Of mice and motion : Behavioural-EEG phenotyping of Alzheimer’s disease mouse models

This work was supported by the Alzheimer’s Society [project grant number AS-PG-14-039] to BP and GR.Peer reviewedPostprin

Prüfung und Entwicklung von Sojabohnenzuchtmaterial für die Fütterung mit dem Ziel der Implementierung mittelständischer Züchtungsaktivitäten unter besonderer Berücksichtigung der Merkmale Frühzeitigkeit, Kältetoleranz und Proteinertrag

Mit dem Vorhaben soll im Rahmen der Eiweißstrategie des BMEL durch die Stärkung der Züchtungswirtschaft eine Ausweitung und Verbesserung des Sojabohnenanbaus und damit der Produktion von gentechnikfreiem, heimischem Eiweißfutter unterstützt werden. An der Landesanstalt wird ein Soja-Zuchtprogramm neu aufgebaut. Im Verbund mit privaten bayerischen Züchtungsunternehmen werden Methoden zur Selektion von Zuchtstämmen bezüglich der Merkmale Frühreife, Kornertrag, Proteinertrag und Kältetoleranz entwickelt, sowie die Grundlage für eine markergestützte Selektion geschaffen. In den drei Vegetationsperioden (2015-2017) wurden aus über zwölftausend Kreuzungsnachkommen interessante Zuchtstämme selektiert und in einer Leistungsprüfung mit aktuellen Sorten in Ertrag, Proteingehalt und Abreife verglichen. Dabei konnten mehrere Zuchtstämme identifiziert werden, die bei hohem Ertrag früher abreifen als aktuelle Vergleichssorten bzw. höhere Proteinerträge liefern. Das entwickelte Zuchtmaterial fand Eingang in die Zuchtprogramme bei den privaten Verbundpartnern und wird auf die Sortenzulassung vorbereitet. Die molekulargenetischen Analysen auf der Basis von 6000 SNP-Markern zeigten eine nur geringe genetische Diversität im aktuell genutzten Sortenpanel. Die in Clusteranalysen nachgewiesene große genetische Diversität in weltweiten Genbankakzessionen kann als wertvoller Genpool für die Züchtung genutzt werden. Die aufwändige phänotypische Selektion soll langfristig durch molekulare Marker effizienter gestaltet werden. Der erste Schritt wurde mit der Etablierung und Anwendung publizierter Marker für die Merkmale Blüte und Reife gemacht

Alternative Geometries for 3D Bioprinting of Calcium Phosphate Cement as Bone Substitute

In the literature, many studies have described the 3D printing of ceramic-based scaffolds (e.g., printing with calcium phosphate cement) in the form of linear structures with layer rotations of 90°, although no right angles can be found in the human body. Therefore, this work focuses on the adaptation of biological shapes, including a layer rotation of only 1°. Sample shapes were printed with calcium phosphate cement using a 3D Bioplotter from EnvisionTec. Both straight and wavy spokes were printed in a round structure with 12 layers. Depending on the strand diameter (200 and 250 µm needle inner diameter) and strand arrangement, maximum failure loads of 444.86 ± 169.39 N for samples without subsequent setting in PBS up to 1280.88 ± 538.66 N after setting in PBS could be achieved

The atypical kinase RIOK1 promotes tumor growth and invasive behavior

Despite being overexpressed in different tumor entities, RIO kinases are hardly characterized in mammalian cells. We investigated the role of these atypical kinases in different cancer cells. Using isogenic colon-, breast- and lung cancer cell lines, we demonstrate that knockdown of RIOK1, but not of RIOK2 or RIOK3, strongly impairs proliferation and invasiveness in conventional and 3D culture systems. Interestingly, these effects were mainly observed in RAS mutant cancer cells. In contrast, growth of RAS wildtype Caco-2 and Bcr-Abl-driven K562 cells is not affected by RIOK1 knockdown, suggesting a specific requirement for RIOK1 in the context of oncogenic RAS signaling. Furthermore, we show that RIOK1 activates NF-κB signaling and promotes cell cycle progression. Using proteomics, we identified the pro-invasive proteins Metadherin and Stathmin1 to be regulated by RIOK1. Additionally, we demonstrate that RIOK1 promotes lung colonization in vivo and that RIOK1 is overexpressed in different subtypes of human lung- and breast cancer. Altogether, our data suggest RIOK1 as a potential therapeutic target, especially in RAS-driven cancers

A survey and classification of software-defined storage systems

The exponential growth of digital information is imposing increasing scale and efficiency demands on modern storage infrastructures. As infrastructure complexity increases, so does the difficulty in ensuring quality of service, maintainability, and resource fairness, raising unprecedented performance, scalability, and programmability challenges. Software-Defined Storage (SDS) addresses these challenges by cleanly disentangling control and data flows, easing management, and improving control functionality of conventional storage systems. Despite its momentum in the research community, many aspects of the paradigm are still unclear, undefined, and unexplored, leading to misunderstandings that hamper the research and development of novel SDS technologies. In this article, we present an in-depth study of SDS systems, providing a thorough description and categorization of each plane of functionality. Further, we propose a taxonomy and classification of existing SDS solutions according to different criteria. Finally, we provide key insights about the paradigm and discuss potential future research directions for the field.This work was financed by the Portuguese funding agency FCT-Fundacao para a Ciencia e a Tecnologia through national funds, the PhD grant SFRH/BD/146059/2019, the project ThreatAdapt (FCT-FNR/0002/2018), the LASIGE Research Unit (UIDB/00408/2020), and cofunded by the FEDER, where applicable

