Orientia tsutsugamushi is the etiological agent of scrub typhus, a mite-borne, febrile illness that occurs in the Asia-Pacific region. We conducted strain characterization of O. tsutsugamushi isolates from chiggers obtained from rodents based the nucleotide sequence of the 56-kDa outer membrane protein gene. With the use of PCR, a total of 68 DNA sequences of 56-kDa antigen genes were amplified. Phylogenetic analysis revealed that there were at least six definable clusters among the 68 isolates: 37% Karp-related strains (25/68), 27% TA763 strains (18/68), 12% JG-related strains (8/68), 19% Kato-related strains (13/68), 4% divergent strains (3/68), and 1% representing a Gilliam prototype strain (1/68). Overall, the O. tsutsugamushi genotypes exhibited a high degree of diversity, similar to that seen in strains from the rest of the areas where scrub typhus is endemic. Moreover, the 56-kDa protein sequence similarity between O. tsutsugamushi isolates from mites and those from human patients (H. Y. Lu et al., Am. J. Trop. Med. Hyg. 83:658-663, 2010) were striking, thus highlighting potential risk factors for this emerging zoonotic disease. 相似文献
Aims Carbon (C) sequestration in terrestrial ecosystems is strongly regulated by nitrogen (N) processes. However, key parameters that determine the degree of N regulation on terrestrial C sequestration have not been well quantified.Methods Here, we used a Bayesian probabilistic inversion approach to estimate 14 target parameters related to ecosystem C and N interactions from 19 datasets obtained from Duke Forests under ambient and elevated carbon dioxide (CO2).Important findings Our results indicated that 8 of the 14 target parameters, such as C:N ratios in most ecosystem compartments, plant N uptake and external N input, were well constrained by available datasets whereas the others, such as N allocation coefficients, N loss and the initial value of mineral N pool were poorly constrained. Our analysis showed that elevated CO2 led to the increases in C:N ratios in foliage, fine roots and litter. Moreover, elevated CO2 stimulated plant N uptake and increased ecosystem N capital in Duke Forests by 25.2 and 8.5%, respectively. In addition, elevated CO2 resulted in the decrease of C exit rates (i.e. increases in C residence times) in foliage, woody biomass, structural litter and passive soil organic matter, but the increase of C exit rate in fine roots. Our results demonstrated that CO2 enrichment substantially altered key parameters in determining terrestrial C and N interactions, which have profound implications for model improvement and predictions of future C sequestration in terrestrial ecosystems in response to global change. 相似文献
Many proteins involved in intracellular signal transduction contain a small, 50-60 amino acid domain, termed the Src homology 3 (SH3) domain. This domain appears to mediate critical protein-protein interactions that are involved in responses to extracellular signals. Previous studies have shown that the SH3 domains from several proteins recognize short, contiguous amino acid sequences that are rich in proline residues. While all SH3 recognition sequences identified to date share a conserved P-X-X-P motif, the sequence recognition specificity of individual SH3 domains is poorly understood. We have employed a novel modification of phage display involving biased libraries to identify peptide ligands of the Src, Fyn, Lyn, PI3K and Abl SH3 domains. With biased libraries, we probed SH3 recognition over a 12 amino acid window. The Src SH3 domain prefers the sequence XXXRPLPPLPXP, Fyn prefers XXXRPLPP(I/L)PXX, Lyn prefers RXXRPLPPLPXP, PI3K prefers RXXRPLPPLPP while the Abl SH3 domain selects phage containing the sequence PPPYPPPP(I/V)PXX. We have also analysed the binding properties of Abl and Src SH3 ligands. We find that although the phage-displayed Abl and Src SH3 ligands are proline rich, they are distinct. In surface plasmon resonance binding assays, these SH3 domains displayed highly selective binding to their cognate ligands when the sequences were displayed on the surface of the phage or as synthetic peptides. The selection of these high affinity SH3 peptide ligands provides valuable information on the recognition motifs of SH3 domains, serve as new tools to interfere with the cellular functions of SH3 domain-mediated processes and form the basis for the design of SH3-specific inhibitors of disease pathways. 相似文献
One of the most common and recurrent vaginal infections is bacterial vaginosis (BV). The diagnosis is based on changes to the “normal” vaginal microbiome; however, the normal microbiome appears to differ according to reproductive status and ethnicity, and even among individuals within these groups. The Amsel criteria and Nugent score test are widely used for diagnosing BV; however, these tests are based on different criteria, and so may indicate distinct changes in the vaginal microbial community. Nevertheless, few studies have compared the results of these test against metagenomics analysis.
Methods
Vaginal flora samples from 77 participants were classified according to the Amsel criteria and Nugent score test. The microbiota composition was analyzed using 16S ribosome RNA gene amplicon sequencing. Bioinformatics analysis and multivariate statistical analysis were used to evaluate the microbial diversity and function.
