Tau Protein Modulates Perineuronal Extracellular Matrix Expression in the TauP301L-acan Mouse Model

Tau mutations promote the formation of tau oligomers and filaments, which are neuropathological signs of several tau-associated dementias. Types of neurons in the CNS are spared of tau pathology and are surrounded by a specialized form of extracellular matrix; called perineuronal nets (PNs). Aggrecan, the major PN proteoglycans, is suggested to mediate PNs neuroprotective function by forming an external shield preventing the internalization of misfolded tau. We recently demonstrated a correlation between aggrecan amount and the expression and phosphorylation of tau in a TauP310L-acan mouse model, generated by crossbreeding heterozygous aggrecan mice with a significant reduction of aggrecan and homozygous TauP301L mice. Neurodegenerative processes have been associated with changes of PN structure and protein signature. In this study, we hypothesized that the structure and protein expression of PNs in this TauP310L-acan mouse is regulated by tau. Immunohistochemical and biochemical analyses demonstrate that protein levels of PN components differ between TauP301LHET-acanWT and TauP301LHET-acanHET mice, accompanied by changes in the expression of protein phosphatase 2 A. In addition, tau can modulate PN components such as brevican. Co-immunoprecipitation experiments revealed a physical connection between PN components and tau. These data demonstrate a complex, mutual interrelation of tau and the proteoglycans of the PN

Investigating the Usability of a Head-Mounted Display Augmented Reality Device in Elementary School Children

Augmenting reality via head-mounted displays (HMD-AR) is an emerging technology in education. The interactivity provided by HMD-AR devices is particularly promising for learning, but presents a challenge to human activity recognition, especially with children. Recent technological advances regarding speech and gesture recognition concerning Microsoft’s HoloLens 2 may address this prevailing issue. In a within-subjects study with 47 elementary school children (2nd to 6th grade), we examined the usability of the HoloLens 2 using a standardized tutorial on multimodal interaction in AR. The overall system usability was rated “good”. However, several behavioral metrics indicated that specific interaction modes differed in their efficiency. The results are of major importance for the development of learning applications in HMD-AR as they partially deviate from previous findings. In particular, the well-functioning recognition of children’s voice commands that we observed represents a novelty. Furthermore, we found different interaction preferences in HMD-AR among the children. We also found the use of HMD-AR to have a positive effect on children’s activity-related achievement emotions. Overall, our findings can serve as a basis for determining general requirements, possibilities, and limitations of the implementation of educational HMD-AR environments in elementary school classrooms

Digital ink and differentiated subjective ratings for cognitive load measurement in middle childhood

Background: New methods are constantly being developed to adapt cognitive load measurement to different contexts. However, research on middle childhood students' cognitive load measurement is rare. Research indicates that the three cognitive load dimensions (intrinsic, extraneous, and germane) can be measured well in adults and teenagers using differentiated subjective rating instruments. Moreover, digital ink recorded by smartpens could serve as an indicator for cognitive load in adults. Aims: With the present research, we aimed at investigating the relation between subjective cognitive load ratings, velocity and pressure measures recorded with a smartpen, and performance in standardized sketching tasks in middle childhood students. Sample: Thirty-six children (age 7–12) participated at the university's laboratory. Methods: The children performed two standardized sketching tasks, each in two versions. The induced intrinsic cognitive load or the extraneous cognitive load was varied between the versions. Digital ink was recorded while the children drew with a smartpen on real paper and after each task, they were asked to report their perceived intrinsic and extraneous cognitive load using a newly developed 5-item scale. Results: Results indicated that cognitive load ratings as well as velocity and pressure measures were substantially related to the induced cognitive load and to performance in both sketching tasks. However, cognitive load ratings and smartpen measures were not substantially related. Conclusions: Both subjective rating and digital ink hold potential for cognitive load and performance measurement. However, it is questionable whether they measure the exact same constructs

Finding the best clearing approach - Towards 3D wide-scale multimodal imaging of aged human brain tissue

The accessibility of new wide-scale multimodal imaging techniques led to numerous clearing techniques emerging over the last decade. However, clearing mesoscopic-sized blocks of aged human brain tissue remains an extremely challenging task. Homogenizing refractive indices and reducing light absorption and scattering are the foundation of tissue clearing. Due to its dense and highly myelinated nature, especially in white matter, the human brain poses particular challenges to clearing techniques. Here, we present a comparative study of seven tissue clearing approaches and their impact on aged human brain tissue blocks (> 5 mm). The goal was to identify the most practical and efficient method in regards to macroscopic transparency, brief clearing time, compatibility with immunohistochemical processing and wide-scale multimodal microscopic imaging. We successfully cleared 26 × 26 × 5 mm3-sized human brain samples with two hydrophilic and two hydrophobic clearing techniques. Optical properties as well as light and antibody penetration depths highly vary between these methods. In addition to finding the best clearing approach, we compared three microscopic imaging setups (the Zeiss Laser Scanning Microscope (LSM) 880 , the Miltenyi Biotec Ultramicroscope ll (UM ll) and the 3i Marianas LightSheet microscope) regarding optimal imaging of large-scale tissue samples. We demonstrate that combining the CLARITY technique (Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging compatible Tissue hYdrogel) with the Zeiss LSM 880 and combining the iDISCO technique (immunolabeling-enabled three-dimensional imaging of solvent-cleared organs) with the Miltenyi Biotec UM ll are the most practical and efficient approaches to sufficiently clear aged human brain tissue and generate 3D microscopic images. Our results point out challenges that arise from seven clearing and three imaging techniques applied to non-standardized tissue samples such as aged human brain tissue

