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.

Early changes in frequency of peripheral blood lymphocyte subpopulations in severe traumatic brain-injured patients.

Abstract: Infections are leading causes of increased morbidity and mortality of severe traumatic brain-injured (STBI) patients. The mechanism underlying the susceptibility to the infections is still unexplained. The purpose of the study was to investigate changes in frequency of leucocytes subpopulations in peripheral blood of patients with STBI during the course of intensive care treatment. Twenty patients with STBI were included in the study. Healthy age- and sex- volunteers served as control. Peripheral blood samples were taken from these patients at day 1, 4 and 7, and peripheral blood mononuclear cells (PBMC) were isolated. The percentage of T, B lymphocyte, NK and NKT cells as well as monocytes was analysed by simultaneous detection of surface antigens using fluorochrome-conjugated monoclonal antibodies. The two major subsets of T lymphocytes (CD3(+)CD56(-)CD4(+) and CD3(+)CD56(-)CD8(+)) and NK cells (CD3(-)CD56(+dim) and CD3(-)CD56(+bright)) were also analysed by flow cytometry. Extracranial infections were presented in 55% patients with STBI. At day 4, the percentage of T lymphocytes with cytotoxic phenotype significantly diminished and their numbers restored at day 7. The frequency of NKT cells showed the identical time-dependent pattern, whereas the percentage of NK cells diminished on day 4 but did not restore after 7 days. The frequency of B lymphocytes did not change significantly during the time investigated, whereas the percentage of monocytes increased immediately after the injury and gradually diminished. The decrease in cells with cytotoxic phenotype might explain high incidence of susceptibility to infection of patients with STBI.

Murine Cytomegalovirus m38.5 Protein Inhibits Bax-Mediated Cell Death

Abstract: Many viruses encode proteins that inhibit the induction of programmed cell death at the mitochondrial checkpoint. Murine cytomegalovirus (MCMV) encodes the m38.5 protein, which localizes to mitochondria and protects human HeLa cells and fibroblasts from apoptosis triggered by proteasome inhibitors but not from Fas-induced apoptosis. However, the ability of this protein to suppress the apoptosis of murine cells and its role during MCMV infection have not been investigated previously. Here we show that m38.5 is expressed at early time points during MCMV infection. Cells infected with MCMVs lacking m38.5 showed increased sensitivity to cell death induced by staurosporine, MG132, or the viral infection itself compared to the sensitivity of cells infected with wild-type MCMV. This defect was eliminated when an m38.5 or Bcl-XL gene was inserted into the genome of a deletion mutant. Using fibroblasts deficient in the proapoptotic Bcl-2 family proteins Bak and/or Bax, we further demonstrated that m38.5 protected from Bax- but not Bak-mediated apoptosis and interacted with Bax in infected cells. These results consolidate the role of m38.5 as a viral mitochondrion-localized inhibitor of apoptosis and its functional similarity to the human cytomegalovirus UL37x1 gene product. Although the m38.5 gene is not homologous to the UL37x1 gene at the sequence level, m38.5 is conserved among rodent cytomegaloviruses. Moreover, the fact that MCMV-infected cells are protected from both Bak- and Bax-mediated cell death suggests that MCMV possesses an additional, as-yet-unidentified mechanism to block Bak-mediated apoptosis.

Intact NKG2D-independent function of NK cells chronically stimulated with the NKG2D ligand Rae-1.

Abstract: Human tumors frequently express membrane-bound or soluble NK group 2, member D (NKG2D) ligands. This results in chronic engagement of NKG2D on the surfaces of NK and CD8+ T cells and rapid internalization of the receptor. Although it is well appreciated that this phenomenon impairs NKG2D-dependent function, careful analysis of NKG2D-independent functions in cells chronically stimulated through NKG2D is lacking. Using a mouse model of chronic NKG2D ligand expression, we show that constant exposure to NKG2D ligands does not functionally impair NK cells and CD8+ T cells in the context of viral infection.

Inflammatory monocytes and NK cells play a crucial role in DNAM-1-dependent control of cytomegalovirus infection

Abstract: The poliovirus receptor (PVR) is a ubiquitously expressed glycoprotein involved in cellular adhesion and immune response. It engages the activating receptor DNAX accessory molecule (DNAM)-1, the inhibitory receptor TIGIT, and the CD96 receptor with both activating and inhibitory functions. Human cytomegalovirus (HCMV) down-regulates PVR expression, but the significance of this viral function in vivo remains unknown. Here, we demonstrate that mouse CMV (MCMV) also down-regulates the surface PVR. The m20.1 protein of MCMV retains PVR in the endoplasmic reticulum and promotes its degradation. A MCMV mutant lacking the PVR inhibitor was attenuated in normal mice but not in mice lacking DNAM-1. This attenuation was partially reversed by NK cell depletion, whereas the simultaneous depletion of mononuclear phagocytes abolished the virus control. This effect was associated with the increased expression of DNAM-1, whereas TIGIT and CD96 were absent on these cells. An increased level of proinflammatory cytokines in sera of mice infected with the virus lacking the m20.1 and an increased production of iNOS by inflammatory monocytes was observed. Blocking of CCL2 or the inhibition of iNOS significantly increased titer of the virus lacking m20.1. In this study, we have demonstrated that inflammatory monocytes, together with NK cells, are essential in the early control of CMV through the DNAM-1-PVR pathway.

Observations of the Blazar 3C 66A with the MAGIC Telescopes in Stereoscopic Mode

Abstract: We report new observations of the intermediate-frequency peaked BL Lacertae object 3C 66A with the MAGIC telescopes. The data sample we use were taken in 2009 December and 2010 January, and comprises 2.3 hr of good quality data in stereoscopic mode. In this period, we find a significant signal from the direction of the blazar 3C 66A. The new MAGIC stereoscopic system is shown to play an essential role for the separation between 3C 66A and the nearby radio galaxy 3C 66B, which is at a distance of only $6^\prime$. The derived integral flux above $100\eh{GeV}$ is 8.3% of Crab Nebula flux and the energy spectrum is reproduced by a power law of photon index $3.64 \pm 0.39_{\rm stat} \pm 0.25_{\rm sys}$. Within errors, this is compatible with the one derived by VERITAS in 2009. From the spectra corrected for absorption by the extragalactic background light, we only find small differences between the four models that we applied, and constrain the redshift of the blazar to $z < 0.68$.