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The paracingulate sulcus -PCGS- has been considered for a long time to be specific to the human brain. Its presence/absence has been discussed in relation to interindividual variability of personality traits and cognitive abilities. Recently, a putative PCGS has been observed in chimpanzee brains. To demonstrate that this newly discovered sulcus is the homologue of the PCGS in the human brain, we analyzed cytoarchitectonic and resting-state functional magnetic resonance imaging data in chimpanzee brains which did or did not display a PCGS. The results show that the organization of the mid-cingulate cortex of the chimpanzee brain is comparable to that of the human brain, both cytoarchitectonically and in terms of functional connectivity with the lateral frontal cortex. These results demonstrate that the PCGS is not human-specific but is a shared feature of the primate brain since at least the last common ancestor to humans and great apes ~6 mya.The G protein-coupled receptor 109 A (GPR109A) is robustly expressed in osteoclastic precursor macrophages. Previous studies suggested that GPR109A mediates effects of diet-derived phenolic acids such as hippuric acid (HA) and 3-(3-hydroxyphenyl) propionic acid (3-3-PPA) on promoting bone formation. However, the role of GPR109A in metabolic bone homeostasis and osteoclast differentiation has not been investigated. Using densitometric, bone histologic and molecular signaling analytic methods, we uncovered that bone mass and strength were significantly higher in tibia and spine of standard rodent diet weaned 4-week-old and 6-month-old GPR109A gene deletion (GPR109A-/-) mice, compared to their wild type controls. Osteoclast numbers in bone and in ex vivo bone marrow cell cultures were significantly decreased in GPR109A-/- mice compared to wild type controls. In accordance with these data, CTX-1 in bone marrow plasma and gene expression of bone resorption markers (TNFα, TRAP, Cathepsin K) were significantly decreased in GPR109A-/- mice, while on the other hand, P1NP was increased in serum from both male and female GPR109A-/- mice compared to their respective controls. GPR109A deletion led to suppressed Wnt/β-catenin signaling in osteoclast precursors to inhibit osteoclast differentiation and activity. Indeed, HA and 3-3-PPA substantially inhibited RANKL-induced GPR109A expression and Wnt/β-catenin signaling in osteoclast precursors and osteoclast differentiation. Resultantly, HA significantly inhibited bone resorption and increased bone mass in wild type mice, but had no additional effects on bone in GPR109A-/- mice compared with their respective untreated control mice. These results suggest an important role for GPR109A during osteoclast differentiation and bone resorption mediating effects of HA and 3-3-PPA on inhibiting bone resorption during skeletal development.Interleukin (IL)-33 is a cytokine that appears to mediate fibrosis by signaling via its receptor ST2 (IL-33R/IL1RL1). [https://www.selleckchem.com/products/ide397-gsk-4362676.html GSK-4362676 solubility dmso] It is also, however, a protein that after synthesis is sorted to the cell nucleus, where it appears to affect chromatin folding. Here we describe a novel role for nuclear IL-33 in regulating the fibroblast phenotype in murine kidney fibrosis driven by unilateral ureteral obstruction. Transcriptional profiling of IL-33-deficient kidneys 24 h after ligation revealed enhanced expression of fibrogenic genes and enrichment of gene sets involved in extracellular matrix formation and remodeling. These changes relied on intracellular effects of IL-33, because they were not reproduced by treatment with a neutralizing antibody to IL-33 that prevents IL-33R/ST2L receptor signaling nor were they observed in IL-33R/ST2-deficient kidneys. To further explore the intracellular function of IL-33, we established transcription profiles of human fibroblasts, observing that knockdown of IL-33 skewed the transcription profile from an inflammatory towards a myofibroblast phenotype, reflected in higher levels of COL3A1, COL5A1 and transgelin protein, as well as lower expression levels of IL6, CXCL8, CLL7 and CCL8. In conclusion, our findings suggest that nuclear IL-33 in fibroblasts dampens the initial profibrotic response until persistent stimuli, as enforced by UUO, can override this protective mechanism.Phenotypic convergence, describing the independent evolution of similar characteristics, offers unique insights into how natural selection influences developmental and molecular processes to generate shared adaptations. The extinct marsupial thylacine and placental gray wolf represent one of the most extraordinary cases of convergent evolution in mammals, sharing striking cranial similarities despite 160 million years of independent evolution. We digitally reconstructed their cranial ontogeny from birth to adulthood to examine how and when convergence arises through patterns of allometry, mosaicism, modularity, and integration. We find the thylacine and wolf crania develop along nearly parallel growth trajectories, despite lineage-specific constraints and heterochrony in timing of ossification. These constraints were found to enforce distinct cranial modularity and integration patterns during development, which were unable to explain their adult convergence. Instead, we identify a developmental origin for their convergent cranial morphologies through patterns of mosaic evolution, occurring within bone groups sharing conserved embryonic tissue origins. Interestingly, these patterns are accompanied by homoplasy in gene regulatory networks associated with neural crest cells, critical for skull patterning. Together, our findings establish empirical links between adaptive phenotypic and genotypic convergence and provides a digital resource for further investigations into the developmental basis of mammalian evolution.Slow deformations associated with a subducting slab can affect quasi-static displacements and seismicity over a wide range of depths. Here, we analyse the seismotectonic activities in the Tonga subduction zone, which is the world's most active area with regard to deep earthquakes. In our study, we combine data from global navigation satellite systems with an earthquake catalogue. We focus on the deep earthquakes that are below 400 km at the lower part of the Wadati-Benioff zone. We find that trenchward transient displacements and quiescence of deep earthquakes, in terms of background seismicity, were bounded in time by large intraslab earthquakes in 2009 and 2013. This "slow deformation event" between 2009 and 2013 may have been triggered by a distant and shallow M8.1 earthquake, which implies a slow slip event at the plate interface or a temporal acceleration of the subduction of the Pacific Plate. These findings provide new insights into the relationship between shallow and deep earthquakes in the subduction zone.