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Interdisciplinarity and transdisciplinarity are seen as promising ways to address societies' grand challenges and so have become important topics in academic and policy discourses, particularly as part of discussions about mission-oriented knowledge production and research funding processes. However, there is an important disconnect between the way these terms are defined and used in the academic literature and the way they are defined and used in the policy literature. Academic writing on interdisciplinarity and transdisciplinarity offers plural understandings of both terms, whereas policy documents argue for concrete and simplified definitions. In this paper, we analyse the implications of these differences for research and funding. On the basis of an extensive literature review, we argue that the heterogeneity of understandings in interdisciplinarity and transdisciplinarity constitutes an asset. We advocate for the plurality of understandings to be used constructively in order to strengthen and promote effective research and research funding., Science and Public Policy, 49 (6), ISSN:0302-3427, ISSN:1471-5430

Integration is a key process in transdisciplinary research and knowledge co-production. Nonetheless, it is often used as a buzzword without specifying what exactly it means or what actually happens during integration. We propose conceptualizing integration as a multidimensional interactive process. We characterize it as an open-ended learning process without pre-determined outcomes. Integration designates relations established throughout a transdisciplinary research process between elements that were not previously related. Those elements are participants in the process and their thought-styles and thought-collectives and more specifically pieces of knowledge, ideas, or practices from different thought-collectives as well as views of individual researchers and practitioners. Integration can happen at manifold instances of a transdisciplinary research process. It can take place among two, several, or all participants and can be one-sided or mutual. It might include insights, practices, frameworks, or concepts shared by two, several, or all participants. Consensus is only one along with other ways of retaining plurality of thought-styles and seeing integration as a balance between them that remains subject to continuous revision. To analyse or achieve effective integration, further dimensions beyond the cognitive have to be taken into account including at least an emotional and a social-interactional dimension.

Rivers are important transport pathways of microplastics from terrestrial to marine environments. They also interact with terrestrial ecosystems, in particular during flood events, when microplastics can be deposited in or eroded from floodplains. The spatial distribution of these riverine microplastics in alluvial floodplains remains widely unclear. However, the knowledge on their abundance and distribution in floodplain soils is essentially important for ecological risk assessment.We analysed the distribution of microplastics in three transects of a floodplain soil in a nature reserve in Cologne (Germany). We took soil samples in two different depths (0-5 cm and 5-20 cm), described the soil profiles and plant cover and determined the soil texture. Additionally, we used a hydrodynamic model (MIKE21 software by DHI) and time series of Rhine's water level to analyse the frequency of past flood events from 1950 to 2020. We analysed concentrations of microplastics via ATR-FTIR and µ-FPA-FTIR spectroscopy after density separation and enzymatic-oxidative purification of soil samples. We found elevated microplastic concentrations per kg of dry soil with increasing distance to the river ranging from 25,616 particles/kg to 84,824 particles/kg. Combining the analysis of flood events, the digital terrain model and quantification of microplastics, we show how the local topography (e.g., depressions), flood frequency and soil properties (e.g., grain size) interact and affect the spatial and vertical distribution of microplastics.

The aim of this study was to assess the characteristics of asylum-seeking children with medical complexity visiting a tertiary care hospital in Switzerland, detailing their underlying medical conditions and management. Asylum-seeking patients with frequent visits between January 2016 and December 2017 were identified using administrative and electronic health records. Of 462 patients, 19 (4%) fulfilled the inclusion criteria with 811 (45%) visits. The age of the 19 patients ranged from 0 to 16.7 years (median of 7 years) with two main age groups identified: 12 years. Nine (47%) patients originated from Syria. A total of 34/811(4%) visits were hospital admissions, 66/811 (8%) emergency department visits and 320/811(39%) outpatient department visits. In children

