Pathways to resilience: how drawings reveal pre-service teachers’ core narratives underpinning their future teacher-selves

For this study of teacher-identity, which is part of a larger research project on teacher resilience, preservice teachers were invited to draw “the kind of teacher you hope to become”. In this, our study recognises drawing as a semiotic system of meaning-making and communication. The drawings were examined in terms of the “stories” they told. Using an emergent design approach to the data, drawings were synthesised into categories that were distilled into theme clusters. A hermeneutic reading revealed the core identity narrative underpinning each teacher-identity story. This story was told in sociocultural terms, or constructed around functioning at work or couched in terms of personal validation and achievement. These core identity narratives signal what “matters” to preservice teachers’ sense of their teacher-selves. Since there is an observed correlation between teacher-identity and resilience, knowing what matters is a helpful basis for building resilience

Werken de KRW- en Natura 2000-criteria voor sloten en veenplassen?

Toepassing van de Kaderrichtlijn Water en de normen conform Natura 2000 vragen om een evaluatie van de effectiviteit. De KRW blijkt een correct middel om maatregelen te nemen, maar in de hoogste klasse is het onderscheid (te) gering. Worden de doelen van de Natura 2000-habitats 'evenwichtige laagveensystemen met daarmee verbonden laagveenverlanding' ook gehaald? Onderzoek van waterplanten in twee Natura 2000-habitats, namelijk laagveenplassen en -sloten, toont duidelijk aan dat essentiele schakels in de systemen niet meer voldoende aanwezig zijn. De waarnemingen bestaan vrijwel geheel uit losse individuele planten, indien al aanwezig. Losse krabbenscheerplanten in een zee grof hoornblad vormen geen eindstadium van verlanding in veenplassen zoals de criteria voor Natura 2000 aangeve

Lymph node topology dictates T cell migration behavior

Adaptive immunity is initiated by T cell recognition of foreign peptides presented on dendritic cells (DCs) by major histocompatibility molecules. These interactions take place in secondary lymphoid tissues, such as lymph nodes (LNs) and spleen, and hence the anatomical structure of these tissues plays a crucial role in the development of immune responses. Two-photon microscopy (2PM) imaging in LNs suggests that T cells walk in a consistent direction for several minutes, pause briefly with a regular period, and then take off in a new, random direction. Here, we construct a spatially explicit model of T cell and DC migration in LNs and show that all dynamical properties of T cells could be a consequence of the densely packed LN environment. By means of 2PM experiments, we confirm that the large velocity fluctuations of T cells are indeed environmentally determined rather than resulting from an intrinsic motility program. Our simulations further predict that T cells self-organize into microscopically small, highly dynamic streams. We present experimental evidence for the presence of such turbulent streams in LNs. Finally, the model allows us to estimate the scanning rates of DCs (2,000 different T cells per hour) and T cells (100 different DCs per hour)

Tumor-mediated immunosuppression and cytokine spreading affects the relation between EMT and PD-L1 status

Epithelial-mesenchymal transition (EMT) and immune resistance mediated by Programmed Death-Ligand 1 (PD-L1) upregulation are established drivers of tumor progression. Their bi-directional crosstalk has been proposed to facilitate tumor immunoevasion, yet the impact of immunosuppression and spatial heterogeneity on the interplay between these processes remains to be characterized. Here we study the role of these factors using mathematical and spatial models. We first designed models incorporating immunosuppressive effects on T cells mediated via PD-L1 and the EMT-inducing cytokine Transforming Growth Factor beta (TGFβ). Our models predict that PD-L1-mediated immunosuppression merely reduces the difference in PD-L1 levels between EMT states, while TGFβ-mediated suppression also causes PD-L1 expression to correlate negatively with TGFβ within each EMT phenotype. We subsequently embedded the models in multi-scale spatial simulations to explicitly describe heterogeneity in cytokine levels and intratumoral heterogeneity. Our multi-scale models show that Interferon gamma (IFNγ)-induced partial EMT of a tumor cell subpopulation can provide some, albeit limited protection to bystander tumor cells. Moreover, our simulations show that the true relationship between EMT status and PD-L1 expression may be hidden at the population level, highlighting the importance of studying EMT and PD-L1 status at the single-cell level. Our findings deepen the understanding of the interactions between EMT and the immune response, which is crucial for developing novel diagnostics and therapeutics for cancer patients

