The Potential Role of Small-Molecule PERK Inhibitor LDN-0060609 in Primary Open-Angle Glaucoma Treatment

Primary open-angle glaucoma (POAG) constitutes the most common type of glaucoma. Emerging evidence suggests that Endoplasmic Reticulum (ER) stress and the protein kinase RNA-like endoplasmic reticulum kinase (PERK)-mediated Unfolded Protein Response (UPR) signaling pathway play a key role in POAG pathogenesis. Thus, the main aim of the study was to evaluate the effectiveness of the PERK inhibitor LDN-0060609 in cellular model of glaucoma using primary human trabecular meshwork (HTM) cells. To evaluate the level of the ER stress marker proteins, Western blotting and TaqMan gene expression assay were used. The cytotoxicity was measured by XTT, LDH assays and Giemsa staining, whereas genotoxicity via comet assay. Changes in cell morphology were assessed by phase-contrast microscopy. Analysis of apoptosis was performed by caspase-3 assay and flow cytometry (FC), whereas cell cycle progression by FC. The results obtained have demonstrated that LDN-0060609 triggered a significant decrease of ER stress marker proteins within HTM cells with induced ER stress conditions. Moreover, LDN-0060609 effectively increased viability, reduced DNA damage, increased proliferation, restored normal morphology, reduced apoptosis and restored normal cell cycle distribution of HTM cells with induced ER stress conditions. Thereby, PERK inhibitors, such as LDN-0060609, may provide an innovative, ground-breaking treatment strategy against POAG.     

Anti-Inflammatory Activity of Oat Beta-Glucans in a Crohn’s Disease Model: Time- and Molar Mass-Dependent Effects

Background: The incidence of Crohn’s disease (CD) is increasing worldwide, and it has currently become a serious public health issue in society. The treatment of CD continues throughout a patient’s lifetime, and therefore, it is necessary to develop new, effective treatment methods, including dietotherapy. The present study aimed to determine the effects of consumption of oat beta-glucans with different molar mass on colon inflammation (colitis) in the early stages of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced CD in an animal model. Methods: Sprague–Dawley rats (control and TNBS-induced CD) were divided into three dietary groups and fed for 3 days (reflecting acute inflammation) or 7 days (reflecting remission) with a feed containing 1% low (βGl) or high (βGh) molar mass oat beta-glucan or a feed without this polysaccharide. The level of colon inflammatory markers and the expression of cytokines and their receptor genes were measured by ELISA and RT-PCR methods, respectively. Results: Acute inflammation or remission (3 or 7 days after TNBS administration, respectively) stages of experimentally induced CD were characterized by an increase in the level of inflammatory markers (IL-1, IL-6, IL-10, IL-12, TNF-α, CRP, MPO, COX, and PGE2) and the disruption of some cytokine signaling pathways as well as macro- and microscopic changes of colon tissue. The consumption of oat beta-glucans reduced the level of inflammatory markers and recovered the signaling pathways and histological changes, with stronger effects of βGl after 7 days of colitis. Conclusions: Dietary oat beta-glucans can reduce colitis at the molecular and organ level and accelerate CD remission.     

Interplay between Coumarin Accumulation,Iron Deficiency and Plant Resistance to Dickeya spp.

Coumarins belong to a group of secondary metabolites well known for their high biological activities including antibacterial and antifungal properties. Recently, an important role of coumarins in plant resistance to pathogens and their release into the rhizosphere upon pathogen infection was discovered. It is also well documented that coumarins play a crucial role in the Arabidopsis thaliana growth under Fe-limited conditions. However, the mechanisms underlying interplay between plant resistance, accumulation of coumarins and Fe status, remain largely unknown. In this work, we investigated the effect of both mentioned factors on the disease severity using the model system of Arabidopsis/Dickeya spp. molecular interactions. We evaluated the disease symptoms in Arabidopsis plants, wild-type Col-0 and its mutants defective in coumarin accumulation, grown in hydroponic cultures with contrasting Fe regimes and in soil mixes. Under all tested conditions, Arabidopsis plants inoculated with Dickeya solani IFB0099 strain developed more severe disease symptoms compared to lines inoculated with Dickeya dadantii 3937. We also showed that the expression of genes encoding plant stress markers were strongly affected by D. solani IFB0099 infection. Interestingly, the response of plants to D. dadantii 3937 infection was genotype-dependent in Fe-deficient hydroponic solution.     

Effect of coumarin and xanthotoxin on mitochondrial structure,oxygen uptake,and succinate dehydrogenase activity in onion root cells

At concentrations in which they occur on the plant surface and retard mitosis, coumarin and xanthotoxin lowered uptake of oxygen (by 60 and 30%, respectively) by meristematic cells ofAllium cepa root tips. They caused changes in the structure of the mitochondrial matrix to become dense, and protrusions of mitochondrial membranes were visible parallelling their hypertrophy, indicating alteration in the structure and physiology of these organelles. Coumarin and, to a lesser extent, xanthotoxin increased succinate dehydrogenase production in mitochondria and also in the cytoplasm, indicating changes in membrane permeability. Changes in oxygen uptake and mitochondrial structure, in addition to the retardation of mitosis, may be the reason these compounds act as allelochemicals after they have been removed from the plant surface and reach the root meristem.     

