ALBERT

Description: We study the effect of thermal annealing on the electrical properties of the nanoscale p-n heterojunctions based on single n-type ZnO nanorods on p-type GaN substrates. The ZnO nanorods are prepared by chemical bath deposition on both plain GaN substrates and on the substrates locally patterned by focused ion beam lithography. Electrical properties of single nanorod heterojunctions are measured with a nanoprobe in the vacuum chamber of a scanning electron microscope. The focused ion beam lithography provides a uniform nucleation of ZnO, which results in a uniform growth of ZnO nanorods. The specific configuration of the interface between the ZnO nanorods and GaN substrate created by the focused ion beam suppresses the surface leakage current and improves the current-voltage characteristics. Further improvement of the electrical characteristics is achieved by annealing of the structures in nitrogen, which limits the defect-mediated leakage current and increases the carrier injection efficiency.

Description: Protein kinase N3 (PKN3) is a serine/threonine kinase implicated in tumor progression of multiple cancer types, however, its substrates and effector proteins still remain largely understudied. In the present work we aimed to identify novel PKN3 substrates in a phosphoproteomic screen using analog sensitive PKN3. Among the identified putative substrates we selected ARHGAP18, a protein from RhoGAP family, for validation of the screen and further study. We confirmed that PKN3 can phosphorylate ARHGAP18 in vitro and we also characterized the interaction of the two proteins, which is mediated via the N-terminal part of ARHGAP18. We present strong evidence that PKN3-ARHGAP18 interaction is increased upon ARHGAP18 phosphorylation and that the phosphorylation of ARHGAP18 by PKN3 enhances its GAP domain activity and contributes to negative regulation of active RhoA. Taken together, we identified new set of potential PKN3 substrates and revealed a new negative feedback regulatory mechanism of Rho signaling mediated by PKN3-induced ARHGAP18 activation.

Description: Interleukin-6 (IL-6) is a cytokine with multifaceted effects playing a remarkable role in the initiation of the immune response. The increased level of this cytokine in the elderly seems to be associated with the chronic inflammatory setting of the microenvironment in aged individuals. IL-6 also represents one of the main signals in communication between cancer cells and their non-malignant neighbours within the tumour niche. IL-6 also participates in the development of a premetastatic niche and in the adjustment of the metabolism in terminal-stage patients suffering from a malignant disease. IL-6 is a fundamental factor of the cytokine storm in patients with severe COVID-19, where it is responsible for the fatal outcome of the disease. A better understanding of the role of IL-6 under physiological as well as pathological conditions and the preparation of new strategies for the therapeutic control of the IL-6 axis may help to manage the problems associated with the elderly, cancer, and serious viral infections.

Description: Monazite is a common accessory phosphate mineral that occurs under a wide range of pressure and temperature conditions in sedimentary, metamorphic and igneous rocks. Monazite contains high amounts of Th and U, rendering single monazite grains suitable for in-situ U-Th/Pb dating using laser ablation inductively-coupled mass spectrometry (LA-ICP-MS). Two key aspects of monazite dating that are critical for accurate age data with maximum precision are (i) optimized instrumental conditions to minimize analytical scatter and (ii) a well characterized reference material to ensure the accuracy of the obtained aged. Here, we analyzed five monazite reference materials (USGS 44069, 94-222, MAdel, Moacir and Thompson Mine Monazite) for their U-Th/Pb ages using LA-ICP-MS technique and applied a variety of laser spot diameters and repetition rates to find the best operational conditions to achieve accurate age data while maintaining maximum precision. We find that a spot diameter of 10 µm and a repetition rate of 10 Hz yield the most precise ages with a deviation of ±2.0% from their respective high-precision U/Pb literature age data. Ages were reproduced in three different LA-ICP-MS laboratories using these parameters. Each reference material was tested for its suitability as a matrix-matched age reference material. For this, a rotating, iterative approach was adopted in which one reference monazite was used as calibration reference material against all others, which were treated as unknowns. The results reveal that USGS 44069, 94-222, Thompson Mine Monazite and MAdel all agree with their respective calculated ages and ID-TIMS reference ages and thus are suggested as suitable calibration reference materials. Moacir, however, appears slightly older than previously suggested (up to 4%), thus, caution is advised here when using Moacir as reference material for U-Th/Pb LA-ICP-MS dating in the absence of further absolute age calibration.

