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Conventionally, the size, shape, and biomechanics of cartilages are determined by their voluminous extracellular matrix. By contrast, we found that multiple murine cartilages consist of lipid-filled cells called lipochondrocytes. Despite resembling adipocytes, lipochondrocytes were molecularly distinct and produced lipids exclusively through de novo lipogenesis. Consequently, lipochondrocytes grew uniform lipid droplets that resisted systemic lipid surges and did not enlarge upon obesity. Lipochondrocytes also lacked lipid mobilization factors, which enabled exceptional vacuole stability and protected cartilage from shrinking upon starvation. Lipid droplets modulated lipocartilage biomechanics by decreasing the tissue’s stiffness, strength, and resilience. Lipochondrocytes were found in multiple mammals, including humans, but not in nonmammalian tetrapods. Thus, analogous to bubble wrap, superstable lipid vacuoles confer skeletal tissue with cartilage-like properties without “packing foam–like” extracellular matrix. 

Abstract The past decade has experienced renewed interest in the physical processes that fold the developing cerebral cortex. Biomechanical models and experiments suggest that growth of the cortex, outpacing growth of underlying subcortical tissue (prospective white matter), is sufficient to induce folding. However, current models do not explain the well-established links between white matter organization and fold morphology, nor do they consider subcortical remodeling that occurs during the period of folding. Here we propose a framework by which cortical folding may induce subcortical fiber growth and organization. Simulations incorporating stress-induced fiber elongation indicate that subcortical stresses resulting from folding are sufficient to induce stereotyped fiber organization beneath gyri and sulci. Model predictions are supported by high-resolution ex vivo diffusion tensor imaging of the developing rhesus macaque brain. Together, results provide support for the theory of cortical growth-induced folding and indicate that mechanical feedback plays a significant role in brain connectivity. 

Abstract Niche signals maintain stem cells in a prolonged quiescence or transiently activate them for proper regeneration 1 . Altering balanced niche signalling can lead to regenerative disorders. Melanocytic skin nevi in human often display excessive hair growth, suggesting hair stem cell hyperactivity. Here, using genetic mouse models of nevi 2,3 , we show that dermal clusters of senescent melanocytes drive epithelial hair stem cells to exit quiescence and change their transcriptome and composition, potently enhancing hair renewal. Nevus melanocytes activate a distinct secretome, enriched for signalling factors. Osteopontin, the leading nevus signalling factor, is both necessary and sufficient to induce hair growth. Injection of osteopontin or its genetic overexpression is sufficient to induce robust hair growth in mice, whereas germline and conditional deletions of either osteopontin or CD44, its cognate receptor on epithelial hair cells, rescue enhanced hair growth induced by dermal nevus melanocytes. Osteopontin is overexpressed in human hairy nevi, and it stimulates new growth of human hair follicles. Although broad accumulation of senescent cells, such as upon ageing or genotoxic stress, is detrimental for the regenerative capacity of tissue 4 , we show that signalling by senescent cell clusters can potently enhance the activity of adjacent intact stem cells and stimulate tissue renewal. This finding identifies senescent cells and their secretome as an attractive therapeutic target in regenerative disorders. 

Objectives Oral direct-acting antivirals (DAAs) for hepatitis C virus (HCV) have dramatically changed the treatment paradigm. Our aim was to project temporal trends in HCV diagnosis, treatment and disease burden in France, Germany, Italy, Spain and the UK. Design A mathematical simulation model of natural history of HCV infection. Participants HCV-infected patients defined based on country-specific age, fibrosis and genotype distributions. Interventions HCV screening practice and availability of different waves of DAA treatment in each country. Outcome measures Temporal trends in the number of patients who achieve sustained virological response (SVR), fail treatment (by drug regimen) and develop advanced sequelae from 2014 to 2030 in each country. Results We projected that 1 324 000 individuals would receive treatment from 2014 to 2030 in the five European countries and 12 000–37 000 of them would fail to achieve SVR. By 2021, the number of individuals cured of HCV would supersede the number of actively infected individuals in France, Germany, Spain and the UK. Under status quo, the diagnosis rate would reach between 65% and 75% and treatment coverage between 65% and 74% by 2030 in these countries. The number of patients who fail treatment would decrease over time, with the majority of those who fail treatment having been exposed to non-structural protein 5A inhibitors. Conclusions In the era of DAAs, the number of people with HCV who achieved a cure will exceed the number of viraemic patients, but many patients will remain undiagnosed, untreated, fail multiple treatments and develop advanced sequelae. Scaling-up screening and treatment capacity, and timely and effective retreatment are needed to avail the full benefits of DAAs and to meet HCV elimination targets set by WHO. 

High-energy cosmic rays that hit the Earth can be used to study large-scale atmospheric perturbations. After a first interaction in the upper parts of the atmosphere, cosmic rays produce a shower of particles that sample it down to the detector level. The HAWC (High-Altitude Water Cherenkov) gamma-ray observatory in Central Mexico at 4,100 m elevation detects air shower particles continuously with 300 water Cherenkov detectors with an active area of 12,500 m2. On January 15th, 2022, HAWC detected the passage of the pressure wave created by the explosion of the Hunga volcano in the Tonga islands, 9,000 km away, as an anomaly in the measured rate of shower particles. The HAWC measurements are used to determine the propagation speed of four pressure wave passages, and correlate the variations of the shower particle rates with the barometric pressure changes. The profile of the shower particle rate and atmospheric pressure variations for the first transit of the pressure wave at HAWC is compared to the pressure measurements at the Tonga island, near the volcanic explosion. By using the cosmic-ray propagation in the atmosphere as a probe for the pressure, it is possible to achieve very high time-resolution measurements. Moreover, the high-altitude data from HAWC allows to observe the shape of the pressure anomaly with less perturbations compared to sea level detectors. Given the particular location and the detection method of HAWC, our high-altitude data provides valuable information that contributes to fully characterize this once-in-a-century phenomenon.