Eltern-Kind-Interaktionen mit Bilderbüchern und / oder Tablet PC?

Mit der zunehmenden Mediatisierung unserer Gesellschaft wird auch die Gruppe der 1-3 Jährigen als Zielgruppe für digitale Mediennutzung (Tablet-PCs, Smart-Phones etc.) entdeckt. Im Beitrag werden bestehende Studien zur Nutzung und insbesondere zur Qualität der Nutzung von e-books und Tablet PCs und deren Einfluss auf die Entwicklung von Fähigkeiten der „Literacy“ vorgestellt und diskutiert. Im anglo-amerikanischen / kanadischen Raum konnte in verschiedenen Studien festgestellt werden, dass Eltern auch mit Kindern der jüngeren Altersgruppe bereits digitale Medien nutzen. Für die Erstellung von e-books wurden bereits Leitlinien zu „best practice“ entwickelt. Darüber hinaus finden sich in Studien zum Leseverhalten mit e-books kontroverse Forschungsergebnisse. In einigen Studien konnte festgestellt werden, dass es zwar zu einem unterschiedlichen Leseverhalten bei e-books, insbesondere bei „enhanced e-books“ und klassischen Bilderbüchern kommt, dass aber bezogen auf den Erwerb verschiedener Aspekte der Literacy keine Unterschiede zu erwarten sind, bzw. dass sogar bei „enhanced e-books“ ein besseres Geschichtenverständnis erreicht werden kann und mehr Informationen zum Verhältnis Schrift - Sprache für die Kinder vermittelt wird. Im Gegensatz dazu konnte in anderen Studien festgestellt werden, dass gerade die übermäßige Verwendung von „hotspots“ in „enhanced e-books“ dazu führen kann, dass ein Verständnis der gesamten Geschichte bei den Kindern erschwert wird und dass das gemeinsame Lesen gegenüber der Aufmerksamkeit auf Spiele und andere Ablenker verloren geht. So scheint die Qualität der verwendeten e-books einen erheblichen Einfluss auf die zu erwartenden Ergebnisse zu haben. Im Beitrag wird das Nutzungsverhalten und die Qualität der angebotenen Medien (Apps, e-books...) auch im deutschsprachigen Raum, insbesondere für die Zielgruppe der 1-3jährgen diskutiert

A mechanistic model for the negative binomial distribution of single-cell mRNA counts

Amrhein L, Harsha K, Fuchs C. A mechanistic model for the negative binomial distribution of single-cell mRNA counts. bioRxiv. 2019.SummarySeveral tools analyze the outcome of single-cell RNA-seq experiments, and they often assume a probability distribution for the observed sequencing counts. It is an open question of which is the most appropriate discrete distribution, not only in terms of model estimation, but also regarding interpretability, complexity and biological plausibility of inherent assumptions. To address the question of interpretability, we investigate mechanistic transcription and degradation models underlying commonly used discrete probability distributions. Known bottom-up approaches infer steady-state probability distributions such as Poisson or Poisson-beta distributions from different underlying transcription-degradation models. By turning this procedure upside down, we show how to infer a corresponding biological model from a given probability distribution, here the negative binomial distribution. Realistic mechanistic models underlying this distributional assumption are unknown so far. Our results indicate that the negative binomial distribution arises as steady-state distribution from a mechanistic model that produces mRNA molecules in bursts. We empirically show that it provides a convenient trade-off between computational complexity and biological simplicity.Graphical Abstract</jats:sec

PRAS40 and TSC2 regulate apoptosis during early development of embryoid bodies via mTOR

