The sorting Nexin 3 retromer pathway regulates the cell surface localization and activity of a Wnt-activated polycystin channel complex

Autosomal dominant polycystic kidney disease (ADPKD) is caused by inactivating mutations in PKD1 (85%) or PKD2 (15%). The ADPKD proteins encoded by these genes, polycystin-1 (PC1) and polycystin-2 (PC2), form a plasma membrane receptor–ion channel complex. However, the mechanisms controlling the subcellular localization of PC1 and PC2 are poorly understood. Here, we investigated the involvement of the retromer complex, an ancient protein module initially discovered in yeast that regulates the retrieval, sorting, and retrograde transport of membrane receptors. Using yeast two-hybrid, biochemical, and cellular assays, we determined that PC2 binds two isoforms of the retromer-associated protein sorting nexin 3 (SNX3), including a novel isoform that binds PC2 in a direct manner. Knockdown of SNX3 or the core retromer protein VPS35 increased the surface expression of endogenous PC1 and PC2 in vitro and in vivo and increased Wnt-activated PC2-dependent whole-cell currents. These findings indicate that an SNX3-retromer complex regulates the surface expression and function of PC1 and PC2. Molecular targeting of proteins involved in the endosomal sorting of PC1 and PC2 could lead to new therapeutic approaches in ADPKD

Novel Protein Sources for Applications in Meat-Alternative Products—Insight and Challenges

Many people are increasingly interested in a vegetarian or vegan diet. Looking at the research and the available options in the market, there are two generations of products based on typical proteins, such as soy or gluten, and newer generation proteins, such as peas or faba beans, or even proteins based on previously used feed proteins. In the review, we present the characteristics of several proteins that can be consumed as alternatives to first-generation proteins used in vegan foods. In the following part of the work, we describe the research in which novel protein sources were used in terms of the product they are used for. The paper describes protein sources such as cereal proteins, oilseeds proteins coming from the cakes after oil pressing, and novel sources such as algae, insects, and fungus for use in meat analog products. Technological processes that can make non-animal proteins similar to meat are also discussed, as well as the challenges faced by technologists working in the field of vegan products

Investigations of reinforced concrete members strengthened by laminates under explosive loading. Part 2, Experimental results for reinforced concrete beams and columns

W pracy przedstawiono wyniki badań doświadczalnych belek i słupów żelbetowych. Badania przeprowadzono dla elementów żelbetowych zwykłych bez dodatkowego wzmocnienia oraz dla elementów wzmocnionych wysokowytrzymałościowymi powłokowymi laminatami z włókien aramidowych, szklanych i węglowych. Zasadniczym celem pracy jest prezentacja wyników badań, na które składają się schematy mechanizmów zniszczenia oraz podstawowe parametry reakcji dynamicznej badanych elementów.The results of the experimental investigations of reinforced concrete beams were introduced in the present part of the paper. Investigations were carried out for two kinds of reinforced concrete elements, i.e. plain elements without the additional strengthening and for elements strengthened by high-strength coating laminates made from aramide, glass and carbon fibres. Principal aim of the paper is introduction of the results of the investigations, i.e., the schemes of the failure mechanisms, change in the time of the support force, displacements and acceleration parameters

Investigations of reinforced concrete members strengthened by laminatesunder explosive loading. Part 3, Experimental results for reinforced concrete beams and columns

W pracy przedstawiono wyniki badań doświadczalnych płyt żelbetowych. Badania przeprowadzono dla elementów żelbetowych, zwykłych bez dodatkowego wzmocnienia oraz dla elementów wzmocnionych wysokowytrzymałościowymi powłokowymi laminatami z włókien aramidowych, szklanych i węglowych. Zasadniczą częścią pracy jest prezentacja wyników badań, na które składają się schematy mechanizmów zniszczenia oraz trwałe przemieszczenia płyt.The results of experimental investigations of reinforced concrete plates were introduced in the present part of the paper. Investigations were carried out for two kinds of reinforced concrete elements, i.e., plain elements without additional strengthening and for elements strengthened by high-strength coating laminates made from aramide, glass, and carbon fibres. The schemes of failure mechanisms and the permanent displacements of plates were presented as the principal results of the investigations. It was stated in the result of investigations, that reinforced concrete structural elements strengthened by high-strength laminates show, under the explosive loading enlargement the carrying capacity, decrease in displacements, the limitation of the destruction areas of the concrete, enlarged ability to absorption of the energy. The respective parameters of effort and deformation depend on the kind of material strengthening and the configuration of the strengthening. It was confirmed that the application of coating strengthening generates the new effects of local type in reinforced concrete elements, namely swelling the concrete under laminate, the thread and superficial separation of the laminate, in this on the whole surface, the tearing the laminate and, first of all, decrease in the range of the failure of the element and elimination of the spread of the damaged fragments of the concrete

