Oligomerization of Human Cystatin C—An Amyloidogenic Protein: An Analysis of Small Oligomeric Subspecies

Human cystatin C (HCC), an amyloidogenic protein, forms dimers and higher oligomers (trimers, tetramers and donut like large oligomers) via a domain-swapping mechanism. The aim of this study was the characterization of the HCC oligomeric states observed within the pH range from 2.2 to 10.0 and also in conditions promoting oligomerization. The HCC oligomeric forms obtained in different conditions were characterized using size exclusion chromatography, dynamic light scattering and small-angle X-ray scattering. The marked ability of HCC to form tetramers at low pH (2.3 or 3.0) and dimers at pH 4.0–5.0 was observed. HCC remains monomeric at pH levels above 6.0. Based on the SAXS data, the structure of the HCC tetramer was proposed. Changes in the environment (from acid to neutral) induced a breakdown of the HCC tetramers to dimers. The tetrameric forms of human cystatin C are formed by the association of the dimers without a domain-swapping mechanism. These observations were confirmed by their dissociation to dimers at pH 7.4.     

Rhus Coriaria L. Extract: Antioxidant Effect and Modulation of Bioenergetic Capacity in Fibroblasts from Parkinson’s Disease Patients and THP-1 Macrophages

Sumac, Rhus coriaria L., is a Mediterranean plant showing several useful properties, such as antioxidant and neuroprotective effects. Currently, there is no evidence about its possible neuroprotective action in Parkinson’s disease (PD). We hypothesized that sumac could modulate mitochondrial functionality in fibroblasts of familial early-onset PD patients showing PARK2 mutations. Sumac extract volatile profile, polyphenolic content and antioxidant activity have been previously characterized. We evaluated ROS and ATP levels on sumac-treated patients’ and healthy control fibroblasts. In PD fibroblasts, all treatments were effective in reducing H₂O₂ levels, while patients’ ATP content was modulated differently, probably due to the varying mutations in the PARK2 gene found in individual patients which are also involved in different mitochondrial phenotypes. We also investigated the effect of sumac extract on THP-1-differentiated macrophages, which show different embryogenic origin with respect to fibroblasts. In THP-1 macrophages, sumac treatment determined a reduction in H₂O₂ levels and an increase in the mitochondrial ATP content in M1, assuming that sumac could polarize the M1 to M2 phenotype, as demonstrated with other food-derived compounds rich in polyphenols. In conclusion, Rhus coriaria L. extracts could represent a potential nutraceutical approach to PD.     

The Role of Cancer Stem Cells and Their Extracellular Vesicles in the Modulation of the Antitumor Immunity

Cancer stem cells (CSCs) are a population of tumor cells that share similar properties to normal stem cells. CSCs are able to promote tumor progression and recurrence due to their resistance to chemotherapy and ability to stimulate angiogenesis and differentiate into non-CSCs. Cancer stem cells can also create a significant immunosuppressive environment around themselves by suppressing the activity of effector immune cells and recruiting cells that support tumor escape from immune response. The immunosuppressive effect of CSCs can be mediated by receptors located on their surface, as well as by secreted molecules, which transfer immunosuppressive signals to the cells of tumor microenvironment. In this article, the ability of CSCs to regulate the antitumor immune response and a contribution of CSC-derived EVs into the avoidance of the immune response are discussed.     

IL-17A in Human Liver: Significant Source of Inflammation and Trigger of Liver Fibrosis Initiation

IL-17A is considered to guide liver inflammation and fibrosis. From twenty-two human liver samples of different fibrosis stages (F0 to F4), IL-17A, IL-22, and TGFβ1 protein expression in liver tissue lysates were analyzed. Ten paired samples of liver tissue (F0–F1 stage) and blood from the same patient were used to analyze intrahepatic and blood T-lymphoid IL-17A⁺ cells by flow cytometry. The analyses have been performed regardless of pathology, considering the stage of fibrosis. Human liver tissue was used for the primary human liver slice cultures, followed by subsequent cytokine stimulation and fibrotic markers’ analysis by ELISA. IL-17A production in human liver tissue was significantly higher in the early fibrotic stage compared with the advanced stage. Th17 T cells and, to a lesser extent, MAIT cells were the main sources of IL-17A in both compartments, the liver and the blood. Moreover, the presence of liver Th17IL-17A⁺INFγ⁺ cells was detected in the liver. IL-17A stimulation of human liver slice culture increased the expression of profibrotic and pro-inflammatory markers. IL-17A, secreted by Th17 and MAIT cells in the liver, triggered fibrosis by inducing the expression of IL-6 and profibrotic markers and could be a target for antifibrotic treatment. Further amplitude studies are needed to confirm the current results.     

