Performance of a Whole-Blood Interferon-Gamma Release Assay with Mycobacterium RD1-Specific Antigens among HIV-Infected Persons

Objective. To evaluate the usefulness of one of IGRAs, QuantiFERON-TB Gold (QFT-G), in human immunodeficiency virus- (HIV- ) infected patients with various CD4+ T cell counts. Methods. The QFT-G assay was performed using QFT-G kits among 107 HIV-infected patients including 9 cases with active tuberculosis (TB). Results. In HIV-infected patients with CD4+ > 50/μL, QFT-G positive rate for active TB patients was 5/6 (sensitivity = 83%), and that for those without active disease was 1/69 (specificity = 99%). The frequency of indeterminate QFT-G test was significantly higher in those with CD4+ less than 50/μL (P < .0001). At the same time there was a proportional relationship between CD4+ and interferon-gamma response to mitogen (positive control) in QFT-G test (P = .0001). Conclusions. Our data suggested that QFT-G had high sensitivity and specificity in HIV-infected populations with CD4+ greater than 50/μL. However, QFT-G did not perform well in HIV-positive patients with CD4+ less than 50/μL

The genotype-dependent phenotypic landscape of quinoa in salt tolerance and key growth traits

スーパー作物キヌアの多様性を解明 --高い環境適応性と優れた栄養特性をもつキヌアの品種改良に期待--. 京都大学プレスリリース. 2020-10-15.Cultivation of quinoa (Chenopodium quinoa), an annual pseudocereal crop that originated in the Andes, is spreading globally. Because quinoa is highly nutritious and resistant to multiple abiotic stresses, it is emerging as a valuable crop to provide food and nutrition security worldwide. However, molecular analyses have been hindered by the genetic heterogeneity resulting from partial outcrossing. In this study, we generated 136 inbred quinoa lines as a basis for the molecular identification and characterization of gene functions in quinoa through genotyping and phenotyping. Following genotyping-by-sequencing analysis of the inbred lines, we selected 5, 753 single-nucleotide polymorphisms (SNPs) in the quinoa genome. Based on these SNPs, we show that our quinoa inbred lines fall into three genetic sub-populations. Moreover, we measured phenotypes, such as salt tolerance and key growth traits in the inbred quinoa lines and generated a heatmap that provides a succinct overview of the genotype–phenotype relationship between inbred quinoa lines. We also demonstrate that, in contrast to northern highland lines, most lowland and southern highland lines can germinate even under high salinity conditions. These findings provide a basis for the molecular elucidation and genetic improvement of quinoa and improve our understanding of the evolutionary process underlying quinoa domestication

Histomorphometric analysis of minimodeling in the vertebrae in postmenopausal patients treated with anti-osteoporotic agents

AbstractMinimodeling is a type of focal bone formation that is characterized by the lack of precedent bone erosion by osteoclasts. Although this form of bone formation has been described for more than a decade, how anti-osteoporotic agents that are currently used in clinical practice affect the kinetics of minimodeling is not fully understood. We performed a bone morphometric analysis using human vertebral specimens collected from postmenopausal patients who underwent spinal surgery. Patients were divided into three groups according to osteoporosis medication; non-treated, Eldecalcitol (ELD, a vitamin D derivative that has recently been approved to treat patients with osteoporosis in Japan)-treated, and bisphosphonate-treated groups. Five to six patients were enrolled in each group. There was a trend toward enhanced minimodeling in ELD-treated patients and suppressed of it in bisphosphonate-treated patients compared with untreated patients. The differences of minimodeling activity between ELD-treated and bisphosphonate-treated patients were statistically significant. The present study suggests that ELD and bisphosphonates have opposite effects on minimodeling from one another, and show that minimodeling also takes place in vertebrae as has been described for the ilium and femoral head in humans

Inhibition of Hepatitis C Virus Replication and Viral Helicase by Ethyl Acetate Extract of the Marine Feather Star Alloeocomatella polycladia

Hepatitis C virus (HCV) is a causative agent of acute and chronic hepatitis, leading to the development of hepatic cirrhosis and hepatocellular carcinoma. We prepared extracts from 61 marine organisms and screened them by an in vitro fluorescence assay targeting the viral helicase (NS3), which plays an important role in HCV replication, to identify effective candidates for anti-HCV agents. An ethyl acetate-soluble fraction of the feather star Alloeocomatella polycladia exhibited the strongest inhibition of NS3 helicase activity, with an IC50 of 11.7 µg/mL. The extract of A. polycladia inhibited interaction between NS3 and RNA but not ATPase of NS3. Furthermore, the replication of the replicons derived from three HCV strains of genotype 1b in cultured cells was suppressed by the extract with an EC50 value of 23 to 44 µg/mL, which is similar to the IC50 value of the NS3 helicase assay. The extract did not induce interferon or inhibit cell growth. These results suggest that the unknown compound(s) included in A. polycladia can inhibit HCV replication by suppressing the helicase activity of HCV NS3. This study may present a new approach toward the development of a novel therapy for chronic hepatitis C

