Luminal Rank loss decreases cell fitness leading to basal cell bipotency in parous mammary glands

Rank signaling pathway regulates mammary gland homeostasis and epithelial cell differentiation. Although Rank receptor is expressed by basal cells and luminal progenitors, its role in each individual cell lineage remains unclear. By combining temporal/lineage specific Rank genetic deletion with lineage tracing techniques, we found that loss of luminal Rank reduces the luminal progenitor pool and leads to aberrant alveolar-like differentiation with high protein translation capacity in virgin mammary glands. These Rank-deleted luminal cells are unable to expand during the first pregnancy, leading to lactation failure and impairment of protein synthesis potential in the parous stage. The unfit parous Rank-deleted luminal cells in the alveoli are progressively replaced by Rank-proficient cells early during the second pregnancy, thereby restoring lactation. Transcriptomic analysis and functional assays point to the awakening of basal bipotency after pregnancy by the induction of Rank/NF-kappa B signaling in basal parous cell to restore lactation and tissue homeostasis. Rocha and co-authors show that loss of luminal Rank signaling causes abnormal alveolar differentiation and lactation failure. Subsequent pregnancies activate bipotency in basal cells, replacing unfit luminal cells, and restoring lactation

RANK links senescence to stemness in the mammary epithelia, delaying tumor onset but increasing tumor aggressiveness

Rank signaling enhances stemness in mouse and human mammary epithelial cells (MECs) and mediates mammary tumor initiation. Mammary tumors initiated by oncogenes or carcinogen exposure display high levels of Rank and Rank pathway inhibitors have emerged as a new strategy for breast cancer prevention and treatment. Here, we show that ectopic Rank expression in the mammary epithelia unexpectedly delays tumor onset and reduces tumor incidence in the oncogene-driven Neu and PyMT models. Mechanistically, we have found that ectopic expression of Rank or exposure to Rankl induces senescence, even in the absence of other oncogenic mutations. Rank leads to DNA damage and senescence through p16/p19. Moreover, RANK-induced senescence is essential for Rank-driven stemness, and although initially translates into delayed tumor growth, eventually promotes tumor progression and metastasis. We uncover a dual role for Rank in the mammary epithelia: Rank induces senescence and stemness, delaying tumor initiation but increasing tumor aggressiveness

Sex-Related Effects of an Immune Challenge on Growth and Begging Behavior of Barn Swallow Nestlings

Parent-offspring conflicts lead the offspring to evolve reliable signals of individual quality, including parasite burden, which may allow parents to adaptively modulate investment in the progeny. Sex-related variation in offspring reproductive value, however, may entail differential investment in sons and daughters. Here, we experimentally manipulated offspring condition in the barn swallow (Hirundo rustica) by subjecting nestlings to an immune challenge (injection with bacterial lipopolysaccharide, LPS) that simulates a bacterial infection, and assessed the effects on growth, feather quality, expression of morphological (gape coloration) and behavioral (posture) begging displays involved in parent-offspring communication, as well as on food allocation by parents. Compared to sham-injected controls, LPS-treated chicks suffered a depression of body mass and a reduction of palate color saturation. In addition, LPS treatment resulted in lower feather quality, with an increase in the occurrence of fault bars on wing feathers. The color of beak flanges, feather growth and the intensity of postural begging were affected by LPS treatment only in females, suggesting that chicks of either sex are differently susceptible to the immune challenge. However, irrespective of the effects of LPS, parents equally allocated food among control and challenged offspring both under normal food provisioning and after a short period of food deprivation of the chicks. These results indicate that bacterial infection and the associated immune response entail different costs to offspring of either sex, but a decrease in nestling conditions does not affect parental care allocation, possibly because the barn swallow adopts a brood-survival strategy. Finally, we showed that physiological stress induced by pathogens impairs plumage quality, a previously neglected major negative impact of bacterial infection which could severely affect fitness, particularly among long-distance migratory birds

Overview of recent TJ-II stellarator results

The main results obtained in the TJ-II stellarator in the last two years are reported. The most important topics investigated have been modelling and validation of impurity transport, validation of gyrokinetic simulations, turbulence characterisation, effect of magnetic configuration on transport, fuelling with pellet injection, fast particles and liquid metal plasma facing components. As regards impurity transport research, a number of working lines exploring several recently discovered effects have been developed: the effect of tangential drifts on stellarator neoclassical transport, the impurity flux driven by electric fields tangent to magnetic surfaces and attempts of experimental validation with Doppler reflectometry of the variation of the radial electric field on the flux surface. Concerning gyrokinetic simulations, two validation activities have been performed, the comparison with measurements of zonal flow relaxation in pellet-induced fast transients and the comparison with experimental poloidal variation of fluctuations amplitude. The impact of radial electric fields on turbulence spreading in the edge and scrape-off layer has been also experimentally characterized using a 2D Langmuir probe array. Another remarkable piece of work has been the investigation of the radial propagation of small temperature perturbations using transfer entropy. Research on the physics and modelling of plasma core fuelling with pellet and tracer-encapsulated solid-pellet injection has produced also relevant results. Neutral beam injection driven Alfvénic activity and its possible control by electron cyclotron current drive has been examined as well in TJ-II. Finally, recent results on alternative plasma facing components based on liquid metals are also presentedThis work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014–2018 under Grant Agreement No. 633053. It has been partially funded by the Ministerio de Ciencia, Inovación y Universidades of Spain under projects ENE2013-48109-P, ENE2015-70142-P and FIS2017-88892-P. It has also received funds from the Spanish Government via mobility grant PRX17/00425. The authors thankfully acknowledge the computer resources at MareNostrum and the technical support provided by the Barcelona S.C. It has been supported as well by The Science and Technology Center in Ukraine (STCU), Project P-507F