Explore the vast range of titles available.

Emerging insights into cellular senescence highlight the relevance of senescence in musculoskeletal disorders, which represent the leading global cause of disability. Cellular senescence was initially described by Hayflick et al. in 1961 as an irreversible nondividing state in in vitro cell culture studies. We now know that cellular senescence can occur in vivo in response to various stressors as a heterogeneous and tissue-specific cell state with a secretome phenotype acquired after the initial growth arrest. In the past two decades, compelling evidence from preclinical models and human data show an accumulation of senescent cells in many components of the musculoskeletal system. Cellular senescence is therefore a defining feature of age-related musculoskeletal disorders, and targeted elimination of these cells has emerged recently as a promising therapeutic approach to ameliorate tissue damage and promote repair and regeneration of the skeleton and skeletal muscles. In this review, we summarize evidence of the role of senescent cells in the maintenance of bone homeostasis during childhood and their contribution to the pathogenesis of chronic musculoskeletal disorders, including osteoporosis, osteoarthritis, and sarcopenia. We highlight the diversity of the senescent cells in the microenvironment of bone, joint, and skeletal muscle tissue, as well as the mechanisms by which these senescent cells are involved in musculoskeletal diseases. In addition, we discuss how identifying and targeting senescent cells might positively affect pathologic progression and musculoskeletal system regeneration.

Copper ore deposits accumulate at relatively shallow depths in the crust, but it is unclear how the metal is transported. Laboratory experiments show that metals may hitch a ride on magma bubbles and float towards shallower depths. Emissions of sulphur 1 , 2 and metals 3 , 4 from magmas in Earth’s shallow crust can have global impacts on human society. Sulphur-bearing gases emitted into the atmosphere during volcanic eruptions affect climate 5 , 6 , and metals and sulphur can accumulate in the crust above a magma reservoir to form giant copper and gold ore deposits, as well as massive sulphur anomalies 3 , 4 , 7 , 8 . The volumes of sulphur and metals that accumulate in the crust over time exceed the amounts that could have been derived from an isolated magma reservoir 2 . They are instead thought to come from injections of multiple new batches of vapour- and sulphide-saturated magmas into the existing reservoirs 1 , 4 , 9 , 10 . However, the mechanism for the selective upward transfer of sulphur and metals is poorly understood because their main carrier phase, sulphide melt, is dense and is assumed to settle to the bottoms of magma reservoirs. Here we use laboratory experiments as well as gas-speciation and mass-balance models to show that droplets of sulphide melt can attach to vapour bubbles to form compound drops 11 that float. We demonstrate the feasibility of this mechanism for the upward mobility of sulphide liquids to the shallow crust. Our work provides a mechanism for the atmospheric release of large amounts of sulphur, and contradicts the widely held assumption that dense sulphide liquids rich in sulphur, copper and gold will remain sequestered in the deep crust.

The C-H-O-N-S elements that constitute the outgassed atmosphere and exosphere have likely been delivered by chondritic materials to the Earth during planetary accretion and subsequently processed over billions of years of planetary differentiation. Although these elements are generally considered to be volatile, a large part of the accreted C-H-O-N-S on Earth must have been sequestered in the core and mantle, with the remaining part concentrated at the Earth’s surface (exosphere: atmosphere + ocean + crust ). The likely reason for this is that, depending on the prevailing pressure (P), temperature (T) and oxidation state (oxygen fugacity, fO 2 ) in the planet’s interior, the C-H-O-N-S elements can behave as siderophile, lithophile, refractory, magmatophile, or atmophile. It is not clear if these elements might be sequestered in the interiors of planets elsewhere, since the governing parameters of P-T-fO 2 during the diverse magmatic processes controlling magmatic differentiation vary greatly over time and from planet to planet. The magma ocean outgassed the first atmosphere, which was probably also the largest in terms of mass, but its nature and composition remain poorly known. Meanwhile, a significant, but unknown, part of the accreted C-H-O-N-S elements was sequestered in the core. These will probably never be liberated into the atmosphere. A secondary atmosphere was then fuelled by volcanism, driven by mantle convection and most likely enhanced by plate tectonics. The Earth still has active volcanism, and the volume and volatile contents of its magma are closely linked to geodynamics. Earth’s volcanoes have long emitted relatively oxidized gases, in contrast to Mars and Mercury. Mantle oxidation state seems to increase with planetary size, although the role of plate tectonics in changing the Earth’s mantle oxidation state remains poorly understood. Water contents of magma from elsewhere in the solar system are not so different from those produced by the Earth’s depleted mantle. Other elements (e.g. N, S, C) are unevenly distributed. A great diversity of speciation and quantity of magmatic gas emitted is found in planetary systems, with the key inputs being: 1 – degassing of the magma ocean, 2 – mantle oxidation state (and its evolution), and 3 – plate tectonics (vs. other styles of mantle convection). Many other parameters can affect these three inputs, of which planetary size is probably one of the most important.

