University of Graz

About: University of Graz is a education organization based out in Graz, Steiermark, Austria. It is known for research contribution in the topics: Population & Context (language use). The organization has 17934 authors who have published 37489 publications receiving 1110980 citations. The organization is also known as: Carolo Franciscea Graecensis & Karl Franzens Universität.

Molecular and Translational Classifications of DAMPs in Immunogenic Cell Death

Abstract: The immunogenicity of malignant cells has recently been acknowledged as a critical determinant of efficacy in cancer therapy. Thus, besides developing direct immunostimulatory regimens, including dendritic cell-based vaccines, checkpoint-blocking therapies, and adoptive T-cell transfer, researchers have started to focus on the overall immunobiology of neoplastic cells. It is now clear that cancer cells can succumb to some anticancer therapies by undergoing a peculiar form of cell death that is characterized by an increased immunogenic potential, owing to the emission of the so-called "damage-associated molecular patterns" (DAMPs). The emission of DAMPs and other immunostimulatory factors by cells succumbing to immunogenic cell death (ICD) favors the establishment of a productive interface with the immune system. This results in the elicitation of tumor-targeting immune responses associated with the elimination of residual, treatment-resistant cancer cells, as well as with the establishment of immunological memory. Although ICD has been characterized with increased precision since its discovery, several questions remain to be addressed. Here, we summarize and tabulate the main molecular, immunological, preclinical, and clinical aspects of ICD, in an attempt to capture the essence of this phenomenon, and identify future challenges for this rapidly expanding field of investigation.

4-Hydroxynonenal in the pathomechanisms of oxidative stress.

Abstract: Here we review the current knowledge on the biochemistry and molecular pathology of oxidative stress with specific regard to a major aldehydic end-product stemming from peroxidation of biomembranes, that is 4-hydroxynonenal (HNE). This multifunctional molecule, which derives from the most represented class of polyunsaturated fatty acids in the membranes, is potentially able to undergo a number of reactions with proteins, phospholipids, and nucleic acids. Despite an active metabolism in most of the cell types, HNE can be detected in several biological tissues by means of sufficiently precise methods, although with different sensitivity. In particular, relatively high steady-state levels of HNE are often detectable in a large variety of human disease processes, pointing to some involvement of the aldehyde in their pathogenesis. Among the prominent pathobiochemical effects of HNE is its remarkable stimulation of fibrogenesis and inflammation, which indicates a potential contribution of the aldehyde to the pathogenesis of several chronic diseases, whose progression is indeed supported by inflammatory reactions and characterized by fibrosis. Further, of interest appears to be the ability of HNE to modulate cell proliferation through interference with the activity of cyclins and protein kinases and with the apoptotic machinery. Finally, on the basis of the already achieved evidence, pursuing investigation of the role of HNE in signal transduction and gene expression seems very promising.

Femtosecond-laser-induced nanocavitation in water: implications for optical breakdown threshold and cell surgery.

Abstract: We determined the bubble radius ${R}_{\mathrm{max} }$ for femtosecond optical breakdown in water at 347, 520, and 1040 nm with an unprecedented accuracy ($\ifmmode\pm\else\textpm\fi{}10\text{ }\text{ }\mathrm{nm}$). At threshold, ${R}_{\mathrm{max} }$ was smaller than the diffraction-limited focus radius and ranged from 190 nm to 320 nm. The increase of ${R}_{\mathrm{max} }$ with laser energy ${E}_{L}$ is slowest at 347 nm, providing optimum control of cell surgery. Experimental results agree with a model of bubble formation in heated and thermoelastically stretched liquids. Theory predicts a threshold temperature ${T}_{\mathrm{th}}\ensuremath{\approx}168\text{ }\ifmmode^\circ\else\textdegree\fi{}\mathrm{C}$. For $Tg300\text{ }\ifmmode^\circ\else\textdegree\fi{}\mathrm{C}$, a phase explosion sets in, and ${R}_{\mathrm{max} }$ increases rapidly with ${E}_{L}$.

A novel mechanism for the biogenesis of outer membrane vesicles in Gram-negative bacteria

Abstract: Bacterial outer membrane vesicles (OMVs) have important biological roles in pathogenesis and intercellular interactions, but a general mechanism of OMV formation is lacking. Here we show that the VacJ/Yrb ABC (ATP-binding cassette) transport system, a proposed phospholipid transporter, is involved in OMV formation. Deletion or repression of VacJ/Yrb increases OMV production in two distantly related Gram-negative bacteria, Haemophilus influenzae and Vibrio cholerae. Lipidome analyses demonstrate that OMVs from VacJ/Yrb-defective mutants in H. influenzae are enriched in phospholipids and certain fatty acids. Furthermore, we demonstrate that OMV production and regulation of the VacJ/Yrb ABC transport system respond to iron starvation. Our results suggest a new general mechanism of OMV biogenesis based on phospholipid accumulation in the outer leaflet of the outer membrane. This mechanism is highly conserved among Gram-negative bacteria, provides a means for regulation, can account for OMV formation under all growth conditions, and might have important pathophysiological roles in vivo. Bacteria release outer membrane vesicles (OMVs) that play important roles in pathogenesis and intercellular interactions. Here, Roier et al. provide evidence supporting that phospholipid accumulation in the outer leaflet of the outer membrane participates in OMV formation in Gram-negative bacteria.