High level expression of human epithelial β-defensins (hBD-1, 2 and 3) in papillomavirus induced lesions

BACKGROUND: Epithelial defensins including human β-defensins (hBDs) and α-defensins (HDs) are antimicrobial peptides that play important roles in the mucosal defense system. However, the role of defensins in papillomavirus induced epithelial lesions is unknown. RESULTS: Papilloma tissues were prospectively collected from 15 patients with recurrent respiratory papillomatosis (RRP) and analyzed for defensins and chemokine IL-8 expression by quantitative, reverse-transcriptase polymerase chain reaction (RT-PCR) assays. HBD-1, -2 and -3 mRNAs were detectable in papilloma samples from all RRP patients and the levels were higher than in normal oral mucosal tissues from healthy individuals. Immunohistochemical analysis showed that both hBD-1 and 2 were localized in the upper epithelial layers of papilloma tissues. Expression of hBD-2 and hBD-3 appeared to be correlated as indicated by scatter plot analysis (r = 0.837, p < 0.01) suggesting that they were co-inducible in papillomavirus induced lesions. Unlike hBDs, only low levels of HD5 and HD6 were detectable in papillomas and in oral mucosa. CONCLUSION: Human β-defensins are upregulated in respiratory papillomas. This novel finding suggests that hBDs might contribute to innate and adaptive immune responses targeted against papillomavirus-induced epithelial lesions

Using Resistant Prey Demonstrates That Bt Plants Producing Cry1Ac, Cry2Ab, and Cry1F Have No Negative Effects on Geocoris punctipes and Orius insidiosus

Geocoris punctipes (Say) and Orius insidiosus (Say) are generalist predators found in a wide range of crops, including cotton (Gossypium hirsutum L.) and maize (Zea mays L.), where they provide important biological control services by feeding on an array of pests, including eggs and small larvae of caterpillars. A high percentage of cotton and maize in the United States and several other countries are transgenic cultivars that produce one or more of the insecticidal Cry proteins of Bacillus thuringiensis Berliner (Bt). Here we quantify effects of three Cry proteins on the life history of these predators over two generations when they are exposed to these Cry proteins indirectly through their prey. To eliminate the confounding prey quality effects that can be introduced by Bt-susceptible prey, we used Cry1Ac/Cry2Ab-resistant Trichoplusia ni (Hübner) and Cry1 F-resistant Spodoptera frugiperda (J.E. Smith) in a series of tri-trophic studies. Survival, development, adult mass, fecundity, and fertility were similar when predators consumed larvae feeding on Cry1Ac/Cry2Ab cotton or Cry1 F maize compared with prey feeding on isogenic or near-isogenic cotton or maize. Repeated exposure of the same initial cohort over a second generation also resulted in no differences in life-history traits when feeding on non-Bt- or Bt-fed prey. Enzyme-linked immunosorbent assay showed that predators were exposed to Bt Cry proteins from their prey and that these proteins became increasingly diluted as they moved up the food chain. Results show a clear lack of effect of three common and widespread Cry proteins on these two important predator species. The use of resistant insects to eliminate prey quality effects provides a robust and meaningful assessment of exposure and hazar

Current–Voltage Characteristics in Individual Polypyrrole Nanotube, Poly(3,4-ethylenedioxythiophene) Nanowire, Polyaniline Nanotube, and CdS Nanorope

In this paper, we focus on current–voltage (I–V) characteristics in several kinds of quasi-one-dimensional (quasi-1D) nanofibers to investigate their electronic transport properties covering a wide temperature range from 300 down to 2 K. Since the complex structures composed of ordered conductive regions in series with disordered barriers in conducting polymer nanotubes/wires and CdS nanowires, all measured nonlinearI–Vcharacteristics show temperature and field-dependent features and are well fitted to the extended fluctuation-induced tunneling and thermal excitation model (Kaiser expression). However, we find that there are surprisingly similar deviations emerged between theI–Vdata and fitting curves at the low bias voltages and low temperatures, which can be possibly ascribed to the electron–electron interaction in such quasi-1D systems with inhomogeneous nanostructures

Quantum Correlation in One-dimensional Extend Quantum Compass Model

We study the correlations in the one-dimensional extended quantum compass model in a transverse magnetic field. By exactly solving the Hamiltonian, we find that the quantum correlation of the ground state of one-dimensional quantum compass model is vanishing. We show that quantum discord can not only locate the quantum critical points, but also discern the orders of phase transitions. Furthermore, entanglement quantified by concurrence is also compared.Comment: 8 pages, 14 figures, to appear in Eur. Phys. J.