Background Immune checkpoint inhibitors (ICI), a type of cancer immunotherapy, can cause side effects including inflammatory arthritis (ICI-IA). Previous studies of ICI-IA do not include a thorough characterization of associated immune responses to provide potential targets for treatment. We aimed to identify cytokines uniquely increased in ICI-IA and determine correlations with IA severity and persistence. Methods We evaluated patients diagnosed with ICI-IA by a rheumatologist ( n  = 80); control serum was obtained from ICI-treated cancer patients without any diagnosed irAEs ( n  = 17) or diagnosed with an unrelated irAE ( n  = 19). Serum was assayed to quantify 9 cytokine levels (IFN-γ, IL-4, IL-6, IL-10, IL-12p70, IL-1α, TNF-α, IL-17a, VEGF-A) using MSD U-PLEX assay. Mann-Whitney U tests were performed to evaluate differences in cytokine levels between control and ICI-IA groups. The Kruskal-Wallis test and multivariable ordinal logistic regression were used to determine difference in cytokine levels between patients of differing disease activity. Results VEGF-A and TNFα were significantly elevated in patients with ICI-IA compared to ICI-controls; results persisted when restricting analyses to patients not treated with immunosuppressants at the time of sampling. ICI-IA patients were stratified by IA severity using CDAI score; there was significantly higher VEGF-A in those with higher disease activity. Ordinal logistic regression showed higher levels of IL-6 and VEGF-A were associated with higher disease activity. Conclusion Elevated levels of VEGF-A and TNFα are associated with ICI-IA. There was also higher IL-6 and VEGF-A among those with higher disease activity when controlling for confounding. These cytokines could be used as biomarkers of ICI-IA severity and present therapeutic targets.

The sea surface salinity (SSS) measured from space by the Soil Moisture and Ocean Salinity (SMOS) mission has recently been revisited by the European Space Agency first campaign reprocessing. We show that, with respect to the previous version, biases close to land and ice greatly decrease. The accuracy of SMOS SSS averaged over 10 days, 100 × 100 km2 in the open ocean and estimated by comparison to ARGO (Array for Real-Time Geostrophic Oceanography) SSS is on the order of 0.3–0.4 in tropical and subtropical regions and 0.5 in a cold region. The averaged negative SSS bias (−0.1) observed in the tropical Pacific Ocean between 5° N and 15° N, relatively to other regions, is suppressed when SMOS observations concomitant with rain events, as detected from SSM/Is (Special Sensor Microwave Imager) rain rates, are removed from the SMOS–ARGO comparisons. The SMOS freshening is linearly correlated to SSM/Is rain rate with a slope estimated to −0.14 mm−1 h, after correction for rain atmospheric contribution. This tendency is the signature of the temporal SSS variability between the time of SMOS and ARGO measurements linked to rain variability and of the vertical salinity stratification between the first centimeter of the sea surface layer sampled by SMOS and the 5 m depth sampled by ARGO. However, given that the whole set of collocations includes situations with ARGO measurements concomitant with rain events collocated with SMOS measurements under no rain, the mean −0.1 bias and the negative skewness of the statistical distribution of SMOS minus ARGO SSS difference are very likely the mean signature of the vertical salinity stratification. In the future, the analysis of ongoing in situ salinity measurements in the top 50 cm of the sea surface and of Aquarius satellite SSS are expected to provide complementary information about the sea surface salinity stratification.

