Androgen receptor signalling in Vascular Endothelial cells is dispensable for spermatogenesis and male fertility

<p>Abstract</p> <p>Background</p> <p>Androgen signalling is essential both for male development and function of the male reproductive system in adulthood. Within the adult testis, Germ cells (GC) do not express androgen receptor (AR) suggesting androgen-mediated promotion of spermatogenesis must act via AR-expressing somatic cell-types. Several recent studies have exploited the Cre/lox system of conditional gene-targeting to ablate AR function from key somatic cell-types in order to establish the cell-specific role of AR in promotion of male fertility. In this study, we have used a similar approach to specifically ablate AR-signalling from Vascular Endothelial (VE) cells, with a view to defining the significance of androgen signalling within this cell-type on spermatogenesis.</p> <p>Findings</p> <p>AR expression in VE cells of the testicular vasculature was confirmed using an antibody against AR. A Cre-inducible fluorescent reporter line was used to empirically establish the utility of a mouse line expressing Cre Recombinase driven by the Tie2-Promoter, for targeting VE cells. Immunofluorescent detection revealed expression of YFP (and therefore Cre Recombinase function) limited to VE cells and an interstitial population of cells, believed to be macrophages, that did not express AR. Mating of Tie2-Cre males to females carrying a floxed AR gene produced Vascular Endothelial Androgen Receptor Knockout (VEARKO) mice and littermate controls. Ablation of AR from all VE cells was confirmed; however, no significant differences in bodyweight or reproductive tissue weights could be detected in VEARKO animals and spermatogenesis and fertility was unaffected.</p> <p>Conclusions</p> <p>We demonstrate the successful generation and empirical validation of a cell-specific knockout of AR from VE cells, and conclude that AR expression in VE cells is not essential for spermatogenesis or male fertility.</p

Getting around Antarctica: new high-resolution mappings of the grounded and freely-floating boundaries of the Antarctic ice sheet created for the International Polar Year.

The boundary of grounded ice and the location of ice transitioning to a freely floating state are mapped at 15-m resolution around the entire continent of Antarctica. These data products are produced by participants of the International Polar Year project ASAID using customized software combining Landsat-7 imagery and ICESat laser altimetry. The grounded ice boundary is 53 610 km long; 74% of it abuts to floating ice shelves or outlet glaciers, 19% is adjacent to open or sea-ice covered ocean, and 7% of the boundary are land terminations with bare rock. Elevations along each line are selected from 6 candidate digital elevation models: two created from the input ICESat laser altimetry and Landsat data, two from stereo satellite imagery, and two from compilations of primarily radar altimetry. Elevation selection and an assignment of confidence in the elevation value are based on agreement with ICESat elevation values and shape of the surface inferred from the Landsat imagery. Elevations along the freely-floating boundary (called the hydrostatic line) are converted to ice thicknesses by applying a firn-correction factor and a flotation criterion. The relationship between the seaward offset of the hydrostatic line from the grounding line only weakly matches a prediction based on beam theory. Airborne data are used to validate the technique of grounding line mapping, elevation selection and ice thickness derivation. The mapped products along with the customized software to generate them and a variety of intermediate products are available from the National Snow and Ice Data Center

Bacterial ribosome collision sensing by a MutS DNA repair ATPase paralogue

Ribosome stalling during translation is detrimental to cellular fitness, but how this is sensed and elicits recycling of ribosomal subunits and quality control of associated mRNA and incomplete nascent chains is poorly understood(1,2). Here we uncover Bacillus subtilis MutS2, a member of the conserved MutS family of ATPases that function in DNA mismatch repair(3), as an unexpected ribosome-binding protein with an essential function in translational quality control. Cryo-electron microscopy analysis of affinity-purified native complexes shows that MutS2 functions in sensing collisions between stalled and translating ribosomes and suggests how ribosome collisions can serve as platforms to deploy downstream processes: MutS2 has an RNA endonuclease small MutS-related (SMR) domain, as well as an ATPase/clamp domain that is properly positioned to promote ribosomal subunit dissociation, which is a requirement both for ribosome recycling and for initiation of ribosome-associated protein quality control (RQC). Accordingly, MutS2 promotes nascent chain modification with alanine-tail degrons-an early step in RQC-in an ATPase domain-dependent manner. The relevance of these observations is underscored by evidence of strong co-occurrence of MutS2 and RQC genes across bacterial phyla. Overall, the findings demonstrate a deeply conserved role for ribosome collisions in mounting a complex response to the interruption of translation within open reading frames