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Sample records for global phosphoproteomic effects

  1. SILAC for global phosphoproteomic analysis.

    PubMed

    Pimienta, Genaro; Chaerkady, Raghothama; Pandey, Akhilesh

    2009-01-01

    Establishing the phosphorylation pattern of proteins in a comprehensive fashion is an important goal of a majority of cell signaling projects. Phosphoproteomic strategies should be designed in such a manner as to identify sites of phosphorylation as well as to provide quantitative information about the extent of phosphorylation at the sites. In this chapter, we describe an experimental strategy that outlines such an approach using stable isotope labeling with amino acids in cell culture (SILAC) coupled to LC-MS/MS. We highlight the importance of quantitative strategies in signal transduction as a platform for a systematic and global elucidation of biological processes.

  2. SELPHI: correlation-based identification of kinase-associated networks from global phospho-proteomics data sets

    PubMed Central

    Petsalaki, Evangelia; Helbig, Andreas O.; Gopal, Anjali; Pasculescu, Adrian; Roth, Frederick P.; Pawson, Tony

    2015-01-01

    While phospho-proteomics studies have shed light on the dynamics of cellular signaling, they mainly describe global effects and rarely explore mechanistic details, such as kinase/substrate relationships. Tools and databases, such as NetworKIN and PhosphoSitePlus, provide valuable regulatory details on signaling networks but rely on prior knowledge. They therefore provide limited information on less studied kinases and fewer unexpected relationships given that better studied signaling events can mask condition- or cell-specific ‘network wiring’. SELPHI is a web-based tool providing in-depth analysis of phospho-proteomics data that is intuitive and accessible to non-bioinformatics experts. It uses correlation analysis of phospho-sites to extract kinase/phosphatase and phospho-peptide associations, and highlights the potential flow of signaling in the system under study. We illustrate SELPHI via analysis of phospho-proteomics data acquired in the presence of erlotinib—a tyrosine kinase inhibitor (TKI)—in cancer cells expressing TKI-resistant and -sensitive variants of the Epidermal Growth Factor Receptor. In this data set, SELPHI revealed information overlooked by the reporting study, including the known role of MET and EPHA2 kinases in conferring resistance to erlotinib in TKI sensitive strains. SELPHI can significantly enhance the analysis of phospho-proteomics data contributing to improved understanding of sample-specific signaling networks. SELPHI is freely available via http://llama.mshri.on.ca/SELPHI. PMID:25948583

  3. Machine learning of global phosphoproteomic profiles enables discrimination of direct versus indirect kinase substrates.

    PubMed

    Kanshin, Evgeny; Giguere, Sebastien; Cheng, Jing; Tyers, Michael D; Thibault, Pierre

    2017-03-06

    Mass spectrometry allows quantification of tens of thousands of phosphorylation sites from minute amounts of cellular material. Despite this wealth of information, our understanding of phosphorylation-based signaling is limited, in part because it is not possible to deconvolute substrate phosphorylation that is directly mediated by a particular kinase versus phosphorylation that is mediated by downstream kinases. Here, we describe a framework for assignment of direct in-vivo kinase substrates using a combination of selective chemical inhibition, quantitative phosphoproteomics, and machine learning techniques. Our workflow allows classification of phosphorylation events following inhibition of an analog-sensitive kinase into kinase-independent effects of the inhibitor, direct effects on cognate substrates and indirect effects mediated by downstream kinases or phosphatases. We applied this method to identify many direct targets of Cdc28 and Snf1 kinases in the budding yeast S. cerevisiae. Global phosphoproteome analysis of acute time-series demonstrated that dephosphorylation of direct kinase substrates occurs more rapidly compared to indirect substrates, both after inhibitor treatment and under a physiological nutrient shift in wild-type cells. Mutagenesis experiments revealed a high proportion of functionally relevant phosphorylation sites on Snf1 targets. For example, Snf1 itself was inhibited through autophosphorylation on S391 and new phosphosites were discovered that modulate the activity of the Reg1 regulatory subunit of the Glc7 phosphatase and the Gal83 β-subunit of SNF1 complex. This methodology applies to any kinase for which a functional analog sensitive version can be constructed to facilitate the dissection of the global phosphorylation network.

  4. Hydrophilic interaction chromatography reduces the complexity of the phosphoproteome and improves global phosphopeptide isolation and detection.

    PubMed

    McNulty, Dean E; Annan, Roland S

    2008-05-01

    The diversity and complexity of proteins and peptides in biological systems requires powerful liquid chromatography-based separations to optimize resolution and detection of components. Proteomics strategies often combine two orthogonal separation modes to meet this challenge. In nearly all cases, the second dimension is a reverse phase separation interfaced directly to a mass spectrometer. Here we report on the use of hydrophilic interaction chromatography (HILIC) as part of a multidimensional chromatography strategy for proteomics. Tryptic peptides are separated on TSKgel Amide-80 columns using a shallow inverse organic gradient. Under these conditions, peptide retention is based on overall hydrophilicity, and a separation truly orthogonal to reverse phase is produced. Analysis of tryptic digests from HeLa cells yielded numbers of protein identifications comparable to that obtained using strong cation exchange. We also demonstrate that HILIC represents a significant advance in phosphoproteomics analysis. We exploited the strong hydrophilicity of the phosphate group to selectively enrich and fractionate phosphopeptides based on their increased retention under HILIC conditions. Subsequent IMAC enrichment of phosphopeptides from HILIC fractions showed better than 99% selectivity. This was achieved without the use of derivatization or chemical modifiers. In a 300-microg equivalent of HeLa cell lysate we identified over 1000 unique phosphorylation sites. More than 700 novel sites were added to the HeLa phosphoproteome.

  5. TiSH--a robust and sensitive global phosphoproteomics strategy employing a combination of TiO2, SIMAC, and HILIC.

    PubMed

    Engholm-Keller, Kasper; Birck, Pernille; Størling, Joachim; Pociot, Flemming; Mandrup-Poulsen, Thomas; Larsen, Martin R

    2012-10-22

    Large scale quantitative phosphoproteomics depends upon multidimensional strategies for peptide fractionation, phosphopeptide enrichment, and mass spectrometric analysis. Previously, most robust comprehensive large-scale phosphoproteomics strategies have relied on milligram amounts of protein. We have set up a multi-dimensional phosphoproteomics strategy combining a number of well-established enrichment and fraction methods: An initial TiO(2) phosphopeptide pre-enrichment step is followed by post-fractionation using sequential elution from IMAC (SIMAC) to separate multi- and mono-phosphorylated peptides, and hydrophilic interaction liquid chromatography (HILIC) of the mono-phosphorylated peptides (collectively abbreviated "TiSH"). The advantages of the strategy include a high specificity and sample preparation workload reduction due to the TiO(2) pre-enrichment step, as well as low adsorptive losses. We demonstrate the capability of this strategy by quantitative investigation of early interferon-γ signaling in low quantities of insulinoma cells. We identified ~6600 unique phosphopeptides from 300 μg of peptides/condition (22 unique phosphopeptides/μg) in a duplex dimethyl labeling experiment, with an enrichment specificity>94%. When doing network analysis of putative phosphorylation changes it could be noted that the identified protein interaction network centered upon proteins known to be affected by the interferon-γ pathway, thereby supporting the utility of this global phosphoproteomics strategy. This strategy thus shows great potential for interrogating signaling networks from low amounts of sample with high sensitivity and specificity.

  6. Phosphoproteomics in Cancer

    PubMed Central

    Harsha, H. C.; Pandey, Akhilesh

    2010-01-01

    Reversible protein phosphorylation serves as a basis for regulating a number of cellular processes. Aberrant activation of kinase signaling pathways is commonly associated with several cancers. Recent developments in phosphoprotein/phosphopeptide enrichment strategies and quantitative mass spectrometry have resulted in robust pipelines for high-throughput characterization of phosphorylation in a global fashion. Today, it is possible to profile site-specific phosphorylation events on thousands of proteins in a single experiment. The potential of this approach is already being realized to characterize signaling pathways that govern oncogenesis. In addition, chemical proteomic strategies have been used to unravel targets of kinase inhibitors, which are otherwise difficult to characterize. This review summarizes various approaches used for analysis of the phosphoproteome in general, and protein kinases in particular, highlighting key cancer phosphoproteomic studies. PMID:20937571

  7. Global Phosphoproteomic Analysis Reveals the Involvement of Phosphorylation in Aflatoxins Biosynthesis in the Pathogenic Fungus Aspergillus flavus

    PubMed Central

    Ren, Silin; Yang, Mingkun; Li, Yu; Zhang, Feng; Chen, Zhuo; Zhang, Jia; Yang, Guang; Yue, Yuewei; Li, Siting; Ge, Feng; Wang, Shihua

    2016-01-01

    Aspergillus flavus is a pathogenic fungus that produces toxic and carcinogenic aflatoxins and is the causative agent of aflatoxicosis. A growing body of evidence indicates that reversible phosphorylation plays important roles in regulating diverse functions in this pathogen. However, only a few phosphoproteins of this fungus have been identified, which hampers our understanding of the roles of phosphorylation in A. flavus. So we performed a global and site-specific phosphoproteomic analysis of A. flavus. A total of 598 high-confidence phosphorylation sites were identified in 283 phosphoproteins. The identified phosphoproteins were involved in various biological processes, including signal transduction and aflatoxins biosynthesis. Five identified phosphoproteins associated with MAPK signal transduction and aflatoxins biosynthesis were validated by immunoblotting using phospho-specific antibodies. Further functional studies revealed that phosphorylation of the MAP kinase kinase kinase Ste11 affected aflatoxins biosynthesis in A. flavus. Our data represent the results of the first global survey of protein phosphorylation in A. flavus and reveal previously unappreciated roles for phosphorylation in the regulation of aflatoxins production. The generated dataset can serve as an important resource for the functional analysis of protein phosphorylation in A. flavus and facilitate the elucidation of phosphorylated signaling networks in this pathogen. PMID:27667718

  8. Phosphoproteomic profiling of the myocyte.

    PubMed

    Edwards, Alistair V G; Cordwell, Stuart J; White, Melanie Y

    2011-10-01

    Protein phosphorylation underpins major cellular processes including energy metabolism, signal transduction, excitation-contraction coupling, apoptosis, and cell survival mechanisms and is thus critical to the myocyte. Targeted approaches, whereby a handful of phosphoproteins are investigated, can suffer from a relatively narrow view of cellular phosphorylation. In contrast, recent technical advances have allowed for the comprehensive documentation of phosphorylation events in complex biological environments, providing a deeper view of the "phosphoproteome." A global, high-throughput characterization of the myocardial phosphoproteome, however, has not yet been achieved. Efficient analysis of phosphorylated proteins and their roles in a dynamic cellular environment requires high-resolution strategies that can identify, localize, and quantify many thousands of phosphorylation sites in a single experiment. Such an approach requires specific enrichment and purification techniques, developed to align with high-end instrumentation for analysis. Cutting-edge phosphoproteomics is no longer restricted to gel-based technology, instead focusing on affinity enrichment prior to liquid chromatography and mass spectrometry. We will describe the best current methods and how they can be applied, as well as the challenges associated with them. We also present current phosphoproteomic investigations in the myocyte and its subcompartments. Although the techniques and instrumentation required to achieve the goal of a myocardial phosphoprotein catalog in physiological and diseased states are highly specialized, the potential biological insight provided by such an approach makes phosphoproteomics an important new avenue of investigation for the cardiovascular researcher.

  9. Combined Quantification of the Global Proteome, Phosphoproteome, and Proteolytic Cleavage to Characterize Altered Platelet Functions in the Human Scott Syndrome*

    PubMed Central

    Solari, Fiorella A.; Mattheij, Nadine J.A.; Burkhart, Julia M.; Swieringa, Frauke; Collins, Peter W.; Cosemans, Judith M.E.M.; Sickmann, Albert; Heemskerk, Johan W.M.; Zahedi, René P.

    2016-01-01

    The Scott syndrome is a very rare and likely underdiagnosed bleeding disorder associated with mutations in the gene encoding anoctamin-6. Platelets from Scott patients are impaired in various Ca2+-dependent responses, including phosphatidylserine exposure, integrin closure, intracellular protein cleavage, and cytoskeleton-dependent morphological changes. Given the central role of anoctamin-6 in the platelet procoagulant response, we used quantitative proteomics to understand the underlying molecular mechanisms and the complex phenotypic changes in Scott platelets compared with control platelets. Therefore, we applied an iTRAQ-based multi-pronged strategy to quantify changes in (1) the global proteome, (2) the phosphoproteome, and (3) proteolytic events between resting and stimulated Scott and control platelets. Our data indicate a limited number of proteins with decreased (70) or increased (64) expression in Scott platelets, among those we confirmed the absence of anoctamin-6 and the strong up-regulation of aquaporin-1 by parallel reaction monitoring. The quantification of 1566 phosphopeptides revealed major differences between Scott and control platelets after stimulation with thrombin/convulxin or ionomycin. In Scott platelets, phosphorylation levels of proteins regulating cytoskeletal or signaling events were increased. Finally, we quantified 1596 N-terminal peptides in activated Scott and control platelets, 180 of which we identified as calpain-regulated, whereas a distinct set of 23 neo-N termini was caspase-regulated. In Scott platelets, calpain-induced cleavage of cytoskeleton-linked and signaling proteins was downregulated, in accordance with an increased phosphorylation state. Thus, multipronged proteomic profiling of Scott platelets provides detailed insight into their protection against detrimental Ca2+-dependent changes that are normally associated with phosphatidylserine exposure. PMID:27535140

  10. Biphasic Affinity Chromatographic Approach for Deep Tyrosine Phosphoproteome Analysis.

    PubMed

    Deng, Zhenzhen; Dong, Mingming; Wang, Yan; Dong, Jing; Li, Shawn S-C; Zou, Hanfa; Ye, Mingliang

    2017-02-21

    Tyrosine phosphorylation (pTyr) is important for normal physiology and implicated in many human diseases, particularly cancer. Identification of pTyr sites is critical to dissecting signaling pathways and understanding disease pathologies. However, compared with serine/threonine phosphorylation (pSer/pThr), the analysis of pTyr at the proteome level is more challenging due to its low abundance. Here, we developed a biphasic affinity chromatographic approach where Src SH2 superbinder was coupled with NeutrAvidin affinity chromatography, for tyrosine phosphoproteome analysis. With the use of competitive elution agent biotin-pYEEI, this strategy can distinguish high-affinity phosphotyrosyl peptides from low-affinity ones, while the excess competitive agent is readily removed by using NeutrAvidin agarose resin in an integrated tip system. The excellent performance of this system was demonstrated by analyzing tyrosine phosphoproteome of Jurkat cells from which 3,480 unique pTyr sites were identified. The biphasic affinity chromatography method for deep Tyr phosphoproteome analysis is rapid, sensitive, robust, and cost-effective. It is widely applicable to the global analysis of the tyrosine phosphoproteome associated with tyrosine kinase signal transduction.

  11. Phosphoproteomics and molecular cardiology: techniques, applications and challenges.

    PubMed

    Sun, Zeyu; Hamilton, Karyn L; Reardon, Kenneth F

    2012-09-01

    Protein phosphorylation has been widely documented as a key regulatory and signaling mechanism associated with many cardiac diseases. Recent advances in phosphoproteomic technologies such as phosphopeptide enrichment, novel mass spectrometry applications, and bioinformatic tools have resulted in high-throughput identification and quantitation of protein phosphorylation in a global manner. This review summarizes mainstream phosphoproteomic workflows and highlights the most recent applications of phosphoproteomics used in a range of molecular cardiology research.

  12. Identifying drug effects via pathway alterations using an integer linear programming optimization formulation on phosphoproteomic data.

    PubMed

    Mitsos, Alexander; Melas, Ioannis N; Siminelakis, Paraskeuas; Chairakaki, Aikaterini D; Saez-Rodriguez, Julio; Alexopoulos, Leonidas G

    2009-12-01

    Understanding the mechanisms of cell function and drug action is a major endeavor in the pharmaceutical industry. Drug effects are governed by the intrinsic properties of the drug (i.e., selectivity and potency) and the specific signaling transduction network of the host (i.e., normal vs. diseased cells). Here, we describe an unbiased, phosphoproteomic-based approach to identify drug effects by monitoring drug-induced topology alterations. With our proposed method, drug effects are investigated under diverse stimulations of the signaling network. Starting with a generic pathway made of logical gates, we build a cell-type specific map by constraining it to fit 13 key phopshoprotein signals under 55 experimental conditions. Fitting is performed via an Integer Linear Program (ILP) formulation and solution by standard ILP solvers; a procedure that drastically outperforms previous fitting schemes. Then, knowing the cell's topology, we monitor the same key phosphoprotein signals under the presence of drug and we re-optimize the specific map to reveal drug-induced topology alterations. To prove our case, we make a topology for the hepatocytic cell-line HepG2 and we evaluate the effects of 4 drugs: 3 selective inhibitors for the Epidermal Growth Factor Receptor (EGFR) and a non-selective drug. We confirm effects easily predictable from the drugs' main target (i.e., EGFR inhibitors blocks the EGFR pathway) but we also uncover unanticipated effects due to either drug promiscuity or the cell's specific topology. An interesting finding is that the selective EGFR inhibitor Gefitinib inhibits signaling downstream the Interleukin-1alpha (IL1alpha) pathway; an effect that cannot be extracted from binding affinity-based approaches. Our method represents an unbiased approach to identify drug effects on small to medium size pathways which is scalable to larger topologies with any type of signaling interventions (small molecules, RNAi, etc). The method can reveal drug effects on

  13. Phosphoproteome Discovery in Human Biological Fluids

    PubMed Central

    Giorgianni, Francesco; Beranova-Giorgianni, Sarka

    2016-01-01

    Phosphorylation plays a critical role in regulating protein function and thus influences a vast spectrum of cellular processes. With the advent of modern bioanalytical technologies, examination of protein phosphorylation on a global scale has become one of the major research areas. Phosphoproteins are found in biological fluids and interrogation of the phosphoproteome in biological fluids presents an exciting opportunity for discoveries that hold great potential for novel mechanistic insights into protein function in health and disease, and for translation to improved diagnostic and therapeutic approaches for the clinical setting. This review focuses on phosphoproteome discovery in selected human biological fluids: serum/plasma, urine, cerebrospinal fluid, saliva, and bronchoalveolar lavage fluid. Bioanalytical workflows pertinent to phosphoproteomics of biological fluids are discussed with emphasis on mass spectrometry-based approaches, and summaries of studies on phosphoproteome discovery in major fluids are presented. PMID:28248247

  14. Global phosphoproteomic profiling reveals perturbed signaling in a mouse model of dilated cardiomyopathy.

    PubMed

    Kuzmanov, Uros; Guo, Hongbo; Buchsbaum, Diana; Cosme, Jake; Abbasi, Cynthia; Isserlin, Ruth; Sharma, Parveen; Gramolini, Anthony O; Emili, Andrew

    2016-11-01

    Phospholamban (PLN) plays a central role in Ca(2+) homeostasis in cardiac myocytes through regulation of the sarco(endo)plasmic reticulum Ca(2+)-ATPase 2A (SERCA2A) Ca(2+) pump. An inherited mutation converting arginine residue 9 in PLN to cysteine (R9C) results in dilated cardiomyopathy (DCM) in humans and transgenic mice, but the downstream signaling defects leading to decompensation and heart failure are poorly understood. Here we used precision mass spectrometry to study the global phosphorylation dynamics of 1,887 cardiac phosphoproteins in early affected heart tissue in a transgenic R9C mouse model of DCM compared with wild-type littermates. Dysregulated phosphorylation sites were quantified after affinity capture and identification of 3,908 phosphopeptides from fractionated whole-heart homogenates. Global statistical enrichment analysis of the differential phosphoprotein patterns revealed selective perturbation of signaling pathways regulating cardiovascular activity in early stages of DCM. Strikingly, dysregulated signaling through the Notch-1 receptor, recently linked to cardiomyogenesis and embryonic cardiac stem cell development and differentiation but never directly implicated in DCM before, was a prominently perturbed pathway. We verified alterations in Notch-1 downstream components in early symptomatic R9C transgenic mouse cardiomyocytes compared with wild type by immunoblot analysis and confocal immunofluorescence microscopy. These data reveal unexpected connections between stress-regulated cell signaling networks, specific protein kinases, and downstream effectors essential for proper cardiac function.

  15. Global phosphoproteomic profiling reveals perturbed signaling in a mouse model of dilated cardiomyopathy

    PubMed Central

    Kuzmanov, Uros; Guo, Hongbo; Buchsbaum, Diana; Cosme, Jake; Abbasi, Cynthia; Isserlin, Ruth; Sharma, Parveen; Gramolini, Anthony O.; Emili, Andrew

    2016-01-01

    Phospholamban (PLN) plays a central role in Ca2+ homeostasis in cardiac myocytes through regulation of the sarco(endo)plasmic reticulum Ca2+-ATPase 2A (SERCA2A) Ca2+ pump. An inherited mutation converting arginine residue 9 in PLN to cysteine (R9C) results in dilated cardiomyopathy (DCM) in humans and transgenic mice, but the downstream signaling defects leading to decompensation and heart failure are poorly understood. Here we used precision mass spectrometry to study the global phosphorylation dynamics of 1,887 cardiac phosphoproteins in early affected heart tissue in a transgenic R9C mouse model of DCM compared with wild-type littermates. Dysregulated phosphorylation sites were quantified after affinity capture and identification of 3,908 phosphopeptides from fractionated whole-heart homogenates. Global statistical enrichment analysis of the differential phosphoprotein patterns revealed selective perturbation of signaling pathways regulating cardiovascular activity in early stages of DCM. Strikingly, dysregulated signaling through the Notch-1 receptor, recently linked to cardiomyogenesis and embryonic cardiac stem cell development and differentiation but never directly implicated in DCM before, was a prominently perturbed pathway. We verified alterations in Notch-1 downstream components in early symptomatic R9C transgenic mouse cardiomyocytes compared with wild type by immunoblot analysis and confocal immunofluorescence microscopy. These data reveal unexpected connections between stress-regulated cell signaling networks, specific protein kinases, and downstream effectors essential for proper cardiac function. PMID:27742792

  16. Global Phosphoproteomic Mapping of Early Mitotic Exit in Human Cells Identifies Novel Substrate Dephosphorylation Motifs

    PubMed Central

    McCloy, Rachael A.; Parker, Benjamin L.; Rogers, Samuel; Chaudhuri, Rima; Gayevskiy, Velimir; Hoffman, Nolan J.; Ali, Naveid; Watkins, D. Neil; Daly, Roger J.; James, David E.; Lorca, Thierry; Castro, Anna; Burgess, Andrew

    2015-01-01

    Entry into mitosis is driven by the coordinated phosphorylation of thousands of proteins. For the cell to complete mitosis and divide into two identical daughter cells it must regulate dephosphorylation of these proteins in a highly ordered, temporal manner. There is currently a lack of a complete understanding of the phosphorylation changes that occur during the initial stages of mitotic exit in human cells. Therefore, we performed a large unbiased, global analysis to map the very first dephosphorylation events that occur as cells exit mitosis. We identified and quantified the modification of >16,000 phosphosites on >3300 unique proteins during early mitotic exit, providing up to eightfold greater resolution than previous studies. The data have been deposited to the ProteomeXchange with identifier PXD001559. Only a small fraction (∼10%) of phosphorylation sites were dephosphorylated during early mitotic exit and these occurred on proteins involved in critical early exit events, including organization of the mitotic spindle, the spindle assembly checkpoint, and reformation of the nuclear envelope. Surprisingly this enrichment was observed across all kinase consensus motifs, indicating that it is independent of the upstream phosphorylating kinase. Therefore, dephosphorylation of these sites is likely determined by the specificity of phosphatase/s rather than the activity of kinase/s. Dephosphorylation was significantly affected by the amino acids at and surrounding the phosphorylation site, with several unique evolutionarily conserved amino acids correlating strongly with phosphorylation status. These data provide a potential mechanism for the specificity of phosphatases, and how they co-ordinate the ordered events of mitotic exit. In summary, our results provide a global overview of the phosphorylation changes that occur during the very first stages of mitotic exit, providing novel mechanistic insight into how phosphatase/s specifically regulate this critical

  17. Global Phosphoproteomic Mapping of Early Mitotic Exit in Human Cells Identifies Novel Substrate Dephosphorylation Motifs.

    PubMed

    McCloy, Rachael A; Parker, Benjamin L; Rogers, Samuel; Chaudhuri, Rima; Gayevskiy, Velimir; Hoffman, Nolan J; Ali, Naveid; Watkins, D Neil; Daly, Roger J; James, David E; Lorca, Thierry; Castro, Anna; Burgess, Andrew

    2015-08-01

    Entry into mitosis is driven by the coordinated phosphorylation of thousands of proteins. For the cell to complete mitosis and divide into two identical daughter cells it must regulate dephosphorylation of these proteins in a highly ordered, temporal manner. There is currently a lack of a complete understanding of the phosphorylation changes that occur during the initial stages of mitotic exit in human cells. Therefore, we performed a large unbiased, global analysis to map the very first dephosphorylation events that occur as cells exit mitosis. We identified and quantified the modification of >16,000 phosphosites on >3300 unique proteins during early mitotic exit, providing up to eightfold greater resolution than previous studies. The data have been deposited to the ProteomeXchange with identifier PXD001559. Only a small fraction (∼ 10%) of phosphorylation sites were dephosphorylated during early mitotic exit and these occurred on proteins involved in critical early exit events, including organization of the mitotic spindle, the spindle assembly checkpoint, and reformation of the nuclear envelope. Surprisingly this enrichment was observed across all kinase consensus motifs, indicating that it is independent of the upstream phosphorylating kinase. Therefore, dephosphorylation of these sites is likely determined by the specificity of phosphatase/s rather than the activity of kinase/s. Dephosphorylation was significantly affected by the amino acids at and surrounding the phosphorylation site, with several unique evolutionarily conserved amino acids correlating strongly with phosphorylation status. These data provide a potential mechanism for the specificity of phosphatases, and how they co-ordinate the ordered events of mitotic exit. In summary, our results provide a global overview of the phosphorylation changes that occur during the very first stages of mitotic exit, providing novel mechanistic insight into how phosphatase/s specifically regulate this critical

  18. Phosphoproteomics reveals the effect of ethylene in soybean root under flooding stress.

    PubMed

    Yin, Xiaojian; Sakata, Katsumi; Komatsu, Setsuko

    2014-12-05

    Flooding has severe negative effects on soybean growth. To explore the flooding-responsive mechanisms in early-stage soybean, a phosphoproteomic approach was used. Two-day-old soybean plants were treated without or with flooding for 3, 6, 12, and 24 h, and root tip proteins were then extracted and analyzed at each time point. After 3 h of flooding exposure, the fresh weight of soybeans increased, whereas the ATP content of soybean root tips decreased. Using a gel-free proteomic technique, a total of 114 phosphoproteins were identified in the root tip samples, and 34 of the phosphoproteins were significantly changed with respect to phosphorylation status after 3 h of flooding stress. Among these phosphoproteins, eukaryotic translation initiation factors were dephosphorylated, whereas several protein synthesis-related proteins were phosphorylated. The mRNA expression levels of sucrose phosphate synthase 1F and eukaryotic translation initiation factor 4 G were down-regulated, whereas UDP-glucose 6-dehydrogenase mRNA expression was up-regulated during growth but down-regulated under flooding stress. Furthermore, bioinformatic protein interaction analysis of flooding-responsive proteins based on temporal phosphorylation patterns indicated that eukaryotic translation initiation factor 4 G was located in the center of the network during flooding. Soybean eukaryotic translation initiation factor 4 G has homology to programmed cell death 4 protein and is implicated in ethylene signaling. The weight of soybeans was increased with treatment by an ethylene-releasing agent under flooding condition, but it was decreased when plants were exposed to an ethylene receptor antagonist. These results suggest that the ethylene signaling pathway plays an important role, via the protein phosphorylation, in mechanisms of plant tolerance to the initial stages of flooding stress in soybean root tips.

  19. iTRAQ labeling is superior to mTRAQ for quantitative global proteomics and phosphoproteomics.

    PubMed

    Mertins, Philipp; Udeshi, Namrata D; Clauser, Karl R; Mani, D R; Patel, Jinal; Ong, Shao-en; Jaffe, Jacob D; Carr, Steven A

    2012-06-01

    Labeling of primary amines on peptides with reagents containing stable isotopes is a commonly used technique in quantitative mass spectrometry. Isobaric labeling techniques such as iTRAQ™ or TMT™ allow for relative quantification of peptides based on ratios of reporter ions in the low m/z region of spectra produced by precursor ion fragmentation. In contrast, nonisobaric labeling with mTRAQ™ yields precursors with different masses that can be directly quantified in MS1 spectra. In this study, we compare iTRAQ- and mTRAQ-based quantification of peptides and phosphopeptides derived from EGF-stimulated HeLa cells. Both labels have identical chemical structures, therefore precursor ion- and fragment ion-based quantification can be directly compared. Our results indicate that iTRAQ labeling has an additive effect on precursor intensities, whereas mTRAQ labeling leads to more redundant MS2 scanning events caused by triggering on the same peptide with different mTRAQ labels. We found that iTRAQ labeling quantified nearly threefold more phosphopeptides (12,129 versus 4,448) and nearly twofold more proteins (2,699 versus 1,597) than mTRAQ labeling. Although most key proteins in the EGFR signaling network were quantified with both techniques, iTRAQ labeling allowed quantification of twice as many kinases. Accuracy of reporter ion quantification by iTRAQ is adversely affected by peptides that are cofragmented in the same precursor isolation window, dampening observed ratios toward unity. However, because of tighter overall iTRAQ ratio distributions, the percentage of statistically significantly regulated phosphopeptides and proteins detected by iTRAQ and mTRAQ was similar. We observed a linear correlation of logarithmic iTRAQ to mTRAQ ratios over two orders of magnitude, indicating a possibility to correct iTRAQ ratios by an average compression factor. Spike-in experiments using peptides of defined ratios in a background of nonregulated peptides show that i

  20. Phosphoproteomic analysis reveals compensatory effects in the piriform cortex of VX nerve agent exposed rats.

    PubMed

    Nirujogi, Raja Sekhar; Wright, James D; Manda, Srikanth S; Zhong, Jun; Na, Chan Hyun; Meyerhoff, James; Benton, Bernard; Jabbour, Rabih; Willis, Kristen; Kim, Min-Sik; Pandey, Akhilesh; Sekowski, Jennifer W

    2015-01-01

    To gain insights into the toxicity induced by the nerve agent VX, an MS-based phosphoproteomic analysis was carried out on the piriform cortex region of brains from VX-treated rats. Using isobaric tag based TMT labeling followed by titanium dioxide enrichment strategy, we identified 9975 unique phosphosites derived from 3287 phosphoproteins. Temporal changes in the phosphorylation status of peptides were observed over a time period of 24 h in rats exposed to a 1× LD50, intravenous (i.v.) dose with the most notable changes occurring at the 1 h postexposure time point. Five major functional classes of proteins exhibited changes in their phosphorylation status: (i) ion channels/transporters, including ATPases, (ii) kinases/phosphatases, (iii) GTPases, (iv) structural proteins, and (v) transcriptional regulatory proteins. This study is the first quantitative phosphoproteomic analysis of VX toxicity in the brain. Understanding the toxicity and compensatory signaling mechanisms will improve the understanding of the complex toxicity of VX in the brain and aid in the elucidation of novel molecular targets that would be important for development of improved countermeasures. All MS data have been deposited in the ProteomeXchange with identifier PXD001184 (http://proteomecentral.proteomexchange.org/dataset/PXD001184).

  1. Phosphoproteomic differences in major depressive disorder postmortem brains indicate effects on synaptic function.

    PubMed

    Martins-de-Souza, Daniel; Guest, Paul C; Vanattou-Saifoudine, Natacha; Rahmoune, Hassan; Bahn, Sabine

    2012-12-01

    There is still a lack in the molecular comprehension of major depressive disorder (MDD) although this condition affects approximately 10% of the world population. Protein phosphorylation is a posttranslational modification that regulates approximately one-third of the human proteins involved in a range of cellular and biological processes such as cellular signaling. Whereas phosphoproteome studies have been carried out extensively in cancer research, few such investigations have been carried out in studies of psychiatric disorders. Here, we present a comparative phosphoproteome analysis of postmortem dorsolateral prefrontal cortex tissues from 24 MDD patients and 12 control donors. Tissue extracts were analyzed using liquid chromatography mass spectrometry in a data-independent manner (LC-MS(E)). Our analyses resulted in the identification of 5,195 phosphopeptides, corresponding to 802 non-redundant proteins. Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls, being 20 differentially phosphorylated in at least 2 peptides. The majority of these phosphorylated proteins were associated with synaptic transmission and cellular architecture not only pointing out potential biomarker candidates but mainly shedding light to the comprehension of MDD pathobiology.

  2. Databases for plant phosphoproteomics.

    PubMed

    Schulze, Waltraud X; Yao, Qiuming; Xu, Dong

    2015-01-01

    Phosphorylation is the most studied posttranslational modification involved in signal transduction in stress responses, development, and growth. In the recent years large-scale phosphoproteomic studies were carried out using various model plants and several growth and stress conditions. Here we present an overview of online resources for plant phosphoproteomic databases: PhosPhAt as a resource for Arabidopsis phosphoproteins, P3DB as a resource expanding to crop plants, and Medicago PhosphoProtein Database as a resource for the model plant Medicago trunculata.

  3. Phosphoproteomics in cereals.

    PubMed

    Yang, Pingfang

    2015-01-01

    Cereals are the most important crop plant supplying staple food throughout the world. The economic importance and continued breeding of crop plants such as rice, maize, wheat, or barley require a detailed scientific understanding of adaptive and developmental processes. Protein phosphorylation is one of the most important regulatory posttranslational modifications and its analysis allows deriving functional and regulatory principles in plants. This minireview summarizes the current knowledge of phosphoproteomic studies in cereals.

  4. Insights Regarding Fungal Phosphoproteomic Analysis.

    PubMed

    Ribeiro, Liliane F C; Chelius, Cynthia L; Harris, Steven D; Marten, Mark R

    2017-03-10

    Protein phosphorylation is a major means of regulation for cellular processes, and is important in cell signaling, growth, and cell proliferation. To study phosphorylated proteins, high throughput phosphoproteomic technologies, such as reverse phase protein array, phospho-specific flow cytometry, and mass spectrometry (MS) based technologies, have been developed. Among them, mass spectrometry has become the primary tool employed for the identification of phosphoproteins and phosphosites in fungi, leading to an improved understanding of a number of signaling pathways. Using mass spectrometry techniques, researchers have discovered new kinase substrates, established connections between kinases and fungal pathogenicity, and studied the evolutionary lineage of kinases between different fungal species. Further, many specific phosphorylation sites recognized by individual kinases have been described. In this review, we will focus on recent discoveries made in yeast and filamentous fungi using phosphoproteomic analysis.

  5. Functional phosphoproteomic mass spectrometry-based approaches

    PubMed Central

    2012-01-01

    Mass Spectrometry (MS)-based phosphoproteomics tools are crucial for understanding the structure and dynamics of signaling networks. Approaches such as affinity purification followed by MS have also been used to elucidate relevant biological questions in health and disease. The study of proteomes and phosphoproteomes as linked systems, rather than research studies of individual proteins, are necessary to understand the functions of phosphorylated and un-phosphorylated proteins under spatial and temporal conditions. Phosphoproteome studies also facilitate drug target protein identification which may be clinically useful in the near future. Here, we provide an overview of general principles of signaling pathways versus phosphorylation. Likewise, we detail chemical phosphoproteomic tools, including pros and cons with examples where these methods have been applied. In addition, basic clues of electrospray ionization and collision induced dissociation fragmentation are detailed in a simple manner for successful phosphoproteomic clinical studies. PMID:23369623

  6. Quantitative Phosphoproteomics Analysis of ERBB3/ERBB4 Signaling

    PubMed Central

    Jacobs, Kris; Klammer, Martin; Jordan, Nicole; Elschenbroich, Sarah; Parade, Marc; Jacoby, Edgar; Linders, Joannes T. M.; Brehmer, Dirk; Cools, Jan; Daub, Henrik

    2016-01-01

    The four members of the epidermal growth factor receptor (EGFR/ERBB) family form homo- and heterodimers which mediate ligand-specific regulation of many key cellular processes in normal and cancer tissues. While signaling through the EGFR has been extensively studied on the molecular level, signal transduction through ERBB3/ERBB4 heterodimers is less well understood. Here, we generated isogenic mouse Ba/F3 cells that express full-length and functional membrane-integrated ERBB3 and ERBB4 or ERBB4 alone, to serve as a defined cellular model for biological and phosphoproteomics analysis of ERBB3/ERBB4 signaling. ERBB3 co-expression significantly enhanced Ba/F3 cell proliferation upon neuregulin-1 (NRG1) treatment. For comprehensive signaling studies we performed quantitative mass spectrometry (MS) experiments to compare the basal ERBB3/ERBB4 cell phosphoproteome to NRG1 treatment of ERBB3/ERBB4 and ERBB4 cells. We employed a workflow comprising differential isotope labeling with mTRAQ reagents followed by chromatographic peptide separation and final phosphopeptide enrichment prior to MS analysis. Overall, we identified 9686 phosphorylation sites which could be confidently localized to specific residues. Statistical analysis of three replicate experiments revealed 492 phosphorylation sites which were significantly changed in NRG1-treated ERBB3/ERBB4 cells. Bioinformatics data analysis recapitulated regulation of mitogen-activated protein kinase and Akt pathways, but also indicated signaling links to cytoskeletal functions and nuclear biology. Comparative assessment of NRG1-stimulated ERBB4 Ba/F3 cells revealed that ERBB3 did not trigger defined signaling pathways but more broadly enhanced phosphoproteome regulation in cells expressing both receptors. In conclusion, our data provide the first global picture of ERBB3/ERBB4 signaling and provide numerous potential starting points for further mechanistic studies. PMID:26745281

  7. Wrangling Phosphoproteomic Data to Elucidate Cancer Signaling Pathways

    PubMed Central

    Grimes, Mark L.; Lee, Wan-Jui; van der Maaten, Laurens; Shannon, Paul

    2013-01-01

    The interpretation of biological data sets is essential for generating hypotheses that guide research, yet modern methods of global analysis challenge our ability to discern meaningful patterns and then convey results in a way that can be easily appreciated. Proteomic data is especially challenging because mass spectrometry detectors often miss peptides in complex samples, resulting in sparsely populated data sets. Using the R programming language and techniques from the field of pattern recognition, we have devised methods to resolve and evaluate clusters of proteins related by their pattern of expression in different samples in proteomic data sets. We examined tyrosine phosphoproteomic data from lung cancer samples. We calculated dissimilarities between the proteins based on Pearson or Spearman correlations and on Euclidean distances, whilst dealing with large amounts of missing data. The dissimilarities were then used as feature vectors in clustering and visualization algorithms. The quality of the clusterings and visualizations were evaluated internally based on the primary data and externally based on gene ontology and protein interaction networks. The results show that t-distributed stochastic neighbor embedding (t-SNE) followed by minimum spanning tree methods groups sparse proteomic data into meaningful clusters more effectively than other methods such as k-means and classical multidimensional scaling. Furthermore, our results show that using a combination of Spearman correlation and Euclidean distance as a dissimilarity representation increases the resolution of clusters. Our analyses show that many clusters contain one or more tyrosine kinases and include known effectors as well as proteins with no known interactions. Visualizing these clusters as networks elucidated previously unknown tyrosine kinase signal transduction pathways that drive cancer. Our approach can be applied to other data types, and can be easily adopted because open source software

  8. Identifying differentially regulated subnetworks from phosphoproteomic data

    PubMed Central

    2010-01-01

    Background Various high throughput methods are available for detecting regulations at the level of transcription, translation or posttranslation (e.g. phosphorylation). Integrating these data with protein networks should make it possible to identify subnetworks that are significantly regulated. Furthermore, such integration can support identification of regulated entities from often noisy high throughput data. In particular, processing mass spectrometry-based phosphoproteomic data in this manner may expose signal transduction pathways and, in the case of experiments with drug-treated cells, reveal the drug's mode of action. Results Here, we introduce SubExtractor, an algorithm that combines phosphoproteomic data with protein network information from STRING to identify differentially regulated subnetworks and individual proteins. The method is based on a Bayesian probabilistic model combined with a genetic algorithm and rigorous significance testing. The Bayesian model accounts for information about both differential regulation and network topology. The method was tested with artificial data and subsequently applied to a comprehensive phosphoproteomics study investigating the mode of action of sorafenib, a small molecule kinase inhibitor. Conclusions SubExtractor reliably identifies differentially regulated subnetworks from phosphoproteomic data by integrating protein networks. The method can also be applied to gene or protein expression data. PMID:20584295

  9. Quantitative Proteomic and Phosphoproteomic Comparison of 2D and 3D Colon Cancer Cell Culture Models.

    PubMed

    Yue, Xiaoshan; Lukowski, Jessica K; Weaver, Eric M; Skube, Susan B; Hummon, Amanda B

    2016-12-02

    Cell cultures are widely used model systems. Some immortalized cell lines can be grown in either two-dimensional (2D) adherent monolayers or in three-dimensional (3D) multicellular aggregates, or spheroids. Here, the quantitative proteome and phosphoproteome of colon carcinoma HT29 cells cultures in 2D monolayers and 3D spheroids were compared with a stable isotope labeling of amino acids (SILAC) labeling strategy. Two biological replicates from each sample were examined, and notable differences in both the proteome and the phosphoproteome were determined by nanoliquid chromatography tandem mass spectrometry (LC-MS/MS) to assess how growth configuration affects molecular expression. A total of 5867 protein groups, including 2523 phosphoprotein groups and 8733 phosphopeptides were identified in the samples. The Gene Ontology analysis revealed enriched GO terms in the 3D samples for RNA binding, nucleic acid binding, enzyme binding, cytoskeletal protein binding, and histone binding for their molecular functions (MF) and in the process of cell cycle, cytoskeleton organization, and DNA metabolic process for the biological process (BP). The KEGG pathway analysis indicated that 3D cultures are enriched for oxidative phosphorylation pathways, metabolic pathways, peroxisome pathways, and biosynthesis of amino acids. In contrast, analysis of the phosphoproteomes indicated that 3D cultures have decreased phosphorylation correlating with slower growth rates and lower cell-to-extracellular matrix interactions. In sum, these results provide quantitative assessments of the effects on the proteome and phosphoproteome of culturing cells in 2D versus 3D cell culture configurations.

  10. Phosphorylation of proteins during human myometrial contractions: A phosphoproteomic approach.

    PubMed

    Hudson, Claire A; López Bernal, Andrés

    2017-01-22

    Phasic myometrial contractility is a key component of human parturition and the contractions are driven by reversible phosphorylation of myosin light chains catalyzed by the calcium (Ca(2+))-dependent enzyme myosin light chain kinase (MYLK). Other yet unknown phosphorylation or de-phosphorylation events may contribute to myometrial contraction and relaxation. In this study we have performed a global phosphoproteomic analysis of human myometrial tissue using tandem mass tagging to detect changes in the phosphorylation status of individual myometrial proteins during spontaneous and oxytocin-driven phasic contractions. We were able to detect 22 individual phosphopeptides whose relative ratio changed (fold > 2 or < 0.5) in response to spontaneous or oxytocin-stimulated contraction. The most significant changes in phosphorylation were to MYLK on serine 1760, a site associated with reductions in calmodulin binding and subsequent kinase activity. Phosphorylated MYLK (ser1760) increased significantly during spontaneous (9.83 ± 3.27 fold, P < 0.05) and oxytocin -induced (18.56 ± 8.18 fold, P < 0.01) contractions and we were able to validate these data using immunoblotting. Pathway analysis suggested additional proteins involved in calcium signalling, cGMP-PRKG signalling, adrenergic signalling and oxytocin signalling were also phosphorylated during contractions. This study demonstrates that a global phosphoproteomic analysis of myometrial tissue is a sensitive approach to detect changes in the phosphorylation of proteins during myometrial contractions, and provides a platform for further validation of these changes and for identification of their functional significance.

  11. Comparative Phosphoproteomics Reveals an Important Role of MKK2 in Banana (Musa spp.) Cold Signal Network

    PubMed Central

    Gao, Jie; Zhang, Sheng; He, Wei-Di; Shao, Xiu-Hong; Li, Chun-Yu; Wei, Yue-Rong; Deng, Gui-Ming; Kuang, Rui-Bin; Hu, Chun-Hua; Yi, Gan-Jun; Yang, Qiao-Song

    2017-01-01

    Low temperature is one of the key environmental stresses, which greatly affects global banana production. However, little is known about the global phosphoproteomes in Musa spp. and their regulatory roles in response to cold stress. In this study, we conducted a comparative phosphoproteomic profiling of cold-sensitive Cavendish Banana and relatively cold tolerant Dajiao under cold stress. Phosphopeptide abundances of five phosphoproteins involved in MKK2 interaction network, including MKK2, HY5, CaSR, STN7 and kinesin-like protein, show a remarkable difference between Cavendish Banana and Dajiao in response to cold stress. Western blotting of MKK2 protein and its T31 phosphorylated peptide verified the phosphoproteomic results of increased T31 phosphopeptide abundance with decreased MKK2 abundance in Daojiao for a time course of cold stress. Meanwhile increased expression of MKK2 with no detectable T31 phosphorylation was found in Cavendish Banana. These results suggest that the MKK2 pathway in Dajiao, along with other cold-specific phosphoproteins, appears to be associated with the molecular mechanisms of high tolerance to cold stress in Dajiao. The results also provide new evidence that the signaling pathway of cellular MKK2 phosphorylation plays an important role in abiotic stress tolerance that likely serves as a universal plant cold tolerance mechanism. PMID:28106078

  12. Comparative Phosphoproteomics Reveals an Important Role of MKK2 in Banana (Musa spp.) Cold Signal Network.

    PubMed

    Gao, Jie; Zhang, Sheng; He, Wei-Di; Shao, Xiu-Hong; Li, Chun-Yu; Wei, Yue-Rong; Deng, Gui-Ming; Kuang, Rui-Bin; Hu, Chun-Hua; Yi, Gan-Jun; Yang, Qiao-Song

    2017-01-20

    Low temperature is one of the key environmental stresses, which greatly affects global banana production. However, little is known about the global phosphoproteomes in Musa spp. and their regulatory roles in response to cold stress. In this study, we conducted a comparative phosphoproteomic profiling of cold-sensitive Cavendish Banana and relatively cold tolerant Dajiao under cold stress. Phosphopeptide abundances of five phosphoproteins involved in MKK2 interaction network, including MKK2, HY5, CaSR, STN7 and kinesin-like protein, show a remarkable difference between Cavendish Banana and Dajiao in response to cold stress. Western blotting of MKK2 protein and its T31 phosphorylated peptide verified the phosphoproteomic results of increased T31 phosphopeptide abundance with decreased MKK2 abundance in Daojiao for a time course of cold stress. Meanwhile increased expression of MKK2 with no detectable T31 phosphorylation was found in Cavendish Banana. These results suggest that the MKK2 pathway in Dajiao, along with other cold-specific phosphoproteins, appears to be associated with the molecular mechanisms of high tolerance to cold stress in Dajiao. The results also provide new evidence that the signaling pathway of cellular MKK2 phosphorylation plays an important role in abiotic stress tolerance that likely serves as a universal plant cold tolerance mechanism.

  13. Phosphoproteomic analysis of protein phosphorylation networks in Tetrahymena thermophila, a model single-celled organism.

    PubMed

    Tian, Miao; Chen, Xiulan; Xiong, Qian; Xiong, Jie; Xiao, Chuanle; Ge, Feng; Yang, Fuquan; Miao, Wei

    2014-02-01

    Tetrahymena thermophila is a widely used unicellular eukaryotic model organism in biological research and contains more than 1000 protein kinases and phosphatases with specificity for Ser/Thr/Tyr residues. However, only a few dozen phosphorylation sites in T. thermophila are known, presenting a major obstacle to further understanding of the regulatory roles of reversible phosphorylation in this organism. In this study, we used high-accuracy mass-spectrometry-based proteomics to conduct global and site-specific phosphoproteome profiling of T. thermophila. In total, 1384 phosphopeptides and 2238 phosphorylation sites from 1008 T. thermophila proteins were identified through the combined use of peptide prefractionation, TiO2 enrichment, and two-dimensional LC-MS/MS analysis. The identified phosphoproteins are implicated in the regulation of various biological processes such as transport, gene expression, and mRNA metabolic process. Moreover, integrated analysis of the T. thermophila phosphoproteome and gene network revealed the potential biological functions of many previously unannotated proteins and predicted some putative kinase-substrate pairs. Our data provide the first global survey of phosphorylation in T. thermophila using a phosphoproteomic approach and suggest a wide-ranging regulatory scope of this modification. The provided dataset is a valuable resource for the future understanding of signaling pathways in this important model organism.

  14. TSLP Signaling Network Revealed by SILAC-Based Phosphoproteomics*

    PubMed Central

    Zhong, Jun; Kim, Min-Sik; Chaerkady, Raghothama; Wu, Xinyan; Huang, Tai-Chung; Getnet, Derese; Mitchell, Christopher J.; Palapetta, Shyam M.; Sharma, Jyoti; O'Meally, Robert N.; Cole, Robert N.; Yoda, Akinori; Moritz, Albrecht; Loriaux, Marc M.; Rush, John; Weinstock, David M.; Tyner, Jeffrey W.; Pandey, Akhilesh

    2012-01-01

    Thymic stromal lymphopoietin (TSLP) is a cytokine that plays diverse roles in the regulation of immune responses. TSLP requires a heterodimeric receptor complex consisting of IL-7 receptor α subunit and its unique TSLP receptor (gene symbol CRLF2) to transmit signals in cells. Abnormal TSLP signaling (e.g. overexpression of TSLP or its unique receptor TSLPR) contributes to the development of a number of diseases including asthma and leukemia. However, a detailed understanding of the signaling pathways activated by TSLP remains elusive. In this study, we performed a global quantitative phosphoproteomic analysis of the TSLP signaling network using stable isotope labeling by amino acids in cell culture. By employing titanium dioxide in addition to antiphosphotyrosine antibodies as enrichment methods, we identified 4164 phosphopeptides on 1670 phosphoproteins. Using stable isotope labeling by amino acids in cell culture-based quantitation, we determined that the phosphorylation status of 226 proteins was modulated by TSLP stimulation. Our analysis identified activation of several members of the Src and Tec families of kinases including Btk, Lyn, and Tec by TSLP for the first time. In addition, we report TSLP-induced phosphorylation of protein phosphatases such as Ptpn6 (SHP-1) and Ptpn11 (Shp2), which has also not been reported previously. Co-immunoprecipitation assays showed that Shp2 binds to the adapter protein Gab2 in a TSLP-dependent manner. This is the first demonstration of an inducible protein complex in TSLP signaling. A kinase inhibitor screen revealed that pharmacological inhibition of PI-3 kinase, Jak family kinases, Src family kinases or Btk suppressed TSLP-dependent cellular proliferation making them candidate therapeutic targets in diseases resulting from aberrant TSLP signaling. Our study is the first phosphoproteomic analysis of the TSLP signaling pathway that greatly expands our understanding of TSLP signaling and provides novel therapeutic targets

  15. Quantitative Measurement of Phosphoproteome Response to Osmotic Stress in Arabidopsis Based on Library-Assisted eXtracted Ion Chromatogram (LAXIC)*

    PubMed Central

    Xue, Liang; Wang, Pengcheng; Wang, Lianshui; Renzi, Emily; Radivojac, Predrag; Tang, Haixu; Arnold, Randy; Zhu, Jian-Kang; Tao, W. Andy

    2013-01-01

    Global phosphorylation changes in plants in response to environmental stress have been relatively poorly characterized to date. Here we introduce a novel mass spectrometry-based label-free quantitation method that facilitates systematic profiling plant phosphoproteome changes with high efficiency and accuracy. This method employs synthetic peptide libraries tailored specifically as internal standards for complex phosphopeptide samples and accordingly, a local normalization algorithm, LAXIC, which calculates phosphopeptide abundance normalized locally with co-eluting library peptides. Normalization was achieved in a small time frame centered to each phosphopeptide to compensate for the diverse ion suppression effect across retention time. The label-free LAXIC method was further treated with a linear regression function to accurately measure phosphoproteome responses to osmotic stress in Arabidopsis. Among 2027 unique phosphopeptides identified and 1850 quantified phosphopeptides in Arabidopsis samples, 468 regulated phosphopeptides representing 497 phosphosites have shown significant changes. Several known and novel components in the abiotic stress pathway were identified, illustrating the capability of this method to identify critical signaling events among dynamic and complex phosphorylation. Further assessment of those regulated proteins may help shed light on phosphorylation response to osmotic stress in plants. PMID:23660473

  16. Refined phosphopeptide enrichment by phosphate additive and the analysis of human brain phosphoproteome.

    PubMed

    Tan, Haiyan; Wu, Zhiping; Wang, Hong; Bai, Bing; Li, Yuxin; Wang, Xusheng; Zhai, Bo; Beach, Thomas G; Peng, Junmin

    2015-01-01

    Alzheimer's disease (AD) is the most common form of dementia, characterized by progressive loss of cognitive function. One of the pathological hallmarks of AD is the formation of neurofibrillary tangles composed of abnormally hyperphosphorylated tau protein, but global deregulation of protein phosphorylation in AD is not well analyzed. Here, we report a pilot investigation of AD phosphoproteome by titanium dioxide enrichment coupled with high resolution LC-MS/MS. During the optimization of the enrichment method, we found that phosphate ion at a low concentration (e.g. 1 mM) worked efficiently as a nonphosphopeptide competitor to reduce background. The procedure was further tuned with respect to peptide-to-bead ratio, phosphopeptide recovery, and purity. Using this refined method and 9 h LC-MS/MS, we analyzed phosphoproteome in one milligram of digested AD brain lysate, identifying 5243 phosphopeptides containing 3715 nonredundant phosphosites on 1455 proteins, including 31 phosphosites on the tau protein. This modified enrichment method is simple and highly efficient. The AD case study demonstrates its feasibility of dissecting phosphoproteome in a limited amount of postmortem human brain. All MS data have been deposited in the ProteomeXchange with identifier PXD001180 (http://proteomecentral.proteomexchange.org/dataset/PXD001180).

  17. Phosphoproteome of the cyanobacterium Synechocystis sp. PCC 6803 and its dynamics during nitrogen starvation

    PubMed Central

    Spät, Philipp; Maček, Boris; Forchhammer, Karl

    2015-01-01

    Cyanobacteria have shaped the earth's biosphere as the first oxygenic photoautotrophs and still play an important role in many ecosystems. The ability to adapt to changing environmental conditions is an essential characteristic in order to ensure survival. To this end, numerous studies have shown that bacteria use protein post-translational modifications such as Ser/Thr/Tyr phosphorylation in cell signaling, adaptation, and regulation. Nevertheless, our knowledge of cyanobacterial phosphoproteomes and their dynamic response to environmental stimuli is relatively limited. In this study, we applied gel-free methods and high accuracy mass spectrometry toward the detection of Ser/Thr/Tyr phosphorylation events in the model cyanobacterium Synechocystis sp. PCC 6803. We could identify over 300 phosphorylation events in cultures grown on nitrate as exclusive nitrogen source. Chemical dimethylation labeling was applied to investigate proteome and phosphoproteome dynamics during nitrogen starvation. Our dataset describes the most comprehensive (phospho)proteome of Synechocystis to date, identifying 2382 proteins and 183 phosphorylation events and quantifying 2111 proteins and 148 phosphorylation events during nitrogen starvation. Global protein phosphorylation levels were increased in response to nitrogen depletion after 24 h. Among the proteins with increased phosphorylation, the PII signaling protein showed the highest fold-change, serving as positive control. Other proteins with increased phosphorylation levels comprised functions in photosynthesis and in carbon and nitrogen metabolism. This study reveals dynamics of Synechocystis phosphoproteome in response to environmental stimuli and suggests an important role of protein Ser/Thr/Tyr phosphorylation in fundamental mechanisms of homeostatic control in cyanobacteria. PMID:25873915

  18. The proteome and phosphoproteome of Neurospora crassa in response to cellulose, sucrose and carbon starvation

    DOE PAGES

    Xiong, Yi; Coradetti, Samuel T.; Li, Xin; ...

    2014-05-29

    Improving cellulolytic enzyme production by plant biomass degrading fungi holds great potential in reducing costs associated with production of next-generation biofuels generated from lignocellulose. How fungi sense cellulosic materials and respond by secreting enzymes has mainly been examined by assessing function of transcriptional regulators and via transcriptional profiling. Here, we obtained global proteomic and phosphoproteomic profiles of the plant biomass degrading filamentous fungus Neurospora crassa grown on different carbon sources, i.e. sucrose, no carbon, and cellulose, by performing isobaric tags for relative and absolute quantification (iTRAQ) -based LC-MS/MS analyses. A comparison between proteomes and transcriptomes under identical carbon conditions suggestsmore » that extensive post-transcriptional regulation occurs in N. crassa in response to exposure to cellulosic material. Several hundred amino acid residues with differential phosphorylation levels on crystalline cellulose (Avicel) or carbon-free medium versus sucrose medium were identified, including phosphorylation sites in a major transcriptional activator for cellulase genes, CLR1, as well as a cellobionic acid transporter, CBT1. Finally, we found mutation of phosphorylation sites on CLR1 did not have a major effect on transactivation of cellulase production, while mutation of phosphorylation sites in CBT1 increased its transporting capacity. Our data provides rich information at both the protein and phosphorylation levels of the early cellular responses to carbon starvation and cellulosic induction and aids in a greater understanding of the underlying post-transcriptional regulatory mechanisms in filamentous fungi.« less

  19. The proteome and phosphoproteome of Neurospora crassa in response to cellulose, sucrose and carbon starvation

    SciTech Connect

    Xiong, Yi; Coradetti, Samuel T.; Li, Xin; Gritsenko, Marina A.; Clauss, Therese; Petyuk, Vlad; Camp, David; Smith, Richard; Cate, Jamie H. D.; Yang, Feng; Glass, N. Louise

    2014-05-29

    Improving cellulolytic enzyme production by plant biomass degrading fungi holds great potential in reducing costs associated with production of next-generation biofuels generated from lignocellulose. How fungi sense cellulosic materials and respond by secreting enzymes has mainly been examined by assessing function of transcriptional regulators and via transcriptional profiling. Here, we obtained global proteomic and phosphoproteomic profiles of the plant biomass degrading filamentous fungus Neurospora crassa grown on different carbon sources, i.e. sucrose, no carbon, and cellulose, by performing isobaric tags for relative and absolute quantification (iTRAQ) -based LC-MS/MS analyses. A comparison between proteomes and transcriptomes under identical carbon conditions suggests that extensive post-transcriptional regulation occurs in N. crassa in response to exposure to cellulosic material. Several hundred amino acid residues with differential phosphorylation levels on crystalline cellulose (Avicel) or carbon-free medium versus sucrose medium were identified, including phosphorylation sites in a major transcriptional activator for cellulase genes, CLR1, as well as a cellobionic acid transporter, CBT1. Finally, we found mutation of phosphorylation sites on CLR1 did not have a major effect on transactivation of cellulase production, while mutation of phosphorylation sites in CBT1 increased its transporting capacity. Our data provides rich information at both the protein and phosphorylation levels of the early cellular responses to carbon starvation and cellulosic induction and aids in a greater understanding of the underlying post-transcriptional regulatory mechanisms in filamentous fungi.

  20. Phosphoproteomics technologies and applications in plant biology research

    PubMed Central

    Li, Jinna; Silva-Sanchez, Cecilia; Zhang, Tong; Chen, Sixue; Li, Haiying

    2015-01-01

    Protein phosphorylation has long been recognized as an essential mechanism to regulate many important processes of plant life. However, studies on phosphorylation mediated signaling events in plants are challenged with low stoichiometry and dynamic nature of phosphorylated proteins. Significant advances in mass spectrometry based phosphoproteomics have taken place in recent decade, including phosphoprotein/phosphopeptide enrichment, detection and quantification, and phosphorylation site localization. This review describes a variety of separation and enrichment methods for phosphoproteins and phosphopeptides, the applications of technological innovations in plant phosphoproteomics, and highlights significant achievement of phosphoproteomics in the areas of plant signal transduction, growth and development. PMID:26136758

  1. Concerted Changes in the Phosphoproteome and Metabolome Under Different CO2/O2 Gaseous Conditions in Arabidopsis Rosettes.

    PubMed

    Abadie, Cyril; Mainguet, Samuel; Davanture, Marlène; Hodges, Michael; Zivy, Michel; Tcherkez, Guillaume

    2016-07-01

    Considerable efforts are currently devoted to understanding the regulation of primary carbon metabolism in plant leaves, which is known to change dramatically with environmental conditions, e.g. during light/dark transitions. Protein phosphorylation is believed to be a key factor in such a metabolic control. In fact, some studies have suggested modifications in the phosphorylation status of key enzymes in the dark compared with the light, or when photosynthesis varies. However, a general view of the phosphoproteome and reciprocal alterations in both the phosphoproteome and metabolome under a wide spectrum of CO2 and O2 conditions so as to vary both gross photosynthesis and photorespiration is currently lacking. Here, we used an instant sampling system and strictly controlled gaseous conditions to examine short-term metabolome and phosphoproteome changes in Arabidopsis rosettes. We show that light/dark, CO2 and O2 mole fraction have differential effects on enzyme phosphorylation. Phosphorylation events that appear to be the most important to regulate metabolite contents when photosynthesis varies are those associated with sugar and pyruvate metabolism: sucrose and starch synthesis are major phosphorylation-controlled steps but pyruvate utilization (by phosphoenolpyruvate carboxylase and pyruvate dehydrogenase) and pyruvate reformation (by pyruvate orthophosphate dikinase) are also subjected to phosphorylation control. Our results thus show that the phosphoproteome response to light/dark transition and gaseous conditions (CO2, O2) contributes to the rapid adjustment of major pathways of primary C metabolism.

  2. Selecting Sample Preparation Workflows for Mass Spectrometry-Based Proteomic and Phosphoproteomic Analysis of Patient Samples with Acute Myeloid Leukemia

    PubMed Central

    Hernandez-Valladares, Maria; Aasebø, Elise; Selheim, Frode; Berven, Frode S.; Bruserud, Øystein

    2016-01-01

    Global mass spectrometry (MS)-based proteomic and phosphoproteomic studies of acute myeloid leukemia (AML) biomarkers represent a powerful strategy to identify and confirm proteins and their phosphorylated modifications that could be applied in diagnosis and prognosis, as a support for individual treatment regimens and selection of patients for bone marrow transplant. MS-based studies require optimal and reproducible workflows that allow a satisfactory coverage of the proteome and its modifications. Preparation of samples for global MS analysis is a crucial step and it usually requires method testing, tuning and optimization. Different proteomic workflows that have been used to prepare AML patient samples for global MS analysis usually include a standard protein in-solution digestion procedure with a urea-based lysis buffer. The enrichment of phosphopeptides from AML patient samples has previously been carried out either with immobilized metal affinity chromatography (IMAC) or metal oxide affinity chromatography (MOAC). We have recently tested several methods of sample preparation for MS analysis of the AML proteome and phosphoproteome and introduced filter-aided sample preparation (FASP) as a superior methodology for the sensitive and reproducible generation of peptides from patient samples. FASP-prepared peptides can be further fractionated or IMAC-enriched for proteome or phosphoproteome analyses. Herein, we will review both in-solution and FASP-based sample preparation workflows and encourage the use of the latter for the highest protein and phosphorylation coverage and reproducibility. PMID:28248234

  3. Phosphoproteomic analysis of the response of maize leaves to drought, heat and their combination stress.

    PubMed

    Hu, Xiuli; Wu, Liuji; Zhao, Feiyun; Zhang, Dayong; Li, Nana; Zhu, Guohui; Li, Chaohao; Wang, Wei

    2015-01-01

    Drought and heat stress, especially their combination, greatly affect crop production. Many studies have described transcriptome, proteome and phosphoproteome changes in response of plants to drought or heat stress. However, the study about the phosphoproteomic changes in response of crops to the combination stress is scare. To understand the mechanism of maize responses to the drought and heat combination stress, phosphoproteomic analysis was performed on maize leaves by using multiplex iTRAQ-based quantitative proteomic and LC-MS/MS methods. Five-leaf-stage maize was subjected to drought, heat or their combination, and the leaves were collected. Globally, heat, drought and the combined stress significantly changed the phosphorylation levels of 172, 149, and 144 phosphopeptides, respectively. These phosphopeptides corresponded to 282 proteins. Among them, 23 only responded to the combined stress and could not be predicted from their responses to single stressors; 30 and 75 only responded to drought and heat, respectively. Notably, 19 proteins were phosphorylated on different sites in response to the single and combination stresses. Of the seven significantly enriched phosphorylation motifs identified, two were common for all stresses, two were common for heat and the combined stress, and one was specific to the combined stress. The signaling pathways in which the phosphoproteins were involved clearly differed among the three stresses. Functional characterization of the phosphoproteins and the pathways identified here could lead to new targets for the enhancement of crop stress tolerance, which will be particularly important in the face of climate change and the increasing prevalence of abiotic stressors.

  4. Mass spectrometric phosphoproteome analysis of HIV-infected brain reveals novel phosphorylation sites and differential phosphorylation patterns

    PubMed Central

    Uzasci, Lerna; Auh, Sungyoung; Cotter, Robert J.; Nath, Avindra

    2016-01-01

    Purpose To map the phosphoproteome and identify changes in the phosphorylation patterns in the HIV-infected and uninfected brain using high-resolution mass spectrometry. Experimental Design Parietal cortex from brain of individuals with and without HIV infection were lysed and trypsinized. The peptides were labeled with iTRAQ reagents, combined, phospho-enriched by titanium dioxide chromatography, and analyzed by LC-MS/MS with high-resolution. Results Our phosphoproteomic workflow resulted in the identification of 112 phosphorylated proteins and 17 novel phosphorylation sites in all the samples that were analyzed. The phosphopeptide sequences were searched for kinase substrate motifs which revealed potential kinases involved in important signaling pathways. The site-specific phosphopeptide quantification showed that peptides from neurofilament medium polypeptide, myelin basic protein, and 2′–3′-cyclic nucleotide-3′ phosphodiesterase have relatively higher phosphorylation levels during HIV infection. Clinical Relevance This study has enriched the global phosphoproteome knowledge of the human brain by detecting novel phosphorylation sites on neuronal proteins and identifying differentially phosphorylated brain proteins during HIV infection. Kinases that lead to unusual phosphorylations could be therapeutic targets for the treatment of HIV-associated neurocognitive disorders (HAND). PMID:26033855

  5. Multidimensional electrostatic repulsion-hydrophilic interaction chromatography (ERLIC) for quantitative analysis of the proteome and phosphoproteome in clinical and biomedical research.

    PubMed

    Loroch, Stefan; Schommartz, Tim; Brune, Wolfram; Zahedi, René Peiman; Sickmann, Albert

    2015-05-01

    Quantitative proteomics and phosphoproteomics have become key disciplines in understanding cellular processes. Fundamental research can be done using cell culture providing researchers with virtually infinite sample amounts. In contrast, clinical, pre-clinical and biomedical research is often restricted to minute sample amounts and requires an efficient analysis with only micrograms of protein. To address this issue, we generated a highly sensitive workflow for combined LC-MS-based quantitative proteomics and phosphoproteomics by refining an ERLIC-based 2D phosphoproteomics workflow into an ERLIC-based 3D workflow covering the global proteome as well. The resulting 3D strategy was successfully used for an in-depth quantitative analysis of both, the proteome and the phosphoproteome of murine cytomegalovirus-infected mouse fibroblasts, a model system for host cell manipulation by a virus. In a 2-plex SILAC experiment with 150 μg of a tryptic digest per condition, the 3D strategy enabled the quantification of ~75% more proteins and even ~134% more peptides compared to the 2D strategy. Additionally, we could quantify ~50% more phosphoproteins by non-phosphorylated peptides, concurrently yielding insights into changes on the levels of protein expression and phosphorylation. Beside its sensitivity, our novel three-dimensional ERLIC-strategy has the potential for semi-automated sample processing rendering it a suitable future perspective for clinical, pre-clinical and biomedical research.

  6. Shotguns in the front line: phosphoproteomics in plants.

    PubMed

    Nakagami, Hirofumi; Sugiyama, Naoyuki; Ishihama, Yasushi; Shirasu, Ken

    2012-01-01

    The emergence of 'shotgun proteomics' has paved the way for high-throughput proteome analysis, by which thousands of proteins can be identified simultaneously from complex samples. Although the shotgun approach has the potential to monitor many different post-translational modifications, further technological development is needed to enrich each post-translational 'modificome'. Large-scale in vivo phosphorylation site mapping, so-called shotgun phosphoproteomics, has become feasible in various organisms, including plants, owing to recent technological breakthroughs. Shotgun phosphoproteomics is not a mature technology, but progress has been rapid. In this review, we highlight the scope and limitations of current methods, and some key technological issues in this field.

