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Aagaard Levesque posted an update 6 months ago
The way organelles are viewed by cell biologists is quickly changing. For many years, these cellular entities were thought to be unique and singular structures that performed specific roles. However, in recent decades, researchers have discovered that organelles are dynamic and form physical contacts. In addition, organelle interactions modulate several vital biological functions, and the dysregulation of these contacts is involved in cell dysfunction and different pathologies, including neurodegenerative diseases. Mitochondria-ER contact sites (MERCS) are among the most extensively studied and understood juxtapositioned interorganelle structures. In this review, we summarise the major biological and ultrastructural dysfunctions of MERCS in neurodegeneration, with a particular focus on Alzheimer’s disease as well as Parkinson’s disease, amyotrophic lateral sclerosis and frontotemporal dementia. We also propose an updated version of the MERCS hypothesis in Alzheimer’s disease based on new findings. Finally, we discuss the possibility of MERCS being used as possible drug targets to halt cell death and neurodegeneration.We prepared overlap soldered joints of high-temperature superconducting tapes, using various materials and preparation conditions. In order to select the joints with optimal performance, we correlated their electrical properties (derived from current-voltage curves) with the microstructure of the respective joint cross-section by scanning electron microscopy. With the first group of joints, we focused on the effect of used materials on joint resistivity and critical current, and we found that the dominant role was played by the quality of the internal interfaces of the superconducting tape. Initial joint resistivities ranged in the first group from 41 to 341 nΩ·cm2. The second group of joints underwent a series of thermal cyclings, upon which the initial resistivity range of 35-49 nΩ·cm2 broadened to 25-128 nΩ·cm2. After the total of 135 thermal cycles, three out of four joints showed no signs of significant degradation. Within the limit of 100 thermal cycles, reliable soldered joints can be thus prepared, with normalized resistivity not exceeding 1.4 and with normalized critical current above the value of 0.85.The drying unit of a continuous from-powder-to-tablet manufacturing line based on twin-screw granulation (TSG) is a crucial intermediate process step to achieve the desired tablet quality. Understanding the size reduction of pharmaceutical granules before, during, and after the fluid bed drying process is, however, still lacking. buy GPNA A first major goal was to investigate the breakage and attrition phenomena during transport of wet and dry granules, the filling phase, and drying phase on a ConsiGma-25 system (C25). Pneumatic transport of the wet granules after TSG towards the dryer induced extensive breakage, whereas the turbulent filling and drying phase of the drying cells caused rather moderate breakage and attrition. Subsequently, the dry transfer line was responsible for additional extensive breakage and attrition. The second major goal was to compare the influence of drying air temperature and drying time on granule size and moisture content for granules processed with a commercial-scale ConsiGma-25 system and with the R&D-scale ConsiGma-1 (C1) system. Generally, the granule quality obtained after drying with C1 was not predictive for the C25, making it challenging during process development with the C1 to obtain representative granules for the C25.Long-term high fat-carbohydrates diet (HF-CD) contributes to the formation of irreversible changes in the organism that lead to the emergence of civilization diseases. In this study, the impact of three-month high-fat diet on the physical properties of erythrocytes (RBCs) was studied. Furthermore, the biological activity of Cistus incanus L. extracts, plant known with high pro-health potential, in relation to normal and HF-CD RBCs, was determined. Obtained results have shown that, applied HF-CD modified shape, membrane potential and osmotic resistance of erythrocytes causing changes in membrane lipid composition and the distribution of lipids. The impact of HF-CD on physical properties of RBCs along with atherosclerotic lesions of the artery was visible, despite the lack of statistically significant changes in blood morphology and plasma lipid profile. This suggests that erythrocytes may be good markers of obesity-related diseases. The studies of biological activity of Cistus incanus L. extracts have demonstrated that they may ameliorate the effect of HF-CD on erythrocytes through the membrane-modifying and antioxidant activity.Parasitic organisms especially those of the Apicomplexan phylum, harbour a cytosol localised canonical Hsp70 chaperone. One of the defining features of this protein is the presence of GGMP repeat residues sandwiched between α-helical lid and C-terminal EEVD motif. The role of the GGMP repeats of Hsp70s remains unknown. In the current study, we introduced GGMP mutations in the cytosol localised Hsp70-1 of Plasmodium falciparum (PfHsp70-1) and a chimeric protein (KPf), constituted by the ATPase domain of E. coli DnaK fused to the C-terminal substrate binding domain of PfHsp70-1. A complementation assay conducted using E. coli dnaK756 cells demonstrated that the GGMP motif was essential for chaperone function of the chimeric protein, KPf. Interestingly, insertion of GGMP motif of PfHsp70-1 into DnaK led to a lethal phenotype in E. coli dnaK756 cells exposed to elevated growth temperature. Using biochemical and biophysical assays, we established that the GGMP motif accounts for the elevated basal ATPase activity of PfHsp70-1. Furthermore, we demonstrated that this motif is important for interaction of the chaperone with peptide substrate and a co-chaperone, PfHop. Our findings suggest that the GGMP may account for both the specialised chaperone function and reportedly high catalytic efficiency of PfHsp70-1.With the increase in the aging population worldwide, social interest in having a vibrant and valuable old age has been increasing with changes in the perspectives on old age. This study aimed to determine the relationship between active aging and health-related quality of life (HRQOL) in middle-aged and older Korean using national data. The subjects were 14,117 adults aged ≥55 years. HRQOL was evaluated using the EuroQol-5 Dimension (EQ-5D) questionnaire, and active aging was defined based on the health factors, participation factors, and security factors. The average EQ-5D score was 91.04 ± 0.143. Hierarchical multiple regression analysis sequentially inputting the health, participation, and security factors showed that health factors had the strongest influence on HRQOL (F = 216.656, p less then 0.001). In the final model, which included all variables, activity limit (B = -10.477, p less then 0.001) and subjective health status (B = -7.282, p less then 0.001) were closely related to the HRQOL. In addition, economic activity, income level, home ownership, private health insurance, and unmet healthcare needs were associated with HRQOL.
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