Recent empirical studies show a persistent gap between ‘socially robust’ knowledge produced by transdisciplinary research projects and its ability to promote change on a large scale. Current discourses about the ‘project-to-science-and-practice-at-large gap’ have focused mainly on exploring various conditions that need to be fulfilled to produce ‘socially robust’ knowledge. Yet, those discourses have rarely built on the broader literature of knowledge utilization, which Greenhalgh and Wieringa (2011) emphasize acknowledges ‘the fundamentally social ways in which knowledge emerges, circulates, and gets applied in practice.’ Their insights are helpful in advancing our understanding of why transdisciplinary research projects do or do not contribute to sustainability on a large scale. Expanding Jahn et al. (2012)’s model of transdisciplinary research, we present a revised conceptual model of an ideal-typical, interactive and iterative transdisciplinary research process that adds two new phases from the field of knowledge utilization to their original three-phase model and accounts for the social and relational nature of knowledge utilization. The revised model includes five phases through which transdisciplinary projects operate in different order: (i) defining sustainability problems, (ii) producing new knowledge, (iii) assessing new knowledge, (iv) disseminating new knowledge in realms of both science and practice and (v) using new knowledge in both realms.

Discoidin domain receptors 1 and 2 (DDR1/2) play a central role in fibrotic disorders, such as renal and pulmonary fibrosis, atherosclerosis, and various forms of cancer. Potent and selective inhibitors, so-called chemical probe compounds, have been developed to study DDR1/2 kinase signaling. However, these inhibitors showed undesired activity on other kinases such as the tyrosine protein kinase receptor TIE or tropomyosin receptor kinases, which are related to angiogenesis and neuronal toxicity. In this study, we optimized our recently published p38 mitogen-activated protein kinase inhibitor 7 toward a potent and cell-active dual DDR/p38 chemical probe and developed a structurally related negative control. The structure-guided design approach used provided insights into the P-loop folding process of p38 and how targeting of non-conserved amino acids modulates inhibitor selectivity. The developed and comprehensively characterized DDR/p38 probe, 30 (SR-302), is a valuable tool for studying the role of DDR kinase in normal physiology and in disease development.

CASK (Ca

BackgroundTo assess the prognostic value of early echocardiographic indices of right ventricular function and vasoactive peptides for prediction of bronchopulmonary dysplasia (BPD) or death in very preterm infants.MethodsProspective study involving 294 very preterm infants (median [IQR] gestational age 28.4 [26.4–30.4] weeks, birth weight 1065 [800–1380] g), of whom 57 developed BPD (oxygen supplementation at 36 weeks postmenstrual age) and 10 died. Tricuspid annular plane systolic excursion (TAPSE), right ventricular index of myocardial performance (RIMP), plasma concentrations of mid-regional pro-atrial natriuretic peptide (MR-proANP) and C-terminal pro-endothelin-1 (CT-proET1) were measured on day 7 of life.ResultsRIMP was significantly increased (median [IQR] 0.3 [0.23–0.38] vs 0.22 [0.15–0.29]), TAPSE decreased (median [IQR] 5.0 [5.0–6.0] vs 6.0 [5.4–7.0] mm), MR-proANP increased (median [IQR] 784 [540–936] vs 353 [247–625] pmol/L), and CT-proET1 increased (median [IQR] 249 [190–345] vs 199 [158–284] pmol/L) in infants who developed BPD or died, as compared to controls. All variables showed significant but weak correlations with each other (rS-0.182 to 0.359) and predicted BPD/death with similar accuracy (areas under receiver operator characteristic curves 0.62 to 0.77). Multiple regression revealed only RIMP and birth weight as independent predictors of BPD or death.ConclusionsVasoactive peptide concentrations and echocardiographic assessment employing standardized measures, notably RIMP, on day 7 of life are useful to identify preterm infants at increased risk for BPD or death.