Selective CO-oxidation over Ru-based catalysts in H2-rich gas for fuel cell applications

Topics in Catalysis - Ru-based catalysts supported on A zeolites and alumina were synthesised, characterised (XRD, SEM-EDS, TPR) and tested under realistic conditions for the preferential oxidation...     

The over-claiming technique: Measuring self-enhancement independent of ability.

Over-claiming is a concrete operalization of self-enhancement based on respondents' ratings of their knowledge of various persons, events, products, and so on. Because 20% of the items are nonexistent, responses can be analyzed with signal detection formulas to index both response bias (over-claiming) and accuracy (knowledge). Study 1 demonstrated convergence of over-claiming with alternative measures of self-enhancement but independence from cognitive ability. In Studies 2-3, the validity of the over-claiming index held even when respondents were (a) warned about the foils or (b) asked to fake good. Study 3 also showed the utility of the over-claiming index for diagnosing faking. In Study 4, the over-claiming technique was applied to the debate over the adaptive value of positive illusions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Application of Inhibitor‐Loaded Halloysite Nanotubes in Active Anti‐Corrosive Coatings

Halloysite particles are aluminum‐silicate hollow cylinders with a length of 0.5–1 µm, an outer diameter of ca. 50 nm and a lumen of 15 nm. These nanotubes are used for loading and sustained release of corrosion inhibitors. The inhibitor is kept inside the particles infinitely long under dry conditions. Here, halloysite nanotubes filled with anticorrosive agents are embedded into a SiO_x–ZrO_x hybrid film. An aluminum plate is dip‐coated and immersed into 0.1 M sodium chloride aqueous solution for corrosion tests. A defect in the sol–gel coating induces pitting corrosion on the metal accompanied by a strong anodic activity. The inhibitor is released within one hour from halloysite nanotubes at corrosion spots and suppresses the corrosion process. The anodic activity is successfully restrained and the protection remains for a long time period of immersion in NaCl water solution. The self‐healing effect of the sol–gel coating doped with inhibitor‐loaded halloysite nanotubes is demonstrated in situ via scanning vibrating electrode technique measurements.     

Organochlorine compounds in Lake Superior: chiral polychlorinated biphenyls and biotransformation in the aquatic food web

The enantiomeric composition of seven chiral PCB congeners was measured in the Lake Superior aquatic food web sampled in 1998, to determine the extent of enantioselective biotransformation in aquatic biota. All chiral PCB congeners studied (CBs 91, 95, 136, 149, 174, 176, and 183) biomagnified in the Lake Superior aquatic food web, based on biomagnification and food web magnification factors greater than unity. PCB atropisomers were racemic in phytoplankton and zooplankton, suggesting no biotransformation potential toward PCBs for these low trophic level organisms. However, Diporeia and mysids had significantly nonracemic residues for most chiral congeners studied. This observation suggests that these macrozooplankton can stereoselectively metabolize chiral congeners. Alternatively, macrozooplankton obtained nonracemic residues from feeding on organic-rich suspended particles and sediments, which would imply that stereoselective microbial PCB biotransformation may be occurring in Lake Superior sediments at PCB concentrations far lower than that previously associated with such activity. Widely nonracemic PCB residues in forage fish (lake herring, rainbow smelt, and slimy sculpin) and lake trout suggest a combination of both in vivo biotransformation and uptake of nonracemic residues from prey for these species. Minimum biotransformation rates, calculated from enantiomer mass balances between predators and prey, suggest metabolic half-lives on the order of 8 yr for CB 136 in lake trout and 2.6 yr for CB 95 in sculpins. This result suggests that significant biotransformation may occur for metabolizable PCB congeners over the lifespan of these biota. This study highlights the potential of chiral analysis to study biotransformation processes in food webs.