Search

Taking stock of global progress towards achieving the Paris Agreement requires measuring aggregate national action against modelled mitigation pathways. A key gap exists, however, in how scientific studies and national inventories account for the role of anthropogenic land-based carbon fluxes, resulting in a 5.5-6.0 GtCO2yr-1 difference between the respective present-day land-use estimates. Modelled pathways mainly include direct human-induced fluxes, while inventories submitted by countries to the UNFCCC (NGHGIs) generally include a wider definition of managed land area as well as the indirect removals on that land caused by environmental changes (e.g., the CO2 fertilization effect). This difference hinders comparability between targets set by countries and scientific benchmarks. Scenarios assessed in AR6 show that a combination of deep near-term gross emissions reductions and medium-term carbon removal from the atmosphere are needed to reach net-zero and eventually net-negative CO2 emissions to limit warming in line with the Paris Agreement temperature goal. However, scenarios lacked key information needed to estimate land-based removals and to align their LULUCF projections with NGHGIs. Here, we estimate the land-based removals consistent with NGHGIs using a reduced complexity climate model with explicit treatment of the land-use sector, OSCAR, one of the models used by the Global Carbon Project. Of the 1202 pathways that passed IPCC vetting, 914 provide sufficient land-use change data to allow us to fill this information gap and enable alignment between pathways and inventories.Across both 1.5°C and 2°C scenarios, pathways aligned with NGHGIs show a strong increase in the total land sink until around mid-century. However, the ‘NGHGI alignment gap’ decreases over this period, converging in the 2050-2060s for 1.5°C scenarios and 2070s-2080s for 2°C scenarios. These dynamics lead to land-based emissions reversing their downward trend in most NGHGI-aligned scenarios by mid-century, and result in the LULUCF sector becoming a net-source of emissions by 2100 in about 25% of deep mitigation scenarios.Our results do not change any climate outcome or mitigation benchmark produced by the IPCC, but rather provide a translational lens to view those outcomes. We find that net-zero timings on average advance by around 5 years; however, this does not imply that 5 years have been lost in the race to net-zero, but rather that following the reporting conventions for natural sinks results in net-zero being reached 5 years earlier. Understanding how these different accounting frameworks can be mutually interpreted is a fundamental challenge for evaluating progress towards the Paris Agreement, given the reality that direct and indirect carbon removals cannot be estimated separately with direct observations.We propose three primary ways to address this science-policy gap. First, targets can be formulated separately for gross emission reductions, land-based removals, and technical carbon removals, allowing for nations to clearly define their expected contributions and to measure progress in each domain separately. Second, nations can clarify the nature of their deforestation pledges. Third, modelling teams can provide their assumptions for the NGHGI correction as part of their standard output which future IPCC assessments can use to vet scenarios.

Taking stock of global progress towards achieving the Paris Agreement requires measuring aggregate national action against modelled mitigation pathways. Because of differences in how land-based carbon removals are defined, scientific sources report higher global carbon emissions than national emissions inventories, a gap which will evolve in the future. We establish a first estimate aligning IPCC-assessed pathways with inventories using a climate model to explicitly include indirect carbon removal dynamics on land area reported as managed for by countries. After alignment, we find that key global mitigation benchmarks can appear more ambitious when considering this extra land sink, though changes vary amongst world regions and temperature outcomes. Our results highlight the need to enhance communication between scientific and policy communities to enable more robust alignment in the future.

The vitamin D endocrine system is essential for calcium metabolism and skeletal integrity. 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] regulates bone mineral homeostasis and acts directly on osteoblasts. In the present study we characterized the transcriptional regulation of the class 3 semaphorin (Sema3) gene family by 1,25(OH)2D3 in osteoblastic cells. Class 3 semaphorins are secreted proteins that regulate cell growth, morphology and migration, and were recently shown to be involved in bone homeostasis. In ST2, MC3T3-E1 and primary calvarial osteoblast cell cultures we found that all members of the Sema3 gene family were expressed, and that Sema3e and Sema3f were the most strongly induced 1,25(OH)2D3 target genes among the studied cell types. In addition, transcription of Sema3b and Sema3c was upregulated, whereas Sema3d and Sema3g was downregulated by 1,25(OH)2D3 in different osteoblastic cells. Chromatin immunoprecipitation analysis linked to DNA sequencing (ChIP-seq analysis) revealed the presence of the vitamin D receptor at multiple genomic loci in the proximity of Sema3 genes, demonstrating that the genes are primary 1,25(OH)2D3 targets. Furthermore, we showed that recombinant SEMA3E and SEMA3F protein were able to inhibit osteoblast proliferation. However, recombinant SEMA3s did not affect ST2 cell migration. The expression of class 3 semaphorins in osteoblasts together with their regulation by 1,25(OH)2D3 suggests that these genes, involved in the regulation of bone homeostasis, are additional mediators for 1,25(OH)2D3 signaling in osteoblasts.

