Development of a quick, robust and chemically-defined differentiation protocol from human induced pluripotent stem cells towards cortical neurons to phenotype Alzheimer’s Disease

In an aging world, neurodegenerative diseases, such as Alzheimer’s Diseases start to appear more and more in society. Unfortunately, only drugs ameliorating the symptoms, but no preventive or curative medications are available. One underlying reason is that only animal models exist that do not fully reflect the human pathophysiology, leading to the difficulty of translating findings into humans. Therefore, it is of great importance to access an authentic in vitro cell culture system to study disease. Such a cell culture system would also have the potential to be used in later stages of drug discovery and drug development. Here, a quick, robust and chemically-defined xeno-free differentiation protocol was developed to obtain a human induced pluripotent stem cell (hiPSC)-derived cortical neuron cell culture system. Several factors influencing variability of differentiation were addressed and identified, leading to faster generation of cells, greater robustness and wide applicability among different hiPSC lines. Further, it was shown that the derived culture system is suitable for disease modeling in Alzheimer’s Disease as the Aβ-pathology could be recapitulated in the cells, already at a very early time point of differentiation. The established differentiation protocol is a promising tool in disease modeling of Alzheimer’s Disease and other tauopathies, without the need of animal-derived cell culture supplements and reagents

The Anaphase-Promoting Complex (APC) ubiquitin ligase affects chemosensory behavior in \u3cem\u3eC. elegans\u3c/em\u3e

The regulation of fundamental aspects of neurobiological function has been linked to the ubiquitin signaling system (USS), which regulates the degradation and activity of proteins and is catalyzed by E1, E2, and E3 enzymes. The Anaphase-Promoting Complex (APC) is a multi-subunit E3 ubiquitin ligase that controls diverse developmental and signaling processes in post-mitotic neurons; however, potential roles for the APC in sensory function have yet to be explored. In this study, we examined the effect of the APC ubiquitin ligase on chemosensation in Caenorhabditis elegans by testing chemotaxis to the volatile odorants, diacetyl, pyrazine, and isoamyl alcohol, to which wild-type worms are attracted. Animals with loss of function mutations in either of two alleles (g48 and ye143) of the gene encoding the APC subunit EMB-27 APC6 showed increased chemotaxis towards diacetyl and pyrazine, odorants sensed by AWA neurons, but exhibited normal chemotaxis to isoamyl alcohol, which is sensed by AWC neurons. The statistically significant increase in chemotaxis in the emb-27 APC6 mutants suggests that the APC inhibits AWA-mediated chemosensation in C. elegans. Increased chemotaxis to pyrazine was also seen with mutants lacking another essential APC subunit, MAT-2 APC1; however, mat-2 APC1 mutants exhibited wild type responses to diacetyl. The difference in responsiveness of these two APC subunit mutants may be due to differential strength of these hypomorphic alleles or may indicate the presence of functional sub-complexes of the APC at work in this process. These findings are the first evidence for APC-mediated regulation of chemosensation and lay the groundwork for further studies aimed at identifying the expression levels, function, and targets of the APC in specific sensory neurons. Because of the similarity between human and C. elegans nervous systems, the role of the APC in sensory neurons may also advance our understanding of human sensory function and disease

Experience of Environmental Education using Responsible Research and Innovation of the Pontifical Catholic University of Paraná in the European Project Engage

This study investigates how the research group Pedagogical Practice in Distance Learning: Innovative Methodologies and Learning Resources PRAPETEC – of the Pontifical Catholic University of Paraná (PUCPR) in partnership with the European project Engage, promoted activities with high school students and to develop new strategies for equipping students to apply scientific knowledge and to develop RRI (Responsible Research and Innovation) research skills during the year 2015. The European project Engage (engagementingscience.eu) aims to increase awareness of Responsible Research and Innovation (RRI). PUCPR in partnership with the Engage project carried out a series of activities, which promoted environmental education involving Agrobiodiversity – Transgenics, through Open Educational Resources (OER) and co-creation. In this context, teachers play an important role in making environmental education more relevant to students' concerns, which are known to be forward-looking. This can increase the likelihood that students can apply what they have learned out of school and respond to social challenges

Thermochemistry of Protective Coatings and Molten Silicate Debris

The durability of gas-turbine engine components can be significantly affected by the ingestion of siliceous particles, which can melt at high temperature and corrode protective coatings that are essential for long life requirements. The silicate debris consists mainly of CaO-MgO-Al2O3-SiO2 (CMAS) and is usually ingested by aircraft engines during and after take-off, sticking to their hot surfaces and resulting in the formation of calcium rare-earth silicate oxyapatites. The thermochemistry of coatings and their reaction products with molten silicate debris are crucial to understand in order to improve the durability of gas-turbine engines. Here we discuss results of high temperature drop solution calorimetry, drop-and-catch calorimetry (DnC) and differential thermal analysis (DTA) techniques for the thermodynamic properties of both thermal barrier coatings (TBCs) and environmental barrier coatings (EBCs) and their reaction with CMAS compositions. The enthalpies of solution of Y2Si2O7, Yb2Si2O7, 31YSZ, and 16RESZ based coatings and the oxyapatite are moderately positive. However, oxyapatite formation is only favorable over coating dissolution in terms of enthalpy for 7YSZ. The enthalpies of mixing between the coatings and the molten silicate are less exothermic for Yb2Si2O7 and CaYb4Si3O13 than for 7YSZ, indicating lower energetic stability of the latter against molten silicate corrosion. We also report for the first time the calorimetric measurements of the enthalpies of formation of rare-earth silicate based EBC coatings and oxyapatites (rare-earth, RE = Y, Yb, Gd, Dy, Er, Nd and Sm)

