Skeletal muscles connect bones and tendons for locomotion and posture. Understanding the regenerative processes of muscle, bone and tendon is of importance to basic research and clinical applications. Despite their interconnections, distinct transcription factors have been reported to orchestrate each tissue developmental and regenerative processes. Here we show that Scx expression is not detectable in adult muscle stem cells (also known as satellite cells, SCs) during quiescence. Scx expression begins in activated SCs and continues throughout regenerative myogenesis after injury. By SC-specific Scx gene inactivation (ScxcKO), we show that Scx function is required for SC expansion/renewal and robust new myofiber formation after injury. We combined single-cell RNA-sequencing and CUT&RUN to identify direct Scx target genes during muscle regeneration. These target genes help explain the muscle regeneration defects of ScxcKO, and are not overlapping with Scx-target genes identified in tendon development. Together with a recent finding of a subpopulation of Scx-expressing connective tissue fibroblasts with myogenic potential during early embryogenesis, we propose that regenerative and developmental myogenesis co-opt the Scx gene via different mechanisms.

Peripheral neurons terminate at the surface of tendons partly to relay nociceptive pain signals; however, the role of peripheral nerves in tendon injury and repair remains unclear. Here, we show that after Achilles tendon injury in mice, there is new nerve growth near tendon cells that express nerve growth factor (NGF). Conditional deletion of the Ngf gene in either myeloid or mesenchymal mouse cells limited both innervation and tendon repair. Similarly, inhibition of the NGF receptor tropomyosin receptor kinase A (TrkA) abrogated tendon healing in mouse tendon injury. Sural nerve transection blocked the postinjury increase in tendon sensory innervation and the expansion of tendon sheath progenitor cells (TSPCs) expressing tubulin polymerization promoting protein family member 3. Single cell and spatial transcriptomics revealed that disruption of sensory innervation resulted in dysregulated inflammatory signaling and transforming growth factor-beta (TGF beta) signaling in injured mouse tendon. Culture of mouse TSPCs with conditioned medium from dorsal root ganglia neuron further supported a role for neuronal mediators and TGF beta signaling in TSPC proliferation. Transcriptomic and histologic analyses of injured human tendon biopsy samples supported a role for innervation and TGF beta signaling in human tendon regeneration. Last, treating mice after tendon injury systemically with a small-molecule partial agonist of TrkA increased neurovascular response, TGF beta signaling, TSPC expansion, and tendon tissue repair. Although further studies should investigate the potential effects of denervation on mechanical loading of tendon, our results suggest that peripheral innervation is critical for the regenerative response after acute tendon injury.

Coral growth depends on the partnership between the animal hosts and their intracellular, photosynthetic dinoflagellate symbionts. In this study, we used the sea anemone Aiptasia, a laboratory model for coral biology, to investigate the poorly understood mechanisms that mediate symbiosis establishment and maintenance. We found that initial colonization of both adult polyps and larvae by a compatible algal strain was more effective when the algae were able to photosynthesize and that the long-term maintenance of the symbiosis also depended on photosynthesis. In the dark, algal cells were taken up into host gastrodermal cells and not rapidly expelled, but they seemed unable to reproduce and thus were gradually lost. When we used confocal microscopy to examine the interaction of larvae with two algal strains that cannot establish stable symbioses with Aiptasia, it appeared that both pre- and post-phagocytosis mechanisms were involved. With one strain, algae entered the gastric cavity but appeared to be completely excluded from the gastrodermal cells. With the other strain, small numbers of algae entered the gastrodermal cells but appeared unable to proliferate there and were slowly lost upon further incubation. We also asked if the exclusion of either incompatible strain could result simply from their cells' being too large for the host cells to accommodate. However, the size distributions of the compatible and incompatible strains overlapped extensively. Moreover, examination of macerates confirmed earlier reports that individual gastrodermal cells could expand to accommodate multiple algal cells.This article is part of the theme issue 'Sculpting the microbiome: how host factors determine and respond to microbial colonization'.