Effectgerichte maatregelen tegen verdroging, verzuring en stikstofdepositie op trilvenen (Noord-Hollland, Utrecht en Noordwest- Overijsssel)

De centrale probleemstelling van het obn onderzoek is of het mogelijk is met lokale maatregelen de natuur, zich manifesterend in soortensamenstelling, soortenrijkdom en bedekking van plantengemeenschappen te herstellen in laagvenen

ATF6 Is a Critical Determinant of CHOP Dynamics during the Unfolded Protein Response

The unfolded protein response (UPR) pathway senses unfolded proteins and regulates proteostasis and cell fate through activity of the transcription factors ATM, ATF6, and XBP1 within a complex network of three main branches. Here, we investigated contributions of the three branches to UPR activity in single cells using microscopy-based quantification and dynamic modeling. BAC-GFP HepG2 reporter cell lines were exposed to tunicamydn, and activation of various UPR components was monitored for 24 h. We constructed a dynamic model to describe the adaptive UPR signaling network, for which incorporation of all three branches was required to match the data. Our calibrated model suggested that ATF6 shapes the early dynamics of pro-apoptotic CHOP. We confirmed this hypothesis by measurements beyond 24 h, by perturbing single siRNA knockdowns and by ATF6 measurements. Overall, our work indicates that ATF6 is an important regulator of CHOP, which in turn regulates cell fate decisions.Toxicolog

Random Migration and Signal Integration Promote Rapid and Robust T Cell Recruitment

To fight infections, rare T cells must quickly home to appropriate lymph nodes (LNs), and reliably localize the antigen (Ag) within them. The first challenge calls for rapid trafficking between LNs, whereas the second may require extensive search within each LN. Here we combine simulations and experimental data to investigate which features of random T cell migration within and between LNs allow meeting these two conflicting demands. Our model indicates that integrating signals from multiple random encounters with Ag-presenting cells permits reliable detection of even low-dose Ag, and predicts a kinetic feature of cognate T cell arrest in LNs that we confirm using intravital two-photon data. Furthermore, we obtain the most reliable retention if T cells transit through LNs stochastically, which may explain the long and widely distributed LN dwell times observed in vivo. Finally, we demonstrate that random migration, both between and within LNs, allows recruiting the majority of cognate precursors within a few days for various realistic infection scenarios. Thus, the combination of two-scale stochastic migration and signal integration is an efficient and robust strategy for T cell immune surveillance

Density-dependent migration characteristics of cancer cells driven by pseudopod interaction

The ability of cancer cells to invade neighboring tissue from primary tumors is an important determinant of metastatic behavior. Quantification of cell migration characteristics such as migration speed and persistence helps to understand the requirements for such invasiveness. One factor that may influence invasion is how local tumor cell density shapes cell migration characteristics, which we here investigate with a combined experimental and computational modeling approach. First, we generated and analyzed time-lapse imaging data on two aggressive Triple-Negative Breast Cancer (TNBC) cell lines, HCC38 and Hs578T, during 2D migration assays at various cell densities. HCC38 cells exhibited a counter-intuitive increase in speed and persistence with increasing density, whereas Hs578T did not exhibit such an increase. Moreover, HCC38 cells exhibited strong cluster formation with active pseudopod-driven migration, especially at low densities, whereas Hs578T cells maintained a dispersed positioning. In order to obtain a mechanistic understanding of the density-dependent cell migration characteristics and cluster formation, we developed realistic spatial simulations using a Cellular Potts Model (CPM) with an explicit description of pseudopod dynamics. Model analysis demonstrated that pseudopods exerting a pulling force on the cell and interacting via increased adhesion at pseudopod tips could explain the experimentally observed increase in speed and persistence with increasing density in HCC38 cells. Thus, the density-dependent migratory behavior could be an emergent property of single-cell characteristics without the need for additional mechanisms. This implies that pseudopod dynamics and interaction may play a role in the aggressive nature of cancers through mediating dispersal.NWO864.12.013Toxicolog