  7. Versatile nanocomposites in phosphoproteomics: a review.

    PubMed

    Najam-ul-Haq, Muhammad; Jabeen, Fahmida; Hussain, Dilshad; Saeed, Adeela; Musharraf, Syed Ghulam; Huck, Christian W; Bonn, Günther K

    2012-10-17

    Protein phosphorylation is one of the most important post-translational modifications. Phosphorylated peptides are present in low abundance in blood serum but play a vital role in regulatory mechanisms and may serve as casual factors in diseases. The enrichment and analysis of phosphorylated peptides directly from human serum and mapping the phosphorylation sites is a challenging task. Versatile nanocomposites of different materials have been synthesized using simple but efficient methodologies for their enrichment. The nanocomposites include magnetic, coated, embedded as well as chemically derivatized materials. Different base materials such as polymers, carbon based and metal oxides are used. The comparison of nanocomposites with respective nanoparticles provides sufficient facts about their efficiency in terms of loading capacity and capture efficiency. The cost for preparing them is low and they hold great promise to be used as chromatographic materials for phosphopeptide enrichment. This review gives an overview of different nanocomposites in phosphoproteomics, discussing the improved efficiency than the individual counterparts and highlighting their significance in phosphopeptide enrichment.

  8. Quantitative analysis of changes in the phosphoproteome of maize induced by the plant hormone salicylic acid

    PubMed Central

    Wu, Liuji; Hu, Xiuli; Wang, Shunxi; Tian, Lei; Pang, Yanjie; Han, Zanping; Wu, Liancheng; Chen, Yanhui

    2015-01-01

    Phytohormone salicylic acid (SA) plays an important role in regulating various physiological and biochemical processes. Our previous study identified several protein kinases responsive to SA, suggesting that phosphorylation events play an important role in the plant response to SA. In this study, we characterized the phosphoproteome of maize in response to SA using isotope tags for relative and absolute quantification (iTRAQ) technology and TiO2 enrichment method. Based on LC-MS/MS analysis, we found a total of 858 phosphoproteins among 1495 phosphopeptides. Among them, 291 phosphopeptides corresponding to 244 phosphoproteins were found to be significantly changed after SA treatment. The phosphoproteins identified are involved in a wide range of biological processes, which indicate that the response to SA encompasses a reformatting of major cellular processes. Furthermore, some of the phosphoproteins which were not previously known to be involved with SA were found to have significantly changed phosphorylation levels. Many of these changes are phosphorylation decreases, indicating that other currently unknown SA signaling pathways that result in decreased phosphorylation of downstream targets must be involved. Our study represents the first attempt at global phosphoproteome profiling in response to SA, and provides a better understanding of the molecular mechanisms regulated by SA. PMID:26659305

  9. Quantitative phosphoproteomic analysis of early seed development in rice (Oryza sativa L.).

    PubMed

    Qiu, Jiehua; Hou, Yuxuan; Tong, Xiaohong; Wang, Yifeng; Lin, Haiyan; Liu, Qing; Zhang, Wen; Li, Zhiyong; Nallamilli, Babi R; Zhang, Jian

    2016-02-01

    Rice (Oryza sativa L.) seed serves as a major food source for over half of the global population. Though it has been long recognized that phosphorylation plays an essential role in rice seed development, the phosphorylation events and dynamics in this process remain largely unknown so far. Here, we report the first large scale identification of rice seed phosphoproteins and phosphosites by using a quantitative phosphoproteomic approach. Thorough proteomic studies in pistils and seeds at 3, 7 days after pollination resulted in the successful identification of 3885, 4313 and 4135 phosphopeptides respectively. A total of 2487 proteins were differentially phosphorylated among the three stages, including Kip related protein 1, Rice basic leucine zipper factor 1, Rice prolamin box binding factor and numerous other master regulators of rice seed development. Moreover, differentially phosphorylated proteins may be extensively involved in the biosynthesis and signaling pathways of phytohormones such as auxin, gibberellin, abscisic acid and brassinosteroid. Our results strongly indicated that protein phosphorylation is a key mechanism regulating cell proliferation and enlargement, phytohormone biosynthesis and signaling, grain filling and grain quality during rice seed development. Overall, the current study enhanced our understanding of the rice phosphoproteome and shed novel insight into the regulatory mechanism of rice seed development.

  10. Quantitative analysis of changes in the phosphoproteome of maize induced by the plant hormone salicylic acid.

    PubMed

    Wu, Liuji; Hu, Xiuli; Wang, Shunxi; Tian, Lei; Pang, Yanjie; Han, Zanping; Wu, Liancheng; Chen, Yanhui

    2015-12-11

    Phytohormone salicylic acid (SA) plays an important role in regulating various physiological and biochemical processes. Our previous study identified several protein kinases responsive to SA, suggesting that phosphorylation events play an important role in the plant response to SA. In this study, we characterized the phosphoproteome of maize in response to SA using isotope tags for relative and absolute quantification (iTRAQ) technology and TiO2 enrichment method. Based on LC-MS/MS analysis, we found a total of 858 phosphoproteins among 1495 phosphopeptides. Among them, 291 phosphopeptides corresponding to 244 phosphoproteins were found to be significantly changed after SA treatment. The phosphoproteins identified are involved in a wide range of biological processes, which indicate that the response to SA encompasses a reformatting of major cellular processes. Furthermore, some of the phosphoproteins which were not previously known to be involved with SA were found to have significantly changed phosphorylation levels. Many of these changes are phosphorylation decreases, indicating that other currently unknown SA signaling pathways that result in decreased phosphorylation of downstream targets must be involved. Our study represents the first attempt at global phosphoproteome profiling in response to SA, and provides a better understanding of the molecular mechanisms regulated by SA.

  11. Identification of Putative Mek1 Substrates during Meiosis in Saccharomyces cerevisiae Using Quantitative Phosphoproteomics

    PubMed Central

    Suhandynata, Raymond T.; Wan, Lihong; Zhou, Huilin; Hollingsworth, Nancy M.

    2016-01-01

    Meiotic recombination plays a key role in sexual reproduction as it generates crossovers that, in combination with sister chromatid cohesion, physically connect homologous chromosomes, thereby promoting their proper segregation at the first meiotic division. Meiotic recombination is initiated by programmed double strand breaks (DSBs) catalyzed by the evolutionarily conserved, topoisomerase-like protein Spo11. Repair of these DSBs is highly regulated to create crossovers between homologs that are distributed throughout the genome. This repair requires the presence of the mitotic recombinase, Rad51, as well as the strand exchange activity of the meiosis-specific recombinase, Dmc1. A key regulator of meiotic DSB repair in Saccharomyces cerevisiae is the meiosis-specific kinase Mek1, which promotes interhomolog strand invasion and is required for the meiotic recombination checkpoint and the crossover/noncrossover decision. Understanding how Mek1 regulates meiotic recombination requires the identification of its substrates. Towards that end, an unbiased phosphoproteomic approach utilizing Stable Isotope Labeling by Amino Acids in Cells (SILAC) was utilized to generate a list of potential Mek1 substrates, as well as proteins containing consensus phosphorylation sites for cyclin-dependent kinase, the checkpoint kinases, Mec1/Tel1, and the polo-like kinase, Cdc5. These experiments represent the first global phosphoproteomic dataset for proteins in meiotic budding yeast. PMID:27214570

  12. Large-Scale Phosphoproteomics Analysis of Whole Saliva Reveals a Distinct Phosphorylation Pattern

    PubMed Central

    Stone, Matthew D.; Chen, Xiaobing; McGowan, Thomas; Bandhakavi, Sricharan; Cheng, Bin; Rhodus, Nelson L.; Griffin, Timothy J.

    2011-01-01

    In-depth knowledge of bodily fluid phosphoproteomes, such as whole saliva, is limited. To better understand the whole saliva phosphoproteome, we generated a large-scale catalog of phosphorylated proteins. To circumvent the wide dynamic range of phosphoprotein abundance in whole saliva, we combined dynamic range compression using hexapeptide beads, strong cation exchange HPLC peptide fractionation, and immobilized metal affinity chromatography prior to mass spectrometry. In total, 217 unique phosphopeptides sites were identified representing 85 distinct phosphoproteins at 2.3% global FDR. From these peptides, 129 distinct phosphorylation sites were identified of which 57 were previously known, but only 11 of which had been previously identified in whole saliva. Cellular localization analysis revealed salivary phosphoproteins had a distribution similar to all known salivary proteins, but with less relative representation in “extracellular” and “plasma membrane” categories compared to salivary glycoproteins. Sequence alignment showed that phosphorylation occurred at acidic-directed kinase, proline-directed, and basophilic motifs. This differs from plasma phosphoproteins, which predominantly occur at Golgi casein kinase recognized sequences. Collectively, these results suggest diverse functions for salivary phosphoproteins and multiple kinases involved in their processing and secretion. In all, this study should lay groundwork for future elucidation of the functions of salivary protein phosphorylation. PMID:21299198

  13. Phosphoproteomic analysis of Methanohalophilus portucalensis FDF1T identified the role of protein phosphorylation in methanogenesis and osmoregulation

    PubMed Central

    Wu, Wan-Ling; Lai, Shu-Jung; Yang, Jhih-Tian; Chern, Jeffy; Liang, Suh-Yuen; Chou, Chi-Chi; Kuo, Chih-Horng; Lai, Mei-Chin; Wu, Shih-Hsiung

    2016-01-01

    Methanogens have gained much attention for their metabolic product, methane, which could be an energy substitute but also contributes to the greenhouse effect. One factor that controls methane emission, reversible protein phosphorylation, is a crucial signaling switch, and phosphoproteomics has become a powerful tool for large-scale surveying. Here, we conducted the first phosphorylation-mediated regulation study in halophilic Methanohalophilus portucalensis FDF1T, a model strain for studying stress response mechanisms in osmoadaptation. A shotgun approach and MS-based analysis identified 149 unique phosphoproteins. Among them, 26% participated in methanogenesis and osmolytes biosynthesis pathways. Of note, we uncovered that protein phosphorylation might be a crucial factor to modulate the pyrrolysine (Pyl) incorporation and Pyl-mediated methylotrophic methanogenesis. Furthermore, heterologous expression of glycine sarcosine N-methyltransferase (GSMT) mutant derivatives in the osmosensitive Escherichia coli MKH13 revealed that the nonphosphorylated T68A mutant resulted in increased salt tolerance. In contrast, mimic phosphorylated mutant T68D proved defective in both enzymatic activity and salinity tolerance for growth. Our study provides new insights into phosphorylation modification as a crucial role of both methanogenesis and osmoadaptation in methanoarchaea, promoting biogas production or reducing future methane emission in response to global warming and climate change. PMID:27357474

  14. Quantitative phosphoproteomics of murine Fmr1-KO cell lines provides new insights into FMRP-dependent signal transduction mechanisms.

    PubMed

    Matic, Katarina; Eninger, Timo; Bardoni, Barbara; Davidovic, Laetitia; Macek, Boris

    2014-10-03

    Fragile X mental retardation protein (FMRP) is an RNA-binding protein that has a major effect on neuronal protein synthesis. Transcriptional silencing of the FMR1 gene leads to loss of FMRP and development of Fragile X syndrome (FXS), the most common known hereditary cause of intellectual impairment and autism. Here we utilize SILAC-based quantitative phosphoproteomics to analyze murine FMR1(-) and FMR1(+) fibroblastic cell lines derived from FMR1-KO embryos to identify proteins and phosphorylation sites dysregulated as a consequence of FMRP loss. We quantify FMRP-related changes in the levels of 5,023 proteins and 6,133 phosphorylation events and map them onto major signal transduction pathways. Our study confirms global downregulation of the MAPK/ERK pathway and decrease in phosphorylation level of ERK1/2 in the absence of FMRP, which is connected to attenuation of long-term potentiation. We detect differential expression of several key proteins from the p53 pathway, pointing to the involvement of p53 signaling in dysregulated cell cycle control in FXS. Finally, we detect differential expression and phosphorylation of proteins involved in pre-mRNA processing and nuclear transport, as well as Wnt and calcium signaling, such as PLC, PKC, NFAT, and cPLA2. We postulate that calcium homeostasis is likely affected in molecular pathogenesis of FXS.

  15. Quantitative Phosphoproteomic Analysis of T-Cell Receptor Signaling.

    PubMed

    Ahsan, Nagib; Salomon, Arthur R

    2017-01-01

    TCR signaling critically depends on protein phosphorylation across many proteins. Localization of each phosphorylation event relative to the T-cell receptor (TCR) and canonical T-cell signaling proteins will provide clues about the structure of TCR signaling networks. Quantitative phosphoproteomic analysis by mass spectrometry provides a wide-scale view of cellular phosphorylation networks. However, analysis of phosphorylation by mass spectrometry is still challenging due to the relative low abundance of phosphorylated proteins relative to all proteins and the extraordinary diversity of phosphorylation sites across the proteome. Highly selective enrichment of phosphorylated peptides is essential to provide the most comprehensive view of the phosphoproteome. Optimization of phosphopeptide enrichment methods coupled with highly sensitive mass spectrometry workflows significantly improves the sequencing depth of the phosphoproteome to over 10,000 unique phosphorylation sites from complex cell lysates. Here we describe a step-by-step method for phosphoproteomic analysis that has achieved widespread success for identification of serine, threonine, and tyrosine phosphorylation. Reproducible quantification of relative phosphopeptide abundance is provided by intensity-based label-free quantitation. An ideal set of mass spectrometry analysis parameters is also provided that optimize the yield of identified sites. We also provide guidelines for the bioinformatic analysis of this type of data to assess the quality of the data and to comply with proteomic data reporting requirements.

  16. Characterization of the Phosphoproteome in SLE Patients

    PubMed Central

    Huang, Jianrong; Dai, Yong

    2012-01-01

    Protein phosphorylation is a complex regulatory event that is involved in the signaling networks that affect virtually every cellular process. The protein phosphorylation may be a novel source for discovering biomarkers and drug targets. However, a systematic analysis of the phosphoproteome in patients with SLE has not been performed. To clarify the pathogenesis of systemic lupus erythematosus (SLE), we compared phosphoprotein expression in PBMCs from SLE patients and normal subjects using proteomics analyses. Phosphopeptides were enriched using TiO2 from PBMCs isolated from 15 SLE patients and 15 healthy subjects and then analyzed by automated LC-MS/MS analysis. Phosphorylation sites were identified and quantitated by MASCOT and MaxQuant. A total of 1035 phosphorylation sites corresponding to 618 NCBI-annotated genes were identified in SLE patients compared with normal subjects. Differentially expressed proteins, peptides and phosphorylation sites were then subjected to bioinformatics analyses. Gene ontology(GO) and pathway analyses showed that nucleic acid metabolism, cellular component organization, transport and multicellular organismal development pathways made up the largest proportions of the differentially expressed genes. Pathway analyses showed that the mitogen-activated protein kinase (MAPK) signaling pathway and actin cytoskeleton regulators made up the largest proportions of the metabolic pathways. Network analysis showed that rous sarcoma oncogene (SRC), v-rel reticuloendotheliosis viral oncogene homolog A (RELA), histone deacetylase (HDA1C) and protein kinase C, delta (PRKCD) play important roles in the stability of the network. These data suggest that aberrant protein phosphorylation may contribute to SLE pathogenesis. PMID:23285258

  17. Deep Phosphoproteomic Measurements Pinpointing Drug Induced Protective Mechanisms in Neuronal Cells

    PubMed Central

    Yu, Chengli; Gao, Jing; Zhou, Yanting; Chen, Xiangling; Xiao, Ruoxuan; Zheng, Jing; Liu, Yansheng; Zhou, Hu

    2016-01-01

    Alzheimer's disease (AD) is a progressive and irreversible neurological disorder that impairs the living quality of old population and even life spans. New compounds have shown potential inneuroprotective effects in AD, such as GFKP-19, a 2-pyrrolidone derivative which has been proved to enhance the memory of dysmnesia mouse. The molecular mechanisms remain to be established for these drug candidates. Large-scale phosphoproteomic approach has been evolved rapidly in the last several years, which holds the potential to provide a useful toolkit to understand cellular signaling underlying drug effects. To establish and test such a method, we accurately analyzed the deep quantitative phosphoproteome of the neuro-2a cells treated with and without GFKP-19 using triple SILAC labeling. A total of 14,761 Class I phosphosites were quantified between controls, damaged, and protected conditions using the high resolution mass spectrometry, with a decent inter-mass spectrometer reproducibility for even subtle regulatory events. Our data suggests that GFKP-19 can reverse Aβ25−35 induced phosphorylation change in neuro-2a cells, and might protect the neuron system in two ways: firstly, it may decrease oxidative damage and inflammation induced by NO via down regulating the phosphorylation of nitric oxide synthase NOS1 at S847; Secondly, it may decrease tau protein phosphorylation through down-regulating the phosphorylation level of MAPK14 at T180. All mass spectrometry data are available via ProteomeXchange with identifier PXD005312. PMID:28066266

  18. Global Cooling: Effect of Urban Albedo on Global Temperature

    SciTech Connect

    Akbari, Hashem; Menon, Surabi; Rosenfeld, Arthur

    2007-05-22

    In many urban areas, pavements and roofs constitute over 60% of urban surfaces (roof 20-25%, pavements about 40%). The roof and the pavement albedo can be increased by about 0.25 and 0.10, respectively, resulting in a net albedo increase for urban areas of about 0.1. Many studies have demonstrated building cooling-energy savings in excess of 20% upon raising roof reflectivity from an existing 10-20% to about 60%. We estimate U.S. potential savings in excess of $1 billion (B) per year in net annual energy bills. Increasing albedo of urban surfaces can reduce the summertime urban temperature and improve the urban air quality. Increasing the urban albedo has the added benefit of reflecting more of the incoming global solar radiation and countering the effect of global warming. We estimate that increasing albedo of urban areas by 0.1 results in an increase of 3 x 10{sup -4} in Earth albedo. Using a simple global model, the change in air temperature in lowest 1.8 km of the atmosphere is estimated at 0.01K. Modelers predict a warming of about 3K in the next 60 years (0.05K/year). Change of 0.1 in urban albedo will result in 0.01K global cooling, a delay of {approx}0.2 years in global warming. This 0.2 years delay in global warming is equivalent to 10 Gt reduction in CO2 emissions.

  19. Phosphoproteomic analysis of Her2/neu signaling and inhibition

    PubMed Central

    Bose, Ron; Molina, Henrik; Patterson, A. Scott; Bitok, John K.; Periaswamy, Balamurugan; Bader, Joel S.; Pandey, Akhilesh; Cole, Philip A.

    2006-01-01

    Her2/neu (Her2) is a tyrosine kinase belonging to the EGF receptor (EGFR)/ErbB family and is overexpressed in 20–30% of human breast cancers. We sought to characterize Her2 signal transduction pathways further by using MS-based quantitative proteomics. Stably transfected cell lines overexpressing Her2 or empty vector were generated, and the effect of an EGFR and Her2 selective tyrosine kinase inhibitor, PD168393, on these cells was characterized. Quantitative measurements were obtained on 462 proteins by using the SILAC (stable isotope labeling with amino acids in cell culture) method to monitor three conditions simultaneously. Of these proteins, 198 showed a significant increase in tyrosine phosphorylation in Her2-overexpressing cells, and 81 showed a significant decrease in phosphorylation. Treatment of Her2-overexpressing cells with PD168393 showed rapid reversibility of the majority of the Her2-triggered phosphorylation events. Phosphoproteins that were identified included many known Her2 signaling molecules as well as known EGFR signaling proteins that had not been previously linked to Her2, such as Stat1, Dok1, and δ-catenin. Importantly, several previously uncharacterized Her2 signaling proteins were identified, including Axl tyrosine kinase, the adaptor protein Fyb, and the calcium-binding protein Pdcd-6/Alg-2. We also identified a phosphorylation site in Her2, Y877, which is located in the activation loop of the kinase domain, is distinct from the known C-terminal tail autophosphorylation sites, and may have important implications for regulation of Her2 signaling. Network modeling, which combined phosphoproteomic results with literature-curated protein–protein interaction data, was used to suggest roles for some of the previously unidentified Her2 signaling proteins. PMID:16785428

  20. HOPE-fixation of lung tissue allows retrospective proteome and phosphoproteome studies.

    PubMed

    Shevchuk, Olga; Abidi, Nada; Klawonn, Frank; Wissing, Josef; Nimtz, Manfred; Kugler, Christian; Steinert, Michael; Goldmann, Torsten; Jänsch, Lothar

    2014-11-07

    Hepes-glutamic acid buffer-mediated organic solvent protection effect (HOPE)-fixation has been introduced as an alternative to formalin fixation of clinical samples. Beyond preservation of morphological structures for histology, HOPE-fixation was demonstrated to be compatible with recent methods for RNA and DNA sequencing. However, the suitability of HOPE-fixed materials for the inspection of proteomes by mass spectrometry so far remained undefined. This is of particular interest, since proteins constitute a prime resource for drug research and can give valuable insights into the activity status of signaling pathways. In this study, we extracted proteins from human lung tissue and tested HOPE-treated and snap-frozen tissues comparatively by proteome and phosphoproteome analyses. High confident data from accurate mass spectrometry allowed the identification of 2603 proteins and 3036 phosphorylation sites. HOPE-fixation did not hinder the representative extraction of proteins, and investigating their biochemical properties, covered subcellular localizations, and cellular processes revealed no bias caused by the type of fixation. In conclusion, proteome as well as phosphoproteome data of HOPE lung samples were qualitatively equivalent to results obtained from snap-frozen tissues. Thus, HOPE-treated tissues match clinical demands in both histology and retrospective proteome analyses of patient samples by proteomics.

  1. Climate Effects of Global Land Cover Change

    SciTech Connect

    Gibbard, S G; Caldeira, K; Bala, G; Phillips, T; Wickett, M

    2005-08-24

    There are two competing effects of global land cover change on climate: an albedo effect which leads to heating when changing from grass/croplands to forest, and an evapotranspiration effect which tends to produce cooling. It is not clear which effect would dominate in a global land cover change scenario. We have performed coupled land/ocean/atmosphere simulations of global land cover change using the NCAR CAM3 atmospheric general circulation model. We find that replacement of current vegetation by trees on a global basis would lead to a global annual mean warming of 1.6 C, nearly 75% of the warming produced under a doubled CO{sub 2} concentration, while global replacement by grasslands would result in a cooling of 0.4 C. These results suggest that more research is necessary before forest carbon storage should be deployed as a mitigation strategy for global warming. In particular, high latitude forests probably have a net warming effect on the Earth's climate.

  2. Proteomics and Phosphoproteomics Analysis of Human Lens Fiber Cell Membranes

    PubMed Central

    Wang, Zhen; Han, Jun; David, Larry L.; Schey, Kevin L.

    2013-01-01

    Purpose. The human lens fiber cell insoluble membrane fraction contains important membrane proteins, cytoskeletal proteins, and cytosolic proteins that are strongly associated with the membrane. The purpose of this study was to characterize the lens fiber cell membrane proteome and phosphoproteome from human lenses. Methods. HPLC-mass spectrometry–based multidimensional protein identification technology (MudPIT), without or with phosphopeptide enrichment, was applied to study the proteome and phosphoproteome of lens fiber cell membranes, respectively. Results. In total, 951 proteins were identified, including 379 integral membrane and membrane-associated proteins. Enriched gene categories and pathways based on the proteomic analysis include carbohydrate metabolism (glycolysis/gluconeogenesis, pentose phosphate pathway, pyruvate metabolism), proteasome, cell-cell signaling and communication (GTP binding, gap junction, focal adhesion), glutathione metabolism, and actin regulation. The combination of TiO2 phosphopeptide enrichment and MudPIT analysis revealed 855 phosphorylation sites on 271 proteins, including 455 phosphorylation sites that have not been previously identified. PKA, PKC, CKII, p38MAPK, and RSK are predicted as the major kinases for phosphorylation on the sites identified in the human lens membrane fraction. Conclusions. The results presented herein significantly expand the characterized proteome and phosphoproteome of the human lens fiber cell and provide a valuable reference for future research in studies of lens development and disease. PMID:23349431

  3. Ecological effects of global change

    NASA Astrophysics Data System (ADS)

    Menzel, A.

    2010-03-01

    Mankind actually puts manifolds loads on our earth including stratospheric ozone depletion, rising freshwater use, changes of land cover and land use. For several of these threats, critical loads and thresholds may be already exceeded, e.g. nitrogen input, climate change and biodiversity loss (Röckström et al. 2009). The working group on Impacts, Adaptation and Vulnerability of the last IPCC report (AR4, 2007) concluded that anthropogenic warming over the last three decades has had a discernible influence on many physical and biological systems, thus global fingerprint of anthropogenic climate change was detectable on all continents and almost all ocean areas (Rosenzweig et al. 2007, 2008). 90% of the significant temperature related changes in 29000 records analysed were consistent with climate warming, e.g. in warming climates earlier spring events, distributional shifts pole wards and to higher altitudes, or community changes with reduced cold adapted species were observed. These impacts, already visible and only related to less than 1°C global warming, allow a limited glance at future changes and pressures on our ecosystems, as the rate of warming may accelerate and will be linked to stronger and more frequent extreme events. Vegetation is an important component of the climate system, part of biogeochemical cycles and the lower boundary of GCMs characterised by certain albedo and roughness. Thus, climate change impacts on vegetation exert feedbacks. The most striking and challenging problems in analysing climate change impacts on ecosystems are related to cases where one would expect major changes due to warming however there is reduced, limited or no reaction in the observed systems. This feature is known as divergence problem in tree ring research, called resilience in ecosystem dynamics or might be simply a time-lag or environmental monitoring problem. However, there are various other pressures by global change, e.g. land use change or pollution, leading

  4. Global Effects of Increased Use of Energy

    ERIC Educational Resources Information Center

    Weinberg, Alvin M.; Hammond, R. Philip

    1972-01-01

    This paper, which speculates on the effects of man's energy releases on world climate, concludes that global upsets are very unlikely if we are able to distribute the energy widely or into the sea. (AL)

  5. Phosphoproteome Profiling Reveals Circadian Clock Regulation of Posttranslational Modifications in the Murine Hippocampus.

    PubMed

    Chiang, Cheng-Kang; Xu, Bo; Mehta, Neel; Mayne, Janice; Sun, Warren Y L; Cheng, Kai; Ning, Zhibin; Dong, Jing; Zou, Hanfa; Cheng, Hai-Ying Mary; Figeys, Daniel

    2017-01-01

    The circadian clock is an endogenous oscillator that drives daily rhythms in physiology, behavior, and gene expression. The underlying mechanisms of circadian timekeeping are cell-autonomous and involve oscillatory expression of core clock genes that is driven by interconnecting transcription-translation feedback loops (TTFLs). Circadian clock TTFLs are further regulated by posttranslational modifications, in particular, phosphorylation. The hippocampus plays an important role in spatial memory and the conversion of short- to long-term memory. Several studies have reported the presence of a peripheral oscillator in the hippocampus and have highlighted the importance of circadian regulation in memory formation. Given the general importance of phosphorylation in circadian clock regulation, we performed global quantitative proteome and phosphoproteome analyses of the murine hippocampus across the circadian cycle, applying spiked-in labeled reference and high accuracy mass spectrometry (MS). Of the 3,052 proteins and 2,868 phosphosites on 1,368 proteins that were accurately quantified, 1.7% of proteins and 5.2% of phosphorylation events exhibited time-of-day-dependent expression profiles. The majority of circadian phosphopeptides displayed abrupt fluctuations at mid-to-late day without underlying rhythms of protein abundance. Bioinformatic analysis of cyclic phosphorylation events revealed their diverse distribution in different biological pathways, most notably, cytoskeletal organization and neuronal morphogenesis. This study provides the first large-scale, quantitative MS analysis of the circadian phosphoproteome and proteome of the murine hippocampus and highlights the significance of rhythmic regulation at the posttranslational level in this peripheral oscillator. In addition to providing molecular insights into the hippocampal circadian clock, our results will assist in the understanding of genetic factors that underlie rhythms-associated pathological states of

  6. Systematic Analysis of the Phosphoproteome and Kinase-substrate Networks in the Mouse Testis*

    PubMed Central

    Qi, Lin; Liu, Zexian; Wang, Jing; Cui, Yiqiang; Guo, Yueshuai; Zhou, Tao; Zhou, Zuomin; Guo, Xuejiang; Xue, Yu; Sha, Jiahao

    2014-01-01

    Spermatogenesis is a complex process closely associated with the phosphorylation-orchestrated cell cycle. Elucidating the phosphorylation-based regulations should advance our understanding of the underlying molecular mechanisms. Here we present an integrative study of phosphorylation events in the testis. Large-scale phosphoproteome profiling in the adult mouse testis identified 17,829 phosphorylation sites in 3955 phosphoproteins. Although only approximately half of the phosphorylation sites enriched by IMAC were also captured by TiO2, both the phosphoprotein data sets identified by the two methods significantly enriched the functional annotation of spermatogenesis. Thus, the phosphoproteome profiled in this study is a highly useful snapshot of the phosphorylation events in spermatogenesis. To further understand phosphoregulation in the testis, the site-specific kinase-substrate relations were computationally predicted for reconstructing kinase-substrate phosphorylation networks. A core sub-kinase-substrate phosphorylation networks among the spermatogenesis-related proteins was retrieved and analyzed to explore the phosphoregulation during spermatogenesis. Moreover, network-based analyses demonstrated that a number of protein kinases such as MAPKs, CDK2, and CDC2 with statistically more site-specific kinase-substrate relations might have significantly higher activities and play an essential role in spermatogenesis, and the predictions were consistent with previous studies on the regulatory roles of these kinases. In particular, the analyses proposed that the activities of POLO-like kinases (PLKs) might be dramatically higher, while the prediction was experimentally validated by detecting and comparing the phosphorylation levels of pT210, an indicator of PLK1 activation, in testis and other tissues. Further experiments showed that the inhibition of POLO-like kinases decreases cell proliferation by inducing G2/M cell cycle arrest. Taken together, this systematic

  7. Phosphoproteome Profiling Reveals Circadian Clock Regulation of Posttranslational Modifications in the Murine Hippocampus

    PubMed Central

    Chiang, Cheng-Kang; Xu, Bo; Mehta, Neel; Mayne, Janice; Sun, Warren Y. L.; Cheng, Kai; Ning, Zhibin; Dong, Jing; Zou, Hanfa; Cheng, Hai-Ying Mary; Figeys, Daniel

    2017-01-01

    The circadian clock is an endogenous oscillator that drives daily rhythms in physiology, behavior, and gene expression. The underlying mechanisms of circadian timekeeping are cell-autonomous and involve oscillatory expression of core clock genes that is driven by interconnecting transcription–translation feedback loops (TTFLs). Circadian clock TTFLs are further regulated by posttranslational modifications, in particular, phosphorylation. The hippocampus plays an important role in spatial memory and the conversion of short- to long-term memory. Several studies have reported the presence of a peripheral oscillator in the hippocampus and have highlighted the importance of circadian regulation in memory formation. Given the general importance of phosphorylation in circadian clock regulation, we performed global quantitative proteome and phosphoproteome analyses of the murine hippocampus across the circadian cycle, applying spiked-in labeled reference and high accuracy mass spectrometry (MS). Of the 3,052 proteins and 2,868 phosphosites on 1,368 proteins that were accurately quantified, 1.7% of proteins and 5.2% of phosphorylation events exhibited time-of-day-dependent expression profiles. The majority of circadian phosphopeptides displayed abrupt fluctuations at mid-to-late day without underlying rhythms of protein abundance. Bioinformatic analysis of cyclic phosphorylation events revealed their diverse distribution in different biological pathways, most notably, cytoskeletal organization and neuronal morphogenesis. This study provides the first large-scale, quantitative MS analysis of the circadian phosphoproteome and proteome of the murine hippocampus and highlights the significance of rhythmic regulation at the posttranslational level in this peripheral oscillator. In addition to providing molecular insights into the hippocampal circadian clock, our results will assist in the understanding of genetic factors that underlie rhythms-associated pathological states of

  8. Quantitative Phosphoproteome Analysis of Bacillus subtilis Reveals Novel Substrates of the Kinase PrkC and Phosphatase PrpC*

    PubMed Central

    Ravikumar, Vaishnavi; Shi, Lei; Krug, Karsten; Derouiche, Abderahmane; Jers, Carsten; Cousin, Charlotte; Kobir, Ahasanul; Mijakovic, Ivan; Macek, Boris

    2014-01-01

    Reversible protein phosphorylation on serine, threonine, and tyrosine (Ser/Thr/Tyr) residues plays a critical role in regulation of vital processes in the cell. Despite of considerable progress in our understanding of the role of this modification in bacterial physiology, the dynamics of protein phosphorylation during bacterial growth has rarely been systematically addressed. In addition, little is known about in vivo substrates of bacterial Ser/Thr/Tyr kinases and phosphatases. An excellent candidate to study these questions is the Gram-positive bacterium Bacillus subtilis, one of the most intensively investigated bacterial model organism with both research and industrial applications. Here we employed gel-free phosphoproteomics combined with SILAC labeling and high resolution mass spectrometry to study the proteome and phosphoproteome dynamics during the batch growth of B. subtilis. We measured the dynamics of 1666 proteins and 64 phosphorylation sites in five distinct phases of growth. Enzymes of the central carbon metabolism and components of the translation machinery appear to be highly phosphorylated in the stationary phase, coinciding with stronger expression of Ser/Thr kinases. We further used the SILAC workflow to identify novel putative substrates of the Ser/Thr kinase PrkC and the phosphatase PrpC during stationary phase. The overall number of putative substrates was low, pointing to a high kinase and phosphatase specificity. One of the phosphorylation sites affected by both, PrkC and PrpC, was the Ser281 on the oxidoreductase YkwC. We showed that PrkC phosphorylates and PrpC dephosphorylates YkwC in vitro and that phosphorylation at Ser281 abolishes the oxidoreductase activity of YkwC in vitro and in vivo. Our results present the most detailed phosphoproteomic analysis of B. subtilis growth to date and provide the first global in vivo screen of PrkC and PrpC substrates. PMID:24390483

  9. Overview of global greenhouse effects

    SciTech Connect

    Reck, R.A.

    1993-09-01

    This report reviews the factors that influence the evolution of climate and climate change. Recent studies have confirmed that CO{sub 2}, O{sub 3}, N{sub 2}O, CH{sub 4}, and chlorofluorocarbos are increasing in abundance in the atmosphere and can alter the radiation balance by means of the so-called greenhouse effect. The greenhouse effect is as well-accepted phenomenon, but the prediction of its consequences is much less certain. Attempts to detect a human-caused temperature change are still inconclusive. This report presents a discussion of the scientific basis for the greenhouse effect, its relationship to the abundances of greenhouse gases, and the evidence confirming the increases in the abundances. The basis for climate modeling is presented together with an example of the model outputs from one of the most sophisticated modeling efforts. Uncertainties in the present understanding of climate are outlined.

  10. Phosphoproteomics by mass spectrometry and classical protein chemistry approaches.

    PubMed

    Salih, Erdjan

    2005-01-01

    The general fields of biological sciences have seen phenomenal transformations in the past two decades at the level of data acquisition, understanding biological processes, and technological developments. Those advances have been made partly because of the advent of molecular biology techniques (which led to genomics) coupled to the advances made in mass spectrometry (MS) to provide the current capabilities and developments in proteomics. However, our current knowledge that approximately 30,000 human genes may code for up to 1 million or more proteins disengage the interface between the genome sequence database algorithms and MS to generate a major interest in independent de novo MS/MS sequence determination. Significant progress has been made in this area through procedures to covalently modify peptide N- and C-terminal amino-acids by sulfonation and guanidination to permit rapid de novo sequence determination by MS/MS analysis. A number of strategies that have been developed to perform qualitative and quantitative proteomics range from 2D-gel electrophoresis, affinity tag reagents, and stable-isotope labeling. Those procedures, combined with MS/MS peptide sequence analysis at the subpicomole level, permit the rapid and effective identification and quantification of a large number of proteins within a given biological sample. The identification of proteins per se, however, is not always sufficient to interpret biological function because many of the naturally occurring proteins are post-translationally modified. One such modification is protein phosphorylation, which regulates a large array of cellular biochemical pathways of the biological system. Traditionally, the study of phosphoprotein structure-function relationships involved classical protein chemistry approaches that required protein purification, peptide mapping, and the identification of the phosphorylated peptide regions and sites by N-terminal sequence analysis. Recent advances made in mass

  11. Quantitative phosphoproteomic analysis reveals system-wide signaling pathways regulated by site-specific phosphorylation on Keratin-8 in skin squamous cell carcinoma derived cell- line.

    PubMed

    Tiwari, Richa; Sahu, Indrajit; Soni, Bihari Lal; Sathe, Gajanan J; Datta, Keshava K; Thapa, Pankaj; Sinha, Shruti; Vadivel, Chella Krishna; Dhaka, Bharti; Gowda, Harsha; Vaidya, Milind M

    2017-02-07

    Keratin 8/18, a simple epithelia specific keratin pair, is often aberrantly expressed in squamous cell carcinomas (SCC) where its expression is correlated with increased invasion and poor prognosis. Majority of Keratin 8 (K8) functions are governed by its phosphorylation at Serine(73) (head-domain) and Serine(431) (tail-domain) residues. Although, deregulation of K8 phosphorylation is associated with progression of different carcinomas, its role in skin-SCC and the underlying mechanism is obscure. In this direction, we performed TMT-based quantitative phosphoproteomics by expressing K8 wild type, phosphodead and phosphomimetic mutants in K8-deficient A431 cells. Further analysis of our phosphoproteomics data showed a significant proportion of total phosphoproteome associated with migratory, proliferative and invasive potential of these cells to be differentially phosphorylated. Differential phosphorylation of CDK1(T14,Y15) , EIF4EBP1(T46,T50) , EIF4B(S422) , AKT1S1T246,S247, CTTN1(T401,S405,) Y421 & CAP1(S307/309) in K8-S73A/D mutant and CTTN1(T401,S405,Y421) , BUB1B(S1043) & CARHSP1(S30,S32) in K8-S431A/D mutants as well as some anonymous phosphosites including MYC(S176) , ZYX(S344) and PNN(S692) could be potential candidates associated with K8 phosphorylation mediated tumorigenicity. Biochemical validation followed by phenotypic analysis further confirmed our quantitative phosphoproteomics data. In conclusion, our study provides the first global picture of K8 site- specific phosphorylation function in neoplastic progression of A431 cells and suggests various potential starting points for further mechanistic studies. This article is protected by copyright. All rights reserved.

  12. Potential effects on health of global warming

    SciTech Connect

    Haines, A. . Whittington Hospital); Parry, M. . Environmental Change Unit)

    1993-12-01

    Prediction of the impacts of global climate change on health is complicated by a number of factors. These include: the difficulty in predicting regional changes in climate, the capacity for adaptation to climate change, the interactions between the effects of global climate change and a number of other key determinants of health, including population growth and poverty, and the availability of adequate preventive and curative facilities for diseases that may be effected by climate change. Nevertheless, it is of importance to consider the potential health impacts of global climate change for a number of reasons. It is also important to monitor diseases which could be effected by climate change in order to detect changes in incidence as early as possible and study possible interactions with other factors. It seems likely that the possible impacts on health of climate change will be a major determinant of the degree to which policies aimed at reducing global warming are followed, as perceptions of the effect of climate change to human health and well-being are particularly likely to influence public opinion. The potential health impacts of climate change can be divided into direct (primary) and indirect (secondary and tertiary) effects. Primary effects are those related to the effect of temperature on human well-being and disease. Secondary effects include the impacts on health of changes in food production, availability of water and of sea level rise. A tertiary level of impacts can also be hypothesized.

  13. Mitochondrial tyrosine phosphoproteome: new insights from an up-to-date analysis.

    PubMed

    Cesaro, Luca; Salvi, Mauro

    2010-01-01

    Tyrosine phosphorylation is a newcomer in the mitochondrial signaling and is currently emerging as an important mechanism for regulating mitochondrial processes. But to what extent? By analyzing an updated draft of the mitochondrial tyrosine phosphoproteome, the following observations can be drawn: more than a hundred mitochondrial proteins undergo tyrosine phosphorylation, phosphotyrosine proteins are distributed in each of the submitochondrial compartments, and mitochondrial tyrosine phosphorylated proteins are involved in a variety of functions as metabolism (electron transport chain, Krebs cycle, fatty acid and amino acid metabolism), solute and protein transport, mitochondrial translation machinery, quality protein assessment, oxidative stress, apoptosis, fission, and other. This large and varied collection suggests that tyrosine phosphorylation could be a widespread mechanism in modulating mitochondrial functions. Moreover the in silico model is here used to explore potential effects of tyrosine phosphorylation on selected mitochondrial proteins pointing out some future perspectives in this field.

  14. Automated Immobilized Metal Affinity Chromatography System for Enrichment of Escherichia coli Phosphoproteome

    SciTech Connect

    Qu, Yi; Wu, Si; Zhao, Rui; Zink, Erika M.; Orton, Daniel J.; Moore, Ronald J.; Meng, Da; Clauss, Therese RW; Aldrich, Joshua T.; Lipton, Mary S.; Pasa-Tolic, Ljiljana

    2013-06-05

    Enrichment of bacterial phosphopeptides is an essential step prior to bottom-up mass spectrometry-based analysis of the phosphoproteome, which is fundamental to understanding the role of phosphoproteins in cell signaling and regulation of protein activity. We developed an automated IMAC system to enrich strong cation exchange-fractionated phosphopeptides from the soluble proteome of Escherichia coli MG1655 grown on minimal medium. Initial demonstration of the system resulted in identification of 75 phosphopeptides covering 52 phosphoproteins. Consistent with previous studies, many of these phosphoproteins are involved in the carbohydrate portion of central metabolism. The automated system utilizes a large capacity IMAC column that can effectively enrich phosphopeptides from a bacterial sample by increasing peptide loading and reducing the wash time. An additional benefit of the automated IMAC system is reduced labor and associated costs.

  15. Quantitative Phosphoproteomics Reveals Novel Phosphorylation Events in Insulin Signaling Regulated by Protein Phosphatase 1 Regulatory Subunit 12A

    PubMed Central

    Zhang, Xiangmin; Ma, Danjun; Caruso, Michael; Lewis, Monique; Qi, Yue; Yi, Zhengping

    2014-01-01

    Serine/threonine protein phosphatase 1 regulatory subunit 12A (PPP1R12A) modulates the activity and specificity of the catalytic subunit of protein phosphatase 1, regulating various cellular processes via dephosphorylation. Nonetheless, little is known about phosphorylation events controlled by PPP1R12A in skeletal muscle insulin signaling. Here, we used quantitative phosphoproteomics to generate a global picture of phosphorylation events regulated by PPP1R12A in a L6 skeletal muscle cell line, which were engineered for inducible PPP1R12A knockdown. Phosphoproteomics revealed 3876 phosphorylation sites (620 were novel) in these cells. Furthermore, PPP1R12A knockdown resulted in increased overall phosphorylation in L6 cells at the basal condition, and changed phosphorylation levels for 698 sites (assigned to 295 phosphoproteins) at the basal and/or insulin-stimulated conditions. Pathway analysis on the 295 phosphoproteins revealed multiple significantly enriched pathways related to insulin signaling, such as mTOR signaling and RhoA signaling. Moreover, phosphorylation levels for numerous regulatory sites in these pathways were significantly changed due to PPP1R12A knockdown. These results indicate that PPP1R12A indeed plays a role in skeletal muscle insulin signaling, providing novel insights into the biology of insulin action. This new information may facilitate the design of experiments to better understand mechanisms underlying skeletal muscle insulin resistance and type 2 diabetes. PMID:24972320

  16. Integration of conventional quantitative and phospho-proteomics reveals new elements in activated Jurkat T-cell receptor pathway maintenance.

    PubMed

    Jouy, Florent; Müller, Stephan A; Wagner, Juliane; Otto, Wolfgang; von Bergen, Martin; Tomm, Janina M

    2015-01-01

    Recent years have seen a constant development of tools for the global assessment of phosphoproteins. Here, we outline a concept for integrating approaches for quantitative proteomics and phosphoproteomics. The strategy was applied to the analysis of changes in signalling and protein synthesis occurring after activation of the T-cell receptor (TCR) pathway in a T-cell line (Jurkat cells). For this purpose, peptides were obtained from four biological replicates of activated and control Jurkat T-cells and phosphopeptides enriched via a TiO2-based chromatographic step. Both phosphopeptide-enriched and flow-through fractions were analyzed by LC-MS. We observed 1314 phosphopeptides in the enriched fraction whereas 19 were detected in the flow-through, enabling the quantification of 414 and eight phosphoproteins in the respective fractions. Pathway analysis revealed the differential regulation of many metabolic pathways. Among the quantified proteins, 11 kinases with known TCR-related function were detected. A kinase-substrate database search for the phosphosites identified also confirmed the activity of a further ten kinases. In total, these two approaches provided evidence of 19 unique TCR-related kinases. The combination of phosphoproteomics and conventional quantitative shotgun analysis leads to a more comprehensive assessment of the signalling networks needed for the maintenance of the activated status of Jurkat T-cells.

  17. Phosphoproteomic profiling of human myocardial tissues distinguishes ischemic from non-ischemic end stage heart failure.

    PubMed

    Schechter, Matthew A; Hsieh, Michael K H; Njoroge, Linda W; Thompson, J Will; Soderblom, Erik J; Feger, Bryan J; Troupes, Constantine D; Hershberger, Kathleen A; Ilkayeva, Olga R; Nagel, Whitney L; Landinez, Gina P; Shah, Kishan M; Burns, Virginia A; Santacruz, Lucia; Hirschey, Matthew D; Foster, Matthew W; Milano, Carmelo A; Moseley, M Arthur; Piacentino, Valentino; Bowles, Dawn E

    2014-01-01

    The molecular differences between ischemic (IF) and non-ischemic (NIF) heart failure are poorly defined. A better understanding of the molecular differences between these two heart failure etiologies may lead to the development of more effective heart failure therapeutics. In this study extensive proteomic and phosphoproteomic profiles of myocardial tissue from patients diagnosed with IF or NIF were assembled and compared. Proteins extracted from left ventricular sections were proteolyzed and phosphopeptides were enriched using titanium dioxide resin. Gel- and label-free nanoscale capillary liquid chromatography coupled to high resolution accuracy mass tandem mass spectrometry allowed for the quantification of 4,436 peptides (corresponding to 450 proteins) and 823 phosphopeptides (corresponding to 400 proteins) from the unenriched and phospho-enriched fractions, respectively. Protein abundance did not distinguish NIF from IF. In contrast, 37 peptides (corresponding to 26 proteins) exhibited a ≥ 2-fold alteration in phosphorylation state (p<0.05) when comparing IF and NIF. The degree of protein phosphorylation at these 37 sites was specifically dependent upon the heart failure etiology examined. Proteins exhibiting phosphorylation alterations were grouped into functional categories: transcriptional activation/RNA processing; cytoskeleton structure/function; molecular chaperones; cell adhesion/signaling; apoptosis; and energetic/metabolism. Phosphoproteomic analysis demonstrated profound post-translational differences in proteins that are involved in multiple cellular processes between different heart failure phenotypes. Understanding the roles these phosphorylation alterations play in the development of NIF and IF has the potential to generate etiology-specific heart failure therapeutics, which could be more effective than current therapeutics in addressing the growing concern of heart failure.

  18. Phosphoproteomic Profiling of Human Myocardial Tissues Distinguishes Ischemic from Non-Ischemic End Stage Heart Failure

    PubMed Central

    Njoroge, Linda W.; Thompson, J. Will; Soderblom, Erik J.; Feger, Bryan J.; Troupes, Constantine D.; Hershberger, Kathleen A.; Ilkayeva, Olga R.; Nagel, Whitney L.; Landinez, Gina P.; Shah, Kishan M.; Burns, Virginia A.; Santacruz, Lucia; Hirschey, Matthew D.; Foster, Matthew W.; Milano, Carmelo A.; Moseley, M. Arthur; Piacentino, Valentino; Bowles, Dawn E.

    2014-01-01

    The molecular differences between ischemic (IF) and non-ischemic (NIF) heart failure are poorly defined. A better understanding of the molecular differences between these two heart failure etiologies may lead to the development of more effective heart failure therapeutics. In this study extensive proteomic and phosphoproteomic profiles of myocardial tissue from patients diagnosed with IF or NIF were assembled and compared. Proteins extracted from left ventricular sections were proteolyzed and phosphopeptides were enriched using titanium dioxide resin. Gel- and label-free nanoscale capillary liquid chromatography coupled to high resolution accuracy mass tandem mass spectrometry allowed for the quantification of 4,436 peptides (corresponding to 450 proteins) and 823 phosphopeptides (corresponding to 400 proteins) from the unenriched and phospho-enriched fractions, respectively. Protein abundance did not distinguish NIF from IF. In contrast, 37 peptides (corresponding to 26 proteins) exhibited a ≥2-fold alteration in phosphorylation state (p<0.05) when comparing IF and NIF. The degree of protein phosphorylation at these 37 sites was specifically dependent upon the heart failure etiology examined. Proteins exhibiting phosphorylation alterations were grouped into functional categories: transcriptional activation/RNA processing; cytoskeleton structure/function; molecular chaperones; cell adhesion/signaling; apoptosis; and energetic/metabolism. Phosphoproteomic analysis demonstrated profound post-translational differences in proteins that are involved in multiple cellular processes between different heart failure phenotypes. Understanding the roles these phosphorylation alterations play in the development of NIF and IF has the potential to generate etiology-specific heart failure therapeutics, which could be more effective than current therapeutics in addressing the growing concern of heart failure. PMID:25117565

  19. The current state of the art of quantitative phosphoproteomics and its applications to diabetes research.

    PubMed

    Chan, Chi Yuet X'avia; Gritsenko, Marina A; Smith, Richard D; Qian, Wei-Jun

    2016-01-01

    Protein phosphorylation is a fundamental regulatory mechanism in many cellular processes and aberrant perturbation of phosphorylation has been implicated in various human diseases. Kinases and their cognate inhibitors have been considered as hotspots for drug development. Therefore, the emerging tools, which enable a system-wide quantitative profiling of phosphoproteome, would offer a powerful impetus in unveiling novel signaling pathways, drug targets and/or biomarkers for diseases of interest. This review highlights recent advances in phosphoproteomics, the current state of the art of the technologies and the challenges and future perspectives of this research area. Finally, some exemplary applications of phosphoproteomics in diabetes research are underscored.

  20. The current state of the art of quantitative phosphoproteomics and its applications to diabetes research

    SciTech Connect

    Chan, Chi Yuet X’avia; Gritsenko, Marina A.; Smith, Richard D.; Qian, Wei-Jun

    2016-03-17

    Protein phosphorylation is a fundamental regulatory mechanism in many cellular processes and aberrant perturbation of phosphorylation has been revealed in various human diseases. Kinases and their cognate inhibitors have been hotspot for drug development. Therefore, the emerging tools, which enable a system-wide quantitative profiling of phosphoproteome, would offer a powerful impetus in unveiling novel signaling pathways, drug targets and/or biomarkers for the disease of interest. In this review, we will highlight recent advances in phosphoproteomics, the current state-of-the-art of the technologies, and the challenges and future perspectives of this research area. Finally, we will underscore some exemplary applications of phosphoproteomics in diabetes research.

  1. GLOBAL CHANGE EFFECTS ON CORAL REEF CONDITION

    EPA Science Inventory

    Fisher, W., W. Davis, J. Campbell, L. Courtney, P. Harris, B. Hemmer, M. Parsons, B. Quarles and D. Santavy. In press. Global Change Effects on Coral Reef Condition (Abstract). To be presented at the EPA Science Forum: Healthy Communities and Ecosystems, 1-3 June 2004, Washington...

  2. Cloud effects on middle ultraviolet global radiation

    NASA Technical Reports Server (NTRS)

    Borkowski, J.; Chai, A.-T.; Mo, T.; Green, A. E. O.

    1977-01-01

    An Eppley radiometer and a Robertson-Berger sunburn meter are employed along with an all-sky camera setup to study cloud effects on middle ultraviolet global radiation at the ground level. Semiempirical equations to allow for cloud effects presented in previous work are compared with the experimental data. The study suggests a means of defining eigenvectors of cloud patterns and correlating them with the radiation at the ground level.

  3. Technical phosphoproteomic and bioinformatic tools useful in cancer research

    PubMed Central

    2011-01-01

    Reversible protein phosphorylation is one of the most important forms of cellular regulation. Thus, phosphoproteomic analysis of protein phosphorylation in cells is a powerful tool to evaluate cell functional status. The importance of protein kinase-regulated signal transduction pathways in human cancer has led to the development of drugs that inhibit protein kinases at the apex or intermediary levels of these pathways. Phosphoproteomic analysis of these signalling pathways will provide important insights for operation and connectivity of these pathways to facilitate identification of the best targets for cancer therapies. Enrichment of phosphorylated proteins or peptides from tissue or bodily fluid samples is required. The application of technologies such as phosphoenrichments, mass spectrometry (MS) coupled to bioinformatics tools is crucial for the identification and quantification of protein phosphorylation sites for advancing in such relevant clinical research. A combination of different phosphopeptide enrichments, quantitative techniques and bioinformatic tools is necessary to achieve good phospho-regulation data and good structural analysis of protein studies. The current and most useful proteomics and bioinformatics techniques will be explained with research examples. Our aim in this article is to be helpful for cancer research via detailing proteomics and bioinformatic tools. PMID:21967744

  4. Search Databases and Statistics: Pitfalls and Best Practices in Phosphoproteomics.

    PubMed

    Refsgaard, Jan C; Munk, Stephanie; Jensen, Lars J

    2016-01-01

    Advances in mass spectrometric instrumentation in the past 15 years have resulted in an explosion in the raw data yield from typical phosphoproteomics workflows. This poses the challenge of confidently identifying peptide sequences, localizing phosphosites to proteins and quantifying these from the vast amounts of raw data. This task is tackled by computational tools implementing algorithms that match the experimental data to databases, providing the user with lists for downstream analysis. Several platforms for such automated interpretation of mass spectrometric data have been developed, each having strengths and weaknesses that must be considered for the individual needs. These are reviewed in this chapter. Equally critical for generating highly confident output datasets is the application of sound statistical criteria to limit the inclusion of incorrect peptide identifications from database searches. Additionally, careful filtering and use of appropriate statistical tests on the output datasets affects the quality of all downstream analyses and interpretation of the data. Our considerations and general practices on these aspects of phosphoproteomics data processing are presented here.

  5. Comparative phosphoproteomics of zebrafish Fyn/Yes morpholino knockdown embryos.

    PubMed

    Lemeer, Simone; Jopling, Chris; Gouw, Joost; Mohammed, Shabaz; Heck, Albert J R; Slijper, Monique; den Hertog, Jeroen

    2008-11-01

    The coordinated movement of cells is indispensable for normal vertebrate gastrulation. Several important players and signaling pathways have been identified in convergence and extension (CE) cell movements during gastrulation, including non-canonical Wnt signaling. Fyn and Yes, members of the Src family of kinases, are key regulators of CE movements as well. Here we investigated signaling pathways in early development by comparison of the phosphoproteome of wild type zebrafish embryos with Fyn/Yes knockdown embryos that display specific CE cell movement defects. For quantitation we used differential stable isotope labeling by reductive amination of peptides. Equal amounts of labeled peptides from wild type and Fyn/Yes knockdown embryos were mixed and analyzed by on-line reversed phase TiO(2)-reversed phase LC-MS/MS. Phosphorylated and non-phosphorylated peptides were quantified, and significant changes in protein expression and/or phosphorylation were detected. We identified 348 phosphoproteins of which 69 showed a decrease in phosphorylation in Fyn/Yes knockdown embryos and 72 showed an increase in phosphorylation. Among these phosphoproteins were known regulators of cell movements, including Adducin and PDLIM5. Our results indicate that quantitative phosphoproteomics combined with morpholino-mediated knockdowns can be used to identify novel signaling pathways that act in zebrafish development in vivo.

  6. Fast and easy phosphopeptide fractionation by combinatorial ERLIC-SCX solid-phase extraction for in-depth phosphoproteome analysis.

    PubMed

    Zarei, Mostafa; Sprenger, Adrian; Rackiewicz, Michal; Dengjel, Joern

    2016-01-01

    Mass spectrometry-based phosphoproteomic analysis is a powerful method for gaining a global, unbiased understanding of cellular signaling. Its accuracy and comprehensiveness stands or falls with the quality and choice of the applied phosphopeptide prefractionation strategy. This protocol covers a powerful but simple and rapid strategy for phosphopeptide prefractionation. The combinatorial use of two distinct chromatographic techniques that address the inverse physicochemical properties of peptides allows for superior fractionation efficiency of multiple phosphorylated peptides. In the first step, multiphosphorylated peptides are separated according to the number of negatively charged phosphosites by electrostatic repulsion-hydrophilic interaction chromatography (ERLIC). A subsequent strong cation exchange (SCX) step separates mostly singly phosphorylated peptides in the ERLIC flow-through according to their positive charge. The presented strategy is inexpensive and adaptable to large and small amounts of starting material, and it allows highly multiplexed sample preparation. Because of its implementation as solid-phase extraction, the entire workflow takes only 2 h to complete.

  7. Chronic low-dose-rate ionising radiation affects the hippocampal phosphoproteome in the ApoE−/− Alzheimer's mouse model

    PubMed Central

    Kempf, Stefan J.; Janik, Dirk; Barjaktarovic, Zarko; Braga-Tanaka, Ignacia; Tanaka, Satoshi; Neff, Frauke; Saran, Anna; Larsen, Martin R.; Tapio, Soile

    2016-01-01

    Accruing data indicate that radiation-induced consequences resemble pathologies of neurodegenerative diseases such as Alzheimer's. The aim of this study was to elucidate the effect on hippocampus of chronic low-dose-rate radiation exposure (1 mGy/day or 20 mGy/day) given over 300 days with cumulative doses of 0.3 Gy and 6.0 Gy, respectively. ApoE deficient mutant C57Bl/6 mouse was used as an Alzheimer's model. Using mass spectrometry, a marked alteration in the phosphoproteome was found at both dose rates. The radiation-induced changes in the phosphoproteome were associated with the control of synaptic plasticity, calcium-dependent signalling and brain metabolism. An inhibition of CREB signalling was found at both dose rates whereas Rac1-Cofilin signalling was found activated only at the lower dose rate. Similarly, the reduction in the number of activated microglia in the molecular layer of hippocampus that paralleled with reduced levels of TNFα expression and lipid peroxidation was significant only at the lower dose rate. Adult neurogenesis, investigated by Ki67, GFAP and NeuN staining, and cell death (activated caspase-3) were not influenced at any dose or dose rate. This study shows that several molecular targets induced by chronic low-dose-rate radiation overlap with those of Alzheimer's pathology. It may suggest that ionising radiation functions as a contributing risk factor to this neurodegenerative disease. PMID:27708245

  8. Label-free quantitative phosphoproteomics with novel pairwise abundance normalization reveals synergistic RAS and CIP2A signaling

    PubMed Central

    Kauko, Otto; Laajala, Teemu Daniel; Jumppanen, Mikael; Hintsanen, Petteri; Suni, Veronika; Haapaniemi, Pekka; Corthals, Garry; Aittokallio, Tero; Westermarck, Jukka; Imanishi, Susumu Y.

    2015-01-01

    Hyperactivated RAS drives progression of many human malignancies. However, oncogenic activity of RAS is dependent on simultaneous inactivation of protein phosphatase 2A (PP2A) activity. Although PP2A is known to regulate some of the RAS effector pathways, it has not been systematically assessed how these proteins functionally interact. Here we have analyzed phosphoproteomes regulated by either RAS or PP2A, by phosphopeptide enrichment followed by mass-spectrometry-based label-free quantification. To allow data normalization in situations where depletion of RAS or PP2A inhibitor CIP2A causes a large uni-directional change in the phosphopeptide abundance, we developed a novel normalization strategy, named pairwise normalization. This normalization is based on adjusting phosphopeptide abundances measured before and after the enrichment. The superior performance of the pairwise normalization was verified by various independent methods. Additionally, we demonstrate how the selected normalization method influences the downstream analyses and interpretation of pathway activities. Consequently, bioinformatics analysis of RAS and CIP2A regulated phosphoproteomes revealed a significant overlap in their functional pathways. This is most likely biologically meaningful as we observed a synergistic survival effect between CIP2A and RAS expression as well as KRAS activating mutations in TCGA pan-cancer data set, and synergistic relationship between CIP2A and KRAS depletion in colony growth assays. PMID:26278961

  9. Label-free quantitative phosphoproteomic profiling of cellular response induced by an insect cytokine paralytic peptide.

    PubMed

    Song, Liang; Wang, Fei; Dong, Zhaoming; Hua, Xiaoting; Xia, Qingyou

    2017-02-10

    Paralytic peptide (PP) participates in diverse physiological processes as an insect cytokine, such as immunity control, paralysis induction, regulation of cell morphology and proliferation. To investigate the molecular mechanism underlying those physiological activities, we systematically investigated the global phosphorylation events in fat body of silkworm larvae induced by PP through label-free quantitative phosphoproteomics. 2534 phosphosites were finally identified, of which the phosphorylation level of 620 phosphosites on 244 proteins was significantly up-regulated and 67 phosphosites on 43 proteins was down-regulated. Among those proteins, 13 were protein kinases (PKs), 13 were transcription factors (TFs) across 10 families and 17 were metabolism related enzymes. Meanwhile, Motif-X analysis of the phosphorylation sites showed that 16 motifs are significantly enriched, including 8 novel phosphorylation motifs. In addition, KEGG and functional interacting network analysis revealed that phosphorylation cascades play the crucial regulation roles in PP-dependent signaling pathways, and highlighted the potential central position of the mitogen-activated protein kinases (MAPKs) in them. These analyses provide direct insights into the molecule mechanisms of cellular response induced by PP.

  10. Phosphoproteomics Identifies CK2 as a Negative Regulator of Beige Adipocyte Thermogenesis and Energy Expenditure.

    PubMed

    Shinoda, Kosaku; Ohyama, Kana; Hasegawa, Yutaka; Chang, Hsin-Yi; Ogura, Mayu; Sato, Ayaka; Hong, Haemin; Hosono, Takashi; Sharp, Louis Z; Scheel, David W; Graham, Mark; Ishihama, Yasushi; Kajimura, Shingo

    2015-12-01

    Catecholamines promote lipolysis both in brown and white adipocytes, whereas the same stimuli preferentially activate thermogenesis in brown adipocytes. Molecular mechanisms for the adipose-selective activation of thermogenesis remain poorly understood. Here, we employed quantitative phosphoproteomics to map global and temporal phosphorylation profiles in brown, beige, and white adipocytes under β3-adrenenoceptor activation and identified kinases responsible for the adipose-selective phosphorylation profiles. We found that casein kinase2 (CK2) activity is preferentially higher in white adipocytes than brown/beige adipocytes. Genetic or pharmacological blockade of CK2 in white adipocytes activates the thermogenic program in response to cAMP stimuli. Such activation is largely through reduced CK2-mediated phosphorylation of class I HDACs. Notably, inhibition of CK2 promotes beige adipocyte biogenesis and leads to an increase in whole-body energy expenditure and ameliorates diet-induced obesity and insulin resistance. These results indicate that CK2 is a plausible target to rewire the β3-adrenenoceptor signaling cascade that promotes thermogenesis in adipocytes.

  11. Quantitative phosphoproteomics by mass spectrometry: Past, present, and future

    PubMed Central

    Nita-Lazar, Aleksandra; Saito-Benz, Hideshiro; White, Forest M.

    2009-01-01

    Protein phosphorylation-mediated signaling networks regulate much of the cellular response to external stimuli, and dysregulation in these networks has been linked to multiple disease states. Significant advancements have been made over the past decade to enable the analysis and quantification of cellular protein phosphorylation events, but comprehensive analysis of the phosphoproteome is still lacking, as is the ability to monitor signaling at the network level while comprehending the biological implications of each phosphorylation site. In this review we highlight many of the technological advances over the past decade and describe some of the latest applications of these tools to uncover signaling networks in a variety of biological settings. We finish with a concise discussion of the future of the field, including additional advances that are required to link protein phosphorylation analysis with biological insight. PMID:18846511

  12. Phosphoproteomic Analysis of Aurora Kinase Inhibition in Monopolar Cytokinesis.

    PubMed

    Polat, Ayse Nur; Karayel, Özge; Giese, Sven H; Harmanda, Büşra; Sanal, Erdem; Hu, Chi-Kuo; Renard, Bernhard Y; Özlü, Nurhan

    2015-09-04

    Cytokinesis is the last step of the cell cycle that requires coordinated activities of the microtubule cytoskeleton, actin cytoskeleton, and membrane compartments. Aurora B kinase is one of the master regulatory kinases that orchestrate multiple events during cytokinesis. To reveal targets of the Aurora B kinase, we combined quantitative mass spectrometry with chemical genetics. Using the quantitative proteomic approach, SILAC (stable isotope labeling with amino acids in cell culture), we analyzed the phosphoproteome of monopolar cytokinesis upon VX680- or AZD1152-mediated aurora kinase inhibition. In total, our analysis quantified over 20 000 phosphopeptides in response to the Aurora-B kinase inhibition; 246 unique phosphopeptides were significantly down-regulated and 74 were up-regulated. Our data provide a broad analysis of downstream effectors of Aurora kinase and offer insights into how Aurora kinase regulates cytokinesis.

  13. Effects of Global Warming on Vibrio Ecology.

    PubMed

    Vezzulli, Luigi; Pezzati, Elisabetta; Brettar, Ingrid; Höfle, Manfred; Pruzzo, Carla

    2015-06-01

    Vibrio-related infections are increasing worldwide both in humans and aquatic animals. Rise in global sea surface temperature (SST), which is approximately 1 °C higher now than 140 years ago and is one of the primary physical impacts of global warming, has been linked to such increases. In this chapter, major known effects of increasing SST on the biology and ecology of vibrios are described. They include the effects on bacterial growth rate, both in the field and in laboratory, culturability, expression of pathogenicity traits, and interactions with aquatic organisms and abiotic surfaces. Special emphasis is given to the effect of ocean warming on Vibrio interactions with zooplankters, which represent one of the most important aquatic reservoirs for these bacteria. The reported findings highlight the biocomplexity of the interactions between vibrios and their natural environment in a climate change scenario, posing the need for interdisciplinary studies to properly understand the connection between ocean warming and persistence and spread of vibrios in sea waters and the epidemiology of the diseases they cause.

  14. Microscale Effects from Global Hot Plasma Imagery

    NASA Technical Reports Server (NTRS)

    Moore, T. E.; Fok, M.-C.; Perez, J. D.; Keady, J. P.

    1995-01-01

    We have used a three-dimensional model of recovery phase storm hot plasmas to explore the signatures of pitch angle distributions (PADS) in global fast atom imagery of the magnetosphere. The model computes mass, energy, and position-dependent PADs based on drift effects, charge exchange losses, and Coulomb drag. The hot plasma PAD strongly influences both the storm current system carried by the hot plasma and its time evolution. In turn, the PAD is strongly influenced by plasma waves through pitch angle diffusion, a microscale effect. We report the first simulated neutral atom images that account for anisotropic PADs within the hot plasma. They exhibit spatial distribution features that correspond directly to the PADs along the lines of sight. We investigate the use of image brightness distributions along tangent-shell field lines to infer equatorial PADS. In tangent-shell regions with minimal spatial gradients, reasonably accurate PADs are inferred from simulated images. They demonstrate the importance of modeling PADs for image inversion and show that comparisons of models with real storm plasma images will reveal the global effects of these microscale processes.

  15. Discovery of mouse spleen signaling responses to anthrax using label-free quantitative phosphoproteomics via mass spectrometry.

    PubMed

    Manes, Nathan P; Dong, Li; Zhou, Weidong; Du, Xiuxia; Reghu, Nikitha; Kool, Arjan C; Choi, Dahan; Bailey, Charles L; Petricoin, Emanuel F; Liotta, Lance A; Popov, Serguei G

    2011-03-01

    Inhalational anthrax is caused by spores of the bacterium Bacillus anthracis (B. anthracis), and is an extremely dangerous disease that can kill unvaccinated victims within 2 weeks. Modern antibiotic-based therapy can increase the survival rate to ∼50%, but only if administered presymptomatically (within 24-48 h of exposure). To discover host signaling responses to presymptomatic anthrax, label-free quantitative phosphoproteomics via liquid chromatography coupled to mass spectrometry was used to compare spleens from uninfected and spore-challenged mice over a 72 h time-course. Spleen proteins were denatured using urea, reduced using dithiothreitol, alkylated using iodoacetamide, and digested into peptides using trypsin, and the resulting phosphopeptides were enriched using titanium dioxide solid-phase extraction and analyzed by nano-liquid chromatography-Linear Trap Quadrupole-Orbitrap-MS(/MS). The fragment ion spectra were processed using DeconMSn and searched using both Mascot and SEQUEST resulting in 252,626 confident identifications of 6248 phosphopeptides (corresponding to 5782 phosphorylation sites). The precursor ion spectra were deisotoped using Decon2LS and aligned using MultiAlign resulting in the confident quantitation of 3265 of the identified phosphopeptides. ANOVAs were used to produce a q-value ranked list of host signaling responses. Late-stage (48-72 h postchallenge) Sterne strain (lethal) infections resulted in global alterations to the spleen phosphoproteome. In contrast, ΔSterne strain (asymptomatic; missing the anthrax toxin) infections resulted in 188 (5.8%) significantly altered (q<0.05) phosphopeptides. Twenty-six highly tentative phosphorylation responses to early-stage (24 h postchallenge) anthrax were discovered (q<0.5), and ten of these originated from eight proteins that have known roles in the host immune response. These tentative early-anthrax host response signaling events within mouse spleens may translate into presymptomatic

  16. Human R1441C LRRK2 regulates the synaptic vesicle proteome and phosphoproteome in a Drosophila model of Parkinson's disease.