The symbioses between leguminous plants and nitrogen-fixing bacteria known as rhizobia are well known for promoting plant growth and sustainably increasing soil nitrogen. Recent evidence indicates that hopanoids, a family of steroid-like lipids, promote Bradyrhizobium symbioses with tropical legumes. To characterize hopanoids in Bradyrhizobium symbiosis with soybean, we validated a recently published cumate-inducible hopanoid mutant of Bradyrhizobium diazoefficiens USDA110, Pcu-shc:: increment shc. GC-MS analysis showed that this strain does not produce hopanoids without cumate induction, and under this condition, is impaired in growth in rich medium and under osmotic, temperature, and pH stress. In planta, Pcu-shc:: increment shc is an inefficient soybean symbiont with significantly lower rates of nitrogen fixation and low survival within the host tissue. RNA-seq revealed that hopanoid loss reduces the expression of flagellar motility and chemotaxis-related genes, further confirmed by swim plate assays, and enhances the expression of genes related to nitrogen metabolism and protein secretion. These results suggest that hopanoids provide a significant fitness advantage to B. diazoefficiens in legume hosts and provide a foundation for future mechanistic studies of hopanoid function in protein secretion and motility. IMPORTANCE A major problem for global sustainability is feeding our exponentially growing human population while available arable land decreases. Harnessing the power of plant-beneficial microbes is a potential solution, including increasing our reliance on the symbioses of leguminous plants and nitrogen-fixing rhizobia. This study examines the role of hopanoid lipids in the symbiosis between Bradyrhizobium diazoefficiens USDA110, an important commercial inoculant strain, and its economically significant host soybean. Our research extends our knowledge of the functions of bacterial lipids in symbiosis to an agricultural context, which may one day help improve the practical applications of plant-beneficial microbes in agriculture.

The potential of enhanced agricultural management practices to drive sustainability is rarely quantified at grassroots level. Here we analyse nitrogen use and loss in Chinese cropland, drawing from data collected in 2,238,550 sites in two national agricultural pollution source censuses from 2007 to 2017. We find an upswing of 10% in crop yields and an 8% reduction in nitrogen pollution during this period, owing to the promotion and adoption of various management practices (including the combination of organic and chemical fertilizers, straw recycling and deep placement of fertilizer). These practices have collectively contributed to an 18% increase in nitrogen use efficiency in the country. By fully embracing them, we project that annual cropland pollution could be further reduced by up to 1.4Mt of nitrogen without compromising crop yields. Environmental and human health benefits are projected to consistently outweigh implementation costs in the future, with total benefits reaching US$15 billion.

Oxygen 3-isotope ratios of magnetite and carbonates in aqueously altered carbonaceous chondrites provide important clues to understanding the evolution of the fluid in the asteroidal parent bodies. We conducted oxygen 3-isotope analyses of magnetite, dolomite, and breunnerite in two sections of asteroid Ryugu returned samples, A0058 and C0002, using a secondary ion mass spectrometer (SIMS). Magnetite was analyzed by using a lower primary ion energy that reduced instrumental biases due to the crystal orientation effect. We found two groups of magnetite data identified from the SIMS pit morphologies: (1) higher delta O-18 (from 3 parts per thousand to 7 parts per thousand) and Delta O-17 (similar to 2 parts per thousand) with porous SIMS pits mostly from spherulitic magnetite, and (2) lower delta O-18 (similar to -3 parts per thousand) and variable Delta O-17 (0 parts per thousand-2 parts per thousand) mostly from euhedral magnetite. Dolomite and breunnerite analyses were conducted using multi-collection Faraday cup detectors with precisions <= 0.3 parts per thousand. The instrumental bias correction was applied based on carbonate compositions in two ways, using Fe and (Fe + Mn) contents, respectively, because Ryugu dolomite contains higher amounts of Mn than the terrestrial standard. Results of dolomite and breunnerite analyses show a narrow range of Delta O-17; 0.0 parts per thousand-0.3 parts per thousand for dolomite in A0058 and 0.2 parts per thousand-0.8 parts per thousand for dolomite and breunnerite in C0002. The majority of breunnerite, including large >= 100 mu m grains, show systematically lower delta O-18 (similar to 21 parts per thousand) than dolomite (25 parts per thousand-30 parts per thousand and 23 parts per thousand-27 parts per thousand depending on the instrumental bias corrections). The equilibrium temperatures between magnetite and dolomite from the coarse-grained lithology in A0058 are calculated to be 51 +/- 11 degrees C and 78 +/- 14 degrees C, depending on the instrumental bias correction scheme for dolomite; a reliable temperature estimate would require a Mn-bearing dolomite standard to evaluate the instrumental bias corrections, which is not currently available. These results indicate that the oxygen isotope ratios of aqueous fluids in the Ryugu parent asteroid were isotopically heterogeneous, either spatially, or temporary. Initial water ice accreted to the Ryugu parent body might have Delta O-17 > 2 parts per thousand that was melted and interacted with anhydrous solids with the initial Delta O-17 < 0 parts per thousand. In the early stage of aqueous alteration, spherulitic magnetite and calcite formed from aqueous fluid with Delta O-17 similar to 2 parts per thousand that was produced by isotope exchange between water (Delta O-17 > 2 parts per thousand) and anhydrous solids (Delta O-17 < 0 parts per thousand). Dolomite and breunnerite, along with some magnetite, formed at the later stage of aqueous alteration under higher water-to-rock ratios where the oxygen isotope ratios were nearly at equilibrium between fluid and solid phases. Including literature data, delta O-18 of carbonates decreased in the order calcite, dolomite, and breunnerite, suggesting that the temperature of alteration might have increased with the degree of aqueous alteration.

