Thifluzamide is a SDHI (succinate dehydrogenase inhibitor) fungicide, which interferes with succinate ubiquinone reductase in the mitochondrial electron transport chain of fungi. Presently, ...jinggangmycin is the major fungicide extensively used for the control of rice sheath blight caused by Rhizoctonia solani and resistance to jinggangmycin was first reported to occur in China. A total of 128 isolates of R. solani from Anhui Province of China were characterised for the baseline sensitivity to thifluzamide. The isolates were very sensitive to thifluzamide and the baseline sensitivity curve was unimodal with an average EC50 value of 0.058 ± 0.012 µg mL−1. However, EC50 values of boscalid (another SDHI fungicide) for inhibition of mycelial growth of 22 arbitrarily selected R. solani isolates ranged from 1.89 to 2.68 µg mL−1. Thifluzamide applied at 110 µg mL−1 exhibited excellent protective and curative activity against rice sheath blight and provided 81.1–91.0% protective or curative control efficacy. In field trials in 2010 and 2011, control efficacies of thifluzamide at 82 g.a.i ha−1 15 and 30 days after second application were 84.2% and 86.7%, respectively, suggesting excellent activity against sheath blight. There was a statistically significant difference in the efficacy between thifluzamide and boscalid or jinggangmycin. These results suggested that thifluzamide should be a good alternative fungicide to jinggangmycin for the control of rice sheath blight.
Wearable and skin electronics benefit from mechanically soft and stretchable materials to conform to curved and dynamic surfaces, thereby enabling seamless integration with the human body. However, ...such materials are challenging to process using traditional microelectronics techniques. Here, stretchable transistor arrays are patterned exclusively from solution by inkjet printing of polymers and carbon nanotubes. The additive, non-contact and maskless nature of inkjet printing provides a simple, inexpensive and scalable route for stacking and patterning these chemically-sensitive materials over large areas. The transistors, which are stable at ambient conditions, display mobilities as high as 30 cm
V
s
and currents per channel width of 0.2 mA cm
at operation voltages as low as 1 V, owing to the ionic character of their printed gate dielectric. Furthermore, these transistors with double-layer capacitive dielectric can mimic the synaptic behavior of neurons, making them interesting for conformal brain-machine interfaces and other wearable bioelectronics.
Currently there is great interest in detecting associations between complex traits and rare variants. In this report, we describe Variant Association Tools (VAT) and the VAT pipeline, which ...implements best practices for rare-variant association studies. Highlights of VAT include variant-site and call-level quality control (QC), summary statistics, phenotype- and genotype-based sample selection, variant annotation, selection of variants for association analysis, and a collection of rare-variant association methods for analyzing qualitative and quantitative traits. The association testing framework for VAT is regression based, which readily allows for flexible construction of association models with multiple covariates and weighting themes based on allele frequencies or predicted functionality. Additionally, pathway analyses, conditional analyses, and analyses of gene-gene and gene-environment interactions can be performed. VAT is capable of rapidly scanning through data by using multi-process computation, adaptive permutation, and simultaneously conducting association analysis via multiple methods. Results are available in text or graphic file formats and additionally can be output to relational databases for further annotation and filtering. An interface to R language also facilitates user implementation of novel association methods. The VAT's data QC and association-analysis pipeline can be applied to sequence, imputed, and genotyping array, e.g., “exome chip,” data, providing a reliable and reproducible computational environment in which to analyze small- to large-scale studies with data from the latest genotyping and sequencing technologies. Application of the VAT pipeline is demonstrated through analysis of data from the 1000 Genomes project.
Exciton-polaritons are hybrid light-matter quasiparticles formed by strongly interacting photons and excitons (electron-hole pairs) in semiconductor microcavities. They have emerged as a robust ...solid-state platform for next-generation optoelectronic applications as well as for fundamental studies of quantum many-body physics. Importantly, exciton-polaritons are a profoundly open (that is, non-Hermitian) quantum system, which requires constant pumping of energy and continuously decays, releasing coherent radiation. Thus, the exciton-polaritons always exist in a balanced potential landscape of gain and loss. However, the inherent non-Hermitian nature of this potential has so far been largely ignored in exciton-polariton physics. Here we demonstrate that non-Hermiticity dramatically modifies the structure of modes and spectral degeneracies in exciton-polariton systems, and, therefore, will affect their quantum transport, localization and dynamical properties. Using a spatially structured optical pump, we create a chaotic exciton-polariton billiard--a two-dimensional area enclosed by a curved potential barrier. Eigenmodes of this billiard exhibit multiple non-Hermitian spectral degeneracies, known as exceptional points. Such points can cause remarkable wave phenomena, such as unidirectional transport, anomalous lasing/absorption and chiral modes. By varying parameters of the billiard, we observe crossing and anti-crossing of energy levels and reveal the non-trivial topological modal structure exclusive to non-Hermitian systems. We also observe mode switching and a topological Berry phase for a parameter loop encircling the exceptional point. Our findings pave the way to studies of non-Hermitian quantum dynamics of exciton-polaritons, which may uncover novel operating principles for polariton-based devices.
