University of Rijeka

About: University of Rijeka is a education organization based out in Rijeka, Croatia. It is known for research contribution in the topics: Population & Tourism. The organization has 3471 authors who have published 7993 publications receiving 110386 citations. The organization is also known as: Rijeka University & Sveučilište u Rijeci.

Role of interleukin-1 inhibitors in osteoarthritis: an evidence-based review.

Abstract: Osteoarthritis (OA), the most common chronic musculoskeletal disease, represents a leading cause of disability in the elderly population worldwide. At present, there is no aetiological treatment for OA patients. Also, current therapeutic regimens for OA are only partially effective, and that is the main reason for most physicians’ complaints. Therefore, one of the biggest challenges in the future will be to find the most appropriate therapy or therapies for OA. Currently, there are three basic modalities of treatment: nonpharmacological, pharmacological and surgical. Regarding pharmacological treatment, numerous molecular pathways involved in the pathophysiology of OA have been investigated as potential therapeutic targets. In preclinical and clinical trials, many compounds and agents have been tested, and some of them have already shown positive effects on the progression of knee and/or hip OA. One such possible pharmacological treatment of OA is anticytokine therapy. Interleukin-1 (IL-1), as a main inflammatory and catabolic cytokine in the pathophysiology of OA, represents one of the possible treatment targets. For specific inhibition of IL-1 production or activity, various treatment strategies could be used. These include the inhibition or modification of IL-1 action through the application of IL-1 receptor antagonist proteins, soluble IL-1 receptors, monoclonal antibodies against IL-1 or against IL-1 receptor I, blocking the formation of active IL-1β, blocking the IL-1 cellular signalling pathways, or using gene therapy. All the abovementioned treatment strategies for specific inhibition of IL-1 production or activity have been investigated in numerous preclinical and clinical studies. Some of these investigations led to the discovery of new potential drugs for the treatment of OA. However, the results of treatment with these drugs were not entirely satisfactory, and further research is required to achieve the desired goals of therapy.

The herpesviral Fc receptor fcr-1 down-regulates the NKG2D ligands MULT-1 and H60

Abstract: Members of the α- and β-subfamily of herpesviridae encode glycoproteins that specifically bind to the Fc part of immunoglobulin (Ig)G. Plasma membrane resident herpesviral Fc receptors seem to prevent virus-specific IgG from activating antibody-dependent effector functions. We show that the mouse cytomegalovirus (MCMV) molecule fcr-1 promotes a rapid down-regulation of NKG2D ligands murine UL16-binding protein like transcript (MULT)-1 and H60 from the cell surface. Deletion of the m138/fcr-1 gene from the MCMV genome attenuates viral replication to natural killer (NK) cell response in an NKG2D-dependent manner in vivo. A distinct N-terminal module within the fcr-1 ectodomain in conjunction with the fcr-1 transmembrane domain was required to dispose MULT-1 to degradation in lysosomes. In contrast, down-modulation of H60 required the complete fcr-1 ectodomain, implying independent modes of fcr-1 interaction with the NKG2D ligands. The results establish a novel viral strategy for down-modulating NK cell responses and highlight the impressive diversity of Fc receptor functions.

Multiwavelength Study Of Quiescent States Of Mrk 421 With Unprecedented Hard X-Ray Coverage Provided By Nustar In 2013

Abstract: We present coordinated multiwavelength observations of the bright, nearby BL Lacertae object Mrk 421 taken in 2013 January–March, involving GASP-WEBT, Swift, NuSTAR, Fermi-LAT, MAGIC, VERITAS, and other collaborations and instruments, providing data from radio to very high energy (VHE) γ-ray bands. NuSTAR yielded previously unattainable sensitivity in the 3–79 keV range, revealing that the spectrum softens when the source is dimmer until the X-ray spectral shape saturates into a steep Γ ≈ 3 power law, with no evidence for an exponential cutoff or additional hard components up to ~80 keV. For the first time, we observed both the synchrotron and the inverse-Compton peaks of the spectral energy distribution (SED) simultaneously shifted to frequencies below the typical quiescent state by an order of magnitude. The fractional variability as a function of photon energy shows a double-bump structure that relates to the two bumps of the broadband SED. In each bump, the variability increases with energy, which, in the framework of the synchrotron self-Compton model, implies that the electrons with higher energies are more variable. The measured multi band variability, the significant X-ray-to-VHE correlation down to some of the lowest fluxes ever observed in both bands, the lack of correlation between optical/UV and X-ray flux, the low degree of polarization and its significant (random) variations, the short estimated electron cooling time, and the significantly longer variability timescale observed in the NuSTAR light curves point toward in situ electron acceleration and suggest that there are multiple compact regions contributing to the broadband emission of Mrk 421 during low-activity states.

The p53 Tumor Suppressor Causes Congenital Malformations in Rpl24-Deficient Mice and Promotes Their Survival

Abstract: Hypomorphic mutation in one allele of ribosomal protein l24 gene (Rpl24) is responsible for the Belly Spot and Tail (Bst) mouse, which suffers from defects of the eye, skeleton, and coat pigmentation. It has been hypothesized that these pathological manifestations result exclusively from faulty protein synthesis. We demonstrate here that upregulation of the p53 tumor suppressor during the restricted period of embryonic development significantly contributes to the Bst phenotype. However, in the absence of p53 a large majority of Rpl24(Bst/+) embryos die. We showed that p53 promotes survival of these mice via p21-dependent mechanism. Our results imply that activation of a p53-dependent checkpoint mechanism in response to various ribosomal protein deficiencies might also play a role in the pathogenesis of congenital malformations in humans.