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The sculpting of germ layers during gastrulation relies on coordinated migration of progenitor cells, yet the cues controlling these long-range directed movements remain largely unknown. While directional migration often relies on a chemokine gradient generated from a localized source, we find that zebrafish ventrolateral mesoderm is guided by the uniformly expressed and secreted protein Toddler/ELABELA/Apela, acting as a self-generated gradient. We show that the Apelin receptor, which is specifically expressed in mesodermal cells, has a dual role during gastrulation, acting as a scavenger receptor to generate a Toddler gradient, and as a chemokine receptor to sense this guidance cue. Thus, we uncover a single receptor-based self-generated gradient as the enigmatic guidance cue that can robustly steer the directional migration of mesoderm through the complex and continuously changing environment of the gastrulating embryo.One sentence summaryAplnr has a dual role to self-generate and sense a Toddler gradient directing mesodermal cells during zebrafish gastrulation.

Wenn vom Innovationsstandort Deutschland die Rede ist, wird von Forschungs- und Entwicklungsaktivitaten der Wirtschaft und Wissenschaft ebenso gesprochen wie von den institutionellen Rahmenbedingungen, die von der Politik gesetzt werden. Die Anwender der Innovationen bleiben hingegen in aller Regel unberucksichtigt. So stellt die Expertenkommission Forschung und Innovation(EFI) der Bundesregierung in ihrem Gutachten zwar fest, dass es in Bezug auf die eingeleitete Energiewende „eines engagierten, koordinierten Einsatzes aller Akteure“ bedarf (vgl. EFI 2012: 5), doch von Nutzer/-innen innovativer umweltfreundlicher Produkte ist darin nicht die Rede. Dies ist insofern uberraschend, als der Erfolg innovativer Technologien von ihrer Akzeptanz und Bereitschaft zur Nutzung unmittelbar abhangt. Das gilt fur endverbraucherorientierte Produkte wie das Elektroauto in besonderem Mase: Wenn das Elektroauto einen signifikanten Beitrag zur Verringerung der CO2-Emissionen und zur Verminderung der Abhangigkeit vom Erdol leisten soll, muss die Nachfrage nach Elektroautos deutlich steigen. Elektrofahrrader haben es im Zuge eines befristeten „Hypes“ um die Elektromobilitat bereits zu einigermasen erfolgreichen Produkten gebracht. Sie werden bisher allerdings lediglich als Erganzung zur schon vorhandenen Verkehrsmittelwahl genutzt.

When we talk about Germany as a location for innovation, we have in mind the research and development activities of industry and science as well as the institutional framework established by political policy. The users of the innovations, on the other hand, are generally not taken into account. Thus, the Commission of Experts for Research and Innovation (EFI) of the Federal Government stated in its report that the transformation of the energy system requires “a committed, coordinated effort on the part of all actors” (cf. EFI 2012: 5), but it does not mention the users of innovative, environmentally friendly products. This is surprising in that the success of innovative technologies depends directly on their acceptance and the public’s willingness to use them. This applies particularly to consumer-oriented products such as the electric car: if the electric car is to make a significant contribution to reducing CO2-emissions and reducing the dependence on oil, the demand for electric cars must increase significantly. Electric bicycles have already achieved some success in the course of a temporary “hype” about electric mobility. So far, however, they have only been used as a supplement to the existing choices in means of transport.

Myosin A (MyoA) is a Class XIV myosin implicated in gliding motility and host cell and tissue invasion by malaria parasites. MyoA is part of a membrane-associated protein complex called the glideosome, which is essential for parasite motility and includes the MyoA light chain myosin tail domain-interacting protein (MTIP) and several glideosome-associated proteins (GAPs). However, most studies of MyoA have focused on single stages of the parasite life cycle. We examined MyoA expression throughout the Plasmodium berghei life cycle in both mammalian and insect hosts. In extracellular ookinetes, sporozoites, and merozoites, MyoA was located at the parasite periphery. In the sexual stages, zygote formation and initial ookinete differentiation precede MyoA synthesis and deposition, which occurred only in the developing protuberance. In developing intracellular asexual blood stages, MyoA was synthesized in mature schizonts and was located at the periphery of segmenting merozoites, where it remained throughout maturation, merozoite egress, and host cell invasion. Besides the known GAPs in the malaria parasite, the complex included GAP40, an additional myosin light chain designated essential light chain (ELC), and several other candidate components. This ELC bound the MyoA neck region adjacent to the MTIP-binding site, and both myosin light chains co-located to the glideosome. Co-expression of MyoA with its two light chains revealed that the presence of both light chains enhances MyoA-dependent actin motility. In conclusion, we have established a system to study the interplay and function of the three glideosome components, enabling the assessment of inhibitors that target this motor complex to block host cell invasion.

