Acid-sensing ion channels (ASICs) are proton-gated cation channels and key mediators of responses to neuronal injury. ASICs exhibit unique patterns of distribution in the brain, with high expression ...in neurons and low expression in glial cells. While there has been a lot of focus on ASIC in neurons, less is known about the roles of ASICs in glial cells. ASIC1a is expressed in astrocytes and might contribute to synaptic transmission and long-term potentiation. In oligodendrocytes, constitutive activation of ASIC1a participates in demyelinating diseases. ASIC1a, ASIC2a, and ASIC3, found in microglial cells, could mediate the inflammatory response. Under pathological conditions, ASIC dysregulation in glial cells can contribute to disease states. For example, activation of astrocytic ASIC1a may worsen neurodegeneration and glioma staging, activation of microglial ASIC1a and ASIC2a may perpetuate ischemia and inflammation, while oligodendrocytic ASIC1a might be involved in multiple sclerosis. This review concentrates on the unique ASIC components in each of the glial cells and integrates these glial-specific ASICs with their physiological and pathological conditions. Such knowledge provides promising evidence for targeting of ASICs in individual glial cells as a therapeutic strategy for a diverse range of conditions.
Innovative approaches for lightweight design of components can contribute significantly to reduced fuel consumption and emissions of future aircraft. Within the framework of the European aviation ...research program Clean Sky 2, an innovative design of an aircraft nose wheel for the A320 is developed using carbon fiber reinforced plastics (CFRP) in order to demonstrate a weight reduction potential of 27% compared to conventional designs. In the present paper, the approach of the development process and the final detailed design of the composite aircraft wheel as well as a manufacturing concept are presented, various design challenges are highlighted and the solutions developed to meet them are discussed. Within a concept phase different structural design principles for the wheel are analyzed, taking into account the challenging load cases during different phases of aircraft operation. The selected innovative design principle is further elaborated into a detailed design considering design challenges such as space, installation, and safety requirements, as well as integration of bearings, seals and joint solutions. Also, structural analysis of the composite components via FEA and experimental validation of the joints are discussed. In addition, the manufacturing concept for the complex wheel geometry via resin transfer molding (RTM) using carbon non-crimp fabrics is presented and an outlook on the future manufacturing and testing of wheel prototypes is given.
Malfunction of hERG potassium channels, due to inherited mutations or inhibition by drugs, can cause long QT syndrome, which can lead to life-threatening arrhythmias. A three-dimensional structure of ...hERG is a prerequisite to understand the molecular basis of hERG malfunction. To achieve a consensus model, we carried out an extensive analysis of hERG models based on various alignments of helix S5. We analyzed seven models using a combination of conventional geometry/packing/normality validation methods as well as molecular dynamics simulations and molecular docking. A synthetic test set with the X-ray crystal structure of K(v)1.2 with artificially shifted S5 sequences modeled into the structure served as a reference case. We docked the known hERG inhibitors (+)-cisapride, (S)-terfenadine, and MK-499 into the hERG models and simulation snapshots. None of the single analyses unambiguously identified a preferred model, but the combination of all three revealed that there is only one model that fulfils all quality criteria. This model is confirmed by a recent mutation scanning experiment (P. Ju, G. Pages, R. P. Riek, P. C. Chen, A. M. Torres, P. S. Bansal, S. Kuyucak, P. W. Kuchel, J. I. Vandenberg, J. Biol. Chem. 2009, 284, 1000-1008). We expect the modeled structure to be useful as a basis both for computational studies of channel function and kinetics as well as the design of experiments.
Acid-sensing ion channels (ASICs) are proton-gated, voltage-independent sodium channels widely expressed throughout the central and peripheral nervous systems. They are involved in synaptic ...plasticity, learning/memory, fear conditioning and pain. Zinc, an important trace metal in the body, contributes to numerous physiological functions, with neurotransmission being of note. Zinc has been implicated in the modulation of ASICs by binding to specific sites on these channels and exerting either stimulatory or inhibitory effects depending on the ASIC subtype. ASICs have been linked to several neurological and psychological disorders, such as Alzheimer's disease, Parkinson's disease, ischemic stroke, epilepsy and cocaine addiction. Different ASIC isoforms contribute to the persistence of each of these neurological and psychological disorders. It is critical to understand how various zinc concentrations can modulate specific ASIC subtypes and how zinc regulation of ASICs can contribute to neurological and psychological diseases. This review elucidates zinc's structural interactions with ASICs and discusses the potential therapeutic implications zinc may have on neurological and psychological diseases through targeting ASICs.
...DECT may be a helpful imaging method for tophus assessment and follow-up in clinical trials as well as during urate lowering therapy in patients with the established diagnosis of chronic gout. 7 - ...9 It could also be a valuable diagnostic tool in patients with 'unclassified' acute or relapsing arthritides.
