Tumorigenic WAP-T Mouse Mammary Carcinoma Cells: A Model for a Self-Reproducing Homeostatic Cancer Cell System

BACKGROUND: In analogy to normal stem cell differentiation, the current cancer stem cell (CSC) model presumes a hierarchical organization and an irreversible differentiation in tumor tissue. Accordingly, CSCs should comprise only a small subset of the tumor cells, which feeds tumor growth. However, some recent findings raised doubts on the general applicability of the CSC model and asked for its refinement. METHODOLOGY/PRINCIPAL FINDINGS: In this study we analyzed the CSC properties of mammary carcinoma cells derived from transgenic (WAP-T) mice. We established a highly tumorigenic WAP-T cell line (G-2 cells) that displays stem-like traits. G-2 cells, as well as their clonal derivates, are closely related to primary tumors regarding histology and gene expression profiles, and reflect heterogeneity regarding their differentiation states. G-2 cultures comprise cell populations in distinct differentiation states identified by co-expression of cytoskeletal proteins (cytokeratins and vimentin), a combination of cell surface markers and a set of transcription factors. Cellular subsets sorted according to expression of CD24a, CD49f, CD61, Epcam, Sca1, and Thy1 cell surface proteins, or metabolic markers (e.g. ALDH activity) are competent to reconstitute the initial cellular composition. Repopulation efficiency greatly varies between individual subsets and is influenced by interactions with the respective complementary G-2 cellular subset. The balance between differentiation states is regulated in part by the transcription factor Sox10, as depletion of Sox10 led to up-regulation of Twist2 and increased the proportion of Thy1-expressing cells representing cells in a self-renewable, reversible, quasi-mesenchymal differentiation state. CONCLUSIONS/SIGNIFICANCE: G-2 cells constitute a self-reproducing cancer cell system, maintained by bi- and unidirectional conversion of complementary cellular subsets. Our work contributes to the current controversial discussion on the existence and nature of CSC and provides a basis for the incorporation of alternative hypotheses into the CSC model

Impact of Spatial Soil and Climate Input Data Aggregation on Regional Yield Simulations

This work was financially supported by the German Federal Ministry of Food and Agriculture (BMEL) through the Federal Office for Agriculture and Food (BLE), (2851ERA01J). FT and RPR were supported by FACCE MACSUR (3200009600) through the Finnish Ministry of Agriculture and Forestry (MMM). EC, HE and EL were supported by The Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (220-2007-1218) and by the strategic funding ‘Soil-Water-Landscape’ from the faculty of Natural Resources and Agricultural Sciences (Swedish University of Agricultural Sciences) and thank professor P-E Jansson (Royal Institute of Technology, Stockholm) for support. JC, HR and DW thank the INRA ACCAF metaprogramm for funding and Eric Casellas from UR MIAT INRA for support. CB was funded by the Helmholtz project “REKLIM—Regional Climate Change”. CK was funded by the HGF Alliance “Remote Sensing and Earth System Dynamics” (EDA). FH was funded by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) under the Grant FOR1695. FE and SS acknowledge support by the German Science Foundation (project EW 119/5-1). HH, GZ, SS, TG and FE thank Andreas Enders and Gunther Krauss (INRES, University of Bonn) for support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Quantifying sources of variability in infancy research using the infant-directed-speech preference

Psychological scientists have become increasingly concerned with issues related to methodology and replicability, and infancy researchers in particular face specific challenges related to replicability: For example, high-powered studies are difficult to conduct, testing conditions vary across labs, and different labs have access to different infant populations. Addressing these concerns, we report on a large-scale, multisite study aimed at (a) assessing the overall replicability of a single theoretically important phenomenon and (b) examining methodological, cultural, and developmental moderators. We focus on infants’ preference for infant-directed speech (IDS) over adult-directed speech (ADS). Stimuli of mothers speaking to their infants and to an adult in North American English were created using seminaturalistic laboratory-based audio recordings. Infants’ relative preference for IDS and ADS was assessed across 67 laboratories in North America, Europe, Australia, and Asia using the three common methods for measuring infants’ discrimination (head-turn preference, central fixation, and eye tracking). The overall meta-analytic effect size (Cohen’s d) was 0.35, 95% confidence interval = [0.29, 0.42], which was reliably above zero but smaller than the meta-analytic mean computed from previous literature (0.67). The IDS preference was significantly stronger in older children, in those children for whom the stimuli matched their native language and dialect, and in data from labs using the head-turn preference procedure. Together, these findings replicate the IDS preference but suggest that its magnitude is modulated by development, native-language experience, and testing procedure. (This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 798658.

