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81.
Victor X Jin Gregory AC Singer Francisco J Agosto-Pérez Sandya Liyanarachchi Ramana V Davuluri 《BMC bioinformatics》2006,7(1):114-13
Background
The canonical core promoter elements consist of the TATA box, initiator (Inr), downstream core promoter element (DPE), TFIIB recognition element (BRE) and the newly-discovered motif 10 element (MTE). The motifs for these core promoter elements are highly degenerate, which tends to lead to a high false discovery rate when attempting to detect them in promoter sequences. 相似文献82.
Christophe Rodriguez Cathia Soulié Anne-Geneviève Marcelin Vincent Calvez Diane Descamps Charlotte Charpentier Philippe Flandre Patricia Recordon-Pinson Pantxika Bellecave Jean-Michel Pawlotsky Bernard Masquelier the ANRS AC Study Group 《PloS one》2015,10(6)
Background
Maraviroc is an HIV entry inhibitor that alters the conformation of CCR5 and is poorly efficient in patients infected by viruses that use CXCR4 as an entry coreceptor. The goal of this study was to assess the capacity of ultra-deep pyrosequencing (UDPS) and different data analysis approaches to characterize HIV tropism at baseline and predict the therapeutic outcome on maraviroc treatment.Methods
113 patients with detectable HIV-1 RNA on HAART were treated with maraviroc. The virological response was assessed at months 1, 3 and 6. The sequence of the HIV V3 loop was determined at baseline and prediction of maraviroc response by different software and interpretation algorithms was analyzed.Results
UDPS followed by analysis with the Pyrotrop software or geno2pheno algorithm provided better prediction of the response to maraviroc than Sanger sequencing. We also found that the H34Y/S substitution in the V3 loop was the strongest individual predictor of maraviroc response, stronger than substitutions at positions 11 or 25 classically used in interpretation algorithms.Conclusions
UDPS is a powerful tool that can be used with confidence to predict maraviroc response in HIV-1-infected patients. Improvement of the predictive value of interpretation algorithms is possible and our results suggest that adding the H34S/Y substitution would substantially improve the performance of the 11/25/charge rule. 相似文献83.
Denusa M Veríssimo Renata FC Leit?o S?nia D Figueiró Júlio C Góes Vilma Lima Charles O Silveira Gerly AC Brito 《Experimental biology and medicine (Maywood, N.J.)》2015,240(2):175-184
The aim of this study was to evaluate the bone regenerative effect of glutaraldehyde (GA) cross-linking on mineralized polyanionic collagen membranes in critical-sized defects on rat calvarias. Bone calvarial defects were induced in Wistar rats, which were then divided into five groups: a sham group; a control group, which received a commercial membrane; and GA, 25GA, and 75GA groups, which received one of three different polyanionic collagen membranes mineralized by 0, 25, or 75 hydroxyapatite cycles and then cross-linked by GA. Bone formation was evaluated based on digital radiography and computerized tomography. Histological analyses were performed 4 and 12 weeks after the surgical procedure to observe bone formation, membrane resorption, and fibrous tissue surrounding the membranes. Measurement of myeloperoxidase activity, tumor necrosis factor alpha, and interleukin 1beta production was performed 24 h after surgery. The percentage of new bone formation in the GA, 25GA, and 75GA groups was higher compared with the control and sham groups. In the GA and 25 GA groups, the membranes were still in place and were contained in a thick fibrous capsule after 12 weeks. No significant difference was found among the groups regarding myeloperoxidase activity and interleukin 1beta levels, although the GA, 25GA, and 75GA groups presented decreased levels of tumor necrosis factor alpha compared with the control group. These new GA cross-linked membranes accelerated bone healing of the calvarium defects and did not induce inflammation. In addition, unlike the control membrane, the experimental membranes were not absorbed during the analyzed period, so they may offer advantages in large bone defects where prolonged membrane barrier functions are desirable. 相似文献
84.
Hwang WC Lin Y Santelli E Sui J Jaroszewski L Stec B Farzan M Marasco WA Liddington RC 《The Journal of biological chemistry》2006,281(45):34610-34616
Severe acute respiratory syndrome (SARS) is a newly emerged infectious disease that caused pandemic spread in 2003. The etiological agent of SARS is a novel coronavirus (SARS-CoV). The coronaviral surface spike protein S is a type I transmembrane glycoprotein that mediates initial host binding via the cell surface receptor angiotensin-converting enzyme 2 (ACE2), as well as the subsequent membrane fusion events required for cell entry. Here we report the crystal structure of the S1 receptor binding domain (RBD) in complex with a neutralizing antibody, 80R, at 2.3 A resolution, as well as the structure of the uncomplexed S1 RBD at 2.2 A resolution. We show that the 80R-binding epitope on the S1 RBD overlaps very closely with the ACE2-binding site, providing a rationale for the strong binding and broad neutralizing ability of the antibody. We provide a structural basis for the differential effects of certain mutations in the spike protein on 80R versus ACE2 binding, including escape mutants, which should facilitate the design of immunotherapeutics to treat a future SARS outbreak. We further show that the RBD of S1 forms dimers via an extensive interface that is disrupted in receptor- and antibody-bound crystal structures, and we propose a role for the dimer in virus stability and infectivity. 相似文献
85.
