Subnormal Cytokine Profile in the Tear Fluid of Keratoconus Patients

Keratoconus, historically viewed as a non-inflammatory disease, is an ectatic corneal disorder associated with progressive thinning of the corneal stroma. Recently, a few inflammatory mediators have been reported to be elevated in the tear fluid of keratoconus patients. Consequently, we investigated a wide range of inflammation regulating cytokines in the tears and sera of keratoconus and control subjects. Interleukin (IL)-1β, IL-4, IL-6, IL-10, IL-12, IL-13, IL-17, interferon (IFN)-γ, chemokine C-C motif ligand 5 (CCL5) and tumor necrosis factor (TNF)-α were tested in tear samples and sera of keratoconus and control individuals by multiplex immuno-bead assays. Selected cytokines were further tested by standard ELISA on pooled tear samples. All cytokines in the sera were generally low, with no significant changes between keratoconus and control subjects. However, in tear fluids, clear differences were detected between the two groups. These differences include increased IL-6, and decreased IL-12, TNF-α, IFN-γ, IL-4, IL-13 and CCL5 in keratoconus compared to control tear fluids. The decreases in IL-12, TNF-α and CCL5 were statistically significant, while the IL-13 decrease was statistically significant in the severe keratoconus group only. IL-17 could not be detected by multiplex immuno-bead assay, but showed an increase in keratoconus by conventional ELISA on a limited number of pooled tear samples. Our findings confirm increased IL-6, but dispute earlier reports of increased TNF-α, and suggest a cytokine imbalance in keratoconus disrupting corneal homeostasis. Moreover, an increase in IL-17 suggests tissue degenerative processes at work, contributing to the thinning and weakening of the corneal connective tissue in keratoconus

TCP and MADS-Box Transcription Factor Networks Regulate Heteromorphic Flower Type Identity in Gerbera hybrida

The large sunflower family, Asteraceae, is characterized by compressed, flower-like inflorescences that may bear phenotypically distinct flower types. The CYCLOIDEA (CYC)/TEOSINTE BRANCHED1-like transcription factors (TFs) belonging to the TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR (TCP) protein family are known to regulate bilateral symmetry in single flowers. In Asteraceae, they function at the inflorescence level, and were recruited to define differential flower type identities. Here, we identified upstream regulators of GhCYC3, a gene that specifies ray flower identity at the flower head margin in the model plant Gerbera hybrida. We discovered a previously unidentified expression domain and functional role for the paralogous CINCINNATA-like TCP proteins. They function upstream of GhCYC3 and affect the developmental delay of marginal ray primordia during their early ontogeny. At the level of single flowers, the Asteraceae CYC genes show a unique function in regulating the elongation of showy ventral ligules that play a major role in pollinator attraction. We discovered that during ligule development, the E class MADS-box TF GRCD5 activates GhCYC3 expression. We propose that the C class MADS-box TF GAGA1 contributes to stamen development upstream of GhCYC3. Our data demonstrate how interactions among and between the conserved floral regulators, TCP and MADS-box TFs, contribute to the evolution of the elaborate inflorescence architecture of Asteraceae.Peer reviewe

A Possible Detection of M31* with Chandra

Two independent sets of Chandra and HST images of the nuclear region of M31 allow registration of X-ray and optical images to 0.1''. This registration shows that none of the bright (10^{37} erg/s) X-ray sources near the nucleus is coincident with the central super-massive black hole, M31*. A 50ks Chandra HRC image shows 2.5 sigma evidence for a faint (3 x 10^{35} erg/s), apparently resolved source which is consistent with the position of the M31*. The Bondi radius of M31* is 0.9'', making it one of the few super-massive black holes with a resolvable accretion flow. This large radius and the previous detections of diffuse, X-ray emitting gas in the nuclear region make M31* one of the most secure cases for a radiatively inefficient accretion flow and place some of the most severe constraints on the radiative processes in such a flow.Comment: 14 pages, 5 figures, submitted to Ap

Ultrasound-evoked immediate early gene expression in the brainstem of the Chinese torrent frog, Odorrana tormota

The concave-eared torrent frog, Odorrana tormota, has evolved the extraordinary ability to communicate ultrasonically (i.e., using frequencies>20kHz), and electrophysiological experiments have demonstrated that neurons in the frog’s midbrain (torus semicircularis) respond to frequencies up to 34kHz. However, at this time, it is unclear which region(s) of the torus and what other brainstem nuclei are involved in the detection of ultrasound. To gain insight into the anatomical substrate of ultrasound detection, we mapped expression of the activity-dependent gene, egr-1, in the brain in response to a full-spectrum mating call, a filtered, ultrasound-only call, and no sound. We found that the ultrasound-only call elicited egr-1 expression in the superior olivary and principal nucleus of the torus semicircularis. In sampled areas of the principal nucleus, the ultrasound-only call tended to evoke higher egr-1 expression than the full-spectrum call and, in the center of the nucleus, induced significantly higher egr-1 levels than the no-sound control. In the superior olivary nucleus, the full-spectrum and ultrasound-only calls evoked similar levels of expression that were significantly greater than the control, and egr-1 induction in the laminar nucleus showed no evidence of acoustic modulation. These data suggest that the sampled areas of the principal nucleus are among the regions sensitive to ultrasound in this species

Ultrasound-evoked immediate early gene expression in the brainstem of the Chinese torrent frog, Odorrana tormota