    PubMed

    Islam, Md Shariful; Nolte, Hendrik; Jacob, Wright; Ziegler, Anna B; Pütz, Stefanie; Grosjean, Yael; Szczepanowska, Karolina; Trifunovic, Aleksandra; Braun, Thomas; Heumann, Hermann; Heumann, Rolf; Hovemann, Bernhard; Moore, Darren J; Krüger, Marcus

    2016-10-29

    Mutations in leucine-rich repeat kinase 2 (LRRK2) cause late-onset, autosomal dominant familial Parkinson's disease (PD) and variation at the LRRK2 locus contributes to the risk for idiopathic PD. LRRK2 can function as a protein kinase and mutations lead to increased kinase activity. To elucidate the pathophysiological mechanism of the R1441C mutation in the GTPase domain of LRRK2, we expressed human wild-type or R1441C LRRK2 in dopaminergic neurons of Drosophila and observe reduced locomotor activity, impaired survival and an age-dependent degeneration of dopaminergic neurons thereby creating a new PD-like model. To explore the function of LRRK2 variants in vivo, we performed mass spectrometry and quantified 3,616 proteins in the fly brain. We identify several differentially-expressed cytoskeletal, mitochondrial and synaptic vesicle proteins (SV), including synaptotagmin-1, syntaxin-1A and Rab3, in the brain of this LRRK2 fly model. In addition, a global phosphoproteome analysis reveals the enhanced phosphorylation of several SV proteins, including synaptojanin-1 (pThr1131) and the microtubule-associated protein futsch (pSer4106) in the brain of R1441C hLRRK2 flies. The direct phosphorylation of human synaptojanin-1 by R1441C hLRRK2 could further be confirmed by in vitro kinase assays. A protein-protein interaction screen in the fly brain confirms that LRRK2 robustly interacts with numerous SV proteins, including synaptojanin-1 and EndophilinA. Our proteomic, phosphoproteomic and interactome study in the Drosophila brain provides a systematic analyses of R1441C hLRRK2-induced pathobiological mechanisms in this model. We demonstrate for the first time that the R1441C mutation located within the LRRK2 GTPase domain induces the enhanced phosphorylation of SV proteins in the brain.

  17. Discovery of Mouse Spleen Signaling Responses to Anthrax using Label-Free Quantitative Phosphoproteomics via Mass Spectrometry*

    PubMed Central

    Manes, Nathan P.; Dong, Li; Zhou, Weidong; Du, Xiuxia; Reghu, Nikitha; Kool, Arjan C.; Choi, Dahan; Bailey, Charles L.; Petricoin, Emanuel F.; Liotta, Lance A.; Popov, Serguei G.

    2011-01-01

    Inhalational anthrax is caused by spores of the bacterium Bacillus anthracis (B. anthracis), and is an extremely dangerous disease that can kill unvaccinated victims within 2 weeks. Modern antibiotic-based therapy can increase the survival rate to ∼50%, but only if administered presymptomatically (within 24–48 h of exposure). To discover host signaling responses to presymptomatic anthrax, label-free quantitative phosphoproteomics via liquid chromatography coupled to mass spectrometry was used to compare spleens from uninfected and spore-challenged mice over a 72 h time-course. Spleen proteins were denatured using urea, reduced using dithiothreitol, alkylated using iodoacetamide, and digested into peptides using trypsin, and the resulting phosphopeptides were enriched using titanium dioxide solid-phase extraction and analyzed by nano-liquid chromatography-Linear Trap Quadrupole-Orbitrap-MS(/MS). The fragment ion spectra were processed using DeconMSn and searched using both Mascot and SEQUEST resulting in 252,626 confident identifications of 6248 phosphopeptides (corresponding to 5782 phosphorylation sites). The precursor ion spectra were deisotoped using Decon2LS and aligned using MultiAlign resulting in the confident quantitation of 3265 of the identified phosphopeptides. ANOVAs were used to produce a q-value ranked list of host signaling responses. Late-stage (48–72 h postchallenge) Sterne strain (lethal) infections resulted in global alterations to the spleen phosphoproteome. In contrast, ΔSterne strain (asymptomatic; missing the anthrax toxin) infections resulted in 188 (5.8%) significantly altered (q<0.05) phosphopeptides. Twenty-six highly tentative phosphorylation responses to early-stage (24 h postchallenge) anthrax were discovered (q<0.5), and ten of these originated from eight proteins that have known roles in the host immune response. These tentative early-anthrax host response signaling events within mouse spleens may translate into presymptomatic

  18. Mechanisms of Soybean Roots' Tolerances to Salinity Revealed by Proteomic and Phosphoproteomic Comparisons Between Two Cultivars*

    PubMed Central

    Pi, Erxu; Qu, Liqun; Hu, Jianwen; Huang, Yingying; Qiu, Lijuan; Lu, Hongfei; Jiang, Bo; Liu, Cong; Peng, Tingting; Zhao, Ying; Wang, Huizhong; Tsai, Sau-Na; Ngai, Saiming; Du, Liqun

    2016-01-01

    Understanding molecular mechanisms underlying plant salinity tolerance provides valuable knowledgebase for effective crop improvement through genetic engineering. Current proteomic technologies, which support reliable and high-throughput analyses, have been broadly used for exploring sophisticated molecular networks in plants. In the current study, we compared phosphoproteomic and proteomic changes in roots of different soybean seedlings of a salt-tolerant cultivar (Wenfeng07) and a salt-sensitive cultivar (Union85140) induced by salt stress. The root samples of Wenfeng07 and Union85140 at three-trifoliate stage were collected at 0 h, 0.5 h, 1 h, 4 h, 12 h, 24 h, and 48 h after been treated with 150 mm NaCl. LC-MS/MS based phosphoproteomic analysis of these samples identified a total of 2692 phosphoproteins and 5509 phosphorylation sites. Of these, 2344 phosphoproteins containing 3744 phosphorylation sites were quantitatively analyzed. Our results showed that 1163 phosphorylation sites were differentially phosphorylated in the two compared cultivars. Among them, 10 MYB/MYB transcription factor like proteins were identified with fluctuating phosphorylation modifications at different time points, indicating that their crucial roles in regulating flavonol accumulation might be mediated by phosphorylated modifications. In addition, the protein expression profiles of these two cultivars were compared using LC MS/MS based shotgun proteomic analysis, and expression pattern of all the 89 differentially expressed proteins were independently confirmed by qRT-PCR. Interestingly, the enzymes involved in chalcone metabolic pathway exhibited positive correlations with salt tolerance. We confirmed the functional relevance of chalcone synthase, chalcone isomerase, and cytochrome P450 monooxygenase genes using soybean composites and Arabidopsis thaliana mutants, and found that their salt tolerance were positively regulated by chalcone synthase, but was negatively regulated by

  19. Integrative Proteomics and Phosphoproteomics Profiling Reveals Dynamic Signaling Networks and Bioenergetics Pathways Underlying T Cell Activation.

    PubMed

    Tan, Haiyan; Yang, Kai; Li, Yuxin; Shaw, Timothy I; Wang, Yanyan; Blanco, Daniel Bastardo; Wang, Xusheng; Cho, Ji-Hoon; Wang, Hong; Rankin, Sherri; Guy, Cliff; Peng, Junmin; Chi, Hongbo

    2017-03-21

    The molecular circuits by which antigens activate quiescent T cells remain poorly understood. We combined temporal profiling of the whole proteome and phosphoproteome via multiplexed isobaric labeling proteomics technology, computational pipelines for integrating multi-omics datasets, and functional perturbation to systemically reconstruct regulatory networks underlying T cell activation. T cell receptors activated the T cell proteome and phosphoproteome with discrete kinetics, marked by early dynamics of phosphorylation and delayed ribosome biogenesis and mitochondrial activation. Systems biology analyses identified multiple functional modules, active kinases, transcription factors and connectivity between them, and mitochondrial pathways including mitoribosomes and complex IV. Genetic perturbation revealed physiological roles for mitochondrial enzyme COX10-mediated oxidative phosphorylation in T cell quiescence exit. Our multi-layer proteomics profiling, integrative network analysis, and functional studies define landscapes of the T cell proteome and phosphoproteome and reveal signaling and bioenergetics pathways that mediate lymphocyte exit from quiescence.

  20. Glucose-regulated and drug-perturbed phosphoproteome reveals molecular mechanisms controlling insulin secretion

    PubMed Central

    Sacco, Francesca; Humphrey, Sean J.; Cox, Jürgen; Mischnik, Marcel; Schulte, Anke; Klabunde, Thomas; Schäfer, Matthias; Mann, Matthias

    2016-01-01

    Insulin-secreting beta cells play an essential role in maintaining physiological blood glucose levels, and their dysfunction leads to the development of diabetes. To elucidate the signalling events regulating insulin secretion, we applied a recently developed phosphoproteomics workflow. We quantified the time-resolved phosphoproteome of murine pancreatic cells following their exposure to glucose and in combination with small molecule compounds that promote insulin secretion. The quantitative phosphoproteome of 30,000 sites clustered into three main groups in concordance with the modulation of the three key kinases: PKA, PKC and CK2A. A high-resolution time course revealed key novel regulatory sites, revealing the importance of methyltransferase DNMT3A phosphorylation in the glucose response. Remarkably a significant proportion of these novel regulatory sites is significantly downregulated in diabetic islets. Control of insulin secretion is embedded in an unexpectedly broad and complex range of cellular functions, which are perturbed by drugs in multiple ways. PMID:27841257

  1. Combining Metabolic ¹⁵N Labeling with Improved Tandem MOAC for Enhanced Probing of the Phosphoproteome.

    PubMed

    Thomas, Martin; Huck, Nicola; Hoehenwarter, Wolfgang; Conrath, Uwe; Beckers, Gerold J M

    2015-01-01

    that is based on the successive enrichment of light and heavy nitrogen-labeled phosphoproteins and peptides. This improved strategy combines metabolic labeling of whole plants with the stable heavy nitrogen isotope ((15)N), protein extraction under denaturing conditions, phosphoprotein enrichment using Al(OH)3-based MOAC, and tryptic digest of enriched phosphoproteins followed by TiO2-based MOAC of phosphopeptides and quantitative phosphopeptide measurement by liquid chromatography (LC) and high-resolution accurate mass (HR/AM) mass spectrometry (MS). Thus, tandem MOAC effectively targets the phosphate moiety of phosphoproteins and phosphopeptides and allows probing of the phosphoproteome to unprecedented depth, while (15)N metabolic labeling enables accurate relative quantification of measured peptides and direct comparison between samples.

  2. Phosphoproteome and Transcriptome of RA-Responsive and RA-Resistant Breast Cancer Cell Lines

    PubMed Central

    Carrier, Marilyn; Joint, Mathilde; Lutzing, Régis; Page, Adeline; Rochette-Egly, Cécile

    2016-01-01

    Retinoic acid (RA), the main active vitamin A metabolite, controls multiple biological processes such as cell proliferation and differentiation through genomic programs and kinase cascades activation. Due to these properties, RA has proven anti-cancer capacity. Several breast cancer cells respond to the antiproliferative effects of RA, while others are RA-resistant. However, the overall signaling and transcriptional pathways that are altered in such cells have not been elucidated. Here, in a large-scale analysis of the phosphoproteins and in a genome-wide analysis of the RA-regulated genes, we compared two human breast cancer cell lines, a RA-responsive one, the MCF7 cell line, and a RA-resistant one, the BT474 cell line, which depicts several alterations of the “kinome”. Using high-resolution nano-LC-LTQ-Orbitrap mass spectrometry associated to phosphopeptide enrichment, we found that several proteins involved in signaling and in transcription, are differentially phosphorylated before and after RA addition. The paradigm of these proteins is the RA receptor α (RARα), which was phosphorylated in MCF7 cells but not in BT474 cells after RA addition. The panel of the RA-regulated genes was also different. Overall our results indicate that RA resistance might correlate with the deregulation of the phosphoproteome with consequences on gene expression. PMID:27362937

  3. Recent advances in enrichment and separation strategies for mass spectrometry-based phosphoproteomics

    PubMed Central

    Yang, Chenxi; Zhong, Xuefei; Li, Lingjun

    2016-01-01

    Due to the significance of protein phosphorylation in various biological processes and signaling events, new analytical techniques for enhanced phosphoproteomics have been rapidly introduced in recent years. The combinatorial use of the phospho-specific enrichment techniques and prefractionation methods prior to MS analysis enables comprehensive profiling of the phosphoproteome and facilitates deciphering the critical roles that phosphorylation plays in signaling pathways in various biological systems. This review places special emphasis on the recent five-year (2009–2013) advances for enrichment and separation techniques that have been utilized for phosphopeptides prior to MS analysis. PMID:24687451

  4. Quantitative label-free phosphoproteomics strategy for multifaceted experimental designs.

    PubMed

    Soderblom, Erik J; Philipp, Melanie; Thompson, J Will; Caron, Marc G; Moseley, M Arthur

    2011-05-15

    Protein phosphorylation is a critical regulator of signaling in nearly all eukaryotic cellular pathways and dysregulated phosphorylation has been implicated in an array of diseases. The majority of MS-based quantitative phosphorylation studies are currently performed from transformed cell lines because of the ability to generate large amounts of starting material with incorporated isotopically labeled amino acids during cell culture. Here we describe a general label-free quantitative phosphoproteomic strategy capable of directly analyzing relatively small amounts of virtually any biological matrix, including human tissue and biological fluids. The strategy utilizes a TiO(2) enrichment protocol in which the selectivity and recovery of phosphopeptides were optimized by assessing a twenty-point condition matrix of binding modifier concentrations and peptide-to-resin capacity ratios. The quantitative reproducibility of the TiO(2) enrichment was determined to be 16% RSD through replicate enrichments of a wild-type Danio rerio (zebrafish) lysate. Measured phosphopeptide fold-changes from alpha-casein spiked into wild-type zebrafish lysate backgrounds were within 5% of the theoretical value. Application to a morpholino induced knock-down of G protein-coupled receptor kinase 5 (GRK5) in zebrafish embryos resulted in the quantitation of 719 phosphorylated peptides corresponding to 449 phosphorylated proteins from 200 μg of zebrafish embryo lysates.

  5. Large-Scale Proteomics and Phosphoproteomics of Urinary Exosomes

    PubMed Central

    Gonzales, Patricia A.; Pisitkun, Trairak; Hoffert, Jason D.; Tchapyjnikov, Dmitry; Star, Robert A.; Kleta, Robert; Wang, Nam Sun; Knepper, Mark A.

    2009-01-01

    Normal human urine contains large numbers of exosomes, which are 40- to 100-nm vesicles that originate as the internal vesicles in multivesicular bodies from every renal epithelial cell type facing the urinary space. Here, we used LC-MS/MS to profile the proteome of human urinary exosomes. Overall, the analysis identified 1132 proteins unambiguously, including 177 that are represented on the Online Mendelian Inheritance in Man database of disease-related genes, suggesting that exosome analysis is a potential approach to discover urinary biomarkers. We extended the proteomic analysis to phosphoproteomic profiling using neutral loss scanning, and this yielded multiple novel phosphorylation sites, including serine-811 in the thiazide-sensitive Na-Cl co-transporter, NCC. To demonstrate the potential use of exosome analysis to identify a genetic renal disease, we carried out immunoblotting of exosomes from urine samples of patients with a clinical diagnosis of Bartter syndrome type I, showing an absence of the sodium-potassium-chloride co-transporter 2, NKCC2. The proteomic data are publicly accessible at http://dir.nhlbi.nih.gov/papers/lkem/exosome/. PMID:19056867

  6. Cross-Species PTM Mapping from Phosphoproteomic Data.

    PubMed

    Chaudhuri, Rima; Yang, Jean Yee Hwa

    2017-01-01

    Protein post-translational modifications (PTMs) are crucial for signal transduction in cells. In order to understand key cell signaling events, identification of functionally important PTMs, which are more likely to be evolutionarily conserved, is necessary. In recent times, high-throughput mass spectrometry (MS) has made quantitative datasets in diverse species readily available, which has led to a growing need for tools to facilitate cross-species comparison of PTM data. Cross-species comparison of PTM sites is difficult since they often lie in structurally disordered protein domains. Current tools that address this can only map known PTMs between species based on previously annotated orthologous phosphosites and do not enable cross-species mapping of newly identified modification sites. Here, we describe an automated web-based tool, PhosphOrtholog, that accurately maps annotated and novel orthologous PTM sites from high-throughput MS-based experimental data obtained from different species without relying on existing PTM databases. Identification of conserved PTMs across species from large-scale experimental data increases our knowledgebase of evolutionarily conserved and functional PTM sites that influence most biological processes. In this Chapter, we illustrate with examples how to use PhosphOrtholog to map novel PTM sites from cross-species MS-based phosphoproteomics data.

  7. Quantitative Phosphoproteomic Analysis Reveals a Role for Serine and Threonine Kinases in the Cytoskeletal Reorganization in Early T Cell Receptor Activation in Human Primary T Cells*

    PubMed Central

    Ruperez, Patricia; Gago-Martinez, Ana; Burlingame, A. L.; Oses-Prieto, Juan A.

    2012-01-01

    Protein phosphorylation-dephosphorylation events play a primary role in regulation of almost all aspects of cell function including signal transduction, cell cycle, or apoptosis. Thus far, T cell phosphoproteomics have focused on analysis of phosphotyrosine residues, and little is known about the role of serine/threonine phosphorylation in early activation of the T cell receptor (TCR). Therefore, we performed a quantitative mass spectrometry-based analysis of the global phosphoproteome of human primary T cells in response to 5 min of TCR activation with anti-CD3 antibody. Combining immunoprecipitation with an antiphosphotyrosine antibody, titanium dioxide phosphopeptide enrichment, isobaric tag for the relative and absolute quantitation methodology, and strong cation exchange separation, we were able to identify 2814 phosphopeptides. These unique sites were employed to investigate the site-specific phosphorylation dynamics. Five hundred and seventeen phosphorylation sites showed TCR-responsive changes. We found that upon 5 min of stimulation of the TCR, specific serine and threonine kinase motifs are overrepresented in the set of responsive phosphorylation sites. These phosphorylation events targeted proteins with many different activities and are present in different subcellular locations. Many of these proteins are involved in intracellular signaling cascades related mainly to cytoskeletal reorganization and regulation of small GTPase-mediated signal transduction, probably involved in the formation of the immune synapse. PMID:22499768

  8. Effect of global climate on termites population. Effect of termites population on global climate

    NASA Astrophysics Data System (ADS)

    Sapunov, Valentin

    2010-05-01

    The global climate is under control of factors having both earth and space origin. Global warming took place from XVII century till 1997. Then global cold snap began. This dynamics had effect on global distribution of some animals including termites. Direct human effect on climate is not significant. At the same time man plays role of trigger switching on significant biosphere processes controlling climate. The transformation of marginal lands, development of industry and building, stimulated increase of termite niche and population. Termite role in green house gases production increases too. It may have regular effect on world climate. The dry wood is substrate for metabolism of termites living under symbiosis with bacteria Hypermastigina (Flagellata). The use of dry wood by humanity increased from 18 *108 ton in XVIII to 9*109 to the middle of XX century. Then use of wood decreased because of a new technology development. Hence termite population is controlled by microevolution depending on dry wood and climate dynamics. Producing by them green house gases had reciprocal effect on world climate. It is possible to describe and predict dynamic of termite population using methods of mathematical ecology and analogs with other well studied insects (Colorado potatoes beetle, Chrisomelid beetle Zygogramma and so on). Reclamation of new ecological niche for such insects as termites needs 70 - 75 years. That is delay of population dynamics in relation to dynamics of dry wood production. General principles of population growth were described by G.Gause (1934) and some authors of the end of XX century. This works and analogs with other insects suggest model of termite distribution during XXI century. The extremum of population and its green house gases production would be gotten during 8 - 10 years. Then the number of specimens and sum biological mass would be stabilized and decreased. Termite gas production is not priority for climate regulation, but it has importance as

  9. Effects of three global change drivers on terrestrial C:N:P stoichiometry: a global synthesis.

    PubMed

    Yue, Kai; Fornara, Dario A; Yang, Wanqin; Peng, Yan; Li, Zhijie; Wu, Fuzhong; Peng, Changhui

    2016-11-17

    Over the last few decades, there has been an increasing number of controlled-manipulative experiments to investigate how plants and soils might respond to global change. These experiments typically examined the effects of each of three global change drivers [i.e., nitrogen (N) deposition, warming, and elevated CO2 ] on primary productivity and on the biogeochemistry of carbon (C), N, and phosphorus (P) across different terrestrial ecosystems. Here, we capitalize on this large amount of information by performing a comprehensive meta-analysis (>2000 case studies worldwide) to address how C:N:P stoichiometry of plants, soils, and soil microbial biomass might respond to individual vs. combined effects of the three global change drivers. Our results show that (i) individual effects of N addition and elevated CO2 on C:N:P stoichiometry are stronger than warming, (ii) combined effects of pairs of global change drivers (e.g., N addition + elevated CO2 , warming + elevated CO2 ) on C:N:P stoichiometry were generally weaker than the individual effects of each of these drivers, (iii) additive interactions (i.e., when combined effects are equal to or not significantly different from the sum of individual effects) were more common than synergistic or antagonistic interactions, (iv) C:N:P stoichiometry of soil and soil microbial biomass shows high homeostasis under global change manipulations, and (v) C:N:P responses to global change are strongly affected by ecosystem type, local climate, and experimental conditions. Our study is one of the first to compare individual vs. combined effects of the three global change drivers on terrestrial C:N:P ratios using a large set of data. To further improve our understanding of how ecosystems might respond to future global change, long-term ecosystem-scale studies testing multifactor effects on plants and soils are urgently required across different world regions.

  10. Integration of phosphoproteomic, chemical, and biological strategies for the functional analysis of targeted protein phosphorylation.

    PubMed

    Guo, Mingquan; Huang, Bill X

    2013-02-01

    Reversible phosphorylation, tightly controlled by protein kinases and phosphatases, plays a central role in mediating biological processes, such as protein-protein interactions, subcellular translocation, and activation of cellular enzymes. MS-based phosphoproteomics has now allowed the detection and quantification of tens of thousands of phosphorylation sites from a typical biological sample in a single experiment, which has posed new challenges in functional analysis of each and every phosphorylation site on specific signaling phosphoproteins of interest. In this article, we review recent advances in the functional analysis of targeted phosphorylation carried out by various chemical and biological approaches in combination with the MS-based phosphoproteomics. This review focuses on three types of strategies, including forward functional analysis, defined for the result-driven phosphoproteomics efforts in determining the substrates of a specific protein kinase; reverse functional analysis, defined for tracking the kinase(s) for specific phosphosite(s) derived from the discovery-driven phosphoproteomics efforts; and MS-based analysis on the structure-function relationship of phosphoproteins. It is expected that this review will provide a state-of-the-art overview of functional analysis of site-specific phosphorylation and explore new perspectives and outline future challenges.

  11. Synaptic activity bidirectionally regulates a novel sequence-specific S-Q phosphoproteome in neurons

    PubMed Central

    Siddoway, Benjamin; Hou, Hailong; Yang, Hongtian; Petralia, Ronald; Xia, Houhui

    2013-01-01

    Protein phosphorylation plays a critical role in neuronal transcription, translation, cell viability, and synaptic plasticity. In neurons, phospho-enzymes and specific substrates directly link glutamate release and post-synaptic depolarization to these cellular functions; however, many of these enzymes and their protein substrates remain uncharacterized or unidentified. In this article, we identify a novel, synaptically-driven neuronal phosphoproteome characterized by a specific motif of serine/threonine-glutamine ([S/T]-Q, abbreviated as SQ). These SQ-containing substrates are predominantly localized to dendrites, synapses, the soma; and activation of this SQ phosphoproteome by bicuculline application is induced via calcium influx through L-type calcium channels. On the other hand, acute application of NMDA can inactivate this SQ phosphoproteome. We demonstrate that the SQ motif kinase Ataxia-telangiectasia mutated (ATM) can also localize to dendrites and dendritic spines, in addition to other subcellular compartments, and is activated by bicuculline application. Pharmacology studies indicate that ATM and its sister kinase ATR up-regulate these neuronal SQ substrates. Phosphoproteomics identified over 150 SQ-containing substrates whose phosphorylation is bidirectionally-regulated by synaptic activity. PMID:24117848

  12. Quantitative Proteomic and Phosphoproteomic Analysis of Trypanosoma cruzi Amastigogenesis*

    PubMed Central

    Queiroz, Rayner M. L.; Charneau, Sébastien; Mandacaru, Samuel C.; Schwämmle, Veit; Lima, Beatriz D.; Roepstorff, Peter; Ricart, Carlos A. O.

    2014-01-01

    Chagas disease is a tropical neglected disease endemic in Latin America caused by the protozoan Trypanosoma cruzi. The parasite has four major life stages: epimastigote, metacyclic trypomastigote, bloodstream trypomastigote, and amastigote. The differentiation from infective trypomastigotes into replicative amastigotes, called amastigogenesis, takes place in vivo inside mammalian host cells after a period of incubation in an acidic phagolysosome. This differentiation process can be mimicked in vitro by incubating tissue-culture-derived trypomastigotes in acidic DMEM. Here we used this well-established differentiation protocol to perform a comprehensive quantitative proteomic and phosphoproteomic analysis of T. cruzi amastigogenesis. Samples from fully differentiated forms and two biologically relevant intermediate time points were Lys-C/trypsin digested, iTRAQ-labeled, and multiplexed. Subsequently, phosphopeptides were enriched using a TiO2 matrix. Non-phosphorylated peptides were fractionated via hydrophilic interaction liquid chromatography prior to LC-MS/MS analysis. LC-MS/MS and bioinformatics procedures were used for protein and phosphopeptide quantitation, identification, and phosphorylation site assignment. We were able to identify regulated proteins and pathways involved in coordinating amastigogenesis. We also observed that a significant proportion of the regulated proteins were membrane proteins. Modulated phosphorylation events coordinated by protein kinases and phosphatases that are part of the signaling cascade induced by incubation in acidic medium were also evinced. To our knowledge, this work is the most comprehensive quantitative proteomics study of T. cruzi amastigogenesis, and these data will serve as a trustworthy basis for future studies, and possibly for new potential drug targets. PMID:25225356

  13. Phosphoproteomic Profiling of Selenate-Treated Alzheimer's Disease Model Cells

    PubMed Central

    Wang, Yong; Li, Shuiming; Shen, Liming; Liu, Qiong; Ni, Jiazuan

    2014-01-01

    The reversible phosphorylation of proteins regulates most biological processes, while abnormal phosphorylation is a cause or consequence of many diseases including Alzheimer's disease (AD). One of the hallmarks of AD is the formation of neurofibrillary tangles (NFTs), which is composed of hyperphosphorylated tau proteins. Sodium selenate has been recently found to reduce tau hyperphosphorylation and NFTs formation, and to improve spatial learning and motor performance in AD mice. In the current study, the phosphoproteomics of N2aSW cells treated with selenate were investigated. To avoid missing low-abundance phosphoproteins, both the total proteins of cells and the phosphor-enriched proteins were extracted and subjected to the two-dimensional gel electrophoresis with Pro-Q diamond staining and then LC-MS/MS analysis. A total of 65 proteins were altered in phosphorylation level, of which 39 were up-regulated and 26 were down-regulated. All identified phosphoproteins were bioinformatically annotated according to their physiochemical features, subcellular location, and biological function. Most of these significantly changed phosphoproteins are involved in crucial neural processes such as protesome activity, oxidative stress, cysteine and methionine metabolism, and energy metabolism. Furthermore, decreases were found in homocysteine, phosphor-tau and amyloid β upon selenate treatment. Our results suggest that selenate may intervene in the pathological process of AD by altering the phosphorylation of some key proteins involved in oxidative stress, energy metabolism and protein degradation, thus play important roles in maintaining redox homeostasis, generating ATP, and clearing misfolded proteins and aggregates. The present paper provides some new clues to the mechanism of selenate in AD prevention. PMID:25485856

  14. Estimating human effects on global extinction

    NASA Astrophysics Data System (ADS)

    Wright, D. H.

    1987-12-01

    A quantitative technique for estimating extinctions due to clearing of natural ecosystems is described. Applied on a global scale, the method yields preliminary figures on extinctions of flowering plants, butterflies, land birds and land mammals ranging from 5.4 to 15.3% for the period from the beginning of agriculture until the year 1980. Actual numbers of extinctions of mammals and birds to date are much lower, possibly in part due to a tendency for the technique to overestimate species loss at the global scale. However, delayed extinctions of species whose populations have been reduced but not exterminated by habitat destruction are likely, suggesting that human impacts may be more serious than they currently appear.

  15. Hippocampal phosphoproteomics of F344 rats exposed to 1-bromopropane

    SciTech Connect

    Huang, Zhenlie; Ichihara, Sahoko; Oikawa, Shinji; Chang, Jie; Zhang, Lingyi; Hu, Shijie; Huang, Hanlin; Ichihara, Gaku

    2015-01-15

    1-Bromopropane (1-BP) is neurotoxic in both experimental animals and human. To identify phosphorylated modification on the unrecognized post-translational modifications of proteins and investigate their role in 1-BP-induced neurotoxicity, changes in hippocampal phosphoprotein expression levels were analyzed quantitatively in male F344 rats exposed to 1-BP inhalation at 0, 400, or 1000 ppm for 8 h/day for 1 or 4 weeks. Hippocampal protein extracts were analyzed qualitatively and quantitatively by Pro-Q Diamond gel staining and SYPRO Ruby staining coupled with two-dimensional difference in gel electrophoresis (2D-DIGE), respectively, as well as by matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) to identify phosphoproteins. Changes in selected proteins were further confirmed by Manganese II (Mn{sup 2+})-Phos-tag SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Bax and cytochrome c protein levels were determined by western blotting. Pro-Q Diamond gel staining combined with 2D-DIGE identified 26 phosphoprotein spots (p < 0.05), and MALDI-TOF/MS identified 18 up-regulated proteins and 8 down-regulated proteins. These proteins are involved in the biological process of response to stimuli, metabolic processes, and apoptosis signaling. Changes in the expression of phosphorylated 14-3-3 θ were further confirmed by Mn{sup 2+}-Phos-tag SDS-PAGE. Western blotting showed overexpression of Bax protein in the mitochondria with down-regulation in the cytoplasm, whereas cytochrome c expression was high in the cytoplasm but low in the mitochondria after 1-BP exposure. Our results suggest that the pathogenesis of 1-BP-induced hippocampal damage involves inhibition of antiapoptosis process. Phosphoproteins identified in this study can potentially serve as biomarkers for 1-BP-induced neurotoxicity. - Highlights: • 1-BP modified hippocampal phosphoproteome in rat and 23 altered proteins were identified. • 1-BP changed phosphorylation

  16. Reactive Oxygen Species (ROS)-Activated ATM-Dependent Phosphorylation of Cytoplasmic Substrates Identified by Large-Scale Phosphoproteomics Screen.

    PubMed

    Kozlov, Sergei V; Waardenberg, Ashley J; Engholm-Keller, Kasper; Arthur, Jonathan W; Graham, Mark E; Lavin, Martin

    2016-03-01

    Ataxia-telangiectasia, mutated (ATM) protein plays a central role in phosphorylating a network of proteins in response to DNA damage. These proteins function in signaling pathways designed to maintain the stability of the genome and minimize the risk of disease by controlling cell cycle checkpoints, initiating DNA repair, and regulating gene expression. ATM kinase can be activated by a variety of stimuli, including oxidative stress. Here, we confirmed activation of cytoplasmic ATM by autophosphorylation at multiple sites. Then we employed a global quantitative phosphoproteomics approach to identify cytoplasmic proteins altered in their phosphorylation state in control and ataxia-telangiectasia (A-T) cells in response to oxidative damage. We demonstrated that ATM was activated by oxidative damage in the cytoplasm as well as in the nucleus and identified a total of 9,833 phosphorylation sites, including 6,686 high-confidence sites mapping to 2,536 unique proteins. A total of 62 differentially phosphorylated peptides were identified; of these, 43 were phosphorylated in control but not in A-T cells, and 19 varied in their level of phosphorylation. Motif enrichment analysis of phosphopeptides revealed that consensus ATM serine glutamine sites were overrepresented. When considering phosphorylation events, only observed in control cells (not observed in A-T cells), with predicted ATM sites phosphoSerine/phosphoThreonine glutamine, we narrowed this list to 11 candidate ATM-dependent cytoplasmic proteins. Two of these 11 were previously described as ATM substrates (HMGA1 and UIMCI/RAP80), another five were identified in a whole cell extract phosphoproteomic screens, and the remaining four proteins had not been identified previously in DNA damage response screens. We validated the phosphorylation of three of these proteins (oxidative stress responsive 1 (OSR1), HDGF, and ccdc82) as ATM dependent after H2O2 exposure, and another protein (S100A11) demonstrated ATM

  17. Quantitative Phosphoproteome Analysis of Lysophosphatidic Acid Induced Chemotaxis applying Dual-step ¹⁸O Labeling Coupled with Immobilized Metal-ion Affinity Chromatography

    SciTech Connect

    Ding, Shi-Jian; Wang, Yingchun; Jacobs, Jon M.; Qian, Weijun; Yang, Feng; Tolmachev, Aleksey V.; Du, Xiuxia; Wang, Wei; Moore, Ronald J.; Monroe, Matthew E.; Purvine, Samuel O.; Waters, Katrina M.; Heibeck, Tyler H.; Adkins, Joshua N.; Camp, David G.; Klemke, Richard L.; Smith, Richard D.

    2008-10-01

    Reversible protein phosphorylation is a central cellular regulatory mechanism in modulating protein activity and propagating signals within cellular pathways and networks. Development of more effective methods for the simultaneous identification of phosphorylation sites and quantification of temporal changes in protein phosphorylation could provide important insights into molecular signaling mechanisms in a variety of different cellular processes. Here we present an integrated quantitative phosphoproteomics approach and its applications for comparative analysis of Cos-7 cells in response to lysophosphatidic acid (LPA) gradient stimulation. The approach combines trypsin-catalyzed 16O/18O labeling plus 16O/18O-methanol esterification labeling for quantitation, a macro- Immobilized Metal-ion Affinity Chromatography trap for phosphopeptide enrichment, and a monolithic capillary column with integrated electrospray emitter. LC separation and MS/MS is followed by neutral loss-dependent MS/MS/MS for phosphopeptide identification using a linear ion trap (LTQ)-FT mass spectrometer and complementary searching algorithms for interpreting MS/MS spectra. Protein phosphorylation involved in various signaling pathways of cell migration were identified and quantified, such as mitogen-activated protein kinase 1, dual-specificity mitogen-activated protein kinase kinase 2, and dual-specificity tyrosine-phosphorylation regulated kinase 1b, and a number of Rho GTPase-activating proteins. These results demonstrate the efficiency of this quantitative phosphoproteomics approach and its application for rapid discovery of phosphorylation events associated with gradient sensing and cell chemotaxis.

  18. The effect of global warming on infectious diseases.

    PubMed

    Kurane, Ichiro

    2010-12-01

    Global warming has various effects on human health. The main indirect effects are on infectious diseases. Although the effects on infectious diseases will be detected worldwide, the degree and types of the effect are different, depending on the location of the respective countries and socioeconomical situations. Among infectious diseases, water- and foodborne infectious diseases and vector-borne infectious diseases are two main categories that are forecasted to be most affected. The effect on vector-borne infectious diseases such as malaria and dengue fever is mainly because of the expansion of the infested areas of vector mosquitoes and increase in the number and feeding activity of infected mosquitoes. There will be increase in the number of cases with water- and foodborne diarrhoeal diseases. Even with the strongest mitigation procedures, global warming cannot be avoided for decades. Therefore, implementation of adaptation measures to the effect of global warming is the most practical action we can take. It is generally accepted that the impacts of global warming on infectious diseases have not been apparent at this point yet in East Asia. However, these impacts will appear in one form or another if global warming continues to progress in future. Further research on the impacts of global warming on infectious diseases and on future prospects should be conducted.

  19. The effects of variable biome distribution on global climate

    SciTech Connect

    Noever, D.A.; Brittain, A.; Matsos, H.C.; Baskaran, S.; Obenhuber, D.

    1996-12-31

    In projecting climatic adjustments to anthropogenically elevated atmospheric carbon dioxide, most global climate models fix biome distribution to current geographic conditions. The authors develop a model that examines the albedo-related effects of biome distribution on global temperature. The model was tested on historical biome changes since 1860 and the results fit both the observed trend and order of magnitude change in global temperature. Once backtested in this way on historical data, the model is then used to generate an optimized future biome distribution which minimizes projected greenhouse effects on global temperature. Because of the complexity of this combinatorial search an artificial intelligence method, the genetic algorithm, was employed. The genetic algorithm assigns various biome distributions to the planet, then adjusts their percentage area and albedo effects to regulate or moderate temperature changes.

  20. Global relativistic effects in chaotic scattering

    NASA Astrophysics Data System (ADS)

    Bernal, Juan D.; Seoane, Jesús M.; Sanjuán, Miguel A. F.

    2017-03-01

    The phenomenon of chaotic scattering is very relevant in different fields of science and engineering. It has been mainly studied in the context of Newtonian mechanics, where the velocities of the particles are low in comparison with the speed of light. Here, we analyze global properties such as the escape time distribution and the decay law of the Hénon-Heiles system in the context of special relativity. Our results show that the average escape time decreases with increasing values of the relativistic factor β . As a matter of fact, we have found a crossover point for which the KAM islands in the phase space are destroyed when β ≃0.4 . On the other hand, the study of the survival probability of particles in the scattering region shows an algebraic decay for values of β ≤0.4 , and this law becomes exponential for β >0.4 . Surprisingly, a scaling law between the exponent of the decay law and the β factor is uncovered where a quadratic fitting between them is found. The results of our numerical simulations agree faithfully with our qualitative arguments. We expect this work to be useful for a better understanding of both chaotic and relativistic systems.

  1. A Simple Model of Global Aerosol Indirect Effects

    SciTech Connect

    Ghan, Steven J.; Smith, Steven J.; Wang, Minghuai; Zhang, Kai; Pringle, K. J.; Carslaw, K. S.; Pierce, Jeffrey; Bauer, Susanne E.; Adams, P. J.

    2013-06-28

    Most estimates of the global mean indirect effect of anthropogenic aerosol on the Earth’s energy balance are from simulations by global models of the aerosol lifecycle coupled with global models of clouds and the hydrologic cycle. Extremely simple models have been developed for integrated assessment models, but lack the flexibility to distinguish between primary and secondary sources of aerosol. Here a simple but more physically-based model expresses the aerosol indirect effect using analytic representations of droplet nucleation, cloud and aerosol vertical structure, and horizontal variability in cloud water and aerosol concentration. Although the simple model is able to produce estimates of aerosol indirect effects that are comparable to those from some global aerosol models using the same global mean aerosol properties, the estimates are found to be sensitive to several uncertain parameters, including the preindustrial cloud condensation nuclei concentration, primary and secondary anthropogenic emissions, the size of the primary particles, the fraction of the secondary anthropogenic emissions that accumulates on the coarse mode, the fraction of the secondary mass that forms new particles, and the sensitivity of liquid water path to droplet number concentration. Aerosol indirect effects are surprisingly linear in emissions. This simple model provides a much stronger physical basis for representing aerosol indirect effects than previous representations in integrated assessment models designed to quickly explore the parameter space of emissions-climate interactions. The model also produces estimates that depend on parameter values in ways that are consistent with results from detailed global aerosol-climate simulation models.

  2. Phosphoproteomic Analysis of Cell-Based Resistance to BRAF Inhibitor Therapy in Melanoma

    PubMed Central

    Parker, Robert; Vella, Laura J.; Xavier, Dylan; Amirkhani, Ardeshir; Parker, Jimmy; Cebon, Jonathan; Molloy, Mark P.

    2015-01-01

    The treatment of melanoma by targeted inhibition of the mutated kinase BRAF with small molecules only temporarily suppresses metastatic disease. In the face of chemical inhibition tumor plasticity, both innate and adaptive, promotes survival through the biochemical and genetic reconfiguration of cellular pathways that can engage proliferative and migratory systems. To investigate this process, high-resolution mass spectrometry was used to characterize the phosphoproteome of this transition in vitro. A simple and accurate, label-free quantitative method was used to localize and quantitate thousands of phosphorylation events. We also correlated changes in the phosphoproteome with the proteome to more accurately determine changes in the activity of regulatory kinases determined by kinase landscape profiling. The abundance of phosphopeptides with sites that function in cytoskeletal regulation, GTP/GDP exchange, protein kinase C, IGF signaling, and melanosome maturation were highly divergent after transition to a drug resistant phenotype. PMID:26029660

  3. Dataset of the Botrytis cinerea phosphoproteome induced by different plant-based elicitors.

    PubMed

    Liñeiro, Eva; Chiva, Cristina; Cantoral, Jesús M; Sabido, Eduard; Fernández-Acero, Francisco Javier

    2016-06-01

    Phosphorylation is one of the main post-translational modification (PTM) involved in signaling network in the ascomycete Botrytis cinerea, one of the most relevant phytopathogenic fungus. The data presented in this article provided a differential mass spectrometry-based analysis of the phosphoproteome of B. cinerea under two different phenotypical conditions induced by the use of two different elicitors: glucose and deproteinized Tomate Cell Walls (TCW). A total 1138 and 733 phosphoproteins were identified for glucose and TCW culture conditions respectively. Raw data are deposited at the ProteomeXchange Consortium via the PRIDE partner repository with the data set identifier (PRIDE: http://www.ebi.ac.uk/pride/archive/projects/PXD003099). Further interpretation and discussion of these data are provided in our research article entitled "Phosphoproteome analysis of B.cinerea in response to different plant-based elicitors" (Liñeiro et al., 2016) [1].

  4. StageTip-based HAMMOC, an efficient and inexpensive phosphopeptide enrichment method for plant shotgun phosphoproteomics.

    PubMed

    Nakagami, Hirofumi

    2014-01-01

    Phosphopeptide enrichment is the most critical step for successful LC-MS/MS-based shotgun phosphoproteomics. Recent technological improvements have made selective phosphopeptide enrichment from non-fractionated whole cell lysate digests with a single-step procedure possible. Here, a handy protocol is described for phosphopeptide enrichment from plant materials using hydroxy acid-modified metal oxide chromatography (HAMMMOC) with a stop-and-go-extraction tip (StageTip).

  5. The proteome and phosphoproteome of maize pollen uncovers fertility candidate proteins.

    PubMed

    Chao, Qing; Gao, Zhi-Fang; Wang, Yue-Feng; Li, Zhe; Huang, Xia-He; Wang, Ying-Chun; Mei, Ying-Chang; Zhao, Biligen-Gaowa; Li, Liang; Jiang, Yu-Bo; Wang, Bai-Chen

    2016-06-01

    Maize is unique since it is both monoecious and diclinous (separate male and female flowers on the same plant). We investigated the proteome and phosphoproteome of maize pollen containing modified proteins and here we provide a comprehensive pollen proteome and phosphoproteome which contain 100,990 peptides from 6750 proteins and 5292 phosphorylated sites corresponding to 2257 maize phosphoproteins, respectively. Interestingly, among the total 27 overrepresented phosphosite motifs we identified here, 11 were novel motifs, which suggested different modification mechanisms in plants compared to those of animals. Enrichment analysis of pollen phosphoproteins showed that pathways including DNA synthesis/chromatin structure, regulation of RNA transcription, protein modification, cell organization, signal transduction, cell cycle, vesicle transport, transport of ions and metabolisms, which were involved in pollen development, the following germination and pollen tube growth, were regulated by phosphorylation. In this study, we also found 430 kinases and 105 phosphatases in the maize pollen phosphoproteome, among which calcium dependent protein kinases (CDPKs), leucine rich repeat kinase, SNF1 related protein kinases and MAPK family proteins were heavily enriched and further analyzed. From our research, we also uncovered hundreds of male sterility-associated proteins and phosphoproteins that might influence maize productivity and serve as targets for hybrid maize seed production. At last, a putative complex signaling pathway involving CDPKs, MAPKs, ubiquitin ligases and multiple fertility proteins was constructed. Overall, our data provides new insight for further investigation of protein phosphorylation status in mature maize pollen and construction of maize male sterile mutants in the future.

  6. Application of Phosphoproteomics to Find Targets of Casein Kinase 1 in the Flagellum of Chlamydomonas

    PubMed Central

    Boesger, Jens; Wagner, Volker; Weisheit, Wolfram; Mittag, Maria

    2012-01-01

    The green biflagellate alga Chlamydomonas reinhardtii serves as model for studying structural and functional features of flagella. The axoneme of C. reinhardtii anchors a network of kinases and phosphatases that control motility. One of them, Casein Kinase 1 (CK1), is known to phosphorylate the Inner Dynein Arm I1 Intermediate Chain 138 (IC138), thereby regulating motility. CK1 is also involved in regulating the circadian rhythm of phototaxis and is relevant for the formation of flagella. By a comparative phosphoproteome approach, we determined phosphoproteins in the flagellum that are targets of CK1. Thereby, we applied the specific CK1 inhibitor CKI-7 that causes significant changes in the flagellum phosphoproteome and reduces the swimming velocity of the cells. In the CKI-7-treated cells, 14 phosphoproteins were missing compared to the phosphoproteome of untreated cells, including IC138, and four additional phosphoproteins had a reduced number of phosphorylation sites. Notably, inhibition of CK1 causes also novel phosphorylation events, indicating that it is part of a kinase network. Among them, Glycogen Synthase Kinase 3 is of special interest, because it is involved in the phosphorylation of key clock components in flies and mammals and in parallel plays an important role in the regulation of assembly in the flagellum. PMID:23316220

  7. Application of phosphoproteomics to find targets of casein kinase 1 in the flagellum of chlamydomonas.

    PubMed

    Boesger, Jens; Wagner, Volker; Weisheit, Wolfram; Mittag, Maria

    2012-01-01

    The green biflagellate alga Chlamydomonas reinhardtii serves as model for studying structural and functional features of flagella. The axoneme of C. reinhardtii anchors a network of kinases and phosphatases that control motility. One of them, Casein Kinase 1 (CK1), is known to phosphorylate the Inner Dynein Arm I1 Intermediate Chain 138 (IC138), thereby regulating motility. CK1 is also involved in regulating the circadian rhythm of phototaxis and is relevant for the formation of flagella. By a comparative phosphoproteome approach, we determined phosphoproteins in the flagellum that are targets of CK1. Thereby, we applied the specific CK1 inhibitor CKI-7 that causes significant changes in the flagellum phosphoproteome and reduces the swimming velocity of the cells. In the CKI-7-treated cells, 14 phosphoproteins were missing compared to the phosphoproteome of untreated cells, including IC138, and four additional phosphoproteins had a reduced number of phosphorylation sites. Notably, inhibition of CK1 causes also novel phosphorylation events, indicating that it is part of a kinase network. Among them, Glycogen Synthase Kinase 3 is of special interest, because it is involved in the phosphorylation of key clock components in flies and mammals and in parallel plays an important role in the regulation of assembly in the flagellum.

  8. Phosphoproteome Analysis Links Protein Phosphorylation to Cellular Remodeling and Metabolic Adaptation during Magnaporthe oryzae Appressorium Development.

    PubMed

    Franck, William L; Gokce, Emine; Randall, Shan M; Oh, Yeonyee; Eyre, Alex; Muddiman, David C; Dean, Ralph A

    2015-06-05

    The rice pathogen, Magnaporthe oryzae, undergoes a complex developmental process leading to formation of an appressorium prior to plant infection. In an effort to better understand phosphoregulation during appressorium development, a mass spectrometry based phosphoproteomics study was undertaken. A total of 2924 class I phosphosites were identified from 1514 phosphoproteins from mycelia, conidia, germlings, and appressoria of the wild type and a protein kinase A (PKA) mutant. Phosphoregulation during appressorium development was observed for 448 phosphosites on 320 phosphoproteins. In addition, a set of candidate PKA targets was identified encompassing 253 phosphosites on 227 phosphoproteins. Network analysis incorporating regulation from transcriptomic, proteomic, and phosphoproteomic data revealed new insights into the regulation of the metabolism of conidial storage reserves and phospholipids, autophagy, actin dynamics, and cell wall metabolism during appressorium formation. In particular, protein phosphorylation appears to play a central role in the regulation of autophagic recycling and actin dynamics during appressorium formation. Changes in phosphorylation were observed in multiple components of the cell wall integrity pathway providing evidence that this pathway is highly active during appressorium development. Several transcription factors were phosphoregulated during appressorium formation including the bHLH domain transcription factor MGG_05709. Functional analysis of MGG_05709 provided further evidence for the role of protein phosphorylation in regulation of glycerol metabolism and the metabolic reprogramming characteristic of appressorium formation. The data presented here represent a comprehensive investigation of the M. oryzae phosphoproteome and provide key insights on the role of protein phosphorylation during infection-related development.

  9. Phosphoproteomic Analysis of Platelets Activated by Pro-Thrombotic Oxidized Phospholipids and Thrombin

    PubMed Central

    Zimman, Alejandro; Titz, Bjoern; Komisopoulou, Evangelia; Biswas, Sudipta; Graeber, Thomas G.; Podrez, Eugene A.

    2014-01-01

    Specific oxidized phospholipids (oxPCCD36) promote platelet hyper-reactivity and thrombosis in hyperlipidemia via the scavenger receptor CD36, however the signaling pathway(s) induced in platelets by oxPCCD36 are not well defined. We have employed mass spectrometry-based tyrosine, serine, and threonine phosphoproteomics for the unbiased analysis of platelet signaling pathways induced by oxPCCD36 as well as by the strong physiological agonist thrombin. oxPCCD36 and thrombin induced differential phosphorylation of 115 proteins (162 phosphorylation sites) and 181 proteins (334 phosphorylation sites) respectively. Most of the phosphoproteome changes induced by either agonist have never been reported in platelets; thus they provide candidates in the study of platelet signaling. Bioinformatic analyses of protein phosphorylation dependent responses were used to categorize preferential motifs for (de)phosphorylation, predict pathways and kinase activity, and construct a phosphoproteome network regulating integrin activation. A putative signaling pathway involving Src-family kinases, SYK, and PLCγ2 was identified in platelets activated by oxPCCD36. Subsequent ex vivo studies in human platelets demonstrated that this pathway is downstream of the scavenger receptor CD36 and is critical for platelet activation by oxPCCD36. Our results provide multiple insights into the mechanism of platelet activation and specifically in platelet regulation by oxPCCD36. PMID:24400094

  10. Global analogue of the Aharonov-Bohm effect

    SciTech Connect

    Navin, R.L.

    1993-12-31

    This thesis deals with a global analogue of the Aharonov-Bohm effect previously pointed out by other authors. The effect was not well understood because the pure Aharonov-Bohm cross section was thought to be merely an approximate low energy limit. This thesis provides a detailed analysis and reveals that in the particular model considered, there is an exact Aharonov-Bohm cross section over the energy range that a mass splitting occurs. At energies slightly above the mass splitting, the effect has completely disappeared and there is effectively no scattering at large distances. This is a curious observation as it was previously thought that a global theory would not act exactly like a local one over an extended range of energies. It begs the heretical speculation that experimentally observed forces modelled with Lagrangians possessing local symmetries may have an underlying global theory.

  11. Phosphoproteomic Analysis of Protein Kinase C Signaling in Saccharomyces cerevisiae Reveals Slt2 Mitogen-activated Protein Kinase (MAPK)-dependent Phosphorylation of Eisosome Core Components*

    PubMed Central

    Mascaraque, Victoria; Hernáez, María Luisa; Jiménez-Sánchez, María; Hansen, Rasmus; Gil, Concha; Martín, Humberto; Cid, Víctor J.; Molina, María

    2013-01-01

    The cell wall integrity (CWI) pathway of the model organism Saccharomyces cerevisiae has been thoroughly studied as a paradigm of the mitogen-activated protein kinase (MAPK) pathway. It consists of a classic MAPK module comprising the Bck1 MAPK kinase kinase, two redundant MAPK kinases (Mkk1 and Mkk2), and the Slt2 MAPK. This module is activated under a variety of stimuli related to cell wall homeostasis by Pkc1, the only member of the protein kinase C family in budding yeast. Quantitative phosphoproteomics based on stable isotope labeling of amino acids in cell culture is a powerful tool for globally studying protein phosphorylation. Here we report an analysis of the yeast phosphoproteome upon overexpression of a PKC1 hyperactive allele that specifically activates CWI MAPK signaling in the absence of external stimuli. We found 82 phosphopeptides originating from 43 proteins that showed enhanced phosphorylation in these conditions. The MAPK S/T-P target motif was significantly overrepresented in these phosphopeptides. Hyperphosphorylated proteins provide putative novel targets of the Pkc1–cell wall integrity pathway involved in diverse functions such as the control of gene expression, protein synthesis, cytoskeleton maintenance, DNA repair, and metabolism. Remarkably, five components of the plasma-membrane-associated protein complex known as eisosomes were found among the up-regulated proteins. We show here that Pkc1-induced phosphorylation of the eisosome core components Pil1 and Lsp1 was not exerted directly by Pkc1, but involved signaling through the Slt2 MAPK module. PMID:23221999

  12. The Effects of Global Change upon United States Air Quality

    EPA Science Inventory

    To understand more fully the effects of global changes on ambient concentrations of ozone and particulate matter with aerodynamic diameter smaller than 2.5 μm (PM2.5) in the US, we conducted a comprehensive modeling effort to evaluate explicitly the effects of change...

  13. Global University Rankings--Impacts and Unintended Side Effects

    ERIC Educational Resources Information Center

    Kehm, Barbara M.

    2014-01-01

    In this article, global and other university rankings are critically assessed with regard to their unintended side effects and their impacts on the European and national landscape of universities, as well as on individual institutions. An emphasis is put on the effects of ranking logics rather than on criticising their methodology. Nevertheless,…

  14. Energetic particle effects on global magnetohydrodynamic modes

    NASA Astrophysics Data System (ADS)

    Cheng, C. Z.

    1990-06-01

    The effects of energetic particles on magnetohydrodynamic (MHD) type modes are studied using analytical theories and the nonvariational kinetic-MHD stability code (nova-k) [Workshop on Theory of Fusion Plasmas, (Societa Italiana di Fisica, Bologna, 1987), p. 185]. In particular, the problems of (1) the stabilization of ideal MHD internal kink modes and the excitation of resonant ``fishbone'' internal modes and (2) the alpha particle destabilization of toroidicity-induced Alfvén eigenmodes (TAE) via transit resonances are addressed. Analytical theories are presented to help explain the nova-k results. For energetic trapped particles generated by neutral beam injection or ion cyclotron resonant heating, a stability window for the n=1 internal kink mode in the hot particle beta space exists even in the absence of core ion finite Larmor radius effect. On the other hand, the trapped alpha particles are found to resonantly excite instability of the n=1 internal mode and can lower the critical beta threshold. The circulating alpha particles can strongly destabilize TAE modes via inverse Landau damping associated with the spatial gradient of the alpha-particle pressure.

  15. Energetic particle effects on global magnetohydrodynamic modes

    SciTech Connect

    Cheng, C.Z. )

    1990-06-01

    The effects of energetic particles on magnetohydrodynamic (MHD) type modes are studied using analytical theories and the nonvariational kinetic-MHD stability code (NOVA-K) ({ital Workshop} {ital on} {ital Theory} {ital of} {ital Fusion} {ital Plasmas}, (Societa Italiana di Fisica, Bologna, 1987), p. 185). In particular, the problems of (1) the stabilization of ideal MHD internal kink modes and the excitation of resonant fishbone'' internal modes and (2) the alpha particle destabilization of toroidicity-induced Alfven eigenmodes (TAE) via transit resonances are addressed. Analytical theories are presented to help explain the NOVAresults. For energetic trapped particles generated by neutral beam injection or ion cyclotron resonant heating, a stability window for the {ital n}=1 internal kink mode in the hot particle beta space exists even in the absence of core ion finite Larmor radius effect. On the other hand, the trapped alpha particles are found to resonantly excite instability of the {ital n}=1 internal mode and can lower the critical beta threshold. The circulating alpha particles can strongly destabilize TAE modes via inverse Landau damping associated with the spatial gradient of the alpha-particle pressure.

  16. A Simple Model of Global Aerosol Indirect Effects

    NASA Technical Reports Server (NTRS)

    Ghan, Steven J.; Smith, Steven J.; Wang, Minghuai; Zhang, Kai; Pringle, Kirsty; Carslaw, Kenneth; Pierce, Jeffrey; Bauer, Susanne; Adams, Peter

    2013-01-01

    Most estimates of the global mean indirect effect of anthropogenic aerosol on the Earth's energy balance are from simulations by global models of the aerosol lifecycle coupled with global models of clouds and the hydrologic cycle. Extremely simple models have been developed for integrated assessment models, but lack the flexibility to distinguish between primary and secondary sources of aerosol. Here a simple but more physically based model expresses the aerosol indirect effect (AIE) using analytic representations of cloud and aerosol distributions and processes. Although the simple model is able to produce estimates of AIEs that are comparable to those from some global aerosol models using the same global mean aerosol properties, the estimates by the simple model are sensitive to preindustrial cloud condensation nuclei concentration, preindustrial accumulation mode radius, width of the accumulation mode, size of primary particles, cloud thickness, primary and secondary anthropogenic emissions, the fraction of the secondary anthropogenic emissions that accumulates on the coarse mode, the fraction of the secondary mass that forms new particles, and the sensitivity of liquid water path to droplet number concentration. Estimates of present-day AIEs as low as 5 W/sq m and as high as 0.3 W/sq m are obtained for plausible sets of parameter values. Estimates are surprisingly linear in emissions. The estimates depend on parameter values in ways that are consistent with results from detailed global aerosol-climate simulation models, which adds to understanding of the dependence on AIE uncertainty on uncertainty in parameter values.

  17. Global non-linear effect of temperature on economic production

    NASA Astrophysics Data System (ADS)

    Burke, Marshall; Hsiang, Solomon M.; Miguel, Edward

    2015-11-01

    Growing evidence demonstrates that climatic conditions can have a profound impact on the functioning of modern human societies, but effects on economic activity appear inconsistent. Fundamental productive elements of modern economies, such as workers and crops, exhibit highly non-linear responses to local temperature even in wealthy countries. In contrast, aggregate macroeconomic productivity of entire wealthy countries is reported not to respond to temperature, while poor countries respond only linearly. Resolving this conflict between micro and macro observations is critical to understanding the role of wealth in coupled human-natural systems and to anticipating the global impact of climate change. Here we unify these seemingly contradictory results by accounting for non-linearity at the macro scale. We show that overall economic productivity is non-linear in temperature for all countries, with productivity peaking at an annual average temperature of 13 °C and declining strongly at higher temperatures. The relationship is globally generalizable, unchanged since 1960, and apparent for agricultural and non-agricultural activity in both rich and poor countries. These results provide the first evidence that economic activity in all regions is coupled to the global climate and establish a new empirical foundation for modelling economic loss in response to climate change, with important implications. If future adaptation mimics past adaptation, unmitigated warming is expected to reshape the global economy by reducing average global incomes roughly 23% by 2100 and widening global income inequality, relative to scenarios without climate change. In contrast to prior estimates, expected global losses are approximately linear in global mean temperature, with median losses many times larger than leading models indicate.

  18. Global non-linear effect of temperature on economic production.

    PubMed

    Burke, Marshall; Hsiang, Solomon M; Miguel, Edward

    2015-11-12

    Growing evidence demonstrates that climatic conditions can have a profound impact on the functioning of modern human societies, but effects on economic activity appear inconsistent. Fundamental productive elements of modern economies, such as workers and crops, exhibit highly non-linear responses to local temperature even in wealthy countries. In contrast, aggregate macroeconomic productivity of entire wealthy countries is reported not to respond to temperature, while poor countries respond only linearly. Resolving this conflict between micro and macro observations is critical to understanding the role of wealth in coupled human-natural systems and to anticipating the global impact of climate change. Here we unify these seemingly contradictory results by accounting for non-linearity at the macro scale. We show that overall economic productivity is non-linear in temperature for all countries, with productivity peaking at an annual average temperature of 13 °C and declining strongly at higher temperatures. The relationship is globally generalizable, unchanged since 1960, and apparent for agricultural and non-agricultural activity in both rich and poor countries. These results provide the first evidence that economic activity in all regions is coupled to the global climate and establish a new empirical foundation for modelling economic loss in response to climate change, with important implications. If future adaptation mimics past adaptation, unmitigated warming is expected to reshape the global economy by reducing average global incomes roughly 23% by 2100 and widening global income inequality, relative to scenarios without climate change. In contrast to prior estimates, expected global losses are approximately linear in global mean temperature, with median losses many times larger than leading models indicate.

  19. Effects of Globalization on Careers. Myths and Realities.

    ERIC Educational Resources Information Center

    Brown, Bettina Lankard

    Is the positive potential of globalization being realized? Are transnational careers becoming a reality? What effects are uncertainty and continuous change having on career development? There is evidence that a growing number of companies are exporting both blue- and white-collar jobs overseas, although some contend that it is new technologies…

  20. Effects of Information Capitalism and Globalization on Teaching and Learning

    ERIC Educational Resources Information Center

    Adeoye, Blessing F., Ed.; Tomei, Lawrence, Ed.

    2014-01-01

    As computers and Internet connections become widely available in schools and classrooms, it is critical to examine cross-cultural issues in the utilization of information and communication technologies. "Effects of Information Capitalism and Globalization on Teaching and Learning" examines issues concerning emerging multimedia…

  1. Comparative Phosphoproteomics Analysis of VEGF and Angiopoietin-1 Signaling Reveals ZO-1 as a Critical Regulator of Endothelial Cell Proliferation.

    PubMed

    Chidiac, Rony; Zhang, Ying; Tessier, Sylvain; Faubert, Denis; Delisle, Chantal; Gratton, Jean-Philippe

    2016-05-01

    VEGF and angiopoietin-1 (Ang-1) are essential factors to promote angiogenesis through regulation of a plethora of signaling events in endothelial cells (ECs). Although pathways activated by VEGF and Ang-1 are being established, the unique signaling nodes conferring specific responses to each factor remain poorly defined. Thus, we conducted a large-scale comparative phosphoproteomic analysis of signaling pathways activated by VEGF and Ang-1 in ECs using mass spectrometry. Analysis of VEGF and Ang-1 networks of regulated phosphoproteins revealed that the junctional proteins ZO-1, ZO-2, JUP and p120-catenin are part of a cluster of proteins phosphorylated following VEGF stimulation that are linked to MAPK1 activation. Down-regulation of these junctional proteins led to MAPK1 activation and accordingly, increased proliferation of ECs stimulated specifically by VEGF, but not by Ang-1. We identified ZO-1 as the central regulator of this effect and showed that modulation of cellular ZO-1 levels is necessary for EC proliferation during vascular development of the mouse postnatal retina. In conclusion, we uncovered ZO-1 as part of a signaling node activated by VEGF, but not Ang-1, that specifically modulates EC proliferation during angiogenesis.

  2. Phosphoproteomic profiling of tumor tissues identifies HSP27 Ser82 phosphorylation as a robust marker of early ischemia

    PubMed Central

    Zahari, Muhammad Saddiq; Wu, Xinyan; Pinto, Sneha M.; Nirujogi, Raja Sekhar; Kim, Min-Sik; Fetics, Barry; Philip, Mathew; Barnes, Sheri R.; Godfrey, Beverly; Gabrielson, Edward; Nevo, Erez; Pandey, Akhilesh

    2015-01-01

    Delays between tissue collection and tissue fixation result in ischemia and ischemia-associated changes in protein phosphorylation levels, which can misguide the examination of signaling pathway status. To identify a biomarker that serves as a reliable indicator of ischemic changes that tumor tissues undergo, we subjected harvested xenograft tumors to room temperature for 0, 2, 10 and 30 minutes before freezing in liquid nitrogen. Multiplex TMT-labeling was conducted to achieve precise quantitation, followed by TiO2 phosphopeptide enrichment and high resolution mass spectrometry profiling. LC-MS/MS analyses revealed phosphorylation level changes of a number of phosphosites in the ischemic samples. The phosphorylation of one of these sites, S82 of the heat shock protein 27 kDa (HSP27), was especially abundant and consistently upregulated in tissues with delays in freezing as short as 2 minutes. In order to eliminate effects of ischemia, we employed a novel cryogenic biopsy device which begins freezing tissues in situ before they are excised. Using this device, we showed that the upregulation of phosphorylation of S82 on HSP27 was abrogated. We thus demonstrate that our cryogenic biopsy device can eliminate ischemia-induced phosphoproteome alterations, and measurements of S82 on HSP27 can be used as a robust marker of ischemia in tissues. PMID:26329039

  3. Comprehensive effective and efficient global public health surveillance.

    PubMed

    McNabb, Scott J N

    2010-12-03

    At a crossroads, global public health surveillance exists in a fragmented state. Slow to detect, register, confirm, and analyze cases of public health significance, provide feedback, and communicate timely and useful information to stakeholders, global surveillance is neither maximally effective nor optimally efficient. Stakeholders lack a globa surveillance consensus policy and strategy; officials face inadequate training and scarce resources.Three movements now set the stage for transformation of surveillance: 1) adoption by Member States of the World Health Organization (WHO) of the revised International Health Regulations (IHR[2005]); 2) maturation of information sciences and the penetration of information technologies to distal parts of the globe; and 3) consensus that the security and public health communities have overlapping interests and a mutual benefit in supporting public health functions. For these to enhance surveillance competencies, eight prerequisites should be in place: politics, policies, priorities, perspectives, procedures, practices, preparation, and payers.To achieve comprehensive, global surveillance, disparities in technical, logistic, governance, and financial capacities must be addressed. Challenges to closing these gaps include the lack of trust and transparency; perceived benefit at various levels; global governance to address data power and control; and specified financial support from globa partners.We propose an end-state perspective for comprehensive, effective and efficient global, multiple-hazard public health surveillance and describe a way forward to achieve it. This end-state is universal, global access to interoperable public health information when it's needed, where it's needed. This vision mitigates the tension between two fundamental human rights: first, the right to privacy, confidentiality, and security of personal health information combined with the right of sovereign, national entities to the ownership and stewardship

  4. The effects of missing data on global ozone estimates

    NASA Technical Reports Server (NTRS)

    Drewry, J. W.; Robbins, J. L.

    1981-01-01

    The effects of missing data and model truncation on estimates of the global mean, zonal distribution, and global distribution of ozone are considered. It is shown that missing data can introduce biased estimates with errors that are not accounted for in the accuracy calculations of empirical modeling techniques. Data-fill techniques are introduced and used for evaluating error bounds and constraining the estimate in areas of sparse and missing data. It is found that the accuracy of the global mean estimate is more dependent on data distribution than model size. Zonal features can be accurately described by 7th order models over regions of adequate data distribution. Data variance accounted for by higher order models appears to represent climatological features of columnar ozone rather than pure error. Data-fill techniques can prevent artificial feature generation in regions of sparse or missing data without degrading high order estimates over dense data regions.

  5. An Effective Model for Improving Global Health Nursing Competence

    PubMed Central

    Kang, Sun-Joo

    2016-01-01

    This paper proposed an effective model for improving global health nursing competence among undergraduate students. A descriptive case study was conducted by evaluation of four implemented programs by the author. All programs were conducted with students majoring in nursing and healthcare, where the researcher was a program director, professor, or facilitator. These programs were analyzed in terms of students’ needs assessment, program design, and implementation and evaluation factors. The concept and composition of global nursing competence, identified within previous studies, were deemed appropriate in all of our programs. Program composition varied from curricular to extracurricular domains. During the implementation phase, some of the programs included non-Korean students to improve cultural diversity and overcome language barriers. Qualitative and quantitative surveys were conducted to assess program efficacy. Data triangulation from students’ reflective journals was examined. Additionally, students’ awareness regarding changes within global health nursing, improved critical thinking, cultural understanding, and global leadership skills were investigated pre- and post-program implementation. The importance of identifying students’ needs regarding global nursing competence when developing appropriate curricula is discussed. PMID:27679793

  6. An Effective Model for Improving Global Health Nursing Competence.

    PubMed

    Kang, Sun-Joo

    2016-01-01

    This paper proposed an effective model for improving global health nursing competence among undergraduate students. A descriptive case study was conducted by evaluation of four implemented programs by the author. All programs were conducted with students majoring in nursing and healthcare, where the researcher was a program director, professor, or facilitator. These programs were analyzed in terms of students' needs assessment, program design, and implementation and evaluation factors. The concept and composition of global nursing competence, identified within previous studies, were deemed appropriate in all of our programs. Program composition varied from curricular to extracurricular domains. During the implementation phase, some of the programs included non-Korean students to improve cultural diversity and overcome language barriers. Qualitative and quantitative surveys were conducted to assess program efficacy. Data triangulation from students' reflective journals was examined. Additionally, students' awareness regarding changes within global health nursing, improved critical thinking, cultural understanding, and global leadership skills were investigated pre- and post-program implementation. The importance of identifying students' needs regarding global nursing competence when developing appropriate curricula is discussed.

  7. The global land Cryosphere Radiative Effect during the MODIS era

    NASA Astrophysics Data System (ADS)

    Singh, D.; Flanner, M. G.; Perket, J.