Autophagic flux can be quantified based on the accumulation of lipidated LC3B in the presence of late-stage autophagy inhibitors. This method has been widely applied to identify novel compounds that activate autophagy. Here we scrutinize this approach and show that bafilomycin A1 (BafA) but not chloroquine is suitable for flux quantification due to the stimulating effect of chloroquine on non-canonical LC3B-lipidation. Significant autophagic flux increase by rapamycin could only be observed when combining it with BafA concentrations not affecting basal flux, a condition which created a bottleneck, rather than fully blocking autophagosome-lysosome fusion, concomitant with autophagy stimulation. When rapamycin was combined with saturating concentrations of BafA, no significant further increase of LC3B lipidation could be detected over the levels induced by the late-stage inhibitor. The large assay window obtained by this approach enables an effective discrimination of autophagy activators based on their cellular potency. To demonstrate the validity of this approach, we show that a novel inhibitor of the acetyltransferase EP300 activates autophagy in a mTORC1-dependent manner. We propose that the creation of a sensitized background rather than a full block of autophagosome progression is required to quantitatively capture changes in autophagic flux.

Rivers are major pathways for the transport of microplastics towards the oceans, and many studies focus on microplastic abundance in fluvial ecosystems. Although flooding strongly affects transport of microplastics, knowledge about the potential input via floodwaters, spatial distribution, and fate of microplastics in adjacent floodplains remains very limited. In this study, we suggest that local topography and flood frequency could influence the abundance of microplastics in floodplains. Based on this concept, we took soil samples in a Rhine River floodplain in two different depths (0-5 cm and 5-20 cm) along three transects with increasing distance to the river and analysed the abundance of microplastics via FTIR spectroscopy. Flood frequency of the transects was estimated by a combination of hydrodynamic modelling with MIKE 21 (DHI, Hørsholm Denmark) and analysis of time series of water levels. Microplastic abundance per kg dry soil varied between 25,502 to 51,119 particles in the top 5 cm and 25,616 to 84,824 particles in the deeper soil (5-20 cm). The results of our study indicate that local topography and resulting flooding patterns are responsible for the amount of microplastics found at the respective transect. Differences in soil properties, vegetation cover and signs of earthworm activity in the soil profile seem to be related to microplastic migration and accumulation in the deeper soil. The interdisciplinary approach we used in our work can be applied to other floodplains to elucidate the respective processes. This information is essentially important both for locating potential microplastic sinks for process-informed sampling designs and to identify areas of increased bioavailability of microplastics for proper ecological risk assessment.

CD3-bispecific antibodies are a new class of immunotherapeutic drugs against cancer. The pharmacological activity of CD3-bispecifics is typically assessed through in vitro assays of cancer cell lines co-cultured with human peripheral blood mononuclear cells (PBMCs). Assay results depend on experimental conditions such as incubation time and the effector-to-target cell ratio, which can hinder robust quantification of pharmacological activity. In order to overcome these limitations, we developed a new, holistic approach for quantification of the in vitro dose–response relationship. Our experimental design integrates a time-independent analysis of the dose–response across different time points as an alternative to the static, “snap-shot” analysis based on a single time point commonly used in dose–response assays. We show that the potency values derived from static in vitro experiments depend on the incubation time, which leads to inconsistent results across multiple assays and compounds. We compared the potency values from the time-independent analysis with a model-based approach. We find comparably accurate potency estimates from the model-based and time-independent analyses and that the time-independent analysis provides a robust quantification of pharmacological activity. This approach may allow for an improved head-to-head comparison of different compounds and test systems and may prove useful for supporting first-in-human dose selection.

Mitophagy is essential to maintain mitochondrial function and prevent diseases. It activates upon mitochondria depolarization, which causes PINK1 stabilization on the mitochondrial outer membrane. Strikingly, a number of conditions, including mitochondrial protein misfolding, can induce mitophagy without a loss in membrane potential. The underlying molecular details remain unclear. Here, we report that a loss of mitochondrial protein import, mediated by the pre-sequence translocase-associated motor complex PAM, is sufficient to induce mitophagy in polarized mitochondria. A genome-wide CRISPR/Cas9 screen for mitophagy inducers identifies components of the PAM complex. Protein import defects are able to induce mitophagy without a need for depolarization. Upon mitochondrial protein misfolding, PAM dissociates from the import machinery resulting in decreased protein import and mitophagy induction. Our findings extend the current mitophagy model to explain mitophagy induction upon conditions that do not affect membrane polarization, such as mitochondrial protein misfolding.

