Survival effect of PDGF-CC rescues neurons from apoptosis in both brain and retina by regulating GSK3β phosphorylation

Platelet-derived growth factor CC (PDGF-CC) is the third member of the PDGF family discovered after more than two decades of studies on the original members of the family, PDGF-AA and PDGF-BB. The biological function of PDGF-CC remains largely to be explored. We report a novel finding that PDGF-CC is a potent neuroprotective factor that acts by modulating glycogen synthase kinase 3β (GSK3β) activity. In several different animal models of neuronal injury, such as axotomy-induced neuronal death, neurotoxin-induced neuronal injury, 6-hydroxydopamine–induced Parkinson’s dopaminergic neuronal death, and ischemia-induced stroke, PDGF-CC protein or gene delivery protected different types of neurons from apoptosis in both the retina and brain. On the other hand, loss-of-function assays using PDGF-C null mice, neutralizing antibody, or short hairpin RNA showed that PDGF-CC deficiency/inhibition exacerbated neuronal death in different neuronal tissues in vivo. Mechanistically, we revealed that the neuroprotective effect of PDGF-CC was achieved by regulating GSK3β phosphorylation and expression. Our data demonstrate that PDGF-CC is critically required for neuronal survival and may potentially be used to treat neurodegenerative diseases. Inhibition of the PDGF-CC–PDGF receptor pathway for different clinical purposes should be conducted with caution to preserve normal neuronal functions

A conserved motif flags acyl carrier proteins for β-branching in polyketide synthesis

Type I PKSs often utilise programmed β-branching, via enzymes of an “HMG-CoA synthase (HCS) cassette”, to incorporate various side chains at the second carbon from the terminal carboxylic acid of growing polyketide backbones. We identified a strong sequence motif in Acyl Carrier Proteins (ACPs) where β-branching is known. Substituting ACPs confirmed a correlation of ACP type with β-branching specificity. While these ACPs often occur in tandem, NMR analysis of tandem β-branching ACPs indicated no ACP-ACP synergistic effects and revealed that the conserved sequence motif forms an internal core rather than an exposed patch. Modelling and mutagenesis identified ACP Helix III as a probable anchor point of the ACP-HCS complex whose position is determined by the core. Mutating the core affects ACP functionality while ACP-HCS interface substitutions modulate system specificity. Our method for predicting β-carbon branching expands the potential for engineering novel polyketides and lays a basis for determining specificity rules

Dosing practice of low molecular weight heparins and its efficacy and safety in cardiovascular inpatients: a retrospective study in a Chinese teaching hospital

Abstract Background Low-molecular-weight heparins (LMWHs) are safe and effective anticoagulant options for cardiovascular patients when applied as body weight-adjusted doses. However, there are some barriers that make it difficult to implement weight-adjusted doses in clinical practice. Therefore, it is vital to learn the dosing practices of LMWH and its efficacy and safety in clinical practice. Methods A retrospective study was conducted in cardiovascular inpatients who had received at least one dose of LMWH during a 6-month period. Appropriateness of LMWH dosing was determined and major clinical outcomes (major adverse vascular events and major bleeding) during hospitalization were evaluated. Results A total of 376 admissions representing 364 patients received LMWH treatment. Of these, 17.0% (64/376) of admissions did not have body weight records. Of the 312 admissions included for the outcome study, only 34 cases (10.9%) received the recommended doses of LMWH, while 51 cases (16.3%) received mild underdoses, 223 cases (71.5%) received major underdoses and 4 (1.3%) received excess doses. There were 10 major adverse vascular events, which occurred more often in patients receiving excess doses of LMWH than in patients receiving recommended, mild or major underdoses (50%, 2.9%, 2.0% and 2.7%, respectively, P P Conclusions Underdose of LMWH is commonly used in cardiovascular inpatients, which was suboptimal according to guidelines. Using LMWH at a fixed, low dose for treatment purposes in patients without severe renal insufficiency was not associated with a higher risk of adverse vascular events in the current study, though larger studies with extended follow-ups are required to fully assess the long-term consequences of LMWH underdosing.</p

Data for: "Financing Carbon Lock-in in Developing Countries: Bilateral Financing for Power Generation Technologies from China, Japan, and the United States"

This dataset contains bilateral power generation financing data from China, Japan, and the United States in the paper "Financing Carbon Lock-in in Developing Countries: Bilateral Financing for Power Generation Technologies from China, Japan, and the United States” by Xu Chen, Zhongshu Li, Kevin P. Gallagher, and Denise L. Mauzerall published in Applied Energy.Power sector decarbonization requires a fundamental redirection of global finance from fossil fuel infrastructure towards low carbon technologies. Bilateral finance plays an important role in the global energy transition to non-fossil energy, but an understanding of its impact is limited. Here, for the first time, we compare the influence of overseas finance from the three largest economies – United States, China, and Japan – on power generation development beyond their borders and evaluate the associated long-term CO2 emissions. We construct a new dataset of Japanese and U.S. overseas power generation finance between 2000-2018 by analyzing their national development finance institutions’ press releases and annual reports and tracking their foreign direct investment at the power plant level. Synthesizing this new data with previously developed datasets for China, we find that the three countries’ overseas financing concentrated in fossil fuel power technologies over the studied period. Financing commitments from China, Japan, and the United States facilitated 101 GW, 95 GW, and 47 GW overseas power capacity additions, respectively. The majority of facilitated capacity additions are fossil fuel plants (64% for China, 87% for Japan, and 66% for the United States). Each of the countries’ contributions to non-hydro renewable generation was less than 15% of their facilitated capacity additions. Together, we estimate that overseas fossil fuel power financing through 2018 from these three countries will lock in 24 Gt CO2 emissions by 2060. If climate targets are to be met, replacing bilateral fossil fuel financing with financing of renewable technologies is crucial