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

First-Time Users of ADHD Medication Among Children and Adolescents in Germany: An Evaluation of Adherence to Prescribing Guidelines Based on Claims Data

BACKGROUND: Drug utilization studies based on real-world data are vital for the identification of potentially needed improvements to rational prescribing. This is particularly important for the pharmacological treatment of children and adolescents with attention-deficit hyperactivity disorder (ADHD) due to the associated potential side effects and the frequent use. Whereas prevalent use is well-characterized, studies on first-time use of ADHD medication are scarce. This study aimed to evaluate off-label prescribing in first-time users of ADHD medication among children and adolescents in Germany based on three criteria: (i) lack of a documented ADHD diagnosis; (ii) first-time pharmacological treatment with a second-line drug; and (iii) patient age below 6 years. METHODS: Based on German claims data, we included children and adolescents aged 0–17 years with a first-time dispensation of any ADHD medication in the period 2015–2017. These first-time users were characterized with regard to sex, age, specialty of the prescribing physician, documentation of an ADHD diagnosis, psychiatric hospitalization, psychiatric comorbidities, and history of other psychopharmacological drugs at first-time use. RESULTS: The study population comprised 18,703 pediatric first-time users of ADHD medication. Of these, 9.8% had no documented ADHD diagnosis. Most of the ADHD drug users received first-line ADHD pharmacotherapy (methylphenidate, atomoxetine), whereas 2.6% were prescribed second-line ADHD medication (lisdexamfetamine, guanfacine, dexamfetamine, multiple ADHD drugs) as first drug. Overall, 1.2% of first-time users were aged below 6 years. A total of 12.7% of the study population met any off-label criterion. CONCLUSIONS: About 13% of pediatric first-time users of ADHD medication in Germany received an off-label pharmacotherapy at first-time use. Prescribing ADHD medication without a confirmed ADHD diagnosis was the most common of the three assessed off-label criteria. Off-label prescribing regarding drug choice and age of patients only occurred in a small percentage of initial pharmacological ADHD treatment. Our results suggest the need for improvement in rational prescribing, especially with regard to diagnostic requirements

Predictors for Receiving Medication and/or Psychotherapy in Children Newly Diagnosed With ADHD: A Longitudinal Population-Based Cohort Study

OBJECTIVE: The aim of this study is to identify characteristics predicting the use of medication and/or psychotherapy after a first ADHD diagnosis. METHOD: This cohort study was based on German claims data including 12,250 treatment-naïve children aged 5 to 12 years with an incident ADHD diagnosis in 2010. Logistic regression models were used to estimate associations between children’s characteristics at first diagnosis and the chosen treatment within the following 5 years. RESULTS: Medication use was associated with male sex, an ADHD diagnosis “with hyperactivity,” comorbid depression, and comorbid developmental and conduct disorders. Male sex and comorbid neurotic and somatoform, conduct, and emotional disorders were associated with psychotherapy only. Receiving both treatments—instead of medication only—was associated with comorbid depression, neurotic and somatoform, conduct, and emotional disorders. CONCLUSION: In case of equal access to both treatment options, patients, for example, with externalizing symptoms were more prone to receive medication and/or psychotherapy than the average child diagnosed with ADHD

Influence of 3D Printing Parameters on the Mechanical Stability of PCL Scaffolds and the Proliferation Behavior of Bone Cells

Introduction The use of scaffolds in tissue engineering is becoming increasingly important as solutions need to be found for the problem of preserving human tissue, such as bone or cartilage. In this work, scaffolds were printed from the biomaterial known as polycaprolactone (PCL) on a 3D Bioplotter. Both the external and internal geometry were varied to investigate their influence on mechanical stability and biocompatibility. Materials and Methods: An Envisiontec 3D Bioplotter was used to fabricate the scaffolds. First, square scaffolds were printed with variations in the strand width and strand spacing. Then, the filling structure was varied: either lines, waves, and honeycombs were used. This was followed by variation in the outer shape, produced as either a square, hexagon, octagon, or circle. Finally, the internal and external geometry was varied. To improve interaction with the cells, the printed PCL scaffolds were coated with type-I collagen. MG-63 cells were then cultured on the scaffolds and various tests were performed to investigate the biocompatibility of the scaffolds. Results: With increasing strand thickness and strand spacing, the compressive strengths decreased from 86.18 + 2.34 MPa (200 µm) to 46.38 + 0.52 MPa (600 µm). The circle was the outer shape with the highest compressive strength of 76.07 + 1.49 MPa, compared to the octagon, which had the lowest value of 52.96 ± 0.98 MPa. Varying the external shape (toward roundness) geometry, as well as the filling configuration, resulted in the highest values of compressive strength for the round specimens with honeycomb filling, which had a value of 91.4 + 1.4 MPa. In the biocompatibility tests, the round specimens with honeycomb filling also showed the highest cell count per mm2, with 1591 ± 239 live cells/mm2 after 10 days and the highest value in cell proliferation, but with minimal cytotoxic effects (9.19 ± 2.47% after 3 days)