Hair-bearing human skin generated entirely from pluripotent stem cells

The skin is a multilayered organ, equipped with appendages (that is, follicles and glands), that is critical for regulating body temperature and the retention of bodily fluids, guarding against external stresses and mediating the sensation of touch and pain1,2. Reconstructing appendage-bearing skin in cultures and in bioengineered grafts is a biomedical challenge that has yet to be met3-9. Here we report an organoid culture system that generates complex skin from human pluripotent stem cells. We use stepwise modulation of the transforming growth factor β (TGFβ) and fibroblast growth factor (FGF) signalling pathways to co-induce cranial epithelial cells and neural crest cells within a spherical cell aggregate. During an incubation period of 4-5 months, we observe the emergence of a cyst-like skin organoid composed of stratified epidermis, fat-rich dermis and pigmented hair follicles that are equipped with sebaceous glands. A network of sensory neurons and Schwann cells form nerve-like bundles that target Merkel cells in organoid hair follicles, mimicking the neural circuitry associated with human touch. Single-cell RNA sequencing and direct comparison to fetal specimens suggest that the skin organoids are equivalent to the facial skin of human fetuses in the second trimester of development. Moreover, we show that skin organoids form planar hair-bearing skin when grafted onto nude mice. Together, our results demonstrate that nearly complete skin can self-assemble in vitro and be used to reconstitute skin in vivo. We anticipate that our skin organoids will provide a foundation for future studies of human skin development, disease modelling and reconstructive surgery

Barriers to Predicting the Mechanisms and Risk Factors of Non-Contact Anterior Cruciate Ligament Injury

High incidences of non-contact anterior cruciate ligament (ACL) injury, frequent requirements for ACL reconstruction, and limited understanding of ACL mechanics have engendered considerable interest in quantifying the ACL loading mechanisms. Although some progress has been made to better understand non-contact ACL injuries, information on how and why non-contact ACL injuries occur is still largely unavailable. In other words, research is yet to yield consensus on injury mechanisms and risk factors. Biomechanics, video analysis, and related study approaches have elucidated to some extent how ACL injuries occur. However, these approaches are limited because they provide estimates, rather than precise measurements of knee - and more specifically ACL - kinematics at the time of injury. These study approaches are also limited in their inability to simultaneously capture many of the contributing factors to injury

Quantitative palaeobathymetric reconstructions based on foraminiferal proxies: a case study from the Neogene of south‐west Spain

International audienceQuantitative palaeobathymetric reconstructions based on foraminiferal proxies have been used in a wide variety of geological studies on tectonic, climatic and environmental changes in sedimentary basins. However, palaeo-water-depth estimates are frequently biased due to taphonomic processes (dissolution, transport) as well as local conditions (primary productivity, oxygen content, and organic matter fluxes). This study evaluated the level of reliability of three commonly used transfer equations based on planktic and benthic foraminiferal proxies that produce different palaeobathymetric results, using Neogene sediments from the Guadalquivir Basin, south-west Spain. The most trustworthy method involves removing abundant infaunal benthic foraminifera before applying the palaeo-water-depth equation based on benthic foraminiferal water-depth ranges and presence/absence of species. This new approach provides sound palaeobathymetric results that improve estimations of long and short-term relative sea-level changes with negligible influence of taphonomic as well as ecological factors. When using one equation based on planktic/benthic ratios (P/B ratios), removing all infaunal benthic foraminiferal species improves the accuracy of P/B ratios, which yields more accurate palaeodepth reconstructions despite the low level of trustworthiness of this equation for both long and short-term relative sea-level variations

Foraminiferal Patterns in Deglacial Sediment in the Western Ross Sea, Antarctica: Life Near Grounding Lines

Improved multibeam swath bathymetry allows targeted coring of glacial landforms aiming at improving our understanding of sedimentary facies that developed in glacimarine settings during the post-Last Glacial Maximum (LGM) deglaciation. Coupled with radiocarbon dates, we explore foraminiferal records from 18 sediment cores from the western Ross Sea largely from sites near paleo–grounding lines. We investigate post-LGM foraminiferal assemblages from glacimarine environments, including those proximal and more distal to paleo–grounding lines, including environments influenced by subglacial meltwater outflow and further removed from direct glacial influence and subject to different oceanographic conditions. Agglutinated benthic foraminiferal assemblages dominate open marine facies deposited under the presence of High Salinity Shelf Water and significant primary production, while calcareous foraminiferal assemblages characterize grounding line-proximal settings, some of which were potentially influenced by Modified Circumpolar Deep Water. Rapid deposition of meltwater plume deposits inhibited and, in some cases, significantly altered foraminifera abundance and diversity. Broadly in the Ross Sea, it appears that the high bathymetric gradient of grounding zone wedges is a key factor promoting rich benthic foraminiferal communities in habitats proximal to grounding lines. Therefore, we demonstrate that paleo–grounding line settings may archive high quality in situ foraminiferal data, which is imperative for paleoenvironmental and geochemical studies on glaciated continental margins worldwide

Prehospital use of a modified HEART Pathway and point-of-care troponin to predict cardiovascular events.

Clinical trial registrationclinicaltrials.gov (NCT02709135)