ER Stress in ERp57 Knockout Knee Joint Chondrocytes Induces Osteoarthritic Cartilage Degradation and Osteophyte Formation

Ageing or obesity are risk factors for protein aggregation in the endoplasmic reticulum (ER) of chondrocytes. This condition is called ER stress and leads to induction of the unfolded protein response (UPR), which, depending on the stress level, restores normal cell function or initiates apoptotic cell death. Here the role of ER stress in knee osteoarthritis (OA) was evaluated. It was first tested in vitro and in vivo whether a knockout (KO) of the protein disulfide isomerase ERp57 in chondrocytes induces sufficient ER stress for such analyses. ER stress in ERp57 KO chondrocytes was confirmed by immunofluorescence, immunohistochemistry, and transmission electron microscopy. Knee joints of wildtype (WT) and cartilage-specific ERp57 KO mice (ERp57 cKO) were analyzed by indentation-type atomic force microscopy (IT-AFM), toluidine blue, and immunofluorescence/-histochemical staining. Apoptotic cell death was investigated by a TUNEL assay. Additionally, OA was induced via forced exercise on a treadmill. ER stress in chondrocytes resulted in a reduced compressive stiffness of knee cartilage. With ER stress, 18-month-old mice developed osteoarthritic cartilage degeneration with osteophyte formation in knee joints. These degenerative changes were preceded by apoptotic death in articular chondrocytes. Young mice were not susceptible to OA, even when subjected to forced exercise. This study demonstrates that ER stress induces the development of age-related knee osteoarthritis owing to a decreased protective function of the UPR in chondrocytes with increasing age, while apoptosis increases. Therefore, inhibition of ER stress appears to be an attractive therapeutic target for OA.     

Lymphatic transport in rats of interesterified oils containing conjugated linoleic acids

In this study we examined the lymphatic transport in rats of FA after administration of interesterified oils containing CLA, with emphasis on the location of CLA and octanoic acid in the TAG. The oils were produced by enzymatic interesterification. Eight oils with different structures or FA profiles were examined in this study: MCM, CMC, OCO, and COC, where M was expected to be octanoic acid and O oleic acid. In group 1, C was CLA as a mixture of the two CLA isomers c9, t11 or t10, c12, and in group 2, C was mainly the isomer t10, c12. Rats were subjected to cannulation of the mesenteric lymph duct, and the following day they were intragastrically administered one of the oils and lymph samples were collected for 24 h. The lymphatic transport of total FA from 0 to 8 h in group 1 was significantly (P < 0.05) higher for the OCO-1 and the COC-1 oils than for the CMC-1 oil. Similarly, in group 2 the transport was higher for the OCO-2 oil than for the CMC-2 oil. The recovery of both of the CLA isomers examined was similar (50-70%) and independent of the isomer, oil structure, and FA profile, whereas more octanoic acid was recovered from the CMC oils than from the MCM oils. The results indicated that the FA profiles and the position of octanoic acid had only a minor influence on the absorption of CLA.     

Biotransformation of 2-Benzoxazolinone to 2-Amino-(3<Emphasis Type="Italic">H</Emphasis>)-Phenoxazin-3-one and 2-Acetylamino-(3<Emphasis Type="Italic">H</Emphasis>)-Phenoxazin-3-one in Soil

An alternative to the use of synthetic pesticides is to exploit the natural defense chemicals produced by cereals. An important class of allelochemicals is cyclic hydroxamic acids and related benzoxazolinones. A prolonged degradation experiment of the allelochemical compound from rye 2-benzoxazolinone (BOA) was carried out for up to 90 d at 15°C at three different concentration levels, 3, 3000, and 30,000 nmol BOA· g soil^–1, respectively, in a sandy loam soil. Two main degradation products, 2-amino-(3H)-phenoxazin-3-one (APO) and 2-acetylamino-(3H)-phenoxazin-3-one (AAPO), were identified and quantified by LC-ESI-MS-MS. The half-life of BOA increased with higher levels of BOA added to the soil. Half-lives of BOA, APO, and AAPO were determined by fitting a single first-order model to the degradation data. Half-life of BOA was determined to be 0.6 d in the 3 nmol BOA g soil^–1 treatment. Half-lives of BOA, APO, and AAPO were 3.1, 2.7, and 2.1 d, respectively, in the 3000 nmol BOA· g soil^–1 treatment. In the 30,000 nmol BOA· g soil^–1 treatment, the half-lives were 31 d for BOA and 45 d for APO. The microbial community structure was not affected by addition of BOA to the soil as investigated by analysis of signature fatty acids. The results suggest that the exploitability of BOA for crop protection is dependent on the existing concentration of BOA in the soil and the timing of incorporation of hydroxamic acid synthesizing crops into the soil.     

