 cells; only the oven hall samples gave results that were statistically significantly different from those obtained with street-air samples. The receiving hall and the urban air samples were similarly inflammatory (relative IL-8 mRNA expression), whereas the oven hall did not cause a statistically significant increase in IL-8 mRNA expression. A principal component analysis separated the oven hall and the receiving hall by the first principal component. These two sites were separated from street and background air with the second principal component. Several clusters of constituents were identified. One cluster consisted of all the polycyclic aromatic hydrocarbons (PAH), several groups of metals and one group of the biological endpoints (DNA damage, IL-6 and IL-8 mRNA expression). The PAH and the inorganic content of the air in the receiving hall may be due to vehicle emissions and suspended waste particles. The inorganic content in the street and background air may have been influenced by break wear, road emissions and long-range transport. The results from a partial least-square regression analysis predicted that both PAHs and a group of metals including Fe and Mn contributed to IL-6 and IL-8 induction. Only Mn and Sr were predicted to influence DNA damage statistically significantly. Among the PAHs only chrysene had influence on DNA damage. The PM from the oven hall was markedly different from the PM at other locations in particle size distribution, chemical composition and the resulting biological effects when A549 cells were incubated with the PM. These characteristics and observations in the oven hall indicated that the PM source was oven exhaust, which was well combusted. 相似文献
754.
Structure-function analysis of a bacterial deoxyadenosine kinase reveals the basis for substrate specificity 总被引:2,自引:0,他引:2
Deoxyribonucleoside kinases (dNKs) catalyze the transfer of a phosphoryl group from ATP to a deoxyribonucleoside (dN), a key step in DNA precursor synthesis. Recently structural information concerning dNKs has been obtained, but no structure of a bacterial dCK/dGK enzyme is known. Here we report the structure of such an enzyme, represented by deoxyadenosine kinase from Mycoplasma mycoides subsp. mycoides small colony type (Mm-dAK). Superposition of Mm-dAK with its human counterpart's deoxyguanosine kinase (dGK) and deoxycytidine kinase (dCK) reveals that the overall structures are very similar with a few amino acid alterations in the proximity of the active site. To investigate the substrate specificity, Mm-dAK has been crystallized in complex with dATP and dCTP, as well as the products dCMP and dCDP. Both dATP and dCTP bind to the enzyme in a feedback-inhibitory manner with the dN part in the deoxyribonucleoside binding site and the triphosphates in the P-loop. Substrate specificity studies with clinically important nucleoside analogs as well as several phosphate donors were performed. Thus, in this study we combine structural and kinetic data to gain a better understanding of the substrate specificity of the dCK/dGK family of enzymes. The structure of Mm-dAK provides a starting point for making new anti bacterial agents against pathogenic bacteria. 相似文献
755.
Marushchak D Grenklo S Johansson T Karlsson R Johansson LB 《Biophysical journal》2007,93(9):3291-3299
A new method, in which a genetic algorithm was combined with Brownian dynamics and Monte Carlo simulations, was developed to analyze fluorescence depolarization data collected by the time-correlated single photon-counting technique. It was applied to studies of BODIPY-labeled filamentous actin (F-actin). The technique registered the local order and reorienting motions of the fluorophores, which were covalently coupled to cysteine 374 (C374) in actin and interacted by electronic energy migration within the actin polymers. Analyses of F-actin samples composed of different fractions of labeled actin molecules revealed the known helical organization of F-actin, demonstrating the usefulness of this technique for structure determination of complex protein polymers. The distance from the filament axis to the fluorophore was found to be considerably less than expected from the proposed position of C374 at a high filament radius. In addition, polymerization experiments with BODIPY-actin suggest a 25-fold more efficient signal for filament formation than pyrene-actin. 相似文献
756.
