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2.
Nat Commun ; 14(1): 6218, 2023 10 06.
Article in English | MEDLINE | ID: mdl-37803032

ABSTRACT

The year 2022 saw record breaking temperatures in Europe during both summer and fall. Similar to the recent 2018 drought, close to 30% (3.0 million km2) of the European continent was under severe summer drought. In 2022, the drought was located in central and southeastern Europe, contrasting the Northern-centered 2018 drought. We show, using multiple sets of observations, a reduction of net biospheric carbon uptake in summer (56-62 TgC) over the drought area. Specific sites in France even showed a widespread summertime carbon release by forests, additional to wildfires. Partial compensation (32%) for the decreased carbon uptake due to drought was offered by a warm autumn with prolonged biospheric carbon uptake. The severity of this second drought event in 5 years suggests drought-induced reduced carbon uptake to no longer be exceptional, and important to factor into Europe's developing plans for net-zero greenhouse gas emissions that rely on carbon uptake by forests.


Subject(s)
Carbon , Forests , Temperature , Carbon/analysis , Europe , Hot Temperature , Droughts , Climate Change
3.
Front Genet ; 12: 705505, 2021.
Article in English | MEDLINE | ID: mdl-34447412

ABSTRACT

Osteogenesis imperfecta (OI), which is most often due to a collagen type 1 gene mutation, is characterized by low bone density and bone fragility. In OI patients, gender-related differences were reported, but data in the literature are not convergent. We previously observed that sclerostin antibody (Scl-Ab), which stimulates osteoblast Wnt pathway via sclerostin inactivation, improved spine and long-bone parameters and biomechanical strength in female oim/oim mice, a validated model of human type 3 OI. Here, we wanted to highlight the effect of Scl-Ab on male oim/oim bones in order to identify a possible distinct therapeutic effect from that observed in females. According to the same protocol as our previous study with female mice, male wild-type (Wt) and oim/oim mice received vehicle or Scl-Ab from 5 to 14 weeks of age. Clinimetric and quantitative bone parameters were studied using X-rays, peripheral quantitative computed tomography, microradiography, and dynamic histomorphometry and compared to those of females. Contrary to Wt mice, male oim/oim had significantly lower weight, snout-sacrum length, and bone mineral content than females at 5 weeks. No significant difference in these clinimetric parameters was observed at 14 weeks, whereas male oim showed significantly more long-bone fractures than females. Scl-Ab improved bone mineral density and bone volume/total volume ratio (BV/TV) of vertebral body in Wt and oim/oim, without significant difference between male and female at 14 weeks. Male vehicle oim/oim had a significantly lower cortical thickness (Ct.Th) and BV/TV of tibial diaphysis than female and showed a higher number of fractures at 14 weeks. Scl-Ab increased midshaft periosteal apposition rate in such a way that tibial Ct.Th of male oim/oim was not significantly different from the female one at 14 weeks. The number of fractures was lower in male than female oim/oim after 14 weeks of Scl-Ab treatment, but this difference was not significant. Nevertheless, Scl-Ab-treated oim/oim male and female mice remained smaller than the Wt ones. In conclusion, our results highlighted differences between male and female oim/oim at 4 and 14 weeks of age, as well as some male-specific response of cortical bone to Scl-Ab. These gender-related particularities of oim/oim should be considered when testing experimental treatments.