The myosin superfamily comprises of actin‐dependent eukaryotic molecular motors important in a variety of cellular functions. Although well studied in many systems, knowledge of their functions in Plasmodium, the causative agent of malaria, is restricted. Previously, six myosins were identified in this genus, including three Class XIV myosins found only in Apicomplexa and some Ciliates. The well characterized MyoA is a Class XIV myosin essential for gliding motility and invasion. Here, we characterize all other Plasmodium myosins throughout the parasite life cycle and show that they have very diverse patterns of expression and cellular location. MyoB and MyoE, the other two Class XIV myosins, are expressed in all invasive stages, with apical and basal locations, respectively. Gene deletion revealed that MyoE is involved in sporozoite traversal, MyoF and MyoK are likely essential in the asexual blood stages, and MyoJ and MyoB are not essential. Both MyoB and its essential light chain (MCL‐B) are localised at the apical end of ookinetes but expressed at completely different time points. This work provides a better understanding of the role of actomyosin motors in Apicomplexan parasites, particularly in the motile and invasive stages of Plasmodium during sexual and asexual development within the mosquito., Very little was known about the family of six myosins in malaria‐causing parasites, except for a role of one in motility. We show here that myosins have a diverse pattern of expression and subcellular location through the parasite life cycle in both the mammalian host and mosquito vector. Three are essential for parasite development and growth in the mammalian bloodstream and one has a role in parasite migration to the mosquito salivary gland.

In our innovative society, forms of innovation created by civilian actors are gaining in importance. By conducting a detailed analysis of the innovation practices of a civil innovation community in the field of electromobility, this study traces how innovation can become an ideology that guides innovative action. Electromobilists represent an exclusive community in the German-speaking world that has existed for about 30 years. Their innovation activities focus on the diffusion of the electric vehicle and on a new social mobility culture. At the same time, they ideologise electromobility itself and use this ideology to coordinate their innovation practice. By coupling climate change and new mobility technologies, they show the potential to trigger innovation practice among (parts of) civil society and thus also to increase people’s willingness to accept the introduction of new mobility technologies and practices.

Myosin A (MyoA) is a Class XIV myosin implicated in gliding motility and host cell and tissue invasion by malaria parasites. MyoA is part of a membrane-associated protein complex called the glideosome, which is essential for parasite motility and includes the MyoA light chain myosin tail domain–interacting protein (MTIP) and several glideosome-associated proteins (GAPs). However, most studies of MyoA have focused on single stages of the parasite life cycle. We examined MyoA expression throughout the Plasmodium berghei life cycle in both mammalian and insect hosts. In extracellular ookinetes, sporozoites, and merozoites, MyoA was located at the parasite periphery. In the sexual stages, zygote formation and initial ookinete differentiation precede MyoA synthesis and deposition, which occurred only in the developing protuberance. In developing intracellular asexual blood stages, MyoA was synthesized in mature schizonts and was located at the periphery of segmenting merozoites, where it remained throughout maturation, merozoite egress, and host cell invasion. Besides the known GAPs in the malaria parasite, the complex included GAP40, an additional myosin light chain designated essential light chain (ELC), and several other candidate components. This ELC bound the MyoA neck region adjacent to the MTIP-binding site, and both myosin light chains co-located to the glideosome. Co-expression of MyoA with its two light chains revealed that the presence of both light chains enhances MyoA-dependent actin motility. In conclusion, we have established a system to study the interplay and function of the three glideosome components, enabling the assessment of inhibitors that target this motor complex to block host cell invasion.

Apicomplexa exhibit a unique form of substrate-dependent gliding motility central for host cell invasion and parasite dissemination. Gliding is powered by rearward translocation of apically secreted transmembrane adhesins via their interaction with the parasite actomyosin system. We report a conserved armadillo and pleckstrin homology (PH) domain-containing protein, termed glideosome-associated connector (GAC), that mediates apicomplexan gliding motility, invasion, and egress by connecting the micronemal adhesins with the actomyosin system. TgGAC binds to and stabilizes filamentous actin and specifically associates with the transmembrane adhesin TgMIC2. GAC localizes to the apical pole in invasive stages of Toxoplasma gondii and Plasmodium berghei, and apical positioning of TgGAC depends on an apical lysine methyltransferase, TgAKMT. GAC PH domain also binds to phosphatidic acid, a lipid mediator associated with microneme exocytosis. Collectively, these findings indicate a central role for GAC in spatially and temporally coordinating gliding motility and invasion.

The authors of this article believe that the current structure of lesson plans impede differentiation, individualization, and innovation and offer little in assessing the quality of teaching and learning. Concrete steps will be offered for planning to better respond to student diversity in meeting lesson objectives.