Postoperative peak serum C-reactive protein is a predictor of outcome following liver transplantation for hepatocellular carcinoma

Context: C-reactive protein (CRP), a biomarker of inflammation, may correlate with prognosis in several malignancies.

Objective: To investigate the prognostic impact of early postoperative peak serum levels of CRP on tumor-specific outcome in 106 liver transplant patients with hepatocellular carcinoma (HCC).

Methods and results: In multivariate Cox regression analysis, a posttransplant elevated peak CRP level (>versus?≤?3.5?mg/dl) was identified as an independent predictor of poor recurrence-free survival (p?=?0.01; HR?=?4.04; CI?=?1.399–11.640).

Conclusion: Early postoperative serum CRP may serve as a useful inflammation-based biomarker of outcome in liver transplant patients with HCC.     

Antigen presentation in Syrian hamster cells: substrate selectivity of TAP controlled by polymorphic residues in TAP1 and differential requirements for loading of H2 class I molecules

Expression of mouse major histocompatibility complex (MHC) class I molecules in different cell lines derived from Syrian hamsters has revealed antigen presentation deficiencies of some H2 allelic products in two cell lines (BHK and NIL-2) which were overcome by transient expression of the rat transporter associated with antigen processing (TAP; Lobigs et al. 1995). Here we show that in both cell lines the endogenous MHC class I cell surface expression was completely down-regulated. Lymphokine treatment induced endogenous and recombinant mouse MHC class I cell surface expression to levels similar to that in other Syrian hamster cell lines competent for antigen presentation through transduced H2 molecules. Accordingly, constitutive downregulation of expression of accessory molecules of the MHC class I pathway can reveal differences between H2 class I alleles in antigen presentation not encountered when the expression levels are augmented. In addition to the differential expression of MHC class I pathway genes, two cell lines representing competent (FF) and defective (BHK) antigen presentation phenotypes for mouse class I MHC restriction elements demonstrated substantial sequence polymorphism in Tap1 but not Tap2. Cytokine-treated FF or BHK cells and human TAP-deficient T2 cells transfected with FF or BHK TAP1 in combination with FF TAP2 differed in their preference for C-terminal peptide residues, as shown by an in vitro peptide transport assay. Thus, polymorphic residues in TAP1 can influence the substrate selectivity of the Syrian hamster peptide transporter.     

The ubiquitin ligation machinery in the defense against bacterial pathogens

The ubiquitin system is an important part of the host cellular defense program during bacterial infection. This is in particular evident for a number of bacteria including Salmonella Typhimurium and Mycobacterium tuberculosis which—inventively as part of their invasion strategy or accidentally upon rupture of seized host endomembranes—become exposed to the host cytosol. Ubiquitylation is involved in the detection and clearance of these bacteria as well as in the activation of innate immune and inflammatory signaling. Remarkably, all these defense responses seem to emanate from a dense layer of ubiquitin which coats the invading pathogens. In this review, we focus on the diverse group of host cell E3 ubiquitin ligases that help to tailor this ubiquitin coat. In particular, we address how the divergent ubiquitin conjugation mechanisms of these ligases contribute to the complexity of the anti‐bacterial coating and the recruitment of different ubiquitin‐binding effectors. We also discuss the activation and coordination of the different E3 ligases and which strategies bacteria evolved to evade the activities of the host ubiquitin system.     

Spatial correlograms of soil cover as an indicator of landscape heterogeneity

Soil cover, which is one of the most informative and integrative landscape factors, can be used for the analysis of landscape patterns. We studied the spatial autocorrelation (Moran's I) of raster format soil maps (1:10,000; 10 m pixel size) in 35 study areas representing all landscape regions in Estonia. The carbonate concentration of soils, volumetric soil moisture (%) and the depth of the groundwater table were taken into consideration in compiling a scale of contrast of 17 soil groups. We introduce a simple characteristic based on spatial correlograms: a half-value distance lag, h_I = 0.5—a distance where Moran's I drops below 0.5. Spatial autocorrelation decreased very rapidly in the case of heights with a very heterogeneous landscape composition, showing low values of h_I = 0.5 (<100 m in all 6 study areas). In uplands and depressions, the spatial autocorrelation also decreased relatively rapidly (h_I = 0.5 < 200 m). In most of the plains, coastal lowlands, sea islands and inland paludified lowlands, the values of Moran's I did decrease slowly with increasing lag, being >200 m in all forest and bog areas with complex topographical conditions due to the variety of glacial landforms and peatlands. All of the eight FRAGSTATS landscape metrics studied demonstrated significant correlations with h_I = 0.5, whereas five of them – Contrast Weighted Edge Density (CWED); Percentage of Like Adjacencies (PLADJ), Edge Density (ED), Patch Density (PD) and Mean Patch Area Distribution (AREA_MN) – had Spearman Rank Order Correlation values higher than 0.8. Landscapes with high ED, PD, and CWED values have a low autocorrelation: PD, ED, and CWED correlated negatively with h_I = 0.5. PD, ED, and CWED decreased and PLADJ increased with the power-law relationship with increasing h_I = 0.5. Spatial autocorrelation is lower in landscapes with complex structure and high contrast. The positive relationship with PLADJ indicates the same. Thus, spatial correlograms of potential landscape structure based on soil cover analysis can be used for the characterization of human-influenced landscape (land use) structure.