4.
Philos Trans R Soc Lond B Biol Sci ; 375(1810): 20190524, 2020 10 26.
Article in English | MEDLINE | ID: mdl-32892732

ABSTRACT

Drought and heat events, such as the 2018 European drought, interact with the exchange of energy between the land surface and the atmosphere, potentially affecting albedo, sensible and latent heat fluxes, as well as CO2 exchange. Each of these quantities may aggravate or mitigate the drought, heat, their side effects on productivity, water scarcity and global warming. We used measurements of 56 eddy covariance sites across Europe to examine the response of fluxes to extreme drought prevailing most of the year 2018 and how the response differed across various ecosystem types (forests, grasslands, croplands and peatlands). Each component of the surface radiation and energy balance observed in 2018 was compared to available data per site during a reference period 2004-2017. Based on anomalies in precipitation and reference evapotranspiration, we classified 46 sites as drought affected. These received on average 9% more solar radiation and released 32% more sensible heat to the atmosphere compared to the mean of the reference period. In general, drought decreased net CO2 uptake by 17.8%, but did not significantly change net evapotranspiration. The response of these fluxes differed characteristically between ecosystems; in particular, the general increase in the evaporative index was strongest in peatlands and weakest in croplands. This article is part of the theme issue 'Impacts of the 2018 severe drought and heatwave in Europe: from site to continental scale'.


Subject(s)
Atmosphere/analysis , Climate Change , Droughts , Farms , Forests , Grassland , Wetlands , Europe
5.
Calcif Tissue Int ; 106(5): 494-508, 2020 05.
Article in English | MEDLINE | ID: mdl-32025752

ABSTRACT

In osteogenesis imperfecta (OI), vertebrae brittleness causes thorax deformations and leads to cardiopulmonary failure. As sclerostin-neutralizing antibodies increase bone mass and strength in animal models of osteoporosis, their administration in two murine models of severe OI enhanced the strength of vertebrae in growing female Crtap-/- mice but not in growing male Col1a1Jrt/+ mice. However, these two studies ignored the impact of antibodies on spine growth, fracture rates, and compressive mechanical properties. Here, we conducted a randomized controlled trial in oim/oim mice, an established model of human severe OI type III due to a mutation in Col1a2. Five-week-old female WT and oim/oim mice received either PBS or sclerostin antibody (Scl-Ab) for 9 weeks. Analyses included radiography, histomorphometry, pQCT, microcomputed tomography, and biomechanical testing. Though it did not modify vertebral axial growth, Scl-Ab treatment markedly reduced the fracture prevalence in the pelvis and caudal vertebrae, enhanced osteoblast activity (L4), increased cervico-sacral spine BMD, and improved the lumbosacral spine bone cross-sectional area. Scl-Ab did not impact vertebral height and body size but enhanced the cortical thickness and trabecular bone volume significantly in the two Scl-Ab groups. At lumbar vertebrae and tibial metaphysis, the absolute increase in cortical and trabecular bone mass was higher in Scl-Ab WT than in Scl-Ab oim/oim. The effects on trabecular bone mass were mainly due to changes in trabecular number at vertebrae and in trabecular thickness at metaphyses. Additionally, Scl-Ab did not restore a standard trabecular network, but improved bone compressive ultimate load with more robust effects at vertebrae than at metaphysis. Overall, Scl-Ab treatment may be beneficial for reducing vertebral fractures and spine deformities in patients with severe OI.


Subject(s)
Adaptor Proteins, Signal Transducing/antagonists & inhibitors , Antibodies, Neutralizing/therapeutic use , Fractures, Bone/prevention & control , Osteogenesis Imperfecta/drug therapy , Adaptor Proteins, Signal Transducing/immunology , Animals , Bone and Bones/pathology , Collagen Type I/genetics , Disease Models, Animal , Extracellular Matrix Proteins/genetics , Female , Male , Mice , Mice, Knockout , Molecular Chaperones/genetics , Phenotype , Random Allocation , X-Ray Microtomography
6.
Bone ; 124: 137-147, 2019 07.
Article in English | MEDLINE | ID: mdl-31051315

