286 research outputs found

    Structure of the Protein Phosphatase 2A Holoenzyme

    Get PDF
    SummaryProtein Phosphatase 2A (PP2A) plays an essential role in many aspects of cellular physiology. The PP2A holoenzyme consists of a heterodimeric core enzyme, which comprises a scaffolding subunit and a catalytic subunit, and a variable regulatory subunit. Here we report the crystal structure of the heterotrimeric PP2A holoenzyme involving the regulatory subunit B′/B56/PR61. Surprisingly, the B′/PR61 subunit has a HEAT-like (huntingtin-elongation-A subunit-TOR-like) repeat structure, similar to that of the scaffolding subunit. The regulatory B′/B56/PR61 subunit simultaneously interacts with the catalytic subunit as well as the conserved ridge of the scaffolding subunit. The carboxyterminus of the catalytic subunit recognizes a surface groove at the interface between the B′/B56/PR61 subunit and the scaffolding subunit. Compared to the scaffolding subunit in the PP2A core enzyme, formation of the holoenzyme forces the scaffolding subunit to undergo pronounced conformational rearrangements. This structure reveals significant ramifications for understanding the function and regulation of PP2A

    Increased Frequency and Compromised Function of T Regulatory Cells in Systemic Sclerosis (SSc) Is Related to a Diminished CD69 and TGFβ Expression

    Get PDF
    Contains fulltext : 80239.pdf (publisher's version ) (Open Access)BACKGROUND: Regulatory T cells (Tregs) are essential in the control of tolerance. Evidence implicates Tregs in human autoimmune conditions. Here we investigated their role in systemic sclerosis (SSc). METHODS/PRINCIPAL FINDINGS: Patients were subdivided as having limited cutaneous SSc (lcSSc, n = 20) or diffuse cutaneous SSc (dcSSc, n = 48). Further subdivision was made between early dcSSc (n = 24) and late dcSSc (n = 24) based upon the duration of disease. 26 controls were studied for comparison. CD3+ cells were isolated using FACS and subsequently studied for the expression of CD4, CD8, CD25, FoxP3, CD127, CD62L, GITR, CD69 using flow cytometry. T cell suppression assays were performed using sorted CD4CD25(high)CD127(-) and CD4CD25(low)CD127(high) and CD3(+) cells. Suppressive function was correlated with CD69 surface expression and TGFbeta secretion/expression. The frequency of CD4(+)CD25(+) and CD25(high)FoxP3(high)CD127(neg) T cells was highly increased in all SSc subgroups. Although the expression of CD25 and GITR was comparable between groups, expression of CD62L and CD69 was dramatically lower in SSc patients, which correlated with a diminished suppressive function. Co-incubation of Tregs from healthy donors with plasma from SSc patients fully abrogated suppressive activity. Activation of Tregs from healthy donors or SSc patients with PHA significantly up regulated CD69 expression that could be inhibited by SSc plasma. CONCLUSIONS/SIGNIFICANCE: These results indicate that soluble factors in SSc plasma inhibit Treg function specifically that is associated with altered Treg CD69 and TGFbeta expression. These data suggest that a defective Treg function may underlie the immune dysfunction in systemic sclerosis

    Mariana Serpentinite Mud Volcanism Exhumes Subducted Seamount Materials: Implications for the Origin of Life.

    Get PDF
    The subduction of seamounts and ridge features at convergent plate boundaries plays an important role in the deformation of the overriding plate and influences geochemical cycling and associated biological processes. Active serpentinization of forearc mantle and serpentinite mud volcanism on the Mariana forearc (between the trench and active volcanic arc) provides windows on subduction processes.  Here, we present (1) the first observation of an extensive exposure of an undeformed Cretaceous seamount currently being subducted at the Mariana Trench inner slope; (2) vertical deformation of the forearc region related to subduction of Pacific Plate seamounts and thickened crust; (3) recovered Ocean Drilling Program and International Ocean Discovery Program cores of serpentinite mudflows that confirm exhumation of various Pacific Plate lithologies, including subducted reef limestone; (4) petrologic, geochemical and paleontological data from the cores that show that Pacific Plate seamount exhumation covers greater spatial and temporal extents; (5) the inference that microbial communities associated with serpentinite mud volcanism may also be exhumed from the subducted plate seafloor and/or seamounts; and (6) the implications for effects of these processes with regard to evolution of life. This article is part of a discussion meeting issue ‘Serpentine in the Earth system’

    Uncovering the economic value of natural enemies and true costs of chemical insecticides to cotton farmers in China

