REPEDEZETT, METAMORF KŐZETTESTEK KOMPLEX VIZSGÁLATA A TISZAI EGYSÉG ALJZATÁBAN = Complex evaluation of the fractured metamorphic basement of the Tisza Unit

A projekt témájában a futamidő alatt 1 MTA doktori és 3 PhD dolgozat született, 1 további PhD értekezés hamarosan beadásra kerül. Eredményeinket ezek mellett több mint 30 publikációban foglaltuk össze. A legfontosabb eredmények: - A Tiszai Egység kristályos aljzatának vizsgált részterületeit számottevően eltérő metamorf P-T-d-t fejlődésű blokkok építik fel, jelentős mértékű posztmetamorf tektonikai aktivitásra utalva - Az aljzat szerkezetét meghatározó kompressziós (kréta) és extenziós (neogén) tektonikai események egymásutánja geofizikai és kőzettani módszerek együttes alkalmazásával igazolható - A különböző kőzettípusok (gneiszek, amfibolit, márvány, milonit) kőzetmechanikai tulajdonságai, és törésgeometriai képe lényegesen eltér egymásétól. Ennek eredményeként egyes kőzetblokkokat (amfibolit és márvány testeket) kommunikáló, másokat (főleg a gyakori ortogneisz testeket) nem kommunikáló repedéshálózat jellemez - A nem kommunikáló törés alrendszerek repedéscementáció története, paleofluidum evolúciója akár kis területen belül is eltérő lehet - Minden vizsgált területen kimutatható a metamorf aljzat kommunikáló törés alrendszerei és a fedő üledékes képződmények közötti intenzív hidrodinamikai kapcsolat folyamatos megléte a palohidrológiai (töréscementáció) és a recens kúthidraulikai adatok alapján - Mindezek alapján a vizsgált kőzettestek litológiai felépítésük és szerkezetfejlődésük függvényében meglehetősen komplex repedezett szénhidrogén, illetve geotermikus rezervoárok | During the project one DSc and three PhD dissertation was finished. Moreover, we published 36 papers and book chapters. The most important results are the following: - In each study area the metamorphic basement consists of blocks of significantly different metamorphic P-T-t-d evolutions. Among these blocks post-metamorphic tectonic zones can be presumed. - Both the subsequent compressional (probably Cretaceous) and the extensional (Neogene) structural events can be proved by different geophysical methods. - Rock mechanical features and parameters of fracture network geometry of the basic lithologies (gneiss varieties, amphibolite, marple, mylonites) differs significantly. As a result, amphibolite and marble dominated blocks exhibit communicating fracture systems and good reservoir parameters, while the most common orthogneiss zones are well below percolation threshold. - For those rock bodies, which represent not communicating fracture systems, divergent paleofluid evolution and vein cementacion history may be typical even in small sub-areas. - In case of each studied crystalline realm a mutual communication between the fractured basement rocks and overlying sediments can be proved

CRP Enhances the Innate Killing Mechanisms Phagocytosis and ROS Formation in a Conformation and Complement-Dependent Manner

Phagocytosis and the formation of reactive oxygen species (ROS) in phagocytic leukocytes are an effective killing mechanism of the innate host defense. These cellular processes of innate immunity function in a complex interplay with humoral factors. C-reactive protein (CRP) in its activated, monomeric isoform (mCRP) has been shown to activate immune cells via the classical complement pathway. We investigated the complement-dependent effects of monomeric CRP (mCRP) on neutrophils and monocyte subtypes using complement-specific inhibitors by both flow cytometry and confocal fluorescence microscopy. We demonstrate that CRP-induced ROS generation is a conformation-specific and complement-dependent process in leukocyte subsets with classical monocytes as the primary source of ROS amongst human monocyte subsets. Elucidation of this complex interplay of CRP and complement in inflammation pathophysiology might help to improve anti-inflammatory therapeutic strategies

Serum PlGF and EGF are independent prognostic markers in non-metastatic colorectal cancer

The aim of this study was to determine the prognostic value of circulating angiogenic cytokines in non-metastatic colorectal cancer (CRC) patients. Preoperative serum samples of a training (TC) (n = 219) and a validation cohort (VC) (n = 168) were analyzed via ELISA to determine PlGF, EGF, VEGF, Ang1, PDGF-A, PDGF-B, IL-8 and bFGF levels. In addition, survival was correlated with PlGF and EGF expression measured by microarray and RNAseq in two publicly available, independent cohorts (n = 550 and n = 463, respectively). Prognostic values for overall (OS) and disease-free survival (DFS) were determined using uni- and multivariate Cox proportional hazard analyses. Elevated PlGF is predictive for impaired OS (TC: HR 1.056; p = 0.046; VC: HR 1.093; p = 0.001) and DFS (TC: HR 1.052; p = 0.029; VC: HR 1.091; p = 0.009). Conversely, elevated EGF is associated with favorable DFS (TC: HR 0.998; p = 0.045; VC: HR 0.998; p = 0.018) but not OS (TC: p = 0.201; VC: p = 0.453). None of the other angiogenic cytokines correlated with prognosis. The prognostic value of PlGF (OS + DFS) and EGF (DFS) was confirmed in both independent retrospective cohorts. Serum PlGF and EGF may serve as prognostic markers in non-metastatic CRC

A novel phosphocholine‐mimetic inhibits a pro‐inflammatory conformational change in C‐reactive protein

Abstract C‐reactive protein (CRP) is an early‐stage acute phase protein and highly upregulated in response to inflammatory reactions. We recently identified a novel mechanism that leads to a conformational change from the native, functionally relatively inert, pentameric CRP (pCRP) structure to a pentameric CRP intermediate (pCRP*) and ultimately to the monomeric CRP (mCRP) form, both exhibiting highly pro‐inflammatory effects. This transition in the inflammatory profile of CRP is mediated by binding of pCRP to activated/damaged cell membranes via exposed phosphocholine lipid head groups. We designed a tool compound as a low molecular weight CRP inhibitor using the structure of phosphocholine as a template. X‐ray crystallography revealed specific binding to the phosphocholine binding pockets of pCRP. We provide in vitro and in vivo proof‐of‐concept data demonstrating that the low molecular weight tool compound inhibits CRP‐driven exacerbation of local inflammatory responses, while potentially preserving pathogen‐defense functions of CRP. The inhibition of the conformational change generating pro‐inflammatory CRP isoforms via phosphocholine‐mimicking compounds represents a promising, potentially broadly applicable anti‐inflammatory therapy