Transmembrane routes of cationic liposome-mediated gene delivery using human throat epidermis cancer cells

For studying the mechanism of cationic liposome-mediated transmembrane routes for gene delivery, various inhibitors of endocytosis were used to treat human throat epidermis cancer cells, Hep-2, before transfection with Lipofectamine 2000/pGFP-N2 or Lipofectamine 2000/pGL3. To eliminate the effect of inhibitor toxicity on transfection, the RLU/survival rate was used to represent the transfection efficiency. Chlorpromazine and wortmannin, clathrin inhibitors, decreased transfection efficiency by 44 % (100 μM) and 31 % (100 nM), respectively. At the same time, genistein, a caveolin inhibitor, decreased it by 30 % (200 μM). Thus combined transmembrane routes through the clathrin and caveolae-mediated pathways were major mechanisms of cell uptake for the cationic liposome-mediated gene delivery. After entering the cells, microtubules played an important role on gene delivery as vinblastine, a microtubulin inhibitor, could reduce transfection efficiency by 41 % (200 nM)

Tri-peptide cationic lipids for gene delivery

A novel tri-peptide cationic lipid can efficiently transfer DNA and siRNA into tumor cells and tumors of mice with little in vitro and in vivo toxicity

Relative importance of climatic variables, soil properties and plant traits to spatial variability in net CO2 exchange across global forests and grasslands

Compared to the well-known drivers of spatial variability in gross primary productivity (GPP), the relative importance of climatic variables, soil properties and plant traits to the spatial variability in net ecosystem exchange of CO2 between terrestrial ecosystem and atmosphere (NEE) is poorly understood. We used principal component regression to analyze data from 147 eddy flux sites to disentangle effects of climatic variables, soil properties and plant traits on the spatial variation in annual NEE and its components (GPP and ecosystem respiration (RE)) across global forests and grasslands. Our results showed that the largest unique contribution (proportion of variance only explained by one class of variables) to NEE variance came from climatic variables for forests (24%-30%) and soil properties for grasslands (41%-54%). Specifically, mean annual precipitation and potential evapotranspiration were the most important climatic variables driving forest NEE, whereas available soil water capacity, clay content and cation exchange capacity mainly influenced grassland NEE. Plant traits showed a small unique contribution to NEE in both forests and grasslands. However, leaf phosphorus content strongly interacted with soil total nitrogen density and clay content, and these combined factors represented a major contribution for grassland NEE. For GPP and RE, the majority of spatial variance was attributed to the common contribution of climate, soil and plant traits (50% - 62%, proportion of variance explained by more than one class of variables), rather than their unique contributions. Interestingly, those factors with only minor influences on GPP and RE variability (e.g., soil properties) have significant contributions to the spatial variability in NEE. Such emerging factors and the interactions between climatic variables, soil properties and plant traits are not well represented in current terrestrial biosphere models, which should be considered in future model improvement to accurately predict the spatial pattern of carbon cycling across forests and grasslands globally.Peer reviewe

Prevention of Fetal/Neonatal Alloimmune Thrombocytopenia in Mice: Biochemical and Cell Biological Characterization of Isoforms of a Human Monoclonal Antibody

Maternal alloantibodies toward paternally inherited Ags on fetal platelets can cause thrombocytopenia and bleeding complications in the fetus or neonate, referred to as fetal and neonatal alloimmune thrombocytopenia (FNAIT). This is most commonly caused by Abs against the human platelet Ag (HPA)-1a in Caucasians, and a prophylactic regimen to reduce the risk for alloimmunization to women at risk would be beneficial. We therefore aimed to examine the prophylactic potential of a fully human anti–HPA-1a IgG1 (mAb 26.4) with modified Fc region or altered N-glycan structures. The mAb 26.4 wild-type (WT) variants all showed efficient platelet clearance capacity and ability to mediate phagocytosis independent of their N-glycan structure, compared with an effector silent variant (26.4.AAAG), although the modified N-glycan variants showed differential binding to FcγRs measured in vitro. In an in vivo model, female mice were transfused with platelets from transgenic mice harboring an engineered integrin β3 containing the HPA-1a epitope. When these preimmunized mice were bred with transgenic males, Abs against the introduced epitope induced thrombocytopenia in the offspring, mimicking FNAIT. Prophylactic administration of the mAb 26.4.WT, and to some extent the mAb 26.4.AAAG, prior to platelet transfusion resulted in reduced alloimmunization in challenged mice and normal platelet counts in neonates. The notion that the effector silent variant hampered alloimmunization demonstrates that rapid platelet clearance, as seen with mAb 26.4.WT, is not the sole mechanism in action. Our data thus successfully demonstrate efficient Ab-mediated immunosuppression and prevention of FNAIT by anti–HPA-1a monoclonal variants, providing support for potential use in humans