Hot carrier generation in two-dimensional silver nanoparticle arrays at different excitation wavelengths under on-resonant conditions

We evaluated the hot carrier generation in two-dimensional (2D) silver nanoparticle (AgNP) arrays under light illumination at different wavelengths, 458, 532, 671, and 785 nm. The 2D AgNP arrays were tailored to match the plasmon resonance to each excitation wavelength in order to fulfill the on-resonant condition. We selected para-aminothiophenol (p-ATP) as a probe molecule, which is chemically transformed into 4,4'-dimercaptoazobenzene (DMAB) upon light illumination. The reaction is driven by hot carriers emitted from a plasmonic surface. For evaluation of hot carrier generation, we monitored the chemical transformation from p-ATP into DMAB with surface-enhanced Raman scattering. The normalized Raman intensity of DMAB was plotted against the total exposure, where the peak intensity increased as the total exposure increased because of the increase of the number of DMAB molecules. The saturation of the peak growth was observed, indicating that the chemical transformation was completed, at different exposures for each wavelength. The total exposure required for completing the chemical transformation was smaller at 458 nm by at least ~105 times than that at 785 nm, although the difference of the photon energy was only 1.7 times. The growth of the Raman peak was related to the laser intensity as well, where the higher laser intensity showed a more rapid growth. These results indicated that more hot carriers with sufficient energy for the chemical transformation were generated at shorter excitation wavelengths as well as at higher laser intensities

Customized chemotherapy based on epidermal growth factor receptormutation status for elderly patients with advanced non-small-cell lung cancer: a phase II trial

BACKGROUND: Elderly patients are more vulnerable to toxicity from chemotherapy. Activating epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC) are associated with enhanced response to EGFR tyrosine-kinase inhibitors. We studied patients with advanced NSCLC for whom treatment was customized based on EGFR mutation status. METHODS: We screened 57 chemotherapy-naïve patients with histologically or cytologically confirmed NSCLC, stage IIIB or IV, aged 70 years or older, and with an Eastern Cooperative Oncology Group performance status 0 or 1, for EGFR exon 19 codon 746–750 deletion and exon 21 L858R mutation. Twenty-two patients with EGFR mutations received gefitinib; 32 patients without mutations received vinorelbine or gemcitabine. The primary endpoint was the response rate. RESULTS: The response rate was 45.5% (95% confidence interval [CI]: 24.4%, 67.8%) in patients with EGFR mutations and 18.8% (95% CI: 7.2%, 36.4%) in patients without EGFR mutations. The median overall survival was 27.9 months (95%CI: 24.4 months, undeterminable months) in patients with EGFR mutations and 14.9 months (95%CI: 11.0 months, 22.4 months) in patients without EGFR mutations. In the gefitinib group, grade 3/4 hepatic dysfunction and dermatitis occurred in 23% and 5% of patients, respectively. In patients treated with vinorelbine or gemcitabine, the most common grade 3 or 4 adverse events were neutropenia (47%; four had febrile neutropenia), anemia (13%), and anorexia (9%). No treatment-related deaths occurred. CONCLUSIONS: Treatment customization based on EGFR mutation status deserves consideration, particularly for elderly patients who often cannot receive second-line chemotherapy due to poor organ function or comorbidities. TRIAL REGISTRATION: This trial is registered at University hospital Medical Information Network-clinical trial registration (http://www.umin.ac.jp/ctr/index/htm) with the registration identification number C000000436

IL-17F Induces CCL20 in Bronchial Epithelial Cells

IL-17F plays a crucial role in airway inflammatory diseases including asthma, but its function has not been fully elucidated. CCL20 is also involved in allergic airway inflammation, while its regulatory mechanisms remain to be defined. To further identify a novel role of IL-17F, the expression of CCL20 by IL-17F in bronchial epithelial cells and the signaling mechanisms involved were investigated. Bronchial epithelial cells were stimulated with IL-17F, and the levels of CCL20 gene and protein measured, with the effects of the addition of various kinase inhibitors and siRNAs also investigated. IL-17F significantly induced the expression of CCL20 gene and protein. Pretreatment with inhibitors for MEK1/2, Raf1 and MSK1, and overexpression of a Raf1 dominant-negative mutant significantly diminished IL-17F-induced CCL20 production. Moreover, transfection of the siRNAs targeting MSK1, p90RSK, and CREB blocked CCL20 expression. These findings suggest that IL-17F is able to induce CCL20 via Raf1-MEK1/2-ERK1/2-MSK1/p90RSK-CREB signaling pathway in bronchial epithelial cells. The IL-17F/CCL20 axis may be a novel pharmacological target for asthma