    Get PDF
    Little empirical evidence on economic value of biological control of pests at farm level is available to improve economic decision-making by farmers and policy makers. Using insect sampling and household survey in an integrated bio-economic analysis framework, this paper studies farmers' crop management practices in cotton in the North China Plain, and estimates the marginal value of natural enemies and costs of chemical insecticides to farmers. Ladybeetles (mainly Harmonia axyridis, Propylea japonica, and Coccinella septempunctata), the dominant natural enemy group that controls the primary pest (aphid) in cotton in our study area, provide a significant economic benefit that is unknown to the farmers. Even at the current high levels of insecticide use, additional ladybeetle provides an economic benefit of 0.05 CNY (USD 0.01) to farmers. The use of broad-spectrum insecticides by farmers is alarmingly excessive, not only undermining farmers' profitability but also inducing social costs as well as disruption of the natural pest suppression system. Doubling current ladybeetle density in cotton field could gain an estimated USD 300 million for cotton farmers in China, providing a strong economic case for policies to move the pest control system toward a more ecologically-based regime, with positive consequences for farm income and environmental health. With rising use of biological control service provided by natural enemies in cotton fields, significant falls in farmers' insecticide use would be expected, which could raise the value of ladybeetles and other natural enemies even further. The results indicate that there is an urgent need to rationalize inputs and move forward to improved agro-ecosystem management in smallholder farming system. Raising knowledge and awareness on the costs and value of biological pest control versus insecticides among farmers and policy makers and having effective extension service are priorities toward achieving a more ecologically-based approach to crop protection on smallholder farms

    Greening China naturally

    Get PDF
    Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in AMBIO: A Journal of the Human Environment 40 (2011): 828-831, doi:10.1007/s13280-011-0150-8.China leads the world in afforestation, and is one of the few countries whose forested area is increasing. However, this massive ‘‘greening’’ effort has been less effective than expected; afforestation has sometimes produced unintended environmental, ecological, and socioeconomic consequences, and has failed to achieve the desired ecological benefits. Where afforestation has succeeded, the approach was tailored to local environmental conditions. Using the right plant species or species composition for the site and considering alternatives such as grassland restoration have been important success factors. To expand this success, government policy should shift from a forest-based approach to a results-based approach. In addition, long-term monitoring must be implemented to provide the data needed to develop a cost-effective, scientifically informed restoration policy.This work was supported by the Fundamental Research Funds for the Central Universities (HJ2010-3) and the CAS/ SAFEA International Partnership Program for Creative Research Teams of ‘‘Ecosystem Processes and Services’’

    Self-Cleaning Glass of Photocatalytic Anatase TiO2@Carbon Nanotubes Thin Film by Polymer-Assisted Approach

    Get PDF
    Due to the good photocatalytic activity, the TiO2@CNTs thin film is highly desirable to apply to the self-cleaning glass for green intelligent building. Here, the TiO2@CNTs thin film has been successfully achieved by polymer-assisted approach of an aqueous chemical solution method. The polymer, polyethylenimine, aims to combine the Ti4+ with CNTs for film formation of TiO2@CNTs. The resultant thin film was uniform, highly transparent, and super-hydrophilic. Owing to fast electron transport and effectively hindering electron-hole recombination, the TiO2@CNTs thin film has nearly twofold photocatalytic performance than pure TiO2. The TiO2@CNTs thin films show a good application for self-cleaning glasses

    Tissue-Autonomous Function of Drosophila Seipin in Preventing Ectopic Lipid Droplet Formation

    Get PDF
    Obesity is characterized by accumulation of excess body fat, while lipodystrophy is characterized by loss or absence of body fat. Despite their opposite phenotypes, these two conditions both cause ectopic lipid storage in non-adipose tissues, leading to lipotoxicity, which has health-threatening consequences. The exact mechanisms underlying ectopic lipid storage remain elusive. Here we report the analysis of a Drosophila model of the most severe form of human lipodystrophy, Berardinelli-Seip Congenital Lipodystrophy 2, which is caused by mutations in the BSCL2/Seipin gene. In addition to reduced lipid storage in the fat body, dSeipin mutant flies accumulate ectopic lipid droplets in the salivary gland, a non-adipose tissue. This phenotype was suppressed by expressing dSeipin specifically within the salivary gland. dSeipin mutants display synergistic genetic interactions with lipogenic genes in the formation of ectopic lipid droplets. Our data suggest that dSeipin may participate in phosphatidic acid metabolism and subsequently down-regulate lipogenesis to prevent ectopic lipid droplet formation. In summary, we have demonstrated a tissue-autonomous role of dSeipin in ectopic lipid storage in lipodystrophy
    corecore