Jennie Ursum Wouter H Bos Rob J van de Stadt Ben AC Dijkmans Dirkjan van Schaardenburg 《Arthritis research & therapy》2009,11(3):R75-6
Introduction
The aim of this study was to examine seroconversion and the relationship with age and inflammation of autoantibodies in a large group of patients attending an outpatient rheumatology clinic. 相似文献86.
Hennie G Raterman Alexandre E Voskuyl Ben AC Dijkmans Michael T Nurmohamed 《Arthritis research & therapy》2009,11(5):413-2
With great interest, we read the article by Toms and colleagues [1] in the previous issue of Arthritis Research & Therapy, in which they assessed prevalences of metabolic syndrome (MetS) in rheumatoid arthritis (RA) patients. Moreover, they identified demographic and clinical factors that may be associated with MetS. Toms and colleagues found prevalences of up to 45% of MetS and demonstrated older age and health status (health assessment questionnaire) to be associated with MetS irrespectively of the definition used. Of most interest, an association between methotrexate (MTX) use and decreased presence of MetS was observed in patients more than 60 years of age. The investigators hypothesized that this may be attributed to a drug-specific effect (and not to an anti-inflammatory effect) either by changing levels of adenosine, which is known to interact with glucose and lipid metabolism, or by an indirect effect mediated through concomitant folic acid administration, thereby decreasing homocysteine levels.Recently, we also examined the prevalence of MetS in (a subgroup of) RA patients in the CARRÉ investigation, a prospective cohort study on prevalent and incident cardiovascular disease and its underlying cardiovascular risk factors [2]. The findings of Toms and colleagues stimulated us to perform additional analyses in our total study population (n = 353).The prevalences of MetS were 35% and 25% (Table (Table1)1) according to criteria of National Cholesterol Education Program (NCEP) 2004 and NCEP 2001, respectively. In multivariate backward regression analyses, we found significant associations between body mass index, pulse rate, creatinine levels, hypothyroidism and diabetes mellitus and the presence of MetS independently of the criteria used (Table (Table2).2). However, an independent association between single use of MTX or use of MTX in combination with other disease-modifying antirheumatic drugs, on the one hand, and a decreased prevalence of MetS, on the other hand, could not be demonstrated (even in the subgroup of patients over the age of 60).
Open in a separate windowaMetabolic syndrome (MetS) according to National Cholesterol Education Program (NCEP) 2001; bMetS according to NCEP 2004. Continuous variables are presented as means (± standard deviations) in cases of normal distribution or as medians (interquartile ranges) in cases of non-normal distribution. BMI, body mass index; CRP, C-reactive protein; DAS28, disease activity score using 28 joint counts; DMARD, disease-modifying antirheumatic drug; ESR, erythrocyte sedimentation rate; HCQ, hydroxychloroquine; MTX, methotrexate; RA, rheumatoid arthritis; SSZ, sulfasalazine; TNF, tumour necrosis factor.