Investigations of reinforced concrete elements strengthened by laminates under explosive loading. Part 1, Description of investigation programme and investigations of structural materials

W pracy przedstawiono motywację podjęcia oraz koncepcję realizacji zamierzenia badawczego. W pierwszej części pracy przedstawiono opis programu badań doświadczalnych elementów żelbetowych. Badania przeprowadzono dla trzech rodzajów elementów żelbetowych zwykłych bez dodatkowego wzmocnienia oraz dla elementów wzmocnionych wysokowytrzymałościowymi powłokowymi laminatami z włókien aramidowych, szklanych i węglowych. Opisano stanowiska do badania elementów obciążonych wybuchowo. Przedstawiono charakterystykę oddziaływania wybuchu na badane elementy wraz z metodą szacowania obciążenia wybuchowego. Zaprezentowano wyniki badań materiałów konstrukcyjnych: betonu, stali zbrojeniowej i laminatów wykorzystanych do wykonania belek, słupów i płyt żelbetowych będących przedmiotem badań w pracy.The justification of undertaking and a conception of realization of the investigations of reinforced concrete elements under the explosive load were presented in the paper. The description of the experimental investigations programme of reinforced concrete elements was introduced in the present part of the paper. The investigative stands and the method of the investigations in which impulsive loading was generated by the explosive material were described. The characteristics of influence of explosion on investigative elements were introduced and the method of estimation of the loading values on the considered elements was given. The results of the investigations of the structural materials of which studied reinforced concrete elements were made were introduced in the present part of the paper. Investigations concerned to the concrete, reinforcing steel, and laminates from aramide, glass, and carbon fibres

Skeletal muscle response to endurance training in IL-6^{-/-} mice

We examined effects of moderate-intensity endurance training on muscle COX/CS activities and V’O2max in control WT and IL-6−/− mice. Animals were exercised for 10 weeks on treadmill for 1 h, 5 days a week at velocity of 6 m·min−1 which was increased by 0.5 m·min−1 every 2 weeks up to 8 m·min−1 . Training triggered an increase of enzyme activities in soleus muscle of WT mice (COX: 480.3±8.9 U·g−1 in sedentary group vs. 773.3±62.6 U·g−1 in trained group, P<0.05 and CS: 374.0±6.0 U·g−1 in sedentary group vs. 534.2±20.5 U·g−1 in trained group, P<0.01, respectively) whereas no changes were observed in soleus of IL6−/− mice. Moreover, in mixed gastrocnemius muscle of trained IL-6−/− mice enzyme activities tended to be lower (COX: 410.7±48.4 U·g−1 for sedentary vs. 277.0±36.5 U·g−1 for trained group and CS: 343.8±24.6 U·g−1 for sedentary vs. 251.7±27.1 U·g−1 for trained group). No changes in V’O2max were observed in WT and IL-6−/− mice after training. Concluding, moderate-velocity endurance training-induced increase in COX and CS activities in muscles of WT mice only which suggests that IL-6 regulates training-induced skeletal muscle responses to exercise. Copyright © 2015, Georg Thieme Verlag KG. All rights reserved

3-Methylglutaconic aciduria--lessons from 50 genes and 977 patients

Elevated urinary excretion of 3-methylglutaconic acid is considered rare in patients suspected of a metabolic disorder. In 3-methylglutaconyl-CoA hydratase deficiency (mutations in AUH), it derives from leucine degradation. In all other disorders with 3-methylglutaconic aciduria the origin is unknown, yet mitochondrial dysfunction is thought to be the common denominator. We investigate the biochemical, clinical and genetic data of 388 patients referred to our centre under suspicion of a metabolic disorder showing 3-methylglutaconic aciduria in routine metabolic screening. Furthermore, we investigate 591 patients with 50 different, genetically proven, mitochondrial disorders for the presence of 3-methylglutaconic aciduria. Three percent of all urine samples of the patients referred showed 3-methylglutaconic aciduria, often in correlation with disorders not reported earlier in association with 3-methylglutaconic aciduria (e.g. organic acidurias, urea cycle disorders, haematological and neuromuscular disorders). In the patient cohort with genetically proven mitochondrial disorders 11% presented 3-methylglutaconic aciduria. It was more frequently seen in ATPase related disorders, with mitochondrial DNA depletion or deletion, but not in patients with single respiratory chain complex deficiencies. Besides, it was a consistent feature of patients with mutations in TAZ, SERAC1, OPA3, DNAJC19 and TMEM70 accounting for mitochondrial membrane related pathology. 3-methylglutaconic aciduria is found quite frequently in patients suspected of a metabolic disorder, and mitochondrial dysfunction is indeed a common denominator. It is only a discriminative feature of patients with mutations in AUH, TAZ, SERAC1, OPA3, DNAJC19 TMEM70. These conditions should therefore be referred to as inborn errors of metabolism with 3-methylglutaconic aciduria as discriminative feature