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Squamous penile cancer displays a rare human papillomavirus (HPV)–associated tumor entity. Investigations on the molecular pathogenesis of HPV-driven penile cancer are impaired by the rareness of clinical specimens and, in particular, are missing relevant cell culture models. Here, we identified in HPV-positive penile cancer cell lines that HPV16 oncoproteins control TP63 expression by modulating critical regulators, while integration into the TP63 open reading frame facilitates oncogene expression. The resulting feed-forward loop leads to elevated p63 levels that in turn enhance the release of the neutrophil-recruiting chemokine CXCL8. Remarkably, elevated CXCL8 amounts lead to the increased surface exposition of the Fc receptor of human IgA antibodies, FcαRI, on neutrophils and correlated with a higher susceptibility to antibody-dependent neutrophil-mediated cytotoxicity (ADCC) using an EGFR-specific IgA2 antibody. IHC staining of tissue microarrays proved that elevated expression of p63 together with neutrophil infiltration were significantly more frequent in HPV-positive penile cancer displaying a higher tumor grade. In summary, we identified a promising marker profile of patients with penile cancer at higher risk for worse prognosis. However, these patients may benefit from immunotherapeutic approaches efficiently engaging neutrophils for tumor cell killing.

Squamous penile cancer displays a rare human papillomavirus (HPV)–associated tumor entity. Investigations on the molecular pathogenesis of HPV-driven penile cancer are impaired by the rareness of clinical specimens and, in particular, are missing relevant cell culture models. Here, we identified in HPV-positive penile cancer cell lines that HPV16 oncoproteins control TP63 expression by modulating critical regulators, while integration into the TP63 open reading frame facilitates oncogene expression. The resulting feed-forward loop leads to elevated p63 levels that in turn enhance the release of the neutrophil-recruiting chemokine CXCL8. Remarkably, elevated CXCL8 amounts lead to the increased surface exposition of the Fc receptor of human IgA antibodies, FcαRI, on neutrophils and correlated with a higher susceptibility to antibody-dependent neutrophil-mediated cytotoxicity (ADCC) using an EGFR-specific IgA2 antibody. IHC staining of tissue microarrays proved that elevated expression of p63 together with neutrophil infiltration were significantly more frequent in HPV-positive penile cancer displaying a higher tumor grade. In summary, we identified a promising marker profile of patients with penile cancer at higher risk for worse prognosis. However, these patients may benefit from immunotherapeutic approaches efficiently engaging neutrophils for tumor cell killing.

Little morphological information is available about subretinal pigment shields in insect compound eyes, especially ultrastructural information. The latter is however needed in order to detect possible smallest projections that emanate from pigment-granule-bearing cells and pass through the basal matrix (BM), but that are not visible in light micrographs. Previous work on the subretinal pigment shield in Drosophila melanogaster suggests that the pigment cell population located below the BM is closely associated with secondary and tertiary pigment cells. Whether these cells stay in connection throughout life with the subretinal regions via thin projections that pass through the fenestrae of the BM, or whether the subretinal parts later become separated during eye development remained so far unknown. Our investigation of the periphery of the BM by three-dimensional reconstruction based on serial-sectioning transmission electron microscopy has revealed that the secondary and tertiary pigment cells possess thin projections that pass through the fenestrae of the BM and thus connect the cellular regions above and below the BM in the adult compound eye. The subretinal pigment shield of D. melanogaster is therefore of retinal origin and is not composed of additional subretinal pigment cells. The maintained bond allows the active displacement of pigment granules below the BM during the process of dark and light adaptation of the compound eye.

Agricultural intensification is one of the most important drivers of biodiversity loss. To preserve taxonomic diversity in agricultural landscapes, there is an increasing need for refuge areas within agroecosystems, but best practices for providing such sites are debated. Here, we compared the taxonomic diversity and trait composition of spiders, being important terrestrial predators, among cereal fields, grassy field margins, set aside fields sown with wildflowers, and semi-natural sites within an agricultural landscape in western Germany. Spider taxonomic diversity was similarly high in all non-crop habitats, indicating a surprisingly high value of field margins and set-aside fields. Cereal fields, in contrast, were dominated by a few, mainly euryecious species. Moreover, community mean body size was smallest on cereal fields but highest on semi-natural sites, suggesting that spider body size may serve as a valuable indicator of the level of anthropogenic disturbance. Spider communities differed partly among non-crop habitats, stressing the need for combining different conservation measures to maximize taxonomic biodiversity and trait composition. These should also include remnants of natural vegetation, which were especially important for large and red list species and therefore for reaching the aims of nature conservation.

Pigment granules, found in different cell types of the retina in insect compound eyes, fulfill important functions. They isolate the individual ommatidia from stray light, regulate the angular sensitivity, and restrict the light that reaches the photoreceptor according to ambient light intensities. Descriptions of pigment cells within the retina are included in ultrastructural eye descriptions, but knowledge of pigment cell types beneath the retina and basal matrix (BM) are relatively limited in insects. In the miniaturized parasitoid wasp Trichogramma evanescens Westwood 1833, a sub-retinal pigment shield is formed by pigment-bearing cells, which appear in two-dimensional TEM sections to form a separate population beneath the BM. By using three-dimensional reconstructions of serial-section transmission electron microscopy, it was possible to reveal that the sub-retinal pigment shield of T. evanescens is not formed by a separate cell type, but by extensions of the lateral rim pigment cells that penetrate gaps in the BM. The reconstruction is supported by evidence from a statistical analysis of pigment granule volumes of all pigment bearing cell types in the retina and rim region. The study reveals the first known case of the participation of lateral rim cells in a sub-retinal pigment shield in an insect eye. As neither pigmented extensions of secondary pigment cells, nor pigment granules in the extensions of the cone cell projections are present above the BM in T. evanescens, the sub-retinal extensions of the lateral rim cells can be seen as a functional adaptation to miniaturization in order to maintain a proximal shielding function.

Low-fidelity fabrication systems speed up rapid prototyping by printing intermediate versions of a prototype as fast, low-fidelity previews. Only the final version is fabricated as a full high-fidelity 3D print. This allows designers to iterate more quickly-achieving a better design in less time. Depending on what is currently being tested, low-fidelity fabrication is implemented in different ways: (1) faBrickator allows for a modular approach by substituting sub-volumes of the 3D model with building blocks. (2) WirePrint allows for quickly testing the shape of an object, such as the ergonomic fit, by printing wireframe structures. (3) Platener preserves the technical function by substituting 3D print with laser-cut plates of the same size and thickness. At our CHI'15 interactivity booth, we give a combined live demo of all three low-fidelity fabrication systems- putting special focus on our new low-fidelity fabrication system Platener (paper at CHI'15).