    2015-07-01

    Cryosphere Radiative Effect (CrRE) is the instantaneous influence of snow- and ice-cover on Earth's top of atmosphere (TOA) solar energy budget. Here, we apply measurements from the Moderate Resolution Imaging Spectrometer (MODIS), combined with microwave retrievals of snow presence and radiative kernels produced from 4 different models, to derive CrRE over global land during 2001-2013. We estimate global annual mean land CrRE during this period of -2.6 W m-2, with variations from -2.2 to -3.0 W m-2 resulting from use of different kernels, and variations of -2.4 to -2.6 W m-2 resulting from different algorithmic determinations of snow presence and surface albedo. Slightly more than half of the global land CrRE originates from perennial snow on Antarctica, whereas the majority of the Northern Hemisphere effect originates from seasonal snow. Consequently, the Northern Hemisphere land CrRE peaks at -6.0 W m-2 in April, whereas the Southern Hemisphere effect more closely follows the austral insolation cycle, peaking in December. Mountain glaciers resolved in 0.05° MODIS data contribute about -0.037 W m-2 (1.4 %) of the global effect, with the majority (94 %) of this contribution originating from the Himalayas. Inter-annual trends in the global annual mean land CrRE are not statistically significant during the MODIS era, but trends are positive (less negative) over large areas of Northern Asia, especially during spring, and slightly negative over Antarctica, possibly due to increased snowfall. During a common overlap period of 2001-2008, our MODIS estimates of the Northern Hemisphere land CrRE are about 18 % smaller (less negative) than previous estimates derived from coarse-resolution AVHRR data, though inter-annual variations are well correlated (r = 0.78), indicating that these data are useful in determining longer term trends in land CrRE.

  8. Quantitative phosphoproteomics identifies SnRK2 protein kinase substrates and reveals the effectors of abscisic acid action

    PubMed Central

    Wang, Pengcheng; Xue, Liang; Batelli, Giorgia; Lee, Shinyoung; Hou, Yueh-Ju; Van Oosten, Michael J.; Zhang, Huiming; Tao, W. Andy; Zhu, Jian-Kang

    2013-01-01

    Sucrose nonfermenting 1 (SNF1)-related protein kinase 2s (SnRK2s) are central components of abscisic acid (ABA) signaling pathways. The snrk2.2/2.3/2.6 triple-mutant plants are nearly completely insensitive to ABA, suggesting that most of the molecular actions of ABA are triggered by the SnRK2s-mediated phosphorylation of substrate proteins. Only a few substrate proteins of the SnRK2s are known. To identify additional substrate proteins of the SnRK2s and provide insight into the molecular actions of ABA, we used quantitative phosphoproteomics to compare the global changes in phosphopeptides in WT and snrk2.2/2.3/2.6 triple mutant seedlings in response to ABA treatment. Among the 5,386 unique phosphorylated peptides identified in this study, we found that ABA can increase the phosphorylation of 166 peptides and decrease the phosphorylation of 117 peptides in WT seedlings. In the snrk2.2/2.3/2.6 triple mutant, 84 of the 166 peptides, representing 58 proteins, could not be phosphorylated, or phosphorylation was not increased under ABA treatment. In vitro kinase assays suggest that most of the 58 proteins can serve as substrates of the SnRK2s. The SnRK2 substrates include proteins involved in flowering time regulation, RNA and DNA binding, miRNA and epigenetic regulation, signal transduction, chloroplast function, and many other cellular processes. Consistent with the SnRK2 phosphorylation of flowering time regulators, the snrk2.2/2.3/2.6 triple mutant flowered significantly earlier than WT. These results shed new light on the role of the SnRK2 protein kinases and on the downstream effectors of ABA action, and improve our understanding of plant responses to adverse environments. PMID:23776212

  9. Phosphoproteomic analysis of the Chlamydia caviae elementary body and reticulate body forms.

    PubMed

    Fisher, Derek J; Adams, Nancy E; Maurelli, Anthony T

    2015-08-01

    Chlamydia are Gram-negative, obligate intracellular bacteria responsible for significant diseases in humans and economically important domestic animals. These pathogens undergo a unique biphasic developmental cycle transitioning between the environmentally stable elementary body (EB) and the replicative intracellular reticulate body (RB), a conversion that appears to require extensive regulation of protein synthesis and function. However, Chlamydia possess a limited number of canonical mechanisms of transcriptional regulation. Ser/Thr/Tyr phosphorylation of proteins in bacteria has been increasingly recognized as an important mechanism of post-translational control of protein function. We utilized 2D gel electrophoresis coupled with phosphoprotein staining and MALDI-TOF/TOF analysis to map the phosphoproteome of the EB and RB forms of Chlamydia caviae. Forty-two non-redundant phosphorylated proteins were identified (some proteins were present in multiple locations within the gels). Thirty-four phosphorylated proteins were identified in EBs, including proteins found in central metabolism and protein synthesis, Chlamydia-specific hypothetical proteins and virulence-related proteins. Eleven phosphorylated proteins were identified in RBs, mostly involved in protein synthesis and folding and a single virulence-related protein. Only three phosphoproteins were found in both EB and RB phosphoproteomes. Collectively, 41 of 42 C. caviae phosphoproteins were present across Chlamydia species, consistent with the existence of a conserved chlamydial phosphoproteome. The abundance of stage-specific phosphoproteins suggests that protein phosphorylation may play a role in regulating the function of developmental-stage-specific proteins and/or may function in concert with other factors in directing EB-RB transitions.

  10. Quantitative Phosphoproteomic Analysis of Soybean Root Hairs Inoculated with Bradyrhizobium japonicum

    SciTech Connect

    Nguyen, Tran H.; Brechenmacher, Laurent; Aldrich, Joshua T.; Clauss, Therese RW; Gritsenko, Marina A.; Hixson, Kim K.; Libault, Marc; Tanaka, Kiwamu; Yang, Feng; Yao, Qiuming; Pasa-Tolic, Ljiljana; Xu, Dong; Nguyen, Henry T.; Stacey, Gary

    2012-11-11

    Root hairs are single hair-forming cells on roots that function to increase root surface area, enhancing water and nutrient uptake. In leguminous plants, root hairs also play a critical role as the site of infection by symbiotic nitrogen fixing rhizobia, leading to the formation of a novel organ, the nodule. The initial steps in the rhizobia-root hair infection process are known to involve specific receptor kinases and subsequent kinase cascades. Here, we characterize the phosphoproteome of the root hairs and the corresponding stripped roots (i.e., roots from which root hairs were removed) during rhizobial colonization and infection to gain insight into the molecular mechanism of root hair cell biology. We chose soybean (Glycine max L.), one of the most important crop plants in the legume family, for this study because of its larger root size, which permits isolation of sufficient root hair material for phosphoproteomic analysis. Phosphopeptides derived from root hairs and stripped roots, mock inoculated or inoculated with the soybean-specific rhizobium Bradyrhizobium japonicum, were labeled with the isobaric tag 8-plex ITRAQ, enriched using Ni-NTA magnetic beads and subjected to nRPLC-MS/MS analysis using HCD and decision tree guided CID/ETD strategy. A total of 1,625 unique phosphopeptides, spanning 1,659 non-redundant phosphorylation sites, were detected from 1,126 soybean phosphoproteins. Among them, 273 phosphopeptides corresponding to 240 phosphoproteins were found to be significantly regulated (>1.5 fold abundance change) in response to inoculation with B. japonicum. The data reveal unique features of the soybean root hair phosphoproteome, including root hair and stripped root-specific phosphorylation suggesting a complex network of kinase-substrate and phosphatase-substrate interactions in response to rhizobial inoculation.

  11. The effect of subducting slabs in global shear wave tomography

    NASA Astrophysics Data System (ADS)

    Lu, Chang; Grand, Stephen P.

    2016-05-01

    Subducting slabs create strong short wavelength seismic anomalies in the upper mantle where much of Earth's seismicity is located. As such, they have the potential to bias longer wavelength seismic tomography models. To evaluate the effect of subducting slabs in global tomography, we performed a series of inversions using a global synthetic shear wave traveltime data set for a theoretical slab model based on predicted thermal anomalies within slabs. The spectral element method was applied to predict the traveltime anomalies produced by the 3-D slab model for paths corresponding to our current data used in actual tomography models. Inversion tests have been conducted first using the raw traveltime anomalies to check how well the slabs can be imaged in global tomography without the effect of earthquake mislocation. Our results indicate that most of the slabs can be identified in the inversion result but with smoothed and reduced amplitude. The recovery of the total mass anomaly in slab regions is about 88 per cent. We then performed another inversion test to investigate the effect of mislocation caused by subducting slabs. We found that source mislocation largely removes slab signal and significantly degrades the imaging of subducting slabs-potentially reducing the recovery of mass anomalies in slab regions to only 41 per cent. We tested two source relocation procedures-an iterative relocation inversion and joint relocation inversion. Both methods partially recover the true source locations and improve the inversion results, but the joint inversion method worked significantly better than the iterative method. In all of our inversion tests, the amplitudes of artefact structures in the lower mantle caused by the incorrect imaging of slabs (up to ˜0.5 per cent S velocity anomalies) are comparable to some large-scale lower-mantle heterogeneities seen in global tomography studies. Based on our inversion tests, we suggest including a-priori subducting slabs in the

  12. How well can we quantify global black carbon radiative effects?

    NASA Astrophysics Data System (ADS)

    Stier, P.

    2012-12-01

    Atmospheric aerosols play an important role in the global climate system. Carbonaceous aerosols stand out through their potential to warm (through absorption and semi-direct effects) and cool (through scattering and indirect effects) climate, depending on their microphysical properties, regional distribution and their vertical profile. Current global aerosol models vary drastically in simulated abundance, transport and radiative properties of black carbon and show significant biases when compared to observations. At the same time, "host" models used for the calculation of black carbon radiative forcing show significant differences in components relevant for the assessment of forcing, such as clouds, surface albedos and radiative transfer schemes. This presentation will review the current state of the art in the global assessment of black carbon radiative effects from aerosol models and observationally based forcing calculations, with focus on uncertainties. Particular attention will be given to novel observational constraints arising from advances in measurement technologies and observational strategies as well as to uncertainties in the radiative forcing calculations, as highlighted in the direct forcing experiments of the recent Phase II of the AeroCom aerosol intercomparison project. The identified uncertainties in the process chain, from point of emission through microphysical transformation and transport to the actual radiative transfer, could serve as guidance for future measurement strategies as well as for model improvements aiming to reduce the remaining significant uncertainties in the black carbon radiative effects.

  13. Comparative Phosphoproteomics Reveals the Role of AmpC β-lactamase Phosphorylation in the Clinical Imipenem-resistant Strain Acinetobacter baumannii SK17*

    PubMed Central

    Lai, Juo-Hsin; Yang, Jhih-Tian; Chern, Jeffy; Chen, Te-Li; Wu, Wan-Ling; Liao, Jiahn-Haur; Tsai, Shih-Feng; Liang, Suh-Yuen; Chou, Chi-Chi

    2016-01-01

    Nosocomial infectious outbreaks caused by multidrug-resistant Acinetobacter baumannii have emerged as a serious threat to human health. Phosphoproteomics of pathogenic bacteria has been used to identify the mechanisms of bacterial virulence and antimicrobial resistance. In this study, we used a shotgun strategy combined with high-accuracy mass spectrometry to analyze the phosphoproteomics of the imipenem-susceptible strain SK17-S and -resistant strain SK17-R. We identified 410 phosphosites on 248 unique phosphoproteins in SK17-S and 285 phosphosites on 211 unique phosphoproteins in SK17-R. The distributions of the Ser/Thr/Tyr/Asp/His phosphosites in SK17-S and SK17-R were 47.0%/27.6%/12.4%/8.0%/4.9% versus 41.4%/29.5%/17.5%/6.7%/4.9%, respectively. The Ser-90 phosphosite, located on the catalytic motif S88VS90K of the AmpC β-lactamase, was first identified in SK17-S. Based on site-directed mutagenesis, the nonphosphorylatable mutant S90A was found to be more resistant to imipenem, whereas the phosphorylation-simulated mutant S90D was sensitive to imipenem. Additionally, the S90A mutant protein exhibited higher β-lactamase activity and conferred greater bacterial protection against imipenem in SK17-S compared with the wild-type. In sum, our results revealed that in A. baumannii, Ser-90 phosphorylation of AmpC negatively regulates both β-lactamase activity and the ability to counteract the antibiotic effects of imipenem. These findings highlight the impact of phosphorylation-mediated regulation in antibiotic-resistant bacteria on future drug design and new therapies. PMID:26499836

  14. Local and global gravitomagnetic effects in Kerr spacetime

    SciTech Connect

    Tsoubelis, D.; Economou, A.; Stoghianidis, E.

    1987-08-15

    The integral shift in orientation of a gyroscope in closed polar orbit in the Kerr spacetime is examined as an example of a global gravitomagnetic effect. The exact dependence of this effect on the mass and angular momentum parameters of the Kerr field is determined and the well-known weak-field slow-motion limit pertinent to forthcoming experiments is analyzed. The precession of the spin vector of a gyroscope stationed at a given point of the Kerr spacetime's symmetry axis is presented as a local counterpart of the above gravitomagnetic effect.

  15. Health effects of global warming: Problems in assessment

    SciTech Connect

    Longstreth, J.

    1993-06-01

    Global warming is likely to result in a variety of environmental effects ranging from impacts on species diversity, changes in population size in flora and fauna, increases in sea level and possible impacts on the primary productivity of the sea. Potential impacts on human health and welfare have included possible increases in heat related mortality, changes in the distribution of disease vectors, and possible impacts on respiratory diseases including hayfever and asthma. Most of the focus thus far is on effects which are directly related to increases in temperature, e.g., heat stress or perhaps one step removed, e.g., changes in vector distribution. Some of the more severe impacts are likely to be much less direct, e.g., increases in migration due to agricultural failure following prolonged droughts. This paper discusses two possible approaches to the study of these less-direct impacts of global warming and presents information from on-going research using each of these approaches.

  16. Atlantic effects on recent decadal trends in global monsoon

    NASA Astrophysics Data System (ADS)

    Kamae, Youichi; Li, Xichen; Xie, Shang-Ping; Ueda, Hiroaki

    2017-01-01

    Natural climate variability contributes to recent decadal climate trends. Specifically the trends during the satellite era since 1979 include Atlantic and Indian Ocean warming and Pacific cooling associated with phase shifts of the Atlantic Multidecadal Oscillation and the Pacific Decadal Oscillation, and enhanced global monsoon (GM) circulation and rainfall especially in the Northern Hemisphere. Here we evaluate effects of the oceanic changes on the global and regional monsoon trends by partial ocean temperature restoring experiments in a coupled atmosphere-ocean general circulation model. Via trans-basin atmosphere-ocean teleconnections, the Atlantic warming drives a global pattern of sea surface temperature change that resembles observations, giving rise to the enhanced GM. The tropical Atlantic warming and the resultant Indian Ocean warming favor subtropical deep-tropospheric warming in both hemispheres, resulting in the enhanced monsoon circulations and precipitation over North America, South America and North Africa. The extratropical North Atlantic warming makes an additional contribution to the monsoon enhancement via Eurasian continent warming and resultant land-sea thermal gradient over Asia. The results of this study suggest that the Atlantic multidecadal variability can explain a substantial part of global climate variability including the recent decadal trends of GM.

  17. Effect of heterogeneousatmospheric CO2 on simulated global carbon budget

    USGS Publications Warehouse

    Zhang, Zhen; Jiang, Hong; Liu, Jinxun; Ju, Weimin; Zhang, Xiuying

    2013-01-01

    The effects of rising atmospheric carbon dioxide (CO2) on terrestrial carbon (C) sequestration have been a key focus in global change studies. As anthropological CO2 emissions substantially increase, the spatial variability of atmospheric CO2 should be considered to reduce the potential bias on C source and sink estimations. In this study, the global spatial–temporal patterns of near surface CO2 concentrations for the period 2003-2009 were established using the SCIAMACHY satellite observations and the GLOBALVIEW-CO2 field observations. With this CO2 data and the Integrated Biosphere Simulator (IBIS), our estimation of the global mean annual NPP and NEP was 0.5% and 7% respectively which differs from the traditional C sequestration assessments. The Amazon, Southeast Asia, and Tropical Africa showed higher C sequestration than the traditional assessment, and the rest of the areas around the world showed slightly lower C sequestration than the traditional assessment. We find that the variability of NEP is less intense under heterogeneous CO2 pattern on a global scale. Further studies of the cause of CO2 variation and the interactions between natural and anthropogenic processes of C sequestration are needed.

  18. Global change effects on plant chemical defenses against insect herbivores.

    PubMed

    Bidart-Bouzat, M Gabriela; Imeh-Nathaniel, Adebobola

    2008-11-01

    This review focuses on individual effects of major global change factors, such as elevated CO2, O3, UV light and temperature, on plant secondary chemistry. These secondary metabolites are well-known for their role in plant defense against insect herbivory. Global change effects on secondary chemicals appear to be plant species-specific and dependent on the chemical type. Even though plant chemical responses induced by these factors are highly variable, there seems to be some specificity in the response to different environmental stressors. For example, even though the production of phenolic compounds is enhanced by both elevated CO2 and UV light levels, the latter appears to primarily increase the concentrations of flavonoids. Likewise, specific phenolic metabolites seem to be induced by O3 but not by other factors, and an increase in volatile organic compounds has been particularly detected under elevated temperature. More information is needed regarding how global change factors influence inducibility of plant chemical defenses as well as how their indirect and direct effects impact insect performance and behavior, herbivory rates and pathogen attack. This knowledge is crucial to better understand how plants and their associated natural enemies will be affected in future changing environments.

  19. The effects of global change upon United States air quality

    NASA Astrophysics Data System (ADS)

    Gonzalez-Abraham, R.; Chung, S. H.; Avise, J.; Lamb, B.; Salathé, E. P., Jr.; Nolte, C. G.; Loughlin, D.; Guenther, A.; Wiedinmyer, C.; Duhl, T.; Zhang, Y.; Streets, D. G.

    2015-11-01

    To understand more fully the effects of global changes on ambient concentrations of ozone and particulate matter with aerodynamic diameter smaller than 2.5 μm (PM2.5) in the United States (US), we conducted a comprehensive modeling effort to evaluate explicitly the effects of changes in climate, biogenic emissions, land use and global/regional anthropogenic emissions on ozone and PM2.5 concentrations and composition. Results from the ECHAM5 global climate model driven with the A1B emission scenario from the Intergovernmental Panel on Climate Change (IPCC) were downscaled using the Weather Research and Forecasting (WRF) model to provide regional meteorological fields. We developed air quality simulations using the Community Multiscale Air Quality Model (CMAQ) chemical transport model for two nested domains with 220 and 36 km horizontal grid cell resolution for a semi-hemispheric domain and a continental United States (US) domain, respectively. The semi-hemispheric domain was used to evaluate the impact of projected global emissions changes on US air quality. WRF meteorological fields were used to calculate current (2000s) and future (2050s) biogenic emissions using the Model of Emissions of Gases and Aerosols from Nature (MEGAN). For the semi-hemispheric domain CMAQ simulations, present-day global emissions inventories were used and projected to the 2050s based on the IPCC A1B scenario. Regional anthropogenic emissions were obtained from the US Environmental Protection Agency National Emission Inventory 2002 (EPA NEI2002) and projected to the future using the MARKet ALlocation (MARKAL) energy system model assuming a business as usual scenario that extends current decade emission regulations through 2050. Our results suggest that daily maximum 8 h average ozone (DM8O) concentrations will increase in a range between 2 to 12 parts per billion (ppb) across most of the continental US. The highest increase occurs in the South, Central and Midwest regions of the US due to

  20. Comprehensive Analysis of the Membrane Phosphoproteome Regulated by Oligogalacturonides in Arabidopsis thaliana

    PubMed Central

    Mattei, Benedetta; Spinelli, Francesco; Pontiggia, Daniela; De Lorenzo, Giulia

    2016-01-01

    Early changes in the Arabidopsis thaliana membrane phosphoproteome in response to oligogalacturonides (OGs), a class of plant damage-associated molecular patterns (DAMPs), were analyzed by two complementary proteomic approaches. Differentially phosphorylated sites were determined through phosphopeptide enrichment followed by LC-MS/MS using label-free quantification; differentially phosphorylated proteins were identified by 2D-DIGE combined with phospho-specific fluorescent staining (phospho-DIGE). This large-scale phosphoproteome analysis of early OG-signaling enabled us to determine 100 regulated phosphosites using LC-MS/MS and 46 differential spots corresponding to 34 pdhosphoproteins using phospho-DIGE. Functional classification showed that the OG-responsive phosphoproteins include kinases, phosphatases and receptor-like kinases, heat shock proteins (HSPs), reactive oxygen species (ROS) scavenging enzymes, proteins related to cellular trafficking, transport, defense and signaling as well as novel candidates for a role in immunity, for which elicitor-induced phosphorylation changes have not been shown before. A comparison with previously identified elicitor-regulated phosphosites shows only a very limited overlap, uncovering the immune-related regulation of 70 phosphorylation sites and revealing novel potential players in the regulation of elicitor-dependent immunity. PMID:27532006

  1. Phosphoproteomic profiling of mouse primary HSPCs reveals new regulators of HSPC mobilization

    PubMed Central

    Ficarro, Scott B.; Hutchinson, John N.; Csepanyi-Komi, Roland; Nguyen, Phi T.; Wisniewski, Eva; Sullivan, Jessica; Hofmann, Oliver; Ligeti, Erzsebet; Marto, Jarrod A.; Wagers, Amy J.

    2016-01-01

    Protein phosphorylation is a central mechanism of signal transduction that both positively and negatively regulates protein function. Large-scale studies of the dynamic phosphorylation states of cell signaling systems have been applied extensively in cell lines and whole tissues to reveal critical regulatory networks, and candidate-based evaluations of phosphorylation in rare cell populations have also been informative. However, application of comprehensive profiling technologies to adult stem cell and progenitor populations has been challenging, due in large part to the scarcity of such cells in adult tissues. Here, we combine multicolor flow cytometry with highly efficient 3-dimensional high performance liquid chromatography/mass spectrometry to enable quantitative phosphoproteomic analysis from 200 000 highly purified primary mouse hematopoietic stem and progenitor cells (HSPCs). Using this platform, we identify ARHGAP25 as a novel regulator of HSPC mobilization and demonstrate that ARHGAP25 phosphorylation at serine 363 is an important modulator of its function. Our approach provides a robust platform for large-scale phosphoproteomic analyses performed with limited numbers of rare progenitor cells. Data from our study comprises a new resource for understanding the molecular signaling networks that underlie hematopoietic stem cell mobilization. PMID:27365422

  2. Phosphoproteomics reveals ALK promote cell progress via RAS/JNK pathway in neuroblastoma

    PubMed Central

    Xu, Guofeng; Zhang, Min; Wu, Yeming; Wu, Zhixiang

    2016-01-01

    Emerging evidence suggests receptor tyrosine kinase ALK as a promising therapeutic target in neuroblastoma. However, clinical trials reveal that a limited proportion of ALK-positive neuroblastoma patients experience clinical benefits from Crizotinib, a clinically approved specific inhibitor of ALK. The precise molecular mechanisms of aberrant ALK activity in neuroblastoma remain elusive, limiting the clinical application of ALK as a therapeutic target in neuroblastoma. Here, we describe a deep quantitative phosphoproteomic approach in which Crizotinib-treated neuroblastoma cell lines bearing aberrant ALK are used to investigate downstream regulated phosphoproteins. We identified more than 19,500—and quantitatively analyzed approximately 10,000—phosphorylation sites from each cell line, ultimately detecting 450–790 significantly-regulated phosphorylation sites. Multiple layers of bioinformatic analysis of the significantly-regulated phosphoproteins identified RAS/JNK as a downstream signaling pathway of ALK, independent of the ALK variant present. Further experiments demonstrated that ALK/JNK signaling could be inactivated by either ALK- or JNK-specific inhibitors, resulting in cell growth inhibition by induction of cell cycle arrest and cell apoptosis. Our study broadly defines the phosphoproteome in response to ALK inhibition and provides a resource for further clinical investigation of ALK as therapeutic target for the treatment of neuroblastoma. PMID:27732954

  3. NeuCode Labeling in Nematodes: Proteomic and Phosphoproteomic Impact of Ascaroside Treatment in Caenorhabditis elegans*

    PubMed Central

    Rhoads, Timothy W.; Prasad, Aman; Kwiecien, Nicholas W.; Merrill, Anna E.; Zawack, Kelson; Westphall, Michael S.; Schroeder, Frank C.; Kimble, Judith; Coon, Joshua J.

    2015-01-01

    The nematode Caenorhabditis elegans is an important model organism for biomedical research. We previously described NeuCode stable isotope labeling by amino acids in cell culture (SILAC), a method for accurate proteome quantification with potential for multiplexing beyond the limits of traditional stable isotope labeling by amino acids in cell culture. Here we apply NeuCode SILAC to profile the proteomic and phosphoproteomic response of C. elegans to two potent members of the ascaroside family of nematode pheromones. By consuming labeled E. coli as part of their diet, C. elegans nematodes quickly and easily incorporate the NeuCode heavy lysine isotopologues by the young adult stage. Using this approach, we report, at high confidence, one of the largest proteomic and phosphoproteomic data sets to date in C. elegans: 6596 proteins at a false discovery rate ≤ 1% and 6620 phosphorylation isoforms with localization probability ≥75%. Our data reveal a post-translational signature of pheromone sensing that includes many conserved proteins implicated in longevity and response to stress. PMID:26392051

  4. NeuCode Labeling in Nematodes: Proteomic and Phosphoproteomic Impact of Ascaroside Treatment in Caenorhabditis elegans.

    PubMed

    Rhoads, Timothy W; Prasad, Aman; Kwiecien, Nicholas W; Merrill, Anna E; Zawack, Kelson; Westphall, Michael S; Schroeder, Frank C; Kimble, Judith; Coon, Joshua J

    2015-11-01

    The nematode Caenorhabditis elegans is an important model organism for biomedical research. We previously described NeuCode stable isotope labeling by amino acids in cell culture (SILAC), a method for accurate proteome quantification with potential for multiplexing beyond the limits of traditional stable isotope labeling by amino acids in cell culture. Here we apply NeuCode SILAC to profile the proteomic and phosphoproteomic response of C. elegans to two potent members of the ascaroside family of nematode pheromones. By consuming labeled E. coli as part of their diet, C. elegans nematodes quickly and easily incorporate the NeuCode heavy lysine isotopologues by the young adult stage. Using this approach, we report, at high confidence, one of the largest proteomic and phosphoproteomic data sets to date in C. elegans: 6596 proteins at a false discovery rate ≤ 1% and 6620 phosphorylation isoforms with localization probability ≥75%. Our data reveal a post-translational signature of pheromone sensing that includes many conserved proteins implicated in longevity and response to stress.

  5. Quantitative Phosphoproteomics Reveals Signaling Mechanisms Associated with Rapid Cold Hardening in a Chill-Tolerant Fly.

    PubMed

    Teets, Nicholas M; Denlinger, David L

    2016-08-05

    Rapid cold hardening (RCH) is a physiological adaptation in which brief chilling (minutes to hours) significantly enhances the cold tolerance of insects. RCH allows insects to cope with sudden cold snaps and diurnal variation in temperature, but the mechanistic basis of this rapid stress response is poorly understood. Here, we used phosphoproteomics to identify phosphorylation-mediated signaling events that are regulated by chilling that induces RCH. Phosphoproteomic changes were measured in both brain and fat bodies, two tissues that are essential for sensing cold and coordinating RCH at the organismal level. Tissues were chilled ex vivo, and changes in phosphoprotein abundance were measured using 2D electrophoresis coupled with Pro-Q diamond labeling of phosphoproteins followed by protein identification via LC-MS/MS. In both tissues, we observed an abundance of protein phosphorylation events in response to chilling. Some of the proteins regulated by RCH-inducing chilling include proteins involved in cytoskeletal reorganization, heat shock proteins, and proteins involved in the degradation of damaged cellular components via the proteasome and autophagosome. Our results suggest that phosphorylation-mediated signaling cascades are major drivers of RCH and enhance our mechanistic understanding of this complex phenotype.

  6. The phosphoproteome of Fusarium graminearum at the onset of nitrogen starvation.

    PubMed

    Rampitsch, Christof; Subramaniam, Rajagopal; Djuric-Ciganovic, Slavica; Bykova, Natalia V

    2010-01-01

    Fusarium graminearum grown under stress, such as nutrient deprivation, activates, among others, the trichothecene pathway that produces the mycotoxin deoxynivalenol and its derivatives. The kinase inhibitor staurosporine reduced the production of trichothecenes by 39% compared with control in vitro. On the other hand, phosphatase inhibitor okadaic acid increased the amount by 72% compared with the control in vitro. This suggests that phosphorylation events are involved in the signalling pathway, leading to the activation of the trichothecene pathway. Three approaches were used to study the phosphoproteome of F. graminearum under nitrogen-limiting conditions: 2-DE (2-DE: IEFxSDS-PAGE) in combination with MS protein identification; SDS-PAGE in combination with off-line IMAC and TiO(2) enrichment and gel electrophoresis LC-MS analysis; and a gel-free approach using strong anion exchange chromatography, IMAC and LC-MS. A total of 348 phosphorylation sites localized in 301 peptides from 241 proteins were identified. By 2-DE, 20 phosphoproteins were identified, nine of which underwent changes during the time course examined. Using gel electrophoresis LC-MS 231 phosphopeptides were identified from three samples (ten gel slices each) at time points of nitrogen starvation t=0, 6, and 12 h. The gel-free analysis added 70 peptides from 65 proteins to the total. Proteins of unknown function and enzymes of known function comprised the largest groups overall. Ten protein kinases and seven transcription factors were identified. This is the first reported phosphoproteome of F. graminearum.

  7. Temporal proteomic analysis of HIV infection reveals remodelling of the host phosphoproteome by lentiviral Vif variants

    PubMed Central

    Greenwood, Edward JD; Matheson, Nicholas J; Wals, Kim; van den Boomen, Dick JH; Antrobus, Robin; Williamson, James C; Lehner, Paul J

    2016-01-01

    Viruses manipulate host factors to enhance their replication and evade cellular restriction. We used multiplex tandem mass tag (TMT)-based whole cell proteomics to perform a comprehensive time course analysis of >6500 viral and cellular proteins during HIV infection. To enable specific functional predictions, we categorized cellular proteins regulated by HIV according to their patterns of temporal expression. We focussed on proteins depleted with similar kinetics to APOBEC3C, and found the viral accessory protein Vif to be necessary and sufficient for CUL5-dependent proteasomal degradation of all members of the B56 family of regulatory subunits of the key cellular phosphatase PP2A (PPP2R5A-E). Quantitative phosphoproteomic analysis of HIV-infected cells confirmed Vif-dependent hyperphosphorylation of >200 cellular proteins, particularly substrates of the aurora kinases. The ability of Vif to target PPP2R5 subunits is found in primate and non-primate lentiviral lineages, and remodeling of the cellular phosphoproteome is therefore a second ancient and conserved Vif function. DOI: http://dx.doi.org/10.7554/eLife.18296.001 PMID:27690223

  8. Countermeasures for mitigating the effects of global environment changes

    NASA Technical Reports Server (NTRS)

    Jenkins, Lyle M.

    1991-01-01

    Environmental countermeasures for preventing the negative effects of global climate change and ozone depletion are discussed with special emphasis on the possibilities of space-based actions. Among the programs addressed are the Mission to Planet Earth, the Solar Power Satellite (and linkage to the Space Exploration Initiative), and proposed projects such as a lunar-based power generator that utilizes He-3 as a fusion fuel when combined with deuterium. The concept of regional working groups is proposed for initiating the programs for effective countermeasures.

  9. Hormonally mediated maternal effects, individual strategy and global change

    PubMed Central

    Meylan, Sandrine; Miles, Donald B.; Clobert, Jean

    2012-01-01

    A challenge to ecologists and evolutionary biologists is predicting organismal responses to the anticipated changes to global ecosystems through climate change. Most evidence suggests that short-term global change may involve increasing occurrences of extreme events, therefore the immediate response of individuals will be determined by physiological capacities and life-history adaptations to cope with extreme environmental conditions. Here, we consider the role of hormones and maternal effects in determining the persistence of species in altered environments. Hormones, specifically steroids, are critical for patterning the behaviour and morphology of parents and their offspring. Hence, steroids have a pervasive influence on multiple aspects of the offspring phenotype over its lifespan. Stress hormones, e.g. glucocorticoids, modulate and perturb phenotypes both early in development and later into adulthood. Females exposed to abiotic stressors during reproduction may alter the phenotypes by manipulation of hormones to the embryos. Thus, hormone-mediated maternal effects, which generate phenotypic plasticity, may be one avenue for coping with global change. Variation in exposure to hormones during development influences both the propensity to disperse, which alters metapopulation dynamics, and population dynamics, by affecting either recruitment to the population or subsequent life-history characteristics of the offspring. We suggest that hormones may be an informative index to the potential for populations to adapt to changing environments. PMID:22566673

  10. GIS applications to evaluate public health effects of global warming

    SciTech Connect

    Regens, J.L.; Hodges, D.G.

    1996-12-31

    Modeling projections of future climatic conditions suggest changes in temperature and precipitation patterns that might induce direct adverse effects on human health by altering the extent and severity of infectious and vector-borne diseases. The incidence of mosquito-borne diseases, for example, could increase substantially in areas where temperature and relative humidity rise. The application of Geographic Information Systems (GIS) offers new methodologies to evaluate the impact of global warming on changes in the incidence of infectious and vector-borne diseases. This research illustrates the potential analytical and communication uses of GIS for monitoring historical patterns of climate and human health variables and for projecting changes in these health variables with global warming.

  11. The effect of eurasian snow cover on global climate.

    PubMed

    Barnett, T P; Dümenil, L; Schlese, U; Roeckner, E

    1988-01-29

    Numerical simulations with a global atmospheric circulation model suggest that largescale variations in the amount of snowfall over Eurasia in the springtime are linked to the subsequent strength of the Asian summer monsoon. Large-scale changes in Eurasian snow cover are coupled to larger scale changes in the global climate system. There is a large, strong teleconnection to the atmospheric field over North America. The model results also show snow cover effects to subsequently alter other climatic fields known to be intimately associated with the El Niño-Southern Oscillation (ENSO) phenomenon. Thus the model results seem to challenge the current dogma that the ENSO phenomenon is solely the result of close coupling between the atmosphere and ocean by suggesting that processes over continental land masses may also have to be considered.

  12. The Effect of Eurasian Snow Cover on Global Climate

    NASA Astrophysics Data System (ADS)

    Barnett, T. P.; Dumenil, L.; Schlese, U.; Roeckner, E.

    1988-01-01

    Numerical simulations with a global atmospheric circulation model suggest that large-scale variations in the amount of snowfall over Eurasia in the springtime are linked to the subsequent strength of the Asian summer monsoon. Large-scale changes in Eurasian snow cover are coupled to larger scale changes in the global climate system. There is a large, strong teleconnection to the atmospheric field over North America. The model results also show cover effects to subsequently alter other climatic fields known to be intimately associated with the El Nino-Southern Oscillation (ENSO) phenomenon. Thus the model results seem to challenge the current dogma that the ENSO phenomenon is solely the result of close coupling between the atmosphere and ocean by suggesting that processes over continental land masses may also have to be considered.

  13. Biogeophysical effects of CO2-fertilization on global climate

    SciTech Connect

    Bala, G; Caldeira, K; Mirin, A; Wickett, M; Delire, C; Phillips, T J

    2006-04-26

    CO{sub 2}-fertilization affects plant growth, which modifies surface physical properties, altering the surface albedo, and fluxes of sensible and latent heat. We investigate how such CO{sub 2}-fertilization effects on vegetation and surface properties would affect the climate system. Using a global three-dimensional climate-carbon model that simulates vegetation dynamics, we compare two multi-century simulations: a ''Control'' simulation with no emissions, and a ''Physiol-noGHG'' simulation where physiological changes occur as a result of prescribed CO{sub 2} emissions, but where CO{sub 2}-induced greenhouse warming is not included. In our simulations, CO{sub 2}-fertilization produces warming; we obtain an annual- and global-mean warming of about 0.65 K (and land-only warming of 1.4 K) after 430 years. This century-scale warming is mostly due to a decreased surface albedo associated with the expansion of the Northern Hemisphere boreal forests. On decadal time scales, the CO{sub 2} uptake by afforestation should produce a cooling effect that exceeds this albedo-based warming; but if the forests remain in place, the CO{sub 2}-enhanced-greenhouse effect would diminish as the ocean equilibrates with the atmosphere, whereas the albedo effect would persist. Thus, on century time scales, there is the prospect for net warming from CO{sub 2}-fertilization of the land biosphere. Further study is needed to confirm and better quantify our results.

  14. Quantifying the Intercontinental and Global Reach and Effects of Pollution

    NASA Technical Reports Server (NTRS)

    Chatfield, Robert B.; Guo, Zitan

    2000-01-01

    The Atmospheric Chemistry Modeling Group is participating in an international effort to explore the projected interactions of the atmosphere with biota, human activity, and the natural environment over the next three decades. The group uses computer simulations and statistical analyses to compare theory and observations of the composition of the lower atmosphere. This study of global habitability change is part of a more ambitious activity to understand global habitability. This broad planetary understanding is central to planetary habitability, biomarker detection, and similar aspects of Astrobiology. The group has made highly detailed studies of immense intercontinental plumes that affect the chemistry of the global atmosphere, especially the region below the ozone (O3) layer whose chemical composition defines the conditions for healthy humans and the biosphere. For some decades there has been concern about the pollution from cities and industrial burning and its possible effect in increasing smog ozone, not only in continental regions, but also in plumes that spread downwind. Recently, there has been new concern about another kind of pollution plume. Projections for a greatly expanded aircraft fleet imply that there will be plumes of nitrogen oxides (NO(x)) from jet exhaust in the Northern Hemisphere downwind of major air traffic routes. Both of these are tied to large-scale O3 in the troposphere, where it is toxic to humans and plant tissues.

  15. Effects of certain analysis procedures on solar global velocity signals

    SciTech Connect

    Gilman, P.A.; Glatzmaier, G.A.

    1980-10-15

    We examine the data reduction procedures used by Howard and colleagues to deduce global solar velocities from the orginal Mount Wilson Doppler-magnetograph record. We demonstrate that removing daily rotation ''ears,'' and zero offset signals will greatly attenuate east-west global velocities of longitudinal wavenumber m< or =5. In addition we show that, because global velocity patterns are expected on theoretical grounds to have variable phase speeds in longitude, the construction of synoptic maps can severely attenuate high wavenumbers. The combination of these two effects can easily reduce an original periodic east-west flow velocity of peak amplitude 100 m s/sup -1/ to 10 m s/sup -1/ or less for any wavenumber. We demonstrate further that a velocity spectrum, obtained from a nonlinear spherical convection model for a case in which a differential rotation similar in amplitude and profile to the Sun, is attenuated to rms residual velocities close to or within the upper limits obtained by Howard and LaBonte. However, somewhat more power than they find is retained in variations of the daily rotation rate.

  16. Specifying Globalization Effects on National Policy: A Focus on the Mechanisms.

    ERIC Educational Resources Information Center

    Dale, Roger

    1999-01-01

    Clarifies the concept of globalization and explores how globalization affects national education systems. Compares eight mechanisms of external effects (borrowing, learning, teaching, harmonization, dissemination, standardization, interdependence, and imposition) and organizations associated with them. Effects have been largely indirect, the…

  17. Effects of climatic variables on weight loss: a global analysis

    PubMed Central

    Ustulin, Morena; Keum, Changwon; Woo, Junghoon; Woo, Jeong-taek; Rhee, Sang Youl

    2017-01-01

    Several studies have analyzed the effects of weather on factors associated with weight loss. In this study, we directly analyzed the effect of weather on intentional weight loss using global-scale data provided by smartphone applications. Through Weather Underground API and the Noom Coach application, we extracted information on weather and body weight for each user located in each of several geographic areas on all login days. We identified meteorological information (pressure, precipitation, wind speed, dew point, and temperature) and self-monitored body weight data simultaneously. A linear mixed-effects model was performed analyzing 3274 subjects. Subjects in North America had higher initial BMIs than those of subjects in Eastern Asia. During the study period, most subjects who used the smartphone application experienced weight loss in a significant way (80.39%, p-value < 0.001). Subjects who infrequently recorded information about dinner had smaller variations than those of other subjects (βfreq.users dinner*time = 0.007, p-value < 0.001). Colder temperature, lower dew point, and higher values for wind speed and precipitation were significantly associated with weight loss. In conclusion, we found a direct and independent impact of meteorological conditions on intentional weight loss efforts on a global scale (not only on a local level). PMID:28106167

  18. A Grounded Theory Study of Effective Global Leadership Development Strategies: Perspectives from Brazil, India, and Nigeria

    ERIC Educational Resources Information Center

    Lokkesmoe, Karen Jane

    2009-01-01

    This qualitative, grounded theory study focuses on global leadership and global leadership development strategies from the perspective of people from three developing countries, Brazil, India, and Nigeria. The study explores conceptualizations of global leadership, the skills required to lead effectively in global contexts, and recommended…

  19. The effects of global change upon United States air quality

    NASA Astrophysics Data System (ADS)

    Gonzalez-Abraham, R.; Avise, J.; Chung, S. H.; Lamb, B.; Salathé, E. P., Jr.; Nolte, C. G.; Loughlin, D.; Guenther, A.; Wiedinmyer, C.; Duhl, T.; Zhang, Y.; Streets, D. G.

    2014-12-01

    To understand more fully the effects of global changes on ambient concentrations of ozone and particulate matter with aerodynamic diameter smaller than 2.5 μm (PM2.5) in the US, we conducted a comprehensive modeling effort to evaluate explicitly the effects of changes in climate, biogenic emissions, land use, and global/regional anthropogenic emissions on ozone and PM2.5 concentrations and composition. Results from the ECHAM5 global climate model driven with the A1B emission scenario from the Intergovernmental Panel on Climate Change (IPCC) were downscaled using the Weather Research and Forecasting (WRF) model to provide regional meteorological fields. We developed air quality simulations using the Community Multiscale Air Quality Model (CMAQ) chemical transport model for two nested domains with 220 and 36 km horizontal grid cell resolution for a semi-hemispheric domain and a continental United States (US) domain, respectively. The semi-hemispheric domain was used to evaluate the impact of projected Asian emissions changes on US air quality. WRF meteorological fields were used to calculate current (2000s) and future (2050s) biogenic emissions using the Model of Emissions of Gases and Aerosols from Nature (MEGAN). For the semi-hemispheric domain CMAQ simulations, present-day global emissions inventories were used and projected to the 2050s based on the IPCC A1B scenario. Regional anthropogenic emissions were obtained from the US Environmental Protection Agency National Emission Inventory 2002 (EPA NEI2002) and projected to the future using the MARKet ALlocation (MARKAL) energy system model assuming a business as usual scenario that extends current decade emission regulations through 2050. Our results suggest that daily maximum 8 h average ozone (DM8O) concentrations will increase in a range between 2 to 12 ppb across most of the continental US, with the highest increase in the South, Central, and Midwest regions of the US, due to increases in temperature, enhanced

  20. Global model for the lithospheric strength and effective elastic thickness

    NASA Astrophysics Data System (ADS)

    Tesauro, Magdala; Kaban, Mikhail K.; Cloetingh, Sierd A. P. L.

    2013-08-01

    Global distribution of the strength and effective elastic thickness (Te) of the lithosphere are estimated using physical parameters from recent crustal and lithospheric models. For the Te estimation we apply a new approach, which provides a possibility to take into account variations of Young modulus (E) within the lithosphere. In view of the large uncertainties affecting strength estimates, we evaluate global strength and Te distributions for possible end-member 'hard' (HRM) and a 'soft' (SRM) rheology models of the continental crust. Temperature within the lithosphere has been estimated using a recent tomography model of Ritsema et al. (2011), which has much higher horizontal resolution than previous global models. Most of the strength is localized in the crust for the HRM and in the mantle for the SRM. These results contribute to the long debates on applicability of the "crème brulée" or "jelly-sandwich" model for the lithosphere structure. Changing from the SRM to HRM turns most of the continental areas from the totally decoupled mode to the fully coupled mode of the lithospheric layers. However, in the areas characterized by a high thermal regime and thick crust, the layers remain decoupled even for the HRM. At the same time, for the inner part of the cratons the lithospheric layers are coupled in both models. Therefore, rheological variations lead to large changes in the integrated strength and Te distribution in the regions characterized by intermediate thermal conditions. In these areas temperature uncertainties have a greater effect, since this parameter principally determines rheological behavior. Comparison of the Te estimates for both models with those determined from the flexural loading and spectral analysis shows that the 'hard' rheology is likely applicable for cratonic areas, whereas the 'soft' rheology is more representative for young orogens.

  1. Unraveling the phosphoproteome dynamics in mammal mitochondria from a network perspective.

    PubMed

    Padrão, Ana Isabel; Vitorino, Rui; Duarte, José Alberto; Ferreira, Rita; Amado, Francisco

    2013-10-04

    With mitochondrion garnering more attention for its inextricable involvement in pathophysiological conditions, it seems imperative to understand the means by which the molecular pathways harbored in this organelle are regulated. Protein phosphorylation has been considered a central event in cellular signaling and, more recently, in the modulation of mitochondrial activity. Efforts have been made to understand the molecular mechanisms by which protein phosphorylation regulates mitochondrial signaling. With the advances in mass-spectrometry-based proteomics, there is a substantial hope and expectation in the increased knowledge of protein phosphorylation profile and its mode of regulation. On the basis of phosphorylation profiles, attempts have been made to disclose the kinases involved and how they control the molecular processes in mitochondria and, consequently, the cellular outcomes. Still, few studies have focused on mitochondrial phosphoproteome profiling, particularly in diseases. The present study reviews current data on protein phosphorylation profiling in mitochondria, the potential kinases involved and how pathophysiological conditions modulate the mitochondrial phosphoproteome. To integrate data from distinct research papers, we performed network analysis, with bioinformatic tools like Cytoscape, String, and PANTHER taking into consideration variables such as tissue specificity, biological processes, molecular functions, and pathophysiological conditions. For instance, data retrieved from these analyses evidence some homology in the mitochondrial phosphoproteome among liver and heart, with proteins from transport and oxidative phosphorylation clusters particularly susceptible to phosphorylation. A distinct profile was noticed for adipocytes, with proteins form metabolic processes, namely, triglycerides metabolism, as the main targets of phosphorylation. Regarding disease conditions, more phosphorylated proteins were observed in diabetics with some

  2. Phosphoproteomic Analysis Reveals a Novel Mechanism of CaMKIIα Regulation Inversely Induced by Cocaine Memory Extinction versus Reconsolidation

    PubMed Central

    Rich, Matthew T.; Abbott, Thomas B.; Chung, Lisa; Gulcicek, Erol E.; Stone, Kathryn L.; Colangelo, Christopher M.; Lam, TuKiet T.; Nairn, Angus C.; Taylor, Jane R.

    2016-01-01

    Successful addiction treatment depends on maintaining long-term abstinence, making relapse prevention an essential therapeutic goal. However, exposure to environmental cues associated with drug use often thwarts abstinence efforts by triggering drug using memories that drive craving and relapse. We sought to develop a dual approach for weakening cocaine memories through phosphoproteomic identification of targets regulated in opposite directions by memory extinction compared with reconsolidation in male Sprague-Dawley rats that had been trained to self-administer cocaine paired with an audiovisual cue. We discovered a novel, inversely regulated, memory-dependent phosphorylation event on calcium-calmodulin-dependent kinase II α (CaMKIIα) at serine (S)331. Correspondingly, extinction-associated S331 phosphorylation inhibited CaMKIIα activity. Intra-basolateral amygdala inhibition of CaMKII promoted memory extinction and disrupted reconsolidation, leading to a reduction in subsequent cue-induced reinstatement. CaMKII inhibition had no effect if the memory was neither retrieved nor extinguished. Therefore, inhibition of CaMKII represents a novel mechanism for memory-based addiction treatment that leverages both extinction enhancement and reconsolidation disruption to reduce relapse-like behavior. SIGNIFICANCE STATEMENT Preventing relapse to drug use is an important goal for the successful treatment of addictive disorders. Relapse-prevention therapies attempt to interfere with drug-associated memories, but are often hindered by unintentional memory strengthening. In this study, we identify phosphorylation events that are bidirectionally regulated by the reconsolidation versus extinction of a cocaine-associated memory, including a novel site on CaMKIIα. Additionally, using a rodent model of addiction, we show that CaMKII inhibition in the amygdala can reduce relapse-like behavior. Together, our data supports the existence of mechanisms that can be used to enhance

  3. Global single ion effects within the Earth's plasma sheet

    NASA Astrophysics Data System (ADS)

    Rothwell, Paul L.; Yates, G. Kenneth

    Two global properties of single ion motion in the magnetotail are examined. The first effect is caused by the magnetic field in the plasma sheet directing boundary ions to the neutral sheet. Exact solutions to the Lorentz equation indicate that these ions can have sufficient energy to trigger the ion tearing mode if Bo/aBz > 6.0, where Bo is the tail lobe magnetic field, Bz is the magnetic field in the north-south direction and `a' is a parameter related to the growth of the ion tearing instability. It is found that this effect occurs at a lower energy for oxygen than for protons. The second global property is related to the thinning or expansion of the plasma sheet. The results indicate that in the absence of reconnection the plasma sheet adiabatically maintains equilibruim by allowing plasma and magnetic flux to cross the boundaries. The presence of reconnection modifies the flow across the boundaries as well as the spatial distribution of the induced electric field.

  4. Global single ion effects within the earth's plasma sheet

    NASA Astrophysics Data System (ADS)

    Rothwell, P. L.; Yates, G. K.

    Two global properties of single-ion motion in the magnetotail are examined. The first effect is caused by the magnetic field in the plasma sheet directing boundary ions to the neutral sheet. Exact solutions to the Lorentz equation indicate that these ions can have sufficient energy to trigger the ion tearing mode if B0/aBz is greater than 6.0, where B0 is the tail-lobe magnetic field, Bz is the magnetic field in the north-south direction, and a is a parameter related to the growth of the ion tearing instability. It is found that this effect occurs at a lower energy for oxygen than for protons. The second global property is related to the thinning or expansion of the plasma sheet. In the absence of reconnection, the plasma sheet adiabatically maintains equilibrium by allowing plasma and magnetic flux to cross the boundaries. The presence of reconnection modifies the flow across the boundaries as well as the spatial distribution of the induced electric field.

  5. Mercury as a Global Pollutant: Sources, Pathways, and Effects

    PubMed Central

    2013-01-01

    Mercury (Hg) is a global pollutant that affects human and ecosystem health. We synthesize understanding of sources, atmosphere-land-ocean Hg dynamics and health effects, and consider the implications of Hg-control policies. Primary anthropogenic Hg emissions greatly exceed natural geogenic sources, resulting in increases in Hg reservoirs and subsequent secondary Hg emissions that facilitate its global distribution. The ultimate fate of emitted Hg is primarily recalcitrant soil pools and deep ocean waters and sediments. Transfers of Hg emissions to largely unavailable reservoirs occur over the time scale of centuries, and are primarily mediated through atmospheric exchanges of wet/dry deposition and evasion from vegetation, soil organic matter and ocean surfaces. A key link between inorganic Hg inputs and exposure of humans and wildlife is the net production of methylmercury, which occurs mainly in reducing zones in freshwater, terrestrial, and coastal environments, and the subsurface ocean. Elevated human exposure to methylmercury primarily results from consumption of estuarine and marine fish. Developing fetuses are most at risk from this neurotoxin but health effects of highly exposed populations and wildlife are also a concern. Integration of Hg science with national and international policy efforts is needed to target efforts and evaluate efficacy. PMID:23590191

  6. Effects of aerosols on tropospheric oxidants: A global model study

    NASA Astrophysics Data System (ADS)

    Tie, Xuexi; Brasseur, Guy; Emmons, Louisa; Horowitz, Larry; Kinnison, Douglas

    2001-10-01

    The global distributions of sulfate and soot particles in the atmosphere are calculated, and the effect of aerosol particles on tropospheric oxidants is studied using a global chemical/transport/aerosol model. The model is developed in the framework of the National Center for Atmospheric Research (NCAR) global three-dimensional chemical/transport model (Model for Ozone and Related Chemical Tracers (MOZART)). In addition to the gas-phase photochemistry implemented in the MOZART model, the present study also accounts for the formation of sulfate and black carbon aerosols as well as for heterogeneous reactions on particles. The simulated global sulfate aerosol distributions and seasonal variation are compared with observations. The seasonal variation of sulfate aerosols is in agreement with measurements, except in the Arctic region. The calculated vertical profiles of sulfate aerosol agree well with the observations over North America. In the case of black carbon the calculated surface distribution is in fair agreement with observations. The effects of aerosol formation and heterogeneous reactions on the surface of sulfate aerosols are studied. The model calculations show the following: (1) The concentration of H2O2 is reduced when sulfate aerosols are formed due to the reaction of SO2 + H2O2 in cloud droplets. The gas-phase reaction SO2 + OH converts OH to HO2, but the reduction of OH and enhancement of HO2 are insignificant (<3%). (2) The heterogeneous reaction of HO2 on the surface of sulfate aerosols produces up to 10% reduction of hydroperoxyl radical (HO2) with an uptake coefficient of 0.2. However, this uptake coefficient could be overestimated, and the results should be regard as an upper limit estimation. (3) The N2O5 reaction on the surface of sulfate aerosols leads to an 80% reduction of NOx at middle to high latitudes during winter. Because ozone production efficiency is low in winter, ozone decreases by only 10% as a result of this reaction. However

  7. [Effects of global change on soil fauna diversity: A review].

    PubMed

    Wu, Ting-Juan

    2013-02-01

    Terrestrial ecosystem consists of aboveground and belowground components, whose interaction affects the ecosystem processes and functions. Soil fauna plays an important role in biogeochemical cycles. With the recognizing of the significance of soil fauna in ecosystem processes, increasing evidences demonstrated that global change has profound effects on soil faunima diversity. The alternation of land use type, the increasing temperature, and the changes in precipitation pattern can directly affect soil fauna diversity, while the increase of atmospheric CO2 concentration and nitrogen deposition can indirectly affect the soil fauna diversity by altering plant community composition, diversity, and nutrient contents. The interactions of different environmental factors can co-affect the soil fauna diversity. To understand the effects of different driving factors on soil fauna diversity under the background of climate change would facilitate us better predicting how the soil fauna diversity and related ecological processes changed in the future.

  8. Global inospheric effects of the October 1989 geomagnetic storm

    SciTech Connect

    Yeh, K.C.; Lin, K.H.; Ma, S.Y.

    1994-04-01

    Based on a large data base from 40 ionosonde stations distributed worldwide and 12 total electron content stations, a case study is made on the global behavior of ionospheric responses to the great magnetic storm of October 1989. The magnetic storm was triggered by a solar flare with the largest class of X13/4B and started with a sudden storm commencement (ssc) at 0917 UT on October 20. After the initial phase the storm underwent two periods of maximum activities in the following 2 days. Low-latitude auroras were sighted and reported in widely separated areas in both northern and southern hemispheres. In response to these magnetic and auroral activities the ionosphere showed remarkable effects. Depending on the local time of ssc occurrence, the ionospheric response differed appreciably. Impressive changes were long-lasting, large-scale effects, such as the severe depressions of foF2 at higher latitudes, the temporary suppression of the equatorial anomaly and large horizontal gradients at certain latitudes. Also observed were positive storm effects of short duration during the post-sunset period in response to the onset of both ssc and main phase of the magnetic storm. These two positive storm effects showed different patterns suggesting different casual mechanisms. In addition, global propagation of large-scale traveling ionospheric disturbances (TIDs) was seen during 2 nights, identified by dramatic rises of h{prime}F with periodic fluctuations. The equatorward propagation velocities of the TIDs varied between 330 m/s and 680 m/s for the east Asia region. 33 refs., 16 figs., 1 tab.

  9. Acetylome and phosphoproteome modifications in imatinib resistant chronic myeloid leukaemia cells treated with valproic acid.

    PubMed

    Buchi, Francesca; Pastorelli, Roberta; Ferrari, Germano; Spinelli, Elena; Gozzini, Antonella; Sassolini, Francesca; Bosi, Alberto; Tombaccini, Donatella; Santini, Valeria

    2011-07-01

    Chronic myeloid leukaemia has a specific therapy: BCR/ABL inhibitor imatinib. Resistance due to BCR/ABL dependent and independent mechanisms is partially reversible by histone deacetylase inhibitors. We analysed by 2D-electrophoresis and anti-pan-acetylated and anti-phosphotyrosine immunoblots, followed by spot-matching and MALDI-TOF mass spectrometry, which proteome modifications would parallel restoration of sensitivity to imatinib by valproic acid (VPA). VPA plus imatinib significantly increased acetylation of HSP90 and hnRNP L and decreased phosphorylation of HSPs and hnRNPs in imatinib resistant cells. VPA was able to modify profoundly acetylome and phosphoproteome of CML cells, while reverting resistance to imatinib.

  10. Spatial proteomic and phospho-proteomic organization in three prototypical cell migration modes

    PubMed Central

    2014-01-01

    Background Tight spatio-temporal signaling of cytoskeletal and adhesion dynamics is required for localized membrane protrusion that drives directed cell migration. Different ensembles of proteins are therefore likely to get recruited and phosphorylated in membrane protrusions in response to specific cues. Results Here, we use an assay that allows to biochemically purify extending protrusions of cells migrating in response to three prototypical receptors: integrins, recepor tyrosine kinases and G-coupled protein receptors. Using quantitative proteomics and phospho-proteomics approaches, we provide evidence for the existence of cue-specific, spatially distinct protein networks in the different cell migration modes. Conclusions The integrated analysis of the large-scale experimental data with protein information from databases allows us to understand some emergent properties of spatial regulation of signaling during cell migration. This provides the cell migration community with a large-scale view of the distribution of proteins and phospho-proteins regulating directed cell migration. PMID:24987309

  11. Characterization of the human plasma phosphoproteome using linear ion trap mass spectrometry and multiple search engines.

    PubMed

    Carrascal, Montserrat; Gay, Marina; Ovelleiro, David; Casas, Vanessa; Gelpí, Emilio; Abian, Joaquin

    2010-02-05

    Major plasma protein families play different roles in blood physiology and hemostasis and in immunodefense. Other proteins in plasma can be involved in signaling as chemical messengers or constitute biological markers of the status of distant tissues. In this respect, the plasma phosphoproteome holds potentially relevant information on the mechanisms modulating these processes through the regulation of protein activity. In this work we describe for the first time a collection of phosphopeptides identified in human plasma using immunoaffinity separation of the seven major serum protein families from other plasma proteins, SCX fractionation, and TiO(2) purification prior to LC-MS/MS analysis. One-hundred and twenty-seven phosphosites in 138 phosphopeptides mapping 70 phosphoproteins were identified with FDR < 1%. A high-confidence collection of phosphosites was obtained using a combined search with the OMSSA, SEQUEST, and Phenyx search engines.

  12. Phosphoproteomics as an emerging weapon to develop new antibiotics against carbapenem resistant strain of Acinetobacter baumannii.

    PubMed

    Tiwari, Vishvanath; Tiwari, Monalisa

    2015-01-01

    Acinetobacter baumannii causes pneumonia, bloodstream infections, urinary tract infections, respiratory infections and meningitis. A. baumannii has developed resistance against most of the antibiotics including carbapenem. Therefore, to battle carbapenem resistance, there is a need to develop antimicrobial drugs with new modes of action. Phosphoproteomics will help identify the differentially phosphorylated protein and its crucial phosphosites which facilitate the elucidation of molecular mechanism of signaling and regulation of carbapenem resistant strain of A. baumannii as compared to carbapenem sensitive strain. This understanding might be useful for the development of new antibiotics against kinases involved in the phosphorylation of identified phosphosites in carbapenem resistant strain of A. baumannii. The proposed antibiotics selectively inhibit carbapenem resistant strain which further avoids its excessive use against carbapenem sensitive strain and thereafter reduces emergence of resistance.

  13. Celiac Anti-Type 2 Transglutaminase Antibodies Induce Phosphoproteome Modification in Intestinal Epithelial Caco-2 Cells

    PubMed Central

    Marabotti, Anna; Lepretti, Marilena; Salzano, Anna Maria; Scaloni, Andrea; Vitale, Monica; Zambrano, Nicola; Sblattero, Daniele; Esposito, Carla

    2013-01-01

    Background Celiac disease is an inflammatory condition of the small intestine that affects genetically predisposed individuals after dietary wheat gliadin ingestion. Type 2-transglutaminase (TG2) activity seems to be responsible for a strong autoimmune response in celiac disease, TG2 being the main autoantigen. Several studies support the concept that celiac anti-TG2 antibodies may contribute to disease pathogenesis. Our recent findings on the ability of anti-TG2 antibodies to induce a rapid intracellular mobilization of calcium ions, as well as extracellular signal-regulated kinase phosphorylation, suggest that they potentially act as signaling molecules. In line with this concept, we have investigated whether anti-TG2 antibodies can induce phosphoproteome modification in an intestinal epithelial cell line. Methods and Principal Findings We studied phosphoproteome modification in Caco-2 cells treated with recombinant celiac anti-TG2 antibodies. We performed a two-dimensional electrophoresis followed by specific staining of phosphoproteins and mass spectrometry analysis of differentially phosphorylated proteins. Of 14 identified proteins (excluding two uncharacterized proteins), three were hypophosphorylated and nine were hyperphosphorylated. Bioinformatics analyses confirmed the presence of phosphorylation sites in all the identified proteins and highlighted their involvement in several fundamental biological processes, such as cell cycle progression, cell stress response, cytoskeletal organization and apoptosis. Conclusions Identification of differentially phosphorylated proteins downstream of TG2-antibody stimulation suggests that in Caco-2 cells these antibodies perturb cell homeostasis by behaving as signaling molecules. We hypothesize that anti-TG2 autoantibodies may destabilize the integrity of the intestinal mucosa in celiac individuals, thus contributing to celiac disease establishment and progression. Since several proteins here identified in this study

  14. Battle through Signaling between Wheat and the Fungal Pathogen Septoria tritici Revealed by Proteomics and Phosphoproteomics*

    PubMed Central

    Yang, Fen; Melo-Braga, Marcella N.; Larsen, Martin R.; Jørgensen, Hans J. L.; Palmisano, Giuseppe

    2013-01-01

    The fungus Septoria tritici causes the disease septoria tritici blotch in wheat, one of the most economically devastating foliar diseases in this crop. To investigate signaling events and defense responses in the wheat–S. tritici interaction, we performed a time-course study of S. tritici infection in resistant and susceptible wheat using quantitative proteomics and phosphoproteomics, with special emphasis on the initial biotrophic phase of interactions. Our study revealed an accumulation of defense and stress-related proteins, suppression of photosynthesis, and changes in sugar metabolism during compatible and incompatible interactions. However, differential regulation of the phosphorylation status of signaling proteins, transcription and translation regulators, and membrane-associated proteins was observed between two interactions. The proteomic data were correlated with a more rapid or stronger accumulation of signal molecules, including calcium, H2O2, NO, and sugars, in the resistant than in the susceptible cultivar in response to the infection. Additionally, 31 proteins and 5 phosphoproteins from the pathogen were identified, including metabolic proteins and signaling proteins such as GTP-binding proteins, 14–3-3 proteins, and calcium-binding proteins. Quantitative PCR analysis showed the expression of fungal signaling genes and genes encoding a superoxide dismutase and cell-wall degrading enzymes. These results indicate roles of signaling, antioxidative stress mechanisms, and nutrient acquisition in facilitating the initial symptomless growth. Taken in its entirety, our dataset suggests interplay between the plant and S. tritici through complex signaling networks and downstream molecular events. Resistance is likely related to several rapidly and intensively triggered signal transduction cascades resulting in a multiple-level activation of transcription and translation processes of defense responses. Our sensitive approaches and model provide a

  15. Deciphering the acute cellular phosphoproteome response to irradiation with X-rays, protons and carbon ions.

    PubMed

    Winter, Martin; Dokic, Ivana; Schlegel, Julian; Warnken, Uwe; Debus, Jürgen; Abdollahi, Amir; Schnölzer, Martina

    2017-03-16

    Radiotherapy is a cornerstone of cancer therapy. The recently established particle therapy with raster-scanning protons and carbon ions landmarks a new era in the field of high-precision cancer medicine. However, molecular mechanisms governing radiation induced intracellular signaling remain elusive. Here, we present the first comprehensive proteomic and phosphoproteomic study applying stable isotope labeling by amino acids in cell culture (SILAC) in combination with high-resolution mass spectrometry to decipher cellular response to irradiation with X-rays, protons and carbon ions. At protein expression level limited alterations were observed 2h post irradiation of human lung adenocarcinoma cells. In contrast, 181 phosphorylation sites were found to be differentially regulated out of which 151 sites were not hitherto attributed to radiation response as revealed by crosscheck with the PhosphoSitePlus database. Radiation-induced phosphorylation of the p(S/T)Q motif was the prevailing regulation pattern affecting proteins involved in DNA damage response signaling. Since radiation doses were selected to produce same level of cell kill and DNA double-strand breakage for each radiation quality, DNA damage responsive phosphorylation sites were regulated to same extent. However, differential phosphorylation between radiation qualities was observed for 55 phosphorylation sites indicating the existence of distinct signaling circuitries induced by X-ray versus particle (proton/carbon) irradiation beyond the canonical DNA damage response. This unexpected finding was confirmed in targeted spike-in experiments using synthetic isotope labeled phosphopeptides. Herewith, we successfully validated uniform DNA damage response signaling coexisting with altered signaling involved in apoptosis and metabolic processes induced by X-ray and particle based treatments. In summary, the comprehensive insight into the radiation-induced phosphoproteome landscape is instructive for the design of

  16. Phosphatase of Regenerating Liver 3 (PRL3) Provokes a Tyrosine Phosphoproteome to Drive Prometastatic Signal Transduction*

    PubMed Central

    Walls, Chad D.; Iliuk, Anton; Bai, Yunpeng; Wang, Mu; Tao, W. Andy; Zhang, Zhong-Yin

    2013-01-01

    Phosphatase of regenerating liver 3 (PRL3) is suspected to be a causative factor toward cellular metastasis when in excess. To date, the molecular basis for PRL3 function remains an enigma, making efforts at distilling a concerted mechanism for PRL3-mediated metastatic dissemination very difficult. We previously discovered that PRL3 expressing cells exhibit a pronounced increase in protein tyrosine phosphorylation. Here we take an unbiased mass spectrometry-based approach toward identifying the phosphoproteins exhibiting enhanced levels of tyrosine phosphorylation with a goal to define the “PRL3-mediated signaling network.” Phosphoproteomic data support intracellular activation of an extensive signaling network normally governed by extracellular ligand-activated transmembrane growth factor, cytokine, and integrin receptors in the PRL3 cells. Additionally, data implicate the Src tyrosine kinase as the major intracellular kinase responsible for “hijacking” this network and provide strong evidence that aberrant Src activation is a major consequence of PRL3 overexpression. Importantly, the data support a PDGF(α/β)-, Eph (A2/B3/B4)-, and Integrin (β1/β5)-receptor array as being the predominant network coordinator in the PRL3 cells, corroborating a PRL3-induced mesenchymal-state. Within this network, we find that tyrosine phosphorylation is increased on a multitude of signaling effectors responsible for Rho-family GTPase, PI3K-Akt, STAT, and ERK activation, linking observations made by the field as a whole under Src as a primary signal transducer. Our phosphoproteomic data paint the most comprehensive picture to date of how PRL3 drives prometastatic molecular events through Src activation. PMID:24030100

  17. Phosphoproteomic analysis of interacting tumor and endothelial cells identifies regulatory mechanisms of transendothelial migration.

    PubMed

    Locard-Paulet, Marie; Lim, Lindsay; Veluscek, Giulia; McMahon, Kelly; Sinclair, John; van Weverwijk, Antoinette; Worboys, Jonathan D; Yuan, Yinyin; Isacke, Clare M; Jørgensen, Claus

    2016-02-09

    The exit of metastasizing tumor cells from the vasculature, extravasation, is regulated by their dynamic interactions with the endothelial cells that line the internal surface of vessels. To elucidate signals controlling tumor cell adhesion to the endothelium and subsequent transendothelial migration, we performed phosphoproteomic analysis to map cell-specific changes in protein phosphorylation that were triggered by contact between metastatic MDA-MB-231 breast cancer cells and endothelial cells. From the 2669 unique phosphorylation sites identified, 77 and 43 were differentially phosphorylated in the tumor cells and endothelial cells, respectively. The receptor tyrosine kinase ephrin type A receptor 2 (EPHA2) exhibited decreased Tyr(772) phosphorylation in the cancer cells upon endothelial contact. Knockdown of EPHA2 increased adhesion of the breast cancer cells to human umbilical vein endothelial cells (HUVECs) and their transendothelial migration in coculture cell assays, as well as early-stage lung colonization in vivo. EPHA2-mediated inhibition of transendothelial migration of breast cancer cells depended on interaction with the ligand ephrinA1 on HUVECs and phosphorylation of EPHA2-Tyr(772). When EPHA2 phosphorylation dynamics were compared between cell lines of different metastatic ability, EPHA2-Tyr(772) was rapidly dephosphorylated after ephrinA1 stimulation specifically in cells targeting the lung. Knockdown of the phosphatase LMW-PTP reduced adhesion and transendothelial migration of the breast cancer cells. Overall, cell-specific phosphoproteomic analysis provides a bidirectional map of contact-initiated signaling between tumor and endothelial cells that can be further investigated to identify mechanisms controlling the transendothelial cell migration of cancer cells.