Thermal modelling of the multi-stage heating system with variable boundary conditions in the wafer based precision glass moulding process

In the precision glass moulding process, the heat transfer and the resulting transient temperature distributions of the molten glass are of great importance because they significantly affect the productivity as well as the thermally induced residual stresses in the final product. Thermal modelling of the heating system in the glass moulding process considering detailed heating mechanisms therefore plays an important part in optimizing the heating system and the subsequent pressing stage in the lens manufacturing process.The current paper deals with three-dimensional transient thermal modelling of the multi-stage heating system in a wafer based glass moulding process. In order to investigate the importance of the radiation from the interior and surface of the glass, a simple finite volume code is developed to model one dimensional radiation–conduction heat transfer in the glass wafer for an extreme case with very high temperature difference considering temperature dependant thermal conductivity and heat capacity. Afterwards, by using three-dimensional FEM modelling along with a predefined experimental test, the equivalent glass–mould interface contact resistance is determined for two different pressures. Finally, the three-dimensional modelling of the multi-stage heating system in the wafer based glass moulding process is simulated with the FEM software ABAQUS for a particular industrial application for mobile phone camera lenses to obtain the temperature distribution in the glass wafer. In the numerical modelling, the interface boundary conditions for each heating stage are changed according to the determining heat transfer mechanism(s). Numerical results are compared with experimental data to show the validity of the numerical modelling. The obtained results show that the right thermal modelling is highly dependent on the proper choice of thermal boundary conditions in different stages according to the real physical phenomena behind the process.     

Increased Postprandial Triglyceride-Rich Lipoprotein Levels in Elderly Survivors of Myocardial Infarction

Postprandial triglyceride-rich lipoproteins (TRL) levels are a predictor for coronary atherosclerosis. The aim of the study was to compare fasting high density lipoprotein (HDL) cholesterol, plasma lipoprotein lipase (LPL) activity, and postprandial TRL between elderly survivors of myocardial infarction (MI) and healthy controls. A case-control study was performed in 44 elderly patients 65-85 years of age with a previous history of MI and 43 age- and sex-matched healthy controls. Each participant underwent physical examination and was given a standard oral fat load with subsequent blood sampling over the next 8 h. Total and chylomicron triglycerides were assessed by area under the curve (AUC), incremental are under the curve (AUCi) and triglyceride response (TGR). Elderly MI patients had significantly lower postheparin LPL activity (87.4 +/- 36.9 mU/ml) (mean +/- 1 SD) than healthy controls (106.0 +/- 29.0 mU/ml) (P = 0.014). Decreased postheparin LPL activity was accompanied by significant increased and delayed clearance of postprandial TRL. Fasting HDL cholesterol was significantly lower in elderly MI patients than controls (1.45 +/- 0.32 and 1.66 +/- 0.47 mmol/l, respectively, P = 0.048). Multiple regression analysis revealed postheparin LPL activity as an independent predictor for postprandial TRL and fasting HDL cholesterol. Logistic regressions analysis revealed HDL cholesterol, triglycerides measured 2 h after the oral fat load, and postheparin LPL activity as independent predictors for MI. Our findings indicate that decreased fasting HDL cholesterol is associated with increased postprandial triglyceridemia which could be a target for life-style and therapeutic interventions in patients at risk for cardiovascular disease.     

