Nature communications
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Nature communications · Nov 2014
ReviewGlobal potential of biospheric carbon management for climate mitigation.
Elevated concentrations of atmospheric greenhouse gases (GHGs), particularly carbon dioxide (CO2), have affected the global climate. Land-based biological carbon mitigation strategies are considered an important and viable pathway towards climate stabilization. However, to satisfy the growing demands for food, wood products, energy, climate mitigation and biodiversity conservation-all of which compete for increasingly limited quantities of biomass and land-the deployment of mitigation strategies must be driven by sustainable and integrated land management. If executed accordingly, through avoided emissions and carbon sequestration, biological carbon and bioenergy mitigation could save up to 38 billion tonnes of carbon and 3-8% of estimated energy consumption, respectively, by 2050.
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Nature communications · Oct 2014
Cell type-specific plasticity of striatal projection neurons in parkinsonism and L-DOPA-induced dyskinesia.
The striatum is widely viewed as the fulcrum of pathophysiology in Parkinson's disease (PD) and L-DOPA-induced dyskinesia (LID). In these disease states, the balance in activity of striatal direct pathway spiny projection neurons (dSPNs) and indirect pathway spiny projection neurons (iSPNs) is disrupted, leading to aberrant action selection. However, it is unclear whether countervailing mechanisms are engaged in these states. ⋯ Although the synaptic connectivity of dSPNs did not change in PD models, it fell with L-DOPA treatment. In neither case, however, was the strength of corticostriatal connections globally scaled. Thus, SPNs manifested homeostatic adaptations in intrinsic excitability and in the number but not strength of excitatory corticostriatal synapses.
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Nature communications · Jul 2014
Development of pro-apoptotic peptides as potential therapy for peritoneal endometriosis.
Endometriosis is a common gynaecological disease associated with pelvic pain and infertility. Current treatments include oral contraceptives combined with nonsteroidal anti-inflammatory drugs or surgery to remove lesions, all of which provide a temporary but not complete cure. Here we identify an endometriosis-targeting peptide that is internalized by cells, designated z13, using phage display. ⋯ We then linked z13 with an apoptosis-inducing peptide and with an endosome-escaping peptide. When these peptides were co-administered into the peritoneum of baboons with endometriosis, cells in lesions selectively underwent apoptosis with no effect on neighbouring organs. Thus, this study presents a strategy that could be useful to treat peritoneal endometriosis in humans.
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Nature communications · Jul 2014
Treatment of acute lung injury by targeting MG53-mediated cell membrane repair.
Injury to lung epithelial cells has a role in multiple lung diseases. We previously identified mitsugumin 53 (MG53) as a component of the cell membrane repair machinery in striated muscle cells. Here we show that MG53 also has a physiological role in the lung and may be used as a treatment in animal models of acute lung injury. ⋯ Intravenous delivery or inhalation of rhMG53 reduces symptoms in rodent models of acute lung injury and emphysema. Repetitive administration of rhMG53 improves pulmonary structure associated with chronic lung injury in mice. Our data indicate a physiological function for MG53 in the lung and suggest that targeting membrane repair may be an effective means for treatment or prevention of lung diseases.
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Nature communications · Jul 2014
Lysosome sorting of β-glucocerebrosidase by LIMP-2 is targeted by the mannose 6-phosphate receptor.
The integral membrane protein LIMP-2 has been a paradigm for mannose 6-phosphate receptor (MPR) independent lysosomal targeting, binding to β-glucocerebrosidase (β-GCase) and directing it to the lysosome, before dissociating in the late-endosomal/lysosomal compartments. Here we report structural results illuminating how LIMP-2 binds and releases β-GCase according to changes in pH, via a histidine trigger, and suggesting that LIMP-2 localizes the ceramide portion of the substrate adjacent to the β-GCase catalytic site. ⋯ By fluorescence lifetime imaging microscopy, we also demonstrate that LIMP-2 interacts with MPR in living cells. These results revise the accepted view of LIMP-2-β-GCase lysosomal targeting.