The von Hippel-Lindau gene is required to maintain renal proximal tubule and glomerulus integrity in zebrafish larvae

Background: von Hippel-Lindau (VHL) disease is characterized by the development of benign and malignant tumours in many organ systems, including renal cysts and clear cell renal cell carcinoma. It is not completely understood what underlies the development of renal pathology, and the use of murine Vhl models has been challenging due to limitations in disease conservation. We previously described a zebrafish model bearing inactivating mutations in the orthologue of the human VHL gene. Methods: We used histopathological and functional assays to investigate the pronephric and glomerular developmental defects in vhl mutant zebrafish, supported by human cell culture assays. Results: Here, we report that vhl is required to maintain pronephric tubule and glomerulus integrity in zebrafish embryos. vhl mutant glomeruli are enlarged, cxcr4a+ capillary loops are dilated and the Bowman space is widened. While we did not observe pronephric cysts, the cells of the proximal convoluted and anterior proximal straight tubule are enlarged, periodic acid schiff (PAS) and Oil Red O positive, and display a clear cytoplasm after hematoxylin and eosine staining. Ultrastructural analysis showed the vhl–/– tubule to accumulate large numbers of vesicles of variable size and electron density. Microinjection of the endocytic fluorescent marker AM1–43 in zebrafish embryos revealed an accumulation of endocytic vesicles in the vhl mutant pronephric tubule, which we can recapitulate in human cells lacking VHL. Conclusions: Our data indicates that vhl is required to maintain pronephric tubule and glomerulus integrity during zebrafish development, and suggests a role for VHL in endocytic vesicle trafficking

Yersinia effectors target mammalian signalling pathways

Animals have an immune system to fight off challenges from both viruses and bacteria. The first line of defence is innate immunity, which is composed of cells that engulf pathogens as well as cells that release potent signalling molecules to activate an inflammatory response and the adaptive immune system. Pathogenic bacteria have evolved a set of weapons, or effectors, to ensure survival in the host. Yersinia spp. use a type III secretion system to translocate these effector proteins, called Yops, into the host. This report outlines how Yops thwart the signalling machinery of the host immune system.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73466/1/j.1462-5822.2002.00182.x.pd

A New Fuzzy Additive Noise Reduction Method

In this paper we present a new alternative noise reduction method for color images that were corrupted with additive Gaussian noise. We illustrate that color images have to be processed in a different way than most of the state-of-the-art methods. The proposed method consists of two sub-filters. The main concern of the first subfilter is to distinguish between local variations due to noise and local variations due to image structures such as edges. This is realized by using the color component distances instead of component differences as done by most current filters. The second subfilter is used as a complementary filter which especially preserves differences between the color components. This is realized by calculating the local differences in the red, green and blue environment separately. These differences are then combined to calculate the local estimation of the central pixel. Experimental results show the feasibility of the proposed approach

Constraining the neutrino emission of gravitationally lensed Flat-Spectrum Radio Quasars with ANTARES data

This paper proposes to exploit gravitational lensing effects to improve the sensitivity of neutrino telescopes to the intrinsic neutrino emission of distant blazar populations. This strategy is illustrated with a search for cosmic neutrinos in the direction of four distant and gravitationally lensed Flat-Spectrum Radio Quasars. The magnification factor is estimated for each system assuming a singular isothermal profile for the lens. Based on data collected from 2007 to 2012 by the ANTARES neutrino telescope, the strongest constraint is obtained from the lensed quasar B0218+357, providing a limit on the total neutrino luminosity of this source of 1.08 x 10(46) erg s(-1) This limit is about one order of magnitude lower than those previously obtained in the ANTARES standard point source searches with non-lensed Flat-Spectrum Radio Quasars

The energy spectrum of cosmic rays beyond the turn-down around 10^17 eV as measured with the surface detector of the Pierre Auger Observatory

We present a measurement of the cosmic-ray spectrum above 100 PeV using the part of the surface detector of the Pierre Auger Observatory that has a spacing of 750 m. An inflection of the spectrum is observed, confirming the presence of the so-called second-knee feature. The spectrum is then combined with that of the 1500 m array to produce a single measurement of the flux, linking this spectral feature with the three additional breaks at the highest energies. The combined spectrum, with an energy scale set calorimetrically via fluorescence telescopes and using a single detector type, results in the most statistically and systematically precise measurement of spectral breaks yet obtained. These measurements are critical for furthering our understanding of the highest energy cosmic rays

Measurements of differential production cross sections for a Z boson in association with jets in pp collisions at root s=8 TeV

Peer reviewe

Search for leptophobic Z ' bosons decaying into four-lepton final states in proton-proton collisions at root s=8 TeV

Peer reviewe