Leveraging Subgraph Extraction for Performance Portable Programming Frameworks on DL Accelerators

International audienceDeep learning framework plays an important role in connecting hardware platform and algorithm. In recent years, some domain-specific deep learning accelerators with better performance and energy efficiency were proposed by researchers. However, current frameworks lack enough considerations about how to better support the possible new features brought by accelerators. In this paper, we propose to build a performance portable programming framework with subgraph extraction. The intuition is that increasing ratio of optimizations are taken from the top-level framework to the low-level software stack of accelerator. In response to this development trend, framework needs to pay more attention to the splitting strategy of computation graph for the heterogeneous computation

The role of Chinese people's political consultative conference in environmental governance : evidence from environmental proposals

Purpose: This paper aims to examine the role of the Chinese People’s Political Consultative Conference (CPPCC), a political advisory body in China, in addressing environmental challenges. Design/methodology/approach: This study uses 457 CPPCC environmental proposals across 160 cities for the period of 2013 to 2015 and a mediation effect model to examine the effect of CPPCC environmental proposals on environmental quality. Findings: This study shows that CPPCC environmental proposals improve environmental quality; and the relationship between CPPCC environmental proposals and environmental quality is partially mediated by enforcement of environmental laws and regulations only although the proposals positively influence both law enforcement and environmental public budget expenditures. Research limitations/implications: Future research may examine how the interaction between the government and other important stakeholders such as non-governmental organizations can help improve environmental quality. In addition, future research may examine whether other policy tools such as pollution tax and fees, environmental subsidies, and emissions trading can play a role in dealing with environmental issues. Practical implications: This study provides evidence that supports CPPCC members to take an even more active role in public governance by engaging with both the government and the public. Social implications: The CPPCC’s participation in public governance helps the government respond to critical issues more effectively. The government should pay close attention to CPPCC proposals when making public policies. Furthermore, the government probably needs to review its policies in relation to environmental expenditures. Originality/value: This study is the first to examine the role of the CPPCC, a political advisory body, in addressing environmental challenges through functioning as a bridge between government and the public, whereas the extant literature has predominantly focused on the role of government, market and the public

Hydrogen Sulfide as a Potential Therapeutic Target in Fibrosis

Hydrogen sulfide (H2S), produced endogenously by the activation of two major H2S-generating enzymes (cystathionine β-synthase and cystathionine γ-lyase), plays important regulatory roles in different physiologic and pathologic conditions. The abnormal metabolism of H2S is associated with fibrosis pathogenesis, causing damage in structure and function of different organs. A number of in vivo and in vitro studies have shown that both endogenous H2S level and the expressions of H2S-generating enzymes in plasma and tissues are significantly downregulated during fibrosis. Supplement with exogenous H2S mitigates the severity of fibrosis in various experimental animal models. The protective role of H2S in the development of fibrosis is primarily attributed to its antioxidation, antiapoptosis, anti-inflammation, proangiogenesis, and inhibition of fibroblasts activities. Future studies might focus on the potential to intervene fibrosis by targeting the pathway of endogenous H2S-producing enzymes and H2S itself

Monocyte Chemotactic Protein 1-Induced Protein 1 Is Highly Expressed in Inflammatory Bowel Disease and Negatively Regulates Neutrophil Activities

Monocyte chemotactic protein 1-induced protein 1 (MCPIP-1) is highly expressed in activated immune cells and plays an important role in negatively regulating immune responses. However, its role in regulating neutrophil functions in the pathogenesis of inflammatory bowel disease (IBD) is still unclear. Here, we found that MCPIP-1 was markedly increased at both the transcriptional and translational levels in inflamed mucosa of IBD patients compared with healthy controls, which was mainly expressed in neutrophils. Interestingly, MG-132, a proteasome inhibitor reducing the degradation of MCPIP-1, further facilitated neutrophils to express MCPIP-1 in vitro. Importantly, MCPIP-1 markedly downregulated the production of ROS, MPO, and proinflammatory cytokines (e.g., interleukin-1β, interleukin-6, tumor necrosis factor-α, interleukin-8, and interferon-γ) and suppressed the migration of IBD neutrophils. Consistently, the same functional changes were observed in neutrophils from mice with myeloid-targeted overexpression of MCPIP-1 as MG-132 did. Altogether, these findings suggest that MCPIP-1 plays a negative role in regulating neutrophil activities through suppressing the production of ROS, MPO, and proinflammatory cytokines and inhibiting the migration. MG-132 may partially modulate the function of neutrophils via the induction of MCPIP-1. Therefore, targeting MCPIP-1 or exogenous supplementation of MG-132 may provide a therapeutic approach in the treatment of IBD