  18. Health Promotion: An Effective Tool for Global Health

    PubMed Central

    Kumar, Sanjiv; Preetha, GS

    2012-01-01

    Health promotion is very relevant today. There is a global acceptance that health and social wellbeing are determined by many factors outside the health system which include socioeconomic conditions, patterns of consumption associated with food and communication, demographic patterns, learning environments, family patterns, the cultural and social fabric of societies; sociopolitical and economic changes, including commercialization and trade and global environmental change. In such a situation, health issues can be effectively addressed by adopting a holistic approach by empowering individuals and communities to take action for their health, fostering leadership for public health, promoting intersectoral action to build healthy public policies in all sectors and creating sustainable health systems. Although, not a new concept, health promotion received an impetus following Alma Ata declaration. Recently it has evolved through a series of international conferences, with the first conference in Canada producing the famous Ottawa charter. Efforts at promoting health encompassing actions at individual and community levels, health system strengthening and multi sectoral partnership can be directed at specific health conditions. It should also include settings-based approach to promote health in specific settings such as schools, hospitals, workplaces, residential areas etc. Health promotion needs to be built into all the policies and if utilized efficiently will lead to positive health outcomes. PMID:22529532

  19. Effects of mineral dust on global atmospheric nitrate concentrations

    NASA Astrophysics Data System (ADS)

    Karydis, Vlassis; Tsimpidi, Alexandra; Astitha, Marina; Lelieveld, Jos

    2014-05-01

    Inorganic particulate nitrate contributes significantly to the total aerosol mass. While nitrate is predominantly present in the submicron mode, coarse mode aerosol nitrate can also be produced by adsorption of nitric acid onto soil particles. Naturally emitted particles affect the phase partitioning of nitrate, especially in areas where dust comprises a significant portion of total particulate matter, and the simulation of these effects can considerably improve model predictions. However, most thermodynamic models used in global studies lack a realistic treatment of crustal species. This work aims to improve the representation of nitrate aerosols in the global chemistry climate model EMAC, and addresses the shortcomings of previous models. EMAC calculates the aerosol microphysics and gas/aerosol partitioning by using the GMXe aerosol module. The aerosol size distribution is described by 7 interacting lognormal modes (4 hydrophilic and 3 hydrophobic modes). An advanced dust emission module also accounts for the soil particle size distribution of different deserts worldwide. Gas/aerosol partitioning is simulated using the ISORROPIA-II thermodynamic equilibrium model which considers the interaction of K(+), Ca(+2), Mg(+2), NH4(+), Na(+), SO4(-2), NO3(-), Cl(-), H2O aerosol components. The EMAC model is tested in long-term simulations covering the years 2005-2008. Model predictions are compared with data from the European network EMEP, the IMPROVE network in North America, and the EANET Network in East Asia.

  20. Potential effect of global warming on mosquito-borne arboviruses.

    PubMed

    Reeves, W C; Hardy, J L; Reisen, W K; Milby, M M

    1994-05-01

    If global warming occurs in California, daily mean temperatures may increase by 3 to 5 degrees C, precipitation patterns will change, and sea level may rise 1 m. Studies were done on effect of temperature changes on survival of Culex tarsalis Coquillett, the primary vector of western equine encephalomyelitis (WEE) and St. Louis encephalitis (SLE) viruses, in two regions where temperatures differed by 5 degrees C. Daily mortality of adult vectors increased by 1% for each 1 degree C increase in temperature. At 25 degrees C, only 5% of Cx. tarsalis survived for 8 or more days, the time required for extrinsic incubation of these viruses. Extrinsic incubation times for these viruses shortened when temperatures were increased from 18 to 25 degrees C. WEE virus infection was modulated and transmission decreased at 32 degrees C. If temperatures in the warmer region increase by 5 degrees C, WEE virus may disappear and SLE virus would persist. In the cooler region, a 5 degrees C increase would decrease vector survivorship and virus activity in midsummer. In North America, epidemics of WEE have prevailed above a 21 degrees C isotherm and those of SLE below this isotherm. With global warming, epidemics of these viruses could extend into currently unreceptive northern areas. WEE virus would disappear from more southern regions. Geographic distribution of vector, human, and animal populations could be altered. North America could become more receptive to invasion by tropical vectors and diseases.

  1. Global Warming: Understanding and Teaching the Forecast. Part A The Greenhouse Effect.

    ERIC Educational Resources Information Center

    Andrews, Bill

    1993-01-01

    Provides information necessary for an interdisciplinary analysis of the greenhouse effect, enhanced greenhouse effect, global warming, global climate change, greenhouse gases, carbon dioxide, and scientific study of global warming for students grades 4-12. Several activity ideas accompany the information. (LZ)

  2. The global need for effective antibiotics: challenges and recent advances.

    PubMed

    Högberg, Liselotte Diaz; Heddini, Andreas; Cars, Otto

    2010-11-01

    The emerging problem of antibiotic resistance is a serious threat to global public health. The situation is aggravated by a substantial decline in the research and development of antibacterial agents. Hence, very few new antibacterial classes are brought to market when older classes lose their efficacy. There has been renewed and growing attention within policy groups to: (i) address the problem; (ii) discuss incentives for the development of urgently needed new treatments; (iii) preserve the efficacy of existing therapeutic options. We briefly review the basic principles of antibiotic resistance, and contrast the increasing resistance to the dwindling antibacterial 'pipeline'. We also highlight some recent policy initiatives aiming to secure the future need of effective antibiotics.

  3. Plant functional traits have globally consistent effects on competition.

    PubMed

    Kunstler, Georges; Falster, Daniel; Coomes, David A; Hui, Francis; Kooyman, Robert M; Laughlin, Daniel C; Poorter, Lourens; Vanderwel, Mark; Vieilledent, Ghislain; Wright, S Joseph; Aiba, Masahiro; Baraloto, Christopher; Caspersen, John; Cornelissen, J Hans C; Gourlet-Fleury, Sylvie; Hanewinkel, Marc; Herault, Bruno; Kattge, Jens; Kurokawa, Hiroko; Onoda, Yusuke; Peñuelas, Josep; Poorter, Hendrik; Uriarte, Maria; Richardson, Sarah; Ruiz-Benito, Paloma; Sun, I-Fang; Ståhl, Göran; Swenson, Nathan G; Thompson, Jill; Westerlund, Bertil; Wirth, Christian; Zavala, Miguel A; Zeng, Hongcheng; Zimmerman, Jess K; Zimmermann, Niklaus E; Westoby, Mark

    2016-01-14

    Phenotypic traits and their associated trade-offs have been shown to have globally consistent effects on individual plant physiological functions, but how these effects scale up to influence competition, a key driver of community assembly in terrestrial vegetation, has remained unclear. Here we use growth data from more than 3 million trees in over 140,000 plots across the world to show how three key functional traits--wood density, specific leaf area and maximum height--consistently influence competitive interactions. Fast maximum growth of a species was correlated negatively with its wood density in all biomes, and positively with its specific leaf area in most biomes. Low wood density was also correlated with a low ability to tolerate competition and a low competitive effect on neighbours, while high specific leaf area was correlated with a low competitive effect. Thus, traits generate trade-offs between performance with competition versus performance without competition, a fundamental ingredient in the classical hypothesis that the coexistence of plant species is enabled via differentiation in their successional strategies. Competition within species was stronger than between species, but an increase in trait dissimilarity between species had little influence in weakening competition. No benefit of dissimilarity was detected for specific leaf area or wood density, and only a weak benefit for maximum height. Our trait-based approach to modelling competition makes generalization possible across the forest ecosystems of the world and their highly diverse species composition.

  4. Atmospheric pressure loading effects on Global Positioning System coordinate determinations

    NASA Technical Reports Server (NTRS)

    Vandam, Tonie M.; Blewitt, Geoffrey; Heflin, Michael B.

    1994-01-01

    Earth deformation signals caused by atmospheric pressure loading are detected in vertical position estimates at Global Positioning System (GPS) stations. Surface displacements due to changes in atmospheric pressure account for up to 24% of the total variance in the GPS height estimates. The detected loading signals are larger at higher latitudes where pressure variations are greatest; the largest effect is observed at Fairbanks, Alaska (latitude 65 deg), with a signal root mean square (RMS) of 5 mm. Out of 19 continuously operating GPS sites (with a mean of 281 daily solutions per site), 18 show a positive correlation between the GPS vertical estimates and the modeled loading displacements. Accounting for loading reduces the variance of the vertical station positions on 12 of the 19 sites investigated. Removing the modeled pressure loading from GPS determinations of baseline length for baselines longer than 6000 km reduces the variance on 73 of the 117 baselines investigated. The slight increase in variance for some of the sites and baselines is consistent with expected statistical fluctuations. The results from most stations are consistent with approximately 65% of the modeled pressure load being found in the GPS vertical position measurements. Removing an annual signal from both the measured heights and the modeled load time series leaves this value unchanged. The source of the remaining discrepancy between the modeled and observed loading signal may be the result of (1) anisotropic effects in the Earth's loading response, (2) errors in GPS estimates of tropospheric delay, (3) errors in the surface pressure data, or (4) annual signals in the time series of loading and station heights. In addition, we find that using site dependent coefficients, determined by fitting local pressure to the modeled radial displacements, reduces the variance of the measured station heights as well as or better than using the global convolution sum.

  5. Effects of mineral dust on global atmospheric nitrate concentrations

    NASA Astrophysics Data System (ADS)

    Karydis, V. A.; Tsimpidi, A. P.; Pozzer, A.; Astitha, M.; Lelieveld, J.

    2015-04-01

    This study provides an assessment of the chemical composition and global aerosol load of the major inorganic aerosol components and determines the effect of mineral dust on their formation, focusing on aerosol nitrate. To account for this effect, the mineral dust aerosol components (i.e., Ca2+, Mg2+, K+, Na+) and their emissions are added to the ECHAM5/MESSy Atmospheric Chemistry model (EMAC). Gas/aerosol partitioning is simulated using the ISORROPIA-II thermodynamic equilibrium model that considers the interactions of K+-Ca2+-Mg2+-NH4+-Na+-SO42--NO3--Cl--H2O aerosol components. Emissions of mineral dust aerosol components (K+-Ca2+-Mg2+-Na+) are calculated online by taking into account the soil particle size distribution and chemical composition of different deserts worldwide. The presence of the metallic ions on the simulated suite of components can substantially affect the nitrate partitioning into the aerosol phase due to thermodynamic interactions. The updated model improved the nitrate predictions over remote areas and found that the fine aerosol nitrate concentration is highest over urban and industrialized areas (1-3 μg m-3), while coarse aerosol nitrate is highest close to deserts (1-4 μg m-3). The contribution of mineral dust components to nitrate formation is large in areas with high dust concentrations with impacts that can extend across southern Europe, western USA and northeastern China. The tropospheric burden of aerosol nitrate increases by 44% by considering the interactions of nitrate with mineral dust cations. The calculated global average nitrate aerosol concentration near the surface increases by 36% while the coarse and fine mode concentrations of nitrate increase by 53 and 21%, respectively. Sensitivity tests show that nitrate aerosol formation is most sensitive to the chemical composition of the emitted mineral dust, followed by the soil size distribution of dust particles, the magnitude of the mineral dust emissions, and the aerosol state

  6. Comparative Phosphoproteomic Analysis under High-Nitrogen Fertilizer Reveals Central Phosphoproteins Promoting Wheat Grain Starch and Protein Synthesis

    PubMed Central

    Zhen, Shoumin; Deng, Xiong; Zhang, Ming; Zhu, Gengrui; Lv, Dongwen; Wang, Yaping; Zhu, Dong; Yan, Yueming

    2017-01-01

    Nitrogen (N) is a macronutrient important for plant growth and development. It also strongly influences starch and protein synthesis, closely related to grain yield and quality. We performed the first comparative phosphoproteomic analysis of developing wheat grains in response to high-N fertilizer. Physiological and biochemical analyses showed that application of high-N fertilizer resulted in significant increases in leaf length and area, chlorophyll content, the activity of key enzymes in leaves such as nitrate reductase (NR), and in grains such as sucrose phosphate synthase (SPS), sucrose synthase (SuSy), and ADP glucose pyrophosphorylase (AGPase). This enhanced enzyme activity led to significant improvements in starch content, grain yield, and ultimately, bread making quality. Comparative phosphoproteomic analysis of developing grains under the application of high-N fertilizer performed 15 and 25 days post-anthesis identified 2470 phosphosites among 1372 phosphoproteins, of which 411 unique proteins displayed significant changes in phosphorylation level (>2-fold or <0.5-fold). These phosphoproteins are involved mainly in signaling transduction, starch synthesis, energy metabolism. Pro-Q diamond staining and Western blotting confirmed our phosphoproteomic results. We propose a putative pathway to elucidate the important roles of the central phosphoproteins regulating grain starch and protein synthesis. Our results provide new insights into the molecular mechanisms of protein phosphorylation modifications involved in grain development, yield and quality formation. PMID:28194157

  7. Inhomogeneous diffusion and ergodicity breaking induced by global memory effects

    NASA Astrophysics Data System (ADS)

    Budini, Adrián A.

    2016-11-01

    We introduce a class of discrete random-walk model driven by global memory effects. At any time, the right-left transitions depend on the whole previous history of the walker, being defined by an urnlike memory mechanism. The characteristic function is calculated in an exact way, which allows us to demonstrate that the ensemble of realizations is ballistic. Asymptotically, each realization is equivalent to that of a biased Markovian diffusion process with transition rates that strongly differs from one trajectory to another. Using this "inhomogeneous diffusion" feature, the ergodic properties of the dynamics are analytically studied through the time-averaged moments. Even in the long-time regime, they remain random objects. While their average over realizations recovers the corresponding ensemble averages, departure between time and ensemble averages is explicitly shown through their probability densities. For the density of the second time-averaged moment, an ergodic limit and the limit of infinite lag times do not commutate. All these effects are induced by the memory effects. A generalized Einstein fluctuation-dissipation relation is also obtained for the time-averaged moments.

  8. The effects of urbanization on global Plasmodium vivax malaria transmission

    PubMed Central

    2012-01-01

    Background Many recent studies have examined the impact of urbanization on Plasmodium falciparum malaria endemicity and found a general trend of reduced transmission in urban areas. However, none has examined the effect of urbanization on Plasmodium vivax malaria, which is the most widely distributed malaria species and can also cause severe clinical syndromes in humans. In this study, a set of 10,003 community-based P. vivax parasite rate (PvPR) surveys are used to explore the relationships between PvPR in urban and rural settings. Methods The PvPR surveys were overlaid onto a map of global urban extents to derive an urban/rural assignment. The differences in PvPR values between urban and rural areas were then examined. Groups of PvPR surveys inside individual city extents (urban) and surrounding areas (rural) were identified to examine the local variations in PvPR values. Finally, the relationships of PvPR between urban and rural areas within the ranges of 41 dominant Anopheles vectors were examined. Results Significantly higher PvPR values in rural areas were found globally. The relationship was consistent at continental scales when focusing on Africa and Asia only, but in the Americas, significantly lower values of PvPR in rural areas were found, though the numbers of surveys were small. Moreover, except for the countries in the Americas, the same trends were found at national scales in African and Asian countries, with significantly lower values of PvPR in urban areas. However, the patterns at city scales among 20 specific cities where sufficient data were available were less clear, with seven cities having significantly lower PvPR values in urban areas and two cities showing significantly lower PvPR in rural areas. The urban–rural PvPR differences within the ranges of the dominant Anopheles vectors were generally, in agreement with the regional patterns found. Conclusions Except for the Americas, the patterns of significantly lower P. vivax transmission in

  9. Langmuir mixing effects on global climate: WAVEWATCH III in CESM

    NASA Astrophysics Data System (ADS)

    Li, Qing; Webb, Adrean; Fox-Kemper, Baylor; Craig, Anthony; Danabasoglu, Gokhan; Large, William G.; Vertenstein, Mariana

    2016-07-01

    Large-Eddy Simulations (LES) have shown the effects of ocean surface gravity waves in enhancing the ocean boundary layer mixing through Langmuir turbulence. Neglecting this Langmuir mixing process may contribute to the common shallow bias in mixed layer depth in regions of the Southern Ocean and the Northern Atlantic in most state-of-the-art climate models. In this study, a third generation wave model, WAVEWATCH III, has been incorporated as a component of the Community Earth System Model, version 1.2 (CESM1.2). In particular, the wave model is now coupled with the ocean model through a modified version of the K-Profile Parameterization (KPP) to approximate the influence of Langmuir mixing. Unlike past studies, the wind-wave misalignment and the effects of Stokes drift penetration depth are considered through empirical scalings based on the rate of mixing in LES. Wave-Ocean only experiments show substantial improvements in the shallow biases of mixed layer depth in the Southern Ocean. Ventilation is enhanced and low concentration biases of pCFC-11 are reduced in the Southern Hemisphere. A majority of the improvements persist in the presence of other climate feedbacks in the fully coupled experiments. In addition, warming of the subsurface water over the majority of global ocean is observed in the fully coupled experiments with waves, and the cold subsurface ocean temperature biases are reduced.

  10. The Effects of Globalization Phenomena on Educational Concepts

    ERIC Educational Resources Information Center

    Schrottner, Barbara Theresia

    2010-01-01

    It is becoming more and more apparent that globalization processes represent, theoretically as well as practically, a challenge for educational sciences and therefore, it must be addressed within the sphere of education. Accordingly, educational conceptions have to adapt to globalization phenomena and focus more on alternative and innovative…

  11. Quantitative phosphoproteomics reveals genistein as a modulator of cell cycle and DNA damage response pathways in triple-negative breast cancer cells

    PubMed Central

    FANG, YI; ZHANG, QIAN; WANG, XIN; YANG, XUE; WANG, XIANGYU; HUANG, ZHEN; JIAO, YUCHEN; WANG, JING

    2016-01-01

    Around one sixth of breast cancer cases are classified as triple-negative breast cancer (TNBC), named after the absence of the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2); however, patients with TNBC suffer from poor clinical outcome and shortage of targeted therapy. Genistein, an estrogenic soy isoflavone, shows anticancer effects in TNBC cells such as inducing G2/M cell cycle arrest and apoptosis. However, the underlying mechanism of its anticancer effects is poorly understood and its elucidation can help the development of novel therapeutic strategies for TNBC. In this study, by combining isobaric tag-based TMT labeling with titanium dioxide-based phosphopeptide enrichment, we quantitated 5,445 phosphorylation sites on 2,008 phosphoproteins in the TNBC cell line MDA-MB-231, upon genistein treatment. Our analysis revealed 332 genistein-regulated phosphorylation sites on 226 proteins. Our data show that genistein can regulate several biological processes during the cell cycle, including DNA replication, cohesin complex cleavage, and kinetochore formation. Furthermore, genistein can also activate DNA damage response, including activation of ATR and BRCA1 complex. Overall, our study presents evidence at a phosphoproteomic level that genistein is able to inhibit TNBC cell growth by regulating the cell cycle and DNA damage response in a more complex manner. Our findings help elucidate the mechanisms through which genistein exerts its anticancer effects in TNBC cells. PMID:26783066

  12. Novel aspects of grapevine response to phytoplasma infection investigated by a proteomic and phospho-proteomic approach with data integration into functional networks

    PubMed Central

    2013-01-01

    analysis showed that the general main category “response to stimulus” was over-represented in both infected and recovered plants but, in the latter, the specific child category “response to biotic stimulus” was no longer found, suggesting a return to steady-state levels for those proteins specifically required for defence against pathogens. Conclusions Proteomic data were integrated into biological networks and their interactions were represented through a hypothetical model, showing the effects of protein modulation on primary metabolic ways and related secondary pathways. By following a multiplex-staining approach, we obtained new data on grapevine proteome pathways that specifically change at the phosphorylation level during phytoplasma infection and following recovery, focusing for the first time on phosphoproteome changes during pathogen infection in this host. PMID:23327683

  13. Global versus local change effects on a large European river.

    PubMed

    Floury, M; Delattre, C; Ormerod, S J; Souchon, Y

    2012-12-15

    Water temperature and discharge are fundamental to lotic ecosystem function, and both are strongly affected by climate. In large river catchments, however, climatic effects might be difficult to discern from background variability and other cumulative sources of anthropogenic change arising from local land and water management. Here, we use trend analysis and generalised linear modelling on the Loire, the longest river in France to test the hypotheses that i) long-term trends in discharge and river temperature have arisen from climate change and ii) climatic effects on water quality have not been overridden by local effects. Over 32 years (1977-2008), discharge in the Middle Loire fell by about 100 m³/s while water temperature increased by 1.2 °C with greatest effects during the warm period (May-August). Although increasing air temperature explained 80% of variations in water temperature, basin-wide precipitation showed no long-term trend and accounted for only 18% of inter-annual fluctuations in flow. We suggest that trends in abstraction coupled with a potential increase in evapo-transpiration at the catchment scale could be responsible for the majority of the long-term discharge trend. Discharge and water temperature explained only 20% of long-term variations in major water quality variables (conductivity, dissolved oxygen, pH, suspended matter, biochemical oxygen demand, nitrate, phosphate and chlorophyll-a), with phosphate and chlorophyll declining contrary to expectations from global change probably as a consequence of improved wastewater treatment. These data partially support our first hypothesis in revealing how warming in the Loire has been consistent with recent atmospheric warming. However, local management has had larger effects on discharge and water quality in ways that could respectively exacerbate (abstraction) or ameliorate (reduced point-source pollution) warming effects. As one of the first case-studies of its kind, this multi-parametric study

  14. Global priorities for an effective information basis of biodiversity distributions

    PubMed Central

    Meyer, Carsten; Kreft, Holger; Guralnick, Robert; Jetz, Walter

    2015-01-01

    Gaps in digital accessible information (DAI) on species distributions hamper prospects of safeguarding biodiversity and ecosystem services, and addressing central ecological and evolutionary questions. Achieving international targets on biodiversity knowledge requires that information gaps be identified and actions prioritized. Integrating 157 million point records and distribution maps for 21,170 terrestrial vertebrate species, we find that outside a few well-sampled regions, DAI on point occurrences provides very limited and spatially biased inventories of species. Surprisingly, many large, emerging economies are even more under-represented in global DAI than species-rich, developing countries in the tropics. Multi-model inference reveals that completeness is mainly limited by distance to researchers, locally available research funding and participation in data-sharing networks, rather than transportation infrastructure, or size and funding of Western data contributors as often assumed. Our results highlight the urgent need for integrating non-Western data sources and intensifying cooperation to more effectively address societal biodiversity information needs. PMID:26348291

  15. Atmospheric pressure loading effects on Global Positioning System coordinate determinations

    SciTech Connect

    Vandam, T.M.; Blewitt, G.; Heflin, M.B. ||

    1994-12-01

    Earth deformation signals caused by atmospheric pressure loading are detected in vertical position estimates at Global Positioning System (GPS) stations. Surface displacements due to changes in atmospheric pressure account for up to 24% of the total variance in the GPS height estimates. The detected loading signals are larger at higher latitudes where pressure variations are greatest; the largest effect is observed at Fairbanks, Alaska (latitude 65 deg), with a signal root mean square (RMS) of 5 mm. Out of 19 continuously operating GPS sites (with a mean of 281 daily solutions per site), 18 show a positive correlation between the GPS vertical estimates and the modeled loading displacements. Accounting for loading reduces the variance of the vertical station positions on 12 of the 19 sites investigated. Removing the modeled pressure loading from GPS determinations of baseline length for baselines longer than 6000 km reduces the variance on 73 of the 117 baselines investigated. The slight increase in variance for some of the sites and baselines is consistent with expected statistical fluctuations. The results from most stations are consistent with approximately 65% of the modeled pressure load being found in the GPS vertical position measurements. Removing an annual signal from both the measured heights and the modeled load time series leaves this value unchanged.

  16. The global geodynamic effect of the Macquarie Ridge earthquake

    SciTech Connect

    Gross, R.S.; Chao, B. Fong

    1990-06-01

    Besides generating seismic waves, which eventually dissipate, an earthquake also generates a static displacement field everywhere within the Earth. This global displacement field rearranges the Earth's mass distribution, causing the Earth's rotational properties and gravitational field to change. The size of these changes depends, in general, upon the size of the earthquake. The Macquarie Ridge earthquake of May 23, 1989 is considered to be the largest earthquake to have occurred since the 1977 Sumba and Tonga events. As such, the coseismic effect of this earthquake upon the Earth's length-of-day, polar motion, and low-degree harmonic coefficients of the gravitational field are computed. It is found that this earthquake should have caused the length-of-day to decrease by 0.06 {mu}sec, the position of the mean rotation pole to shift 0.11 milli-arcsec towards 323{degree}E longitude, and selected degree l = 2-5 gravitational field coefficients to change by about 1 part in 10{sup 13}. These changes are all smaller than can be detected by current observational techniques. However, changes of this size could perhaps be detected in the future with the implementation of proposed improvements to the techniques of monitoring the Earth's rotation, and (especially for the low-degree gravitational field coefficients) with the placement of GPS receivers onboard orbiting spacecraft.

  17. No globally consistent effect of ectomycorrhizal status on foliar traits.

    PubMed

    Koele, Nina; Dickie, Ian A; Oleksyn, Jacek; Richardson, Sarah J; Reich, Peter B

    2012-11-01

    The concept that ectomycorrhizal plants have a particular foliar trait suite characterized by low foliar nutrients and high leaf mass per unit area (LMA) is widely accepted, but whether this trait suite can be generalized to all ectomycorrhizal clades is unclear. We identified 19 evolutionary clades of ectomycorrhizal plants and used a global leaf traits dataset comprising 11,466 samples across c. 3000 species to test whether there were consistent shifts in leaf nutrients or LMA with the evolution of ectomycorrhiza. There were no consistent effects of ectomycorrhizal status on foliar nutrients or LMA in the 17 ectomycorrhizal/non-ectomycorrhizal pairs for which we had sufficient data, with some ectomycorrhizal groups having higher and other groups lower nutrient status than non-ectomycorrhizal contrasts. Controlling for the woodiness of host species did not alter the results. Our findings suggest that the concepts of ectomycorrhizal plant trait suites should be re-examined to ensure that they are broadly reflective of mycorrhizal status across all evolutionary clades, rather than reflecting the traits of a few commonly studied groups, such as the Pinaceae and Fagales.

  18. Effect of cosmic ray on global high cloud from MODIS

    NASA Astrophysics Data System (ADS)

    Kim, H.-S.; Choi, Y.-S.

    2012-04-01

    than low and middle clouds. Considering the correlations with dependence on regions, a physical cloud process regarding to cosmic ray may not be universal perhaps due to anonymous factors affecting the cloud amount. However, our synthetic conclusion is that the amount of global high cloud increases with increased cosmic ray. This implies that infrared warming effect due to increased high cloud may be intensified when more cosmic ray comes in.

  19. In-depth phosphoproteomic analysis of royal jelly derived from western and eastern honeybee species.

    PubMed

    Han, Bin; Fang, Yu; Feng, Mao; Lu, Xiaoshan; Huo, Xinmei; Meng, Lifeng; Wu, Bin; Li, Jianke

    2014-12-05

    The proteins in royal jelly (RJ) play a pivotal role in the nutrition, immune defense, and cast determination of honeybee larvae and have a wide range of pharmacological and health-promoting functions for humans as well. Although the importance of post-translational modifications (PTMs) in protein function is known, investigation of protein phosphorylation of RJ proteins is still very limited. To this end, two complementary phosphopeptide enrichment materials (Ti(4+)-IMAC and TiO2) and high-sensitivity mass spectrometry were applied to establish a detailed phosphoproteome map and to qualitatively and quantitatively compare the phosphoproteomes of RJ produced by Apis mellifera ligustica (Aml) and Apis cerana cerana (Acc). In total, 16 phosphoproteins carrying 67 phosphorylation sites were identified in RJ derived from western bees, and nine proteins phosphorylated on 71 sites were found in RJ produced by eastern honeybees. Of which, eight phosphorylated proteins were common to both RJ samples, and the same motif ([S-x-E]) was extracted, suggesting that the function of major RJ proteins as nutrients and immune agents is evolutionary preserved in both of these honeybee species. All eight overlapping phosphoproteins showed significantly higher abundance in Acc-RJ than in Aml-RJ, and the phosphorylation of Jelleine-II (an antimicrobial peptide, TPFKLSLHL) at S(6) in Acc-RJ had stronger antimicrobial properties than that at T(1) in Aml-RJ even though the overall antimicrobial activity of Jelleine-II was found to decrease after phosphorylation. The differences in phosphosites, peptide abundance, and antimicrobial activity of the phosphorylated RJ proteins indicate that the two major honeybee species employ distinct phosphorylation strategies that align with their different biological characteristics shaped by evolution. The phosphorylation of RJ proteins are potentially driven by the activity of extracellular serine/threonine protein kinase FAM20C-like protein (FAM20C

  20. Classic Ras Proteins Promote Proliferation and Survival Via Distinct Phosphoproteome Alterations in Neurofibromin-Null Malignant Peripheral Nerve Sheath Tumor Cells

    PubMed Central

    Brossier, Nicole M.; Prechtl, Amanda M.; Longo, Jody Fromm; Barnes, Stephen; Wilson, Landon S.; Byer, Stephanie J.; Brosius, Stephanie N.; Carroll, Steven L.

    2015-01-01

    Neurofibromin, the tumor suppressor encoded by the neurofibromatosis type 1 (NF1) gene, potentially suppresses the activation of H-Ras, N-Ras and K-Ras. However, it is not known whether these classic Ras proteins are hyperactivated in NF1-null nerve sheath tumors, how they contribute to tumorigenesis and what signaling pathways mediate their effects. Here we show that H-Ras, N-Ras and K-Ras are coexpressed with their activators, (guanine nucleotide exchange factors), in neurofibromin-null malignant peripheral nerve sheath tumor (MPNST) cells and that all 3 Ras proteins are activated. Dominant negative (DN) H-Ras, a pan-inhibitor of the classic Ras family, inhibited MPNST proliferation and survival, but not migration. However, NF1-null MPNST cells were variably dependent on individual Ras proteins. In some lines, ablation of H-Ras, N-Ras and/or K-Ras inhibited mitogenesis. In others, ablation of a single Ras protein had no effect on proliferation; in these lines, ablation of a single Ras protein resulted in compensatory increases in the activation and/or expression of other Ras proteins. Using mass spectrometry-based phosphoproteomics, we identified 7 signaling networks affecting morphology, proliferation and survival that are regulated by DN H-Ras. Thus, neurofibromin loss activates multiple classic Ras proteins that promote proliferation and survival by regulating several distinct signaling cascades. PMID:25946318

  1. Understanding the Development and Perception of Global Health for More Effective Student Education

    PubMed Central

    Chen, Xinguang

    2014-01-01

    The concept of “global health” that led to the establishment of the World Health Organization in the 1940s is still promoting a global health movement 70 years later. Today’s global health acts first as a guiding principle for our effort to improve people’s health across the globe. Furthermore, global health has become a branch of science, “global health science,” supporting institutionalized education. Lastly, as a discipline, global health should focus on medical and health issues that: 1) are determined primarily by factors with a cross-cultural, cross-national, cross-regional, or global scope; 2) are local but have global significance if not appropriately managed; and 3) can only be efficiently managed through international or global efforts. Therefore, effective global health education must train students 1) to understand global health status; 2) to investigate both global and local health issues with a global perspective; and 3) to devise interventions to deal with these issues. PMID:25191139

  2. Global Strike 2035: Considerations for Enabling Effective Command and Control

    DTIC Science & Technology

    2012-02-16

    Enabling Theater Time-Sensitive Targeting Much has been learned over the past decade about the command and control attributes required to conduct...future. However, for Global Strike missions in 2035, the lessons learned through theater level operations must be extrapolated to a global scale and...established norms.44 For any organization that must learn to operate in new ways in support of innovative capabilities, leadership must ensure the

  3. Effects of climate variability on global scale flood risk

    NASA Astrophysics Data System (ADS)

    Ward, P.; Dettinger, M. D.; Kummu, M.; Jongman, B.; Sperna Weiland, F.; Winsemius, H.

    2013-12-01

    In this contribution we demonstrate the influence of climate variability on flood risk. Globally, flooding is one of the worst natural hazards in terms of economic damages; Munich Re estimates global losses in the last decade to be in excess of $240 billion. As a result, scientifically sound estimates of flood risk at the largest scales are increasingly needed by industry (including multinational companies and the insurance industry) and policy communities. Several assessments of global scale flood risk under current and conditions have recently become available, and this year has seen the first studies assessing how flood risk may change in the future due to global change. However, the influence of climate variability on flood risk has as yet hardly been studied, despite the fact that: (a) in other fields (drought, hurricane damage, food production) this variability is as important for policy and practice as long term change; and (b) climate variability has a strong influence in peak riverflows around the world. To address this issue, this contribution illustrates the influence of ENSO-driven climate variability on flood risk, at both the globally aggregated scale and the scale of countries and large river basins. Although it exerts significant and widespread influences on flood peak discharges in many parts of the world, we show that ENSO does not have a statistically significant influence on flood risk once aggregated to global totals. At the scale of individual countries, though, strong relationships exist over large parts of the Earth's surface. For example, we find particularly strong anomalies of flood risk in El Niño or La Niña years (compared to all years) in southern Africa, parts of western Africa, Australia, parts of Central Eurasia (especially for El Niño), the western USA (especially for La Niña), and parts of South America. These findings have large implications for both decadal climate-risk projections and long-term future climate change

  4. The ripple effect: why promoting female leadership in global health matters.

    PubMed

    Downs, J A; Mathad, J S; Reif, L K; McNairy, M L; Celum, C; Boutin-Foster, C; Deschamps, M M; Gupta, A; Hokororo, A; Katz, I T; Konopasek, L; Nelson, R; Riviere, C; Glimcher, L H; Fitzgerald, D W

    2016-12-21

    Leadership positions in global health are greatly skewed toward men; the imbalance is more pronounced in low- and middle-income countries (LMICs). The under-representation of women in leadership is a threat to gender equality, and also impacts the improvement of women's health outcomes globally. In this perspectives piece, we assert that the promotion and retention of women in global health leadership has a ripple effect that can achieve improvement in global health outcomes. We present pragmatic, actionable solutions to promote and retain female global health leaders in this field.

  5. The ripple effect: why promoting female leadership in global health matters

    PubMed Central

    Downs, J. A.; Mathad, J. S.; McNairy, M. L.; Celum, C.; Boutin-Foster, C.; Deschamps, M. M.; Gupta, A.; Hokororo, A.; Katz, I. T.; Konopasek, L.; Nelson, R.; Riviere, C.; Glimcher, L. H.; Fitzgerald, D. W.

    2016-01-01

    Leadership positions in global health are greatly skewed toward men; the imbalance is more pronounced in low- and middle-income countries (LMICs). The under-representation of women in leadership is a threat to gender equality, and also impacts the improvement of women's health outcomes globally. In this perspectives piece, we assert that the promotion and retention of women in global health leadership has a ripple effect that can achieve improvement in global health outcomes. We present pragmatic, actionable solutions to promote and retain female global health leaders in this field. PMID:28123954

  6. Phosphoproteomic Analyses of NRAS(G12) and NRAS(Q61) Mutant Melanocytes Reveal Increased CK2α Kinase Levels in NRAS(Q61) Mutant Cells.

    PubMed

    Posch, Christian; Sanlorenzo, Martina; Vujic, Igor; Oses-Prieto, Juan A; Cholewa, Brian D; Kim, Sarasa T; Ma, Jeffrey; Lai, Kevin; Zekhtser, Mitchell; Esteve-Puig, Rosaura; Green, Gary; Chand, Shreya; Burlingame, Alma L; Panzer-Grümayer, Renate; Rappersberger, Klemens; Ortiz-Urda, Susana

    2016-10-01

    In melanoma, mutant and thereby constantly active neuroblastoma rat sarcoma (NRAS) affects 15-20% of tumors, contributing to tumor initiation, growth, invasion, and metastasis. Recent therapeutic approaches aim to mimic RAS extinction by interfering with critical signaling pathways downstream of the mutant protein. This study investigates the phosphoproteome of primary human melanocytes bearing mutations in the two hot spots of NRAS, NRAS(G12) and NRAS(Q61). Stable isotope labeling by amino acids in cell culture followed by mass spectrometry identified 14,155 spectra of 3,371 unique phosphopeptides mapping to 1,159 proteins (false discovery rate < 2%). Data revealed pronounced PI3K/AKT signaling in NRAS(G12V) mutant cells and pronounced mitogen-activated protein kinase (MAPK) signaling in NRAS(Q61L) variants. Computer-based prediction models for kinases involved, revealed that CK2α is significantly overrepresented in primary human melanocytes bearing NRAS(Q61L) mutations. Similar differences were found in human NRAS(Q61) mutant melanoma cell lines that were also more sensitive to pharmacologic CK2α inhibition compared with NRAS(G12) mutant cells. Furthermore, CK2α levels were pronounced in patient samples of NRAS(Q61) mutant melanoma at the mRNA and protein level. The preclinical findings of this study reveal that codon 12 and 61 mutant NRAS cells have distinct signaling characteristics that could allow for the development of more effective, mutation-specific treatment modalities.

  7. Quantitative Phosphoproteomics Identifies Filaggrin and other Targets of Ionizing Radiation in a Human Skin Model

    SciTech Connect

    Yang, Feng; Waters, Katrina M.; Webb-Robertson, Bobbie-Jo M.; Sowa, Marianne B.; Freiin von Neubeck, Claere H.; Aldrich, Joshua T.; Markillie, Lye Meng; Wirgau, Rachel M.; Gristenko, Marina A.; Zhao, Rui; Camp, David G.; Smith, Richard D.; Stenoien, David L.

    2012-04-17

    Our objective here was to perform a quantitative phosphoproteomic study on a reconstituted human skin tissue to identify low and high dose ionizing radiation dependent signaling in a complex 3-dimensional setting. Application of an isobaric labeling strategy using sham and 3 radiation doses (3, 10, 200 cGy) resulted in the identification of 1113 unique phosphopeptides. Statistical analyses identified 151 phosphopeptides showing significant changes in response to radiation and radiation dose. Proteins responsible for maintaining skin structural integrity including keratins and desmosomal proteins (desmoglein, desmoplakin, plakophilin 1 and 2,) had altered phosphorylation levels following exposure to both low and high doses of radiation. A phosphorylation site present in multiple copies in the linker regions of human profilaggrin underwent the largest fold change. Increased phosphorylation of these sites coincided with altered profilaggrin processing suggesting a role for linker phosphorylation in human profilaggrin regulation. These studies demonstrate that the reconstituted human skin system undergoes a coordinated response to ionizing radiation involving multiple layers of the stratified epithelium that serve to maintain skin barrier functions and minimize the damaging consequences of radiation exposure.

  8. Niobium(V) oxide (Nb2O5): application to phosphoproteomics.

    PubMed

    Ficarro, Scott B; Parikh, Jignesh R; Blank, Nathaniel C; Marto, Jarrod A

    2008-06-15

    Proteomics-based analysis of signaling cascades relies on a growing suite of affinity resins and methods aimed at efficient enrichment of phosphorylated peptides from complex biological mixtures. Given the heterogeneity of phosphopeptides and the overlap in chemical properties between phospho- and unmodified peptides, it is likely that the use of multiple resins will provide the best combination of specificity, yield, and coverage for large-scale proteomics studies. Recently titanium and zirconium dioxides have been used successfully for enrichment of phosphopeptides. Here we report the first demonstration that niobium pentoxide (Nb 2O 5) provides for efficient enrichment and recovery ( approximately 50-100%) of phosphopeptides from simple mixtures and facilitates identification of several hundred putative sites of phosphorylation from cell lysate. Comparison of phosphorylated peptides identified from Nb 2O 5 and TiO 2 with sequences in the PhosphoELM database suggests a useful degree of divergence in the selectivity of these metal oxide resins. Collectively our data indicate that Nb 2O 5 provides efficient enrichment for phosphopeptides and offers a complementary approach for large-scale phosphoproteomics studies.

  9. Phosphoproteomic Analysis of Paper Mulberry Reveals Phosphorylation Functions in Chilling Tolerance.

    PubMed

    Pi, Zhi; Zhao, Mei-Ling; Peng, Xian-Jun; Shen, Shi-Hua

    2017-04-13

    Paper mulberry is a valuable woody species with a good chilling tolerance. In this study, phosphoproteomic analysis, physiological measurement, and mRNA quantification were employed to explore the molecular mechanism of chilling (4 °C) tolerance in paper mulberry. After chilling for 6 h, 427 significantly changed phosphoproteins were detected in paper mulberry seedlings without obvious physiological injury. When obvious physiological injury occurred after chilling for 48 h, a total of 611 phosphoproteins were found to be significantly changed at the phosphorylation level. Several protein kinases, especially CKII, were possibly responsible for these changes according to conserved sequence analysis. The results of Gene Ontology analysis showed that phosphoproteins were mainly responsible for signal transduction, protein modification, and translation during chilling. Additionally, transport and cellular component organization were enriched after chilling for 6 and 48 h, respectively. On the basis of the protein-protein interaction network analysis, a protein kinase and phosphatases hub protein (P1959) were found to be involved in cross-talk between Ca(2+), BR, ABA, and ethylene-mediated signaling pathways. We also highlighted the phosphorylation of BpSIZ1 and BpICE1 possibly impacted on the CBF/DREB-responsive pathway. From these results, we developed a schematic for the chilling tolerance mechanism at phosphorylation level.

  10. Phosphoproteomic dynamics of chickpea (Cicer arietinum L.) reveals shared and distinct components of dehydration response.

    PubMed

    Subba, Pratigya; Barua, Pragya; Kumar, Rajiv; Datta, Asis; Soni, Kamlesh Kumar; Chakraborty, Subhra; Chakraborty, Niranjan

    2013-11-01

    Reversible protein phosphorylation is a ubiquitous regulatory mechanism that plays critical roles in transducing stress signals to bring about coordinated intracellular responses. To gain better understanding of dehydration response in plants, we have developed a differential phosphoproteome in a food legume, chickpea (Cicer arietinum L.). Three-week-old chickpea seedlings were subjected to progressive dehydration by withdrawing water, and the changes in the phosphorylation status of a large repertoire of proteins were monitored. The proteins were resolved by 2-DE and stained with phosphospecific fluorescent Pro-Q Diamond dye. Mass spectrometric analysis led to the identification of 91 putative phosphoproteins, presumably involved in a variety of functions including cell defense and rescue, photosynthesis and photorespiration, molecular chaperones, and ion transport, among others. Multiple sites of phosphorylation were predicted on several key elements, which include both the regulatory as well as the functional proteins. A critical survey of the phosphorylome revealed a DREPP (developmentally regulated plasma membrane protein) plasma membrane polypeptide family protein, henceforth designated CaDREPP1. The transcripts of CaDREPP1 were found to be differentially regulated under dehydration stress, further corroborating the proteomic results. This work provides new insights into the possible phosphorylation events triggered by the conditions of progressive water-deficit in plants.

  11. Quantitative Proteomic and Phosphoproteomic Approaches for Deciphering the Signaling Pathway for Tension Wood Formation in Poplar.

    PubMed

    Mauriat, Mélanie; Leplé, Jean-Charles; Claverol, Stéphane; Bartholomé, Jérôme; Negroni, Luc; Richet, Nicolas; Lalanne, Céline; Bonneu, Marc; Coutand, Catherine; Plomion, Christophe

    2015-08-07

    Trees adjust their growth following forced changes in orientation to re-establish a vertical position. In angiosperms, this adjustment involves the differential regulation of vascular cambial activity between the lower (opposite wood) and upper (tension wood) sides of the leaning stem. We investigated the molecular mechanisms leading to the formation of differential wood types through a quantitative proteomic and phosphoproteomic analysis on poplar subjected to a gravitropic stimulus. We identified and quantified 675 phosphopeptides, corresponding to 468 phosphoproteins, and 3 763 nonphosphorylated peptides, corresponding to 1 155 proteins, in the differentiating xylem of straight-growing trees (control) and trees subjected to a gravitational stimulus during 8 weeks. About 1% of the peptides were specific to a wood type (straight, opposite, or tension wood). Proteins quantified in more than one type of wood were more numerous: a mixed linear model showed 389 phosphopeptides and 556 proteins to differ in abundance between tension wood and opposite wood. Twenty-one percent of the phosphoproteins identified here were described in their phosphorylated form for the first time. Our analyses revealed remarkable developmental molecular plasticity, with wood type-specific phosphorylation events, and highlighted the involvement of different proteins in the biosynthesis of cell wall components during the formation of the three types of wood.

  12. Phosphoproteomics Profiling of Tobacco Mature Pollen and Pollen Activated in vitro *

    PubMed Central

    Fíla, Jan; Radau, Sonja; Matros, Andrea; Hartmann, Anja; Scholz, Uwe; Feciková, Jana; Mock, Hans-Peter; Čapková, Věra; Zahedi, René Peiman; Honys, David

    2016-01-01

    Tobacco mature pollen has extremely desiccated cytoplasm, and is metabolically quiescent. Upon re-hydration it becomes metabolically active and that results in later emergence of rapidly growing pollen tube. These changes in cytoplasm hydration and metabolic activity are accompanied by protein phosphorylation. In this study, we subjected mature pollen, 5-min-activated pollen, and 30-min-activated pollen to TCA/acetone protein extraction, trypsin digestion and phosphopeptide enrichment by titanium dioxide. The enriched fraction was subjected to nLC-MS/MS. We identified 471 phosphopeptides that carried 432 phosphorylation sites, position of which was exactly matched by mass spectrometry. These 471 phosphopeptides were assigned to 301 phosphoproteins, because some proteins carried more phosphorylation sites. Of the 13 functional groups, the majority of proteins were put into these categories: transcription, protein synthesis, protein destination and storage, and signal transduction. Many proteins were of unknown function, reflecting the fact that male gametophyte contains many specific proteins that have not been fully functionally annotated. The quantitative data highlighted the dynamics of protein phosphorylation during pollen activation; the identified phosphopeptides were divided into seven groups based on the regulatory trends. The major group comprised mature pollen-specific phosphopeptides that were dephosphorylated during pollen activation. Several phosphopeptides representing the same phosphoprotein had different regulation, which pinpointed the complexity of protein phosphorylation and its clear functional context. Collectively, we showed the first phosphoproteomics data on activated pollen where the position of phosphorylation sites was clearly demonstrated and regulatory kinetics was resolved. PMID:26792808

  13. Phosphoproteomics Profiling of Tobacco Mature Pollen and Pollen Activated in vitro.

    PubMed

    Fíla, Jan; Radau, Sonja; Matros, Andrea; Hartmann, Anja; Scholz, Uwe; Feciková, Jana; Mock, Hans-Peter; Čapková, Věra; Zahedi, René Peiman; Honys, David

    2016-04-01

    Tobacco mature pollen has extremely desiccated cytoplasm, and is metabolically quiescent. Upon re-hydration it becomes metabolically active and that results in later emergence of rapidly growing pollen tube. These changes in cytoplasm hydration and metabolic activity are accompanied by protein phosphorylation. In this study, we subjected mature pollen, 5-min-activated pollen, and 30-min-activated pollen to TCA/acetone protein extraction, trypsin digestion and phosphopeptide enrichment by titanium dioxide. The enriched fraction was subjected to nLC-MS/MS. We identified 471 phosphopeptides that carried 432 phosphorylation sites, position of which was exactly matched by mass spectrometry. These 471 phosphopeptides were assigned to 301 phosphoproteins, because some proteins carried more phosphorylation sites. Of the 13 functional groups, the majority of proteins were put into these categories: transcription, protein synthesis, protein destination and storage, and signal transduction. Many proteins were of unknown function, reflecting the fact that male gametophyte contains many specific proteins that have not been fully functionally annotated. The quantitative data highlighted the dynamics of protein phosphorylation during pollen activation; the identified phosphopeptides were divided into seven groups based on the regulatory trends. The major group comprised mature pollen-specific phosphopeptides that were dephosphorylated during pollen activation. Several phosphopeptides representing the same phosphoprotein had different regulation, which pinpointed the complexity of protein phosphorylation and its clear functional context. Collectively, we showed the first phosphoproteomics data on activated pollen where the position of phosphorylation sites was clearly demonstrated and regulatory kinetics was resolved.

  14. Quantitative phosphoproteomic analyses of the inferior parietal lobule from three different pathological stages of Alzheimer's disease.

    PubMed

    Triplett, Judy C; Swomley, Aaron M; Cai, Jian; Klein, Jon B; Butterfield, D Allan

    2016-01-01

    Alzheimer's disease (AD), the most common age-related neurodegenerative disorder, is clinically characterized by progressive neuronal loss resulting in loss of memory and dementia. AD is histopathologically characterized by the extensive distribution of senile plaques and neurofibrillary tangles, and synapse loss. Amnestic mild cognitive impairment (MCI) is generally accepted to be an early stage of AD. MCI subjects have pathology and symptoms that fall on the scale intermediately between 'normal' cognition with little or no pathology and AD. A rare number of individuals, who exhibit normal cognition on psychometric tests but whose brains show widespread postmortem AD pathology, are classified as 'asymptomatic' or 'preclinical' AD (PCAD). In this study, we evaluated changes in protein phosphorylation states in the inferior parietal lobule of subjects with AD, MCI, PCAD, and control brain using a 2-D PAGE proteomics approach in conjunction with Pro-Q Diamond phosphoprotein staining. Statistically significant changes in phosphorylation levels were found in 19 proteins involved in energy metabolism, neuronal plasticity, signal transduction, and oxidative stress response. Changes in the disease state phosphoproteome may provide insights into underlying mechanisms for the preservation of memory with expansive AD pathology in PCAD and the progressive memory loss in amnestic MCI that escalates to the dementia and the characteristic pathology of AD brain.

  15. Site-Specific Ser/Thr/Tyr Phosphoproteome of Sinorhizobium meliloti at Stationary Phase.

    PubMed

    Liu, Tao; Tian, Chang Fu; Chen, Wen Xin

    2015-01-01

    Sinorhizobium meliloti, a facultative microsymbiont of alfalfa, should fine-tune its cellular processes to live saprophytically in soils characterized with limited nutrients and diverse stresses. In this study, TiO2 enrichment and LC-MS/MS were used to uncover the site-specific Ser/Thr/Tyr phosphoproteome of S. meliloti in minimum medium at stationary phase. There are a total of 96 unique phosphorylated sites, with a Ser/Thr/Tyr distribution of 63:28:5, in 77 proteins. Phosphoproteins identified in S. meliloti showed a wide distribution pattern regarding to functional categories, such as replication, transcription, translation, posttranslational modification, transport and metabolism of amino acids, carbohydrate, inorganic ion, succinoglycan etc. Ser/Thr/Tyr phosphosites identified within the conserved motif in proteins of key cellular function indicate a crucial role of phosphorylation in modulating cellular physiology. Moreover, phosphorylation in proteins involved in processes related to rhizobial adaptation was also discussed, such as those identified in SMa0114 and PhaP2 (polyhydroxybutyrate synthesis), ActR (pH stress and microaerobic adaption), SupA (potassium stress), chaperonin GroEL2 (viability and potentially symbiosis), and ExoP (succinoglycan synthesis and secretion). These Ser/Thr/Tyr phosphosites identified herein would be helpful for our further investigation and understanding of the role of phosphorylation in rhizobial physiology.

  16. Phosphoproteomic analysis reveals interconnected system-wide responses to perturbations of kinases and phosphatases in yeast.

    PubMed

    Bodenmiller, Bernd; Wanka, Stefanie; Kraft, Claudine; Urban, Jörg; Campbell, David; Pedrioli, Patrick G; Gerrits, Bertran; Picotti, Paola; Lam, Henry; Vitek, Olga; Brusniak, Mi-Youn; Roschitzki, Bernd; Zhang, Chao; Shokat, Kevan M; Schlapbach, Ralph; Colman-Lerner, Alejandro; Nolan, Garry P; Nesvizhskii, Alexey I; Peter, Matthias; Loewith, Robbie; von Mering, Christian; Aebersold, Ruedi

    2010-12-21

    The phosphorylation and dephosphorylation of proteins by kinases and phosphatases constitute an essential regulatory network in eukaryotic cells. This network supports the flow of information from sensors through signaling systems to effector molecules and ultimately drives the phenotype and function of cells, tissues, and organisms. Dysregulation of this process has severe consequences and is one of the main factors in the emergence and progression of diseases, including cancer. Thus, major efforts have been invested in developing specific inhibitors that modulate the activity of individual kinases or phosphatases; however, it has been difficult to assess how such pharmacological interventions would affect the cellular signaling network as a whole. Here, we used label-free, quantitative phosphoproteomics in a systematically perturbed model organism (Saccharomyces cerevisiae) to determine the relationships between 97 kinases, 27 phosphatases, and more than 1000 phosphoproteins. We identified 8814 regulated phosphorylation events, describing the first system-wide protein phosphorylation network in vivo. Our results show that, at steady state, inactivation of most kinases and phosphatases affected large parts of the phosphorylation-modulated signal transduction machinery-and not only the immediate downstream targets. The observed cellular growth phenotype was often well maintained despite the perturbations, arguing for considerable robustness in the system. Our results serve to constrain future models of cellular signaling and reinforce the idea that simple linear representations of signaling pathways might be insufficient for drug development and for describing organismal homeostasis.

  17. Urinary proteomic and non-prefractionation quantitative phosphoproteomic analysis during pregnancy and non-pregnancy

    PubMed Central

    2013-01-01

    Background Progress in the fields of protein separation and identification technologies has accelerated research into biofluids proteomics for protein biomarker discovery. Urine has become an ideal and rich source of biomarkers in clinical proteomics. Here we performed a proteomic analysis of urine samples from pregnant and non-pregnant patients using gel electrophoresis and high-resolution mass spectrometry. Furthermore, we also apply a non-prefractionation quantitative phosphoproteomic approach using mTRAQ labeling to evaluate the expression of specific phosphoproteins during pregnancy comparison with non-pregnancy. Results In total, 2579 proteins (10429 unique peptides) were identified, including 1408 from the urine of pregnant volunteers and 1985 from the urine of non-pregnant volunteers. One thousand and twenty-three proteins were not reported in previous studies at the proteome level and were unique to our study. Furthermore, we obtained 237 phosphopeptides, representing 105 phosphoproteins. Among these phosphoproteins, 16 of them were found to be significantly differentially expressed, of which 14 were up-regulated and two were down-regulated in urine samples from women just before vaginal delivery. Conclusion Taken together, these results offer a comprehensive urinary proteomic profile of healthy women during before and after vaginal delivery and novel information on the phosphoproteins that are differentially regulated during the maintenance of normal pregnancy. Our results may provide a better understanding of the mechanisms of pregnancy maintenance, potentially leading to the development of biomarker-based sensitive assays for understanding pregnancy. PMID:24215720

  18. Deoxygenation affects tyrosine phosphoproteome of red cell membrane from patients with sickle cell disease.

    PubMed

    Siciliano, Angela; Turrini, Franco; Bertoldi, Mariarita; Matte, Alessandro; Pantaleo, Antonella; Olivieri, Oliviero; De Franceschi, Lucia

    2010-04-15

    Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder related to the production of a defective form of hemoglobin, hemoglobin S (HbS). One of the hallmarks of SCD is the presence of dense, dehydrate highly adhesive sickle red blood cells (RBCs) that result from persistent membrane damage associated with HbS polymerization, abnormal activation of membrane cation transports and generation of distorted and rigid red cells with membrane perturbation and cytoskeleton dysfunction. Although modulation of phosphorylation state of the proteins from membrane and cytoskeleton networks has been proposed to participate in red cell homeostasis, much still remains to be investigated in normal and diseased red cells. Here, we report that tyrosine (Tyr-) phosphoproteome of sickle red cells was different from normal controls and was affected by deoxygenation. We found proteins, p55 and band 4.1, from the junctional complex, differently Tyr-phosphorylated in SCD RBCs compared to normal RBCs under normoxia and modulated by deoxygenation, while band 4.2 was similarly Tyr-phosphorylated in both conditions. In SCD RBCs we identified the phosphopeptides for protein 4.1R located in the protein FERM domain (Tyr-13) and for alpha-spectrin located near or in a linker region (Tyr-422 and Tyr-1498) involving protein areas crucial for their functions in the context of red cell membrane properties, suggesting that Tyr-phosphorylation may be part of the events involved in maintaining membrane mechanical stability in SCD red cells.

  19. Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases

    PubMed Central

    Steger, Martin; Tonelli, Francesca; Ito, Genta; Davies, Paul; Trost, Matthias; Vetter, Melanie; Wachter, Stefanie; Lorentzen, Esben; Duddy, Graham; Wilson, Stephen; Baptista, Marco AS; Fiske, Brian K; Fell, Matthew J; Morrow, John A; Reith, Alastair D; Alessi, Dario R; Mann, Matthias

    2016-01-01

    Mutations in Park8, encoding for the multidomain Leucine-rich repeat kinase 2 (LRRK2) protein, comprise the predominant genetic cause of Parkinson's disease (PD). G2019S, the most common amino acid substitution activates the kinase two- to threefold. This has motivated the development of LRRK2 kinase inhibitors; however, poor consensus on physiological LRRK2 substrates has hampered clinical development of such therapeutics. We employ a combination of phosphoproteomics, genetics, and pharmacology to unambiguously identify a subset of Rab GTPases as key LRRK2 substrates. LRRK2 directly phosphorylates these both in vivo and in vitro on an evolutionary conserved residue in the switch II domain. Pathogenic LRRK2 variants mapping to different functional domains increase phosphorylation of Rabs and this strongly decreases their affinity to regulatory proteins including Rab GDP dissociation inhibitors (GDIs). Our findings uncover a key class of bona-fide LRRK2 substrates and a novel regulatory mechanism of Rabs that connects them to PD. DOI: http://dx.doi.org/10.7554/eLife.12813.001 PMID:26824392

  20. Quantitative phosphoproteomics reveals new roles for the protein phosphatase PP6 in mitotic cells

    PubMed Central

    Rusin, Scott F.; Schlosser, Kate A.; Adamo, Mark E.; Kettenbach, Arminja N.

    2017-01-01

    Protein phosphorylation is an important regulatory mechanism controlling mitotic progression. Protein phosphatase 6 (PP6) is an essential enzyme with conserved roles in chromosome segregation and spindle assembly from yeast to humans. We applied a baculovirus-mediated gene silencing approach to deplete HeLa cells of the catalytic subunit of PP6 (PP6c) and analyzed changes in the phosphoproteome and proteome in mitotic cells by quantitative mass spectrometry–based proteomics. We identified 408 phosphopeptides on 272 proteins that increased and 298 phosphopeptides on 220 proteins that decreased in phosphorylation upon PP6c depletion in mitotic cells. Motif analysis of the phosphorylated sites combined with bioinformatics pathway analysis revealed previously unknown PP6c–dependent regulatory pathways. Biochemical assays demonstrated that PP6c opposed casein kinase 2–dependent phosphorylation of the condensin I subunit NCAP-G, and cellular analysis showed that depletion of PP6c resulted in defects in chromosome condensation and segregation in anaphase, consistent with dysregulation of condensin I function in the absence of PP6 activity. PMID:26462736

  1. Newly fabricated magnetic lanthanide oxides core-shell nanoparticles in phosphoproteomics.

    PubMed

    Jabeen, Fahmida; Najam-Ul-Haq, Muhammad; Rainer, Matthias; Güzel, Yüksel; Huck, Christian W; Bonn, Guenther K

    2015-01-01

    Metal oxides show high selectivity and sensitivity toward mass spectrometry based enrichment strategies. Phosphopeptides/phosphoproteins enrichment from biological samples is cumbersome because of their low abundance. Phosphopeptides are of interest in enzymes and phosphorylation pathways which lead to the clinical links of a disease. Magnetic core-shell lanthanide oxide nanoparticles (Fe3O4@SiO2-La2O3 and Fe3O4@SiO2-Sm2O3) are fabricated, characterized by SEM, FTIR, and EDX and employed in the enrichment of phosphopeptides. The nanoparticles enrich phosphopeptides from casein variants, nonfat milk, egg yolk, human serum and HeLa cell extract. The materials and enrichment protocols are designed in a way that there are almost no nonspecific bindings. The selectivity is achieved up to 1:8500 using β-casein/BSA mixture and sensitivity down to 1 atto-mole. Batch-to-batch reproducibility is high with the reuse of core-shell nanoparticles up to four cycles. The enrichment followed by MALDI-MS analyses is carried out for the identification of phosphopeptides from serum digest and HeLa cell extract. Characteristic phosphopeptides of phosphoproteins are identified from human serum after the enrichment, which have the diagnostic potential toward prostate cancer. Thus, the lanthanide based magnetic core-shell materials offer a highly selective and sensitive workflow in phosphoproteomics.

  2. Quantitative Phosphoproteomics Reveals the Role of Protein Arginine Phosphorylation in the Bacterial Stress Response*

    PubMed Central

    Schmidt, Andreas; Trentini, Débora Broch; Spiess, Silvia; Fuhrmann, Jakob; Ammerer, Gustav; Mechtler, Karl; Clausen, Tim

    2014-01-01

    Arginine phosphorylation is an emerging protein modification implicated in the general stress response of Gram-positive bacteria. The modification is mediated by the arginine kinase McsB, which phosphorylates and inactivates the heat shock repressor CtsR. In this study, we developed a mass spectrometric approach accounting for the peculiar chemical properties of phosphoarginine. The improved methodology was used to analyze the dynamic changes in the Bacillus subtilis arginine phosphoproteome in response to different stress situations. Quantitative analysis showed that a B. subtilis mutant lacking the YwlE arginine phosphatase accumulated a strikingly large number of arginine phosphorylations (217 sites in 134 proteins), however only a minor fraction of these sites was increasingly modified during heat shock or oxidative stress. The main targets of McsB-mediated arginine phosphorylation comprise central factors of the stress response system including the CtsR and HrcA heat shock repressors, as well as major components of the protein quality control system such as the ClpCP protease and the GroEL chaperonine. These findings highlight the impact of arginine phosphorylation in orchestrating the bacterial stress response. PMID:24263382

  3. Integrating Kinetic Effects into Global Models for Reconnection

    NASA Technical Reports Server (NTRS)

    Antiochos, S. K.

    2012-01-01

    Magnetic reconnection is the most striking example of how the coupling between global and kinetic scales can lead to fast energy release. Explosive solar activity, such as coronal mass ejections and flares for example, is widely believed to be due to the release of magnetic energy stored on global scales by magnetic reconnection operating on kinetic scales. Understanding how processes couple across spatial scales is one of the most difficult challenges in all of physics, and is undoubtedly the main obstacle to developing predictive models for the Sun's activity. Consequently, the NASA Living With a Star Program selected a Focused Science Team to attack the problem of cross-scale coupling in reconnection. In this talk I will present some of the results of the Team and review our latest theories and methods for modeling the global-local coupling in solar reconnection.

  4. Effects of mountain uplift on global monsoon precipitation

    NASA Astrophysics Data System (ADS)

    Lee, June-Yi; Wang, Bin; Seo, Kyong-Hwan; Ha, Kyung-Ja; Kitoh, Akio; Liu, Jian

    2015-08-01

    This study explores the role of the global mountain uplift (MU), which occurred during the middle and late Cenozoic, in modulating global monsoon precipitation using the Meteorological Research Institute atmosphere-ocean coupled model experiments. First, the MU causes changes in the annual mean of major monsoon precipitation. Although the annual mean precipitation over the entire globe remains about the same from the no-mountain experiment (MU0) to the realistic MU (MU1), that over the Asian-Australian monsoon region and Americas increases by about 16% and 9%, respectively. Second, the MU plays an essential role in advancing seasonal march, and summer-monsoon onset, especially in the Northern Hemisphere, by shaping pre-monsoon circulation. The rainy seasons are lengthened as a result of the earlier onset of the summer monsoon since the monsoon retreat is not sensitive to the MU. The East Asian monsoon is a unique consequence of the MU, while other monsoons are attributed primarily to land-sea distribution. Third, the strength of the global monsoon is shown to be substantially affected by the MU. In particular, the second annual cycle (AC) mode of global precipitation (the spring-autumn asymmetry mode) is more sensitive to the progressive MU than the first mode of the AC (the solstice mode), suggesting that the MU may have a greater impact during transition seasons than solstice seasons. Finally, the MU strongly modulates interannual variation in global monsoon precipitation in relation to El Niño and Southern Oscillation (ENSO). The Progressive MU changes not only the spatial distribution but also the periodicity of the first and second AC mode of global precipitation on interannual timescale.

  5. Commercial Complexity and Local and Global Involvement in Programs: Effects on Viewer Responses.

    ERIC Educational Resources Information Center

    Oberman, Heiko; Thorson, Esther

    A study investigated the effects of local (momentary) and global (whole program) involvement in program context and the effects of message complexity on the retention of television commercials. Sixteen commercials, categorized as simple video/simple audio through complex video/complex audio were edited into two globally high- and two globally…

  6. Using Interactive Technology to Support Students' Understanding of the Greenhouse Effect and Global Warming

    ERIC Educational Resources Information Center

    Varma, Keisha; Linn, Marcia C.

    2012-01-01

    In this work, we examine middle school students' understanding of the greenhouse effect and global warming. We designed and refined a technology-enhanced curriculum module called "Global Warming: Virtual Earth". In the module activities, students conduct virtual experiments with a visualization of the greenhouse effect. They analyze data and draw…

  7. EFFECTS OF GLOBAL CHANGE ON CORAL REEF ECOSYSTEMS

    EPA Science Inventory

    Corals and coral reefs of the Caribbean and through the world are deteriorating at an accelerated rate. Several stressors are believed to contrbute to this decline, including global changes in atmospheric gases and land use patterns. In particular, warmer water temperatures and...

  8. iPhos: a toolkit to streamline the alkaline phosphatase-assisted comprehensive LC-MS phosphoproteome investigation

    PubMed Central

    2014-01-01

    Background Comprehensive characterization of the phosphoproteome in living cells is critical in signal transduction research. But the low abundance of phosphopeptides among the total proteome in cells remains an obstacle in mass spectrometry-based proteomic analysis. To provide a solution, an alternative analytic strategy to confidently identify phosphorylated peptides by using the alkaline phosphatase (AP) treatment combined with high-resolution mass spectrometry was provided. While the process is applicable, the key integration along the pipeline was mostly done by tedious manual work. Results We developed a software toolkit, iPhos, to facilitate and streamline the work-flow of AP-assisted phosphoproteome characterization. The iPhos tookit includes one assister and three modules. The iPhos Peak Extraction Assister automates the batch mode peak extraction for multiple liquid chromatography mass spectrometry (LC-MS) runs. iPhos Module-1 can process the peak lists extracted from the LC-MS analyses derived from the original and dephosphorylated samples to mine out potential phosphorylated peptide signals based on mass shift caused by the loss of some multiples of phosphate groups. And iPhos Module-2 provides customized inclusion lists with peak retention time windows for subsequent targeted LC-MS/MS experiments. Finally, iPhos Module-3 facilitates to link the peptide identifications from protein search engines to the quantification results from pattern-based label-free quantification tools. We further demonstrated the utility of the iPhos toolkit on the data of human metastatic lung cancer cells (CL1-5). Conclusions In the comparison study of the control group of CL1-5 cell lysates and the treatment group of dasatinib-treated CL1-5 cell lysates, we demonstrated the applicability of the iPhos toolkit and reported the experimental results based on the iPhos-facilitated phosphoproteome investigation. And further, we also compared the strategy with pure DDA-based LC

  9. Time-varying correlations in global real estate markets: A multivariate GARCH with spatial effects approach

    NASA Astrophysics Data System (ADS)

    Gu, Huaying; Liu, Zhixue; Weng, Yingliang

    2017-04-01

    The present study applies the multivariate generalized autoregressive conditional heteroscedasticity (MGARCH) with spatial effects approach for the analysis of the time-varying conditional correlations and contagion effects among global real estate markets. A distinguishing feature of the proposed model is that it can simultaneously capture the spatial interactions and the dynamic conditional correlations compared with the traditional MGARCH models. Results reveal that the estimated dynamic conditional correlations have exhibited significant increases during the global financial crisis from 2007 to 2009, thereby suggesting contagion effects among global real estate markets. The analysis further indicates that the returns of the regional real estate markets that are in close geographic and economic proximities exhibit strong co-movement. In addition, evidence of significantly positive leverage effects in global real estate markets is also determined. The findings have significant implications on global portfolio diversification opportunities and risk management practices.

  10. Effects of boreal forest vegetation on global climate

    NASA Astrophysics Data System (ADS)

    Bonan, Gordon B.; Pollard, David; Thompson, Starley L.

    1992-10-01

    TERRESTRIAL ecosystems are thought to play an important role in determining regional and global climate1-6 one example of this is in Amazonia, where destruction of the tropical rainforest leads to warmer and drier conditions4-6. Boreal forest ecosystems may also affect climate. As temperatures rise, the amount of continental and oceanic snow and ice is reduced, so the land and ocean surfaces absorb greater amounts of solar radiation, reinforcing the warming in a 'snow/ice/albedo' feedback which results in large climate sensitivity to radiative forcings7-9. This sensitivity is moderated, however, by the presence of trees in northern latitudes, which mask the high reflectance of snow10,11, leading to warmer winter temperatures than if trees were not present12-14. Here we present results from a global climate model which show that the boreal forest warms both winter and summer air temperatures, relative to simulations in which the forest is replaced with bare ground or tundra vegetation. Our results suggest that future redistributions of boreal forest and tundra vegetation (due, for example, to extensive logging, or the influence of global warming) could initiate important climate feedbacks, which could also extend to lower latitudes.

  11. Direct health effects of global warming in Japan and China

    SciTech Connect

    Ando, M.; Yamamoto, S.; Tamura, K.

    1997-12-31

    Combustion of fossil fuels and industrial and agricultural activities are resulting in greater emissions of some greenhouse gases such as carbon dioxide and methane into the atmosphere, therefore contributing to global warming. Using general circulation models, it is estimated that surface temperatures in temperate regions will rise 1 to 3 degrees C during the next 100 years. Because global warming may increase the frequency and length of high temperatures during hot summer months, various health risks caused by heat stress have been studied. According to our epidemiological survey, the incidence of heat-related illness was significantly correlated to hot environments in Tokyo, Japan and in Nanjing and Wuhan, China. The epidemiological results also showed that the incidence of heat-related morbidity and mortality in the elderly increased very rapidly in summer. The regression analysis on these data showed that the number of heat stroke patients increased exponentially when the mean daily temperature and maximum daily temperature exceeded 27C and 32C in Tokyo and 31C and 36C in Wuhan and Nanjing, respectively. Since the incidence of heat-related morbidity and mortality has been shown to increase as a result of exposure to long periods of hot summer temperatures, it is important to determine to what extent the incidence of heat stress-related morbidity and mortality will be affected as a result of global warming.

