Endogenous retroviruses shape pluripotency specification in mouse embryos.

The smooth and precise transition from totipotency to pluripotency is a key process in embryonic development, generating pluripotent stem cells capable of forming all cell types. While endogenous retroviruses (ERVs) are essential for early development, their precise roles in this transition remains mysterious. Using cutting-edge genetic and biochemical techniques in mice, we identify MERVL-gag, a retroviral protein, as a crucial modulator of pluripotent factors OCT4 and SOX2 during lineage specification. MERVL-gag tightly operates with URI, a prefoldin protein that concurs with pluripotency bias in mouse blastomeres, and which is indeed required for totipotency-to-pluripotency transition. Accordingly, URI loss promotes a stable totipotent-like state and embryo arrest at 2C stage. Mechanistically, URI binds and shields OCT4 and SOX2 from proteasome degradation, while MERVL-gag displaces URI from pluripotent factor interaction, causing their degradation. Our findings reveal the symbiotic coevolution of ERVs with their host cells to ensure the smooth and timely progression of early embryo development.

Transit-amplifying cells control R-spondins in the mouse crypt to modulate intestinal stem cell proliferation.

Intestinal epithelium regenerates rapidly through proliferation of intestinal stem cells (ISCs), orchestrated by potent mitogens secreted within the crypt niche. However, mechanisms regulating these mitogenic factors remain largely unknown. Here, we demonstrate that transit-amplifying (TA) cells, marked by unconventional prefoldin RPB5 interactor (URI), control R-spondin production to guide ISC proliferation. Genetic intestinal URI ablation in mice injures TA cells, reducing their survival capacity, leading to an inflamed tissue and subsequently decreasing R-spondin levels, thereby causing ISC quiescence and disruption of intestinal structure. R-spondin supplementation or restoration of R-spondin levels via cell death inhibition by c-MYC elimination or the suppression of inflammation reinstates ISC proliferation in URI-depleted mice. However, selective c-MYC and p53 suppression are required to fully restore TA cell survival and differentiation capacity and preserve complete intestinal architecture. Our data reveal an unexpected role of TA cells, which represent a signaling platform instrumental for controlling inflammatory cues and R-spondin production, essential for maintaining ISC proliferation and tissue regeneration.

Design of Customized TPU Lattice Structures for Additive Manufacturing: Influence on the Functional Properties in Elastic Products.

This work focuses on evaluating and establishing the relationship of the influence of geometrical and manufacturing parameters in stiffness of additively manufactured TPU lattice structures. The contribution of this work resides in the creation of a methodology that focuses on characterizing the behavior of elastic lattice structures. Likewise, resides in the possibility of using the statistical treatment of results as a guide to find favorable possibilities within the range of parameters studied and to predict the behavior of the structures. In order to characterize their behavior, different types of specimens were designed and tested by finite element simulation of a compression process using Computer Aided Engineering (CAE) tools. The tests showed that the stiffness depends on the topology of the cells of the lattice structure. For structures with different cell topologies, it has been possible to obtain an increase in the reaction force against compression from 24.7 N to 397 N for the same manufacturing conditions. It was shown that other parameters with a defined influence on the stiffness of the structure were the temperature and the unit size of the cells, all due to the development of fusion mechanisms and the variation in the volume of material used, respectively.

Influence of 3D-Printed TPU Properties for the Design of Elastic Products.

The design of products with elastic properties is a paradigm for design engineers because the properties of the material define the correct functionality of the product. Fused filament fabrication (FFF) allows for the printing of products in thermoplastic polyurethanes (TPU). Therefore, it offers the ability to design elastic products with the freedom of forms that this technology allows and also with greater variation of elastic properties than with a conventional process. The internal structures and the variation in thickness that can be used facilitate the design of products with different elastic realities, producing variations in the elasticity of the product with the same material. This work studies the influence of the variation of internal density as a function of basic geometries in order to quantify the difference in elasticity produced on a product when it is designed. Likewise, a case study was carried out with the creation of a fully elastic computer keyboard printed in 3D. The specimens were subjected to compression to characterize the behavior of the structures. The tests showed that the elasticity varies depending on the orientation and geometry, with the highest compressive strength observed in the vertical orientation with 80% lightening. In addition, the internal lightening increases the elasticity progressively but not uniformly with respect to the solid geometry, and also the flat faces favour the reduction in elasticity. This study classifies the behavior of TPU with the aim of being applied to the design and manufacture of products with specific properties. In this work, a totally flexible and functional keyboard was designed, obtaining elasticity values that validate the study carried out.

URI is required to maintain intestinal architecture during ionizing radiation.

Ionizing radiation (IR) can cause gastrointestinal syndrome (GIS), a lethal disorder, by means of unknown mechanisms. We show that high-dose irradiation increases unconventional prefoldin RPB5 interactor (URI) levels in mouse intestinal crypt, but organ regeneration correlates with URI reductions. URI overexpression in intestine protects mice from radiation-induced GIS, whereas halving URI expression sensitizes mice to IR. URI specifically inhibits ß-catenin in stem cell-like label-retaining (LR) cells, which are essential for organ regeneration after IR. URI reduction activates ß-catenin-induced c-MYC expression, causing proliferation of and DNA damage to LR cells, rendering them radiosensitive. Therefore, URI labels LR cells which promote tissue regeneration in response to high-dose irradiation, and c-MYC inhibitors could be countermeasures for humans at risk of developing GIS.