Current wearable respiratory monitoring devices provide a basic assessment of the breathing pattern of the examined subjects. More complex monitoring is needed for healthcare applications in patients ...with lung diseases. A multi-sensor vest allowing continuous lung imaging by electrical impedance tomography (EIT) and auscultation at six chest locations was developed for such advanced application. The aims of our study were to determine the vest's capacity to record the intended bio-signals, its safety and the comfort of wearing in a first clinical investigation in healthy adult subjects.
Twenty subjects (age range: 23-65 years) were studied while wearing the vests during a 14-step study protocol comprising phases of quiet and deep breathing, slow and forced full expiration manoeuvres, coughing, breath-holding in seated and three horizontal postures. EIT, chest sound and accelerometer signals were streamed to a tablet using a dedicated application and uploaded to a back-end server. The subjects filled in a questionnaire on the vest properties using a Likert scale.
All subjects completed the full protocol. Good to excellent EIT waveforms and functional EIT images were obtained in 89% of the subjects. Breathing pattern and posture dependent changes in ventilation distribution were properly detected by EIT. Chest sounds were recorded in all subjects. Detection of audible heart sounds was feasible in 44%-67% of the subjects, depending on the sensor location. Accelerometry correctly identified the posture in all subjects. The vests were safe and their properties positively rated, thermal and tactile properties achieved the highest scores.
The functionality and safety of the studied wearable multi-sensor vest and the high level of its acceptance by the study participants were confirmed. Availability of personalized vests might further advance its performance by improving the sensor-skin contact.
Morphing technologies can provide a significant contribution to reduction of noise and fuel consumption for future aircraft. In the framework of the European Aviation research programme Clean Sky 2, ...a design of a morphing leading edge was developed, which allows the simultaneous increase of wing chord and camber to adapt the airfoil to different airspeed conditions. The final design has a sliding contact at the bottom, whereas the upper surface is continuous with variable camber. In contrast to classical high lift devices, the lift coefficient can be increased without adding sources for turbulences at the upper wing surface. CFD analyses have been performed in order to quantify the aerodynamic performance of the designed morphing leading edge. Furthermore, a design concept both for the skin and for the actuation system is presented. The skin is designed using carbon fiber reinforced plastics (CFRP). In order to achieve both the required stiffness and flexibility, a customized non-constant layup is developed. Its feasibility for the high deformations during morphing is demonstrated by means of both numerical analysis and experimental validation. The electro-mechanical actuation system is designed to completely fit inside the morphing leading edge while still considering space for other subsystems. Besides the space requirements also weight, mountability and bird strike aspects are taken into account. Altogether, for the overall design of a morphing system is presented in this paper, various design challenges are highlighted and appropriate solutions for these challenges are discussed.
The German Society for Rheumatology, through its campaign Rheuma2025, aims to improve student teaching in order to ensure patient care for rheumatological patients in the future.
To assess whether ...a combination of traditional and innovative educational methods provide both an improvement in the quality of teaching and an increase in the attractiveness of rheumatology as a discipline.
Establishment of the teaching concept "Rheuma (be-)greifen" consisting of five modules on patient history taking with acting patients, musculoskeletal ultrasound, arthrocentesis, 3D printing of pathological joints and virtual reality applications based on real patient cases in the curricular teaching of medical students.
The evaluation of the teaching concept with 93 students of medicine showed a consistently high acceptance of all modules, which were rated as very effective or rather effective. Direct patient-related modules, such as history taking with acting patients, musculoskeletal ultrasound and arthrocentesis, received even higher acceptance than the visualization methods utilizing 3D printing and virtual reality.
Innovative teaching methods can help to improve the acceptance of teaching in the field of rheumatology, especially when combined with classical teaching contents.
During the last 3 years 4 patients were admitted to this hospital with a wide variety of different symptoms, in whom Erdheim-Chester disease (ECD) was diagnosed via different diagnostic pathways.
...Based on four clinical cases of ECD and using additional information from the literature, this article presents the symptoms of ECD. Furthermore, similarities and differences in comparison to important rheumatological differential diagnoses are presented.
The ECD is a multi-organ orphan disease. Typical for the disease are long bone involvement, periarterial inflammation especially of the aorta, retroperitoneal and perirenal fibrosis with so-called hairy kidneys in abdominal computed tomography (CT) scans. Treatment is increasingly directed towards the presence of a BRAF mutation, which enables targeted and effective treatment with BRAF inhibitors.
The ECD is a rare differential diagnosis to rheumatic diseases that causes various and often nonspecific symptoms. Due to modern diagnostic methods with imaging procedures and biopsies it is possible to establish a precise diagnosis and provide a targeted and effective treatment.
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