By directly altering microscopic interactions, pressure provides a powerful tuning knob for the exploration of condensed phases and geophysical phenomena1. The megabar regime represents an interesting frontier, in which recent discoveries include high-temperature superconductors, as well as structural and valence phase transitions2-6. However, at such high pressures, many conventional measurement techniques fail. Here we demonstrate the ability to perform local magnetometry inside a diamond anvil cell with sub-micron spatial resolution at megabar pressures. Our approach uses a shallow layer of nitrogen-vacancy colour centres implanted directly within the anvil7-9; crucially, we choose a crystal cut compatible with the intrinsic symmetries of the nitrogen-vacancy centre to enable functionality at megabar pressures. We apply our technique to characterize a recently discovered hydride superconductor, CeH9 (ref. 10). By performing simultaneous magnetometry and electrical transport measurements, we observe the dual signatures of superconductivity: diamagnetism characteristic of the Meissner effect and a sharp drop of the resistance to near zero. By locally mapping both the diamagnetic response and flux trapping, we directly image the geometry of superconducting regions, showing marked inhomogeneities at the micron scale. Our work brings quantum sensing to the megabar frontier and enables the closed-loop optimization of superhydride materials synthesis.

The determination of the temperature in and above the slab in subduction zones, using models where the top of the slab is precisely known, is important to test hypotheses regarding the causes of arc volcanism and intermediate-depth seismicity. While 2D and 3D models can predict the thermal structure with high precision for fixed slab geometries, a number of regions are characterized by relatively large geometrical changes over time. Examples include the flat slab segments in South America that evolved from more steeply dipping geometries to the present day flat slab geometry. We devise, implement, and test a numerical approach to model the thermal evolution of a subduction zone with prescribed changes in slab geometry over time. Our numerical model approximates the subduction zone geometry by employing time dependent deformation of a Bezier spline that is used as the slab interface in a finite element discretization of the Stokes and heat equations. We implement the numerical model using the FEniCS open source finite element suite and describe the means by which we compute approximations of the subduction zone velocity, temperature, and pressure fields. We compute and compare the 3D time evolving numerical model with its 2D analogy at cross-sections for slabs that evolve to the present-day structure of a flat segment of the subducting Nazca plate.

Recent discoveries of transiting giant exoplanets around M-dwarf stars (GEMS), aided by the all-sky coverage of TESS, are starting to stretch theories of planet formation through the core-accretion scenario. Recent upper limits on their occurrence suggest that they decrease with lower stellar masses, with fewer GEMS around lower-mass stars compared to solar-type. In this paper, we discuss existing GEMS both through confirmed planets, as well as protoplanetary disk observations, and a combination of tests to reconcile these with theoretical predictions. We then introduce the Searching for GEMS survey, where we utilize multidimensional nonparameteric statistics to simulate hypothetical survey scenarios to predict the required sample size of transiting GEMS with mass measurements to robustly compare their bulk-density with canonical hot Jupiters orbiting FGK stars. Our Monte Carlo simulations predict that a robust comparison requires about 40 transiting GEMS (compared to the existing sample of similar to 15) with 5 sigma mass measurements. Furthermore, we discuss the limitations of existing occurrence estimates for GEMS and provide a brief description of our planned systematic search to improve the occurrence rate estimates for GEMS.