Zurzeit sind chemotherapeutische oder operative Therapie bei Krebs die häufigsten Behandlungsarten und nur selten existieren Therapien für humangenetische Erkrankungen. Deshalb suchen Wissenschafter nach neuen Methoden und legen dabei ihr Augenmerk auf die Stammzellforschung, welche in den letzten Jahren wesentliche Fortschritte gemacht hat. Embryonale Stammzellen besitzen einerseits das Potential in alle drei Keimblätter zu differenzieren und haben eine hohe Proliferationsrate. Neben den ethischen Bedenken besteht auch noch das Risiko einer Tumorentstehung. Andererseits existieren adulte Stammzellen aus den unterschiedlichsten Geweben, welche aber nur begrenzte Proliferationsrate und Differenzierungspotential besitzen. Mit der Entdeckung von Stammzellen in humanem Fruchtwasser im Jahre 2003 wurde frischer Wind in das Gebiet rund um die Stammzellforschung gebracht, da diese Zellen in viele Zellarten der drei Keimblätter differenzieren können, hohe Proliferationsraten haben und keine Teratome formen. Der mTOR Signalweg spielt eine wichtige Rolle bei Zellwachstum, Zellzyklusregulation, Translation, Apoptose, Energie- und Nährstoffhaushalt. Darüber hinaus ist dieser in vielen Krebsarten und genetischen Erkrankungen dereguliert. Ein wesentlicher Regulator des mTOR Signalwegs ist TSC2, das gemeinsam mit TSC1 einen Komplex bildet. Eine Mutation in einem der beiden Gene löst Tuberöse Hirnsklerose aus, eine humangenetische Erkrankung, die 1 von 6000 Geburten betrifft. Im Jahre 2003 wurde ein weiterer Regulator von mTORC1 identifiziert – PRAS40, welcher in manchen Krebserkrankungen dereguliert ist und eine mögliche Rolle bei Diabetes spielt. Wir konnten beweisen, dass es möglich ist, embryoid bodies aus Fruchtwasserstammzellen zu formieren und dass dieser Vorgang mTOR-abhängig ist. Zweitens dazu imstande sind sich in renale Strukturen zu integrieren und dort zu differenzieren. Das Ziel dieses Projekts war es, die Rolle der zwei wichtigsten Regulatoren von mTORC1 – PRAS40 und TSC2 – in der früher embryonalen Entwicklung, anhand von embryoid bodies aus humanen Fruchtwasserstammzellen, zu studieren. Der Knockdown von PRAS40 und TSC2 löste massive Apoptose aus, welche durch den chemischen mTOR Inhibitor Rapamycin nicht verhindert werden konnte. Allerdings konnte diese aber durch den Knockdown von mTOR revertiert werden. Dies brachte uns zur Erkenntnis dass a) PRAS40 und TSC2 wesentliche anti-apoptotische Schlüsselmoleküle in der frühen embryonalen Entwicklung sind und b) diese Regulation von Rapamycin-insensitiven Funktionen mTORs abhängt.To date the current available treatments are chemotherapy and surgery in cancer and only seldomly treatments or cures for human genetic diseases exist. Therefore scientists are seeking for new methods of therapy and many focus their research on stem cells and possible stem cell therapy as major advances were made in the recent years. On the one hand embryonic stem cells harbor the potential to differentiate into lineages of the three germ layers and are rapidly proliferating. However, besides the ethical concerns, they have the risk of teratoma formation in SCID mice. On the other hand adult stem cells derived from various tissues, have limited proliferation capacity and differentiation potential. In 2003 the discovery of stem cells in the human amniotic fluid (hAFS cells) smartened up the field of stem cell biology as these cells can differentiate into cells of the three germ layers, are highly proliferative and do not harbor the risk of teratoma formation. The mTOR pathway plays a critical role in cell growth, cell cycle regulation, translation, apoptosis, energy and nutrient sensing. Furthermore it is deregulated in many cancers and human genetic diseases. One major regulator of the mTOR pathway is TSC2, encoding tuberin, which forms a complex with TSC1 and mutation in either one gene causes tuberous sclerosis (TSC), a human genetic disease affecting 1:6000 births. In 2003 a novel negative regulator of mTORC1 was identified – the proline rich AKT substrate of 40kDa (PRAS40), which was found to be deregulated in some cancers and has a possible role in diabetes. We proved that hAFS cells are able to form embryoid bodies and that this is dependent on mTOR. Secondly, we showed that these cells were capable of integrating and differentiating into renal structures. The major aim of this thesis was to study the role of the two major regulators of mTORC1 – TSC2 and PRAS40 – in development using hAFS cells derived embryoid bodies to recapitulate early embryonic development. Knockdown of PRAS40 and TSC2 led to increased apoptosis in embryoid bodies, which could not be rescued by the mTORC1 inhibitor rapamycin; however it was possible to revert this effect by knocking down mTOR. This led us to the conclusion that a) PRAS40 and TSC2 are major anti-apoptotic gatekeepers in early development and b) this regulation depends on rapamycin- insensitive functions of mTOR

Queerfeindlichkeit in der Wissenschaft

Debatten um eine gleichberechtigte Anerkennung aller Lebens- und Geschlechterverhältnisse werden nicht nur im gesellschaftspolitischen Raum geführt. Auch in der Wissenschaft ist dieses Themenfeld umkämpft. Wissenschaftliche Forschung kann wohl zur Emanzipation beitragen und den Abbau von Diskriminierungen unterstützen. Gleichwohl gibt es aber auch in der Wissenschaft queerfeindliche Tendenzen, die in die Gesellschaft hineinwirken. Christiane Fuchs stellt dazu einige Beispiele vor

Effective treatment of the wastewater from ceramic industry using ceramic membranes

Emissions of organic compounds, heavy metals and chemicals used in the ceramic industry cause significant organic and inorganic pollution of water. The effluent must be treated before it is discharged into a water body. International and EU laws control the chemical oxygen demand (COD) of the wastewater. Conventional technologies, such as sedimentation, flocculation and biological treatment, have lots of drawbacks, whereas membrane technologies give many benefits, as they are chemical-free and allow a reduction of the treatment steps. One-step wastewater nanofiltration with ceramic membranes of 450 Da cut-off is able to reduce the COD of ceramic wastewater to a sufficient level. However, the working time without cleaning is limited and the rejection of membranes can be significantly reduced due to fouling. Multistage filtration can be the solution. Filtration experiments with various combinations (MF, UF and NF) of ceramic membranes were performed at a laboratory scale with single-channel membranes and at pilot scale with 7-, 19- and 151-channel membranes in order to permanently reach the limit value of a COD below 80 mg/L and to increase the operating time. Four types of membranes were sequentially tested in the cross-flow mode: MF (200 nm pore size), UF (2,000 Da), NF (450 Da) and NF (200 Da). 5-day Biological Oxygen Demand (BOD) tests were performed in order to examine the wastewater biodegradability. The test results with single-channel membranes showed that in terms of the highest COD rejection and the highest permeability, the best combination was that of MF and UF membranes. Here, UF membranes were sufficient to reach the limit values. As for the multi-channel membranes, the combination of MF and NF (450 Da) was the best and the final COD concentration ranged from 11 to 48 mg/L. 5-day BOD bottle tests showed a COD/BOD ratio of 3.8, which opened up possibilities for combined treatment