Open in a separate windowaIn multivariate analyses, the following variables were used: gender, age, prednisolone only, methotrexate only, sulfasalazine only, hydroxychloroquine only, tumour necrosis factor-blocking agents, combination of disease-modifying antirheumatic drugs, pack-years, smoking, erosions, DAS28 (disease activity score using 28 joint counts), body mass index, pulse rate, creatinine levels, renal clearance, hypothyroidism and diabetes mellitus. CI, confidence interval; OR, odds ratio.Therefore, to get more support for a drug-specific effect, it is of interest to know whether or not in the study of Toms and colleagues the MTX effect was present only in the group of RA patients with single use of MTX or in the group of MTX-treated patients with other antirheumatic drugs. As patients with MetS were significantly older, it would give further information whether age was an independent risk factor for MetS in regression analyses. Moreover, as readers, we are not informed about comorbidities like diabetes and clinical hypothyroidism, which are notorious cardiometabolic risk factors. On the whole, we could not confirm a plausible protective role for the use of MTX and presence of MetS, and hence further investigation is required to explain the discrepancy between our findings and those of Toms and colleagues. 相似文献
Table 1
Characteristics of the study populationMetS presenta | MetS absenta | MetS presentb | MetS absentb | |||
---|---|---|---|---|---|---|
n = 84 | n = 265 | n = 121 | n = 228 | P valuea | P valueb | |
Demographics | ||||||
Age, years | 63.8 (± 8) | 63.1 (± 7) | 64.3 (± 8) | 62.7 (± 7) | 0.46 | 0.045 |
Female, percentage | 76 | 63 | 74 | 62 | 0.022 | 0.028 |
RA-related characteristics | ||||||
DAS28 | 4.2 (± 1.3) | 3.9 (± 1.4) | 4.1 (± 1.3) | 3.8 (± 1.4) | 0.21 | 0.062 |
ESR, mm/hour | 22 (10-35) | 16 (9-30) | 20 (10-34) | 17 (9-31) | 0.059 | 0.33 |
CRP, mg/L | 11 (4-21) | 6 (3-16) | 8 (3-18) | 6 (3-19) | 0.021 | 0.46 |
RA duration, years | 7 (4-10) | 7 (4-10) | 7 (4-10) | 7 (5-10) | 0.83 | 0.19 |
Erosion, percentage | 77 | 83 | 79 | 83 | 0.20 | 0.36 |
Number of DMARDs | 1 (1-2) | 1 (1-1) | 1 (1-2) | 1 (1-1) | 0.26 | 0.43 |
MTX current, percentage | 62 | 60 | 63 | 59 | 0.71 | 0.46 |
MTX only, percentage | 39 | 39 | 41 | 38 | 0.95 | 0.67 |
SSZ only, percentage | 8 | 13 | 9 | 14 | 0.23 | 0.22 |
HCQ only, percentage | 1 | 4 | 3 | 4 | 0.31 | 0.55 |
Combination of DMARDs, percentage | 31 | 25 | 29 | 25 | 0.24 | 0.38 |
TNF-blocking agent, percentage | 11 | 9 | 11 | 9 | 0.73 | 0.65 |
Prednisolone only, percentage | 1 | 2 | 3 | 1 | 1.00 | 0.42 |
Cardiovascular risk factors | ||||||
Current smoker, percentage | 26 | 31 | 25 | 32 | 0.42 | 0.15 |
Pack-years, years | 17 (0-34) | 19 (2-38) | 19 (0-35) | 18 (2-38) | 0.23 | 0.75 |
BMI, kg/m2 | 30 (± 4) | 26 (± 5) | 29 (± 4) | 25 (± 5) | < 0.001 | < 0.001 |
Creatinine, μmol/L | 89 (± 21) | 89 (± 16) | 91 (± 22) | 87 (± 14) | 0.99 | 0.070 |
Renal clearance, mL/minute | 81 (± 24) | 72 (± 19) | 77 (± 23) | 73 (± 19) | 0.003 | 0.062 |
Pulse, beats per minute | 76 (± 11) | 73 (± 9) | 75 (± 11) | 73 (± 9) | 0.005 | 0.015 |
Diabetes mellitus, percentage | 14 | 3 | 12 | 3 | < 0.001 | 0.001 |
Hypothyroidism, percentage | 12 | 2 | 9 | 2 | 0.001 | 0.003 |
Table 2
Variables associated with metabolic syndromeUnivariate | Multivariatea | |||||
---|---|---|---|---|---|---|
OR | 95% CI | P value | OR | 95% CI | P value | |
Body mass index | 1.2 | 1.1-1.3 | < 0.001 | 1.2 | 1.1-1.3 | < 0.001 |
Pulse | 1.03 | 1.01-1.06 | 0.011 | 1.03 | 1.00-1.06 | 0.020 |
Creatinine | 1.01 | 1.00-1.02 | 0.080 | 1.02 | 1.00-1.03 | 0.017 |
Hypothyroidism | 4.5 | 1.5-13.2 | 0.007 | 4.7 | 1.5-15.0 | 0.009 |
Diabetes mellitus | 4.8 | 1.8-12.9 | 0.002 | 4.5 | 1.4-15.2 | 0.014 |
87.
An efficient synthesis from readily available materials of numerous steroids functionalized at C-11 position, interesting from a biological point of view, is described using our general approach. The characteristic (1)H and (13)C NMR spectroscopic features of the synthesized steroids are reported. 相似文献
88.
89.
Background
The fish, Erythrinus erythrinus, shows an interpopulation diversity, with four karyomorphs differing by chromosomal number, chromosomal morphology and heteromorphic sex chromosomes. Karyomorph A has a diploid number of 2n = 54 and does not have differentiated sex chromosomes. Karyomorph D has 2n = 52 chromosomes in females and 2n = 51 in males, and it is most likely derived from karyomorph A by the differentiation of a multiple X1X2Y sex chromosome system. In this study, we analyzed karyomorphs A and D by means of cytogenetic approaches to evaluate their evolutionary relationship. 相似文献90.
Jennie Ursum Wouter H Bos Nancy van Dillen Ben AC Dijkmans Dirkjan van Schaardenburg 《Arthritis research & therapy》2010,12(1):R8