Bisphosphonates like risedronate inhibit osteoclast-mediated bone resorption and are therefore used in the prevention and treatment of osteoporosis. Also vitamin D3 and calcium supplementation is commonly used in the prevention or treatment of osteoporosis. Combined therapy of risedronate with 1,25(OH)2D3, the active metabolite of vitamin D3, may be advantageous over the use of either monotherapy, but bears a risk of causing hypercalcemia thereby decreasing the therapeutic window for osteoporosis treatment. In this study, we evaluated the effect on bone mass of the combination of risedronate with the 17-methyl 19-nor five-membered D-ring vitamin D3 analog WY 1048 in a mouse ovariectomy model for postmenopausal osteoporosis. Ovariectomy-induced bone loss was restored by administration of risedronate or a combination of risedronate with 1,25(OH)2D3. However, the combination of WY 1048 with risedronate induced an even higher increase on total body and spine bone mineral density and on trabecular and cortical bone mass. Our data indicate that combination therapy of risedronate with WY 1048 was superior in restoring and improving bone mass over a combination of risedronate with 1,25(OH)2D3 with minimal calcemic side effects. ispartof: JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY vol:188 pages:124-130 ispartof: location:England status: published

Bisphosphonates like risedronate inhibit osteoclast-mediated bone resorption and are therefore used in the prevention and treatment of osteoporosis. Also vitamin D

The long-recognized role of the vitamin D endocrine system is to maintain stable serum calcium concentrations, which are ensured by a complex interplay between parathyroid gland, kidney, intestine, and bone. However, although VDR is expressed in osteoclastogenic cells, the contribution of VDR-mediated signaling to osteoclast differentiation and activity remains undefined. We therefore deleted Vdr expression efficiently and specifically in myeloid cells by use of M lysozyme-driven Cre expression, which targets granulocytes, monocytes, macrophages and osteoclasts (Vdrmyel- mice). Bone and calcium homeostasis were investigated under basal conditions and in conditions of increased bone remodeling, by feeding Vdrmyel- and Vdrmyel+ (wildtype) mice either a normal (1%) or a low (0.02%) calcium diet from weaning onwards. Vdrmyel- mice developed normally and were normocalcemic at the age of 8 weeks, both at the normal and the low calcium diet. No differences in trabecular or cortical bone mass were observed between Vdrmyel- mice and their wildtype littermates. Dietary calcium restriction resulted in a comparable reduction of trabecular bone mass (40%) and cortical thickness (48%) in Vdrmyel- and Vdrmyel+ mice, pointing to a massive transfer of calcium from the bone to the serum. In agreement with these results, osteoclastic differentiation of hematopoietic cells of Vdrmyel- mice, either induced by M-CSF and RANKL, or cocultured with osteoblasts, occurred as efficiently as osteoclastogenesis from Vdrmyel+ mice. In conclusion, our data do not support a role for osteoclastic Vdr signaling in the control of bone homeostasis. ispartof: JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY vol:195 ispartof: location:England status: published

The vitamin D endocrine system is essential for calcium metabolism and skeletal integrity. 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] regulates bone mineral homeostasis and acts directly on osteoblasts. In the present study we characterized the transcriptional regulation of the class 3 semaphorin (Sema3) gene family by 1,25(OH)(2)D(3) in osteoblastic cells. Class 3 semaphorins are secreted proteins that regulate cell growth, morphology and migration, and were recently shown to be involved in bone homeostasis. In ST2, MC3T3-E1 and primary calvarial osteoblast cell cultures we found that all members of the Sema3 gene family were expressed, and that Sema3e and Sema3f were the most strongly induced 1,25(OH)(2)D(3) target genes among the studied cell types. In addition, transcription of Sema3b and Sema3c was upregulated, whereas Sema3d and Sema3g was downregulated by 1,25(OH)(2)D(3) in different osteoblastic cells. Chromatin immunoprecipitation analysis linked to DNA sequencing (ChIP-seq analysis) revealed the presence of the vitamin D receptor at multiple genomic loci in the proximity of Sema3 genes, demonstrating that the genes are primary 1,25(OH)(2)D(3) targets. Furthermore, we showed that recombinant SEMA3E and SEMA3F protein were able to inhibit osteoblast proliferation. However, recombinant SEMA3s did not affect ST2 cell migration. The expression of class 3 semaphorins in osteoblasts together with their regulation by 1,25(OH)(2)D(3) suggests that these genes, involved in the regulation of bone homeostasis, are additional mediators for 1,25(OH)(2)D(3) signaling in osteoblasts.

To assess the prevalence of major obstetric haemorrhage managed with peripartum hysterectomy and/or interventional radiology (IR) in Belgium. To describe women characteristics, the circumstances in which the interventions took place, the management of the obstetric haemorrhage, the outcome and additional morbidity of these women., SCOPUS: ar.j, info:eu-repo/semantics/published