  12. Global effects of land use on local terrestrial biodiversity.

    PubMed

    Newbold, Tim; Hudson, Lawrence N; Hill, Samantha L L; Contu, Sara; Lysenko, Igor; Senior, Rebecca A; Börger, Luca; Bennett, Dominic J; Choimes, Argyrios; Collen, Ben; Day, Julie; De Palma, Adriana; Díaz, Sandra; Echeverria-Londoño, Susy; Edgar, Melanie J; Feldman, Anat; Garon, Morgan; Harrison, Michelle L K; Alhusseini, Tamera; Ingram, Daniel J; Itescu, Yuval; Kattge, Jens; Kemp, Victoria; Kirkpatrick, Lucinda; Kleyer, Michael; Correia, David Laginha Pinto; Martin, Callum D; Meiri, Shai; Novosolov, Maria; Pan, Yuan; Phillips, Helen R P; Purves, Drew W; Robinson, Alexandra; Simpson, Jake; Tuck, Sean L; Weiher, Evan; White, Hannah J; Ewers, Robert M; Mace, Georgina M; Scharlemann, Jörn P W; Purvis, Andy

    2015-04-02

    Human activities, especially conversion and degradation of habitats, are causing global biodiversity declines. How local ecological assemblages are responding is less clear--a concern given their importance for many ecosystem functions and services. We analysed a terrestrial assemblage database of unprecedented geographic and taxonomic coverage to quantify local biodiversity responses to land use and related changes. Here we show that in the worst-affected habitats, these pressures reduce within-sample species richness by an average of 76.5%, total abundance by 39.5% and rarefaction-based richness by 40.3%. We estimate that, globally, these pressures have already slightly reduced average within-sample richness (by 13.6%), total abundance (10.7%) and rarefaction-based richness (8.1%), with changes showing marked spatial variation. Rapid further losses are predicted under a business-as-usual land-use scenario; within-sample richness is projected to fall by a further 3.4% globally by 2100, with losses concentrated in biodiverse but economically poor countries. Strong mitigation can deliver much more positive biodiversity changes (up to a 1.9% average increase) that are less strongly related to countries' socioeconomic status.

  13. Global Warming Responses at the Primary Secondary Interface: 2. Potential Effectiveness of Education

    ERIC Educational Resources Information Center

    Skamp, Keith; Boyes, Eddie; Stannistreet, Martin

    2009-01-01

    In an earlier paper (Skamp, Boyes, & Stanisstreet, 2009b), students' beliefs and willingness to act in relation to 16 specific actions related to global warming were compared across the primary secondary interface. More primary students believed in the effectiveness of most actions to reduce global warming and were willing to take those…

  14. Salt-induced changes in cardiac phosphoproteome in a rat model of chronic renal failure.

    PubMed

    Su, Zhengxiu; Zhu, Hongguo; Zhang, Menghuan; Wang, Liangliang; He, Hanchang; Jiang, Shaoling; Hou, Fan Fan; Li, Aiqing

    2014-01-01

    Heart damage is widely present in patients with chronic kidney disease. Salt diet is the most important environmental factor affecting development of chronic renal failure and cardiovascular diseases. The proteins involved in chronic kidney disease -induced heart damage, especially their posttranslational modifications, remain largely unknown to date. Sprague-Dawley rats underwent 5/6 nephrectomy (chronic renal failure model) or sham operation were treated for 2 weeks with a normal-(0.4% NaCl), or high-salt (4% NaCl) diet. We employed TiO2 enrichment, iTRAQ labeling and liquid-chromatography tandem mass spectrometry strategy for phosphoproteomic profiling of left ventricular free walls in these animals. A total of 1724 unique phosphopeptides representing 2551 non-redundant phosphorylation sites corresponding to 763 phosphoproteins were identified. During normal salt feeding, 89 (54%) phosphopeptides upregulated and 76 (46%) phosphopeptides downregulated in chronic renal failure rats relative to sham rats. In chronic renal failure rats, high salt intake induced upregulation of 84 (49%) phosphopeptides and downregulation of 88 (51%) phosphopeptides. Database searches revealed that most of the identified phospholproteins were important signaling molecules such as protein kinases, receptors and phosphatases. These phospholproteins were involved in energy metabolism, cell communication, cell differentiation, cell death and other biological processes. The Search Tool for the Retrieval of Interacting Genes analysis revealed functional links among 15 significantly regulated phosphoproteins in chronic renal failure rats compared to sham group, and 23 altered phosphoproteins induced by high salt intake. The altered phosphorylation levels of two proteins involved in heart damage, lamin A and phospholamban were validated. Expression of the downstream genes of these two proteins, desmin and SERCA2a, were also analyzed.

  15. Temporal quantitative phosphoproteomics of ADP stimulation reveals novel central nodes in platelet activation and inhibition

    PubMed Central

    Beck, Florian; Geiger, Jörg; Gambaryan, Stepan; Solari, Fiorella A.; Dell’Aica, Margherita; Loroch, Stefan; Mattheij, Nadine J.; Mindukshev, Igor; Pötz, Oliver; Jurk, Kerstin; Burkhart, Julia M.; Fufezan, Christian; Heemskerk, Johan W. M.; Walter, Ulrich

    2017-01-01

    Adenosine diphosphate (ADP) enhances platelet activation by virtually any other stimulant to complete aggregation. It binds specifically to the G-protein–coupled membrane receptors P2Y1 and P2Y12, stimulating intracellular signaling cascades, leading to integrin αIIbβ3 activation, a process antagonized by endothelial prostacyclin. P2Y12 inhibitors are among the most successful antiplatelet drugs, however, show remarkable variability in efficacy. We reasoned whether a more detailed molecular understanding of ADP-induced protein phosphorylation could identify (1) critical hubs in platelet signaling toward aggregation and (2) novel molecular targets for antiplatelet treatment strategies. We applied quantitative temporal phosphoproteomics to study ADP-mediated signaling at unprecedented molecular resolution. Furthermore, to mimic the antagonistic efficacy of endothelial-derived prostacyclin, we determined how Iloprost reverses ADP-mediated signaling events. We provide temporal profiles of 4797 phosphopeptides, 608 of which showed significant regulation. Regulated proteins are implicated in well-known activating functions such as degranulation and cytoskeletal reorganization, but also in less well-understood pathways, involving ubiquitin ligases and GTPase exchange factors/GTPase-activating proteins (GEF/GAP). Our data demonstrate that ADP-triggered phosphorylation occurs predominantly within the first 10 seconds, with many short rather than sustained changes. For a set of phosphorylation sites (eg, PDE3ASer312, CALDAG-GEFISer587, ENSASer109), we demonstrate an inverse regulation by ADP and Iloprost, suggesting that these are central modulators of platelet homeostasis. This study demonstrates an extensive spectrum of human platelet protein phosphorylation in response to ADP and Iloprost, which inversely overlap and represent major activating and inhibitory pathways. PMID:28060719

  16. Phosphoproteomic analysis of the non-seed vascular plant model Selaginella moellendorffii

    PubMed Central

    2014-01-01

    Background Selaginella (Selaginella moellendorffii) is a lycophyte which diverged from other vascular plants approximately 410 million years ago. As the first reported non-seed vascular plant genome, Selaginella genome data allow comparative analysis of genetic changes that may be associated with land plant evolution. Proteomics investigations on this lycophyte model have not been extensively reported. Phosphorylation represents the most common post-translational modifications and it is a ubiquitous regulatory mechanism controlling the functional expression of proteins inside living organisms. Results In this study, polyethylene glycol fractionation and immobilized metal ion affinity chromatography were employed to isolate phosphopeptides from wild-growing Selaginella. Using liquid chromatography-tandem mass spectrometry analysis, 1593 unique phosphopeptides spanning 1104 non-redundant phosphosites with confirmed localization on 716 phosphoproteins were identified. Analysis of the Selaginella dataset revealed features that are consistent with other plant phosphoproteomes, such as the relative proportions of phosphorylated Ser, Thr, and Tyr residues, the highest occurrence of phosphosites in the C-terminal regions of proteins, and the localization of phosphorylation events outside protein domains. In addition, a total of 97 highly conserved phosphosites in evolutionary conserved proteins were identified, indicating the conservation of phosphorylation-dependent regulatory mechanisms in phylogenetically distinct plant species. On the other hand, close examination of proteins involved in photosynthesis revealed phosphorylation events which may be unique to Selaginella evolution. Furthermore, phosphorylation motif analyses identified Pro-directed, acidic, and basic signatures which are recognized by typical protein kinases in plants. A group of Selaginella-specific phosphoproteins were found to be enriched in the Pro-directed motif class. Conclusions Our work provides

  17. Comparative phosphoproteomics reveals components of host cell invasion and post-transcriptional regulation during Francisella infection

    SciTech Connect

    Nakayasu, Ernesto S.; Tempel, Rebecca; Cambronne, Xiaolu A.; Petyuk, Vladislav A.; Jones, Marcus B.; Gritsenko, Marina A.; Monroe, Matthew E.; Yang, Feng; Smith, Richard D.; Adkins, Joshua N.; Heffron, Fred

    2013-09-22

    Francisella tularensis is a facultative intracellular bacterium that causes the deadly disease tularemia. Most evidence suggests that Francisella is not well recognized by the innate immune system that normally leads to cytokine expression and cell death. In previous work, we identified new bacterial factors that were hyper-cytotoxic to macrophages. Four of the identified hyper-cytotoxic strains (lpcC, manB, manC and kdtA) had an impaired lipopolysaccharide (LPS) synthesis and produced an exposed lipid A lacking the O-antigen. These mutants were not only hyper-cytotoxic but also were phagocytosed at much higher rates compared to the wild type parent strain. To elucidate the cellular signaling underlying this enhanced phagocytosis and cell death, we performed a large-scale comparative phosphoproteomic analysis of cells infected with wild-type and delta-lpcC F. novicida. Our data suggest that not only actin but also intermediate filaments and microtubules are important for F. novicida entry into the host cells. In addition, we observed differential phosphorylation of tristetraprolin (TTP), a key component of the mRNA-degrading machinery that controls the expression of a variety of genes including many cytokines. Infection with the delta-lpcC mutant induced the hyper-phosphorylation and inhibition of TTP, leading to the production of cytokines such as IL-1beta and TNF-alpha which may kill the host cells by triggering apoptosis. Together, our data provide new insights for Francisella invasion and a post-transcriptional mechanism that prevents the expression of host immune response factors that controls infection by this pathogen.

  18. The Structure of Anarchy or Thinking About the Global Effects of Extreme Tension in Southwest Asia.

    DTIC Science & Technology

    1980-04-01

    D-3 77 HE STRCUR FANARCHY OR THINKING ABOUT THE GLOBAL i/i I EFFECTS OF EXTREME..(U) CENTER FOR NAVAL ANALYSES I ALEXANDRIA VA NAVAL STUDIES GROUP K...TEST CHART NATIONAL HUREAIJ 0F 5FANUAIRDS 1l93 A PROFESSIONAL PAPER 419 / April 1980 In THE STRUCTURE OF ANARCHY OR THINKING ABOUT THE GLOBAL EFFECTS ...ABOUT THE GLOBAL EFFECTS OF EXTREME TENSION IN SOUTHWEST ASIA Kenneth G. Weiss .Naval Studies Group tV CENTER FOR NAVAL ANALYSES 2000 North

  19. Multipath effects in a Global Positioning Satellite system receiver

    NASA Technical Reports Server (NTRS)

    Mcdonald, Malcolm W.

    1992-01-01

    This study, as a part of a large continuing investigation being conducted by the Communications Systems Branch of the Information and Electronic Systems Laboratory at the Marshall Space Flight Center, was undertaken to explore the multipath response characteristics of a particular Global Positioning Satellite (GPS) receiver which was available in the laboratory at the beginning and throughout the entirety of the study, and to develop a suitable regime of experimental procedure which can be applied to other state-of-the-art GPS receivers in the larger investigation.

  20. The effect of global warming on lightning frequencies

    NASA Technical Reports Server (NTRS)

    Price, Colin; Rind, David

    1990-01-01

    The first attempt to model global lightning distributions by using the Goddard Institute for Space Studies (GISS) GCM is reported. Three sets of observations showing the relationship between lightning frequency and cloud top height are shown. Zonally averaged lightning frequency observed by satellite are compared with those calculated using the GISS GCM, and fair agreement is found. The change in lightning frequency for a double CO2 climate is calculated and found to be nearly 2.23 x 10 exp 6 extra lightning flashes per day.

  1. EU effect: Exporting emission standards for vehicles through the global market economy.

    PubMed

    Crippa, M; Janssens-Maenhout, G; Guizzardi, D; Galmarini, S

    2016-12-01

    Emission data from EDGAR (Emissions Database for Global Atmospheric Research), rather than economic data, are used to estimate the effect of policies and of the global exports of policy-regulated goods, such as vehicles, on global emissions. The results clearly show that the adoption of emission standards for the road transport sector in the two main global markets (Europe and North America) has led to the global proliferation of emission-regulated vehicles through exports, regardless the domestic regulation in the country of destination. It is in fact more economically convenient for vehicle manufacturers to produce and sell a standard product to the widest possible market and in the greatest possible amounts. The EU effect (European Union effect) is introduced as a global counterpart to the California effect. The former is a direct consequence of the penetration of the EURO standards in the global markets by European and Japanese manufacturers, which effectively export the standard worldwide. We analyze the effect on PM2.5 emissions by comparing a scenario of non-EURO standards against the current estimates provided by EDGAR. We find that PM2.5 emissions were reduced by more than 60% since the 1990s worldwide. Similar investigations on other pollutants confirm the hypothesis that the combined effect of technological regulations and their diffusion through global markets can also produce a positive effect on the global environment. While we acknowledge the positive feedback, we also demonstrate that current efforts and standards will be totally insufficient should the passenger car fleets in emerging markets reach Western per capita figures. If emerging countries reach the per capita vehicle number of the USA and Europe under current technological conditions, then the world will suffer pre-1990 emission levels.

  2. Meta-Analysis of Arabidopsis thaliana Phospho-Proteomics Data Reveals Compartmentalization of Phosphorylation Motifs[C][W

    PubMed Central

    van Wijk, Klaas J.; Friso, Giulia; Walther, Dirk; Schulze, Waltraud X.

    2014-01-01

    Protein (de)phosphorylation plays an important role in plants. To provide a robust foundation for subcellular phosphorylation signaling network analysis and kinase-substrate relationships, we performed a meta-analysis of 27 published and unpublished in-house mass spectrometry–based phospho-proteome data sets for Arabidopsis thaliana covering a range of processes, (non)photosynthetic tissue types, and cell cultures. This resulted in an assembly of 60,366 phospho-peptides matching to 8141 nonredundant proteins. Filtering the data for quality and consistency generated a set of medium and a set of high confidence phospho-proteins and their assigned phospho-sites. The relation between single and multiphosphorylated peptides is discussed. The distribution of p-proteins across cellular functions and subcellular compartments was determined and showed overrepresentation of protein kinases. Extensive differences in frequency of pY were found between individual studies due to proteomics and mass spectrometry workflows. Interestingly, pY was underrepresented in peroxisomes but overrepresented in mitochondria. Using motif-finding algorithms motif-x and MMFPh at high stringency, we identified compartmentalization of phosphorylation motifs likely reflecting localized kinase activity. The filtering of the data assembly improved signal/noise ratio for such motifs. Identified motifs were linked to kinases through (bioinformatic) enrichment analysis. This study also provides insight into the challenges/pitfalls of using large-scale phospho-proteomic data sets to nonexperts. PMID:24894044

  3. Biosynthesis and Regulation of Wheat Amylose and Amylopectin from Proteomic and Phosphoproteomic Characterization of Granule-binding Proteins

    PubMed Central

    Chen, Guan-Xing; Zhou, Jian-Wen; Liu, Yan-Lin; Lu, Xiao-Bing; Han, Cai-Xia; Zhang, Wen-Ying; Xu, Yan-Hao; Yan, Yue-Ming

    2016-01-01

    Waxy starch has an important influence on the qualities of breads. Generally, grain weight and yield in waxy wheat (Triticum aestivum L.) are significantly lower than in bread wheat. In this study, we performed the first proteomic and phosphoproteomic analyses of starch granule-binding proteins by comparing the waxy wheat cultivar Shannong 119 and the bread wheat cultivar Nongda 5181. These results indicate that reduced amylose content does not affect amylopectin synthesis, but it causes significant reduction of total starch biosynthesis, grain size, weight and grain yield. Two-dimensional differential in-gel electrophoresis identified 40 differentially expressed protein (DEP) spots in waxy and non-waxy wheats, which belonged mainly to starch synthase (SS) I, SS IIa and granule-bound SS I. Most DEPs involved in amylopectin synthesis showed a similar expression pattern during grain development, suggesting relatively independent amylose and amylopectin synthesis pathways. Phosphoproteome analysis of starch granule-binding proteins, using TiO2 microcolumns and LC-MS/MS, showed that the total number of phosphoproteins and their phosphorylation levels in ND5181 were significantly higher than in SN119, but proteins controlling amylopectin synthesis had similar phosphorylation levels. Our results revealed the lack of amylose did not affect the expression and phosphorylation of the starch granule-binding proteins involved in amylopectin biosynthesis. PMID:27604546

  4. SPECHT – Single-stage phosphopeptide enrichment and stable-isotope chemical tagging: Quantitative phosphoproteomics of insulin action in muscle

    PubMed Central

    Kettenbach, Arminja N.; Sano, Hiroyuki; Keller, Susanna R.; Lienhard, Gustav E.; Gerber, Scott A.

    2014-01-01

    The study of cellular signaling remains a significant challenge for translational and clinical research. In particular, robust and accurate methods for quantitative phosphoproteomics in tissues and tumors represent significant hurdles for such efforts. In the present work, we design, implement and validate a method for single-stage phosphopeptide enrichment and stable isotope chemical tagging, or SPECHT, that enables the use of iTRAQ, TMT and/or reductive dimethyl-labeling strategies to be applied to phosphoproteomics experiments performed on primary tissue. We develop and validate our approach using reductive dimethyl-labeling and HeLa cells in culture, and find these results indistinguishable from data generated from more traditional SILAC-labeled HeLa cells mixed at the cell level. We apply the SPECHT approach to the quantitative analysis of insulin signaling in a murine myotube cell line and muscle tissue, identify known as well as new phosphorylation events, and validate these phosphorylation sites using phospho-specific antibodies. Taken together, our work validates chemical tagging post-single-stage phosphoenrichment as a general strategy for studying cellular signaling in primary tissues. PMID:25463755

  5. Data set from a comprehensive phosphoproteomic analysis of rice variety IRBB5 in response to bacterial blight.

    PubMed

    Hou, Yuxuan; Tong, Xiaohong; Wang, Yifeng; Qiu, Jiehua; Li, Zhiyong; Zhang, Wen; Huang, Shiwen; Zhang, Jian

    2016-03-01

    Bacterial blight (BB) caused by Xanthomonas oryzae pv. oryzae (Xoo) has become one of the most devastating diseases for rice, a major food source for over half of the world populations. To investigate the roles of protein phosphorylation in rice bacterial blight resistance, a quantitative phosphoproteomic study was conducted in rice variety IRBB5 at 0 h and 24 h after Xoo infection. 2367 and 2223 phosphosites on 1334 and 1297 representative proteins were identified in 0 h and 24 h after Xoo infection, respectively, out of which 762 proteins were found to be differentially phosphorylated. In associated with the published article "A comprehensive quantitative phosphoproteome analysis of rice in response to bacterial blight" in BMC Plant Biology (Hou et al., 2015) [1], this dataset article provided the detailed information of experimental designing, methods, features as well as the raw data of mass spectrometry (MS) identification. The MS proteomics data could be fully accessed from the ProteomeXchange Consortium with the dataset identifier PXD002222.

  6. In vivo Phosphoproteome of Human Skeletal Muscle Revealed by Phosphopeptide Enrichment and HPLC-ESI-MS/MS

    PubMed Central

    Højlund, Kurt; Bowen, Benjamin P.; Hwang, Hyonson; Flynn, Charles R.; Madireddy, Lohith; Thangiah, Geetha; Langlais, Paul; Meyer, Christian; Mandarino, Lawrence J.; Yi, Zhengping

    2009-01-01

    Protein phosphorylation plays an essential role in signal transduction pathways that regulate substrate and energy metabolism, contractile function, and muscle mass in human skeletal muscle. Abnormal phosphorylation of signaling enzymes has been identified in insulin resistant muscle using phosphoepitope-specific antibodies, but its role in other skeletal muscle disorders remains largely unknown. This may be in part due to insufficient knowledge of relevant targets. Here, we therefore present the first large-scale in vivo phosphoproteomic study of human skeletal muscle from 3 lean, healthy volunteers. Trypsin digestion of 3-5 mg human skeletal muscle protein was followed by phosphopeptide enrichment using SCX and TiO2. The resulting phosphopeptides were analyzed by HPLC-ESI-MS/MS. Using this unbiased approach, we identified 306 distinct in vivo phosphorylation sites in 127 proteins, including 240 phosphoserines, 53 phosphothreonines and 13 phosphotyrosines in at least 2 out of 3 subjects. In addition, 61 ambiguous phosphorylation sites were identified in at least 2 out of 3 subjects. The majority of phosphoproteins detected are involved in sarcomeric function, excitation-contraction coupling (the Ca2+-cycle), glycolysis and glycogen metabolism. Of particular interest, we identified multiple novel phosphorylation sites on several sarcomeric Z-disc proteins known to be involved in signaling and muscle disorders. These results provide numerous new targets for the investigation of human skeletal muscle phosphoproteins in health and disease and demonstrate feasibility of phosphoproteomics research of human skeletal muscle in vivo. PMID:19764811

  7. Up-to-Date Workflow for Plant (Phospho)proteomics Identifies Differential Drought-Responsive Phosphorylation Events in Maize Leaves.

    PubMed

    Vu, Lam Dai; Stes, Elisabeth; Van Bel, Michiel; Nelissen, Hilde; Maddelein, Davy; Inzé, Dirk; Coppens, Frederik; Martens, Lennart; Gevaert, Kris; De Smet, Ive

    2016-12-02

    Protein phosphorylation is one of the most common post-translational modifications (PTMs), which can regulate protein activity and localization as well as protein-protein interactions in numerous cellular processes. Phosphopeptide enrichment techniques enable plant researchers to acquire insight into phosphorylation-controlled signaling networks in various plant species. Most phosphoproteome analyses of plant samples still involve stable isotope labeling, peptide fractionation, and demand a lot of mass spectrometry (MS) time. Here, we present a simple workflow to probe, map, and catalogue plant phosphoproteomes, requiring relatively low amounts of starting material, no labeling, no fractionation, and no excessive analysis time. Following optimization of the different experimental steps on Arabidopsis thaliana samples, we transferred our workflow to maize, a major monocot crop, to study signaling upon drought stress. In addition, we included normalization to protein abundance to identify true phosphorylation changes. Overall, we identified a set of new phosphosites in both Arabidopsis thaliana and maize, some of which are differentially phosphorylated upon drought. All data are available via ProteomeXchange with identifier PXD003634, but to provide easy access to our model plant and crop data sets, we created an online database, Plant PTM Viewer ( bioinformatics.psb.ugent.be/webtools/ptm_viewer/ ), where all phosphosites identified in our study can be consulted.

  8. System-wide effects of Global Fund investments in Nepal.

    PubMed

    Trägård, Anna; Shrestha, Ishwar Bahadur

    2010-11-01

    Nepal, with a concentrated HIV epidemic and high burden of tuberculosis (TB) and malaria, was perceived to have immensely benefited from grants by the Global Fund to Fight AIDS, Tuberculosis and Malaria in addressing the three diseases, amounting to total approved funding of US$80 million. This paper looks at the interaction and integration of Global Fund-supported programmes and national health systems. A mixed method 'case study' approach based on the Systemic Rapid Assessment Toolkit (SYSRA) was used to systematically analyse across the main health systems functional domains. The Country Coordinating Mechanism has been credited with providing the stewardship in attracting additional resources and providing oversight. The involvement of civil society for delivering key HIV and malaria interventions targeting high-risk groups was perceived to be highly beneficial. TB and malaria services were found to be well integrated into the public health care delivery system, while HIV services targeting at-risk groups were often delivered using parallel structures. Political instability, absence of continuity in leadership and sub-optimal investments in health were together perceived to have led to fragmentation of financing and planning activities, especially in HIV the programme. The demand for timely programmatic and financial reporting for donor-supported programmes has contributed to the creation of parallel monitoring and evaluation structures, with missed opportunities for strengthening and utilizing the national health management information systems.

  9. Global Biomass Variation and its Geodynamic Effects, 1982-1998

    NASA Technical Reports Server (NTRS)

    Rodell, M.; Chao, B. F.; Au, A. Y.; Kimball, J. S.; McDonald, K. C.

    2005-01-01

    Redistribution of mass near Earth's surface alters its rotation, gravity field, and geocenter location. Advanced techniques for measuring these geodetic variations now exist, but the ability to attribute the observed modes to individual Earth system processes has been hampered by a shortage of reliable global data on such processes, especially hydrospheric processes. To address one aspect of this deficiency, 17 yrs of monthly, global maps of vegetation biomass were produced by applying field-based relationships to satellite-derived vegetation type and leaf area index. The seasonal variability of biomass was estimated to be as large as 5 kg m(exp -2). Of this amount, approximately 4 kg m(exp -2) is due to vegetation water storage variations. The time series of maps was used to compute geodetic anomalies, which were then compared with existing geodetic observations as well as the estimated measurement sensitivity of the Gravity Recovery and Climate Experiment (GRACE). For gravity, the seasonal amplitude of biomass variations may be just within GRACE'S limits of detectability, but it is still an order of magnitude smaller than current observation uncertainty using the satellite-laser-ranging technique. The contribution of total biomass variations to seasonal polar motion amplitude is detectable in today's measurement, but it is obscured by contributions from various other sources, some of which are two orders of magnitude larger. The influence on the length of day is below current limits of detectability. Although the nonseasonal geodynamic signals show clear interannual variability, they are too small to be detected.

  10. Global stability of the focusing effect of fluid jet flows.

    PubMed

    Montanero, J M; Rebollo-Muñoz, N; Herrada, M A; Gañán-Calvo, A M

    2011-03-01

    The global stability of the steady jetting mode of liquid jets focused by coaxial gas streams is analyzed both theoretically and experimentally. Numerical simulations allow one to identify the physical mechanisms responsible for instability in the low viscosity and very viscous regimes of the focused liquid. The characteristic flow rates for which global instability takes place are estimated by a simple scaling analysis. These flow rates do not depend on the pressure drop (energy) applied to the system to produce the microjet. Their dependencies on the liquid viscosity are opposite for the two extremes studied: the characteristic flow rate increases (decreases) with viscosity for very low (high) viscosity liquids. Experiments confirmed the validity of these conclusions. The minimum flow rates below which the liquid meniscus becomes unstable are practically independent of the applied pressure drop for sufficiently large values of this quantity. For all the liquids analyzed, there exists an optimum value of the capillary-to-orifice distance for which the minimum flow rate attains a limiting value. That limiting value represents the lowest flow rate attainable with a given experimental configuration in the steady jetting regime. A two-dimensional stability map with a high degree of validity is plotted on the plane defined by the Reynolds and capillary numbers based on the limiting flow rate.

  11. Global Magnetospheric Evolution Effected by Sudden Ring Current Injection

    NASA Astrophysics Data System (ADS)

    Park, Geunseok; No, Jincheol; Kim, Kap-Sung; Choe, Gwangson; Lee, Junggi

    2016-04-01

    The dynamical evolution of the Earth's magnetosphere loaded with a transiently enhanced ring current is investigated by global magnetohydrodynamic simulations. Two cases with different values of the primitive ring current are considered. In one case, the initial ring current is strong enough to create a magnetic island in the magnetosphere. The magnetic island readily reconnects with the earth-connected ambient field and is destroyed as the system approaches a steady equilibrium. In the other case, the initial ring current is not so strong, and the initial magnetic field configuration bears no magnetic island, but features a wake of bent field lines, which is smoothed out through the relaxing evolution of the magnetosphere. The relaxation time of the magnetosphere is found to be about five to six minutes, over which the ring current is reduced to about a quarter of its initial value. Before reaching a quasi-steady state, the magnetosphere is found to undergo an overshooting expansion and a subsequent contraction. Fast and slow magnetosonic waves are identified to play an important role in the relaxation toward equilibrium. Our study suggests that a sudden injection of the ring current can generate an appreciable global pulsation of the magnetosphere.

  12. Globalization's effects on world agricultural trade, 1960–2050

    PubMed Central

    Anderson, Kym

    2010-01-01

    Recent globalization has been characterized by a decline in the costs of cross-border trade in farm and other products. It has been driven primarily by the information and communication technology revolution and—in the case of farm products—by reductions in governmental distortions to agricultural production, consumption and trade. Both have boosted economic growth and reduced poverty globally, especially in Asia. The first but maybe not the second of these drivers will continue in coming decades. World food prices will depend also on whether (and if so by how much) farm productivity growth continues to outpace demand growth and to what extent diets in emerging economies move towards livestock and horticultural products at the expense of staples. Demand in turn will be driven not only by population and income growth, but also by crude oil prices if they remain at current historically high levels, since that will affect biofuel demand. Climate change mitigation policies and adaptation, water market developments and market access standards particularly for transgenic foods will add to future production, price and trade uncertainties. PMID:20713399

  13. Globalization's effects on world agricultural trade, 1960-2050.

    PubMed

    Anderson, Kym

    2010-09-27

    Recent globalization has been characterized by a decline in the costs of cross-border trade in farm and other products. It has been driven primarily by the information and communication technology revolution and-in the case of farm products-by reductions in governmental distortions to agricultural production, consumption and trade. Both have boosted economic growth and reduced poverty globally, especially in Asia. The first but maybe not the second of these drivers will continue in coming decades. World food prices will depend also on whether (and if so by how much) farm productivity growth continues to outpace demand growth and to what extent diets in emerging economies move towards livestock and horticultural products at the expense of staples. Demand in turn will be driven not only by population and income growth, but also by crude oil prices if they remain at current historically high levels, since that will affect biofuel demand. Climate change mitigation policies and adaptation, water market developments and market access standards particularly for transgenic foods will add to future production, price and trade uncertainties.

  14. Global comparative healthcare effectiveness research: Evaluating sustainable programmes in low & middle resource settings

    PubMed Central

    Balkrishnan, Rajesh; Chang, Jongwha; Patel, Isha; Yang, Fang; Merajver, Sofia D.

    2013-01-01

    The need to focus healthcare expenditures on innovative and sustainable health systems that efficiently use existing effective therapies are the major drivers stimulating Comparative Effectiveness Research (CER) across the globe. Lack of adequate access and high cost of essential medicines and technologies in many countries increases morbidity and mortality and cost of care that forces people and families into poverty due to disability and out-of-pocket expenses. This review illustrates the potential of value-added global health care comparative effectiveness research in shaping health systems and health care delivery paradigms in the “global south”. Enabling the development of effective CER systems globally paves the way for tangible local and regional definitions of equity in health care because CER fosters the sharing of critical assets, resources, skills, and capabilities and the development of collaborative of multi-sectorial frameworks to improve health outcomes and metrics globally. PMID:23640555

  15. Global impact of biotech crops: environmental effects, 1996-2010.

    PubMed

    Brookes, Graham; Barfoot, Peter

    2012-01-01

    This paper updates the assessment of the impact commercialized agricultural biotechnology is having on global agriculture, from some important environmental perspectives. It focuses on the impact of changes in pesticide use and greenhouse gas emissions arising from the use of biotech crops. The technology has reduced pesticide spraying by 443 million kg (-9.1%) and, as a result, decreased the environmental impact associated with herbicide and insecticide use on these crops [as measured by the indicator the Environmental Impact Quotient (EIQ)] by 17.9%. The technology has also significantly reduced the release of greenhouse gas emissions from this cropping area, which, in 2010, was equivalent to removing 8.6 million cars from the roads.

  16. Thermal analysis of wildfires and effects on global ecosystem cycling

    NASA Technical Reports Server (NTRS)

    Ambrosia, Vincent G.; Brass, James A.

    1988-01-01

    Biomass combustion plays an important role in the earth's biogeochemical cycling. The monitoring of wildfires and their associated variables at global scales is feasible and can lead to predictions of the influence of combustion on biogeochemical cycling and tropospheric chemistry. Remote sensing data collected during the 1985 California wildfire season indicate that the information content of key thermal and infrared/thermal wave band channels centered at 11.5 microns, 3.8 microns, and 2.25 microns are invaluable for discriminating and calculating fire related variables. These variables include fire intensity, rate-of-spread, soil cooling recovery behind the fire front, and plume structure. Coinciding Advanced Very High Resolution Radiometer (AVHRR) data provided information regarding temperature estimations and the movement of the smoke plume from one wildfire into the Los Angeles basin.

  17. Are conservation organizations configured for effective adaptation to global change?

    USGS Publications Warehouse

    Armsworth, Paul R.; Larson, Eric R.; Jackson, Stephen T.; Sax, Dov F.; Simonin, Paul W.; Blossey, Bernd; Green, Nancy; Lester, Liza; Klein, Mary L.; Ricketts, Taylor H.; Runge, Michael C.; Shaw, M. Rebecca

    2015-01-01

    Conservation organizations must adapt to respond to the ecological impacts of global change. Numerous changes to conservation actions (eg facilitated ecological transitions, managed relocations, or increased corridor development) have been recommended, but some institutional restructuring within organizations may also be needed. Here we discuss the capacity of conservation organizations to adapt to changing environmental conditions, focusing primarily on public agencies and nonprofits active in land protection and management in the US. After first reviewing how these organizations anticipate and detect impacts affecting target species and ecosystems, we then discuss whether they are sufficiently flexible to prepare and respond by reallocating funding, staff, or other resources. We raise new hypotheses about how the configuration of different organizations enables them to protect particular conservation targets and manage for particular biophysical changes that require coordinated management actions over different spatial and temporal scales. Finally, we provide a discussion resource to help conservation organizations assess their capacity to adapt.

  18. Cloud and ocean effects on global greenhouse warming

    SciTech Connect

    Hoffert, M.I.

    1991-02-01

    Six months into the above-referenced grant, we are making good progress on our research plan. We intend to develop a new generation of transient climate/ocean model capable of reflecting feedbacks associated with clouds and ocean dynamics, and to use them to better constrain the transient climate response to increased greenhouse gas concentrations in the atmosphere. This is a necessary step in quantifying the links between radiative forcing of the atmosphere and climate response on 10--100 year time scales. The modelling work involves, on the one hand, developing a better characterization of cloud forcing and feedback, and on the other, a new generation of ocean/climate model incorporating feedbacks from the changing stratification of the ocean as heat is absorbed during periods of global warming. 3 figs.

  19. Global impact of biotech crops: environmental effects 1996-2009.

    PubMed

    Brookes, Graham; Barfoot, Peter

    2011-01-01

    This paper updates the assessment of the impact commercialised agricultural biotechnology is having on global agriculture from an environmental perspective. It focuses on the impact of changes in pesticide use and greenhouse gas emissions arising from the use of biotech crops. The technology has reduced pesticide spraying by 393 million kg (-8.7%) and, as a result, decreased the environmental impact associated with herbicide and insecticide use on these crops (as measured by the indicator the Environmental Impact Quotient (EIQ)) by 17.1 %. The technology has also significantly reduced the release of greenhouse gas emissions from this cropping area, which, in 2009, was equivalent to removing 7.8 million cars from the roads.

  20. The effect of global visual flow on simulator sickness

    NASA Technical Reports Server (NTRS)

    Sharkey, Thomas J.; Mccauley, Michael E.

    1991-01-01

    Simulator-induced sickness is investigated in experiments performed at the NASA Ames Army Crew Station Research Facility using the fixed-base helmet-mounted-display flight simulator described by Lypaczewski et al. (1986). The focus of the tests was on the possible roles of (1) global visual flow, as defined by Warren et al. (1982), and (2) maneuvering intensity (in the conflict hypothesis of Reason and Brand, 1975). The results, based on subjective evaluations, physiological measurements, and physical tests on 19 Army helicopter pilots performing a 40-min river-valley following task, are presented in extensive tables and graphs and discussed. The data are found to be in agreement with (1) and inconsistent with (2), indicating more sickness at lower altitude instead of with increased maneuvering. Shorter simulator sessions and postponement of low-altitude work until later in the training period are recommended.

  1. Global and local Joule heating effects seen by DE 2

    NASA Technical Reports Server (NTRS)

    Heelis, R. A.; Coley, W. R.

    1988-01-01

    In the altitude region between 350 and 550 km, variations in the ion temperature principally reflect similar variations in the local frictional heating produced by a velocity difference between the ions and the neutrals. Here, the distribution of the ion temperature in this altitude region is shown, and its attributes in relation to previous work on local Joule heating rates are discussed. In addition to the ion temperature, instrumentation on the DE 2 satellite also provides a measure of the ion velocity vector representative of the total electric field. From this information, the local Joule heating rate is derived. From an estimate of the height-integrated Pedersen conductivity it is also possible to estimate the global (height-integrated) Joule heating rate. Here, the differences and relationships between these various parameters are described.

  2. Effects of future anthropogenic pollution emissions on global air quality

    NASA Astrophysics Data System (ADS)

    Pozzer, A.; Zimmermann, P.; Doering, U.; van Aardenne, J.; Dentener, F.; Lelieveld, J.

    2012-04-01

    The atmospheric chemistry general circulation model EMAC is used to estimate the impact of anthropogenic emission changes on global and regional air quality in recent and future years (2005, 2010, 2025 and 2050). The emission scenario assumes that population and economic growth largely determine energy consumption and consequent pollution sources ("business as usual"). By comparing with recent observations, it is shown that the model reproduces the main features of regional air pollution distributions though with some imprecision inherent to the coarse horizontal resolution (around 100 km). To identify possible future hot spots of poor air quality, a multi pollutant index (MPI) has been applied. It appears that East and South Asia and the Arabian Gulf regions represent such hotspots due to very high pollutant concentrations. In East Asia a range of pollutant gases and particulate matter (PM2.5) are projected to reach very high levels from 2005 onward, while in South Asia air pollution, including ozone, will grow rapidly towards the middle of the century. Around the Arabian Gulf, where natural PM2.5 concentrations are already high (desert dust), ozone levels will increase strongly. By extending the MPI definition, we calculated a Per Capita MPI (PCMPI) in which we combined population projections with those of pollution emissions. It thus appears that a rapidly increasing number of people worldwide will experience reduced air quality during the first half of the 21st century. It is projected that air quality for the global average citizen in 2050 will be comparable to the average in East Asia in the year 2005.

  3. Effects of mineral dust on global atmospheric nitrate concentrations

    NASA Astrophysics Data System (ADS)

    Karydis, V. A.; Tsimpidi, A. P.; Pozzer, A.; Astitha, M.; Lelieveld, J.

    2016-02-01

    This study assesses the chemical composition and global aerosol load of the major inorganic aerosol components, focusing on mineral dust and aerosol nitrate. The mineral dust aerosol components (i.e., Ca2+, Mg2+, K+, Na+) and their emissions are included in the ECHAM5/MESSy Atmospheric Chemistry model (EMAC). Gas/aerosol partitioning is simulated using the ISORROPIA-II thermodynamic equilibrium model that considers K+, Ca2+, Mg2+, NH4+, Na+, SO42-, NO3-, Cl-, and H2O aerosol components. Emissions of mineral dust are calculated online by taking into account the soil particle size distribution and chemical composition of different deserts worldwide. Presence of metallic ions can substantially affect the nitrate partitioning into the aerosol phase due to thermodynamic interactions. The model simulates highest fine aerosol nitrate concentration over urban and industrialized areas (1-3 µg m-3), while coarse aerosol nitrate is highest close to deserts (1-4 µg m-3). The influence of mineral dust on nitrate formation extends across southern Europe, western USA, and northeastern China. The tropospheric burden of aerosol nitrate increases by 44 % when considering interactions of nitrate with mineral dust. The calculated global average nitrate aerosol concentration near the surface increases by 36 %, while the coarse- and fine-mode concentrations of nitrate increase by 53 and 21 %, respectively. Other inorganic aerosol components are affected by reactive dust components as well (e.g., the tropospheric burden of chloride increases by 9 %, ammonium decreases by 41 %, and sulfate increases by 7 %). Sensitivity tests show that nitrate aerosol is most sensitive to the chemical composition of the emitted mineral dust, followed by the soil size distribution of dust particles, the magnitude of the mineral dust emissions, and the aerosol state assumption.

  4. Cloaking of matter waves under the global Aharonov-Bohm effect

    SciTech Connect

    Lin, D.-H.; Luan, P.-G.

    2009-05-15

    We discuss the Aharonov-Bohm effect of a magnetic flux for its influence on a two-dimensional quantum cloak. It is shown that the matter wave of a charged particle under the global influence of the Aharonov-Bohm effect can still be perfectly cloaked and guided by the quantum cloak. Since the presence of the global influence of a magnetic flux on charged particles is universal, the perfect cloaking and guiding nature not only provides an ideal setup to cloak an object from matter waves but also provides an ideal setup to test the global physics of charged matter waves in the presence of a bare magnetic flux.

  5. Ischemia in Tumors Induces Early and Sustained Phosphorylation Changes in Stress Kinase Pathways but Does Not Affect Global Protein Levels*

    PubMed Central

    Mertins, Philipp; Yang, Feng; Liu, Tao; Mani, D. R.; Petyuk, Vladislav A.; Gillette, Michael A.; Clauser, Karl R.; Qiao, Jana W.; Gritsenko, Marina A.; Moore, Ronald J.; Levine, Douglas A.; Townsend, Reid; Erdmann-Gilmore, Petra; Snider, Jacqueline E.; Davies, Sherri R.; Ruggles, Kelly V.; Fenyo, David; Kitchens, R. Thomas; Li, Shunqiang; Olvera, Narciso; Dao, Fanny; Rodriguez, Henry; Chan, Daniel W.; Liebler, Daniel; White, Forest; Rodland, Karin D.; Mills, Gordon B.; Smith, Richard D.; Paulovich, Amanda G.; Ellis, Matthew; Carr, Steven A.

    2014-01-01

    Protein abundance and phosphorylation convey important information about pathway activity and molecular pathophysiology in diseases including cancer, providing biological insight, informing drug and diagnostic development, and guiding therapeutic intervention. Analyzed tissues are usually collected without tight regulation or documentation of ischemic time. To evaluate the impact of ischemia, we collected human ovarian tumor and breast cancer xenograft tissue without vascular interruption and performed quantitative proteomics and phosphoproteomics after defined ischemic intervals. Although the global expressed proteome and most of the >25,000 quantified phosphosites were unchanged after 60 min, rapid phosphorylation changes were observed in up to 24% of the phosphoproteome, representing activation of critical cancer pathways related to stress response, transcriptional regulation, and cell death. Both pan-tumor and tissue-specific changes were observed. The demonstrated impact of pre-analytical tissue ischemia on tumor biology mandates caution in interpreting stress-pathway activation in such samples and motivates reexamination of collection protocols for phosphoprotein analysis. PMID:24719451

  6. Gravity effects obtained from global hydrology models in comparison with high precision gravimetric time series

    NASA Astrophysics Data System (ADS)

    Wziontek, Hartmut; Wilmes, Herbert; Güntner, Andreas; Creutzfeldt, Benjamin

    2010-05-01

    Water mass changes are a major source of variations in residual gravimetric time series obtained from the combination of observations with superconducting and absolute gravimeters. Changes in the local water storage are the main influence, but global variations contribute to the signal significantly. For three European gravity stations, Bad Homburg, Wettzell and Medicina, different global hydrology models are compared. The influence of topographic effects is discussed and due to the long-term stability of the combined gravity time series, inter-annual signals in model data and gravimetric observations are compared. Two sources of influence are discriminated, i.e., the effect of a local zone with an extent of a few kilometers around the gravimetric station and the global contribution beyond 50km. Considering their coarse resolution and uncertainties, local effects calculated from global hydrological models are compared with the in-situ gravity observations and, for the station Wettzell, with local hydrological monitoring data.

  7. Global sea level rise and the greenhouse effect: might they be connected?

    PubMed

    Peltier, W R; Tushingham, A M

    1989-05-19

    Secular sea level trends extracted from tide gauge records of appropriately long duration demonstrate that global sea level may be rising at a rate in excess of 1 millimeter per year. However, because global coverage of the oceans by the tide gauge network is highly nonuniform and the tide gauge data reveal considerable spatial variability, there has been a well-founded reluctance to interpret the observed secular sea level rise as representing a signal of global scale that might be related to the greenhouse effect. When the tide gauge data are filtered so as to remove the contribution of ongoing glacial isostatic adjustment to the local sea level trend at each location, then the individual tide gauge records reveal sharply reduced geographic scatter and suggest that there is a globally coherent signal of strength 2.4 +/- 0.90 millimeters per year that is active in the system. This signal could constitute an indication of global climate warming.

  8. Global sea level rise and the greenhouse effect: might they be connected

    SciTech Connect

    Peltier, W.R.; Tushingham, A.M.

    1989-03-21

    Secular sea level trends extracted from tide gauge records of appropriately long duration demonstrate that global sea level may be rising at a rate in excess of 1 millimeter per year. However, because global coverage of the oceans by the tide gauge network is highly nonuniform and the tide gauge data reveal considerable spatial variability, there has been a well-founded reluctance to interpret the observed secular sea level rise as representing a signal of global scale that might be related to the greenhouse effect. When the tide gauge data are filtered so as to remove the contribution of ongoing glacial isostatic adjustment to the local sea level trend at each location, then the individual tide gauge records reveal sharply reduced geographic scatter and suggest that there is a globally coherent signal of strength 2.4 {+-} 0.90 millimeters per year that is active in the system. This signal could constitute an indication of global climate warming.

  9. The effect of statistical wind corrections on global wave forecasts

    NASA Astrophysics Data System (ADS)

    Durrant, Tom H.; Greenslade, Diana J. M.; Simmonds, Ian

    2013-10-01

    The skill of modern wave models is such that the quality of their forecasts is, to a large degree, determined by errors in the forcing wind field. This work explores the extent to which large-scale systematic biases in modelled waves from a third generation wave model can be attributed to the forcing winds. Three different sets of winds with known global bias characteristics are used to force the WAVEWATCH III model. These winds are based on the Australian Bureau of Meteorology's ACCESS model output, with different statistical corrections applied. Wave forecasts are verified using satellite altimeter data. It is found that a negative bias in modelled Significant Wave Height (Hs) has its origins primarily in the forcing, however, the reduction of systematic wind biases does not result in universal improvement in modelled Hs. A positive bias is present in the Southern Hemisphere due primarily to an overestimation of high Hs values in the Southern Ocean storm tracks. A positive bias is also present in the east Pacific and East Indian Ocean. This is due both to the over-prediction of waves in the Southern Ocean and lack of swell attenuation in the wave model source terms used. Smaller scale features are apparent, such as a positive bias off the Cape of Good Hope, and a negative bias off Cape Horn. In some situations, internal wave model error has been compensated for by error in the forcing winds.

  10. Effects of economics and demographics on global fisheries sustainability.

    PubMed

    Ding, Qi; Wang, Yali; Chen, Xinjun; Chen, Yong

    2016-12-06

    A good understanding of social factors that lead to marine ecological change is important to developing sustainable global fisheries. We used balanced panel models and conducted cross-national time-series analyses (1970-2010) of 122 nations to examine how economic prosperity and population growth affected the sustainability of marine ecosystems. We used catches in economic exclusive zone (EEZ); mean trophic level of fishery landings (MTL); primary production required to sustain catches (expressed as percentage of local primary production [%PPR]); and an index of ecosystem overfishing (i.e., the loss in secondary production index [L index]) as indicators of ecological change in marine ecosystems. The EEZ catch, %PPR, and L index declined gradually after gross domestic product (GDP) per capita reached $15,000, $14,000, and $19,000, respectively, and MTL increased steadily once GDP per capita exceeded $20,000. These relationships suggest that economic growth and biodiversity conservation are compatible goals. However, increasing human populations would degrade marine ecosystems. Specifically, a doubling of human population caused an increase in the %PPR of 17.1% and in the L index of 0.0254 and a decline in the MTL of 0.176. A 1% increase in human population resulted in a 0.744% increase in EEZ catch. These results highlight the importance of considering social and economic factors in developing sustainable fisheries management policy.

  11. Effects of Drake Passage on a strongly eddying global ocean

    NASA Astrophysics Data System (ADS)

    Viebahn, Jan P.; Heydt, Anna S.; Le Bars, Dewi; Dijkstra, Henk A.

    2016-05-01

    The climate impact of ocean gateway openings during the Eocene-Oligocene transition is still under debate. Previous model studies employed grid resolutions at which the impact of mesoscale eddies has to be parameterized. We present results of a state-of-the-art eddy-resolving global ocean model with a closed Drake Passage and compare with results of the same model at noneddying resolution. An analysis of the pathways of heat by decomposing the meridional heat transport into eddy, horizontal, and overturning circulation components indicates that the model behavior on the large scale is qualitatively similar at both resolutions. Closing Drake Passage induces (i) sea surface warming around Antarctica due to equatorward expansion of the subpolar gyres, (ii) the collapse of the overturning circulation related to North Atlantic Deep Water formation leading to surface cooling in the North Atlantic, and (iii) significant equatorward eddy heat transport near Antarctica. However, quantitative details significantly depend on the chosen resolution. The warming around Antarctica is substantially larger for the noneddying configuration (˜5.5°C) than for the eddying configuration (˜2.5°C). This is a consequence of the subpolar mean flow which partitions differently into gyres and circumpolar current at different resolutions. We conclude that for a deciphering of the different mechanisms active in Eocene-Oligocene climate change detailed analyses of the pathways of heat in the different climate subsystems are crucial in order to clearly identify the physical processes actually at work.

  12. Effects of global atmospheric perturbations on forest ecosystems: Predictions of seasonal and cumulative effects

    NASA Technical Reports Server (NTRS)

    Tinus, R. W.; Roddy, D. J.

    1988-01-01

    The physical effects of certain large events, such as giant impacts, explosive volcanism, or combined nuclear explosions, have the potential of inducing global catastrophes in our terrestrial environment. Such highly energetic events can inject substantial quantities of material into the atmosphere. In turn, this changes the amount of sunlight reaching the Earth's surface and modifies atmospheric temperatures to produce a wide range of global effects. One consequence is the introduction of serious stresses in both plants and animals throughout the Earth's biosphere. For example, recent studies predict that forest lands, crop lands, and range lands would suffer specific physical and biological degradations if major physical and chemical disruptions occurred in our atmosphere. Forests, which cover over 4 times 10 to the 9th power hectares (4 times 10 to the 7th power sq km) of our planet, or about 3 times the area now cultivated for crops, are critical to many processes in the biosphere. Forests contribute heavily to the production of atmospheric oxygen, supply the major volume of biomass, and provide a significant percentage of plant and animal habitats.

  13. Canceling effect: a natural mechanism to reduce the effects of global warming

    NASA Astrophysics Data System (ADS)

    Razavi, Bahar S.; Blagodatskaya, Evgenia; kuzyakov, Yakov

    2016-04-01

    The temperature sensitivity of enzymes responsible for organic matter decomposition in soil is crucial for predicting the effects of global warming on the carbon cycle and sequestration. We tested the hypothesis that differences in temperature sensitivity of enzyme kinetic parameters Vmax and Km will lead to a canceling effect: strong reduction of temperature response of catalytic reactions. Short-term temperature response of Vmax and Km of three hydrolytic enzymes responsible for decomposition of cellulose (β-glucosidase, cellobiohydrolase) and hemicelluloses (xylanase) were analyzed in situ from 0 to 40 °C. The apparent activation energy varied between enzymes from 20.7 to 35.2 kJ mol-1 corresponding to the Q10 values of the enzyme activities of 1.4-1.9 (with Vmax-Q10 1.0-2.5 and Km-Q10 0.94-2.3). Temperature response of all tested enzymes fitted well to the Arrhenius equation. Despite that,the fitting of Arrhenius model revealed the non-linear increase of two cellulolytic enzymes activities with two distinct thresholds at 10-15 °C and 25-30 °C, which were less pronounced for xylanase. The nonlinearity between 10 and 15 °C was explained by 30-80% increase in Vmax. At 25-30 °C, however, the abrupt decrease of enzyme-substrate affinity was responsible for non-linear increase of enzyme activities. Our study is the first demonstrating nonlinear response of Vmax and Km to temperature causing canceling effect, which was most strongly pronounced at low substrate concentrations and at temperatures above 15 °C. Under cold climate, however, the regulation of hydrolytic activity by canceling in response to warming is negligible because canceling was never observed below 10 °C. The canceling, therefore, can be considered as natural mechanism reducing the effects of global warming on decomposition of soil organics at moderate temperatures. The non-linearity of enzyme responses to warming and the respective thresholds should therefore be investigated for other enzymes

  14. Quantitative expression proteomics and phosphoproteomics profile of brain from PINK1 knockout mice: insights into mechanisms of familial Parkinson's disease.

    PubMed

    Triplett, Judy C; Zhang, Zhaoshu; Sultana, Rukhsana; Cai, Jian; Klein, Jon B; Büeler, Hansruedi; Butterfield, David Allan

    2015-06-01

    Parkinson's disease (PD) is an age-related, neurodegenerative motor disorder characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta and presence of α-synuclein-containing protein aggregates. Mutations in the mitochondrial Ser/Thr kinase PTEN-induced kinase 1 (PINK1) are associated with an autosomal recessive familial form of early-onset PD. Recent studies have suggested that PINK1 plays important neuroprotective roles against mitochondrial dysfunction by phosphorylating and recruiting Parkin, a cytosolic E3 ubiquitin ligase, to facilitate elimination of damaged mitochondria via autophagy-lysosomal pathways. Loss of PINK1 in cells and animals leads to various mitochondrial impairments and oxidative stress, culminating in dopaminergic neuronal death in humans. Using a 2-D polyacrylamide gel electrophoresis proteomics approach, the differences in expressed brain proteome and phosphoproteome between 6-month-old PINK1-deficient mice and wild-type mice were identified. The observed changes in the brain proteome and phosphoproteome of mice lacking PINK1 suggest that defects in signaling networks, energy metabolism, cellular proteostasis, and neuronal structure and plasticity are involved in the pathogenesis of familial PD. Mutations in PINK1 are associated with an early-onset form of Parkinson's disease (PD). This study examines changes in the proteome and phosphoproteome of the PINK1 knockout mouse brain. Alterations were noted in several key proteins associated with: increased oxidative stress, aberrant cellular signaling, altered neuronal structure, decreased synaptic plasticity, reduced neurotransmission, diminished proteostasis networks, and altered metabolism. 14-3-3ε, 14-3-3 protein epsilon; 3-PGDH, phosphoglycerate dehydrogenase; ALDOA, aldolase A; APT1, acyl-protein thioesterase 1; CaM, calmodulin; CBR3, carbonyl reductase [NADPH] 3; ENO2, gamma-enolase; HPRT, hypoxanthine-guanine phosphoribosyltransferase; HSP70

  15. Quantitative phosphoproteomics reveals the role of the AMPK plant ortholog SnRK1 as a metabolic master regulator under energy deprivation

    PubMed Central

    Nukarinen, Ella; Nägele, Thomas; Pedrotti, Lorenzo; Wurzinger, Bernhard; Mair, Andrea; Landgraf, Ramona; Börnke, Frederik; Hanson, Johannes; Teige, Markus; Baena-Gonzalez, Elena; Dröge-Laser, Wolfgang; Weckwerth, Wolfram

    2016-01-01

    Since years, research on SnRK1, the major cellular energy sensor in plants, has tried to define its role in energy signalling. However, these attempts were notoriously hampered by the lethality of a complete knockout of SnRK1. Therefore, we generated an inducible amiRNA::SnRK1α2 in a snrk1α1 knock out background (snrk1α1/α2) to abolish SnRK1 activity to understand major systemic functions of SnRK1 signalling under energy deprivation triggered by extended night treatment. We analysed the in vivo phosphoproteome, proteome and metabolome and found that activation of SnRK1 is essential for repression of high energy demanding cell processes such as protein synthesis. The most abundant effect was the constitutively high phosphorylation of ribosomal protein S6 (RPS6) in the snrk1α1/α2 mutant. RPS6 is a major target of TOR signalling and its phosphorylation correlates with translation. Further evidence for an antagonistic SnRK1 and TOR crosstalk comparable to the animal system was demonstrated by the in vivo interaction of SnRK1α1 and RAPTOR1B in the cytosol and by phosphorylation of RAPTOR1B by SnRK1α1 in kinase assays. Moreover, changed levels of phosphorylation states of several chloroplastic proteins in the snrk1α1/α2 mutant indicated an unexpected link to regulation of photosynthesis, the main energy source in plants. PMID:27545962

  16. A Global Analysis of Protected Area Management Effectiveness

    NASA Astrophysics Data System (ADS)

    Leverington, Fiona; Costa, Katia Lemos; Pavese, Helena; Lisle, Allan; Hockings, Marc

    2010-11-01

    We compiled details of over 8000 assessments of protected area management effectiveness across the world and developed a method for analyzing results across diverse assessment methodologies and indicators. Data was compiled and analyzed for over 4000 of these sites. Management of these protected areas varied from weak to effective, with about 40% showing major deficiencies. About 14% of the surveyed areas showed significant deficiencies across many management effectiveness indicators and hence lacked basic requirements to operate effectively. Strongest management factors recorded on average related to establishment of protected areas (legal establishment, design, legislation and boundary marking) and to effectiveness of governance; while the weakest aspects of management included community benefit programs, resourcing (funding reliability and adequacy, staff numbers and facility and equipment maintenance) and management effectiveness evaluation. Estimations of management outcomes, including both environmental values conservation and impact on communities, were positive. We conclude that in spite of inadequate funding and management process, there are indications that protected areas are contributing to biodiversity conservation and community well-being.

  17. Representing the Forest before the Trees: A Global Advantage Effect in Monkey Inferotemporal Cortex

    PubMed Central

    Sripati, Arun P.; Olson, Carl R.

    2009-01-01

    Hierarchical stimuli (large shapes composed of small shapes) have long been used to study how humans perceive the global and the local content of a scene – the forest and the trees. Studies using these stimuli have revealed a global advantage effect: humans consistently report global shape faster than local shape. The neuronal underpinnings of this effect remain unclear. Here we demonstrate a correlate and possible mechanism in monkey inferotemporal cortex (IT). Inferotemporal neurons signal the global content of a hierarchical display around 30 ms before they signal its local content. This is a specific expression of a general principle, related to spatial scale or spatial frequency rather than to hierarchical level, whereby the representation of a large shape develops in IT before that of a small shape. These findings provide support for a coarse-to-fine model of visual scene representation. PMID:19535590

  18. The effect of global versus local processing styles on assimilation versus contrast in social judgment.

    PubMed

    Förster, Jens; Liberman, Nira; Kuschel, Stefanie

    2008-04-01

    The authors propose a global/local processing style model (GLOMO) for assimilation and contrast effects in social judgment. GLOMO is based on Schwarz and Bless' (1992, 2007) inclusion-exclusion model, which suggests that when information is included into a category, assimilation occurs, whereas when information is excluded from a category, contrast occurs. According to GLOMO, inclusion versus exclusion should be influenced by whether people process information globally or locally. In 5 experiments, using both disambiguation and social comparison, the authors induced local versus global processing through perceptual tasks and time perspective and showed that global processing produced assimilation, whereas local processing produced contrast. The experiments showed that processing styles elicited in one task can carry over to other tasks and influence social judgments. Furthermore, they found that hemisphere activation and accessibility of judgment-consistent knowledge partially mediated these effects. Implications for current and classic models of social judgment are discussed.

  19. The effects of continental growth on global sea level

    NASA Astrophysics Data System (ADS)

    Sim, S.; Stegman, D. R.; Coltice, N.

    2015-12-01

    The Earth's oceans have played an important role in the evolution of life and tectonics on Earth, and yet our understanding of basic connections between these remains limited. One of the central, and still unanswered questions, is whether Earth's oceans have been present over all of Earth's history, and how deep were any oceans that may have existed. Global tectonics provides a large influence on the long term fluctuations in sea level through varying the volume of ocean basins. The volume of ocean basins over time can be estimated from the seafloor age distribution as observed in plate reconstructions, which gives the proportion of younger, elevated seafloor to older, subsided seafloor. First we establish a relationship between sea level and the age-area distribution of oceanic crust using reconstructed oceanic plate age for recent 140 Myr from Müller et al. (2008), accounting for other major contributions such as the volume of ice sheets, the presence of large igneous provinces on the seafloor and thickness of sediments on the seafloor. We then extend this methodology back into earlier times during Earth's history by using synthetic plate reconstructions derived from numerical models of mantle convection in 3D spherical geometry. To approximate conditions for earlier in Earth's history, we consider that the Rayleigh number would have been higher in the past, resulting in faster surface velocities and, on-average, younger seafloor. Thus, we vary the surface velocity from the modern day value of 4 cm/yr to what is predicted for early Earth conditions of 80 cm/yr (corresponding to Rayleigh number of 10^8 to 10^10, respectively). Coltice et al. (2014) showed that the shape of seafloor age distribution is influenced by the growth of continental area over time, with an increasingly younger-aged, triangular shaped distribution favored for increasing continental surface. We vary the amount of continents on Earth from 0, 10%, to 30% of surface area of the Earth. These

  20. Global dynamics of avian influenza epidemic models with psychological effect.

    PubMed

    Liu, Sanhong; Pang, Liuyong; Ruan, Shigui; Zhang, Xinan

    2015-01-01

    Cross-sectional surveys conducted in Thailand and China after the outbreaks of the avian influenza A H5N1 and H7N9 viruses show a high degree of awareness of human avian influenza in both urban and rural populations, a higher level of proper hygienic practice among urban residents, and in particular a dramatically reduced number of visits to live markets in urban population after the influenza A H7N9 outbreak in China in 2013. In this paper, taking into account the psychological effect toward avian influenza in the human population, a bird-to-human transmission model in which the avian population exhibits saturation effect is constructed. The dynamical behavior of the model is studied by using the basic reproduction number. The results demonstrate that the saturation effect within avian population and the psychological effect in human population cannot change the stability of equilibria but can affect the number of infected humans if the disease is prevalent. Numerical simulations are given to support the theoretical results and sensitivity analyses of the basic reproduction number in terms of model parameters that are performed to seek for effective control measures for avian influenza.

  1. A global simulation of brown carbon: implications for photochemistry and direct radiative effect

    NASA Astrophysics Data System (ADS)

    Jo, Duseong S.; Park, Rokjin J.; Lee, Seungun; Kim, Sang-Woo; Zhang, Xiaolu

    2016-03-01

    Recent observations suggest that a certain fraction of organic carbon (OC) aerosol effectively absorbs solar radiation, which is also known as brown carbon (BrC) aerosol. Despite much observational evidence of its presence, very few global modelling studies have been conducted because of poor understanding of global BrC emissions. Here we present an explicit global simulation of BrC in a global 3-D chemical transport model (GEOS-Chem), including global BrC emission estimates from primary (3.9 ± 1.7 and 3.0 ± 1.3 TgC yr-1 from biomass burning and biofuel) and secondary (5.7 TgC yr-1 from aromatic oxidation) sources. We evaluate the model by comparing the results with observed absorption by water-soluble OC in surface air in the United States, and with single scattering albedo observations at Aerosol Robotic Network (AERONET) sites all over the globe. The model successfully reproduces the seasonal variations of observed light absorption by water-soluble OC, but underestimates the magnitudes, especially in regions with high secondary source contributions. Our global simulations show that BrC accounts for 21 % of the global mean surface OC concentration, which is typically assumed to be scattering. We find that the global direct radiative effect of BrC is nearly zero at the top of the atmosphere, and consequently decreases the direct radiative cooling effect of OC by 16 %. In addition, the BrC absorption leads to a general reduction of NO2 photolysis rates, whose maximum decreases occur in Asia up to -8 % (-17 %) on an annual (spring) mean basis. The resulting decreases of annual (spring) mean surface ozone concentrations are up to -6 % (-13 %) in Asia, indicating a non-negligible effect of BrC on photochemistry in this region.

  2. Effects of foliage clumping on the estimation of global terrestrial gross primary productivity

    NASA Astrophysics Data System (ADS)

    Chen, Jing M.; Mo, Gang; Pisek, Jan; Liu, Jane; Deng, Feng; Ishizawa, Misa; Chan, Douglas

    2012-03-01

    Sunlit and shaded leaf separation proposed by Norman (1982) is an effective way to upscale from leaf to canopy in modeling vegetation photosynthesis. The Boreal Ecosystem Productivity Simulator (BEPS) makes use of this methodology, and has been shown to be reliable in modeling the gross primary productivity (GPP) derived from CO2flux and tree ring measurements. In this study, we use BEPS to investigate the effect of canopy architecture on the global distribution of GPP. For this purpose, we use not only leaf area index (LAI) but also the first ever global map of the foliage clumping index derived from the multiangle satellite sensor POLDER at 6 km resolution. The clumping index, which characterizes the degree of the deviation of 3-dimensional leaf spatial distributions from the random case, is used to separate sunlit and shaded LAI values for a given LAI. Our model results show that global GPP in 2003 was 132 ± 22 Pg C. Relative to this baseline case, our results also show: (1) global GPP is overestimated by 12% when accurate LAI is available but clumping is ignored, and (2) global GPP is underestimated by 9% when the effective LAI is available and clumping is ignored. The clumping effects in both cases are statistically significant (p < 0.001). The effective LAI is often derived from remote sensing by inverting the measured canopy gap fraction to LAI without considering the clumping. Global GPP would therefore be generally underestimated when remotely sensed LAI (actually effective LAI by our definition) is used. This is due to the underestimation of the shaded LAI and therefore the contribution of shaded leaves to GPP. We found that shaded leaves contribute 50%, 38%, 37%, 39%, 26%, 29% and 21% to the total GPP for broadleaf evergreen forest, broadleaf deciduous forest, evergreen conifer forest, deciduous conifer forest, shrub, C4 vegetation, and other vegetation, respectively. The global average of this ratio is 35%.

  3. Protective effect of resveratrol against neuronal damage following transient global cerebral ischemia in mice.

    PubMed

    Hong, Jeong-Ho; Lee, Hyung; Lee, Seong-Ryong

    2016-01-01

    Resveratrol (3,5,4'-trihydroxystilbene) is a natural polyphenol which is rich in grape seeds and skin. Several studies have revealed that resveratrol possesses neuroprotective effects. In the case of global brain ischemia, there are few reports regarding the protective effect of resveratrol. Therefore, the influence of resveratrol on neuronal damage after transient global brain ischemia remains to be clarified. In the current study, C57BL/6 black mice were subjected to 20 min of transient global brain ischemia and followed by 72 h of reperfusion. Resveratrol (20 or 40 mg/kg, once daily, dissolved in 0.5% carboxymethylcellulose) was administered orally for 7 days before ischemia and daily until the mice were euthanized. The effect of lower or higher dose of resveratrol on neuronal damage, matrix metalloproteinase (MMP) activity and in situ DNA fragmentation (TUNEL) assay in the hippocampus after global ischemia was examined. Neuronal damages were remarkable in CA1 and CA2 pyramidal cell layers after global ischemia. In resveratrol-treated mice (40 mg/kg), neuronal damage was significantly reduced compared with vehicle-treated mice. Mice treated with resveratrol showed reduced MMP-9 activity. Resveratrol also inhibited TUNEL staining. These data suggest that resveratrol, a natural polyphenol, reduces hippocampal neuronal cell damage following transient global ischemia by reducing MMP-9 activity.

  4. GLOBAL CHANGE RESEARCH NEWS #7: ENVIRONMENTAL EFFECTS OF OZONE DEPLETION

    EPA Science Inventory

    This edition focuses on a recent UNEP report entitled, "Environmental Effects of Ozone Depletion: 1998 Assessment." Dr. Richard Zepp (ORD/NERL) is one of the Lead Authors of this report. The 1998 assessment focuses on new information produced since 1994. It also includes earlie...