To support societal problem solving, transdisciplinary research (TDR) uses knowledge co-production focusing on relevance and validity in a studied case and its particular social-ecological context. In the first instance, the resulting situated knowledge seems to be restricted to these single cases. However, if some of the knowledge generated in TDR could be used in other research projects, this would imply that there is a body of knowledge representing this special type of research. This study used a qualitative approach based on the methodology of grounded theory to empirically examine what knowledge is considered transferable to other cases, if any. 30 leaders of 12 Swiss-based TDR projects in the field of sustainable development were interviewed, representing both academia and practice. The transferable knowledge we found consists of the following: (1) Transdisciplinary principles, (2) transdisciplinary approaches, (3) systematic procedures, (4) product formats, (5) experiential know-how, (6) framings and (7) insights, data and information. The discussion of TDR has predominantly been focusing on transdisciplinary principles and approaches. In order to take knowledge co-production in TDR beyond an unmanageable field of case studies, more efforts in developing and critically discussing transferable knowledge of the other classes are needed, foremost systematic procedures, product formats and framings., Sustainability Science, 16 (6), ISSN:1862-4065, ISSN:1862-4057

Linking knowledge with action for effective societal responses to persistent problems of unsustainability requires transformed, more open knowledge systems. Drawing on a broad range of academic and practitioner experience, we outline a vision for the coordination and organization of knowledge systems that are better suited to the complex challenges of sustainability than the ones currently in place. This transformation includes inter alia: societal agenda setting, collective problem framing, a plurality of perspectives, integrative research processes, new norms for handling dissent and controversy, better treatment of uncertainty and of diversity of values, extended peer review, broader and more transparent metrics for evaluation, effective dialog processes, and stakeholder participation. We set out institutional and individual roadmaps for achieving this vision, calling for well-designed, properly resourced, longitudinal, international learning programs., Environmental Science & Policy, 28, ISSN:1462-9011, ISSN:1873-6416

Research and policy processes in many fields, such as sustainability and health, are increasingly relying on transdisciplinary cooperation among a multitude of governmental, nongovernmental, and private actors from local to global levels. In the absence of hierarchical chains of command, multistakeholder governance may accommodate conflicting or diverse interests and facilitate collective action, but its effectiveness depends on its capacity to integrate systems, transformation, and target knowledge. Approaches to foster such governance are nascent and quickly evolving, and methodological standards to facilitate comparison and learning from best practice are needed. However, there is currently no evaluation approach that (i) comprehensively assesses the capacity for knowledge integration in multistakeholder governance, (ii) draws on the best available knowledge that is being developed in various fields, and (iii) combines a systematic and transferable methodological design with pragmatic feasibility. We brought together 20 experts from institutions in nine countries, all working on evaluation approaches for collaborative science–policy initiatives. In a synthesis process that included a 2-day workshop and follow-up work among a core group of participants, we developed a tool for evaluating knowledge integration capacity in multistakeholder governance (EVOLvINC). Its 23 indicators incorporate previously defined criteria and components of transdisciplinary evaluations into a single, comprehensive framework that operationalizes the capacity for integrating systems, target, and transformation knowledge during an initiative’s (a) design and planning processes at the policy formulation stage, (b) organization and working processes at the implementation stage, and (c) sharing and learning processes at the evaluation stage of the policy cycle. EVOLvINC is (i) implemented through a questionnaire, (ii) builds on established indicators where possible, (iii) offers a consistent and transparent semiquantitative scoring and aggregation algorithm, and (iv) uses spider diagrams for visualizing results. The tool builds on experience and expertise from both the northern and southern hemispheres and was empirically validated with seven science–policy initiatives in six African and Asian countries. As a generalized framework, EVOLvINC thus enables a structured reflection on the capacity of multistakeholder governance processes to foster knowledge integration. Its emphasis on dialog and exploration allows adaptation to contextual specificities, highlights relative strengths and weaknesses, and suggests avenues for shaping multistakeholder governance toward mutual learning, capacity building, and strengthened networks. The validation suggests that the adaptive capacity of multistakeholder governance could be best enhanced by considering systems characteristics at the policy formulation stage and fostering adaptive and generic learning at the evaluation stage of the policy cycle., Ecology and Society, 24 (2), ISSN:1708-3087