Foci, gaps, and desiderata of documentary research on and in schools. (Intermediate) conclusion and perspectives for further development of the research field

Dieser den Band abschließende Beitrag setzt sich zum Ziel, über Selbstbeobachtungen sowie Fremdbeobachtungen des Forschungsdiskurses in der Würdigung der Potenziale vorliegender Studien einige identifizierte Leerstellen und Desiderate sichtbar zu machen. Dies mündet in zehn Thesen, die in ihrer Relation von gegenstandsbezogenen und methodisch-methodologischen Aspekten Perspektivangebote zur Weiterentwicklung einer Dokumentarischen Schulforschung bieten. (DIPF/Orig.)This concluding contribution of the book aims to make visible some identified gaps and desired outcomes through self-observations and observations of the research discourse in assessing the potential of existing studies. This results in ten theses, which offer perspectives for the further development of documentary school research in their relation to subject-related and methodological-methodical aspects. (DIPF/Orig.

Documentary research on and in schools. Providing an introductory framework for a strand of research

Mit der Einleitung zum Sammelband ist eine dreifache Zielsetzung verbunden. Erstens soll sie in das Themenfeld einer Dokumentarischen Schulforschung einführen. Diese mit der Dokumentarischen Methode operierende Forschungsrichtung stellt eine spezifische Form der qualitativ-rekonstruktiven Erforschung von Schule bzw. des Schulischen dar, in der das Wechselverhältnis von gegenstandsbezogener Erkenntnisgewinnung und Methode sowie Methodologie reflexiv in den Blick genommen wird. Spezifizierend wird in drei Schwerpunkte Dokumentarischer Schulforschung – Forschung zu Schulentwicklung, zu Schulkultur und zu Schule als Organisation – eingeführt. Zweitens soll die Einleitung jenen Projektkontext umreißen, innerhalb dessen die vorgelegte Konzeption Dokumentarischer Schulforschung entstanden ist, d. h. das DFG-geförderte Netzwerk Dokumentarische Schulforschung (NeDoS). Drittens werden die Struktur des Bandes sowie die einzelnen Beiträge vorgestellt. (DIPF/Orig.)The introduction of the present volume has three main objectives: First, the topic of documentary research on and in schools is introduced. This field of research represents a specific form of qualitative-reconstructive research on schools and schooling in which the relationship between object-related knowledge acquisition and the use of the Documentary Method as both a method and a methodology is reflexively examined. Specifically, three subdivisions of documentary research on and in schools are presented: research on school development, research on school culture, and research on school as an organization. Second, the introduction outlines the project context within which the presented conception of documentary research on and in schools was developed – that is, the Network of Documentary Research on and in Schools (NeDoS), which is funded by the German Research Association. Third, the structure of the present volume and its articles is presented. (DIPF/Orig.

Detected fluctuations in SDSS LRG magnitudes: Bulk flow signature or systematic?

In this paper we search for a signature of a large scale bulk flow by looking for fluctuations in the magnitudes of distant LRGs. We take a sample of LRGs from the Sloan Digital Sky Survey with redshifts of z>0.08 over a contiguous area of sky. Neighboring LRG magnitudes are averaged together to find the fluctuation in magnitudes as a function of R.A.. The result is a fluctuation of a few percent in flux across roughly 100 degrees. The source of this fluctuation could be from a large scale bulk flow or a systematic in our treatment of the data set, or the data set itself. A bulk flow model is fitted to the observed fluctuation, and the three bulk flow parameters, its direction and magnitude: alpha_b, delta_b, v_b are constrained. We find that the bulk flow direction is consistent with the direction found by other authors, with alpha_b 180, delta_b -50. The bulk flow magnitude however was found to be anomalously large with v_b>4000km/s. The LRG angular selection function cannot be sufficiently taken into account in our analysis with the available data, and may be the source of either the anomalous magnitude of the bulk flow signal, or possibly the entire fluctuation. However, the fluctuation indicates a bulk flow direction very close to those found using other data sets and analyses. Further investigation with upcoming data is required to confirm this detection.Comment: 10 pages, 7 figures, 1 table. V2: citations added to the introduction and a paragraph to the discussion. V3: Accepted by MNRAS. 1 figure, additional clarifications, discussion and references adde

Bottom-up effects of plant diversity on multitrophic interactions in a biodiversity experiment

Biodiversity is rapidly declining1, and this may negatively affect ecosystem processes, including economically important ecosystem services. Previous studies have shown that biodiversity has positive effects on organisms and processes4 across trophic levels. However, only a few studies have so far incorporated an explicit food-web perspective. In an eight-year biodiversity experiment, we studied an unprecedented range of above- and below-ground organisms and multitrophic interactions. A multitrophic data set originating from a single long-term experiment allows mechanistic insights that would not be gained from meta-analysis of different experiments. Here we show that plant diversity effects dampen with increasing trophic level and degree of omnivory. This was true both for abundance and species richness of organisms. Furthermore, we present comprehensive above-ground/below-ground biodiversity food webs. Both above ground and below ground, herbivores responded more strongly to changes in plant diversity than did carnivores or omnivores. Density and richness of carnivorous taxa was independent of vegetation structure. Below-ground responses to plant diversity were consistently weaker than above-ground responses. Responses to increasing plant diversity were generally positive, but were negative for biological invasion, pathogen infestation and hyperparasitism. Our results suggest that plant diversity has strong bottom-up effects on multitrophic interaction networks, with particularly strong effects on lower trophic levels. Effects on higher trophic levels are indirectly mediated through bottom-up trophic cascades