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521.
BackgroundPsoriasis is a chronic skin disorder manifested by recurrent episodes of scaly, red, itchy skin patches that occur within apparently normal skin.ObjectivesThis study was performed to detect the expression of serum and tissue (lesion and non-lesion) LncRNA MALAT-1 and MiRNA-9 that might be used as biomarkers for psoriasis.MethodsBlood samples were obtained from 60 psoriasis patients and 40 controls, as well as 4 mm punch biopsy from lesional and non lesional skin of psoriatic patient and normal skin of healthy controls. Expression of LncRNA MALAT-1 and miRNNA-9 in serum and tissues was detected by real time qRT-PCR.Resultsa statistically significant increase in the expression of MALAT-1 in lesional and non-lesional skin and serum of psoriatic patients in comparison to controls were detected. Moreover, there was statistically significant increase in serum MiRNA-9 in patients in comparison to controls, while its tissue level was significantly lower in patients.ConclusionThis study highlights the dysregulation of LncRNA MALAT-1 and miRNA-9 in psoriasis. Elevated expression of MALAT-1 in lesional skin of psoriatic patients compared to non-lesional skin may possibly contribute to the development of psoriatic plaques.  相似文献   
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523.
The gram-negative bacterium Coxiella burnetii is the causative agent of Query (Q) fever in humans and coxiellosis in livestock. Host genetics are associated with C. burnetii pathogenesis both in humans and animals; however, it remains unknown if specific genes are associated with severity of infection. We employed the Drosophila Genetics Reference Panel to perform a genome-wide association study to identify host genetic variants that affect host survival to C. burnetii infection. The genome-wide association study identified 64 unique variants (P < 10−5) associated with 25 candidate genes. We examined the role each candidate gene contributes to host survival during C. burnetii infection using flies carrying a null mutation or RNAi knockdown of each candidate. We validated 15 of the 25 candidate genes using at least one method. This is the first report establishing involvement of many of these genes or their homologs with C. burnetii susceptibility in any system. Among the validated genes, FER and tara play roles in the JAK/STAT, JNK, and decapentaplegic/TGF-β signaling pathways which are components of known innate immune responses to C. burnetii infection. CG42673 and DIP-ε play roles in bacterial infection and synaptic signaling but have no previous association with C. burnetii pathogenesis. Furthermore, since the mammalian ortholog of CG13404 (PLGRKT) is an important regulator of macrophage function, CG13404 could play a role in host susceptibility to C. burnetii through hemocyte regulation. These insights provide a foundation for further investigation regarding the genetics of C. burnetii susceptibility across a wide variety of hosts.  相似文献   
524.

Introduction

This study aimed to investigate rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) status and levels as predictors of mortality in two large cohorts of patients with early inflammatory arthritis (EIA).

Methods

Data from the Norfolk Arthritis Register (NOAR) and Leiden Early Arthritis Clinic (EAC) cohorts were used. At baseline, patients had demographic data and smoking status recorded; RF, ACPA and inflammatory markers were measured in the local laboratories. Patients were flagged with national death registers until death or censor date. Antibody status was stratified as negative, low or high positive by RF and ACPA levels individually. In addition, patients were grouped as seronegative, RF positive, ACPA positive or double antibody (RF and ACPA) positive. Cox regression models explored associations between antibody status and mortality adjusting for age, sex, smoking status, inflammatory markers and year of enrolment.

Results

A total of 4962 patients were included, 64% were female. Median age at onset was 56 (NOAR) and 54 (EAC) years. In NOAR and EAC respectively, 35% and 42% of patients were ACPA/RF positive. When antibody status was stratified as negative, low or high positive, there were no consistent findings between the two cohorts. Double antibody positivity was associated with excess mortality in both cohorts compared to seronegative patients: NOAR and EAC respective adjusted HR (95% confidence interval) 1.35 (1.09 to 1.68) and 1.58 (1.16 to 2.15).