ABSTRACT

Osteogenesis imperfecta type III (OI) is a serious genetic condition with poor bone quality and a high fracture rate in children. In a previous study, it was shown that a monoclonal antibody neutralizing sclerostin (Scl-Ab) increases strength and vertebral bone mass while reducing the number of axial fractures in oim/oim, a mouse model of OI type III. Here, we analyze the impact of Scl-Ab on long bones in OI mice. After 9 weeks of treatment, Scl-Ab significantly reduced long bone fractures (3.6 ±â€¯0.3 versus 2.1 ±â€¯0.8 per mouse, p < 0.001). In addition, the cortical thickness of the tibial midshaft was increased (+42%, p < 0.001), as well as BMD (+28%, p < 0.001), ultimate load (+86%, p < 0.05), plastic energy (+184%; p < 0.05) and stiffness (+172%; p < 0.01) in OI Scl-Ab mice compared to OI vehicle controls. Similar effects of Scl-Ab were observed in Wild type (Wt) mice. The plastic energy, which reflects the fragility of the tissue, was lower in the OI than in the Wt and significantly improved with the Scl-Ab treatment. At the tissue level by nanoindentation, Scl-Ab slightly increased the elastic modulus in bones of both OI and Wt, while moderately increasing tissue hardness (+13% compared to the vehicle; p < 0.05) in Wt bones, but not in OI bones. Although it did not change the properties of the OI bone matrix material, Scl-Ab reduced the fracture rate of the long bones by improving its bone mass, density, geometry, and biomechanical strength. These results suggest that Scl-Ab can reduce long-bone fractures in patients with OI.


Subject(s)
Adaptor Proteins, Signal Transducing/immunology , Antibodies/therapeutic use , Fractures, Bone/complications , Fractures, Bone/drug therapy , Osteogenesis Imperfecta/complications , Animals , Antibodies/pharmacology , Biomechanical Phenomena , Bone Density/drug effects , Diaphyses/drug effects , Diaphyses/physiopathology , Disease Models, Animal , Female , Femur/drug effects , Femur/physiopathology , Fractures, Bone/physiopathology , Male , Mice , Survival Analysis , Tibia/drug effects , Tibia/physiopathology
7.
Biomaterials ; 34(18): 4428-38, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23507085

ABSTRACT

For critical size bone defects and bone non-unions, bone tissue engineering using osteoblastic differentiated adipose mesenchymal stem cells (AMSCs) is limited by the need for a biomaterial to support cell transplantation. An osteoblastic three-dimensional autologous graft made of AMSCs (3D AMSC) was developed to solve this issue. This autograft was obtained by supplementing the osteoblastic differentiation medium with demineralized bone matrix. Two surgical models were developed to assess the potential of this 3D osteogenic AMSC autograft. A four-level spinal fusion using polyetheretherketone cages was designed in six pigs to assess the early phase of ossification (8-12 weeks postimplantation). In each pig, four groups were compared: cancellous bone autograft, freeze-dried irradiated cancellous pig bone, 3D AMSC, and an empty cage. A critical size femoral defect (n = 4, bone non-union confirmed 6 months postoperatively) was used to assess the 3D AMSCs' ability to achieve bone fusion. Pigs were followed by CT scan and explanted specimens were analyzed for bone tissue remodeling by micro-CT scan, micro-radiography, and histology/histomorphometry. In the spine fusion model, bone formation with the 3D AMSC was demonstrated by a significant increase in bone content. In the critical-size femoral defect model, the 3D AMSC achieved new bone formation and fusion in a poorly vascularized fibrotic environment. This custom-made 3D osteogenic AMSC autograft is a therapeutic solution for bone non-unions and for critical-size defects.


Subject(s)
Adipose Tissue/cytology , Cell Differentiation , Femur/pathology , Mesenchymal Stem Cells/cytology , Osteogenesis , Regenerative Medicine/methods , Spine/pathology , Animals , Benzophenones , Cell Differentiation/drug effects , Disease Models, Animal , Femur/diagnostic imaging , Femur/drug effects , Fractures, Ununited/diagnostic imaging , Fractures, Ununited/pathology , Implants, Experimental , Ketones/pharmacology , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Osteogenesis/drug effects , Polyethylene Glycols/pharmacology , Polymers , Prosthesis Implantation , Spinal Fusion , Spine/diagnostic imaging , Spine/drug effects , Sus scrofa , Transplantation, Autologous , X-Ray Microtomography
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