Summary
Background
Vitiligo is an autoimmune chronic depigmentation disorder caused by melanocyte loss. Previous studies found that CD4+CD25+ regulatory T‐cell (Treg) dysfunction was involved in the ...pathogenesis of vitiligo and that gene polymorphisms in forkhead box P3 (FOXP3) – a master regulator of Treg development and function – were associated with susceptibility to some autoimmune disorders. Therefore, we hypothesized that functional polymorphisms of the FOXP3 gene might be associated with vitiligo via dysregulation of Treg cells.
Objectives
To evaluate whether FOXP3 polymorphisms are associated with vitiligo risk.
Material and methods
In this hospital‐based case–control study of 682 patients with vitiligo and 682 vitiligo‐free age‐ and sex‐matched controls, we genotyped three single nucleotide polymorphisms (SNPs) of the FOXP3 gene – rs2232365, rs3761548 and rs5902434 – by performing polymerase chain reaction with sequence‐specific primers (PCR‐SSP).
Results
Significantly increased vitiligo risk was associated with the rs2232365 GG odds ratio (OR) 1·68, 95% confidence interval (CI) 1·17–2·39, P = 0·004 and rs3761548 AA (OR 1·82, 95% CI 1·10–3·01, P = 0·033) genotypes compared with the rs2232365 AA and rs3761548 CC genotypes. On combined analysis of these three variant alleles, we found that individuals carrying 2–6 variant alleles had significantly increased vitiligo risk (OR 1·34, 95% CI 1·08–1·66). This risk was more pronounced in the following subgroups: age > 20 years, male sex, active vitiligo, nonsegmental vitiligo and other accompanying autoimmune diseases.
Conclusions
FOXP3 gene polymorphisms contributed to vitiligo risk in a Han Chinese population.
What's already known about this topic?
Previous findings have suggested that forkhead box P3 (FOXP3) is a master regulator of regulatory T cells (Tregs) for maintaining immune tolerance and abrogating autoimmune diseases.
Dysfunction of Tregs is involved in the autoimmune mechanism of vitiligo.
FOXP3 polymorphisms negatively affect the expression and functions of FOXP3 as well as of its target genes.
What does this study add?
Our study suggests an association between FOXP3 gene polymorphisms and vitiligo susceptibility.
ABSTRACT
The merger of two or more galaxies can enhance the inflow of material from galactic scales into the close environments of active galactic nuclei (AGNs), obscuring and feeding the ...supermassive black hole (SMBH). Both recent simulations and observations of AGN in mergers have confirmed that mergers are related to strong nuclear obscuration. However, it is still unclear how AGN obscuration evolves in the last phases of the merger process. We study a sample of 60 luminous and ultra-luminous IR galaxies (U/LIRGs) from the GOALS sample observed by NuSTAR. We find that the fraction of AGNs that are Compton thick (CT; $N_{\rm H}\ge 10^{24}\rm \, cm^{-2}$) peaks at $74_{-19}^{+14}{{\ \rm per\ cent}}$ at a late merger stage, prior to coalescence, when the nuclei have projected separations (dsep) of 0.4–6 kpc. A similar peak is also observed in the median NH $(1.6\pm 0.5)\times 10^{24}\rm \, cm^{-2}$. The vast majority ($85^{+7}_{-9}{{\ \rm per\ cent}}$) of the AGNs in the final merger stages (dsep ≲ 10 kpc) are heavily obscured ($N_{\rm H}\ge 10^{23}\rm \, cm^{-2}$), and the median NH of the accreting SMBHs in our sample is systematically higher than that of local hard X-ray-selected AGN, regardless of the merger stage. This implies that these objects have very obscured nuclear environments, with the $N_{\rm H}\ge 10^{23}\rm \, cm^{-2}$ gas almost completely covering the AGN in late mergers. CT AGNs tend to have systematically higher absorption-corrected X-ray luminosities than less obscured sources. This could either be due to an evolutionary effect, with more obscured sources accreting more rapidly because they have more gas available in their surroundings, or to a selection bias. The latter scenario would imply that we are still missing a large fraction of heavily obscured, lower luminosity ($L_{2-10}\lesssim 10^{43}\rm \, erg\, s^{-1}$) AGNs in U/LIRGs.
Retinoblastoma (Rb) is the most common primary intraocular tumor in children. Local treatment of the intraocular disease is usually effective if diagnosed early; however advanced Rb can metastasize ...through routes that involve invasion of the choroid, sclera and optic nerve or more broadly via the ocular vasculature. Metastatic Rb patients have very high mortality rates. While current therapy for Rb is directed toward blocking tumor cell division and tumor growth, there are no specific treatments targeted to block Rb metastasis. Two such targets are matrix metalloproteinases-2 and -9 (MMP-2, -9), which degrade extracellular matrix as a prerequisite for cellular invasion and have been shown to be involved in other types of cancer metastasis. Cancer Clinical Trials with an anti-MMP-9 therapeutic antibody were recently initiated, prompting us to investigate the role of MMP-2, -9 in Rb metastasis.
