SARS-CoV-2 Infection Dysregulates Cilia and Basal Cell Homeostasis in the Respiratory Epithelium of Hamsters

Similar to many other respiratory viruses, SARS-CoV-2 targets the ciliated cells of the respiratory epithelium and compromises mucociliary clearance, thereby facilitating spread to the lungs and paving the way for secondary infections. A detailed understanding of mechanism involved in ciliary loss and subsequent regeneration is crucial to assess the possible long-term consequences of COVID-19. The aim of this study was to characterize the sequence of histological and ultrastructural changes observed in the ciliated epithelium during and after SARS-CoV-2 infection in the golden Syrian hamster model. We show that acute infection induces a severe, transient loss of cilia, which is, at least in part, caused by cilia internalization. Internalized cilia colocalize with membrane invaginations, facilitating virus entry into the cell. Infection also results in a progressive decline in cells expressing the regulator of ciliogenesis FOXJ1, which persists beyond virus clearance and the termination of inflammatory changes. Ciliary loss triggers the mobilization of p73⁺ and CK14⁺ basal cells, which ceases after regeneration of the cilia. Although ciliation is restored after two weeks despite the lack of FOXJ1, an increased frequency of cilia with ultrastructural alterations indicative of secondary ciliary dyskinesia is observed. In summary, the work provides new insights into SARS-CoV-2 pathogenesis and expands our understanding of virally induced damage to defense mechanisms in the conducting airways.     

Effects of Long-Term Temozolomide Treatment on Glioblastoma and Astrocytoma WHO Grade 4 Stem-like Cells

Glioblastoma leads to a fatal course within two years in more than two thirds of patients. An essential cornerstone of therapy is chemotherapy with temozolomide (TMZ). The effect of TMZ is counteracted by the cellular repair enzyme O⁶-methylguanine-DNA methyltransferase (MGMT). The MGMT promoter methylation, the main regulator of MGMT expression, can change from primary tumor to recurrence, and TMZ may play a significant role in this process. To identify the potential mechanisms involved, three primary stem-like cell lines (one astrocytoma with the mutation of the isocitrate dehydrogenase (IDH), CNS WHO grade 4 (HGA)), and two glioblastoma (IDH-wildtype, CNS WHO grade 4) were treated with TMZ. The MGMT promoter methylation, migration, proliferation, and TMZ-response of the tumor cells were examined at different time points. The strong effects of TMZ treatment on the MGMT methylated cells were observed. Furthermore, TMZ led to a loss of the MGMT promoter hypermethylation and induced migratory rather than proliferative behavior. Cells with the unmethylated MGMT promoter showed more aggressive behavior after treatment, while HGA cells reacted heterogenously. Our study provides further evidence to consider the potential adverse effects of TMZ chemotherapy and a rationale for investigating potential relationships between TMZ treatment and change in the MGMT promoter methylation during relapse.     

Absolute characterization of high numerical aperture microscope objectives utilizing a dipole scatterer

Measuring the aberrations of optical systems is an essential step in the fabrication of high precision optical components. Such a characterization is usually ba...     

An analysis of specialist and non-specialist user requirements for geographic climate change information

The EU EuroClim project developed a system to monitor and record climate change indicator data based on satellite observations of snow cover, sea ice and glaciers in Northern Europe and the Arctic. It also contained projection data for temperature, rainfall and average wind speed for Europe. These were all stored as data sets in a GIS database for users to download. The process of gathering requirements for a user population including scientists, researchers, policy makers, educationalists and the general public is described. Using an iterative design methodology, a user survey was administered to obtain initial feedback on the system concept followed by panel sessions where users were presented with the system concept and a demonstrator to interact with it. The requirements of both specialist and non-specialist users is summarised together with strategies for the effective communication of geographic climate change information.     

Hybrid charge control for stick-slip piezoelectric actuators

The article describes an analog electronic circuit for driving stick-slip piezoelectric linear actuators. The task for the amplifier is to provide a high-voltage asymmetric sawtooth-like signal and feed it into a capacitive load. Generation of excessive heat must be avoided while maximizing the slew rate. In order to guarantee a steady translation, the hysteretic behaviour of the piezoelectric material must be compensated. Combination of a charge control scheme with switching is proposed as an efficient solution. Laboratory experiments confirm the superiority of this tailored solution over other existing techniques based on versatile linear voltage amplifiers.     

Reconfigurable handling system

The demand for more versatile assembly and handling systems to facilitate customized production is gaining in importance, especially with regard to the constantly-increasing cost pressure, to expansion of the range of product versions and the shortening of innovation cycles. As a cost-effective approach for frequently changing assembly tasks, a novel manipulation concept has been developed by combining given robot technologies. This new handling system has a modular and adaptable layout, which consists of several mobile arms to manipulate the object in six-dimensional Cartesian space. After grasping, when the arms are attached to the object, the mechanical architecture is similar to parallel manipulators or cooperating robots. As the mounting and gripping points of the arms can easily be changed, the manipulator can be reconfigured so as to match the user’s preferences and needs. In addition to the kinematic adaption the regarding task, the hardware and new functions can be reconfigured as well. Contact elements, measurement and assembly devices as well as testing modules can easily be in integrated in the concept. A modular automatic control concept combined with a self-optimizing planning tool helps the user to find the optimal configuration and realize it in an economic way.