Many institutions worldwide have developed ocean reanalyses systems (ORAs) utilizing a variety of ocean models and assimilation techniques. However, the quality of salinity reanalyses arising from the various ORAs has not yet been comprehensively assessed. In this study, we assess the upper ocean salinity content (depth-averaged over 0–700 m) from 14 ORAs and 3 objective ocean analysis systems (OOAs) as part of the Ocean Reanalyses Intercomparison Project. Our results show that the best agreement between estimates of salinity from different ORAs is obtained in the tropical Pacific, likely due to relatively abundant atmospheric and oceanic observations in this region. The largest disagreement in salinity reanalyses is in the Southern Ocean along the Antarctic circumpolar current as a consequence of the sparseness of both atmospheric and oceanic observations in this region. The West Pacific warm pool is the largest region where the signal to noise ratio of reanalysed salinity anomalies is >1. Therefore, the current salinity reanalyses in the tropical Pacific Ocean may be more reliable than those in the Southern Ocean and regions along the western boundary currents. Moreover, we found that the assimilation of salinity in ocean regions with relatively strong ocean fronts is still a common problem as seen in most ORAs. The impact of the Argo data on the salinity reanalyses is visible, especially within the upper 500 m, where the interannual variability is large. The increasing trend in global-averaged salinity anomalies can only be found within the top 0–300 m layer, but with quite large diversity among different ORAs. Beneath the 300 m depth, the global-averaged salinity anomalies from most ORAs switch their trends from a slightly growing trend before 2002 to a decreasing trend after 2002. The rapid switch in the trend is most likely an artefact of the dramatic change in the observing system due to the implementation of Argo.

Variations in the world's ocean heat storage and its associated volume changes are a key factor to gauge global warming and to assess the earth's energy and sea level budget. Estimating global ocean heat content (GOHC) and global steric sea level (GSSL) with temperature/salinity data from the Argo network reveals a positive change of 0.5 ± 0.1 W m−2 (applied to the surface area of the ocean) and 0.5 ± 0.1 mm year−1 during the years 2005 to 2012, averaged between 60° S and 60° N and the 10–1500 m depth layer. In this study, we present an intercomparison of three global ocean observing systems: the Argo network, satellite gravimetry from GRACE and satellite altimetry. Their consistency is investigated from an Argo perspective at global and regional scales during the period 2005–2010. Although we can close the recent global ocean sea level budget within uncertainties, sampling inconsistencies need to be corrected for an accurate global budget due to systematic biases in GOHC and GSSL in the Tropical Ocean. Our findings show that the area around the Tropical Asian Archipelago (TAA) is important to closing the global sea level budget on interannual to decadal timescales, pointing out that the steric estimate from Argo is biased low, as the current mapping methods are insufficient to recover the steric signal in the TAA region. Both the large regional variability and the uncertainties in the current observing system prevent us from extracting indirect information regarding deep-ocean changes. This emphasizes the importance of continuing sustained effort in measuring the deep ocean from ship platforms and by beginning a much needed automated deep-Argo network.

The total oxidation of toluene is studied over catalytic systems based on perovskite with general formula AA′CoO3-δ (A = La, A′ = Sr). The systematic and progressive substitution of La3+ by Sr2+ cations in the series (La1−xSrxCoO3−δ system) of the perovskites have been studied to determine their influence in the final properties of these mixed oxides and their corresponding reactivity performance for the total oxidation of toluene as a model volatile organic compound with detrimental effects for health and environment. The structure and morphology of the samples before and after reaction have been characterized by XRD, BET and FE-SEM techniques. Additional experiments of temperature programmed desorption of O2 in vacuum and reduction in H2 were also performed to identify the main surface oxygen species and the reducibility of the different perovskites. It is remarkable that the La1−xSrxCoO3−δ series presents better catalytic performance for the oxidation of toluene, with lower values for the T50 (temperature of 50 % toluene conversion) than the previously studied LaNi1−yCoyO3 series.Graphical abstractThe substitution of La3+ by Sr2+ (La1−xSrxCoO3−δ) have been studied to determine the influence in the final structure of these mixed oxides and their reactivity toward the deep oxidation of toluene, where the α-types oxygen species may play an activerole.

This study of the treatment of aggressive lymphoma in patients 60 years old or younger compared cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), the standard treatment, with an immediate course of high-dose chemotherapy plus transplantation of autologous hematopoietic stem cells. The high-dose therapy was superior to CHOP for patients at high intermediate risk. The high-dose therapy was superior to CHOP for patients at high intermediate risk. The regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) is the standard initial treatment for disseminated aggressive lymphoma in adults. 1 No other multiagent combination has proved superior. 2 However, phase 2 trials of short-term conventional chemotherapy followed by high-dose chemotherapy and the transplantation of autologous hematopoietic stem cells have yielded excellent results. 3 – 8 No formal comparison of such regimens with CHOP has been reported to date. In a randomized study of patients with aggressive lymphoma and a poor prognosis, the Milan group found the duration of failure-free survival was longer after high-dose chemotherapy and autologous stem-cell support than after a chemotherapy . . .