BackgroundAsylum-seeking children represent an increasing and vulnerable group of patients whose health needs are largely unmet. Data on the health care provision to asylum-seeking children in European contexts is scarce. In this study we compare the health care provided to recent asylum-seeking and non-asylum-seeking children at a Swiss tertiary hospital.MethodsWe performed a cross-sectional retrospective study in a pediatric tertiary care hospital in Switzerland. All patients and visits from January 2016 to December 2017were identified, using administrative and medical electronic health records. The asylum-seeking status was systematically assessed and the patients were allocated accordingly in the two study groups.Results A total of 202’316 visits by 55’789 patients were included, of which asylum-seeking patients accounted for 1674 (1%) visits by 439 (1%) individuals. The emergency department recorded the highest number of visits in both groups with a lower proportion in asylum-seeking compared to non-asylum-seeking children: 19% (317/1674) and 32% (64’315/200’642) respectively. The median number of visits per patient was 1 (IQR 1-2) in the asylum-seeking and 2 (IQR 1-4) in the non-asylum-seeking children. Hospital admissions were more common in asylum-seeking compared to non-asylum-seeking patients with 11% (184/1674) and 7% (14’692/200’642). Frequent visits (>15 visits per patient) accounted for 48% (807/1674) of total visits in asylum-seeking and 25% (49’886/200’642) of total visits in non-asylum-seeking patients. ConclusionsHospital visits by asylum-seeking children represented a small proportion of all visits. The emergency department had the highest number of visits in all patients but was less frequently used by asylum-seeking children. Frequent care suggests that asylum-seeking patients also present with more complex diseases. Further studies are needed, focusing on asylum-seeking children with medical complexity.

Umweltproblemlosen (Tackling environmental problems) is a Bachelor-level course that carries on a long tradition of transdisciplinary (td) case studies in the Environmental Sciences curriculum at ETH Zurich. Td case studies introduce students to key features of transdisciplinarity. Two corresponding learning goals of the case studies are 1. to not only analyse problems, but to also suggest solutions, and 2. to take the complexity of the tackled socio-ecological system into account. In the new course we address both learning goals by integrating systems and design thinking. We present this approach in detail to show how features of transdisciplinarity are transferred to learning contexts. We compare it to the approaches of other td case studies by asking how each interprets and addresses the two learning goals. The comparison shows that the case study approaches implicitly impart different ideas about how a td environmental scientist should support societal problem solving. A key difference to previous approaches is that the new course asks students to enter deeply into the world of practice and the stakeholders' divergent needs., GAIA - Ecological Perspectives for Science and Society, 29 (4), ISSN:0940-5550