  5. Effects of grazing on grassland soil carbon: a global review.

    PubMed

    McSherry, Megan E; Ritchie, Mark E

    2013-05-01

    Soils of grasslands represent a large potential reservoir for storing CO2 , but this potential likely depends on how grasslands are managed for large mammal grazing. Previous studies found both strong positive and negative grazing effects on soil organic carbon (SOC) but explanations for this variation are poorly developed. Expanding on previous reviews, we performed a multifactorial meta-analysis of grazer effects on SOC density on 47 independent experimental contrasts from 17 studies. We explicitly tested hypotheses that grazer effects would shift from negative to positive with decreasing precipitation, increasing fineness of soil texture, transition from dominant grass species with C3 to C4 photosynthesis, and decreasing grazing intensity, after controlling for study duration and sampling depth. The six variables of soil texture, precipitation, grass type, grazing intensity, study duration, and sampling depth explained 85% of a large variation (±150 g m(-2)  yr(-1) ) in grazing effects, and the best model included significant interactions between precipitation and soil texture (P = 0.002), grass type, and grazing intensity (P = 0.012), and study duration and soil sampling depth (P = 0.020). Specifically, an increase in mean annual precipitation of 600 mm resulted in a 24% decrease in grazer effect size on finer textured soils, while on sandy soils the same increase in precipitation produced a 22% increase in grazer effect on SOC. Increasing grazing intensity increased SOC by 6-7% on C4 -dominated and C4 -C3 mixed grasslands, but decreased SOC by an average 18% in C3 -dominated grasslands. We discovered these patterns despite a lack of studies in natural, wildlife-dominated ecosystems, and tropical grasslands. Our results, which suggest a future focus on why C3 vs. C4 -dominated grasslands differ so strongly in their response of SOC to grazing, show that grazer effects on SOC are highly context-specific and imply that grazers in different regions might

  6. Time-lag effects of global vegetation responses to climate change.

    PubMed

    Wu, Donghai; Zhao, Xiang; Liang, Shunlin; Zhou, Tao; Huang, Kaicheng; Tang, Bijian; Zhao, Wenqian

    2015-09-01

    Climate conditions significantly affect vegetation growth in terrestrial ecosystems. Due to the spatial heterogeneity of ecosystems, the vegetation responses to climate vary considerably with the diverse spatial patterns and the time-lag effects, which are the most important mechanism of climate-vegetation interactive effects. Extensive studies focused on large-scale vegetation-climate interactions use the simultaneous meteorological and vegetation indicators to develop models; however, the time-lag effects are less considered, which tends to increase uncertainty. In this study, we aim to quantitatively determine the time-lag effects of global vegetation responses to different climatic factors using the GIMMS3g NDVI time series and the CRU temperature, precipitation, and solar radiation datasets. First, this study analyzed the time-lag effects of global vegetation responses to different climatic factors. Then, a multiple linear regression model and partial correlation model were established to statistically analyze the roles of different climatic factors on vegetation responses, from which the primary climate-driving factors for different vegetation types were determined. The results showed that (i) both the time-lag effects of the vegetation responses and the major climate-driving factors that significantly affect vegetation growth varied significantly at the global scale, which was related to the diverse vegetation and climate characteristics; (ii) regarding the time-lag effects, the climatic factors explained 64% variation of the global vegetation growth, which was 11% relatively higher than the model ignoring the time-lag effects; (iii) for the area with a significant change trend (for the period 1982-2008) in the global GIMMS3g NDVI (P < 0.05), the primary driving factor was temperature; and (iv) at the regional scale, the variation in vegetation growth was also related to human activities and natural disturbances. Considering the time-lag effects is quite

  7. Extracellular Matrix Proteome and Phosphoproteome of Potato Reveals Functionally Distinct and Diverse Canonical and Non-Canonical Proteoforms

    PubMed Central

    Elagamey, Eman; Narula, Kanika; Sinha, Arunima; Aggarwal, Pooja Rani; Ghosh, Sudip; Chakraborty, Niranjan; Chakraborty, Subhra

    2016-01-01

    The extracellular matrix (ECM) has a molecular machinery composed of diverse proteins and proteoforms that combine properties of tensile strength with extensibility exhibiting growth-regulatory functions and self- and non-self-recognition. The identification of ECM proteoforms is the prerequisite towards a comprehensive understanding of biological functions accomplished by the outermost layer of the cell. Regulatory mechanisms of protein functions rely on post-translational modifications, phosphorylation in particular, affecting enzymatic activity, interaction, localization and stability. To investigate the ECM proteoforms, we have isolated the cell wall proteome and phosphoproteome of a tuberous crop, potato (Solanum tuberosum). LC-MS/MS analysis led to the identification of 38 proteins and 35 phosphoproteins of known and unknown functions. The findings may provide a better understanding of biochemical machinery and the integrated protein and phosphoprotein network of ECM for future functional studies of different developmental pathways and guidance cues in mechanosensing and integrity signaling. PMID:28248230

  8. Global constraints on vector-like WIMP effective interactions

    SciTech Connect

    Blennow, Mattias; Coloma, Pilar; Fernandez-Martinez, Enrique

    2016-04-07

    In this work we combine information from relic abundance, direct detection, cosmic microwave background, positron fraction, gamma rays, and colliders to explore the existing constraints on couplings between Dark Matter and Standard Model constituents when no underlying model or correlation is assumed. For definiteness, we include independent vector-like effective interactions for each Standard Model fermion. Our results show that low Dark Matter masses below 20 GeV are disfavoured at the 3 σ  level with respect to higher masses, due to the tension between the relic abundance requirement and upper constraints on the Dark Matter couplings. Lastly, large couplings are typically only allowed in combinations which avoid effective couplings to the nuclei used in direct detection experiments.

  9. Global constraints on vector-like WIMP effective interactions

    SciTech Connect

    Blennow, Mattias; Coloma, Pilar; Fernández-Martínez, Enrique; Machado, Pedro A.N.; Zaldívar, Bryan E-mail: pcoloma@fnal.gov E-mail: pedro.machado@uam.es

    2016-04-01

    In this work we combine information from relic abundance, direct detection, cosmic microwave background, positron fraction, gamma rays, and colliders to explore the existing constraints on couplings between Dark Matter and Standard Model constituents when no underlying model or correlation is assumed. For definiteness, we include independent vector-like effective interactions for each Standard Model fermion. Our results show that low Dark Matter masses below 20 GeV are disfavoured at the 3 σ  level with respect to higher masses, due to the tension between the relic abundance requirement and upper constraints on the Dark Matter couplings. Furthermore, large couplings are typically only allowed in combinations which avoid effective couplings to the nuclei used in direct detection experiments.

  10. Global constraints on vector-like WIMP effective interactions

    DOE PAGES

    Blennow, Mattias; Coloma, Pilar; Fernandez-Martinez, Enrique; ...

    2016-04-07

    In this work we combine information from relic abundance, direct detection, cosmic microwave background, positron fraction, gamma rays, and colliders to explore the existing constraints on couplings between Dark Matter and Standard Model constituents when no underlying model or correlation is assumed. For definiteness, we include independent vector-like effective interactions for each Standard Model fermion. Our results show that low Dark Matter masses below 20 GeV are disfavoured at the 3 σ  level with respect to higher masses, due to the tension between the relic abundance requirement and upper constraints on the Dark Matter couplings. Lastly, large couplings are typically onlymore » allowed in combinations which avoid effective couplings to the nuclei used in direct detection experiments.« less

  11. Will Global Change Effect Primary Productivity in Coastal Ecosystems?

    NASA Technical Reports Server (NTRS)

    Rothschild, Lynn J.; Peterson, David L. (Technical Monitor)

    1997-01-01

    Algae are the base of coastal food webs because they provide the source of organic carbon for the remaining members of the community. Thus, the rate that they produce organic carbon to a large extent controls the productivity of the entire ecosystem. Factors that control algal productivity range from the physical (e.g., temperature, light), chemical (e.g., nutrient levels) to the biological (e.g., grazing). Currently, levels of atmospheric carbon dioxide surficial fluxes of ultraviolet radiation are rising. Both of these environmental variables can have a profound effect on algal productivity. Atmospheric carbon dioxide may increase surficial levels of dissolved inorganic carbon. Our laboratory and field studies of algal mats and phytoplankton cultures under ambient and elevated levels of pCO2 show that elevated levels of inorganic carbon can cause an increase in photosynthetic rates. In some cases, this increase will cause an increase in phytoplankton numbers. There may be an increase in the excretion of fixed carbon, which in turn may enhance bacterial productivity. Alternatively, in analogy with studies on the effect of elevated pCO2 on plants, the phytoplankton could change their carbon to nitrogen ratios, which will effect the feeding of the planktonic grazers. The seasonal depletion of stratospheric ozone has resulted in elevated fluxes of UVB radiation superimposed on the normal seasonal variation. Present surface UV fluxes have a significant impact on phytoplankton physiology, including the inhibition of the light and dark reactions of photosynthesis, inhibition of nitrogenase activity, inhibition of heterocyst formation, reduction in motility, increased synthesis of the UV-screening pigment scytonemin, and mutation. After reviewing these issues, recent work in our lab on measuring the effect of UV radiation on phytoplankton in the San Francisco Bay Estuary will be presented.

  12. Global Climate Change: Federal Research on Possible Human Health Effects

    DTIC Science & Technology

    2006-02-10

    conditioning systems.”20 A recent rise in one measure of poverty in the United States is argued by some to suggest that there may be more poor ...conclusions are common to several studies on possible health effects of climate change: the infirm, the elderly, and the poor may be disproportionately...health, particularly in lower income populations, predominantly within tropical/subtropical countries.”3 For more detailed discussion, see CRS Issue

  13. The Global Financial Crisis: Foreign and Trade Policy Effects

    DTIC Science & Technology

    2009-04-07

    when we created them. As indicated in Figure 1, the financial crisis began with a rising default level in subprime mortgages, bankruptcies, an...political crises in Eastern Europe and tug-of- war for influence there between Russia and the EU/U.S. Fundamental Philosophies Rise of state capitalism and...designed to prevent future crises and correct past abuses of the system. The fourth phase has been to deal with political and foreign policy effects of the

  14. Global fits of the dark matter-nucleon effective interactions

    SciTech Connect

    Catena, Riccardo; Gondolo, Paolo E-mail: paolo.gondolo@utah.edu

    2014-09-01

    The effective theory of isoscalar dark matter-nucleon interactions mediated by heavy spin-one or spin-zero particles depends on 10 coupling constants besides the dark matter particle mass. Here we compare this 11-dimensional effective theory to current observations in a comprehensive statistical analysis of several direct detection experiments, including the recent LUX, SuperCDMS and CDMSlite results. From a multidimensional scan with about 3 million likelihood evaluations, we extract the marginalized posterior probability density functions (a Bayesian approach) and the profile likelihoods (a frequentist approach), as well as the associated credible regions and confidence levels, for each coupling constant vs dark matter mass and for each pair of coupling constants. We compare the Bayesian and frequentist approach in the light of the currently limited amount of data. We find that current direct detection data contain sufficient information to simultaneously constrain not only the familiar spin-independent and spin-dependent interactions, but also the remaining velocity and momentum dependent couplings predicted by the dark matter-nucleon effective theory. For current experiments associated with a null result, we find strong correlations between some pairs of coupling constants. For experiments that claim a signal (i.e., CoGeNT and DAMA), we find that pairs of coupling constants produce degenerate results.

  15. The 'island effect' in terrestrial global change experiments: a problem with no solution?

    PubMed

    Leuzinger, Sebastian; Fatichi, Simone; Cusens, Jarrod; Körner, Christian; Niklaus, Pascal A

    2015-07-27

    Most of the currently experienced global environmental changes (rising atmospheric CO2 concentrations, warming, altered amount and pattern of precipitation, and increased nutrient load) directly or indirectly affect ecosystem surface energy balance and plant transpiration. As a consequence, the relative humidity of the air surrounding the vegetation changes, thus creating a feedback loop whose net effect on transpiration and finally productivity is not trivial to quantify. Forcedly, in any global change experiment with the above drivers, we can only treat small plots, or 'islands', of vegetation. This means that the treated plots will likely experience the ambient humidity conditions influenced by the surrounding, non-treated vegetation. Experimental assessments of global change effects will thus systematically lack modifications originating from these potentially important feedback mechanisms, introducing a bias of unknown magnitude in all measurements of processes directly or indirectly depending on plant transpiration. We call this potential bias the 'island effect'. Here, we discuss its implications in various global change experiments with plants. We also suggest ways to complement experiments using modelling approaches and observational studies. Ultimately, there is no obvious solution to deal with the island effect in field experiments and only models can provide an estimate of modification of responses by these feedbacks. However, we suggest that increasing the awareness of the island effect among both experimental researchers and modellers will greatly improve the interpretation of vegetation responses to global change.

  16. Quantitative Proteomic and Phosphoproteomic Analysis of H37Ra and H37Rv Strains of Mycobacterium tuberculosis.

    PubMed

    Verma, Renu; Pinto, Sneha Maria; Patil, Arun Hanumana; Advani, Jayshree; Subba, Pratigya; Kumar, Manish; Sharma, Jyoti; Dey, Gourav; Ravikumar, Raju; Buggi, Shashidhar; Satishchandra, Parthasarathy; Sharma, Kusum; Suar, Mrutyunjay; Tripathy, Srikanth Prasad; Chauhan, Devendra Singh; Gowda, Harsha; Pandey, Akhilesh; Gandotra, Sheetal; Prasad, Thottethodi Subrahmanya Keshava

    2017-03-20

    Mycobacterium tuberculosis, the causative agent of tuberculosis, accounts for 1.5 million human deaths annually worldwide. Despite efforts to eradicate tuberculosis, it still remains a deadly disease. The two best characterized strains of M. tuberculosis, virulent H37Rv and avirulent H37Ra, provide a unique platform to investigate biochemical and signaling pathways associated with pathogenicity. To delineate the biomolecular dynamics that may account for pathogenicity and attenuation of virulence in M. tuberculosis, we compared the proteome and phosphoproteome profiles of H37Rv and H37Ra strains. Quantitative phosphoproteomic analysis was performed using high-resolution Fourier transform mass spectrometry. Analysis of exponential and stationary phases of these strains resulted in identification and quantitation of 2709 proteins along with 512 phosphorylation sites derived from 257 proteins. In addition to confirming the presence of previously described M. tuberculosis phosphorylated proteins, we identified 265 novel phosphorylation sites. Quantitative proteomic analysis revealed more than five-fold upregulation of proteins belonging to virulence associated type VII bacterial secretion system in H37Rv when compared to those in H37Ra. We also identified 84 proteins, which exhibited changes in phosphorylation levels between the virulent and avirulent strains. Bioinformatics analysis of the proteins altered in their level of expression or phosphorylation revealed enrichment of pathways involved in fatty acid biosynthesis and two-component regulatory system. Our data provides a resource for further exploration of functional differences at molecular level between H37Rv and H37Ra, which will ultimately explain the molecular underpinnings that determine virulence in tuberculosis.

  17. Phosphoproteome Dynamics Upon Changes in Plant Water Status Reveal Early Events Associated With Rapid Growth Adjustment in Maize Leaves*

    PubMed Central

    Bonhomme, Ludovic; Valot, Benoît; Tardieu, François; Zivy, Michel

    2012-01-01

    Plant growth adjustment during water deficit is a crucial adaptive response. The rapid fine-tuned control achieved at the post-translational level is believed to be of considerable importance for regulating early changes in plant growth reprogramming. Aiming at a better understanding of early responses to contrasting plant water statuses, we carried out a survey of the protein phosphorylation events in the growing zone of maize leaves upon a range of water regimes. In this study, the impact of mild and severe water deficits were evaluated in comparison with constant optimal watering and with recovery periods lasting 5, 10, 20, 30, 45, and 60 min. Using four biological replicates per treatment and a robust quantitative phosphoproteomic methodology based on stable-isotope labeling, we identified 3664 unique phosphorylation sites on 2496 proteins. The abundance of nearly 1250 phosphorylated peptides was reproducibly quantified and profiled with high confidence among treatments. A total of 138 phosphopeptides displayed highly significant changes according to water regimes and enabled to identify specific patterns of response to changing plant water statuses. Further quantification of protein amounts emphasized that most phosphorylation changes did not reflect protein abundance variation. During water deficit and recovery, extensive changes in phosphorylation status occurred in critical regulators directly or indirectly involved in plant growth and development. These included proteins influencing epigenetic control, gene expression, cell cycle-dependent processes and phytohormone-mediated responses. Some of the changes depended on stress intensity whereas others depended on rehydration duration, including rapid recoveries that occurred as early as 5 or 10 mins after rewatering. By combining a physiological approach and a quantitative phosphoproteomic analysis, this work provides new insights into the in vivo early phosphorylation events triggered by rapid changes in

  18. Phosphoproteome dynamics upon changes in plant water status reveal early events associated with rapid growth adjustment in maize leaves.

    PubMed

    Bonhomme, Ludovic; Valot, Benoît; Tardieu, François; Zivy, Michel

    2012-10-01

    Plant growth adjustment during water deficit is a crucial adaptive response. The rapid fine-tuned control achieved at the post-translational level is believed to be of considerable importance for regulating early changes in plant growth reprogramming. Aiming at a better understanding of early responses to contrasting plant water statuses, we carried out a survey of the protein phosphorylation events in the growing zone of maize leaves upon a range of water regimes. In this study, the impact of mild and severe water deficits were evaluated in comparison with constant optimal watering and with recovery periods lasting 5, 10, 20, 30, 45, and 60 min. Using four biological replicates per treatment and a robust quantitative phosphoproteomic methodology based on stable-isotope labeling, we identified 3664 unique phosphorylation sites on 2496 proteins. The abundance of nearly 1250 phosphorylated peptides was reproducibly quantified and profiled with high confidence among treatments. A total of 138 phosphopeptides displayed highly significant changes according to water regimes and enabled to identify specific patterns of response to changing plant water statuses. Further quantification of protein amounts emphasized that most phosphorylation changes did not reflect protein abundance variation. During water deficit and recovery, extensive changes in phosphorylation status occurred in critical regulators directly or indirectly involved in plant growth and development. These included proteins influencing epigenetic control, gene expression, cell cycle-dependent processes and phytohormone-mediated responses. Some of the changes depended on stress intensity whereas others depended on rehydration duration, including rapid recoveries that occurred as early as 5 or 10 mins after rewatering. By combining a physiological approach and a quantitative phosphoproteomic analysis, this work provides new insights into the in vivo early phosphorylation events triggered by rapid changes in

  19. Phosphoproteomes of Strongylocentrotus purpuratus shell and tooth matrix: identification of a major acidic sea urchin tooth phosphoprotein, phosphodontin

    PubMed Central

    2010-01-01

    Background Sea urchin is a major model organism for developmental biology and biomineralization research. However, identification of proteins involved in larval skeleton formation and mineralization processes in the embryo and adult, and the molecular characterization of such proteins, has just gained momentum with the sequencing of the Strongylocentrotus purpuratus genome and the introduction of high-throughput proteomics into the field. Results The present report contains the determination of test (shell) and tooth organic matrix phosphoproteomes. Altogether 34 phosphoproteins were identified in the biomineral organic matrices. Most phosphoproteins were specific for one compartment, only two were identified in both matrices. The sea urchin phosphoproteomes contained several obvious orthologs of mammalian proteins, such as a Src family tyrosine kinase, protein kinase C-delta 1, Dickkopf-1 and other signal transduction components, or nucleobindin. In most cases phosphorylation sites were conserved between sea urchin and mammalian proteins. However, the majority of phosphoproteins had no mammalian counterpart. The most interesting of the sea urchin-specific phosphoproteins, from the perspective of biomineralization research, was an abundant highly phosphorylated and very acidic tooth matrix protein composed of 35 very similar short sequence repeats, a predicted N-terminal secretion signal sequence, and an Asp-rich C-terminal motif, contained in [Glean3:18919]. Conclusions The 64 phosphorylation sites determined represent the most comprehensive list of experimentally identified sea urchin protein phosphorylation sites at present and are an important addition to the recently analyzed Strongylocentrotus purpuratus shell and tooth proteomes. The identified phosphoproteins included a major, highly phosphorylated protein, [Glean3:18919], for which we suggest the name phosphodontin. Although not sequence-related to such highly phosphorylated acidic mammalian dental

  20. Air Pollution in Megacities: Sources and Regional/Global Effects

    NASA Astrophysics Data System (ADS)

    Artaxo, P.

    2007-12-01

    Air Pollution in Megacities is increasing significantly in all continents. The socio-economic and health problems are escalating, especially in developing countries. In terms of sources, urban transportation is relevant in most cities, as well as industrial pollution. In Latin American Cities such as Sao Paulo, Mexico City and Santiago, serious governmental efforts are being doing to reduce emissions and effects. Latin America has about 300 cities with population above 300.000 people. In Sao Paulo, the significant increase in the use of ethanol as fuel brings important increase in aldehyde concentrations. In all 3 Megacities, high aerosol concentrations are observed, with clear effects on population health. Large studies on aerosol source apportionment were done in these 3 cities, and detailed results will be presented. Quantification of aerosol sources is a problem, especially in the organic aerosol component that is high in most of Megacities. In Asia and Africa, the problems are similar as in Latin America, and the large emissions from these urban centers are relevant and needs to be taken into account in policies to reduce carbon dioxide emissions.

  1. Further evidence of the effects of global warming on lichens, particularly those with Trentepohlia phycobionts.

    PubMed

    Aptroot, A; van Herk, C M

    2007-03-01

    Increasing evidence suggests that lichens are responding to climate change in Western Europe. More epiphytic species appear to be increasing, rather than declining, as a result of global warming. Many terricolous species, in contrast, are declining. Changes to epiphytic floras are markedly more rapid in formerly heavily polluted, generally built-up or open rural areas, as compared to forested regions. Both the distribution (southern) and ecology (warmth-loving) of the newly established or increasing species seem to be determined by global warming. Epiphytic temperate to boreo-montane species appear to be relatively unaffected. Vacant niches caused by other environmental changes are showing the most pronounced effects of global warming. Species most rapidly increasing in forests, although taxonomically unrelated, all contain Trentepohlia as phycobiont in addition to having a southern distribution. This suggests that in this habitat, Trentepohlia algae, rather than the different lichen symbioses, are affected by global warming.

  2. Global Synthesis of Drought Effects on Maize and Wheat Production.

    PubMed

    Daryanto, Stefani; Wang, Lixin; Jacinthe, Pierre-André

    2016-01-01

    Drought has been a major cause of agricultural disaster, yet how it affects the vulnerability of maize and wheat production in combination with several co-varying factors (i.e., phenological phases, agro-climatic regions, soil texture) remains unclear. Using a data synthesis approach, this study aims to better characterize the effects of those co-varying factors with drought and to provide critical information on minimizing yield loss. We collected data from peer-reviewed publications between 1980 and 2015 which examined maize and wheat yield responses to drought using field experiments. We performed unweighted analysis using the log response ratio to calculate the bootstrapped confidence limits of yield responses and calculated drought sensitivities with regards to those co-varying factors. Our results showed that yield reduction varied with species, with wheat having lower yield reduction (20.6%) compared to maize (39.3%) at approximately 40% water reduction. Maize was also more sensitive to drought than wheat, particularly during reproductive phase and equally sensitive in the dryland and non-dryland regions. While no yield difference was observed among regions or different soil texture, wheat cultivation in the dryland was more prone to yield loss than in the non-dryland region. Informed by these results, we discuss potential causes and possible approaches that may minimize drought impacts.

  3. Global Synthesis of Drought Effects on Maize and Wheat Production

    PubMed Central

    Daryanto, Stefani; Wang, Lixin; Jacinthe, Pierre-André

    2016-01-01

    Drought has been a major cause of agricultural disaster, yet how it affects the vulnerability of maize and wheat production in combination with several co-varying factors (i.e., phenological phases, agro-climatic regions, soil texture) remains unclear. Using a data synthesis approach, this study aims to better characterize the effects of those co-varying factors with drought and to provide critical information on minimizing yield loss. We collected data from peer-reviewed publications between 1980 and 2015 which examined maize and wheat yield responses to drought using field experiments. We performed unweighted analysis using the log response ratio to calculate the bootstrapped confidence limits of yield responses and calculated drought sensitivities with regards to those co-varying factors. Our results showed that yield reduction varied with species, with wheat having lower yield reduction (20.6%) compared to maize (39.3%) at approximately 40% water reduction. Maize was also more sensitive to drought than wheat, particularly during reproductive phase and equally sensitive in the dryland and non-dryland regions. While no yield difference was observed among regions or different soil texture, wheat cultivation in the dryland was more prone to yield loss than in the non-dryland region. Informed by these results, we discuss potential causes and possible approaches that may minimize drought impacts. PMID:27223810

  4. Effect of accelerated global expansion on the bending of light

    NASA Astrophysics Data System (ADS)

    Aghili, Mir Emad; Bolen, Brett; Bombelli, Luca

    2017-01-01

    In 2007 Rindler and Ishak showed that, contrary to previous claims, the value of the cosmological constant does have an effect on light deflection by a gravitating object in an expanding universe. In their work they considered a Schwarzschild-de Sitter (SdS) spacetime, which has a constant asymptotic expansion rate H_0. A model with a time-dependent H( t) was studied by Kantowski et al., who consider in their 2010 paper a "Swiss-cheese" model of a Friedmann-Lemaître-Robertson-Walker (FLRW) spacetime with an embedded SdS bubble. In this paper, we generalize the Rindler and Ishak model to time-varying H( t) in another way, by considering light bending in a McVittie metric representing a gravitating object in a FLRW cosmological background. We carry out numerical simulations of the propagation of null geodesics in different McVittie spacetimes, in which we keep the values of the distances from the observer to the lensing object and to the source fixed, and vary the form of H( t).

  5. Global Synthesis of Drought Effects on Food Legume Production.

    PubMed

    Daryanto, Stefani; Wang, Lixin; Jacinthe, Pierre-André

    2015-01-01

    Food legume crops play important roles in conservation farming systems and contribute to food security in the developing world. However, in many regions of the world, their production has been adversely affected by drought. Although water scarcity is a severe abiotic constraint of legume crops productivity, it remains unclear how the effects of drought co-vary with legume species, soil texture, agroclimatic region, and drought timing. To address these uncertainties, we collected literature data between 1980 and 2014 that reported monoculture legume yield responses to drought under field conditions, and analyzed this data set using meta-analysis techniques. Our results showed that the amount of water reduction was positively related with yield reduction, but the extent of the impact varied with legume species and the phenological state during which drought occurred. Overall, lentil (Lens culinaris), groundnut (Arachis hypogaea), and pigeon pea (Cajanus cajan) were found to experience lower drought-induced yield reduction compared to legumes such as cowpea (Vigna unguiculata) and green gram (Vigna radiate). Yield reduction was generally greater when legumes experienced drought during their reproductive stage compared to during their vegetative stage. Legumes grown in soil with medium texture also exhibited greater yield reduction compared to those planted on soil of either coarse or fine texture. In contrast, regions and their associated climatic factors did not significantly affect legume yield reduction. In the face of changing climate, our study provides useful information for agricultural planning and research directions for development of drought-resistant legume species to improve adaptation and resilience of agricultural systems in the drought-prone regions of the world.

  6. Global Synthesis of Drought Effects on Food Legume Production

    PubMed Central

    Daryanto, Stefani; Wang, Lixin; Jacinthe, Pierre-André

    2015-01-01

    Food legume crops play important roles in conservation farming systems and contribute to food security in the developing world. However, in many regions of the world, their production has been adversely affected by drought. Although water scarcity is a severe abiotic constraint of legume crops productivity, it remains unclear how the effects of drought co-vary with legume species, soil texture, agroclimatic region, and drought timing. To address these uncertainties, we collected literature data between 1980 and 2014 that reported monoculture legume yield responses to drought under field conditions, and analyzed this data set using meta-analysis techniques. Our results showed that the amount of water reduction was positively related with yield reduction, but the extent of the impact varied with legume species and the phenological state during which drought occurred. Overall, lentil (Lens culinaris), groundnut (Arachis hypogaea), and pigeon pea (Cajanus cajan) were found to experience lower drought-induced yield reduction compared to legumes such as cowpea (Vigna unguiculata) and green gram (Vigna radiate). Yield reduction was generally greater when legumes experienced drought during their reproductive stage compared to during their vegetative stage. Legumes grown in soil with medium texture also exhibited greater yield reduction compared to those planted on soil of either coarse or fine texture. In contrast, regions and their associated climatic factors did not significantly affect legume yield reduction. In the face of changing climate, our study provides useful information for agricultural planning and research directions for development of drought-resistant legume species to improve adaptation and resilience of agricultural systems in the drought-prone regions of the world. PMID:26061704

  7. Global synthesis of drought effects on cereal production

    NASA Astrophysics Data System (ADS)

    Daryanto, S.; Wang, L.; Jacinthe, P. A.

    2015-12-01

    Cereal grains remain as the most important source of calories for the majority of human population. Yet drought has adversely affected their production which co-varies with factors such as crop species, phenological phases and agro-ecosystem. The extent to which those factors affect the vulnerability of cereal agriculture to drought, however, remains unclear. Using a meta-analysis approach, this study aims to better characterize the effects of these factors and to provide critical information on minimizing yield loss. We collected data from peer-reviewed publications between 1980 and 2015 which examined cereal yield responses to drought using field experiments. We performed unweighted analysis using the log response ratio to calculate the bootstrapped confidence limits of yield responses and calculated drought sensitivities for different species (i.e., maize, wheat, rice, barley, sorghum, millet), phenological phases (i.e., vegetative, reproductive, and throughout growing season), soil texture (i.e., fine, medium, coarse), and agro-ecosystems (i.e., dryland vs non-dryland). Our result showed that yield reduction varied with species, with wheat having lower sensitivity and yield reduction (20.6%) compared to maize (39.3%) at approximately 60% water reduction. Millet had the lowest yield reduction compared to other cereal species while rice showed a sharp decline in yield with greater than 50% of water reduction. Drought that occurred during crop reproductive phase caused greater yield reduction (30%) than that occurred during vegetative phase (20%). Maize was particularly sensitive to yield loss when drought occurred during reproductive phase while other cereal species tended to have similar sensitivity to drought during vegetative or reproductive phase. We also found that cereal cultivation in the drylands was more prone to yield loss than in the non-dryland regions, but no difference was observed among different soil textures.

  8. Radiative Effect of Clouds on Tropospheric Chemistry in a Global Three-Dimensional Chemical Transport Model

    NASA Technical Reports Server (NTRS)

    Liu, Hongyu; Crawford, James H.; Pierce, Robert B.; Norris, Peter; Platnick, Steven E.; Chen, Gao; Logan, Jennifer A.; Yantosca, Robert M.; Evans, Mat J.; Kittaka, Chieko; Feng, Yan; Tie, Xuexi

    2006-01-01

    Clouds exert an important influence on tropospheric photochemistry through modification of solar radiation that determines photolysis frequencies (J-values). We assess the radiative effect of clouds on photolysis frequencies and key oxidants in the troposphere with a global three-dimensional (3-D) chemical transport model (GEOS-CHEM) driven by assimilated meteorological observations from the Goddard Earth Observing System data assimilation system (GEOS DAS) at the NASA Global Modeling and Assimilation Office (GMAO). We focus on the year of 2001 with the GEOS-3 meteorological observations. Photolysis frequencies are calculated using the Fast-J radiative transfer algorithm. The GEOS-3 global cloud optical depth and cloud fraction are evaluated and generally consistent with the satellite retrieval products from the Moderate Resolution Imaging Spectroradiometer (MODIS) and the International Satellite Cloud Climatology Project (ISCCP). Results using the linear assumption, which assumes linear scaling of cloud optical depth with cloud fraction in a grid box, show global mean OH concentrations generally increase by less than 6% because of the radiative effect of clouds. The OH distribution shows much larger changes (with maximum decrease of approx.20% near the surface), reflecting the opposite effects of enhanced (weakened) photochemistry above (below) clouds. The global mean photolysis frequencies for J[O1D] and J[NO2] in the troposphere change by less than 5% because of clouds; global mean O3 concentrations in the troposphere increase by less than 5%. This study shows tropical upper tropospheric O3 to be less sensitive to the radiative effect of clouds than previously reported (approx.5% versus approx.20-30%). These results emphasize that the dominant effect of clouds is to influence the vertical redistribution of the intensity of photochemical activity while global average effects remain modest, again contrasting with previous studies. Differing vertical distributions

  9. Effects of aerosol from biomass burning on the global radiation budget

    NASA Technical Reports Server (NTRS)

    Penner, Joyce E.; Dickinson, Robert E.; O'Neill, Christine A.

    1992-01-01

    An analysis is made of the likely contribution of smoke particles from biomass burning to the global radiation balance. These particles act to reflect solar radiation directly; they also can act as cloud condensation nuclei, increasing the reflectivity of clouds. Together these effects, although uncertain, may add up globally to a cooling effect as large as 2 watts per square meter, comparable to the estimated contribution to sulfate aerosols. Anthropogenic increases of smoke emission thus may have helped weaken the net greenhouse warming from anthropogenic trace gases.

  10. Hawking radiation of Dirac monopoles from the global monopole black hole with quantum gravity effects

    NASA Astrophysics Data System (ADS)

    Jusufi, Kimet; Apostolovska, Gordana

    2016-12-01

    In this paper we study the quantum tunneling of Dirac magnetic monopoles from the global monopole black hole under quantum gravity effects. We start from the modified Maxwell's equations and the Generalized Uncertainty Relation (GUP), to recover the GUP corrected temperature for the global monopole black hole by solving the modified Dirac equation via Hamilton-Jacobi method. Furthermore, we also include the quantum corrections beyond the semiclassical approximation, in particular, first we find the logarithmic corrections of GUP corrected entropy and finally we calculate the GUP corrected specific heat capacity. It is argued that the GUP effects may prevent a black hole from complete evaporation and leave remnants.

  11. Global effects of local food-production crises: a virtual water perspective

    PubMed Central

    Tamea, Stefania; Laio, Francesco; Ridolfi, Luca

    2016-01-01

    By importing food and agricultural goods, countries cope with the heterogeneous global water distribution and often rely on water resources available abroad. The virtual displacement of the water used to produce such goods (known as virtual water) connects together, in a global water system, all countries participating to the international trade network. Local food-production crises, having social, economic or environmental origin, propagate in this network, modifying the virtual water trade and perturbing local and global food availability, quantified in terms of virtual water. We analyze here the possible effects of local crises by developing a new propagation model, parsimonious but grounded on data-based and statistically-verified assumptions, whose effectiveness is proved on the Argentinean crisis in 2008–09. The model serves as the basis to propose indicators of crisis impact and country vulnerability to external food-production crises, which highlight that countries with largest water resources have the highest impact on the international trade, and that not only water-scarce but also wealthy and globalized countries are among the most vulnerable to external crises. The temporal analysis reveals that global average vulnerability has increased over time and that stronger effects of crises are now found in countries with low food (and water) availability. PMID:26804492

  12. Internally Consistent MODIS Estimate of Aerosol Clear-Sky Radiative Effect Over the Global Oceans

    NASA Technical Reports Server (NTRS)

    Remer, Lorraine A.; Kaufman, Yoram J.

    2004-01-01

    Modern satellite remote sensing, and in particular the MODerate resolution Imaging Spectroradiometer (MODIS), offers a measurement-based pathway to estimate global aerosol radiative effects and aerosol radiative forcing. Over the Oceans, MODIS retrieves the total aerosol optical thickness, but also reports which combination of the 9 different aerosol models was used to obtain the retrieval. Each of the 9 models is characterized by a size distribution and complex refractive index, which through Mie calculations correspond to a unique set of single scattering albedo, assymetry parameter and spectral extinction for each model. The combination of these sets of optical parameters weighted by the optical thickness attributed to each model in the retrieval produces the best fit to the observed radiances at the top of the atmosphere. Thus the MODIS Ocean aerosol retrieval provides us with (1) An observed distribution of global aerosol loading, and (2) An internally-consistent, observed, distribution of aerosol optical models that when used in combination will best represent the radiances at the top of the atmosphere. We use these two observed global distributions to initialize the column climate model by Chou and Suarez to calculate the aerosol radiative effect at top of the atmosphere and the radiative efficiency of the aerosols over the global oceans. We apply the analysis to 3 years of MODIS retrievals from the Terra satellite and produce global and regional, seasonally varying, estimates of aerosol radiative effect over the clear-sky oceans.

  13. Global effects of local food-production crises: a virtual water perspective.

    PubMed

    Tamea, Stefania; Laio, Francesco; Ridolfi, Luca

    2016-01-25

    By importing food and agricultural goods, countries cope with the heterogeneous global water distribution and often rely on water resources available abroad. The virtual displacement of the water used to produce such goods (known as virtual water) connects together, in a global water system, all countries participating to the international trade network. Local food-production crises, having social, economic or environmental origin, propagate in this network, modifying the virtual water trade and perturbing local and global food availability, quantified in terms of virtual water. We analyze here the possible effects of local crises by developing a new propagation model, parsimonious but grounded on data-based and statistically-verified assumptions, whose effectiveness is proved on the Argentinean crisis in 2008-09. The model serves as the basis to propose indicators of crisis impact and country vulnerability to external food-production crises, which highlight that countries with largest water resources have the highest impact on the international trade, and that not only water-scarce but also wealthy and globalized countries are among the most vulnerable to external crises. The temporal analysis reveals that global average vulnerability has increased over time and that stronger effects of crises are now found in countries with low food (and water) availability.

  14. Simulated effects of nitrogen saturation on the global carbon budget using the IBIS model

    NASA Astrophysics Data System (ADS)

    Lu, Xuehe; Jiang, Hong; Liu, Jinxun; Zhang, Xiuying; Jin, Jiaxin; Zhu, Qiuan; Zhang, Zhen; Peng, Changhui

    2016-12-01

    Over the past 100 years, human activity has greatly changed the rate of atmospheric N (nitrogen) deposition in terrestrial ecosystems, resulting in N saturation in some regions of the world. The contribution of N saturation to the global carbon budget remains uncertain due to the complicated nature of C-N (carbon-nitrogen) interactions and diverse geography. Although N deposition is included in most terrestrial ecosystem models, the effect of N saturation is frequently overlooked. In this study, the IBIS (Integrated BIosphere Simulator) was used to simulate the global-scale effects of N saturation during the period 1961–2009. The results of this model indicate that N saturation reduced global NPP (Net Primary Productivity) and NEP (Net Ecosystem Productivity) by 0.26 and 0.03 Pg C yr‑1, respectively. The negative effects of N saturation on carbon sequestration occurred primarily in temperate forests and grasslands. In response to elevated CO2 levels, global N turnover slowed due to increased biomass growth, resulting in a decline in soil mineral N. These changes in N cycling reduced the impact of N saturation on the global carbon budget. However, elevated N deposition in certain regions may further alter N saturation and C-N coupling.

  15. Simulated effects of nitrogen saturation on the global carbon budget using the IBIS model

    PubMed Central

    Lu, Xuehe; Jiang, Hong; Liu, Jinxun; Zhang, Xiuying; Jin, Jiaxin; Zhu, Qiuan; Zhang, Zhen; Peng, Changhui

    2016-01-01

    Over the past 100 years, human activity has greatly changed the rate of atmospheric N (nitrogen) deposition in terrestrial ecosystems, resulting in N saturation in some regions of the world. The contribution of N saturation to the global carbon budget remains uncertain due to the complicated nature of C-N (carbon-nitrogen) interactions and diverse geography. Although N deposition is included in most terrestrial ecosystem models, the effect of N saturation is frequently overlooked. In this study, the IBIS (Integrated BIosphere Simulator) was used to simulate the global-scale effects of N saturation during the period 1961–2009. The results of this model indicate that N saturation reduced global NPP (Net Primary Productivity) and NEP (Net Ecosystem Productivity) by 0.26 and 0.03 Pg C yr−1, respectively. The negative effects of N saturation on carbon sequestration occurred primarily in temperate forests and grasslands. In response to elevated CO2 levels, global N turnover slowed due to increased biomass growth, resulting in a decline in soil mineral N. These changes in N cycling reduced the impact of N saturation on the global carbon budget. However, elevated N deposition in certain regions may further alter N saturation and C-N coupling. PMID:27966643

  16. Global effects of local food-production crises: a virtual water perspective

    NASA Astrophysics Data System (ADS)

    Tamea, Stefania; Laio, Francesco; Ridolfi, Luca

    2016-01-01

    By importing food and agricultural goods, countries cope with the heterogeneous global water distribution and often rely on water resources available abroad. The virtual displacement of the water used to produce such goods (known as virtual water) connects together, in a global water system, all countries participating to the international trade network. Local food-production crises, having social, economic or environmental origin, propagate in this network, modifying the virtual water trade and perturbing local and global food availability, quantified in terms of virtual water. We analyze here the possible effects of local crises by developing a new propagation model, parsimonious but grounded on data-based and statistically-verified assumptions, whose effectiveness is proved on the Argentinean crisis in 2008–09. The model serves as the basis to propose indicators of crisis impact and country vulnerability to external food-production crises, which highlight that countries with largest water resources have the highest impact on the international trade, and that not only water-scarce but also wealthy and globalized countries are among the most vulnerable to external crises. The temporal analysis reveals that global average vulnerability has increased over time and that stronger effects of crises are now found in countries with low food (and water) availability.

  17. Simulated effects of nitrogen saturation on the global carbon budget using the IBIS model.

    PubMed

    Lu, Xuehe; Jiang, Hong; Liu, Jinxun; Zhang, Xiuying; Jin, Jiaxin; Zhu, Qiuan; Zhang, Zhen; Peng, Changhui

    2016-12-14

    Over the past 100 years, human activity has greatly changed the rate of atmospheric N (nitrogen) deposition in terrestrial ecosystems, resulting in N saturation in some regions of the world. The contribution of N saturation to the global carbon budget remains uncertain due to the complicated nature of C-N (carbon-nitrogen) interactions and diverse geography. Although N deposition is included in most terrestrial ecosystem models, the effect of N saturation is frequently overlooked. In this study, the IBIS (Integrated BIosphere Simulator) was used to simulate the global-scale effects of N saturation during the period 1961-2009. The results of this model indicate that N saturation reduced global NPP (Net Primary Productivity) and NEP (Net Ecosystem Productivity) by 0.26 and 0.03 Pg C yr(-1), respectively. The negative effects of N saturation on carbon sequestration occurred primarily in temperate forests and grasslands. In response to elevated CO2 levels, global N turnover slowed due to increased biomass growth, resulting in a decline in soil mineral N. These changes in N cycling reduced the impact of N saturation on the global carbon budget. However, elevated N deposition in certain regions may further alter N saturation and C-N coupling.

  18. Simulated effects of nitrogen saturation the global carbon budget using the IBIS model

    USGS Publications Warehouse

    Lu, Xuehe; Jiang, Hong; Liu, Jinxun; Zhang, Xiuying; Jin, Jiaxin; Zhu, Qiuan; Zhang, Zhen; Peng, Changhui

    2016-01-01

    Over the past 100 years, human activity has greatly changed the rate of atmospheric N (nitrogen) deposition in terrestrial ecosystems, resulting in N saturation in some regions of the world. The contribution of N saturation to the global carbon budget remains uncertain due to the complicated nature of C-N (carbon-nitrogen) interactions and diverse geography. Although N deposition is included in most terrestrial ecosystem models, the effect of N saturation is frequently overlooked. In this study, the IBIS (Integrated BIosphere Simulator) was used to simulate the global-scale effects of N saturation during the period 1961–2009. The results of this model indicate that N saturation reduced global NPP (Net Primary Productivity) and NEP (Net Ecosystem Productivity) by 0.26 and 0.03 Pg C yr−1, respectively. The negative effects of N saturation on carbon sequestration occurred primarily in temperate forests and grasslands. In response to elevated CO2 levels, global N turnover slowed due to increased biomass growth, resulting in a decline in soil mineral N. These changes in N cycling reduced the impact of N saturation on the global carbon budget. However, elevated N deposition in certain regions may further alter N saturation and C-N coupling.

  19. Global climate change and effects on Pacific Northwest salmonids: An exploratory case study

    SciTech Connect

    Shankle, S.A.

    1990-09-01

    Recently, a number of papers have addressed global warming and freshwater fisheries. The recent report to Congress by the US Environmental Protection Agency included an analysis of potential effects of global warming on fisheries of the Great Lakes, California, and the Southeast. In California, the report stated that salinity increases in the San Francisco Bay could enhance the abundance of marine fish species, while anadromous species could be adversely affected. This paper discusses global climate changes and the effects on Pacific Northwest Salmonids. The impacts of climate change or Spring Chinook production in the Yakima Sub-basin was simulated using a computer modeling system developed for the Northwest Power planning council. 35 refs., 1 fig., 1 tab.

  20. Diurnal variation in the effect of the weekend in global seismic activity

    NASA Astrophysics Data System (ADS)

    Ruzhin, Yu. Ya.; Chertoprud, V. E.; Ivanov-Kholodnyi, G. S.

    2016-09-01

    The influence of the earthquake probability diurnal variation on specific features in the weekend effect in global seismic activity is revealed. The dependence of the global earthquake number on the local time and its possible relation to a quiet solar diurnal variation ( Sq) in the geomagnetic field have been considered in detail. It has been indicated that a stable diurnal effect, which has a maximum near midnight and a minimum near local noon, exists in the global seismicity of the Earth. The diurnal variation amplitude changes insignificantly during days of week and substantially decreases (by a factor of almost 3) on Saturday and Sunday. The weekend effect is not revealed during "local nights." Since the daily effect of a quiet solar diurnal variation ( Sq) should not depend on days of week, we arrive at the conclusion that the diurnal variation in global seismicity evidently contains the anthropogenic activity product. The Sunday effect in the earthquake number decreases over the course of time and is most probably real but weak and not stationary since weekly variations occur against a background (or under the action) of stronger variations, i.e., an increase in the earthquake number and diurnal variations.

  1. The Effect of Land Use (Deforestation) on Global Changing and its consequences in Turkey

    NASA Astrophysics Data System (ADS)

    Onursal Denli, G.; Denli, H. H.

    2015-12-01

    Land use has generally been considered as a local environmental issue, but it is becoming a force of global importance. Global changes to forests, farmlands, waterways, and air are being driven by the need to provide food, water and shelter to more than six billion people. Global croplands, pastures, plantations and urban areas have expanded in recent decades, accompanied by large increases in energy, water and fertilizer consumption, along with considerable losses of biodiversity. Especially the forests influence climate through physical, chemical and biological processes that affect planetary energetics, the hydrologic cycle, and atmospheric composition. Such changes in land use have enabled humans to appropriate an increasing share of the planet's resources, but they also potentially undermine the capacity of ecosystems to sustain food production, maintain freshwater and forest resources, regulate climate and air quality. Global Warming and Climate Change are the two main fundamental problems facing Turkey as well as the World. The expedition and size of this change is becoming noticeably conspicuous now. According to the International Union for Conservation of Nature (IUCN), the global temperature has been increased of about 0.74 degree Celsius since the Industrial Revolution. Interdisciplinary science that integrates knowledge of the many interacting climate services of forests with the impacts of global change is necessary to identify and understand as yet unexplored feedbacks in the Earth system and the potential of forests to mitigate climate change. The general scientific opinions on the climate change states that in the past 50 years, global warming has effected the human life resulting with very obvious influences. High rates of deforestation within a country are most commonly linked to population growth and poverty. In Turkey, the forests are destroyed for various reasons resulting to a change in the climate. This study examines the causes of

  2. The emergence and effectiveness of global health networks: findings and future research.

    PubMed

    Shiffman, Jeremy; Schmitz, Hans Peter; Berlan, David; Smith, Stephanie L; Quissell, Kathryn; Gneiting, Uwe; Pelletier, David

    2016-04-01

    Global health issues vary in the amount of attention and resources they receive. One reason is that the networks of individuals and organizations that address these issues differ in their effectiveness. This article presents key findings from a research project on the emergence and effectiveness of global health networks addressing tobacco use, alcohol harm, maternal mortality, neonatal mortality, tuberculosis and pneumonia. Although networks are only one of many factors influencing priority, they do matter, particularly for shaping the way the problem and solutions are understood, and convincing governments, international organizations and other global actors to address the issue. Their national-level effects vary by issue and are more difficult to ascertain. Networks are most likely to produce effects when (1) their members construct a compelling framing of the issue, one that includes a shared understanding of the problem, a consensus on solutions and convincing reasons to act and (2) they build a political coalition that includes individuals and organizations beyond their traditional base in the health sector, a task that demands engagement in the politics of the issue, not just its technical aspects. Maintaining a focused frame and sustaining a broad coalition are often in tension: effective networks find ways to balance the two challenges. The emergence and effectiveness of a network are shaped both by its members' decisions and by contextual factors, including historical influences (e.g. prior failed attempts to address the problem), features of the policy environment (e.g. global development goals) and characteristics of the issue the network addresses (e.g. its mortality burden). Their proliferation raises the issue of their legitimacy. Reasons to consider them legitimate include their members' expertise and the attention they bring to neglected issues. Reasons to question their legitimacy include their largely elite composition and the fragmentation they

  3. Effects of Local and Global Context on Processing Sentences with Subject and Object Relative Clauses

    ERIC Educational Resources Information Center

    Yang, Fang; Mo, Lun; Louwerse, Max M.

    2013-01-01

    An eye tracking study investigated the effects of local and global discourse context on the processing of subject and object relative clauses, whereby the contexts favored either a subject relative clause interpretation or an object relative clause interpretation. The fixation data replicated previous studies showing that object relative clause…

  4. Is the Global Solar UV Index an Effective Instrument for Promoting Sun Protection? A Systematic Review

    ERIC Educational Resources Information Center

    Italia, Nadia; Rehfuess, Eva A.

    2012-01-01

    Exposure to ultraviolet radiation is an important risk factor for skin cancer. The Global Solar Ultraviolet Index (UVI) was developed as a tool to visualize the amount of harmful radiation and to encourage people to use sun protection. We conducted a systematic review of the effectiveness of the UVI. We employed a comprehensive search strategy to…

  5. The Need for Cost-Effective Neurosurgical Innovation--A Global Surgery Initiative.

    PubMed

    Ravindra, Vijay M; Kraus, Kristin L; Riva-Cambrin, Jay K; Kestle, John R

    2015-11-01

    The authors discuss the unmet needs for neurosurgical care around the world and some of the innovative work being done to address this need. The growing demonstration of surgical innovation and cost-effective technology represents an opportunity within neurosurgery to achieve the goal of making surgical care more accessible to the global population.

  6. Local effects and global impact in neurotoxicity and neurodegeneration: The Xi’an International Neurotoxicology Conference

    EPA Science Inventory

    “Neurotoxicity and Neurodegeneration: Local Effect and Global Impact” was the theme of the Xi’an International Neurotoxicology Conference (XINC), held in Xi’an, June 2011. The Conference was a joint event of the 13th Biennal Meeting of the International Neurotoxicology Associatio...

  7. Global assessment of avian influenza control strategies, especially the role of vaccine efficacy and vaccination effectiveness

    Technology Transfer Automated Retrieval System (TEKTRAN)

    OFFLU is the joint World Organisation for Animal Health and Food and Agricultural Organization (OIE-FAO) global network of expertise on animal influenzas. OFFLU aims to reduce negative impacts of animal influenza viruses by promoting effective collaboration between animal health experts. OFFLU puts ...

  8. Effects of pressure gradient on global Alfvén eigenmodes in reversed field pinch

    NASA Astrophysics Data System (ADS)

    Cai, Huishan; Fu, Guoyong; Lin, Liang; Liu, D. Y.; Ding, Weixing; Brower, D. L.; Hu, Y. J.

    2014-02-01

    The effects of pressure gradient on the existence of global Alfvén eigenmodes (GAE) in Reversed Field Pinch are studied by numerical calculation. It is found that GAEs near the plasma core can exist when pressure gradient is sufficiently large. The calculated mode frequency and structure are consistent with the experimental results in the Madison Symmetric Torus.

  9. The Effects of the Project Champion's Leadership Style on Global Information Technology User Acceptance and Use

    ERIC Educational Resources Information Center

    Ekiko, Mbong C.

    2014-01-01

    The research problem was the lack of knowledge about the effect of leadership style of the project champion on global information technology (IT) project outcomes, resulting in a high failure rate of IT projects accompanied by significant waste of resources. The purpose of this quantitative, nonexperimental study was to evaluate the relationship…

  10. Effects of pressure gradient on global Alfvén eigenmodes in reversed field pinch

    SciTech Connect

    Cai, Huishan; Fu, Guoyong; Lin, Liang; Ding, Weixing; Brower, D. L.; Liu, D. Y.; Hu, Y. J.

    2014-02-15

    The effects of pressure gradient on the existence of global Alfvén eigenmodes (GAE) in Reversed Field Pinch are studied by numerical calculation. It is found that GAEs near the plasma core can exist when pressure gradient is sufficiently large. The calculated mode frequency and structure are consistent with the experimental results in the Madison Symmetric Torus.

  11. Global climatic change effects on irrigation requirements for the Central Great Plains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rising carbon dioxide and other green house gasses (water vapor, nitrous oxide, methane, etc.) are predicted to have an effect on future climates. These gasses impact crops and global and local weather. The carbon dioxide increase is generally considered to be favorable to agriculture as it increas...

  12. What Effect Did the Global Financial Crisis Have upon Youth Wellbeing? Evidence from Four Australian Cohorts

    ERIC Educational Resources Information Center

    Parker, Philip D.; Jerrim, John; Anders, Jake

    2016-01-01

    Recent research has suggested significant negative effects of the Global Financial Crisis (GFC) on mental health and wellbeing. In this article, the authors suggest that the developmental period of late adolescence may be at particular risk of economic downturns. Harmonizing 4 longitudinal cohorts of Australian youth (N = 38,017), we estimate the…

  13. Mass Media and Global Warming: A Public Arenas Model of the Greenhouse Effect's Scientific Roots.

    ERIC Educational Resources Information Center

    Neuzil, Mark

    1995-01-01

    Uses the Public Arenas model to examine the historical roots of the greenhouse effect issue as communicated in scientific literature from the early 1800s to modern times. Utilizes a constructivist approach to discuss several possible explanations for the rise and fall of global warming as a social problem in the scientific arena. (PA)

  14. Effects of bt crops on arthropod natual enemies: a global synthesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The global adoption of transgenic crops producing the insecticidal proteins from Bacillus thuringiensis Berliner (Bacillaceae), (Bt) continues to grow with 66 M hectares of Bt crops grown in a total of 25 countries in 2011 (James 2011). Unintended environmental effects from the technology continue t...

  15. High School Students' Perceptions of How Major Global Environmental Effects Might Cause Skin Cancer.

    ERIC Educational Resources Information Center

    Boyes, Edward; Stanisstreet, Martin

    1998-01-01

    Quantifies beliefs of high school students about links between skin cancer and global environmental effects. Some students confused the action of heat rays with that of ultraviolet rays and also thought that raised temperatures are culpable. Only one in 10 held the scientifically correct model: that ozone depletion via higher penetration of…

  16. Effects of the Global War on Terror on Retention of Marine Corps Aviators

    DTIC Science & Technology

    2006-03-01

    83 D. COMPARISON OF THE RESULTS FROM THE PRE-9/11 AND GWOT LOGIT MODELS...4.3 Explanatory Variables and Expected Effects on Retention .............................50 Table 5.1 Global Null Hypothesis Test for Pooled Logit ...Models ...................................53 Table 5.2 Generalized R-Square and Max-Rescaled R-Square for the Pooled Logit Models

  17. Climate of Concern--A Search for Effective Strategies for Teaching Children about Global Warming

    ERIC Educational Resources Information Center

    Taber, Fiona; Taylor, Neil

    2009-01-01

    Recent research suggests that the issue of global warming is one of great concern for Australian children. This point to the need for effective teaching about this issue. Children should be properly informed about actions that help reduce carbon emissions as this may give them a sense of empowerment and go some way to alleviating concerns. This…

  18. Course-Specific Intrinsic Motivation: Effects of Instructor Support and Global Academic Motivation

    ERIC Educational Resources Information Center

    Zook, J. M.; Herman, A. P.

    2011-01-01

    This study examined the effects of instructor support and students' global academic motivation on students' course-specific intrinsic motivation. The authors hypothesized, based on self-determination theory (Ryan & Deci, 2000), that instructor support for students' psychological needs would enhance intrinsic motivation. Students reported their…

  19. Microarray as a First Genetic Test in Global Developmental Delay: A Cost-Effectiveness Analysis

    ERIC Educational Resources Information Center

    Trakadis, Yannis; Shevell, Michael

    2011-01-01

    Aim: Microarray technology has a significantly higher clinical yield than karyotyping in individuals with global developmental delay (GDD). Despite this, it has not yet been routinely implemented as a screening test owing to the perception that this approach is more expensive. We aimed to evaluate the effect that replacing karyotype with…

  20. A framework on the emergence and effectiveness of global health networks.

    PubMed

    Shiffman, Jeremy; Quissell, Kathryn; Schmitz, Hans Peter; Pelletier, David L; Smith, Stephanie L; Berlan, David; Gneiting, Uwe; Van Slyke, David; Mergel, Ines; Rodriguez, Mariela; Walt, Gill

    2016-04-01

    Since 1990 mortality and morbidity decline has been more extensive for some conditions prevalent in low- and middle-income countries than for others. One reason may be differences in the effectiveness of global health networks, which have proliferated in recent years. Some may be more capable than others in attracting attention to a condition, in generating funding, in developing interventions and in convincing national governments to adopt policies. This article introduces a supplement on the emergence and effectiveness of global health networks. The supplement examines networks concerned with six global health problems: tuberculosis (TB), pneumonia, tobacco use, alcohol harm, maternal mortality and newborn deaths. This article presents a conceptual framework delineating factors that may shape why networks crystallize more easily surrounding some issues than others, and once formed, why some are better able than others to shape policy and public health outcomes. All supplement papers draw on this framework. The framework consists of 10 factors in three categories: (1) features of the networks and actors that comprise them, including leadership, governance arrangements, network composition and framing strategies; (2) conditions in the global policy environment, including potential allies and opponents, funding availability and global expectations concerning which issues should be prioritized; (3) and characteristics of the issue, including severity, tractability and affected groups. The article also explains the design of the project, which is grounded in comparison of networks surrounding three matched issues: TB and pneumonia, tobacco use and alcohol harm, and maternal and newborn survival. Despite similar burden and issue characteristics, there has been considerably greater policy traction for the first in each pair. The supplement articles aim to explain the role of networks in shaping these differences, and collectively represent the first comparative effort

  1. The challenge of sustaining effectiveness over time: the case of the global network to stop tuberculosis.

    PubMed

    Quissell, Kathryn; Walt, Gill

    2016-04-01

    Where once global health decisions were largely the domain of national governments and the World Health Organization, today networks of international organizations, governments, private philanthropies and other entities are actively shaping public policy. However, there is still limited understanding of how global networks form, how they create institutions, how they promote and sustain collective action, and how they adapt to changes in the policy environment. Understanding these processes is crucial to understanding their effectiveness: whether and how global networks influence policy and public health outcomes. This study seeks to address these gaps through the examination of the global network to stop tuberculosis (TB) and the factors influencing its effectiveness over time. Drawing from ∼ 200 document sources and 16 interviews with key informants, we trace the development of the Global Partnership to Stop TB and its work over the past decade. We find that having a centralized core group and a strategic brand helped the network to coalesce around a primary intervention strategy, directly observed treatment short course. This strategy was created before the network was formalized, and helped bring in donors, ministries of health and other organizations committed to fighting TB-growing the network. Adaptations to this strategy, the creation of a consensus-based Global Plan, and the creation of a variety of participatory venues for discussion, helped to expand and sustain the network. Presently, however, tensions have become more apparent within the network as it struggles with changing internal political dynamics and the evolution of the disease. While centralization and stability helped to launch and grow the network, the institutionalization of governance and strategy may have constrained adaptation. Institutionalization and centralization may, therefore, facilitate short-term success for networks, but may end up complicating longer-term effectiveness.

  2. Global Pickup Oxygen Ion Precipitation in the Martian Thermosphere: Distributions, Effects, and Implications

    NASA Astrophysics Data System (ADS)

    Fang, X.; Bougher, S. W.; Johnson, R. E.; Ma, Y.; Liemohn, M. W.

    2011-12-01

    We apply a coupled set of 3-D numerical models to study the global aeronomical effects of precipitating pickup oxygen ions in the Martian thermosphere. While atmospheric constituents can be ionized, picked up, and then stripped away by the solar wind, a majority of pickup ions are directed by the electromagnetic fields to the planet and then deposit their energy in and sputter neutrals out of the thermosphere. A MHD field-based Monte Carlo pickup ion transport model is applied in this study with billions of test particles, allowing for the calculation of the detailed incident energy spectra and angular distributions of the return oxygen ion flux. More importantly, such detailed information is obtained globally, avoiding the errors arising from global averaging and thus enabling an unprecedented examination of the differences of particle impact between in the dayside and the nightside, within and outside of crustal magnetic anomaly regions. While accelerated return particles represent a significant energy source to the neutral atmosphere at Mars, their aeronomical effects are not included in any global models, which may lead to a serious problem with our understanding of the thermosphere and ionosphere. In this work, the associated sputtering loss and heating effects will be incorporated into the Mars Thermosphere General Circulation Model (MTGCM) to analyze for the first time the response of the thermosphere in a global perspective. The combination of these models allows for a quantitative assessment of the global impact of return pickup ions on the compositional and thermal structures of the thermosphere. The examination of particle impact under extreme solar wind and solar radiation conditions provides physical insight into the processes involved in the Mars-solar wind interaction and their implications on the Martian thermosphere and ionosphere.

  3. A framework on the emergence and effectiveness of global health networks

    PubMed Central

    Shiffman, Jeremy; Quissell, Kathryn; Schmitz, Hans Peter; Pelletier, David L; Smith, Stephanie L; Berlan, David; Gneiting, Uwe; Van Slyke, David; Mergel, Ines; Rodriguez, Mariela; Walt, Gill

    2016-01-01

    Since 1990 mortality and morbidity decline has been more extensive for some conditions prevalent in low- and middle-income countries than for others. One reason may be differences in the effectiveness of global health networks, which have proliferated in recent years. Some may be more capable than others in attracting attention to a condition, in generating funding, in developing interventions and in convincing national governments to adopt policies. This article introduces a supplement on the emergence and effectiveness of global health networks. The supplement examines networks concerned with six global health problems: tuberculosis (TB), pneumonia, tobacco use, alcohol harm, maternal mortality and newborn deaths. This article presents a conceptual framework delineating factors that may shape why networks crystallize more easily surrounding some issues than others, and once formed, why some are better able than others to shape policy and public health outcomes. All supplement papers draw on this framework. The framework consists of 10 factors in three categories: (1) features of the networks and actors that comprise them, including leadership, governance arrangements, network composition and framing strategies; (2) conditions in the global policy environment, including potential allies and opponents, funding availability and global expectations concerning which issues should be prioritized; (3) and characteristics of the issue, including severity, tractability and affected groups. The article also explains the design of the project, which is grounded in comparison of networks surrounding three matched issues: TB and pneumonia, tobacco use and alcohol harm, and maternal and newborn survival. Despite similar burden and issue characteristics, there has been considerably greater policy traction for the first in each pair. The supplement articles aim to explain the role of networks in shaping these differences, and collectively represent the first comparative effort

  4. Assessing the effects of anthropogenic aerosols on Pacific storm track using a multiscale global climate model.

    PubMed

    Wang, Yuan; Wang, Minghuai; Zhang, Renyi; Ghan, Steven J; Lin, Yun; Hu, Jiaxi; Pan, Bowen; Levy, Misti; Jiang, Jonathan H; Molina, Mario J

    2014-05-13

    Atmospheric aerosols affect weather and global general circulation by modifying cloud and precipitation processes, but the magnitude of cloud adjustment by aerosols remains poorly quantified and represents the largest uncertainty in estimated forcing of climate change. Here we assess the effects of anthropogenic aerosols on the Pacific storm track, using a multiscale global aerosol-climate model (GCM). Simulations of two aerosol scenarios corresponding to the present day and preindustrial conditions reveal long-range transport of anthropogenic aerosols across the north Pacific and large resulting changes in the aerosol optical depth, cloud droplet number concentration, and cloud and ice water paths. Shortwave and longwave cloud radiative forcing at the top of atmosphere are changed by -2.5 and +1.3 W m(-2), respectively, by emission changes from preindustrial to present day, and an increased cloud top height indicates invigorated midlatitude cyclones. The overall increased precipitation and poleward heat transport reflect intensification of the Pacific storm track by anthropogenic aerosols. Hence, this work provides, for the first time to the authors' knowledge, a global perspective of the effects of Asian pollution outflows from GCMs. Furthermore, our results suggest that the multiscale modeling framework is essential in producing the aerosol invigoration effect of deep convective clouds on a global scale.

  5. Assessing the effects of anthropogenic aerosols on Pacific storm track using a multiscale global climate model

    PubMed Central

    Wang, Yuan; Wang, Minghuai; Zhang, Renyi; Ghan, Steven J.; Lin, Yun; Hu, Jiaxi; Pan, Bowen; Levy, Misti; Jiang, Jonathan H.; Molina, Mario J.

    2014-01-01

    Atmospheric aerosols affect weather and global general circulation by modifying cloud and precipitation processes, but the magnitude of cloud adjustment by aerosols remains poorly quantified and represents the largest uncertainty in estimated forcing of climate change. Here we assess the effects of anthropogenic aerosols on the Pacific storm track, using a multiscale global aerosol–climate model (GCM). Simulations of two aerosol scenarios corresponding to the present day and preindustrial conditions reveal long-range transport of anthropogenic aerosols across the north Pacific and large resulting changes in the aerosol optical depth, cloud droplet number concentration, and cloud and ice water paths. Shortwave and longwave cloud radiative forcing at the top of atmosphere are changed by −2.5 and +1.3 W m−2, respectively, by emission changes from preindustrial to present day, and an increased cloud top height indicates invigorated midlatitude cyclones. The overall increased precipitation and poleward heat transport reflect intensification of the Pacific storm track by anthropogenic aerosols. Hence, this work provides, for the first time to the authors’ knowledge, a global perspective of the effects of Asian pollution outflows from GCMs. Furthermore, our results suggest that the multiscale modeling framework is essential in producing the aerosol invigoration effect of deep convective clouds on a global scale. PMID:24733923

  6. The Effect of Global and Local Damping on the Perception of Hardness.

    PubMed

    van Beek, Femke Elise; Heck, Dennis J F; Nijmeijer, Henk; Bergmann Tiest, Wouter M; Kappers, Astrid M L

    2016-01-01

    In tele-operation systems, damping is often injected to guarantee system stability during contact with hard objects. In this study, we used psychophysical experiments to assess the effect of adding damping on the user's perception of object hardness. In Experiments 1 and 2, combinations of stiffness and damping were tested to assess their effect on perceived hardness. In both experiments, two tasks were used: an in-contact task, starting at the object's surface, and a contact-transition task, including a free-air movement. In Experiment 3, the difference between inserting damping globally (equally throughout the workspace) and locally (inside the object only) was tested. In all experiments, the correlation between the participant's perceptual decision and force and position data was also investigated. Experiments 1 and 2 show that when injecting damping globally, perceived hardness slightly increased for an in-contact task, while it decreased considerably for a contact-transition task. Experiment 3 shows that this effect was mainly due to inserting damping globally, since there was a large perceptual difference between inserting damping globally and locally. The force and position parameters suggest that participants used the same force profile during the two movements of one trial and assessed the system's reaction to this force to perceive hardness.

  7. Global sea level rise and the greenhouse effect: Might they be connected

    SciTech Connect

    Peltier, W.R.; Tushingham, A.M. )

    1989-05-19

    Secular sea level trends extracted from tide gauge records of appropriately long duration demonstrate that global sea level may be rising at a rate in excess of 1 millimeter per year. However, because global coverage of the oceans by the tide gauge network is highly nonuniform and the tide gauge data reveal considerable spatial variability, there has been a well-founded reluctance to interpret the observed secular sea level rise as representing a signal of global scale that might be related to the greenhouse effect. When the tide gauge data are filtered so as to remove the contribution of ongoing glacial isostatic adjustement to the local sea level trend at each location, then the individual tide gauge records reveal sharply reduced geographic scatter and suggest that there is a globally coherent signal of strength 2.4 {plus minus} 0.90 millimeters per year that is active in the system. This signal could constitute an indication of global climate warming. 15 refs., 8 figs.

  8. Evaluation of atmospheric aerosol and tropospheric ozone effects on global terrestrial ecosystem carbon dynamics

    NASA Astrophysics Data System (ADS)

    Chen, Min

    The increasing human activities have produced large amounts of air pollutants ejected into the atmosphere, in which atmospheric aerosols and tropospheric ozone are considered to be especially important because of their negative impacts on human health and their impacts on global climate through either their direct radiative effect or indirect effect on land-atmosphere CO2 exchange. This dissertation dedicates to quantifying and evaluating the aerosol and tropospheric ozone effects on global terrestrial ecosystem dynamics using a modeling approach. An ecosystem model, the integrated Terrestrial Ecosystem Model (iTem), is developed to simulate biophysical and biogeochemical processes in terrestrial ecosystems. A two-broad-band atmospheric radiative transfer model together with the Moderate-Resolution Imaging Spectroradiometer (MODIS) measured atmospheric parameters are used to well estimate global downward solar radiation and the direct and diffuse components in comparison with observations. The atmospheric radiative transfer modeling framework were used to quantify the aerosol direct radiative effect, showing that aerosol loadings cause 18.7 and 12.8 W m -2 decrease of direct-beam Photosynthetic Active Radiation (PAR) and Near Infrared Radiation (NIR) respectively, and 5.2 and 4.4 W m -2 increase of diffuse PAR and NIR, respectively, leading to a total 21.9 W m-2 decrease of total downward solar radiation over the global land surface during the period of 2003-2010. The results also suggested that the aerosol effect may be overwhelmed by clouds because of the stronger extinction and scattering ability of clouds. Applications of the iTem with solar radiation data and with or without considering the aerosol loadings shows that aerosol loading enhances the terrestrial productions [Gross Primary Production (GPP), Net Primary Production (NPP) and Net Ecosystem Production (NEP)] and carbon emissions through plant respiration (RA) in global terrestrial ecosystems over the

  9. Effects of elastic focusing on global models of Rayleigh wave attenuation

    NASA Astrophysics Data System (ADS)

    Bao, Xueyang; Dalton, Colleen A.; Ritsema, Jeroen

    2016-11-01

    Rayleigh wave amplitudes are the primary data set used for imaging shear attenuation in the upper mantle on a global scale. In addition to attenuation, surface-wave amplitudes are influenced by excitation at the earthquake source, focusing and scattering by elastic heterogeneity, and local structure at the receiver and the instrument response. The challenge of isolating the signal of attenuation from these other effects limits both the resolution of global attenuation models and the level of consistency between different global attenuation studies. While the source and receiver terms can be estimated using relatively simple approaches, focusing effects on amplitude are a large component of the amplitude signal and are sensitive to multiscale velocity anomalies. In this study we investigate how different theoretical treatments for focusing effects on Rayleigh wave amplitude influence the retrieved attenuation models. A new data set of fundamental-mode Rayleigh wave phase and amplitude at periods of 50 and 100 sis analysed. The amplitudes due to focusing effects are predicted using the great-circle ray approximation (GCRA), exact ray theory (ERT), and finite-frequency theory (FFT). Phase-velocity maps expanded to spherical-harmonic degree 20 and degree 40 are used for the predictions. After correction for focusing effects, the amplitude data are inverted for global attenuation maps and frequency-dependent source and receiver correction factors. The degree-12 attenuation maps, based on different corrections for focusing effects, all contain the same large-scale features, though the magnitude of the attenuation variations depends on the focusing correction. The variance reduction of the amplitudes strongly depends on the predicted focusing amplitudes, with the highest variance reduction for the ray-based approaches at 50 s and for FFT at 100 s. Although failure to account for focusing effects introduces artefacts into the attenuation models at higher spherical

  10. Greenhouse effect and the global climate. (Latest citations from the Aerospace database). Published Search

    SciTech Connect

    Not Available

    1993-09-01

    The bibliography contains citations concerning terrestrial climatic changes known as the greenhouse effect. The greenhouse effect is an accumulation of carbon dioxide and other gases that retain solar-induced heat, thereby increasing the average global temperature. Modeling studies, measurements of atmospheric gases, pollutants and temperatures, studies of climatic records for occurrence of similar changes (paleoclimatology), prediction of environmental changes due to the greenhouse effect, government energy policy as a result of possible climate change, and the contributions of manmade and natural pollutants to the greenhouse effect are among the topics discussed. (Contains a minimum of 52 citations and includes a subject term index and title list.)