Romón P Iturrondobeitia JC Gibson K Lindgren BS Goldarazena A 《Environmental entomology》2007,36(4):743-750
The association between 11 species of bark beetles (Coleoptera: Scolytinae) and one weevil (Coleoptera: Entiminae) with the pitch canker fungus, Fusarium circinatum Nirenberg and O'Donnell, was determined by crushing beetles on selective medium and histone H3 gene sequencing. Pityophthorus pubescens (Marsham) (25.00%), Hylurgops palliatus (Gyllenhal) (11.96%), Ips sexdentatus (B?rner) (8.57%), Hypothenemus eruditus Westwood (7.89%), Hylastes attenuatus Erichson (7.40%), and Orthotomicus erosus (Wollaston) (2.73%) were found to carry the inoculum. In addition, the root weevil Brachyderes incanus L. (14.28%) had the second highest frequency of occurrence of the fungus. The responses of the insects to a range of verbenone doses were tested in field bioassays using funnel traps. Catches of P. pubescens, a species colonizing branch tips of live trees, were significantly reduced in a log-linear dose-dependent relationship. Catches of I. sexdentatus, an opportunistic species normally attacking fresh dead host material, were also gradually reduced with increasing verbenone dose. Catches of Tomicus piniperda L., O. erosus, Dryocoetes autographus (Ratzeburg), H. eruditus, Xyleborus dryographus (Ratzeburg), Hylastes ater (Paykull), Hylurgus ligniperda (F.), H. attenuatus, and B. incanus were not significantly affected by verbenone. The effects of verbenone were consistent with differences in host-age preference. Semiochemical disruption by verbenone in P. pubescens and I. sexdentatus could represent an integrated pest management strategy for the prevention of the spread of pitch canker disease between different stands. However, several species associated with F. circinatum were unaffected by verbenone, not supporting this compound for prevention of the establishment of potential vectors in Northern Spain. 相似文献
757.
758.
Lena Innala Ewa Berglin Bozena M?ller Lotta Ljung Torgny Smedby Anna S?dergren Staffan Magnusson Solbritt Rantap??-Dahlqvist Solveig W?llberg-Jonsson 《Arthritis research & therapy》2014,16(2):R94
Introduction
Disease activity, severity and comorbidity contribute to increased mortality in patients with rheumatoid arthritis (RA). We evaluated the impact of age at disease onset on prognostic risk factors and treatment in patients with early disease.Methods
In this study, 950 RA patients were followed regularly from the time of inclusion (<12 months from symptom onset) for disease activity (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tender and/or swollen joints, Visual Analogue Scale pain and global scores, and Disease Activity Score in 28 joints (DAS28)) and function (Health Assessment Questionnaire (HAQ)). Disease severity, measured on the basis of radiographs of the hands and feet (erosions based on Larsen score), extraarticular disease, nodules, and comorbidities and treatment (disease-modifying antirheumatic drugs (DMARDs), corticosteroids, biologics and nonsteroidal anti-inflammatory drugs) were recorded at the time of inclusion and at 5 years. Autoantibodies (rheumatoid factor, antinuclear antibodies and antibodies against cyclic citrullinated peptides (ACPAs)) and genetic markers (human leucocyte antibody (HLA) shared epitope and protein tyrosine phosphatase nonreceptor type 22 (PTPN22)) were analysed at the time of inclusion. Data were stratified as young-onset RA (YORA) and late-onset RA (LORA), which were defined as being below or above the median age at the time of onset of RA (58 years).Results
LORA was associated with lower frequency of ACPA (P < 0.05) and carriage of PTPN22-T variant (P < 0.01), but with greater disease activity at the time of inclusion measured on the basis of ESR (P < 0.001), CRP (P < 0.01) and accumulated disease activity (area under the curve for DAS28 score) at 6 months (P < 0.01), 12 months (P < 0.01) and 24 months (P < 0.05), as well as a higher HAQ score (P < 0.01) compared with YORA patients. At baseline and 24 months, LORA was more often associated with erosions (P < 0.01 for both) and higher Larsen scores (P < 0.001 for both). LORA was more often treated with corticosteroids (P < 0.01) and less often with methotrexate (P < 0.001) and biologics (P < 0.001). YORA was more often associated with early DMARD treatment (P < 0.001). The results of multiple regression analyses supported our findings regarding the impact of age on chosen treatment.Conclusion
YORA patients were more frequently ACPA-positive than LORA patients. LORA was more often associated with erosions, higher Larsen scores, higher disease activity and higher HAQ scores at baseline. Nevertheless, YORA was treated earlier with DMARDs, whilst LORA was more often treated with corticosteroids and less often with DMARDs in early-stage disease. These findings could have implications for the development of comorbidities. 相似文献759.
760.
Praveen Krishnamoorthy Clara Sanchez-Rodriguez Ingo Heilmann Staffan Persson 《Annals of botany》2014,114(6):1049-1057