Fluorescent Probes for Ecto-5′-nucleotidase (CD73)

Ecto-5′-nucleotidase (CD73) catalyzes the hydrolysis of AMP to anti-inflammatory, immunosuppressive adenosine. It is expressed on vascular endothelial, epithelial, and also numerous cancer cells where it strongly contributes to an immunosuppressive microenvironment. In the present study we designed and synthesized fluorescent-labeled CD73 inhibitors with low nanomolar affinity and high selectivity based on N6-benzyl-α,β-methylene-ADP (PSB-12379) as a lead structure. Fluorescein was attached to the benzyl residue via different linkers resulting in PSB-19416 (14b, Ki12.6 nM) and PSB-18332 (14a, Ki2.98 nM) as fluorescent high-affinity probes for CD73. These compounds are anticipated to become useful tools for biological studies, drug screening, and diagnostic applications

Digital Periphery? A Community Case Study of Digitalization Efforts in Swiss Mountain Regions

Rural economies have undergone major changes in recent years as traditional rural economic sectors declined and shifted. At the same time, digital technologies emerged and rural communities experience profound transformations. In this chapter, we analyze how technological change leads to changing rural economies in a Swiss mountain community. Although Switzerland has one of the highest national coverage of broadband in the world, there is a lack of knowledge regarding the transformation of its rural economy due to digitalization. The community case study’s 46 qualitative interviews show that digital connectivity in peripheral mountain communities is experienced differently by various actors. On the one hand, digitalization offers new economic opportunities to larger businesses, larger hotels, schools and health service providers. On the other hand, particularly smaller businesses struggle with the high cost of becoming digital and their owners tend to become more cautious and stressed as competition and price transparencies in the digital economy become intensified. In terms of spatial aspects, we argue that digitalization reduces cognitive distance between core and periphery while physical distance between the urban and the rural still exist

Three-dimensional analysis of the early development of the dentition

Tooth development has attracted the attention of researchers since the 19th century. It became obvious even then that morphogenesis could not fully be appreciated from two-dimensional histological sections. Therefore, methods of three-dimensional (3D) reconstructions were employed to visualize the surface morphology of developing structures and to help appreciate the complexity of early tooth morphogenesis. The present review surveys the data provided by computer-aided 3D analyses to update classical knowledge of early odontogenesis in the laboratory mouse and in humans. 3D reconstructions have demonstrated that odontogenesis in the early stages is a complex process which also includes the development of rudimentary odontogenic structures with different fates. Their developmental, evolutionary, and pathological aspects are discussed. The combination of in situ hybridization and 3D reconstruction have demonstrated the temporo-spatial dynamics of the signalling centres that reflect transient existence of rudimentary tooth primordia at loci where teeth were present in ancestors. The rudiments can rescue their suppressed development and revitalize, and then their subsequent autonomous development can give rise to oral pathologies. This shows that tooth-forming potential in mammals can be greater than that observed from their functional dentitions. From this perspective, the mouse rudimentary tooth primordia represent a natural model to test possibilities of tooth regeneration