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91.
Costas J Carrera N Domínguez E Vilella E Martorell L Valero J Gutiérrez-Zotes A Labad A Carracedo A 《Human genetics》2009,124(6):607-613
The number and frequency of susceptibility alleles at loci associated to most psychiatric disorders is largely unknown, in
spite of its relevance for the design of studies aiming to find these alleles. Both, common polymorphisms and rare mutations
may contribute to the genetic susceptibility to complex psychiatric disorders, being the relative relevance of each type of
variation currently under debate. Here, we confirmed the existence of a common protective haplotype against schizophrenia
at the dopamine D3 receptor (DRD3) gene, by replication and pooled analysis with previous data (Mantel–Haenszel χ2
P value = 0.00227; OR = 0.79, 95% CI 0.68–0.92, based on 794 cases and 1,078 controls from three independent populations of
European origin). This protective haplotype is at very low frequency in Sub-Saharan Africans (median 0.06) and at intermediate
frequencies in other populations (median 0.25). We also revealed, by examining the patterns of linkage disequilibrium around
this gene, that the protective haplotype has reached high frequency in non-African populations due to selection acting, most
probably, on a linked functional polymorphism, the non-synonymous single nucleotide polymorphism Ser9Gly (rs6280), also at
DRD3. Thus, this finding shows that the natural selection may play a role in the existence of common alleles conferring different
susceptibility to schizophrenia.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
92.
Thermodynamic solubility is a decisive physicochemical property in drug development. The Chasing Equilibrium method offers an alternative to the classical procedures to measure the solubility of compounds with acid–base properties. The method is fast and yields accurate results. In this work, the solubility of several compounds including acids and bases was determined through the Chasing Equilibrium approach. A study of experimental conditions in terms of sample weight was performed to measure solubilities. The study shows that only a limited range of weights, depending on the nature and solubility of the compounds, is adequate to obtain reliable results. 相似文献
93.
Niklas Wahlberg Elisabet Weingartner Andrew D Warren S?ren Nylin 《BMC evolutionary biology》2009,9(1):92
Background
Major conflict between mitochondrial and nuclear genes in estimating species relationships is an increasingly common finding in animals. Usually this is attributed to incomplete lineage sorting, but recently the possibility has been raised that hybridization is important in generating such phylogenetic patterns. Just how widespread ancient and/or recent hybridization is in animals and how it affects estimates of species relationships is still not well-known. 相似文献94.
Johanna Gustafsson Iva Gunnarsson Ola B?rjesson Susanne Pettersson Sonia M?ller Guo-Zhong Fei Kerstin Elvin Julia F Simard Lars-Olof Hansson Ingrid E Lundberg Anders Larsson Elisabet Svenungsson 《Arthritis research & therapy》2009,11(6):R186
Introduction
Cardiovascular disease (CVD) is a major cause of premature mortality among Systemic lupus erythematosus (SLE) patients. Many studies have measured and evaluated risk factors for premature subclinical atherosclerosis, but few studies are prospective and few have evaluated risk factors for hard endpoints, i.e. clinically important cardiovascular events (CVE). We investigated the impact of traditional and lupus associated risk factors for the first ever CVE in a longitudinal cohort of SLE patients.Methods
A total of 182 SLE patients (mean age 43.9 years) selected to be free of CVE were included. Cardiovascular and autoimmune biomarkers were measured on samples collected after overnight fasting at baseline. Clinical information was collected at baseline and at follow up. End point was the first ever CVE (ischemic heart, cerebrovascular or peripheral vascular disease or death due to CVD). Impact of baseline characteristics/biomarkers on the risk of having a first CVE was evaluated with Cox regression.Results
Follow up was 99.5% after a mean time of 8.3 years. Twenty-four patients (13%) had a first CVE. In age-adjusted Cox regression, any positive antiphospholipid antibody (aPL), elevated markers of endothelial activation (von Willebrand factor (vWf), soluble vascular cellular adhesion molecule-1 (sVCAM-1)) and fibrinogen predicted CVEs. Of SLE manifestations, arthritis, pleuritis and previous venous occlusion were positively associated with future CVEs while thrombocytopenia was negatively associated. Among traditional risk factors only age and smoking were significant predictors. In a multivariable Cox regression model age, any positive aPL, vWf and absence of thrombocytopenia were all predictors of the first CVE.Conclusions
In addition to age, positive aPL, biomarkers indicating increased endothelial cell activity/damage, and absence of thrombocytopenia were independent predictors of CVEs in this prospective study. Our results indicate that activation of the endothelium and the coagulation system are important features in SLE related CVD. Furthermore, we observed that the risk of CVEs seems to differ between subgroups of SLE patients. 相似文献95.