Background & Methods To compare health care provided to asylum-seeking and non-asylum-seeking children, we performed a cross-sectional study in a paediatric tertiary care hospital in Switzerland. Patients were identified using administrative and medical electronic health records from January 2016 - December 2017. Results A total of 202’316 visits by 55’789 patients were included, of which asylum-seeking patients accounted for 1674 (1%) visits by 439 (1%) patients. The emergency department had the highest number of visits in both groups with a lower proportion in asylum-seeking compared to non-asylum-seeking children: 19% (317/1674) and 32% (64’315/200’642) respectively. Hospital admissions were more common in asylum-seeking patients 11% (184/1674) and 7% (14’692/200’642). Frequent visits accounted for 48% (807/1674) of total visits in asylum-seeking and 25% (49’886/200’642) of total visits in non-asylum-seeking patients. Conclusions Hospital visits by asylum-seeking children represented a small proportion of all visits. The emergency department had the highest number of visits in all patients and was less frequently used in asylum-seeking children. Higher admission rates and a larger proportion of visits from frequently visiting patients suggest that asylum-seeking patients may present with more complex diseases.

The teaching component is widely lacking in the discussion of real-world laboratories. We introduce a sustainability learning lab, where students both profit from this platform and also contribute to the success of the lab.In the discussion of real-world laboratories, the teaching component is widely lacking. We address this by introducing a prototype of a sustainability learning lab (SLL) in the global South using a case study of the Seychelles as an example. In 2015 the Transdisciplinarity Lab (TdLab) of ETH Zurich initiated a long-term collaboration with the University of Seychelles (UniSey) and the Ministry of Environment, Energy and Climate Change (MEECC). Teaching activities include transdisciplinary case studies (tdCS) for students from UniSey and ETH, alternated with courses for UniSey only. BSc and MSc theses as well as internships complement these. In 2016 the TdLab, UniSey and MEECC jointly decided to focus on solid waste in a tdCS that engaged 18 ETH and 18 UniSey students with diverse backgrounds. This collaborative approach in a real-world setting with students from different cultures and engaging with a broad range of stakeholders is promising. Students managed to bring novel observations and insights to the surface. Thus, students both profit from this learning platform and also contribute substantially to the further development of the SLL.

What challenges do researchers face when leading transdisciplinary integration? We address this question by analyzing transdisciplinary integration within four thematic synthesis processes of the Swiss National Research Programme (NRP 61) on Sustainable Water Management. We adapt an existing analytical framework to compare transdisciplinary integration across the four synthesis processes regarding different types of generated knowledge (systems, target and transformation knowledge), different types of involved actors (core team, steering committee, advisory board, scientific experts and practice experts) and different levels of actor involvement (information, consultation and collaboration) at different stages of the processes. Based on a structured ex-post self-evaluation of the four synthesis processes, we present core challenges of transdisciplinary integration as perceived by core team members of the four synthesis processes and formulate empirically derived recommendations for designing and implementing future processes. We suggest that future synthesis processes should be conceptualized and initiated concurrently with all other individual research projects, involving a phasing-in stage where leaders conceptualize transdisciplinary integration, an intermediate stage of intense knowledge integration involving all relevant actor groups in a functional and dynamic way, and a final phasing out stage, where synthesis results are consolidated within the research program, validated by different actor groups and diffused to the target audiences. We argue that transdisciplinary integration requires professional competences, management skills and enough time. Finally, we suggest fostering communities of practice (CoP) to link committed leaders and enable mutual learning processes beyond the boundaries of individual synthesis projects or research programs.