Impaired CK1 Delta Activity Attenuates SV40-Induced Cellular Transformation In Vitro and Mouse Mammary Carcinogenesis In Vivo

Simian virus 40 (SV40) is a powerful tool to study cellular transformation in vitro, as well as tumor development and progression in vivo. Various cellular kinases, among them members of the CK1 family, play an important role in modulating the transforming activity of SV40, including the transforming activity of T-Ag, the major transforming protein of SV40, itself. Here we characterized the effects of mutant CK1δ variants with impaired kinase activity on SV40-induced cell transformation in vitro, and on SV40-induced mammary carcinogenesis in vivo in a transgenic/bi-transgenic mouse model. CK1δ mutants exhibited a reduced kinase activity compared to wtCK1δ in in vitro kinase assays. Molecular modeling studies suggested that mutation N172D, located within the substrate binding region, is mainly responsible for impaired mutCK1δ activity. When stably over-expressed in maximal transformed SV-52 cells, CK1δ mutants induced reversion to a minimal transformed phenotype by dominant-negative interference with endogenous wtCK1δ. To characterize the effects of CK1δ on SV40-induced mammary carcinogenesis, we generated transgenic mice expressing mutant CK1δ under the control of the whey acidic protein (WAP) gene promoter, and crossed them with SV40 transgenic WAP-T-antigen (WAP-T) mice. Both WAP-T mice as well as WAP-mutCK1δ/WAP-T bi-transgenic mice developed breast cancer. However, tumor incidence was lower and life span was significantly longer in WAP-mutCK1δ/WAP-T bi-transgenic animals. The reduced CK1δ activity did not affect early lesion formation during tumorigenesis, suggesting that impaired CK1δ activity reduces the probability for outgrowth of in situ carcinomas to invasive carcinomas. The different tumorigenic potential of SV40 in WAP-T and WAP-mutCK1δ/WAP-T tumors was also reflected by a significantly different expression of various genes known to be involved in tumor progression, specifically of those involved in wnt-signaling and DNA repair. Our data show that inactivating mutations in CK1δ impair SV40-induced cellular transformation in vitro and mouse mammary carcinogenesis in vivo

Do maize crop models catch the impact of future [CO2] on maize yield and water use?

Do maize crop models catch the impact of future [CO2] on maize yield and water use?. iCROPM2016 International Crop Modelling Symposiu

Nutrient leaching losses and nutrient retention efficiencies in temperate agroforestry systems versus conventional agricultural systems

Intensively managed agriculture is often accompanied by detrimental environmental effects such as nutrient leaching losses to the groundwater and greenhouse gas emissions to the atmosphere. This results in a strong need for more environmentally friendly agricultural management systems. Alley-cropping agroforestry systems are an example for innovative management systems that have come to increasing attention in Europe. In these systems, fast growing tree species for bioenergy use are implemented in alternating strips with cropland or grassland, and thus agroforestry systems take advantage of beneficial ecological functions of both of their components, tree and crop/grass.Insuchsystems,treescanactasasafety-netagainstnutrientleachingastheycantakeupnutrientsthat are beyond the reach of shallow grass/crop roots or at times when grass/crop demand is low. However, at present no comparisons of nutrient leaching losses and nutrient retention efficiency have yet been conducted between conventional and agroforestry systems.Our study aimed to 1) quantify nutrient leaching losses in conventional and agroforestry systems of either grassland or cropland, 2) evaluate the nutrient retention efficiency in the soil under these management systems, and 3) assess whether differences in nutrient retention efficiencies between conventional and agroforestry systems are related to differences in nutrient-cycling processes in the soil and/or to differences in plant uptake of nutrients. We hypothesized that conventional systems will have higher nutrient leaching and lower nutrient retention efficiencies than agroforestry systems.This study was conducted at six paired sites of conventional and agroforestry systems (with alley cropping of fast growing trees) of grasslands or croplands, located in central Germany. Measurements in the agroforestry systems were taken within tree strips and at various distances to the tree strips within the grass or crop strips. Soil watersampleswerecollectedmonthlyin2016and2017usingsuctioncuplysimeters.Thesampleswereanalyzed for nitrogen, phosphorus and base cation concentrations. To calculate leaching losses, water drainage flux was estimated using a novel agroforestry module of the model system Expert-N. Nutrient retention efficiency (NRE) was calculated as: 1- (leaching losses/soil-available nutrient).At a cropland site, first results showed that nitrate concentrations in soil water were lower within the tree strips of the agroforestry system compared to the conventional system. Nitrate and ammonium concentrations in soil water did not differ between agroforestry and conventional systems at one grassland site, but were higher in the conventional than in the agroforestry system at another grassland site.This study will provide important information on whether temperate agroforestry systems can be a sustainable alternative to conventional agriculture by reducing nutrient leaching losses to the groundwater and by optimizing nutrient retention in the soil