Background: Rheumatoid arthritis (RA) is a chronic inflammatory joint disorder that may adversely affect health-related quality of life (HRQoL) both in established and early disease.Objectives: In patients with recent onset (<12 months) of RA, this extension of a previous study assessed HRQoL and the effect of disease activity over time.Methods: Consecutive patients with recent onset of RA between March 1996 and November 1998 were followed for 6 years at the Department of Rheumatology of the University Hospital of Umeå in Sweden. Patients were requested to complete the 36-item Short Form (SF-36) Health Survey at 0, 24, 48, and 72 months. Gender differences were examined, and correlations between the SF-36 scales (with higher scores indicating better HRQoL) and data reflecting disease activity were analyzed.Results: Fifty-one patients, 34 women and 17 men (mean age, 50.6 years; range, 20–78 years), participated in the study; in all, 41 patients completed the SF-36 at both 0 and 72 months. At inclusion (0 months), women reported significantly higher scores for physical role functioning, bodily pain, and social functioning compared with men (all, P < 0.05). At 72 months compared with 0 months, women reported significantly better mental health (P < 0.05), whereas men reported significantly better physical role functioning (P < 0.05), bodily pain (P < 0.01), mental health (P < 0.01), and vitality (P < 0.01). Additionally, at 72 months, the entire patient group rated physical role functioning and social functioning (both, P < 0.05), bodily pain and vitality (both, P < 0.01), and mental health (P < 0.001) as significantly better compared with the inclusion assessment. Overall improvement with time was significantly better for men than for women (P < 0.05). There were limited correlations between SF-36 point disease activity parameters and the SF-36 scores at 0 months (erythrocyte sedimentation rate vs physical functioning, mental health [both, P < 0.05], and bodily pain [P < 0.01]; 28-joint Disease Activity Score vs bodily pain [P < 0.05] and emotional role functioning [P < 0.01]) and at 72 months (C-reactive protein vs physical role functioning [P < 0.05]). Most of the physical subscales at inclusion correlated with the physical component summary (PCS) of the SF-36 questionnaire at 6 years.Conclusions: At disease onset, women with early RA reported better HRQoL than did their male counterparts. After 6 years, women and especially men both experienced better HRQoL, and no significant gender differences remained in any of the SF-36 scales or values for disease activity parameters. The PCS score at disease onset was the best predictor of the PCS score after 6 years. 相似文献
96.
Francine M. R. Hughes Mats Johansson Shaojun Xiong Elisabet Carlborg Dawn Hawkins Magnus Svedmark Adrian Hayes Alexander Goodall Keith S. Richards Christer Nilsson 《Plant Ecology》2010,208(1):77-92
River management practices have altered the hydrological regimes of many rivers and also altered the availability of regeneration
niches for riparian species. We investigated the impact of changed hydrological regimes on the sex ratios and the Spatial
Segregation of the Sexes (SSS) in the dioecious species Salix myrsinifolia Salisb.–phylicifolia L. and S. lapponum L. by studying the free-flowing Vindel River and the regulated Ume River in northern Sweden. We surveyed sex ratios of these
species in 12 river reaches on the Vindel River and in 17 reaches on the Ume River. In addition, we surveyed the sex and location
above mean river stage of 1,002 individuals across both river systems to investigate the SSS of both species. Cuttings were
collected from male and female individuals of S. myrsinifolia–phylicifolia from both rivers and subjected to four different water table regimes in a greenhouse experiment to investigate growth response
between the sexes. We found an M/F sex ratio in both river systems similar to the regional norm of 0.62 for S. myrsinifolia–phylicifolia and of 0.42 for S. lapponum. We found no evidence of SSS in either the free-flowing Vindel River or the regulated Ume River. In the greenhouse experiment,
hydrological regime had a significant effect on shoot and root dry weight and on root length. Significantly higher shoot dry
weights were found in females than in males and significantly different shoot and root dry weights were found between cuttings
taken from the two rivers. We concluded that changed hydrological regimes are likely to alter dimensions of the regeneration
niche and therefore to influence sex ratios and SSS at an early successional stage, making it difficult to find clear spatial
patterns once these species reach maturity and can be sexed. 相似文献
97.
