Arve

Plössl, Simon, 1794-1868, austria optikArve vene troonipärijale (Aleksander II) tellitud mikroskoobi koht

The X-linked juvenile retinoschisis protein retinoschisin is a novel regulator of MAP kinase signaling and apoptosis in the retina

X-linked juvenile retinoschisis (XLRS) is a hereditary retinal dystrophy in young males, caused by mutations in the RS1 gene. The function of the encoded protein, termed retinoschisin, and the molecular mechanisms underlying XLRS pathogenesis are still unresolved, although a direct interaction partner of the secreted retinoschisin, the retinal Na/K-ATPase, was recently identified. Earlier gene expression studies in retinoschisin-deficient (Rs1h(-/Y)) mice provided a first indication of pathological up-regulation of mitogen-activated protein (MAP) kinase signalling in disease pathogenesis. To further investigate the role for retinoschisin in MAP kinase regulation, we exposed Y-79 cells and murine Rs1h(-/Y) retinae to recombinant retinoschisin and the XLRS-associated mutant RS1-C59S. Although normal retinoschisin stably bound to retinal cells, RS1-C59S exhibited a strongly reduced binding affinity. Simultaneously, exposure to normal retinoschisin significantly reduced phosphorylation of C-RAF and MAP kinases ERK1/2 in Y-79 cells and murine Rs1h(-/Y) retinae. Expression of MAP kinase target genes C-FOS and EGR1 was also down-regulated in both model systems. Finally, retinoschisin treatment decreased pro-apoptotic BAX-2 transcript levels in Y-79 cells and Rs1h(-/Y) retinae. Upon retinoschisin treatment, these cells showed increased resistance against apoptosis, reflected by decreased caspase-3 activity (in Y-79 cells) and increased photoreceptor survival (in Rs1h(-/Y) retinal explants). RS1-C59S did not influence C-RAF or ERK1/2 activation, C-FOS or EGR1 expression, or apoptosis. Our data imply that retinoschisin is a novel regulator of MAP kinase signalling and exerts an anti-apoptotic effect on retinal cells. We therefore discuss that disturbances of MAP kinase signalling by retinoschisin deficiency could be an initial step in XLRS pathogenesis

Altered Protein Function Caused by AMD-associated Variant rs704 Links Vitronectin to Disease Pathology

PURPOSE. Vitronectin, a cell adhesion and spreading factor, is suspected to play a role in the pathogenesis of age-related macular degeneration (AMD), as it is a major component of AMD-specific extracellular deposits (e.g., soft drusen, subretinal drusenoid deposits). The present study addressed the impact of AMD-associated non-synonymous variant rs704 in the vitronectin-encoding gene VTN on vitronectin functionality. METHODS. Effects of rs704 on vitronectin expression and processing were analyzed by semi-quantitative sequencing of VTN transcripts from retinal pigment epithelium (RPE) cells generated from human induced pluripotent stem cells (hiPSCs) and from human neural retina, as well as by western blot analyses on heterologously expressed vitronectin isoforms. Binding of vitronectin isoforms to retinal and endothelial cells was analyzed by western blot. Immunofluorescence staining followed extracellular matrix (ECM) deposition in cultured RPE cells heterologously expressing the vitronectin isoforms. Adhesion of fluorescently labeled RPE or endothelial cells in dependence of recombinant vitronectin or vitronectin-containing ECM was investigated fluorometrically or microscopically. Tube formation and migration assays addressed effects of vitronectin on angiogenesis-related processes. RESULTS. Variant rs704 affected expression, secretion, and processing but not oligomerization of vitronectin. Cell binding and influence on RPE-mediated ECM deposition differed between AMD-risk-associated and non-AMD-risk-associated protein isoforms. Finally, vitronectin affected adhesion and endothelial tube formation. CONCLUSIONS. The AMD-risk-associated vitronectin isoform exhibits increased expression and altered functionality in cellular processes related to the sub-RPE aspects of AMD pathology. Although further research is required to address the subretinal disease aspects, this initial study supports an involvement of vitronectin in AMD pathogenesis

Two-loop splitting in double parton distributions

Double parton distributions (DPDs) receive a short-distance contribution from a single parton splitting to yield the two observed partons. We investigate this mechanism at next-to-leading order (NLO) in perturbation theory. Technically, we compute the twoloop matching of both the position and momentum space DPDs onto ordinary PDFs. This also yields the 1 -> 2 splitting functions appearing in the evolution of momentum-space DPDs at NLO. We give results for the unpolarised, colour-singlet DPDs in all partonic channels. These quantities are required for calculations of double parton scattering at full NLO. We discuss various kinematic limits of our results, and we verify that the 1 -> 2 splitting functions are consistent with the number and momentum sum rules for DPDs. Copyright M. Diehl et al. This work is licensed under the Creative Commons Attribution 4.0 International License. Published by the SciPost Foundation

Protection mechanisms against phishing attacks

Abstract. Approaches against Phishing can be classified into modifications of the traditional PIN/TAN-authentication on the one hand and approaches that try to reduce the probability of a scammer being successful without changing the existing PIN/TAN-method on the other hand. We present a new approach, based on challenge-response-authentication. Since our proposal does not require any new hardware on the client side, it can be implemented with little additional cost by financial institutions or other web retailers and therefore is a good compromise compared to the other approaches. A big drawback is that it doesn’t protect against man-in-the-middle attacks but most of the other approaches don’t either.

Double parton distributions out of bounds in colour space

We investigate the positivity of double parton distributions with a non-trivial dependence on the parton colour. It turns out that positivity is not preserved by leading-order evolution from lower to higher scales, in contrast to the case in which parton colour is summed over. We also study the positivity properties of the distributions at small distance between the two partons, where they can be computed in terms of perturbative splitting kernels and ordinary parton densities