The unfolded protein response and its relevance to connective tissue diseases

The unfolded protein response (UPR) has evolved to counter the stresses that occur in the endoplasmic reticulum (ER) as a result of misfolded proteins. This sophisticated quality control system attempts to restore homeostasis through the action of a number of different pathways that are coordinated in the first instance by the ER stress-senor proteins IRE1, ATF6 and PERK. However, prolonged ER-stress-related UPR can have detrimental effects on cell function and, in the longer term, may induce apoptosis. Connective tissue cells such as fibroblasts, osteoblasts and chondrocytes synthesise and secrete large quantities of proteins and mutations in many of these gene products give rise to heritable disorders of connective tissues. Until recently, these mutant gene products were thought to exert their effect through the assembly of a defective extracellular matrix that ultimately disrupted tissue structure and function. However, it is now becoming clear that ER stress and UPR, because of the expression of a mutant gene product, is not only a feature of, but may be a key mediator in the initiation and progression of a whole range of different connective tissue diseases. This review focuses on ER stress and the UPR that characterises an increasing number of connective tissue diseases and highlights novel therapeutic opportunities that may arise

Increased classical endoplasmic reticulum stress is sufficient to reduce chondrocyte proliferation rate in the growth plate and decrease bone growth

Copyright: © 2015 Kung et al. Mutations in genes encoding cartilage oligomeric matrix protein and matrilin-3 cause a spectrum of chondrodysplasias called multiple epiphyseal dysplasia (MED) and pseudoachondroplasia (PSACH). The majority of these diseases feature classical endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) as a result of misfolding of the mutant protein. However, the importance and the pathological contribution of ER stress in the disease pathogenesis are unknown. The aim of this study was to investigate the generic role of ER stress and the UPR in the pathogenesis of these diseases. A transgenic mouse line (ColIITgcog) was generated using the collagen II promoter to drive expression of an ER stress-inducing protein (Tgcog) in chondrocytes. The skeletal and histological phenotypes of these ColIITgcog mice were characterised. The expression and intracellular retention of Tgcog induced ER stress and activated the UPR as characterised by increased BiP expression, phosphorylation of eIF2á and spliced Xbp1. ColIITgcog mice exhibited decreased long bone growth and decreased chondrocyte proliferation rate. However, there was no disruption of chondrocyte morphology or growth plate architecture and perturbations in apoptosis were not apparent. Our data demonstrate that the targeted induction of ER stress in chondrocytes was sufficient to reduce the rate of bone growth, a key clinical feature associated with MED and PSACH, in the absence of any growth plate dysplasia. This study establishes that classical ER stress is a pathogenic factor that contributes to the disease mechanism of MED and PSACH. However, not all the pathological features of MED and PSACH were recapitulated, suggesting that a combination of intra- and extra-cellular factors are likely to be responsible for the disease pathology as a whole

Air-inlet system for internal combustion engine, air-conditioning system and combustion engine comprising the air-inlet system

The invention relates to an air-inlet system (10), and relates to an air-conditioning system (100, 101 ) and an internal combustion engine (200) comprising the air-inlet system. The air-inlet system comprises an air intake port (20), an air output port (30) and a turbine (40) for controlling air mass flow into a combustion chamber (202) of an internal combustion engine. The turbine is provided with a propeller hub (42) which comprises at least one blade (44). The propeller hub is arranged between the air intake port and the air output port for propelling the blade of the turbine. The turbine has an air-flow resistance for determining the air mass flow into the combustion chamber. The effect of the air-inlet system according to the invention is that the use of a turbine enables to use at least some of the pressure drop across the turbine to drive the blade of the turbine for generating rotational energy

A liquid fuel composition and the use thereof

The present invention relates to a liquid fuel composition comprising a mixture of hydrocarbons and a cyclic hydrocarbon compound that suppresses the emission of soot particulates. The present invention also relates to a method for reducing the emission of soot particulates in the exhaust gases of an internal combustion engine. It is desirable for the cyclic hydrocarbon compound to contain one or more oxygen atoms

A method for converting C1-C4 alcohols into higher-value hydrocarbon compounds

No abstract available

Liquid injector for a combustion engine

A liquid injector 1 has an injector body 3 provided with an injection passage 7 which is formed by the cavity between the inner wall 9 of the injector body and a needle 5 and the cavity in a hole 13 located in the wall 11 of the injector body. The liquid injector 1 further has a spherical, hollow porous element 15 which extends beyond the injector body 3 and is formed by a semi-sphere which is fixed to the injector body and closes off the injection passage 7. The wall thickness of the porous element 15 is not the same throughout. In the middle the wall is thinner than near the edge, so that during the injection action the fuel vapour 19 has the shape of a semi-ellipse

Air inlet system for an internal combustion engine

An air inlet system (10) for an internal combustion engine (200) is provided. The air- inlet system comprises an air intake port (20), an air output port (30) for providing air for a combustion chamber (202) of the combustion engine (200), and a turbine (40). The turbine (40) is situated in between the air intake port (20) and the air output port (30) for turning kinetic energy from the air intake port (20) to the air output port (30) into mechanical energy. The turbine (40) comprises at least one impeller blade (44) and multiple adjustable vanes (48) for controlling an air flow resistance of the turbine (40), the adjustable vanes (48) being configurable in at least a first position, a second position and a third position. In the first position, two adjacent adjustable vanes (48) form a nozzle (37) for directing the airstream towards the impeller blade (44). In the second position, the two adjacent adjustable vanes (48) form a narrower nozzle (37) for directing the airstream towards the impeller blade (44). In the third position, the two adjacent adjustable vanes (48) are essentially in one line, such that a flow area for the airstream between said adjacent adjustable vanes (48) is minimal

Efficient energy recovering air inlet system for an internal combustion engine

An air inlet system (10) for an internal combustion engine (200) is provided. The air inlet system comprises an air intake port (20), an air output port (30) for providing air for a combustion chamber (202) of the combustion engine (200), and a turbine (40). The turbine (40) is situated in between the air intake port (20) and the air output port (30) for turning kinetic energy of an airstream from the air intake port (20) to the air output port (30) into mechanical energy. The turbine (40) comprises at least one adjustable vane (48) for controlling an air flow resistance of the turbine (40). An electrical generator (46) is coupled to the turbine (40) for converting the mechanical energy into electrical energy. A controller (60) controls a rotational speed of the turbine (40) by controlling a quantity of electric power generated by the electrical generator (46), the controller (60) being configured to adapt the rotational speed of the turbine (40) to the air flow resistance of the turbine (40) in such a way that a substantially optimal turbine efficiency is obtained

Efficient energy recovering air inlet system for an international combustion engine

An air inlet system (10) for an internal combustion engine (200) is provided. The air inlet system comprises an air intake port (20), an air output port (30) for providing air for a combustion chamber (202) of the combustion engine (200), and a turbine (40). The turbine (40) is situated in between the air intake port (20) and the air output port (30) for turning kinetic energy of an airstream from the air intake port (20) to the air output port (30) into mechanical energy. The turbine (40) comprises at least one adjustable vane (48) for controlling an air flow resistance of the turbine (40). An electrical generator (46) is coupled to the turbine (40) for converting the mechanical energy into electrical energy. A controller (60) controls a rotational speed of the turbine (40) by controlling a quantity of electric power generated by the electrical generator (46), the controller (60) being configured to adapt the rotational speed of the turbine (40) to the air flow resistance of the turbine (40) in such a way that a substantially optimal turbine efficiency is obtained