Nutrient losses and nutrient retention efficiencies in temperate agroforestry systems versus conventional agricultural systems

Modern agricultural production is considered unsustainable and often is accompanied by detrimental environmental effects such as nutrient leaching losses. This results in a strong need for more environmentally friendly management systems. Alley-cropping agroforestry systems, with tree components implemented for bioenergy use, are innovative agricultural systems since they take advantage of beneficial ecological functions of both their tree and crop components. In such systems, trees can act as a safety-net against nutrient leaching as they can take up nutrients that are beyond the reach of grass/crop or at times when grass/crop demand is low. However, no comparison of nutrient losses and nutrient retention efficiencyhave yet been conducted between conventional and agroforestry systems. Our study therefore aimed to 1) quantify nutrient losses in grassland/cro pland agroforestry and conventional grassland/cropland, 2) evaluate how efficiently nutrients are being retained in both management systems (nutrient retention efficiency = (1-leaching losses/soil-available nutrient), and 3) assess whether differences in nutrient retention efficiencies between grassland/cropland agroforestry and conventional grassland/cropland are related to differences in microbial nutrient-cycling processes in the soil or differences in plant uptake of nutrients. We hypothesized that conventional systems will have higher nutrient losses and lower nutrient retention efficiencies than agroforestry systems.We investigated six paired sites of conventional grassland/cropland and grassland/cropland agroforestry with alley cropping of fast growing tree species and grass/crop, located in central Germany. Results from the growing season of 2016/2017 will be presented. Measurements in agroforestry were taken within tree strips and at various distances to the tree strips within the grass/crop strips. Soil water samples were collected monthly with lysimeters and the samples analyzed for nutrient concentrations (nitrogen, phosphorus, base cations). To calculate yearly nutrient losses, drainage flux was estimated with the model Expert-N. This study will provide the presently needed information on whether alley-cropping agroforestry systems can reduce the negative environmental impacts through leaching losses while optimizing production and therefore might be a sustainable alternative to conventional agriculture

Vegetation growth models improve surface layer flux simulations of a temperate Grassland

Grassland models represent interactions of plant growth with soil and agricultural management based on underlying processes in different degrees of detail. To better understand the impact of these differences on the simulation of energy and matter exchange at the land-surface layer, we compared the ability of five land-surface models with different degrees of complexity to simulate energy fluxes in an intensively managed grassland in Switzerland. The aim was to evaluate the impacts of biomass growth, biomass harvest, soil profile characterization, and rooting depth on the dynamics of simulated near-surface soil moisture contents and energy fluxes. The case study included a comparison of model results with continuous observations of latent heat, sensible heat, and net radiation for a site-year. Energy fluxes were simulated more accurately by including a biomass growth model, encompassing the abrupt decline in leaf area caused by harvest. Site-specific soil parametrization in combination with the absence of restrictions on rooting depth also improved the simulation results. The simulated energy fluxes of the five models differed significantly in the hot, dry month of July 2010 but were negligible under moist conditions in May. We conclude that the application of dynamic vegetation growth models improves energy flux simulations at the field scale in intensively managed grasslands during summer if biomass harvest dates and site-specific soil profile descriptions are considered. Our results imply that regional-scale simulations of grasslands will benefit significantly from high-resolution input information on soil properties, land use, and management

Remote photoacoustic sensing using speckle-analysis

Laser surgery is a rising surgical technique, which offers several advantages compared to the traditional scalpel. However, laser surgery lacks a contact-free feedback system which offers high imaging contrast to identify the tissue type ablated and also a high penetration depth. Photoacoustic imaging has the potential to fill this gap. Since photoacoustic detection is commonly contact based, a new non-interferometric detection technique based on speckle-analysis for remote detection is presented in this work. Phantom and ex-vivo experiments are carried out in transmission and reflection-mode for proof of concept. In summary, the potential of the remote speckle sensing technique for photoacoustic detection is demonstrated. In future, this technique might be applied for usage as a remote feedback system for laser surgery, which could help to broaden the applications of lasers as smart surgical tools