Description: The availability of in situ snow water equivalent (SWE), snowmelt and run-off measurements is still very limited especially in remote areas as the density of operational stations and field observations is often scarce and usually costly, labour-intense and/or risky. With remote sensing products, spatially distributed information on snow is potentially available, but often lacks the required spatial or temporal requirements for hydrological applications. For the assurance of a high spatial and temporal resolution, however, it is often necessary to combine several methods like Earth Observation (EO), modelling and in situ approaches. Such a combination was targeted within the business applications demonstration project SnowSense (2015–2018), co-funded by the European Space Agency (ESA), where we designed, developed and demonstrated an operational snow hydrological service. During the run-time of the project, the entire service was demonstrated for the island of Newfoundland, Canada. The SnowSense service, developed during the demonstration project, is based on three pillars, including (i) newly developed in situ snow monitoring stations based on signals of the Global Navigation Satellite System (GNSS); (ii) EO snow cover products on the snow cover extent and on information whether the snow is dry or wet; and (iii) an integrated physically based hydrological model. The key element of the service is the novel GNSS based in situ sensor, using two static low-cost antennas with one being mounted on the ground and the other one above the snow cover. This sensor setup enables retrieving the snow parameters SWE and liquid water content (LWC) in the snowpack in parallel, using GNSS carrier phase measurements and signal strength information. With the combined approach of the SnowSense service, it is possible to provide spatially distributed SWE to assess run-off and to provide relevant information for hydropower plant management in a high spatial and temporal resolution. This is particularly needed for so far non, or only sparsely equipped catchments in remote areas. We present the results and validation of (i) the GNSS in situ sensor setup for SWE and LWC measurements at the well-equipped study site Forêt Montmorency near Quebec, Canada and (ii) the entire combined in situ, EO and modelling SnowSense service resulting in assimilated SWE maps and run-off information for two different large catchments in Newfoundland, Canada.

Description: Melanoma phenotype plasticity underlies tumour dissemination and resistance to therapy, yet its regulation is incompletely understood. In vivo switching between a more differentiated, proliferative phenotype and a dedifferentiated, invasive phenotype is directed by the tumour microenvironment. We found that treatment of partially dedifferentiated, invasive A375M2 cells with two structurally unrelated p38 MAPK inhibitors, SB2021920 and BIRB796, induces a phenotype switch in 3D collagen, as documented by increased expression of melanocyte differentiation markers and a loss of invasive phenotype markers. The phenotype is accompanied by morphological change corresponding to amoeboid–mesenchymal transition. We performed RNA sequencing with an Illumina HiSeq platform to fully characterise transcriptome changes underlying the switch. Gene expression results obtained with RNA-seq were validated by comparing them with RT-qPCR. Transcriptomic data generated in the study will extend the present understanding of phenotype plasticity in melanoma and its contribution to invasion and metastasis.

Description: We evaluated the short- and longer-term effects of exercise therapy in hip osteoarthritis patients (OA) at baseline, three, six, and 12 months in a randomized setting, followed by a non-randomized setting. The primary randomized intervention (E = exercise, P = placebo–ultrasound, C = control) was followed by a voluntary three-month exercise therapy for P and C (renamed P-E, C-E). Participants randomized to E were not offered treatment again (E-C). Effect sizes (ES; 95% CI) were calculated for within-group effects across time for bodily pain (SF-36) and WOMAC pain, function, and stiffness. ANCOVAs of post-treatment scores were used for group comparison after the group-specific exercise intervention phase. Exercise adherence was assessed and related to post-treatment scores of clinical outcomes. Data of 115 participants of the RCT eligible for follow-up and completing exercise therapy were included into our analyses. Small to medium beneficial long-term effects of cumulative interventional effects, including exercise training, persisted in all groups. Group E-C (n = 49) showed significant 12 months vs. baseline within-group ES in all outcomes (ES 0.39–0.59) except stiffness. Findings were less prominent for exercise therapy in a non-randomized setting (C-E, P-E, both n = 33). Differences are partially explained by adherence rates, highlighting the relevance of therapy compliance strategies. Short-term between-group differences (ANCOVAs) only showed statistically significant differences for WOMAC function between P-E and E-C in favor of E-C (6.4 (95% CI 1.6–11.2; score range 0–100)).