Results
Only 3 % of the participants diagnosed BV negative using the Amsel criteria (A−) were BV-positive according to the Nugent score test (N+), while over half of the BV-positive patients using the Amsel criteria (A+) were BV-negative according to the Nugent score test (N−). Thirteen genera showed significant differences in distribution among BV status defined by BV tests (e.g., A − N−, A + N− and A + N+). Variations in the four most abundant taxa, Lactobacillus, Gardnerella, Prevotella, and Escherichia, were responsible for most of this dissimilarity. Furthermore, vaginal microbial diversity differed significantly among the three groups classified by the Nugent score test (N−, N+, and intermediate flora), but not between the Amsel criteria groups. Numerous predictive microbial functions, such as bacterial chemotaxis and bacterial invasion of epithelial cells, differed significantly among multiple BV test, but not between the A− and A+ groups.
Conclusions
Metagenomics analysis can greatly expand our current understanding of vaginal microbial diversity in health and disease. Metagenomics profiling may also provide more reliable diagnostic criteria for BV testing.
The current study evaluated the association between tea consumption and head and neck cancer (HNC) in Taiwan, where tea is a major agricultural product and a popular beverage.
Methods
Interviews regarding tea consumption (frequency, duration, and types) were conducted with 396 HNC cases and 413 controls. Unconditional logistic regression was performed to estimate the odds ratio (OR) and 95% confidence interval (CI) of HNC risk associated with tea drinking, adjusted for sex, age, education, cigarette smoking, betel quid chewing, and alcohol drinking.
Results
A reduced HNC risk associated with tea drinking (OR for every cup per day = 0.96, 95% CI: 0.93–0.99; OR for ≧5 cups per day = 0.60, 95% CI: 0.39–0.94) was observed. The association was especially significant for pharyngeal cancer (OR for every cup per day = 0.93, 95% CI: 0.88–0.98; OR for ≧5 cups per day = 0.32, 95% CI: 0.16–0.66). A significant inverse association between HNC and tea consumption was observed particularly for green tea.
Conclusions
This study suggests that tea drinking may reduce the risk of HNC. The anticancer property of tea, if proven, may offer a natural chemopreventive measure to reduce the occurrence of HNC. 相似文献
Several inflammation-based prognostic scoring systems, including Glasgow Prognostic Score (GPS), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) have been reported to predict survival in many malignancies, whereas their role in metastatic nasopharyngeal carcinoma (NPC) remains unclear. The aim of this study is to evaluate the clinical value of these prognostic scoring systems in a cohort of cisplatin-based treated patients with metastatic NPC.
Methods
Two hundred and eleven patients with histologically proven metastatic NPC treated with first-line cisplatin-based chemotherapy were retrospectively evaluated. Demographics, disease-related characteristics and relevant laboratory data before treatment were recorded. GPS, NLR and PLR were calculated as described previously. Response to first-line therapy and survival data were also collected. Survival was analyzed in Cox regressions and stability of the models was examined by bootstrap resampling. The area under the receiver operating characteristics curve (AUC) was calculated to compare the discriminatory ability of each scoring system.
Results
Among the above three inflammation-based prognostic scoring systems, GPS (P<0.001) and NLR (P = 0.019) were independently associated with overall survival, which showed to be stable in a bootstrap resampling study. The GPS consistently showed a higher AUC value at 6-month (0.805), 12-month (0.705), and 24-month (0.705) in comparison with NLR and PLR. Further analysis of the association of GPS with progression-free survival showed GPS was also associated independently with progression-free survival (P<0.001).
Conclusions
Our study demonstrated that the GPS may be of prognostic value in metastatic NPC patients treated with cisplatin-based palliative chemotherapy and facilitate individualized treatment. However a prospective study to validate this prognostic model is still needed. 相似文献
Recent advances in high-throughput (HTP) automated mini-bioreactor systems have significantly improved development timelines for early-stage biologic programs. Automated platforms such as the ambr® 250 have demonstrated the ability, using appropriate scale-down approaches, to provide reliable estimates of process performance and product quality from bench to pilot scale, but data sets comparing to large-scale commercial processes (>10,000 L) are limited. As development moves toward late stages, specifically process characterization (PC), a qualified scale-down model (SDM) of the commercial process is a regulatory requirement as part of Biologics License Application (BLA)-enabling activities. This work demonstrates the qualification of the ambr® 250 as a representative SDM for two monoclonal antibody (mAb) commercial processes at scales >10,000 L. Representative process performance and product quality associated with each mAb were achieved using appropriate scale-down approaches, and special attention was paid to pCO2 to ensure consistent performance and product quality. Principal component analysis (PCA) and univariate equivalence testing were utilized in the qualification of the SDM, along with a statistical evaluation of process performance and product-quality attributes for comparability. The ambr® 250 can predict these two commercial-scale processes (at center-point condition) for cell-culture performance and product quality. The time savings and resource advantages to performing PC studies in a small-scale HTP system improves the potential for the biopharmaceutical industry to get products to patients more quickly. 相似文献