We compare MMP-2, -9 activity in two well-studied Rb cell lines: Y79, which exhibits high metastatic potential and Weri-1, which has low metastatic potential. The effects of inhibitors of MMP-2 (ARP100) and MMP-9 (AG-L-66085) on migration, angiogenesis, and production of immunomodulatory cytokines were determined in both cell lines using qPCR, and ELISA. Cellular migration and potential for invasion were evaluated by the classic wound-healing assay and a Boyden Chamber assay.
Our results showed that both inhibitors had differential effects on the two cell lines, significantly reducing migration in the metastatic Y79 cell line and greatly affecting the viability of Weri-1 cells. The MMP-9 inhibitor (MMP9I) AG-L-66085, diminished the Y79 angiogenic response. In Weri-1 cells, VEGF was significantly reduced and cell viability was decreased by both MMP-2 and MMP-9 inhibitors. Furthermore, inhibition of MMP-2 significantly reduced secretion of TGF-β1 in both Rb models.
Collectively, our data indicates MMP-2 and MMP-9 drive metastatic pathways, including migration, viability and secretion of angiogenic factors in Rb cells. These two subtypes of matrix metalloproteinases represent new potential candidates for targeted anti-metastatic therapy for Rb.
Quartz veins in high‐pressure to ultrahigh‐pressure metamorphic rocks witness channelized fluid flow that transports both mass and heat during collisional orogenesis. This flow can occur in the ...direction of changing temperature/pressure during subduction or exhumation. SHRIMP U‐Pb dating of zircon from a kyanite‐quartz vein within ultrahigh‐pressure eclogite in the Dabie continental collision orogen yields two age groups at 212 ± 7 and 181 ± 13 Ma, which are similar to two groups of LA‐ICPMS age at 210 ± 4 and 180 ± 5 Ma for the same sample. These ages are significantly younger than zircon U‐Pb ages of 224 ± 2 Ma from the host eclogite. Thus the two age groups from the vein date two episodes of fluid flow involving zircon growth: the first due to decompression dehydration during exhumation, and the second due to heating dehydration in response to a cryptic thermal event after continental collision. Laser fluorination O‐isotope analyses gave similar δ18O values for minerals from both vein and eclogite, indicating that the vein‐forming fluid was internally derived. Synchronous cooling between the vein and eclogite is suggested by almost the same quartz–mineral fractionation values, with regularly decreasing temperatures that are in concordance with rates of O diffusion in the minerals. While the quartz veining was caused by decompression dehydration at 700–650 °C in a transition from ultrahigh‐pressure to high‐pressure eclogite‐facies retrogression, the postcollisional fluid flow was retriggered by heating dehydration at ∼500 °C without corresponding metamorphism. In either case, the kyanite–quartz vein formed later than the peak ultrahigh‐pressure metamorphic event at the Middle Triassic, pointing to focused fluid flow during exhumation rather than subduction. The growth of metamorphic zircon in the eclogite appears to have depended on fluid availability, so that their occurrence is a type of geohygrometer besides geochronological applicability to dating of metamorphic events in orogenic cycles.
Oxidative stress has a critical role in the pathogenesis of vitiligo. However, the specific molecular mechanism involved in oxidative stress-induced melanocyte death is not well characterized. Given ...the powerful role of microRNAs (miRNAs) in the regulation of cell survival as well as the fact that the generation of miRNAs can be affected by oxidative stress, we hypothesized that miRNAs may participate in vitiligo pathogenesis by modulating the expression of vital genes in melanocytes. In the present study, we initially found that miR-25 was increased in both serum and lesion samples from vitiligo patients, and its serum level was correlated with the activity of vitiligo. Moreover, restoration of miR-25 promoted the H2O2-induced melanocyte destruction and led to the dysfunction of melanocytes. Further experiments proved that MITF, a master regulator in melanocyte survival and function, accounted for the miR-25-caused damaging impact on melanocytes. Notably, other than the direct role on melanocytes, we observed that miR-25 inhibited the production and secretion of SCF and bFGF from keratinocytes, thus impairing their paracrine protective effect on the survival of melanocytes under oxidative stress. At last, we verified that oxidative stress could induce the overexpression of miR-25 in both melanocytes and keratinocytes possibly by demethylating the promoter region of miR-25. Taken together, our study demonstrates that oxidative stress-induced overexpression of miR-25 in vitiligo has a crucial role in promoting the degeneration of melanocytes by not only suppressing MITF in melanocytes but also impairing the paracrine protective effect of keratinocytes. Therefore, it is worthy to investigate the possibility of miR-25 as a potential drug target for anti-oxidative therapy in vitiligo.
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