The concave-eared torrent frog, Odorrana tormota, has evolved the extraordinary ability to communicate ultrasonically (i.e., using frequencies > 20 kHz), and electrophysiological experiments have demonstrated that neurons in the frog’s midbrain (torus semicircularis) respond to frequencies up to 34 kHz. However, at this time, it is unclear which region(s) of the torus and what other brainstem nuclei are involved in the detection of ultrasound. To gain insight into the anatomical substrate of ultrasound detection, we mapped expression of the activity-dependent gene, egr-1, in the brain in response to a full-spectrum mating call, a filtered, ultrasound-only call, and no sound. We found that the ultrasound-only call elicited egr-1 expression in the superior olivary and principal nucleus of the torus semicircularis. In sampled areas of the principal nucleus, the ultrasound-only call tended to evoke higher egr-1 expression than the full-spectrum call and, in the center of the nucleus, induced significantly higher egr-1 levels than the no-sound control. In the superior olivary nucleus, the full-spectrum and ultrasound-only calls evoked similar levels of expression that were significantly greater than the control, and egr-1 induction in the laminar nucleus showed no evidence of acoustic modulation. These data suggest that the sampled areas of the principal nucleus are among the regions sensitive to ultrasound in this species

Long-term X-ray Variability Study of IC342 from XMM-Newton Observations

We presented the results of an analysis of four XMM-Newton observations of the starburst galaxy IC342 taken over a four-year span from 2001 to 2005, with an emphasis on investigating the long-term flux and spectral variability of the X-ray point sources. We detected a total of 61 X-ray sources within 35' $\times$ 30' of the galaxy down to a luminosity of (1-2)$\times$1037 erg s-1 depending on the local background. We found that 39 of the 61 detected sources showed long-term variability, in which 26 of them were classified as X-ray transients. We also found 19 sources exhibiting variations in hardness ratios or undergoing spectral transitions among observations, and were identified as spectral variables. In particular, 8 of the identified X-ray transients showed spectral variability in addition to flux variability. The diverse patterns of variability observed is indicative of a population of X-ray binaries. We used X-ray colors, flux and spectral variability, and in some cases the optical or radio counterparts to classify the detected X-ray sources into several stellar populations. We identified a total of 11 foreground stars, 1 supersoft sources (SSS), 3 quasisoft sources (QSS), and 2 supernova remnants (SNR). The identified SSS/QSS are located near or on the spiral arms, associate with young stellar populations; the 2 SNR are very close to the starburst nucleus where current star formation activities are dominated. We also discovered a spectral change in the nuclear source of IC342 for the first time by a series of X-ray spectrum analysis.Comment: 45 pages, 6 figures accepted by Ap

Long-term monitoring of the TeV emission from Mrk 421 with the ARGO-YBJ experiment

ARGO-YBJ is an air shower detector array with a fully covered layer of resistive plate chambers. It is operated with a high duty cycle and a large field of view. It continuously monitors the northern sky at energies above 0.3 TeV. In this paper, we report a long-term monitoring of Mrk 421 over the period from 2007 November to 2010 February. This source was observed by the satellite-borne experiments Rossi X-ray Timing Explorer and Swift in the X-ray band. Mrk 421 was especially active in the first half of 2008. Many flares are observed in both X-ray and gamma-ray bands simultaneously. The gamma-ray flux observed by ARGO-YBJ has a clear correlation with the X-ray flux. No lag between the X-ray and gamma-ray photons longer than 1 day is found. The evolution of the spectral energy distribution is investigated by measuring spectral indices at four different flux levels. Hardening of the spectra is observed in both X-ray and gamma-ray bands. The gamma-ray flux increases quadratically with the simultaneously measured X-ray flux. All these observational results strongly favor the synchrotron self-Compton process as the underlying radiative mechanism.Comment: 30 pages, 8 figure

One-Step Generation of Mice Carrying Mutations in Multiple Genes by CRISPR/Cas-Mediated Genome Engineering.

SUMMARY Mice carrying mutations in multiple genes are traditionally generated by sequential recombination in embryonic stem cells and/or time-consuming intercrossing of mice with a single mutation. The CRISPR/Cas system has been adapted as an efficient gene-targeting technology with the potential for multiplexed genome editing. We demonstrate that CRISPR/Cas-mediated gene editing allows the simultaneous disruption of five genes (Tet1, 2, 3, Sry, Uty -8 alleles) in mouse embryonic stem (ES) cells with high efficiency. Coinjection of Cas9 mRNA and single-guide RNAs (sgRNAs) targeting Tet1 and Tet2 into zygotes generated mice with biallelic mutations in both genes with an efficiency of 80%. Finally, we show that coinjection of Cas9 mRNA/sgRNAs with mutant oligos generated precise point mutations simultaneously in two target genes. Thus, the CRISPR/Cas system allows the one-step generation of animals carrying mutations in multiple genes, an approach that will greatly accelerate the in vivo study of functionally redundant genes and of epistatic gene interactions

Longitudinal stage profiles forecasting in rivers for flash floods

Copyright © 2010 Elsevier. NOTICE: this is the author’s version of a work that was accepted for publication in Journal of Hydrology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Hydrology Vol. 388 (2010), DOI: 10.1016/j.jhydrol.2010.05.028A flash flood routing model with artificial neural networks predictions was developed for stage profiles forecasting. The artificial neural network models were used to predict the 1-3 h lead time river stages at gauge stations along a river. The predictions were taken as interior boundaries in the flash flood routing model for the forecast of longitudinal stage profiles, including the un-gauged sites of a whole river. The flash flood routing model was based on the dynamic wave equations with discretization processes of the four-point finite difference method. Five typhoon events were applied to calibrate the rainfall-stage model and the other three events were simulated to verify the model's capability. The results revealed that the flash flood river routing model conjunction with artificial neural networks can provide accurate river stages for flood forecasting.National Science Council of Taiwa