Présentation

La notion de thématisation, couramment utilisée depuis quelques années en linguistique dans le cadre de théories fort diverses (Pragmatique, Perspective fonctionnelle et Linguistique textuelle surtout, Grammaire générative, Typologie, Théorie des opérations énonciatives), a été définie et utilisée sur des bases conceptuelles fort différentes et à des fins diverses et partiellement hétérogènes. Aussi n’est-il pas d’année où ne paraisse un article qui tente, une fois de plus, de définir cette n..

Cross-species evaluation of fibroblast activation protein alpha as potential imaging target for soft tissue sarcoma: a comparative immunohistochemical study in humans, dogs, and cats

INTRODUCTION: Complete surgical tumor resection is paramount in the management of soft tissue sarcoma (STS) in humans, dogs, and cats alike. Near-infrared targeted tracers for fluorescence-guided surgery (FGS) could facilitate intraoperative visualization of the tumor and improve resection accuracy. Target identification is complicated in STS due to the rarity and heterogeneity of the disease. This study aims to validate the expression of fibroblast activation protein alpha (FAP) in selected human, canine, and feline STS subtypes to assess the value of FAP as a target for FGS and to validate companion animals as a translational model. METHODS: Formalin-fixed and paraffin-embedded tissue samples from 53 canine STSs (perivascular wall tumor (PWT), canine fibrosarcoma (cFS), and STS not further specified (NOS)), 24 feline fibrosarcomas, and 39 human STSs (myxofibrosarcoma, undifferentiated pleomorphic sarcoma, dermatofibrosarcoma protuberans, and malignant peripheral nerve sheath tumor) as well as six canine and seven feline healthy controls and 10 inflamed tissue samples were immunohistochemically stained for their FAP expression. FAP labeling in tumor, peritumoral, healthy skin, and inflamed tissue samples was quantified using a visually assessed semiquantitative expression score and digital image analysis. Target selection criteria (TASC) scoring was subsequently performed as previously described. RESULTS: Eighty-five percent (85%) of human (33/39), 76% of canine (40/53), and 92% of feline (22/24) STSs showed FAP positivity in over 10% of the tumor cells. A high expression was determined in 53% canine (28/53), 67% feline (16/24), and 44% human STSs (17/39). The average FAP-labeled area of canine, feline, and human STSs was 31%, 33%, and 42%, respectively (p > 0.8990). The FAP-positive tumor area was larger in STS compared to healthy and peritumoral tissue samples (p < 0.0001). TASC scores were above 18 for all feline and human STS subtypes and canine PWTs but not for canine STS NOS and cFS. CONCLUSION: This study represents the first cross-species target evaluation of FAP for STS. Our results demonstrate that FAP expression is increased in various STS subtypes compared to non-cancerous tissues across species, thereby validating dogs and cats as suitable animal models. Based on a TASC score, FAP could be considered a target for FGS

The Importance of Biophysical and Biochemical Stimuli in Dynamic Skeletal Muscle Models

Classical approaches to engineer skeletal muscle tissue based on current regenerative and surgical procedures still do not meet the desired outcome for patient applications. Besides the evident need to create functional skeletal muscle tissue for the repair of volumetric muscle defects, there is also growing demand for platforms to study muscle-related diseases, such as muscular dystrophies or sarcopenia. Currently, numerous studies exist that have employed a variety of biomaterials, cell types and strategies for maturation of skeletal muscle tissue in 2D and 3D environments. However, researchers are just at the beginning of understanding the impact of different culture settings and their biochemical (growth factors and chemical changes) and biophysical cues (mechanical properties) on myogenesis. With this review we intend to emphasize the need for new in vitro skeletal muscle (disease) models to better recapitulate important structural and functional aspects of muscle development. We highlight the importance of choosing appropriate system components, e.g., cell and biomaterial type, structural and mechanical matrix properties or culture format, and how understanding their interplay will enable researchers to create optimized platforms to investigate myogenesis in healthy and diseased tissue. Thus, we aim to deliver guidelines for experimental designs to allow estimation of the potential influence of the selected skeletal muscle tissue engineering setup on the myogenic outcome prior to their implementation. Moreover, we offer a workflow to facilitate identifying and selecting different analytical tools to demonstrate the successful creation of functional skeletal muscle tissue. Ultimately, a refinement of existing strategies will lead to further progression in understanding important aspects of muscle diseases, muscle aging and muscle regeneration to improve quality of life of patients and enable the establishment of new treatment options