The GAUGAA Motif Is Responsible for the Binding between circSMARCA5 and SRSF1 and Related Downstream Effects on Glioblastoma Multiforme Cell Migration and Angiogenic Potential

Circular RNAs (circRNAs) are a large class of RNAs with regulatory functions within cells. We recently showed that circSMARCA5 is a tumor suppressor in glioblastoma multiforme (GBM) and acts as a decoy for Serine and Arginine Rich Splicing Factor 1 (SRSF1) through six predicted binding sites (BSs). Here we characterized RNA motifs functionally involved in the interaction between circSMARCA5 and SRSF1. Three different circSMARCA5 molecules (Mut1, Mut2, Mut3), each mutated in two predicted SRSF1 BSs at once, were obtained through PCR-based replacement of wild-type (WT) BS sequences and cloned in three independent pcDNA3 vectors. Mut1 significantly decreased its capability to interact with SRSF1 as compared to WT, based on the RNA immunoprecipitation assay. In silico analysis through the “Find Individual Motif Occurrences” (FIMO) algorithm showed GAUGAA as an experimentally validated SRSF1 binding motif significantly overrepresented within both predicted SRSF1 BSs mutated in Mut1 (q-value = 0.0011). U87MG and CAS-1, transfected with Mut1, significantly increased their migration with respect to controls transfected with WT, as revealed by the cell exclusion zone assay. Immortalized human brain microvascular endothelial cells (IM-HBMEC) exposed to conditioned medium (CM) harvested from U87MG and CAS-1 transfected with Mut1 significantly sprouted more than those treated with CM harvested from U87MG and CAS-1 transfected with WT, as shown by the tube formation assay. qRT-PCR showed that the intracellular pro- to anti-angiogenic Vascular Endothelial Growth Factor A (VEGFA) mRNA isoform ratio and the amount of total VEGFA mRNA secreted in CM significantly increased in Mut1-transfected CAS-1 as compared to controls transfected with WT. Our data suggest that GAUGAA is the RNA motif responsible for the interaction between circSMARCA5 and SRSF1 as well as for the circSMARCA5-mediated control of GBM cell migration and angiogenic potential.     

Structure-Activity Relationship Explorations and Discovery of a Potent Antagonist for the Free Fatty Acid Receptor 2

Free fatty acid receptor 2 (FFA2) is a sensor for short-chain fatty acids that has been identified as an interesting potential drug target for treatment of metabolic and inflammatory diseases. Although several ligand series are known for the receptor, there is still a need for improved compounds. One of the most potent and frequently used antagonists is the amide-substituted phenylbutanoic acid known as CATPB ( 1 ). We here report the structure-activity relationship exploration of this compound, leading to the identification of homologues with increased potency. The preferred compound 37 (TUG-1958) was found, besides improved potency, to have high solubility and favorable pharmacokinetic properties.     

Effect of different surface treatments on polypropylene composites reinforced with yerba mate fibers: Physical,mechanical, chemical,and morphological properties

This study presents the preparation of post-consumer polypropylene (r-PP) composites filled with 30 wt% yerba mate (YM) stick particles. To improve the fiber–matrix adhesion, three surface treatments were performed: alkaline treatment with sodium hydroxide (NaOH) and use of 3-aminopropyltriethoxysilane (APTS) and maleic anhydride graft polypropylene copolymer (PP-g-MA) as coupling agents. Mechanical properties including tensile, flexural, and impact resistance were determined, and chemical (Fourier transform infrared spectroscopy [FTIR]), physical (water absorption), and morphological analyses were performed. The main findings show that the treatments were efficient in improving the mechanical properties of the composites, with emphasis on the r-PP/YM30/APTS and r-PP/YM30/PP-g-MA composites, which proved to be superior in tensile, flexion and impact strength and absorption of water compared to the untreated composite. The morphological analysis showed a better interaction between the fiber and the polymeric matrix for the composites with YM/APTS and YM/PP-g-MA, which corroborates the results of tensile and flexural strength, as well as with the spectra of FTIR in which the chemical modification of the fibers is observed. However, the results show that these treatments are promising in obtaining composites with recycled matrix with better properties.     

Fire safe,sustainable loose furnishing

The aim of this exploratory study has been to investigate the fire properties and environmental aspects of different upholstery material combinations, mainly for domestic applications. An analysis of the sustainability and circularity of selected textiles, along with lifecycle assessment, is used to qualitatively evaluate materials from an environmental perspective. The cone calorimeter was the primary tool used to screen 20 different material combinations from a fire performance perspective. It was found that textile covers of conventional fibres such as wool, cotton and polyester, can be improved by blending them with fire resistant speciality fibres. A new three‐dimensional web structure has been examined as an alternative padding material, showing preliminary promising fire properties with regard to ignition time, heat release rates and smoke production.