Nerve fibers accompany blood and lymphatic vessels all over the body. An extensive amount of knowledge has been obtained with regard to tumor angiogenesis and tumor lymphangiogenesis, yet little is known about the potential biological effects of "neoneurogenesis". Cancer cells can exploit the advantage of the factors released by the nerve fibers to generate a positive microenvironment for cell survival and proliferation. At the same time, they can stimulate the formation of neurites by secreting neurotrophic factors and axon guidance molecules. The neuronal influence on the biology of a neoplasm was initially described several decades ago. Since then, an increasing amount of experimental evidence strongly suggests the existence of reciprocal interactions between cancer cells and nerves in humans. Moreover, researchers have been able to demonstrate a crosstalk between cancer cells and nerve fibers as a strategy for survival. Despite all these evidence, a lot remains to be done in order to clarify the role of neurotransmitters, neuropeptides, and their associated receptor-initiated signaling pathways in the development and progression of cancer, and response to therapy. A global-wide characterization of the neurotransmitters or neuropeptides present in the tumor microenvironment would provide insights into the real biological influences of the neuronal tissue on tumor progression. This review is intended to discuss our current understanding of neurosignaling in cancer and its potential implications on cancer prevention and therapy. The review will focus on the soluble factors released by cancer cells and nerve endings, their biological effects and their potential relevance in the treatment of cancer. 相似文献
98.
Fernández Robledo JA Caler E Matsuzaki M Keeling PJ Shanmugam D Roos DS Vasta GR 《International journal for parasitology》2011,41(12):1217-1229
Perkinsus marinus (Phylum Perkinsozoa) is a protozoan parasite that has devastated natural and farmed oyster populations in the USA, significantly affecting the shellfish industry and the estuarine environment. The other two genera in the phylum, Parvilucifera and Rastrimonas, are parasites of microeukaryotes. The Perkinsozoa occupies a key position at the base of the dinoflagellate branch, close to its divergence from the Apicomplexa, a clade that includes parasitic protista, many harbouring a relic plastid. Thus, as a taxon that has also evolved toward parasitism, the Perkinsozoa has attracted the attention of biologists interested in the evolution of this organelle, both in its ultrastructure and the conservation, loss or transfer of its genes. A review of the recent literature reveals mounting evidence in support of the presence of a relic plastid in P. marinus, including the presence of multimembrane structures, characteristic metabolic pathways and proteins with a bipartite N-terminal extension. Further, these findings raise intriguing questions regarding the potential functions and unique adaptation of the putative plastid and/or plastid genes in the Perkinsozoa. In this review we analyse the above-mentioned evidence and evaluate the potential future directions and expected benefits of addressing such questions. Given the rapidly expanding molecular/genetic resources and methodological toolbox for Perkinsus spp., these organisms should complement the currently established models for investigating plastid evolution within the Chromalveolata. 相似文献
99.
100.
Boehm M Romero E Reisinger V Yu J Komenda J Eichacker LA Dekker JP Nixon PJ 《The Journal of biological chemistry》2011,286(17):14812-14819
Biochemical characterization of intermediates involved in the assembly of the oxygen-evolving Photosystem II (PSII) complex is hampered by their low abundance in the membrane. Using the cyanobacterium Synechocystis sp. PCC 6803, we describe here the isolation of the CP47 and CP43 subunits, which, during biogenesis, attach to a reaction center assembly complex containing D1, D2, and cytochrome b(559), with CP47 binding first. Our experimental approach involved a combination of His tagging, the use of a D1 deletion mutant that blocks PSII assembly at an early stage, and, in the case of CP47, the additional inactivation of the FtsH2 protease involved in degrading unassembled PSII proteins. Absorption spectroscopy and pigment analyses revealed that both CP47-His and CP43-His bind chlorophyll a and β-carotene. A comparison of the low temperature absorption and fluorescence spectra in the Q(Y) region for CP47-His and CP43-His with those for CP47 and CP43 isolated by fragmentation of spinach PSII core complexes confirmed that the spectroscopic properties are similar but not identical. The measured fluorescence quantum yield was generally lower for the proteins isolated from Synechocystis sp. PCC 6803, and a 1-3-nm blue shift and a 2-nm red shift of the 77 K emission maximum could be observed for CP47-His and CP43-His, respectively. Immunoblotting and mass spectrometry revealed the co-purification of PsbH, PsbL, and PsbT with CP47-His and of PsbK and Psb30/Ycf12 with CP43-His. Overall, our data support the view that CP47 and CP43 form preassembled pigment-protein complexes in vivo before their incorporation into the PSII complex. 相似文献