Design, synthesis, cytotoxic activity and molecular docking studies of new 20(S)-sulfonylamidine camptothecin derivatives

20(S)-Sulfonylamidine CPT-derivatives were prepared and tested for cytotoxicity.Several analogs showed superior cytotoxic activity compared to irinotecan.Key structural features related to cytotoxicity were identified by SAR analysis.Compounds 9 and 15c interacted with Topo I-DNA by a different binding mode from CPT.These compounds are new generation CPT-derived antitumor agents.In an ongoing investigation of 20-sulfonylamidine derivatives (9, YQL-9a) of camptothecin (1) as potential anticancer agents directly and selectively inhibiting topoisomerase (Topo) I, the sulfonylamidine pharmacophore was held constant, and a camptothecin derivatives with various substitution patterns were synthesized. The new compounds were evaluated for antiproliferative activity against three human tumor cell lines, A-549, KB, and multidrug resistant (MDR) KB subline (KBvin). Several analogs showed comparable or superior antiproliferative activity compared to the clinically prescribed 1 and irinotecan (3). Significantly, the 20-sulfonylamidine derivatives exhibited comparable cytotoxicity against KBvin, while 1 and 3 were less active against this cell line. Among them, compound 15c displayed much better cytotoxic activity than the controls 1, 3, and 9. Novel key structural features related to the antiproliferative activities were identified by structure–activity relationship (SAR) analysis. In a molecular docking model, compounds 9 and 15c interacted with Topo I-DNA through a different binding mode from 1 and 3. The sulfonylamidine side chains of 9 and 15c could likely form direct hydrogen bonds with Topo I, while hydrophobic interaction with Topo I and π–π stacking with double strand DNA were also confirmed as binding driving forces. The results from docking models were consistent with the SAR conclusions. The introduction of bulky substituents at the 20-position contributed to the altered binding mode of the compound by allowing them to form new interactions with Topo I residues. The information obtained in this study will be helpful for the design of new derivatives of 1 with most promising anticancer activity.CPT (green), 9 (magenta), and 15c (blue) in the binding site of DNA-Topo-I

Glutamic acid decarboxylase autoantibodies are dominant but insufficient to identify most Chinese with adult-onset non-insulin requiring autoimmune diabetes: LADA China study 5.

AIMS: Adult-onset autoimmune diabetes is prevalent in China, in contrast to childhood-onset type 1 diabetes mellitus. Islet autoantibodies are the most important immune biomarkers to diagnose autoimmune diabetes. We assayed four different islet autoantibodies in recently diagnosed adult non-insulin-requiring diabetes Chinese subjects to investigate the best antibody assay strategy for the correct diagnosis of these subjects. METHODS: LADA China study is a nation-wide multicenter study conducted in diabetes patients from 46 university-affiliated hospitals in China. Non-insulin-treated newly diagnosed adult diabetes patients (n = 2388) were centrally assayed for glutamic acid decarboxylase autoantibody (GADA), protein tyrosine phosphatase-2 autoantibody (IA-2A), and zinc transporter 8 autoantibody (ZnT8A) by radioligand assay and insulin autoantibody (IAA) by microtiter plate radioimmunoassay. Clinical data were determined locally. RESULTS: Two hundred and six (8.63 %) subjects were autoantibody positive, of which GADA identified 5.78 % (138/2388) of the total, but only 67 % (138/206) of the autoimmune cases. IA-2A, ZnT8A, and IAA were found in 1.51, 1.84, and 1.26 % of the total study subjects, respectively. When assaying three islet autoantibodies, the most effective strategy was the combination of GADA, ZnT8A, and IAA, which could identify 92.2 % (190/206) autoimmune diabetes patients. The clinical data showed that those subjects with positive GADA had lower random C-peptide than autoantibody negative subjects (P < 0.05). CONCLUSIONS: As with Europeans, GADA is the dominant autoantibody in this form of autoimmune diabetes in China, but in contrast to Europeans, screening should include other diabetes-associated autoantibodies

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression

Impact of an Innovative Financing and Payment Model on Tuberculosis Patients’ Financial Burden: is Tuberculosis Care More Affordable for the Poor?

Background: In response to the high financial burden of health services facing tuberculosis (TB) patients in China, the China-Gates TB project, Phase II, has implemented a new financing and payment model as an important component of the overall project in three cities in eastern, central and western China. The model focuses on increasing the reimbursement rate for TB patients and reforming provider payment methods by replacing fee-for-service with a case-based payment approach. This study investigated changes in out-of-pocket (OOP) health expenditure and the financial burden on TB patients before and after the interventions, with a focus on potential differential impacts on patients from different income groups