Conclusions

Patients with EIA who are seropositive for both RF and ACPA have increased mortality compared to those who are single positive or seronegative. Antibody level in seropositive patients was not consistently associated with excess mortality.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-014-0483-3) contains supplementary material, which is available to authorized users.  相似文献   
525.
Many epidemiologic studies of environmental exposures and disease susceptibility measure DNA methylation in white blood cells (WBC). Some studies are also starting to use saliva DNA as it is usually more readily available in large epidemiologic studies. However, little is known about the correlation of methylation between WBC and saliva DNA. We examined DNA methylation in three repetitive elements, Sat2, Alu, and LINE-1, and in four CpG sites, including AHRR (cg23576855, cg05575921), cg05951221 at 2q37.1, and cg11924019 at CYP1A1, in 57 girls aged 6–15 years with blood and saliva collected on the same day. We measured all DNA methylation markers by bisulfite-pyrosequencing, except for Sat2 and Alu, which were measured by the MethyLight assay. Methylation levels measured in saliva DNA were lower than those in WBC DNA, with differences ranging from 2.8% for Alu to 14.1% for cg05575921. Methylation levels for the three repetitive elements measured in saliva DNA were all positively correlated with those in WBC DNA. However, there was a wide range in the Spearman correlations, with the smallest correlation found for Alu (0.24) and the strongest correlation found for LINE-1 (0.73). Spearman correlations for cg05575921, cg05951221, and cg11924019 were 0.33, 0.42, and 0.79, respectively. If these findings are replicated in larger studies, they suggest that, for selected methylation markers (e.g., LINE-1), methylation levels may be highly correlated between blood and saliva, while for others methylation markers, the levels may be more tissue specific. Thus, in studies that differ by DNA source, each interrogated site should be separately examined in order to evaluate the correlation in DNA methylation levels across DNA sources.  相似文献   
526.
527.
We use U2OS cells as in vivo “test tubes” to study how the same cytoplasmic environment has opposite effects on the stability of two different proteins. Protein folding stability and kinetics were compared by fast relaxation imaging, which combines a temperature jump with fluorescence microscopy of FRET (Förster resonance energy transfer)-labeled proteins. While the stability of the cytoplasmic enzyme PGK (phosphoglycerate kinase) increases in cells, the stability of the cell surface antigen VlsE, which presumably did not evolve for stability inside cells, decreases. VlsE folding also slows down more than PGK folding in cells, relative to their respective aqueous buffer kinetics. Our FRET measurements provide evidence that VlsE is more compact inside cells than in aqueous buffer. Two kinetically distinct protein populations exist inside cells, making a connection with previous in vitro crowding studies. In addition, we confirm previous studies showing that VlsE is stabilized by 150 mg/mL of the carbohydrate crowder Ficoll, even though it is destabilized in the cytoplasm relative to aqueous buffer. We propose two mechanisms for the observed destabilization of VlsE in U2OS cells: long-range interactions competing with crowding or shape-dependent crowding favoring more compact states inside the cell over the elongated aqueous buffer native state.  相似文献   
528.
With regard to rheumatoid arthritis, remission as currently used in the literature can have two meanings: either a state with persistent absence of clinical and radiological signs of disease activity without being treated for a specific time period, or it may point to a disease state with minimal disease activity during antirheumatic treatment. A risk factor for the first is absence of autoantibodies, with the anti-CCP-antibodies as best predictors, whereas risk factors for achieving a drug-induced state of minimal disease activity are not well defined. These definitions of remission refer to different disease states; therefore, we propose that the term remission is reserved for patients that are not treated with antirheumatic drugs.  相似文献   
529.
Microtubules are protein filaments that are emerging as potential building blocks in manufacturing nanoscale structures and systems such as interconnecting nanowires. Future development in using microtubules necessitates a control of their nucleation and growth. We report the controlled nucleation and growth of microtubules from functionalized gold on a hydrophilic oxidized silicon wafer. The gold substrate is functionalized with gamma-tubulin, a natural nucleating agent for microtubule growth. We show that the attached gamma-tubulin retains its biological functionality and leads to nucleation and assembly of microtubules from the functionalized gold surface. We also analyze the interplay between the geometry of the nucleating substrates and the morphology of microtubules arrays and networks grown from them. We consider two geometrical arrangements of the substrates: (a) a square lattice of small gold pads on a hydrophilic oxidized silicon wafer and (b) a large flat surface. Fluorescence microscopy and scanning electron microscopy are employed to provide a detailed characterization of the length and morphology of the nucleated and grown microtubules. The observed microtubule morphologies are modeled, analyzed and discussed within the context of reaction-diffusion and nucleation controlled processes.  相似文献   
530.
A series of aminoparthenolide analogs (637) were synthesized and evaluated for their anti-leukemic activity. Eight compounds exhibited good anti-leukemic activity with LD50’s in the low μM range (1.5–3.0 μM). Compounds 16, 24 and 30 were the most potent compounds in the series, causing greater than 90% cell death at 10 μM concentration against primary AML cells in culture, with LD50 values of 1.7, 1.8 and 1.6 μM.  相似文献   
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