Evidence of prognostic relevant expression profiles of heat-shock proteins and glucose-regulated proteins in oesophageal adenocarcinomas

A high percentage of oesophageal adenocarcinomas show an aggressive clinical behaviour with a significant resistance to chemotherapy. Heat-shock proteins (HSPs) and glucose-regulated proteins (GRPs) are molecular chaperones that play an important role in tumour biology. Recently, novel therapeutic approaches targeting HSP90/GRP94 have been introduced for treating cancer. We performed a comprehensive investigation of HSP and GRP expression including HSP27, phosphorylated (p)-HSP27^(Ser15), p-HSP27^(Ser78), p-HSP27^(Ser82), HSP60, HSP70, HSP90, GRP78 and GRP94 in 92 primary resected oesophageal adenocarcinomas by using reverse phase protein arrays (RPPA), immunohistochemistry (IHC) and real-time quantitative RT-PCR (qPCR). Results were correlated with pathologic features and survival. HSP/GRP protein and mRNA expression was detected in all tumours at various levels. Unsupervised hierarchical clustering showed two distinct groups of tumours with specific protein expression patterns: The hallmark of the first group was a high expression of p-HSP27^{(Ser15, Ser78, Ser82)} and low expression of GRP78, GRP94 and HSP60. The second group showed the inverse pattern with low p-HSP27 and high GRP78, GRP94 and HSP60 expression. The clinical outcome for patients from the first group was significantly improved compared to patients from the second group, both in univariate analysis (p = 0.015) and multivariate analysis (p = 0.029). Interestingly, these two groups could not be distinguished by immunohistochemistry or qPCR analysis. In summary, two distinct and prognostic relevant HSP/GRP protein expression patterns in adenocarcinomas of the oesophagus were detected by RPPA. Our approach may be helpful for identifying candidates for specific HSP/GRP-targeted therapies.     

Localization of plant N‐glycan processing enzymes along the secretory pathway

Abstract

N‐glycosylation is an abundant covalent protein modification in all eukaryotic cells. The biosynthesis and processing of protein N‐linked glycans results from a series of highly co‐ordinated step‐by‐step enzymatic conversions occurring mainly in the endoplasmic reticulum (ER) and Golgi apparatus. N‐glycan processing enzymes are thought to act on cargo glycoproteins in a highly ordered fashion in an assembly line. Thus, the subcellular localization of these enzymes together with their in vivo substrate specificity determines the carbohydrate structures of glycoproteins transported through the secretory pathway. While the substrate specificities of many plant N‐glycan processing enzymes are fairly well characterized, the molecular mechanisms underlying enzyme localization to the ER and Golgi have remained largely elusive so far. This review discusses current data on ER and Golgi localization of plant N‐glycan processing enzymes.     

The Risk of Peat Erosion from Climate Change: Land Management Combinations—An Assessment with Bayesian Belief Networks

Modeling risk factors to soils is constrained by the lack of key data and understanding that explicitly and quantitatively link specific threats to risk. Peat erosion results from the complex interaction of climatic, topographic, and anthropogenic influences acting over a long period of time. With numerous contemporary factors operating to perpetuate the erosion processes, it is often difficult to identify with certainty what actually are the initial and subsequent drivers of erosion. In this situation, expert opinion forms a vital source of information. Here we demonstrate how Bayesian Belief Networks (BBN) can be used to combine quantitative data from the National Soils Inventory of Scotland (NSIS) with qualitative expert knowledge to estimate risk of peat erosion in Scotland. This model was used to identify the main factors associated with peat erosion. It was shown that climatic variables (increased temperature, decreased precipitation) are the most important risk factors for perpetuating peatland erosion. However, the BBN approach also indicated that maintaining good vegetation cover is a significant mitigating factor. It would follow that land management practices that impact negatively on vegetation cover would also exacerbate peatland erosion given a hot dry climate.     

Sugar and malic acid utilization and acetic acid formation byLeuconostoc oenos

Leuconostoc oenos ST8, isolated from an Argentinian red wine, utilized glucose, fructose and malic acid and produced acetic acid. Fructose was preferred to glucose as a source of carbohydrate. Malic acid was almost completely degraded in 3 days at 25°C. Acetic acid formation correlated with fructose utilization.     

Phase equilibria and gelation in gelatin/maltodextrin systems — Part III: phase separation in mixed gels

Co-gels of potato maltodextrin Paselli SA-6 with gelatin were prepared by rapid quenching of mixed solutions from 90°C. At fixed setting temperature and fixed concentration of gelatin, the time required to form a self-supporting network showed an initial steady decrease with increasing concentration of SA-6 (as expected from polymer exclusion), but then increased dramatically before again decreasing. The interpretation of this behaviour as phase inversion from a gelatin-continuous network with SA-6 inclusions to a (more slowly-forming) SA-6 network with gelatin inclusions was confirmed by differential scanning calorimetry (showing both components melting separately, with no evidence of specific interaction), mechanical spectroscopy (showing that the mixed gel network was destroyed completely by melting of the gelatin component at low concentrations of SA-6, but only weakened at SA-6 concentrations above the inversion point) and by light microscopy (showing the expected changes in distribution of the two polymers).

In similar studies using the faster-gelling potato maltodextrin Paselli SA-2, microscopy and gel-melting profiles again showed phase-inversion from a gelatin-continuous network at low concentrations of SA-2 to a maltodextrin-continuous network at higher concentrations. Inversion, however, occurred at a lower concentration of maltodextrin than in the gelatin/SA-6 systems, and the accompanying change in gelation rate was confined to a sharp decrease in the dependence of gel-time on SA-2 concentration.     

Effect of poly(ethylene glycol) on the Ca2+-induced fusion of didodecyl phosphate vesicles

This paper reports a study of the effect of the dehydrating agent poly(ethylene glycol) (PEG) on didodecyl phosphate (DDP) bilayers and on the fusion activity of DDP vesicles as a function of the molecular weight of PEG. PEG 8K in a concentration of 10 wt % does not induce fusion. However, Ca2+-induced fusion is promoted as reflected by a lowering of the Ca2+ threshold concentration. This effect can most likely be attributed to the dehydrating capacity of the polymer. Interestingly, low concentrations (0.1 wt %) of PEG 20 K induce a moderate fusion capacity. At higher concentrations (0.5 wt %) fusion is inhibited, irrespective of the presence of Ca2+. These molecular weight dependent effects can be rationalized by taking into account that the clouding temperature differs for PEGs of different molecular weights. In the case of PEG 20K a microscopic phase separation will occur at the bilayer-water interface because PEG-PEG interactions and presumably PEG-DDP interactions are favored over PEG-water interactions. As a consequence, the DDP vesicle surface becomes covered with PEG 20K, resulting in a steric stabilization of the vesicles. This will impede or prevent, depending on the polymer concentration, the vesicles from approaching each other sufficiently close for fusion to occur.