Estimation of Sea Ice Thickness Distributions through the Combination of Snow Depth and Satellite Laser Altimetry Data

Combinations of sea ice freeboard and snow depth measurements from satellite data have the potential to provide a means to derive global sea ice thickness values. However, large differences in spatial coverage and resolution between the measurements lead to uncertainties when combining the data. High resolution airborne laser altimeter retrievals of snow-ice freeboard and passive microwave retrievals of snow depth taken in March 2006 provide insight into the spatial variability of these quantities as well as optimal methods for combining high resolution satellite altimeter measurements with low resolution snow depth data. The aircraft measurements show a relationship between freeboard and snow depth for thin ice allowing the development of a method for estimating sea ice thickness from satellite laser altimetry data at their full spatial resolution. This method is used to estimate snow and ice thicknesses for the Arctic basin through the combination of freeboard data from ICESat, snow depth data over first-year ice from AMSR-E, and snow depth over multiyear ice from climatological data. Due to the non-linear dependence of heat flux on ice thickness, the impact on heat flux calculations when maintaining the full resolution of the ICESat data for ice thickness estimates is explored for typical winter conditions. Calculations of the basin-wide mean heat flux and ice growth rate using snow and ice thickness values at the 70 m spatial resolution of ICESat are found to be approximately one-third higher than those calculated from 25 km mean ice thickness values

Remote Sensing of Antarctic Sea Ice with Coordinated Aircraft and Satellite Data Acquisitions

Remote sensing of Antarctic sea ice is required to characterize properties of the vast sea ice cover to understand its long-term increase in contrast to the decrease of Arctic sea ice. For this objective, the OIB/TanDEM-X Coordinated Science Campaign (OTASC) was successfully conducted in 2017 to obtain contemporaneous and collocated remote sensing data from NASA's Operation IceBridge (OIB) and the German Aerospace Center (DLR) TanDEM-X Synthetic Aperture Radar (SAR) system at X-band together with Sentinel-1 and RADARSAT-2 SARs at C-band in conjunction with WorldView satellite spectral sensors, surface measurements, and field observations. The Weddell Sea and the Ross Sea were two primary regions while SAR data were also collected over six other regions in the Southern Ocean. Satellite SAR data included both polarimetric and interferometric capabilities to infer snow and sea ice information in three dimensions (3D), while OIB/P-3 aircraft data include snow radar together with altimeter data for snow and sea ice observations in 3D over the Weddell Sea. Across the Ross Sea, IcePOD and AntNZ/York-University flights were carried out together with satellite SAR data acquisitions

Systems-level organization of yeast methylotrophic lifestyle

BACKGROUND: Some yeasts have evolved a methylotrophic lifestyle enabling them to utilize the single carbon compound methanol as a carbon and energy source. Among them, Pichia pastoris (syn. Komagataella sp.) is frequently used for the production of heterologous proteins and also serves as a model organism for organelle research. Our current knowledge of methylotrophic lifestyle mainly derives from sophisticated biochemical studies which identified many key methanol utilization enzymes such as alcohol oxidase and dihydroxyacetone synthase and their localization to the peroxisomes. C1 assimilation is supposed to involve the pentose phosphate pathway, but details of these reactions are not known to date. RESULTS: In this work we analyzed the regulation patterns of 5,354 genes, 575 proteins, 141 metabolites, and fluxes through 39 reactions of P. pastoris comparing growth on glucose and on a methanol/glycerol mixed medium, respectively. Contrary to previous assumptions, we found that the entire methanol assimilation pathway is localized to peroxisomes rather than employing part of the cytosolic pentose phosphate pathway for xylulose-5-phosphate regeneration. For this purpose, P. pastoris (and presumably also other methylotrophic yeasts) have evolved a duplicated methanol inducible enzyme set targeted to peroxisomes. This compartmentalized cyclic C1 assimilation process termed xylose-monophosphate cycle resembles the principle of the Calvin cycle and uses sedoheptulose-1,7-bisphosphate as intermediate. The strong induction of alcohol oxidase, dihydroxyacetone synthase, formaldehyde and formate dehydrogenase, and catalase leads to high demand of their cofactors riboflavin, thiamine, nicotinamide, and heme, respectively, which is reflected in strong up-regulation of the respective synthesis pathways on methanol. Methanol-grown cells have a higher protein but lower free amino acid content, which can be attributed to the high drain towards methanol metabolic enzymes and their cofactors. In context with up-regulation of many amino acid biosynthesis genes or proteins, this visualizes an increased flux towards amino acid and protein synthesis which is reflected also in increased levels of transcripts and/or proteins related to ribosome biogenesis and translation. CONCLUSIONS: Taken together, our work illustrates how concerted interpretation of multiple levels of systems biology data can contribute to elucidation of yet unknown cellular pathways and revolutionize our understanding of cellular biology. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12915-015-0186-5) contains supplementary material, which is available to authorized users

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy

We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principle calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI. Supplemental material in the ancillary file