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Abstract Sepsis results from systemic, dysregulated inflammatory responses to infection, culminating in multiple organ failure. Here, we demonstrate the utility of CD5L for treating experimental sepsis caused by cecal ligation and puncture (CLP). We show that CD5L’s important features include its ability to enhance neutrophil recruitment and activation by increasing circulating levels of CXCL1, and to promote neutrophil phagocytosis. CD5L-deficient mice exhibit impaired neutrophil recruitment and compromised bacterial control, rendering them susceptible to attenuated CLP. CD5L-/- peritoneal cells from mice subjected to medium-grade CLP exhibit a heightened pro-inflammatory transcriptional profile, reflecting a loss of control of the immune response to the infection. Intravenous administration of recombinant CD5L (rCD5L) in immunocompetent C57BL/6 wild-type (WT) mice significantly ameliorates measures of disease in the setting of high-grade CLP-induced sepsis. Furthermore, rCD5L lowers endotoxin and damage-associated molecular pattern (DAMP) levels, and protects WT mice from LPS-induced endotoxic shock. These findings warrant the investigation of rCD5L as a possible treatment for sepsis in humans.

Abstract The hindlimb and external genitalia of present-day tetrapods are thought to derive from an ancestral common primordium that evolved to generate a wide diversity of structures adapted for efficient locomotion and mating in the ecological niche occupied by the species. We show that despite long evolutionary distance from the ancestral condition, the early primordium of the mouse external genitalia preserved the capacity to take hindlimb fates. In the absence of Tgfbr1, the pericloacal mesoderm generates an extra pair of hindlimbs at the expense of the external genitalia. It has been shown that the hindlimb and the genital primordia share many of their key regulatory factors. Tgfbr1 controls the response to those factors by modulating the accessibility status of regulatory elements that control the gene regulatory networks leading to the formation of genital or hindlimb structures. Our work uncovers a remarkable tissue plasticity with potential implications in the evolution of the hindlimb/genital area of tetrapods, and identifies an additional mechanism for Tgfbr1 activity that might also contribute to the control of other physiological or pathological processes.

Abstract The patchy distribution of trees typical of savannas often results in a discontinuous distribution of water, nutrient resources, and microbial communities in soil, commonly referred to as “islands of fertility”. We assessed how this phenomenon may affect the establishment and impact of invasive plants, using the invasion of Opuntia stricta in South Africa’s Kruger National Park as case study. We established uninvaded and O. stricta-invaded plots under the most common woody tree species in the study area (Vachellia nilotica subsp. kraussiana and Spirostachys africana) and in open patches with no tree cover. We then compared soil characteristics, diversity and composition of the soil bacterial communities, and germination performance of O. stricta and native trees between soils collected in each of the established plots. We found that the presence of native trees and invasive O. stricta increases soil water content and nutrients, and the abundance and diversity of bacterial communities, and alters soil bacterial composition. Moreover, the percentage and speed of germination of O. stricta were higher in soils conditioned by native trees compared to soils collected from open patches. Finally, while S. africana and V. nilotica trees appear to germinate equally well in invaded and uninvaded soils, O. stricta had lower and slower germination in invaded soils, suggesting the potential release of phytochemicals by O. stricta to avoid intraspecific competition. These results suggest that the presence of any tree or shrub in savanna ecosystems, regardless of origin (i.e. native or alien), can create favourable conditions for the establishment and growth of other plants.