Sexually dimorphic activation of innate antitumor immunity prevents adrenocortical carcinoma development.

Unlike most cancers, adrenocortical carcinomas (ACCs) are more frequent in women than in men, but the underlying mechanisms of this sexual dimorphism remain elusive. Here, we show that inactivation of Znrf3 in the mouse adrenal cortex, recapitulating the most frequent alteration in ACC patients, is associated with sexually dimorphic tumor progression. Although female knockouts develop metastatic carcinomas at 18 months, adrenal hyperplasia regresses in male knockouts. This male-specific phenotype is associated with androgen-dependent induction of senescence, recruitment, and differentiation of highly phagocytic macrophages that clear out senescent cells. In contrast, in females, macrophage recruitment is delayed and dampened, which allows for aggressive tumor progression. Consistently, analysis of TCGA-ACC data shows that phagocytic macrophages are more prominent in men and are associated with better prognosis. Together, these data show that phagocytic macrophages are key players in the sexual dimorphism of ACC that could be previously unidentified allies in the fight against this devastating cancer.

Update on Müller glia regenerative potential for retinal repair.

Retinal regeneration efficiency from Müller glia varies tremendously among vertebrate species, being extremely limited in mammals. Efforts towards the identification of molecular mechanisms underlying Müller cell proliferative and neurogenic potential should help finding strategies to awake them and ensure regeneration in mammals. We provide here an update on the most recent and original progresses made in the field. These include remarkable discoveries regarding (i) unprecedented cross-species comparison of Müller cell transcriptome using single-cell technologies, (ii) the identification of new strategies to promote both the proliferative and the neurogenic potential of mammalian Müller cells, (iii) the role of the epigenome in regulating Müller glia plasticity, (iv) miRNA-based regulatory mechanisms of Müller cell response to injury, and (v) the influence of inflammatory signals on the regenerative process.

Yap haploinsufficiency leads to Müller cell dysfunction and late-onset cone dystrophy.

Hippo signalling regulates eye growth during embryogenesis through its effectors YAP and TAZ. Taking advantage of a Yap heterozygous mouse line, we here sought to examine its function in adult neural retina, where YAP expression is restricted to Müller glia. We first discovered an unexpected temporal dynamic of gene compensation. At postnatal stages, Taz upregulation occurs, leading to a gain of function-like phenotype characterised by EGFR signalling potentiation and delayed cell-cycle exit of retinal progenitors. In contrast, Yap+/- adult retinas no longer exhibit TAZ-dependent dosage compensation. In this context, Yap haploinsufficiency in aged individuals results in Müller glia dysfunction, late-onset cone degeneration, and reduced cone-mediated visual response. Alteration of glial homeostasis and altered patterns of cone opsins were also observed in Müller cell-specific conditional Yap-knockout aged mice. Together, this study highlights a novel YAP function in Müller cells for the maintenance of retinal tissue homeostasis and the preservation of cone integrity. It also suggests that YAP haploinsufficiency should be considered and explored as a cause of cone dystrophies in human.

Desafíos para la enseñanza de ciencias médicas en condiciones de contingencia

La pandemia de COVID-19 contribuyó a la afectación del proceso tradicional de formación de profesionales de la salud, por lo que fueron implementados, de forma abrupta, ajustes y modificaciones que garantizaran la continuidad del proceso de enseñanza-aprendizaje. El objetivo de la revisión bibliográfica consiste en una actualización de las adecuaciones en los métodos de enseñanza en los diferentes escenarios docentes durante las diferentes etapas de contingencia. La revisión incluyó publicaciones, en su mayoría del período 2019-2021, y se emplearon principalmente las bases de datos ESBCO, CUMED y SciELO. Como resultado de la investigación, se plantea la complementación de las clases presenciales por otras modalidades a distancia, ya sea de tipo virtual o en línea: una forma de semipresencialidad, con un mayor empleo de las redes sociales y plataformas virtuales. En conclusión, la enseñanza de ciencias médicas en tiempos de contingencia constituye un reto, ya que ha sido necesario pasar de la enseñanza presencial tradicional a otras modalidades, con énfasis en las tecnologías de la información y de la comunicación, y así reorganizar la educación para garantizar la formación de profesionales de la salud.

The pandemic of COVID-19 contributed to affect the traditional training process of the health professionals, which is why adjustments and modifications were abruptly implemented to guarantee the continuity of the teaching-learning process. The objective of the bibliographical review is to update the adequacy in the teaching methods in the different teaching scenarios during the different contingency stages. The review included publications, mostly from the period 2019-2021, and database used were mainly EBSCO, CUMED and SciELO. As a result of the research, it is proposed the complementation of face-to-face classes by other remote modalities, either virtual or online: a semi-face-to-face form, with a bigger employment of the social networks and virtual platforms. In conclusion, the teaching of medical sciences in times of contingency is a challenge, since it has been necessary to move from traditional face-to-face education to other forms, with emphasis on information and communication technologies, and thus reorganize education to ensure the training of health professionals.

Linking YAP to Müller Glia Quiescence Exit in the Degenerative Retina.

Contrasting with fish or amphibian, retinal regeneration from Müller glia is largely limited in mammals. In our quest toward the identification of molecular cues that may boost their stemness potential, we investigated the involvement of the Hippo pathway effector YAP (Yes-associated protein), which is upregulated in Müller cells following retinal injury. Conditional Yap deletion in mouse Müller cells prevents cell-cycle gene upregulation that normally accompanies reactive gliosis upon photoreceptor cell death. We further show that, in Xenopus, a species endowed with efficient regenerative capacity, YAP is required for their injury-dependent proliferative response. In the mouse retina, where Müller cells do not spontaneously proliferate, YAP overactivation is sufficient to induce their reprogramming into highly proliferative cells. Overall, we unravel a pivotal role for YAP in tuning Müller cell proliferative response to injury and highlight a YAP-EGFR (epidermal growth factor receptor) axis by which Müller cells exit their quiescence state, a critical step toward regeneration.