Kinetics of thermal decomposition of unsaturated polyester resins with reduced flammability

In this article, the kinetics of thermal decomposition of unsaturated maleic–phthalic polyester resins, flame‐retarded with zinc hydroxystannate, was studied by thermogravimetric analysis at different heating rates. At the first stage, it was found, on the basis of isoconversional analysis by the methods of Friedman and of Ozawa–Flynn–Wall, that the value of the (apparent) activation energy (E) characteristically changes in three steps during the degradation. Further kinetic studies using nonlinear regression methods revealed the best fits for both pristine and stabilized resins. It was observed that the course of E versus the degree of conversion (α) during degradation of zinc hydroxystannate‐containing resins (α > 0.8) was characterized by higher values of E—this phenomenon can be explained in terms of the flame‐retardation action of zinc hydroxystannate, which is believed to operate primarily in the condensed phase. At the next stage, kinetic analysis by the nonregression method was performed to find the kinetic model [f(α) function] of the decomposition process; hence, for pristine resin, the best fit was found for the Avrami–Yerofeeyev model (nuclei growth), and for stabilized samples, the nth‐order function with catalysis proved to be the best approximation. The obtained kinetic parameters in the form of E, the preexponential factor A, and the model function f(α) allow a prediction of the polyester resin's thermal behavior in an extrapolated range of degree of conversion, time, and temperature. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 2851–2857, 2003     

Different support effect of M/ZrO2 and M/CeO2 (M = Pd and Pt) catalysts on CO adsorption: A periodic density functional study

CO adsorption over Pd₄ and Pt₄ cluster supported by c-ZrO₂(1 1 1) and CeO₂(1 1 1) catalyst systems was investigated using periodic density functional method in order to clarify the support effect on CO activation. We found that the support increases the CO activation for bridge and three-fold sites but decreases for the atop site. Moreover, it was found that the support changes the site preference for the CO adsorption. Bridge site on both the Pt₄/c-ZrO₂ and Pt₄/CeO₂ show larger CO adsorption energies than those on the other sites while the atop site is energetically preferable on isolated Pt₄ cluster. c-ZrO₂ supported Pd shows the largest CO activation with large charge transfer from the catalyst to the CO molecule. This reveals that ZrO₂ supported Pd can be a good catalyst for CO activation because of its higher probability to the three-fold site CO adsorption. We also found that positively charged M₄ clusters on the support keep their strong electron-donating properties and have enough charge density to contribute to the activation of an adsorbed CO molecule by a charge transfer.     

Calcium Phosphate Materials Prepared from Precipitates with Various Calcium:Phosphorus Molar Ratios

Depending on the calcium:phosphorus molar ratio of the initial precipitates determined by precipitation conditions (calcium:phosphorus molar ratio of reactants and pH of reaction environment), after sintering at 1250°C, monophase, biphase, or triphase ceramics consisting of hydroxyapatite, β-tricalcium phosphate, α-tricalcium phosphate, and calcium oxide were obtained. The phase composition and properties—i.e., density, shrinkage, hardness, bending strength, and roughness—of the fractured surfaces of the isostatically re-pressed sinters were determined.     

XPS spectra of the AFe4Al8 compounds with A=Y, Sc, U and Th

The XPS electronic structures of the AFe₄Al₈ (A=Sc, Y, U, Th) single crystals were measured. The valence band of UFe₄Al₈ exhibits domination of the U 5f states at the Fermi level, while for the other AFe₄Al₈ compounds the valence states are shifted by 0.5 eV toward higher binding energy. The multiplet structure of the U 4f and Th 4f states was analyzed in comparison with the U 4f states of U₃Ge₅ and UNiSb₂.     

Combining knowledge from different sources

Abstract: The present paper deals with the problem of an assessment of symptoms in medical diagnosis. A unified interpretation of symptoms is necessary to estimate their significance in a diagnosis. Yet, even if they are properly defined, different evaluations of them based on experts' knowledge or statistical estimation are possible. The present study aims at combining evaluations that may originate from an expert or can be found from statistical features of the data, as well as those determined for 'easy' and 'difficult' diagnostic cases. A model of diagnostic inference is proposed in the framework of the Dempster–Shafer theory extended for fuzzy focal elements. The basic probability assignment defined in this theory estimates weights of symptoms. Two basic probability assignments can be created and then combined. In this way weights of symptoms represent knowledge common for two kinds of data or obtained from an expert and from data. Thus, a combination of heuristics and data mining results becomes possible. An algorithm of the basic probability assignment calculation is suggested and tested for medical data: a database from the internet and individually gathered data.