Organic carbon accumulation in British saltmarshes.

Saltmarshes are a crucial component of the coastal carbon (C) system and provide a natural climate regulation service through the accumulation and long-term storage of organic carbon (OC) in their soils. These coastal ecosystems are under growing pressure from a changing climate and increasing anthropogenic disturbance. To manage and protect these ecosystems for C and to allow their inclusion in emissions and natural-capital accounting, as well as carbon markets, accurate and reliable estimates of OC accumulation are required. However, globally, such data are rare or of varying quality. Here, we quantify sedimentation rates and OC densities for 21 saltmarshes in Great Britain (GB). We estimate that, on average, saltmarshes accumulate OC at a rate of 110.88 ± 43.12 g C m-2 yr-1. This is considerably less than widely applied global saltmarsh averages. It is therefore highly likely that the contribution of northern European saltmarshes to global saltmarsh OC accumulation has been significantly overestimated. Taking account of the climatic, geomorphological, oceanographic, and ecological characteristics of all GB saltmarshes and the areal extent of different saltmarsh zones, we estimate that the 451.65 km2 of GB saltmarsh accumulates 46,563 ± 4353 t of OC annually. These low OC accumulation rates underline the importance of the 5.20 ± 0.65 million tonnes of OC already stored in these vulnerable coastal ecosystems. Going forward the protection and preservation of the existing stores of OC in GB saltmarshes must be a priority for the UK as this will provide climate benefits through avoided emissions several times more significant than the annual accumulation of OC in these ecosystems.

Imatinib mesylate for plexiform neurofibromas in patients with neurofibromatosis type 1: a phase 2 trial.

BACKGROUND: Plexiform neurofibromas are slow-growing chemoradiotherapy-resistant tumours arising in patients with neurofibromatosis type 1 (NF1). Currently, there are no viable therapeutic options for patients with plexiform neurofibromas that cannot be surgically removed because of their proximity to vital body structures. We undertook an open-label phase 2 trial to test whether treatment with imatinib mesylate can decrease the volume burden of clinically significant plexiform neurofibromas in patients with NF1. METHODS: Eligible patients had to be aged 3-65 years, and to have NF1 and a clinically significant plexiform neurofibroma. Patients were treated with daily oral imatinib mesylate at 220 mg/m(2) twice a day for children and 400 mg twice a day for adults for 6 months. The primary endpoint was a 20% or more reduction in plexiform size by sequential volumetric MRI imaging. Clinical data were analysed on an intention-to-treat basis; a secondary analysis was also done for those patients able to take imatinib mesylate for 6 months. This trial is registered with ClinicalTrials.gov, number NCT01673009. FINDINGS: Six of 36 patients (17%, 95% CI 6-33), enrolled on an intention-to-treat basis, had an objective response to imatinib mesylate, with a 20% or more decrease in tumour volume. Of the 23 patients who received imatinib mesylate for at least 6 months, six (26%, 95% CI 10-48) had a 20% or more decrease in volume of one or more plexiform tumours. The most common adverse events were skin rash (five patients) and oedema with weight gain (six). More serious adverse events included reversible grade 3 neutropenia (two), grade 4 hyperglycaemia (one), and grade 4 increases in aminotransferase concentrations (one). INTERPRETATION: Imatinib mesylate could be used to treat plexiform neurofibromas in patients with NF1. A multi-institutional clinical trial is warranted to confirm these results. FUNDING: Novartis Pharmaceuticals, the Indiana University Simon Cancer Centre, and the Indiana University Herman B Wells Center for Pediatric Research.

Negative regulation of Stat3 by activating PTPN11 mutants contributes to the pathogenesis of Noonan syndrome and juvenile myelomonocytic leukemia.

Noonan syndrome (NS) is an autosomal dominant congenital disorder characterized by multiple birth defects including heart defects and myeloproliferative disease (MPD). Approximately 50% of NS patients have germline gain-of-function mutations in PTPN11, which encodes the protein-tyrosine phosphatase, Shp2. We provide evidence that conditional ablation of Stat3 in hematopoietic cells and cardiac valvular tissues leads to myeloid progenitor hyperplasia and pulmonary stenosis due to the leaflet thickening, respectively. Consistently, STAT3 activation is significantly compromised in peripheral blood cells from NS patients bearing Shp2-activating mutations. Biochemical and functional analyses demonstrate that activated Shp2 is able to down-regulate Tyr(P)-Stat3 and that constitutively active Stat3 rescues activating mutant Shp2-induced granulocyte-macrophage colony-stimulating factor hypersensitivity in bone marrow cells. Collectively, our work demonstrates that Stat3 is an essential signaling component potentially contributing to the pathogenesis of NS and juvenile myelomonocytic leukemia caused by PTPN11 gain-of-function mutations.