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Because of poor self-healing ability, joint cartilage can undergo irreversible degradation in the course of various diseases or after injury. A promising approach for cartilage engineering consists of using of mesenchymal stem cells (MSC) and a differentiation factor combined with an injectable carrier biomaterial. We describe here a novel synthesis route for native collagen microspheres that does not involve the use of potentially toxic crosslinking agents. An emulsion was formed between a type I collagen solution and perfluorinated oil, stabilised by a biocompatible triblock perfluorinated copolymer surfactant. Spherical microparticles of fibrillar collagen were formed through a sol-gel transition induced by ammonia vapours. Electron microscopy observations showed that these self-cross-linked microspheres were constituted by a gel of striated collagen fibrils. Microspheres that were loaded with transforming growth factor beta (TGF-β)3 progressively released this differentiation factor over a four weeks period. Human MSC rapidly adhered to TGF-β3-loaded microspheres and, after 21 d of culture, exhibited typical chondrocyte morphology and produced an uncalcified matrix made of the predominant cartilage components, aggrecan and type II collagen, but devoid of the hypertrophic marker type X collagen. Subcutaneous co-injection of MSC and TGF-β3-loaded microspheres in mice consistently led to the formation of a cartilage-like tissue, which was however hypertrophic, calcified and vascularised. In conclusion, we developed cross-linker free collagen microspheres that allowed chondrogenic differentiation of MSC in vitro and in vivo.

Abstract The human spleen contracts in response to stress‐induced catecholamine secretion, resulting in a temporary rise in haemoglobin concentration ([Hb]). Recent findings highlighted enhanced splenic response to exercise at high altitude in Sherpa, possibly due to a blunted splenic response to hypoxia. To explore the potential blunted splenic contraction in Sherpas at high altitude, we examined changes in spleen volume during hyperoxic breathing, comparing acclimatized Sherpa with acclimatized individuals of lowland ancestry. Our study included 14 non‐Sherpa (7 female) residing at altitude for a mean continuous duration of 3 months and 46 Sherpa (24 female) with an average of 4 years altitude exposure. Participants underwent a hyperoxic breathing test at altitude (4300 m; barrometric pressure = ∼430 torr; PO2 = ∼90 torr). Throughout the test, we measured spleen volume using ultrasonography and monitored oxygen saturation (SpO2). During rest, Sherpa exhibited larger spleens (226 ± 70 mL) compared to non‐Sherpa (165 ± 34 mL; P

Biomarkers are indicators of biological conditions that can be detected and measured in body fluids or tissues. Biomarkers can be detectable before the clinical onset of the disease, and are thus useful for prognosis; they can be measured at early stages of the disease and are useful for stratification and classification of the disease and patients; they can be monitored along the disease course and used as indicators of risk factors and pharmacological response to treatment. Ideally, biomarkers should be sensitive, specific, have high predictive power, and be easily accessible. Rheumatoid arthritis (RA) is the most frequent chronic inflammatory disorder, affecting millions of people worldwide and leading to joint damage and substantial morbidity. RA is a heterogeneous disorder with a fluctuating clinical course and unpredictable prognosis. And although a large panel of biologics is available to clinicians, the main challenge remains to treat patients as early as possible with the most personalised therapy. Today, the most challenging issue in RA is the identification of biomarkers for early disease diagnosis and for prediction of drug response. Among molecules that can fulfil this expectation, micro(mi)-RNAs certainly represent an option. The potential value of miRNAs as a novel class of biomarkers is well documented in cancer. Moreover, the presence and stability of miRNAs in body fluids provide fingerprints that can serve as molecular biomarkers for disease diagnosis and therapeutic outcome. As a growing body of evidences reveals abnormal expression of specific miRNAs in RA tissues, the use of a blood-based miRNA signature for optimal diagnosis and treatment becomes a realistic option.

Abstract Differences in the life history pathways (LHPs) of juvenile animals are often associated with differences in demographic rates in later life stages. For migratory animals, different LHPs often result in animals from the same population occupying distinct habitats subjected to different environmental drivers. Understanding how demographic rates differ among animals expressing different LHPs may reveal fitness trade‐offs that drive the expression of alternative LHPs and enable better prediction of population dynamics in a changing environment. To understand how demographic outcomes and their relationships with environmental variables differ among animals with different LHPs, we analyzed a long‐term (2006–2021) mark–recapture dataset for Chinook salmon (Oncorhynchus tshawytscha) from the Wenatchee River, Washington, USA. Distinct LHPs represented in this population include either remaining in the natal stream until emigrating to the ocean as a 1‐year‐old (natal‐reach rearing) or emigrating from the natal stream and rearing in downstream habitats for several months before completing the emigration to the ocean as a 1‐year‐old (downstream rearing). We found that downstream‐rearing fish emigrated to the ocean 19 days earlier on average and returned as adults from the ocean at higher rates. We detected a positive correlation between rate of return from the ocean by downstream‐rearing fish and coastal upwelling in their spring of outmigration, whereas for natal‐reach‐rearing fish we detected a positive correlation with sea surface temperature during their first marine summer. Different responses to environmental variability should lead to asynchrony in adult abundance among juvenile LHPs. A higher proportion of downstream‐rearing fish returned at younger ages compared with natal‐reach‐rearing fish, which contributed to variability in age at reproduction and greater mixing across generations. Our results demonstrate how diversity in juvenile LHPs is associated with heterogeneity in demographic rates during subsequent life stages, which can in turn affect variance in aggregate population abundance and response to environmental change. Our findings underscore the importance of considering life history diversity in demographic analyses and provide insights into the effects of life history diversity on population dynamics and trade‐offs that contribute to the maintenance of life history diversity.

Stream temperatures in the Pacific Northwest are projected to increase with climate change, placing additional stress on cold-water salmonids. We modeled the potential impact of increased stream temperatures on four anadromous salmonid populations in the Chehalis River Basin (spring-run and fall-run Chinook salmon Oncorhynchus tshawytscha, coho salmon O. kisutch, and steelhead O. mykiss), as well as the potential for floodplain reconnection and stream shade restoration to offset the effects of future temperature increases. In the Chehalis River Basin, peak summer stream temperatures are predicted to increase by as much as 3°C by late-century, but restoration actions can locally decrease temperatures by as much as 6°C. On average, however, basin-wide average stream temperatures are expected to increase because most reaches have low temperature reduction potential for either restoration action relative to climate change. Results from the life cycle models indicated that, without restoration actions, increased summer temperatures are likely to produce significant declines in spawner abundance by late-century for coho (-29%), steelhead (-34%), and spring-run Chinook salmon (-95%), and smaller decreases for fall-run Chinook salmon (-17%). Restoration actions reduced these declines in all cases, although model results suggest that temperature restoration alone may not fully mitigate effects of future temperature increases. Notably, floodplain reconnection provided a greater benefit than riparian restoration for steelhead and both Chinook salmon populations, but riparian restoration provided a greater benefit for coho. This pattern emerged because coho salmon tend to spawn and rear in smaller streams where shade restoration has a larger effect on stream temperature, whereas Chinook and steelhead tend to occupy larger rivers where temperatures are more influenced by floodplain connectivity. Spring-run Chinook salmon are the only population for which peak temperatures affect adult prespawn survival in addition to rearing survival, making them the most sensitive species to increasing stream temperatures.