Expertise in research integration and implementation is an essential but often overlooked component of tackling complex societal and environmental problems. We focus on expertise relevant to any complex problem, especially contributory expertise, divided into ‘knowing-that’ and ‘knowing-how.’ We also deal with interactional expertise and the fact that much expertise is tacit. We explore three questions. First, in examining ‘when is expertise in research integration and implementation required?,’ we review tasks essential (a) to developing more comprehensive understandings of complex problems, plus possible ways to address them, and (b) for supporting implementation of those understandings into government policy, community practice, business and social innovation, or other initiatives. Second, in considering ‘where can expertise in research integration and implementation currently be found?,’ we describe three realms: (a) specific approaches, including interdisciplinarity, transdisciplinarity, systems thinking and sustainability science; (b) case-based experience that is independent of these specific approaches; and (c) research examining elements of integration and implementation, specifically considering unknowns and fostering innovation. We highlight examples of expertise in each realm and demonstrate how fragmentation currently precludes clear identification of research integration and implementation expertise. Third, in exploring ‘what is required to strengthen expertise in research integration and implementation?,’ we propose building a knowledge bank. We delve into three key challenges: compiling existing expertise, indexing and organising the expertise to make it widely accessible, and understanding and overcoming the core reasons for the existing fragmentation. A growing knowledge bank of expertise in research integration and implementation on the one hand, and accumulating success in addressing complex societal and environmental problems on the other, will form a virtuous cycle so that each strengthens the other. Building a coalition of researchers and institutions will ensure this expertise and its application are valued and sustained., Palgrave Communications, 6 (1)

To achieve homeostasis, cells evolved dynamic and self-regulating quality control processes to adapt to new environmental conditions and to prevent prolonged damage. We discuss the importance of two major quality control systems responsible for degradation of proteins and organelles in eukaryotic cells: the ubiquitin-proteasome system (UPS) and autophagy. The UPS and autophagy form an interconnected quality control network where decision-making is self-organized on the basis of biophysical parameters (binding affinities, local concentrations, and avidity) and compartmentalization (through membranes, liquid-liquid phase separation, or the formation of aggregates). We highlight cellular quality control factors that delineate their differential deployment toward macromolecular complexes, liquid-liquid phase-separated subcellular structures, or membrane-bound organelles. Finally, we emphasize the need for continuous promotion of quantitative and mechanistic research into the roles of the UPS and autophagy in human pathophysiology.

We witness a persistent tension between established ways of knowledge production through disciplines, and the urgent need to widen and change, both the production of knowledge and its organization, not least, in order to be able to understand and address the future and its challenges. Witnessing a growing call for inter- and transdisciplinarity (ITD), we set our goal to learn more about scholars who engage in this kind of research by asking these questions: What characterizes inter- and transdisciplinary researchers (ITDRs)? To what extent do these characteristics help ITDRs deal with the challenges of an academic career path? We address both questions by comparing the findings from the relevant literature and semi-structured interviews with ITDRs at different stages in their careers. Our results bring the ITDR personality a step further in taking a form. ITDR personalities can be characterized by a particular mix of motivations, attitudes, skills, and behaviors. However, the academic environment and its career paths do not seem prepared and adapted for such ITDR personalities. Furthermore and in contrast to the literature, the T-shaped training (first, disciplinary depth and then, ITDR) is considered one possible career path, with the other one being a specialization in facilitating knowledge integration and in developing theories, methods, and tools for ITD. Our analysis concludes by exploring the future of ITD if formal training and learning would be available and if the contextual conditions would be more conducive to undertaking this type of research. ISSN:0016-3287

During animal development, it is crucial that cells can sense and adapt to mechanical forces from their environment. Ultimately, these forces are transduced through the actomyosin cortex. How the cortex can simultaneously respond to and create forces during cytokinesis is not well understood. Here we show that under mechanical stress, cortical actomyosin flow switches its polarization during cytokinesis in theC. elegansembryo. In unstressed embryos, longitudinal cortical flows contribute to contractile ring formation, while rotational cortical flow is additionally induced in uniaxially loaded embryos. Rotational cortical flow is required for the redistribution of the actomyosin cortex in loaded embryos. Rupture of longitudinally aligned cortical fibers during cortex rotation releases tension, initiates orthogonal longitudinal flow and thereby contributes to furrowing in loaded embryos. A targeted screen for factors required for rotational flow revealed that actomyosin regulators involved in RhoA regulation, cortical polarity and chirality are all required for rotational flow and become essential for cytokinesis under mechanical stress. In sum, our findings extend the current framework of mechanical stress response during cell division and show scaling of orthogonal cortical flows to the amount of mechanical stress.