  11. Defining and assessing evidence for the effectiveness of technical assistance in furthering global health.

    PubMed

    West, Gary R; Clapp, Sheila P; Averill, E Megan Davidson; Cates, Willard

    2012-01-01

    In an era when health resources are increasingly constrained, international organisations are transitioning from directly managing health services to providing technical assistance (TA) to in-country owners of public health programmes. We define TA as: 'A dynamic, capacity-building process for designing or improving the quality, effectiveness, and efficiency of specific programmes, research, services, products, or systems'. TA can build sustainable capacities, strengthen health systems and support country ownership. However, our assessment of published evaluations found limited evidence for its effectiveness. We summarise socio-behavioural theories relevant to TA, review published evaluations and describe skills required for TA providers. We explore challenges to providing TA including cost effectiveness, knowledge management and sustaining TA systems. Lastly, we outline recommendations for structuring global TA systems. Considering its important role in global health, more rigorous evaluations of TA efforts should be given high priority.

  12. Defining and assessing evidence for the effectiveness of technical assistance in furthering global health

    PubMed Central

    West, Gary R.; Clapp, Sheila P.; Averill, E. Megan Davidson; Cates, Willard

    2012-01-01

    In an era when health resources are increasingly constrained, international organisations are transitioning from directly managing health services to providing technical assistance (TA) to in-country owners of public health programmes. We define TA as: A dynamic, capacity-building process for designing or improving the quality, effectiveness, and efficiency of specific programmes, research, services, products, or systems’. TA can build sustainable capacities, strengthen health systems and support country ownership. However, our assessment of published evaluations found limited evidence for its effectiveness. We summarise socio-behavioural theories relevant to TA, review published evaluations and describe skills required for TA providers. We explore challenges to providing TA including cost effectiveness, knowledge management and sustaining TA systems. Lastly, we outline recommendations for structuring global TA systems. Considering its important role in global health, more rigorous evaluations of TA efforts should be given high priority. PMID:22606939

  13. Relative effects on global warming of halogenated methanes and ethanes of social and industrial interest

    NASA Technical Reports Server (NTRS)

    Fisher, Donald A.; Hales, Charles H.; Wang, Wei-Chyung; Ko, Malcolm K. W.; Sze, N. Dak

    1990-01-01

    The relative potential global warming effects for several halocarbons (chlorofluorocarbons (CFC's)-11, 12, 113, 114, and 115; hydrochlorofluorocarbons (HCFC's) 22, 123, 124, 141b, and 142b; and hydrofluorocarbons (HFC's) 125, 134a, 143a, and 152a; carbon tetrachloride; and methyl chloroform) were calculated by two atmospheric modeling groups. These calculations were based on atmospheric chemistry and radiative convective models to determine the chemical profiles and the radiative processes. The resulting relative greenhouse warming when normalized to the effect of CFC-11 agree reasonably well as long as we account for differences between modeled lifetimes. Differences among results are discussed. Sensitivity of relative warming values is determined with respect to trace gas levels assumed. Transient relative global warming effects are analyzed.

  14. Local and global effects of the cross-field current instability

    NASA Technical Reports Server (NTRS)

    Lui, A. T. Y.

    1996-01-01

    The cross-field current instability (CCI) was proposed elsewhere as a plausible mechanism for the initiation and intensification of substorm expansions. This instability encompasses the modified two stream, the ion-Weibel and the lower hybrid drift modes. The work carried out in relation to this instability and its local and global effects is reviewed. Predicted local effects include current reduction, particle acceleration, the excitation of oblique whistlers and lower hybrid drift waves, and the breakdown of the frozen-in-field condition through anomalous dissipation. The predicted global effects of CCI include the offset of force equilibrium and the generation of field aligned currents at the disruption site, which allow the efficient large scale transportation of mass, momentum and energy within the magnetosphere.

  15. [Effects of global climate change on the C, N, and P stoichiometry of terrestrial plants].

    PubMed

    Hong, Jiang-Tao; Wu, Jian-Bo; Wang, Xiao-Dan

    2013-09-01

    The response patterns of biogeochemical cycle and the adaptation strategies of terrestrial plants under the background of global climate change have received extensive attention. This paper analyzed the effects of climate warming and precipitation change on the plant C:N:P in different ecosystems, the effects of elevated atmospheric CO2 on the plant nutrients in different photosynthetic pathways, and the short-term and long-term effects of the responses of soil-plant nutrients to nitrogen deposition, and explored the possible underlying mechanisms in terms of the plant physiological properties in relation to soil available nutrients, which could provide theoretical bases for studying the nutrients (C, N and P) transmission and regulation mechanisms between soil and plant, the structure and function of terrestrial ecosystems, and the responses of biogeochemical cycle to global climate change. The existing problems and the further research directions in this study area were proposed.

  16. Global Earthquake Casualties due to Secondary Effects: A Quantitative Analysis for Improving PAGER Losses

    USGS Publications Warehouse

    Wald, David J.

    2010-01-01

    This study presents a quantitative and geospatial description of global losses due to earthquake-induced secondary effects, including landslide, liquefaction, tsunami, and fire for events during the past 40 years. These processes are of great importance to the US Geological Survey’s (USGS) Prompt Assessment of Global Earthquakes for Response (PAGER) system, which is currently being developed to deliver rapid earthquake impact and loss assessments following large/significant global earthquakes. An important question is how dominant are losses due to secondary effects (and under what conditions, and in which regions)? Thus, which of these effects should receive higher priority research efforts in order to enhance PAGER’s overall assessment of earthquakes losses and alerting for the likelihood of secondary impacts? We find that while 21.5% of fatal earthquakes have deaths due to secondary (non-shaking) causes, only rarely are secondary effects the main cause of fatalities. The recent 2004 Great Sumatra–Andaman Islands earthquake is a notable exception, with extraordinary losses due to tsunami. The potential for secondary hazards varies greatly, and systematically, due to regional geologic and geomorphic conditions. Based on our findings, we have built country-specific disclaimers for PAGER that address potential for each hazard (Earle et al., Proceedings of the 14th World Conference of the Earthquake Engineering, Beijing, China, 2008). We will now focus on ways to model casualties from secondary effects based on their relative importance as well as their general predictability.

  17. Global earthquake casualties due to secondary effects: A quantitative analysis for improving rapid loss analyses

    USGS Publications Warehouse

    Marano, K.D.; Wald, D.J.; Allen, T.I.

    2010-01-01

    This study presents a quantitative and geospatial description of global losses due to earthquake-induced secondary effects, including landslide, liquefaction, tsunami, and fire for events during the past 40 years. These processes are of great importance to the US Geological Survey's (USGS) Prompt Assessment of Global Earthquakes for Response (PAGER) system, which is currently being developed to deliver rapid earthquake impact and loss assessments following large/significant global earthquakes. An important question is how dominant are losses due to secondary effects (and under what conditions, and in which regions)? Thus, which of these effects should receive higher priority research efforts in order to enhance PAGER's overall assessment of earthquakes losses and alerting for the likelihood of secondary impacts? We find that while 21.5% of fatal earthquakes have deaths due to secondary (non-shaking) causes, only rarely are secondary effects the main cause of fatalities. The recent 2004 Great Sumatra-Andaman Islands earthquake is a notable exception, with extraordinary losses due to tsunami. The potential for secondary hazards varies greatly, and systematically, due to regional geologic and geomorphic conditions. Based on our findings, we have built country-specific disclaimers for PAGER that address potential for each hazard (Earle et al., Proceedings of the 14th World Conference of the Earthquake Engineering, Beijing, China, 2008). We will now focus on ways to model casualties from secondary effects based on their relative importance as well as their general predictability. ?? Springer Science+Business Media B.V. 2009.

  18. Modelling of global boundary effects on harmonic motion imaging of soft tissues.

    PubMed

    Zhao, Xiaodong; Pelegri, Assimina A

    2014-01-01

    Biomechanical imaging techniques have been developed for soft tissue characterisation and detection of breast tumours. Harmonic motion imaging (HMI) uses a focused ultrasound technology to generate a harmonic radiation force in a localised region inside a soft tissue. The resulting dynamic response is used to map the local distribution of the mechanical properties of the tissue. In this study, a finite element (FE) model is developed to investigate the effect of global boundary conditions on the dynamic response of a soft tissue during HMI. The direct-solution steady-state dynamic analysis procedure is used to compute the harmonic displacement amplitude in FE simulations. The model is parameterised in terms of boundary conditions and viscoelastic properties, and the corresponding raster-scan displacement amplitudes are captured to examine its response. The effect of the model's global dimensions on the harmonic response is also investigated. It is observed that the dynamic response of soft tissue with high viscosity is independent of the global boundary conditions for regions remote to the boundary; thus, it can be subjected to local analysis to estimate the underlying mechanical properties. However, the dynamic response is sensitive to global boundary conditions for tissue with low viscosity or regions located near to the boundary.

  19. Globalization, shifting livelihoods, and their effects on natural resources on the Atlantic coast of Nicaragua

    NASA Astrophysics Data System (ADS)

    Kramer, D. B.

    2012-12-01

    Knowledge of local peoples' livelihoods is important in understanding the use of, access to, and regulation of natural resources. Drivers of global change, including climate change and globalization, often result in shifts in local peoples' livelihood portfolios. Here, we use longitudinal data to examine how increasing market access, migration, and technology adoption have affected livelihood portfolios in a dozen communities along Nicaragua's Atlantic coast and the effects of livelihood change on terrestrial and marine wildlife. Our study communities are located in varying proximity to the terminus of the first trans-isthmian highway in this region, completed in 2008. Our results indicate that changes in livelihood portfolios, such as shifts between agriculture, fishing, and tourism, can be explained by a combination of household and community characteristics. Moreover, globalization's effects on specific livelihoods are distinct while varying both spatially and temporally. Trends in fisheries abundance, deforestation, and the management of endangered species and protected areas are better understood in the context of these shifting livelihood patterns. Moreover, this study provides new insights as to how natural resource dependent communities might decrease their vulnerability to the forces of global change.

  20. The effects of different solar flare characteristics on the global thermosphere

    NASA Astrophysics Data System (ADS)

    Pawlowski, David J.; Ridley, Aaron J.

    2011-08-01

    Given the ability of global models of the upper atmosphere to utilize high-resolution solar spectra to specify the solar soft X-ray and EUV irradiance, researchers now have the ability to perform detailed theoretical analysis of the response of the upper atmosphere to dynamic solar forcing more completely than ever before. Therefore, it is possible to develop a more quantitative understanding of the response of the thermosphere to solar flares. In this study, the effect of different characteristics of solar flares on the thermosphere is investigated. This is done in a theoretical manner, using synthetic solar irradiance data that is based on observations as input to the global ionosphere-thermosphere model (GITM). Specifically, the neutral response to the total incident energy, peak flare magnitude, background irradiance magnitude, duration of the impulsive phase, and decay time is investigated. It is found that the density response at 400 km altitude is linearly dependent on the total integrated energy above the background level being deposited into the atmosphere, and that the day-side response is strongly dependent on both the total incident energy into the system and the peak flare magnitude. Also, the decay time of the flare is important in determining the time at which the maximum global response occurs. Finally, the duration of the impulsive phase is found to have little effect on the global response of the system.

  1. Meta-analyses of the effects of major global change drivers on soil respiration across China

    NASA Astrophysics Data System (ADS)

    Feng, Jiguang; Wang, Jingsheng; Ding, Lubin; Yao, Pingping; Qiao, Mengping; Yao, Shuaichen

    2017-02-01

    Soil respiration (Rs) is affected largely by major global change drivers, global meta-analysis studies have synthesized the available information to determine how Rs responds to these drivers. However, little is known about the effects of these drivers on Rs across China. Here, we conducted a meta-analysis to synthesize 80 studies published in the literature with 301 paired comparisons to quantify the responses of Rs to simulated warming, nitrogen addition, precipitation increase and acid rain across Chinese terrestrial ecosystem. Results showed that global change drivers significantly changed Rs across Chinese ecosystems. Warming, nitrogen addition, and precipitation increase significantly increased Rs by 9.08%, 5.21%, 31.68%, respectively, while simulated acid rain decreased Rs by 7.06%. The responses of Rs to warming, nitrogen addition, and precipitation increase are similar in both direction and magnitude to those reported in global syntheses, except for higher response ratio under precipitation increase in China. In addition, the responses of Rs were different among ecosystem types, and among experimental treatments. Warming significantly increased Rs in croplands but did not change in forests and grasslands. The effect magnitude of N addition on Rs in grasslands and croplands was much higher than those in other ecosystems. In general, precipitation increase stimulated Rs in different ecosystems, and its effect magnitudes increased with changed precipitation levels. However, acid rain inhibited Rs in different biomes and intensities of acid rain. Our findings contribute to better understanding of how Rs will change under global change, and provide important parameters for carbon cycle model at the regional scale.

  2. Interactive effects of global change factors on soil respiration and its components: a meta-analysis.

    PubMed

    Zhou, Lingyan; Zhou, Xuhui; Shao, Junjiong; Nie, Yuanyuan; He, Yanghui; Jiang, Liling; Wu, Zhuoting; Hosseini Bai, Shahla

    2016-09-01

    As the second largest carbon (C) flux between the atmosphere and terrestrial ecosystems, soil respiration (Rs) plays vital roles in regulating atmospheric CO2 concentration ([CO2 ]) and climatic dynamics in the earth system. Although numerous manipulative studies and a few meta-analyses have been conducted to determine the responses of Rs and its two components [i.e., autotrophic (Ra) and heterotrophic (Rh) respiration] to single global change factors, the interactive effects of the multiple factors are still unclear. In this study, we performed a meta-analysis of 150 multiple-factor (≥2) studies to examine the main and interactive effects of global change factors on Rs and its two components. Our results showed that elevated [CO2 ] (E), nitrogen addition (N), irrigation (I), and warming (W) induced significant increases in Rs by 28.6%, 8.8%, 9.7%, and 7.1%, respectively. The combined effects of the multiple factors, EN, EW, DE, IE, IN, IW, IEW, and DEW, were also significantly positive on Rs to a greater extent than those of the single-factor ones. For all the individual studies, the additive interactions were predominant on Rs (90.6%) and its components (≈70.0%) relative to synergistic and antagonistic ones. However, the different combinations of global change factors (e.g., EN, NW, EW, IW) indicated that the three types of interactions were all important, with two combinations for synergistic effects, two for antagonistic, and five for additive when at least eight independent experiments were considered. In addition, the interactions of elevated [CO2 ] and warming had opposite effects on Ra and Rh, suggesting that different processes may influence their responses to the multifactor interactions. Our study highlights the crucial importance of the interactive effects among the multiple factors on Rs and its components, which could inform regional and global models to assess the climate-biosphere feedbacks and improve predictions of the future states of the

  3. The global atmospheric electric circuit and its effects on cloud microphysics

    NASA Astrophysics Data System (ADS)

    Tinsley, B. A.

    2008-06-01

    This review is an overview of progress in understanding the theory and observation of the global atmospheric electric circuit, with the focus on its dc aspects, and its short and long term variability. The effects of the downward ionosphere-earth current density, Jz, on cloud microphysics, with its variability as an explanation for small observed changes in weather and climate, will also be reviewed. The global circuit shows responses to external as well as internal forcing. External forcing arises from changes in the distribution of conductivity due to changes in the cosmic ray flux and other energetic space particle fluxes, and at high magnetic latitudes from solar wind electric fields. Internal forcing arises from changes in the generators and changes in volcanic and anthropogenic aerosols in the troposphere and stratosphere. All these result in spatial and temporal variation in Jz. Variations in Jz affect the production of space charge in layer clouds, with the charges being transferred to droplets and aerosol particles. New observations and new analyses are consistent with non-negligible effects of the charges on the microphysics of such clouds. Observed effects are small, but of high statistical significance for cloud cover and precipitation changes, with resulting atmospheric temperature, pressure and dynamics changes. These effects are detectable on the day-to-day timescale for repeated Jz changes of order 10%, and are thus second order electrical effects. The implicit first order effects have not, as yet, been incorporated into basic cloud and aerosol physics. Long term (multidecadal through millennial) global circuit changes, due to solar activity modulating the galactic cosmic ray flux, are an order of magnitude greater at high latitudes and in the stratosphere, as can be inferred from geological cosmogenic isotope records. Proxies for climate change in the same stratified depositories show strong correlations of climate with the inferred global circuit

  4. Discovery of Novel Virulence Factors of Biothreat Agents: Validation of the Phosphoproteome-Based Approach

    DTIC Science & Technology

    2008-06-30

    the Qiagen Mini- Xpress in vitro protein transpcription and translation system. We found this amount to be insufficient and so we obtained an...experiment generated fascinating results, which will contribute to the field of Francisella LPS studies. Finally, by performing a more global comparison...1948 FTT1275 mglA sspA FTT1275 mglA sspA global transcriptional regulation, possibly through binding RNA polymerase allow survival within

  5. Local Versus Global Effects of Isoflurane Anesthesia on Visual Processing in the Fly Brain

    PubMed Central

    2016-01-01

    Abstract What characteristics of neural activity distinguish the awake and anesthetized brain? Drugs such as isoflurane abolish behavioral responsiveness in all animals, implying evolutionarily conserved mechanisms. However, it is unclear whether this conservation is reflected at the level of neural activity. Studies in humans have shown that anesthesia is characterized by spatially distinct spectral and coherence signatures that have also been implicated in the global impairment of cortical communication. We questioned whether anesthesia has similar effects on global and local neural processing in one of the smallest brains, that of the fruit fly (Drosophila melanogaster). Using a recently developed multielectrode technique, we recorded local field potentials from different areas of the fly brain simultaneously, while manipulating the concentration of isoflurane. Flickering visual stimuli (‘frequency tags’) allowed us to track evoked responses in the frequency domain and measure the effects of isoflurane throughout the brain. We found that isoflurane reduced power and coherence at the tagging frequency (13 or 17 Hz) in central brain regions. Unexpectedly, isoflurane increased power and coherence at twice the tag frequency (26 or 34 Hz) in the optic lobes of the fly, but only for specific stimulus configurations. By modeling the periodic responses, we show that the increase in power in peripheral areas can be attributed to local neuroanatomy. We further show that the effects on coherence can be explained by impacted signal-to-noise ratios. Together, our results show that general anesthesia has distinct local and global effects on neuronal processing in the fruit fly brain. PMID:27517084

  6. Global analysis of the effect of local climate on the hatchling output of leatherback turtles

    PubMed Central

    Santidrián Tomillo, Pilar; Saba, Vincent S.; Lombard, Claudia D.; Valiulis, Jennifer M.; Robinson, Nathan J.; Paladino, Frank V.; Spotila, James R.; Fernández, Carlos; Rivas, Marga L.; Tucek, Jenny; Nel, Ronel; Oro, Daniel

    2015-01-01

    The most recent climate change projections show a global increase in temperatures along with precipitation changes throughout the 21st century. However, regional projections do not always match global projections and species with global distributions may exhibit varying regional susceptibility to climate change. Here we show the effect of local climatic conditions on the hatchling output of leatherback turtles (Dermochelys coriacea) at four nesting sites encompassing the Pacific, Atlantic and Indian Oceans. We found a heterogeneous effect of climate. Hatchling output increased with long-term precipitation in areas with dry climatic conditions (Playa Grande, Pacific Ocean and Sandy Point, Caribbean Sea), but the effect varied in areas where precipitation was high (Pacuare, Caribbean Sea) and was not detected at the temperate site (Maputaland, Indian Ocean). High air temperature reduced hatchling output only at the area experiencing seasonal droughts (Playa Grande). Climatic projections showed a drastic increase in air temperature and a mild decrease in precipitation at all sites by 2100. The most unfavorable conditions were projected for Sandy Point where hatching success has already declined over time along with precipitation levels. The heterogeneous effect of climate may lead to local extinctions of leatherback turtles in some areas but survival in others by 2100. PMID:26572897

  7. Global analysis of the effect of local climate on the hatchling output of leatherback turtles

    NASA Astrophysics Data System (ADS)

    Santidrián Tomillo, Pilar; Saba, Vincent S.; Lombard, Claudia D.; Valiulis, Jennifer M.; Robinson, Nathan J.; Paladino, Frank V.; Spotila, James R.; Fernández, Carlos; Rivas, Marga L.; Tucek, Jenny; Nel, Ronel; Oro, Daniel

    2015-11-01

    The most recent climate change projections show a global increase in temperatures along with precipitation changes throughout the 21st century. However, regional projections do not always match global projections and species with global distributions may exhibit varying regional susceptibility to climate change. Here we show the effect of local climatic conditions on the hatchling output of leatherback turtles (Dermochelys coriacea) at four nesting sites encompassing the Pacific, Atlantic and Indian Oceans. We found a heterogeneous effect of climate. Hatchling output increased with long-term precipitation in areas with dry climatic conditions (Playa Grande, Pacific Ocean and Sandy Point, Caribbean Sea), but the effect varied in areas where precipitation was high (Pacuare, Caribbean Sea) and was not detected at the temperate site (Maputaland, Indian Ocean). High air temperature reduced hatchling output only at the area experiencing seasonal droughts (Playa Grande). Climatic projections showed a drastic increase in air temperature and a mild decrease in precipitation at all sites by 2100. The most unfavorable conditions were projected for Sandy Point where hatching success has already declined over time along with precipitation levels. The heterogeneous effect of climate may lead to local extinctions of leatherback turtles in some areas but survival in others by 2100.

  8. Global analysis of the effect of local climate on the hatchling output of leatherback turtles.

    PubMed

    Santidrián Tomillo, Pilar; Saba, Vincent S; Lombard, Claudia D; Valiulis, Jennifer M; Robinson, Nathan J; Paladino, Frank V; Spotila, James R; Fernández, Carlos; Rivas, Marga L; Tucek, Jenny; Nel, Ronel; Oro, Daniel

    2015-11-17

    The most recent climate change projections show a global increase in temperatures along with precipitation changes throughout the 21(st) century. However, regional projections do not always match global projections and species with global distributions may exhibit varying regional susceptibility to climate change. Here we show the effect of local climatic conditions on the hatchling output of leatherback turtles (Dermochelys coriacea) at four nesting sites encompassing the Pacific, Atlantic and Indian Oceans. We found a heterogeneous effect of climate. Hatchling output increased with long-term precipitation in areas with dry climatic conditions (Playa Grande, Pacific Ocean and Sandy Point, Caribbean Sea), but the effect varied in areas where precipitation was high (Pacuare, Caribbean Sea) and was not detected at the temperate site (Maputaland, Indian Ocean). High air temperature reduced hatchling output only at the area experiencing seasonal droughts (Playa Grande). Climatic projections showed a drastic increase in air temperature and a mild decrease in precipitation at all sites by 2100. The most unfavorable conditions were projected for Sandy Point where hatching success has already declined over time along with precipitation levels. The heterogeneous effect of climate may lead to local extinctions of leatherback turtles in some areas but survival in others by 2100.

  9. Anisotropy effect on global minimum structures of clusters: two-center Lennard-Jones model.

    PubMed

    Feng, Yan; Wu, Jing; Cheng, Longjiu; Liu, Haiyan

    2011-12-28

    Using a two-center Lennard-Jones (2CLJ) model, the simplest anisotropic case, we investigated how anisotropy affects global minimum structures of clusters and obtained some interesting results. The anisotropy parameter, R, is defined as the ratio of the bond length of 2CLJ dimer to the LJ equilibrium pair separation, where a larger R value means higher anisotropy. For low R values, the structures resemble those of the Lennard-Jones atomic clusters. However, as the pairwise interaction becomes more anisotropic, the "magic numbers" change, and several novel cluster patterns emerge as particularly stable structures, and the global minima change from icosahedral, to polyicosahedral and to novel irregular structures. Moreover, increasing the anisotropy effectively softens the 2CLJ potential. Given the general importance of the LJ cluster as a simple model cluster, 2CLJ model can provide a straightforward and useful analysis of the effect of molecular shape on the structures of clusters.

  10. The effect of diabetes and undernutrition trends on reaching 2035 global tuberculosis targets.

    PubMed

    Odone, Anna; Houben, Rein M G J; White, Richard G; Lönnroth, Knut

    2014-09-01

    To achieve the post-2015 global tuberculosis target of 90% reduction in tuberculosis incidence by 2035, the present rate of decline must accelerate. Among factors that hinder tuberculosis control, malnutrition and diabetes are key challenges. We review available data to describe the complex relationship between tuberculosis, diabetes, and nutritional status. Additionally, we review past trends, present burden, and available future global projections for diabetes, overweight and obesity, as well as undernutrition and food insecurity. Using a mathematical model, we estimate the potential effect of these factors on tuberculosis burden up to 2035. Great potential exists for reduction of worldwide tuberculosis burden by combination of improved prevention and care of diabetes with reduction of undernutrition. To achieve this combination will require joint efforts and strong cross-programme links, enabling synergistic effects of public health policies that promote good nutrition and optimum clinical care for tuberculosis and diabetes.

  11. Effects of global change during the 21st century onthe nitrogen cycle

    NASA Astrophysics Data System (ADS)

    Fowler, D.; Steadman, C. E.; Stevenson, D.; Coyle, M.; Rees, R. M.; Skiba, U. M.; Sutton, M. A.; Cape, J. N.; Dore, A. J.; Vieno, M.; Simpson, D.; Zaehle, S.; Stocker, B. D.; Rinaldi, M.; Facchini, M. C.; Flechard, C. R.; Nemitz, E.; Twigg, M.; Erisman, J. W.; Butterbach-Bahl, K.; Galloway, J. N.

    2015-12-01

    The global nitrogen (N) cycle at the beginning of the 21st century has been shown to be strongly influenced by the inputs of reactive nitrogen (Nr) from human activities, including combustion-related NOx, industrial and agricultural N fixation, estimated to be 220 Tg N yr-1 in 2010, which is approximately equal to the sum of biological N fixation in unmanaged terrestrial and marine ecosystems. According to current projections, changes in climate and land use during the 21st century will increase both biological and anthropogenic fixation, bringing the total to approximately 600 Tg N yr-1 by around 2100. The fraction contributed directly by human activities is unlikely to increase substantially if increases in nitrogen use efficiency in agriculture are achieved and control measures on combustion-related emissions implemented. Some N-cycling processes emerge as particularly sensitive to climate change. One of the largest responses to climate in the processing of Nr is the emission to the atmosphere of NH3, which is estimated to increase from 65 Tg N yr-1 in 2008 to 93 Tg N yr-1 in 2100 assuming a change in global surface temperature of 5 °C in the absence of increased anthropogenic activity. With changes in emissions in response to increased demand for animal products the combined effect would be to increase NH3 emissions to 135 Tg N yr-1. Another major change is the effect of climate changes on aerosol composition and specifically the increased sublimation of NH4NO3 close to the ground to form HNO3 and NH3 in a warmer climate, which deposit more rapidly to terrestrial surfaces than aerosols. Inorganic aerosols over the polluted regions especially in Europe and North America were dominated by (NH4)2SO4 in the 1970s to 1980s, and large reductions in emissions of SO2 have removed most of the SO42- from the atmosphere in these regions. Inorganic aerosols from anthropogenic emissions are now dominated by NH4NO3, a volatile aerosol which contributes substantially to PM10

  12. Climate change may have limited effect on global risk of potato late blight.

    PubMed

    Sparks, Adam H; Forbes, Gregory A; Hijmans, Robert J; Garrett, Karen A

    2014-12-01

    Weather affects the severity of many plant diseases, and climate change is likely to alter the patterns of crop disease severity. Evaluating possible future patterns can help focus crop breeding and disease management research. We examined the global effect of climate change on potato late blight, the disease that caused the Irish potato famine and still is a common potato disease around the world. We used a metamodel and considered three global climate models for the A2 greenhouse gas emission scenario for three 20-year time-slices: 2000-2019, 2040-2059 and 2080-2099. In addition to global analyses, five regions were evaluated where potato is an important crop: the Andean Highlands, Indo-Gangetic Plain and Himalayan Highlands, Southeast Asian Highlands, Ethiopian Highlands, and Lake Kivu Highlands in Sub-Saharan Africa. We found that the average global risk of potato late blight increases initially, when compared with historic climate data, and then declines as planting dates shift to cooler seasons. Risk in the agro-ecosystems analyzed, varied from a large increase in risk in the Lake Kivu Highlands in Rwanda to decreases in the Southeast Asian Highlands of Indonesia.

  13. Modeled global effects of airborne desert dust on air quality and premature mortality

    NASA Astrophysics Data System (ADS)

    Giannadaki, D.; Pozzer, A.; Lelieveld, J.

    2014-01-01

    Fine particulate matter is one of the most important factors contributing to air pollution. Epidemiological studies have related increased levels of atmospheric particulate matter to premature human mortality caused by cardiopulmonary disease and lung cancer. However, a limited number of investigations have focused on the contribution of airborne desert dust particles. Here we assess the effects of dust particles with an aerodynamic diameter smaller than 2.5 μm (DU2.5) on human mortality for the year 2005. We used the EMAC atmospheric-chemistry general circulation model at high resolution to simulate global atmospheric dust concentrations. We applied a health impact function to estimate premature mortality for the global population of 30 yr and older, using parameters from epidemiological studies. We estimate a global cardiopulmonary mortality of about 402 000 in 2005. The associated years of life lost are about 3.47 million per year. We estimate the global fraction of the cardiopulmonary deaths caused by atmospheric desert dust to be about 1.8%, though in the 20 countries most affected by dust this is much higher, about 15-50%. These countries are primarily found in the so-called "dust belt" from North Africa across the Middle East and South Asia to East Asia

  14. Modeled global effects of airborne desert dust on air quality and premature mortality

    NASA Astrophysics Data System (ADS)

    Giannadaki, D.; Pozzer, A.; Lelieveld, J.

    2013-09-01

    Fine particulate matter is one of the most important factors contributing to air pollution. Epidemiological studies have related increased levels of atmospheric particulate matter to premature human mortality caused by cardiopulmonary disease and lung cancer. However, a limited number of investigations have focused on the contribution of airborne desert dust particles. Here we assess the effects of dust particles with an aerodynamic diameter smaller than 2.5 μm (DU2.5) on human mortality for the year 2005. We used the EMAC atmospheric chemistry general circulation model at high resolution to simulate global atmospheric dust concentrations. We applied a health impact function to estimate premature mortality for the global population of 30 yr and older, using parameters from epidemiological studies. We estimate a global cardiopulmonary mortality of about 402 thousand and about 10 thousand by lung cancer in 2005. The associated years of life lost are about 3.47 million and 96 thousand per year due to cardiopulmonary disease and lung cancer, respectively. We estimate the global fraction of the cardiopulmonary and lung cancer deaths caused by atmospheric desert dust to be about 1.7%, though in the 20 countries most affected by dust this is much higher, about 15-50%. These countries are primarily found in the so-called "dust belt" from North Africa across the Middle East and South Asia to East Asia.

  15. Global Effects of Local Sound-Speed Perturbations in the Sun: A Theoretical Study

    NASA Astrophysics Data System (ADS)

    Hanasoge, S. M.; Larson, T. P.

    2008-09-01

    We study the effect of localized sound-speed perturbations on global mode frequencies by applying techniques of global helioseismology to numerical simulations of the solar acoustic wave field. Extending the method of realization-noise subtraction ( e.g., Hanasoge, Duvall, and Couvidat, Astrophys. J. 664, 1234, 2007) to global modes and exploiting the luxury of full spherical coverage, we are able to achieve very highly resolved frequency differences that are then used to study sensitivities and the signatures of the thermal asphericities. We find that i) global modes are almost twice as sensitive to sound-speed perturbations at the bottom of the convection zone in comparison to anomalies well inside the radiative interior ( r≲0.55 R ⊙), ii) the m degeneracy is lifted ever so slightly, as seen in the a coefficients, and iii) modes that propagate in the vicinity of the perturbations show small amplitude shifts. Through comparisons with error estimates obtained from Michelson Doppler Imager (MDI; Scherrer et al., Solar Phys. 162, 129, 1995) observations, we find that the frequency differences are detectable with a sufficiently long time series (70 642 days).

  16. Effective Strategies for Global Health Research, Training and Clinical Care: A Narrative Review

    PubMed Central

    Walker, Rebekah J.; Campbell, Jennifer A.; Egede, Leonard E.

    2015-01-01

    The purpose of this narrative review was to synthesize the evidence on effective strategies for global health research, training and clinical care in order to identify common structures that have been used to guide program development. A Medline search from 2001 to 2011 produced 951 articles, which were reviewed and categorized. Thirty articles met criteria to be included in this review. Eleven articles discussed recommendations for research, 8 discussed training and 11 discussed clinical care. Global health program development should be completed within the framework of a larger institutional commitment or partnership. Support from leadership in the university or NGO, and an engaged local community are both integral to success and sustainability of efforts. It is also important for program development to engage local partners from the onset, jointly exploring issues and developing goals and objectives. Evaluation is a recommended way to determine if goals are being met, and should include considerations of sustainability, partnership building, and capacity. Global health research programs should consider details regarding the research process, context of research, partnerships, and community relationships. Training for global health should involve mentorship, pre-departure preparation of students, and elements developed to increase impact. Clinical care programs should focus on collaboration, sustainability, meeting local needs, and appropriate process considerations. PMID:25716404

  17. Assessing the Effects of Anthropogenic Aerosols on Pacific Storm Track Using a Multiscale Global Climate Model

    SciTech Connect

    Wang, Yuan; Wang, Minghuai; Zhang, Renyi; Ghan, Steven J.; Lin, Yun; Hu, Jiaxi; Pan, Bowen; Levy, Misti; Jiang, Jonathan; Molina, Mario J.

    2014-05-13

    Atmospheric aerosols impact weather and global general circulation by modifying cloud and precipitation processes, but the magnitude of cloud adjustment by aerosols remains poorly quantified and represents the largest uncertainty in estimated forcing of climate change. Here we assess the impacts of anthropogenic aerosols on the Pacific storm track using a multi-scale global aerosol-climate model (GCM). Simulations of two aerosol scenarios corresponding to the present day and pre-industrial conditions reveal long-range transport of anthropogenic aerosols across the north Pacific and large resulting changes in the aerosol optical depth, cloud droplet number concentration, and cloud and ice water paths. Shortwave and longwave cloud radiative forcing at the top of atmosphere are changed by - 2.5 and + 1.3 W m-2, respectively, by emission changes from pre-industrial to present day, and an increased cloud-top height indicates invigorated mid-latitude cyclones. The overall increased precipitation and poleward heat transport reflect intensification of the Pacific storm track by anthropogenic aerosols. Hence, this work provides for the first time a global perspective of the impacts of Asian pollution outflows from GCMs. Furthermore, our results suggest that the multi-scale modeling framework is essential in producing the aerosol invigoration effect of deep convective clouds on the global scale.

  18. Effective strategies for global health research, training and clinical care: a narrative review.

    PubMed

    Walker, Rebekah J; Campbell, Jennifer A; Egede, Leonard E

    2014-09-29

    The purpose of this narrative review was to synthesize the evidence on effective strategies for global health research, training and clinical care in order to identify common structures that have been used to guide program development. A Medline search from 2001 to 2011 produced 951 articles, which were reviewed and categorized. Thirty articles met criteria to be included in this review. Eleven articles discussed recommendations for research, 8 discussed training and 11 discussed clinical care. Global health program development should be completed within the framework of a larger institutional commitment or partnership. Support from leadership in the university or NGO, and an engaged local community are both integral to success and sustainability of efforts. It is also important for program development to engage local partners from the onset, jointly exploring issues and developing goals and objectives. Evaluation is a recommended way to determine if goals are being met, and should include considerations of sustainability, partnership building, and capacity. Global health research programs should consider details regarding the research process, context of research, partnerships, and community relationships. Training for global health should involve mentorship, pre-departure preparation of students, and elements developed to increase impact. Clinical care programs should focus on collaboration, sustainability, meeting local needs, and appropriate process considerations.

  19. Comparative phosphoproteome profiling reveals a function of the STN8 kinase in fine-tuning of cyclic electron flow (CEF)

    PubMed Central

    Reiland, Sonja; Finazzi, Giovanni; Endler, Anne; Willig, Adrian; Baerenfaller, Katja; Grossmann, Jonas; Gerrits, Bertran; Rutishauser, Dorothea; Gruissem, Wilhelm; Rochaix, Jean-David; Baginsky, Sacha

    2011-01-01

    Important aspects of photosynthetic electron transport efficiency in chloroplasts are controlled by protein phosphorylation. Two thylakoid-associated kinases, STN7 and STN8, have distinct roles in short- and long-term photosynthetic acclimation to changes in light quality and quantity. Although some substrates of STN7 and STN8 are known, the complexity of this regulatory kinase system implies that currently unknown substrates connect photosynthetic performance with the regulation of metabolic and regulatory functions. We performed an unbiased phosphoproteome-wide screen with Arabidopsis WT and stn8 mutant plants to identify unique STN8 targets. The phosphorylation status of STN7 was not affected in stn8, indicating that kinases other than STN8 phosphorylate STN7 under standard growth conditions. Among several putative STN8 substrates, PGRL1-A is of particular importance because of its possible role in the modulation of cyclic electron transfer. The STN8 phosphorylation site on PGRL1-A is absent in both monocotyledonous plants and algae. In dicots, spectroscopic measurements with Arabidopsis WT, stn7, stn8, and stn7/stn8 double-mutant plants indicate a STN8-mediated slowing down of the transition from cyclic to linear electron flow at the onset of illumination. This finding suggests a possible link between protein phosphorylation by STN8 and fine-tuning of cyclic electron flow during this critical step of photosynthesis, when the carbon assimilation is not commensurate to the electron flow capacity of the chloroplast. PMID:21768351

  20. Quantitative Phosphoproteomics Reveals Pathways for Coordination of Cell Growth and Division by the Conserved Fission Yeast Kinase Pom1*

    PubMed Central

    Kettenbach, Arminja N.; Deng, Lin; Wu, Youjun; Baldissard, Suzanne; Adamo, Mark E.; Gerber, Scott A.; Moseley, James B.

    2015-01-01

    Complex phosphorylation-dependent signaling networks underlie the coordination of cellular growth and division. In the fission yeast Schizosaccharomyces pombe, the Dual specificity tyrosine-(Y)-phosphorylation regulated kinase (DYRK) family protein kinase Pom1 regulates cell cycle progression through the mitotic inducer Cdr2 and controls cell polarity through unknown targets. Here, we sought to determine the phosphorylation targets of Pom1 kinase activity by SILAC-based phosphoproteomics. We defined a set of high-confidence Pom1 targets that were enriched for cytoskeletal and cell growth functions. Cdr2 was the only cell cycle target of Pom1 kinase activity that we identified in cells. Mutation of Pom1-dependent phosphorylation sites in the C terminus of Cdr2 inhibited mitotic entry but did not impair Cdr2 localization. In addition, we found that Pom1 phosphorylated multiple substrates that function in polarized cell growth, including Tea4, Mod5, Pal1, the Rho GAP Rga7, and the Arf GEF Syt22. Purified Pom1 phosphorylated these cell polarity targets in vitro, confirming that they are direct substrates of Pom1 kinase activity and likely contribute to regulation of polarized growth by Pom1. Our study demonstrates that Pom1 acts in a linear pathway to control cell cycle progression while regulating a complex network of cell growth targets. PMID:25720772

  1. Phosphoproteomics reveals resveratrol-dependent inhibition of Akt/mTORC1/S6K1 signaling.

    PubMed

    Alayev, Anya; Doubleday, Peter F; Berger, Sara Malka; Ballif, Bryan A; Holz, Marina K

    2014-12-05

    Resveratrol, a plant-derived polyphenol, regulates many cellular processes, including cell proliferation, aging and autophagy. However, the molecular mechanisms of resveratrol action in cells are not completely understood. Intriguingly, resveratrol treatment of cells growing in nutrient-rich conditions induces autophagy, while acute resveratrol treatment of cells in a serum-deprived state inhibits autophagy. In this study, we performed a phosphoproteomic analysis after applying resveratrol to serum-starved cells with the goal of identifying the acute signaling events initiated by resveratrol in a serum-deprived state. We determined that resveratrol in serum-starved conditions reduces the phosphorylation of several proteins belonging to the mTORC1 signaling pathway, most significantly, PRAS40 at T246 and S183. Under these same conditions, we also found that resveratrol altered the phosphorylation of several proteins involved in various biological processes, most notably transcriptional modulators, represented by p53, FOXA1, and AATF. Together these data provide a more comprehensive view of both the spectrum of phosphoproteins upon which resveratrol acts as well as the potential mechanisms by which it inhibits autophagy in serum-deprived cells.

  2. Quantitative phosphoproteomics revealed interplay between Syk and Lyn in the resistance to nilotinib in chronic myeloid leukemia cells.

    PubMed

    Gioia, Romain; Leroy, Cédric; Drullion, Claire; Lagarde, Valérie; Etienne, Gabriel; Dulucq, Stéphanie; Lippert, Eric; Roche, Serge; Mahon, François-Xavier; Pasquet, Jean-Max

    2011-08-25

    In this study, we have addressed how Lyn kinase signaling mediates nilotinib-resistance by quantitative phospho-proteomics using Stable Isotope Labeling with Amino acid in Cell culture. We have found an increased tyrosine phosphorylation of 2 additional tyrosine kinases in nilotinib-resistant cells: the spleen tyrosine kinase Syk and the UFO family receptor tyrosine kinase Axl. This increased tyrosine phosphorylation involved an interaction of these tyrosine kinases with Lyn. Inhibition of Syk by the inhibitors R406 or BAY 61-3606 or by RNA interference restored the capacity of nilotinib to inhibit cell proliferation. Conversely, coexpression of Lyn and Syk were required to fully induce resistance to nilotinib in drug-sensitive cells. Surprisingly, the knockdown of Syk also strongly decreased tyrosine phosphorylation of Lyn and Axl, thus uncovering interplay between Syk and Lyn. We have shown the involvement of the adaptor protein CDCP-1 in resistance to nilotinib. Interestingly, the expression of Axl and CDCP1 were found increased both in a nilotinib-resistant cell line and in nilotinib-resistant CML patients. We conclude that an oncogenic signaling mediated by Lyn and Syk can bypass the need of Bcr-Abl in CML cells. Thus, targeting these kinases may be of therapeutic value to override imatinib or nilotinib resistance in CML.

  3. Large-Scale Phosphoproteome of Human Whole Saliva Using Disulphide-Thiol-Interchange Covalent Chromatography and Mass Spectrometry

    PubMed Central

    Salih, Erdjan; Siqueira, Walter L.; Helmerhorst, Eva J.; Oppenheim, Frank G.

    2010-01-01

    Thus far only a handful of phosphoproteins with important biological functions have been identified and characterized in oral fluids and these include some of the abundant protein constituents of saliva. Whole saliva (WS) samples were trypsin digested followed by chemical derivatization using dithiothreitol (DTT) of the phospho-serine/threonine containing peptides. The DTT-phosphopeptides were enriched by covalent disulphide-thiol-interchange chromatography and analysis by nano-flow LC-ESI-MS/MS. The specificity of DTT chemical derivatization was evaluated separately under different base-catalyzed conditions with NaOH and Ba(OH)2, blocking cysteine residues by iodoacetamide and enzymatic O-deglycosylation prior to DTT reaction. Further analysis of WS samples which were subjected to either of these conditions provided supporting evidence for phosphoprotein identifications. The combined chemical strategies and mass spectrometric analyses identified 65 phosphoproteins in WS of which 28 were based on two or more peptide identification criteria with high confidence, and 37 were based on a single phosphopeptide identification. Most of the identified proteins, ~80%, were hitherto unknown phosphoprotein components. This study represents the first large-scale documentation of phosphoproteins of WS. The origins and identity of WS phosphoproteome suggest significant implications for both basic science and the development of novel biomarkers/diagnostic tools for both systemic and oral disease states. PMID:20659418

  4. Phosphoproteome profiles of the phytopathogenic fungi Alternaria brassicicola and Botrytis cinerea during exponential growth in axenic cultures.

    PubMed

    Davanture, Marlène; Dumur, Jérôme; Bataillé-Simoneau, Nelly; Campion, Claire; Valot, Benoît; Zivy, Michel; Simoneau, Philippe; Fillinger, Sabine

    2014-07-01

    This study describes the gel-free phosphoproteomic analysis of the phytopathogenic fungi Alternaria brassicicola and Botrytis cinerea grown in vitro under nonlimiting conditions. Using a combination of strong cation exchange and IMAC prior to LC-MS, we identified over 1350 phosphopeptides per fungus representing over 800 phosphoproteins. The preferred phosphorylation sites were found on serine (>80%) and threonine (>15%), whereas phosphorylated tyrosine residues were found at less than 1% in A. brassicicola and at a slightly higher ratio in B. cinerea (1.5%). Biological processes represented principally among the phoshoproteins were those involved in response and transduction of stimuli as well as in regulation of cellular and metabolic processes. Most known elements of signal transduction were found in the datasets of both fungi. This study also revealed unexpected phosphorylation sites in histidine kinases, a category overrepresented in filamentous ascomycetes compared to yeast. The data have been deposited to the ProteomeXchange database with identifier PXD000817 (http://proteomecentral.proteomexchange.org/dataset/PXD000817).

  5. Phosphoproteomic Analysis Identifies Focal Adhesion Kinase 2 (FAK2) as a Potential Therapeutic Target for Tamoxifen Resistance in Breast Cancer.

    PubMed

    Wu, Xinyan; Zahari, Muhammad Saddiq; Renuse, Santosh; Nirujogi, Raja Sekhar; Kim, Min-Sik; Manda, Srikanth S; Stearns, Vered; Gabrielson, Edward; Sukumar, Saraswati; Pandey, Akhilesh

    2015-11-01

    Tamoxifen, an estrogen receptor-α (ER) antagonist, is an important agent for the treatment of breast cancer. However, this therapy is complicated by the fact that a substantial number of patients exhibit either de novo or acquired resistance. To characterize the signaling mechanisms underlying this resistance, we treated the MCF7 breast cancer cell line with tamoxifen for over six months and showed that this cell line acquired resistance to tamoxifen in vitro and in vivo. We performed SILAC-based quantitative phosphoproteomic profiling on the tamoxifen resistant and vehicle-treated sensitive cell lines to quantify the phosphorylation alterations associated with tamoxifen resistance. From >5600 unique phosphopeptides identified, 1529 peptides exhibited hyperphosphorylation and 409 peptides showed hypophosphorylation in the tamoxifen resistant cells. Gene set enrichment analysis revealed that focal adhesion pathway was one of the most enriched signaling pathways activated in tamoxifen resistant cells. Significantly, we showed that the focal adhesion kinase FAK2 was not only hyperphosphorylated but also transcriptionally up-regulated in tamoxifen resistant cells. FAK2 suppression by specific siRNA knockdown or a small molecule inhibitor repressed cellular proliferation in vitro and tumor formation in vivo. More importantly, our survival analysis revealed that high expression of FAK2 is significantly associated with shorter metastasis-free survival in estrogen receptor-positive breast cancer patients treated with tamoxifen. Our studies suggest that FAK2 is a potential therapeutic target for the management of hormone-refractory breast cancers.

  6. Phosphoproteomics Reveals Resveratrol-Dependent Inhibition of Akt/mTORC1/S6K1 Signaling

    PubMed Central

    2015-01-01

    Resveratrol, a plant-derived polyphenol, regulates many cellular processes, including cell proliferation, aging and autophagy. However, the molecular mechanisms of resveratrol action in cells are not completely understood. Intriguingly, resveratrol treatment of cells growing in nutrient-rich conditions induces autophagy, while acute resveratrol treatment of cells in a serum-deprived state inhibits autophagy. In this study, we performed a phosphoproteomic analysis after applying resveratrol to serum-starved cells with the goal of identifying the acute signaling events initiated by resveratrol in a serum-deprived state. We determined that resveratrol in serum-starved conditions reduces the phosphorylation of several proteins belonging to the mTORC1 signaling pathway, most significantly, PRAS40 at T246 and S183. Under these same conditions, we also found that resveratrol altered the phosphorylation of several proteins involved in various biological processes, most notably transcriptional modulators, represented by p53, FOXA1, and AATF. Together these data provide a more comprehensive view of both the spectrum of phosphoproteins upon which resveratrol acts as well as the potential mechanisms by which it inhibits autophagy in serum-deprived cells. PMID:25311616

  7. PAPE (Prefractionation-Assisted Phosphoprotein Enrichment): A Novel Approach for Phosphoproteomic Analysis of Green Tissues from Plants

    PubMed Central

    Lassowskat, Ines; Naumann, Kai; Lee, Justin; Scheel, Dierk

    2013-01-01

    Phosphorylation is an important post-translational protein modification with regulatory roles in diverse cellular signaling pathways. Despite recent advances in mass spectrometry, the detection of phosphoproteins involved in signaling is still challenging, as protein phosphorylation is typically transient and/or occurs at low levels. In green plant tissues, the presence of highly abundant proteins, such as the subunits of the RuBisCO complex, further complicates phosphoprotein analysis. Here, we describe a simple, but powerful, method, which we named prefractionation-assisted phosphoprotein enrichment (PAPE), to increase the yield of phosphoproteins from Arabidopsis thaliana leaf material. The first step, a prefractionation via ammonium sulfate precipitation, not only depleted RuBisCO almost completely, but, serendipitously, also served as an efficient phosphoprotein enrichment step. When coupled with a subsequent metal oxide affinity chromatography (MOAC) step, the phosphoprotein content was highly enriched. The reproducibility and efficiency of phosphoprotein enrichment was verified by phospho-specific staining and, further, by mass spectrometry, where it could be shown that the final PAPE fraction contained a significant number of known and additionally novel (potential) phosphoproteins. Hence, this facile two-step procedure is a good prerequisite to probe the phosphoproteome and gain deeper insight into plant phosphorylation-based signaling events. PMID:28250405

  8. Large-scale phosphoproteome of human whole saliva using disulfide-thiol interchange covalent chromatography and mass spectrometry.

    PubMed

    Salih, Erdjan; Siqueira, Walter L; Helmerhorst, Eva J; Oppenheim, Frank G

    2010-12-01

    To date, only a handful of phosphoproteins with important biological functions have been identified and characterized in oral fluids, and these include some of the abundant protein constituents of saliva. Whole saliva (WS) samples were trypsin digested, followed by chemical derivatization using dithiothreitol (DTT) of the phospho-serine/threonine-containing peptides. The DTT-phosphopeptides were enriched by covalent disulfide-thiol interchange chromatography and analysis by nanoflow liquid chromatography and electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). The specificity of DTT chemical derivatization was evaluated separately under different base-catalyzed conditions with NaOH and Ba(OH)(2), blocking cysteine residues by iodoacetamide and enzymatic O-deglycosylation prior to DTT reaction. Further analysis of WS samples that were subjected to either of these conditions provided supporting evidence for phosphoprotein identifications. The combined chemical strategies and mass spectrometric analyses identified 65 phosphoproteins in WS; of these, 28 were based on two or more peptide identification criteria with high confidence and 37 were based on a single phosphopeptide identification. Most of the identified proteins (∼80%) were previously unknown phosphoprotein components. This study represents the first large-scale documentation of phosphoproteins of WS. The origins and identity of WS phosphoproteome suggest significant implications for both basic science and the development of novel biomarkers/diagnostic tools for systemic and oral disease states.

  9. Quantitative phospho-proteomics reveals the Plasmodium merozoite triggers pre-invasion host kinase modification of the red cell cytoskeleton.

    PubMed

    Zuccala, Elizabeth S; Satchwell, Timothy J; Angrisano, Fiona; Tan, Yan Hong; Wilson, Marieangela C; Heesom, Kate J; Baum, Jake

    2016-02-02

    The invasive blood-stage malaria parasite - the merozoite - induces rapid morphological changes to the target erythrocyte during entry. However, evidence for active molecular changes in the host cell that accompany merozoite invasion is lacking. Here, we use invasion inhibition assays, erythrocyte resealing and high-definition imaging to explore red cell responses during invasion. We show that although merozoite entry does not involve erythrocyte actin reorganisation, it does require ATP to complete the process. Towards dissecting the ATP requirement, we present an in depth quantitative phospho-proteomic analysis of the erythrocyte during each stage of invasion. Specifically, we demonstrate extensive increased phosphorylation of erythrocyte proteins on merozoite attachment, including modification of the cytoskeletal proteins beta-spectrin and PIEZO1. The association with merozoite contact but not active entry demonstrates that parasite-dependent phosphorylation is mediated by host-cell kinase activity. This provides the first evidence that the erythrocyte is stimulated to respond to early invasion events through molecular changes in its membrane architecture.

  10. Dynamic Phosphoproteome Analysis of Seedling Leaves in Brachypodium distachyon L. Reveals Central Phosphorylated Proteins Involved in the Drought Stress Response

    PubMed Central

    Yuan, Lin-Lin; Zhang, Ming; Yan, Xing; Bian, Yan-Wei; Zhen, Shou-Min; Yan, Yue-Ming

    2016-01-01

    Drought stress is a major abiotic stress affecting plant growth and development. In this study, we performed the first dynamic phosphoproteome analysis of Brachypodium distachyon L. seedling leaves under drought stress for different times. A total of 4924 phosphopeptides, contained 6362 phosphosites belonging to 2748 phosphoproteins. Rigorous standards were imposed to screen 484 phosphorylation sites, representing 442 unique phosphoproteins. Comparative analyses revealed significant changes in phosphorylation levels at 0, 6, and 24 h under drought stress. The most phosphorylated proteins and the highest phosphorylation level occurred at 6 h. Venn analysis showed that the up-regulated phosphopeptides at 6 h were almost two-fold those at 24 h. Motif-X analysis identified the six motifs: [sP], [Rxxs], [LxRxxs], [sxD], [sF], and [TP], among which [LxRxxs] was also previously identified in B. distachyon. Results from molecular function and protein-protein interaction analyses suggested that phosphoproteins mainly participate in signal transduction, gene expression, drought response and defense, photosynthesis and energy metabolism, and material transmembrane transport. These phosphoproteins, which showed significant changes in phosphorylation levels, play important roles in signal transduction and material transmembrane transport in response to drought conditions. Our results provide new insights into the molecular mechanism of this plant’s abiotic stress response through phosphorylation modification. PMID:27748408

  11. Phosphoproteomic comparison of Pik3ca and Pten signalling identifies the nucleotidase NT5C as a novel AKT substrate

    PubMed Central

    Moniz, Larissa S.; Surinova, Silvia; Ghazaly, Essam; Velasco, Lorena Gonzalez; Haider, Syed; Rodríguez-Prados, Juan Carlos; Berenjeno, Inma M.; Chelala, Claude; Vanhaesebroeck, Bart

    2017-01-01

    To identify novel effectors and processes regulated by PI3K pathway activation, we performed an unbiased phosphoproteomic screen comparing two common events of PI3K deregulation in cancer: oncogenic Pik3ca mutation (Pik3caH1047R) and deletion of Pten. Using mouse embryonic fibroblast (MEF) models that generate inducible, low-level pathway activation as observed in cancer, we quantified 7566 unique phosphopeptides from 3279 proteins. A number of proteins were found to be differentially-regulated by Pik3caH1047R and Pten loss, suggesting unique roles for these two events in processes such as vesicular trafficking, DNA damage repair and RNA splicing. We also identified novel PI3K effectors that were commonly-regulated, including putative AKT substrates. Validation of one of these hits, confirmed NT5C (5′,3′-Nucleotidase, Cytosolic) as a novel AKT substrate, with an unexpected role in actin cytoskeleton regulation via an interaction with the ARP2/3 complex. This study has produced a comprehensive data resource and identified a new link between PI3K pathway activation and actin regulation. PMID:28059163

  12. Proteomic and phosphoproteomic analysis of renal cortex in a salt-load rat model of advanced kidney damage

    PubMed Central

    Jiang, Shaoling; He, Hanchang; Tan, Lishan; Wang, Liangliang; Su, Zhengxiu; Liu, Yufeng; Zhu, Hongguo; Zhang, Menghuan; Hou, Fan Fan; Li, Aiqing

    2016-01-01

    Salt plays an essential role in the progression of chronic kidney disease and hypertension. However, the mechanisms underlying pathogenesis of salt-induced kidney damage remain largely unknown. Here, Sprague-Dawley rats, that underwent 5/6 nephrectomy (5/6Nx, a model of advanced kidney damage) or sham operation, were treated for 2 weeks with a normal or high-salt diet. We employed aTiO2 enrichment, iTRAQ labeling and liquid-chromatography tandem mass spectrometry strategy for proteomic and phosphoproteomic profiling of the renal cortex. We found 318 proteins differentially expressed in 5/6Nx group relative to sham group, and 310 proteins significantly changed in response to salt load in 5/6Nx animals. Totally, 1810 unique phosphopeptides corresponding to 550 phosphoproteins were identified. We identified 113 upregulated and 84 downregulated phosphopeptides in 5/6Nx animals relative to sham animals. Salt load induced 78 upregulated and 91 downregulated phosphopeptides in 5/6Nx rats. The differentially expressed phospholproteins are important transporters, structural molecules, and receptors. Protein-protein interaction analysis revealed that the differentially phosphorylated proteins in 5/6Nx group, Polr2a, Srrm1, Gsta2 and Pxn were the most linked. Salt-induced differential phosphoproteins, Myh6, Lmna and Des were the most linked. Altered phosphorylation levels of lamin A and phospholamban were validated. This study will provide new insight into pathogenetic mechanisms of chronic kidney disease and salt sensitivity. PMID:27775022

  13. Sensitive landscape features for detecting biotic effects of global change. Final report

    SciTech Connect

    Ferson, S.; Kurtz, C.; Slice, D.

    1995-10-01

    Although several global climate models have forecast dramatic changes in future climatological conditions, very little can be predicted with any confidence about the effects on the earth`s vegetation from such environmental changes. Therefore some means is needed by which to monitor the biotic effects of global change, especially at its early stages. Ecotones, the transitional zones between larger, more compositionally well-defined biological communities, may be useful structures for monitoring the effects of climatic and other environmental impacts due to global as well as local perturbations. However, theoretical consideration of the ecological processes that determine the location and form of these structures suggests that ecotones that are sharp and therefore obvious to observers may be relatively insensitive to the types of environmental changes they might be asked to detect. It is necessary, therefore, to develop methods to identify ecotones according to the processes that generate them so that their usefulness in a particular environmental monitoring program can be assessed. This report summarizes the development of analytical methods for the detection, localization and characterization of these potentially important landscape features.

  14. Introduction to the Special Issue: Across the horizon: scale effects in global change research.

    PubMed

    Gornish, Elise S; Leuzinger, Sebastian

    2015-01-01

    As a result of the increasing speed and magnitude in which habitats worldwide are experiencing environmental change, making accurate predictions of the effects of global change on ecosystems and the organisms that inhabit them have become an important goal for ecologists. Experimental and modelling approaches aimed at understanding the linkages between factors of global change and biotic responses have become numerous and increasingly complex in order to adequately capture the multifarious dynamics associated with these relationships. However, constrained by resources, experiments are often conducted at small spatiotemporal scales (e.g. looking at a plot of a few square metres over a few years) and at low organizational levels (looking at organisms rather than ecosystems) in spite of both theoretical and experimental work that suggests ecological dynamics across scales can be dissimilar. This phenomenon has been hypothesized to occur because the mechanisms that drive dynamics across scales differ. A good example is the effect of elevated CO2 on transpiration. While at the leaf level, transpiration can be reduced, at the stand level, transpiration can increase because leaf area per unit ground area increases. The reported net effect is then highly dependent on the spatiotemporal scale. This special issue considers the biological relevancy inherent in the patterns associated with the magnitude and type of response to changing environmental conditions, across scales. This collection of papers attempts to provide a comprehensive treatment of this phenomenon in order to help develop an understanding of the extent of, and mechanisms involved with, ecological response to global change.

  15. The effectiveness of social marketing in global health: a systematic review.

    PubMed

    Firestone, Rebecca; Rowe, Cassandra J; Modi, Shilpa N; Sievers, Dana

    2017-02-01

    Social marketing is a commonly used strategy in global health. Social marketing programmes may sell subsidized products through commercial sector outlets, distribute appropriately priced products, deliver health services through social franchises and promote behaviours not dependent upon a product or service. We aimed to review evidence of the effectiveness of social marketing in low- and middle-income countries, focusing on major areas of investment in global health: HIV, reproductive health, child survival, malaria and tuberculosis. We searched PubMed, PsycInfo and ProQuest, using search terms linking social marketing and health outcomes for studies published from 1995 to 2013. Eligible studies used experimental or quasi-experimental designs to measure outcomes of behavioural factors, health behaviours and/or health outcomes in each health area. Studies were analysed by effect estimates and for application of social marketing benchmark criteria. After reviewing 18 974 records, 125 studies met inclusion criteria. Across health areas, 81 studies reported on changes in behavioural factors, 97 studies reported on changes in behaviour and 42 studies reported on health outcomes. The greatest number of studies focused on HIV outcomes (n = 45) and took place in sub-Saharan Africa (n = 67). Most studies used quasi-experimental designs and reported mixed results. Child survival had proportionately the greatest number of studies using experimental designs, reporting health outcomes, and reporting positive, statistically significant results. Most programmes used a range of methods to promote behaviour change. Programmes with positive, statistically significant findings were more likely to apply audience insights and cost-benefit analyses to motivate behaviour change. Key evidence gaps were found in voluntary medical male circumcision and childhood pneumonia. Social marketing can influence health behaviours and health outcomes in global health; however evaluations

  16. Global warming mitigation by sulphur loading in the atmosphere: Required emissions and possible side effects

    NASA Astrophysics Data System (ADS)

    Eliseev, A. V.; Mokhov, I. I.; Chernokulsky, A. V.; Karpenko, A. A.

    2009-04-01

    An approach to mitigate the global warming via sulphur loading in the stratosphere (geoengineering) is studied employing a large ensemble of numerical experiments with the climate model of intermediate complexity developed at the A.M.Obukhov Institute of Atmospheric Physics RAS (IAP RAS CM). The model is forced by the historical+SRES A1B anthropogenical greenhouse gases+tropospheric sulphates scenario for 1860-2100 with an additional sulphur emissions in the stratosphere in the 21st century. Different ensemble members were constructed by varying emission intensity, residence time, optical properites, and horizontal distributions of stratospheric sulphates. In addition, starting and ending years of applied emissions are varied between different ensemble members. Given global loading of the sulphates in the stratosphere, at the global basis, the most efficient latitudinal distribution of geoengineering aerosols is that peaked between 50∘N and 70∘N. Uniform latitudinal distribution of stratospheric sulphates is slightly less efficient. Sulphur emissions in the stratosphere required to stop the global temperature at the level corresponding to the mean value for 2000-2010 amount 5 - 10 TgS/yr in year 2050 and > 10 TgS/yr in year 2100. This is not a small part of the current emissions of tropospheric sulphates. Moreover, even if the global warming is stopped, temperature changes in different regions still occur with a magnitude up to 1 K. Their horizontal pattern depends on implied latitudinal distribution of stratospheric sulphates. If the geoengineering emissions are stopped, their climatic effect is removed within a few decades. In this period, surface air temperture may change with a rate of several Kelvins per decade. The results obtained with the IAP RAS CM are further interpreted by making use of an energy-balance climate model. As a whole, the results obtained with this simpler model support conclusions made on the basis of the IAP RAS CM simulations.

  17. Effects of chemical aging on global secondary organic aerosol using the volatility basis set approach

    NASA Astrophysics Data System (ADS)

    Jo, D. S.; Park, R. J.; Kim, M. J.; Spracklen, D. V.

    2013-12-01

    A global 3-D chemical transport model (GEOS-Chem) is used with the volatility basis set (VBS) approach to examine the effects of chemical aging on global secondary organic aerosol (SOA) concentrations and budgets. We present full-year simulations and their comparisons with the global aerosol mass spectrometer (AMS) dataset, the Interagency Monitoring of Protected Visual Environments (IMPROVE) dataset from the United States, the European Monitoring and Evaluation Programme (EMEP) dataset from Europe, and water-soluble organic carbon observation data collected over East Asia. Using different chemical aging constants, we find that the model results with 4 × 10-11 cm3 molecule-1 s-1 are in better agreement with all observations relative to the model results with other aging constants, without aging, and with the two-product approach. The model simulations are improved when chemical aging is considered, especially for rural regions. However, the simulations still underestimate observed oxygenated organic aerosol (OOA) in urban areas. Two sensitivity simulations including semi-volatile primary organic aerosol (POA) were conducted. We find that including semi-volatile POA improves the model in terms of the hydrogen-like organic aerosol (HOA) to OOA ratio. However, the total OA concentrations are not improved. The total SOA production is considerably increased by 53%, from 26.0 to 39.9 Tg yr-1, after considering chemical aging, remaining lower than top-down estimates of SOA production. Direct radiative forcing (DRF) increases by -0.07 W m-2 due to the chemical aging of SOA, which is comparable to the mean DRF (-0.13 W m-2) of OA from the AeroCom multi-model study. This result indicates considerable global and, more importantly, regional climate implications. For example, the regional DRF change due to chemical aging of SOA in the eastern US is -0.29 W m-2, which is 4 times greater in magnitude than the global mean value.

  18. What effect did the global financial crisis have upon youth wellbeing? Evidence from four Australian cohorts.

    PubMed

    Parker, Philip D; Jerrim, John; Anders, Jake

    2016-04-01

    Recent research has suggested significant negative effects of the Global Financial Crisis (GFC) on mental health and wellbeing. In this article, the authors suggest that the developmental period of late adolescence may be at particular risk of economic downturns. Harmonizing 4 longitudinal cohorts of Australian youth (N = 38,017), we estimate the impact of the GFC on 1 general and 11 domain specific measures of wellbeing at age 19 and 22. Significant differences in wellbeing in most life domains were found, suggesting that wellbeing is susceptible to economic shocks. Given that the GFC in Australia was relatively mild, the finding of clear negative effects across 2 ages is of international concern.

  19. Compensatory water effects link yearly global land CO2 sink changes to temperature.

    PubMed

    Jung, Martin; Reichstein, Markus; Schwalm, Christopher R; Huntingford, Chris; Sitch, Stephen; Ahlström, Anders; Arneth, Almut; Camps-Valls, Gustau; Ciais, Philippe; Friedlingstein, Pierre; Gans, Fabian; Ichii, Kazuhito; Jain, Atul K; Kato, Etsushi; Papale, Dario; Poulter, Ben; Raduly, Botond; Rödenbeck, Christian; Tramontana, Gianluca; Viovy, Nicolas; Wang, Ying-Ping; Weber, Ulrich; Zaehle, Sönke; Zeng, Ning

    2017-01-26

    Large interannual variations in the measured growth rate of atmospheric carbon dioxide (CO2) originate primarily from fluctuations in carbon uptake by land ecosystems. It remains uncertain, however, to what extent temperature and water availability control the carbon balance of land ecosystems across spatial and temporal scales. Here we use empirical models based on eddy covariance data and process-based models to investigate the effect of changes in temperature and water availability on gross primary productivity (GPP), terrestrial ecosystem respiration (TER) and net ecosystem exchange (NEE) at local and global scales. We find that water availability is the dominant driver of the local interannual variability in GPP and TER. To a lesser extent this is true also for NEE at the local scale, but when integrated globally, temporal NEE variability is mostly driven by temperature fluctuations. We suggest that this apparent paradox can be explained by two compensatory water effects. Temporal water-driven GPP and TER variations compensate locally, dampening water-driven NEE variability. Spatial water availability anomalies also compensate, leaving a dominant temperature signal in the year-to-year fluctuations of the land carbon sink. These findings help to reconcile seemingly contradictory reports regarding the importance of temperature and water in controlling the interannual variability of the terrestrial carbon balance. Our study indicates that spatial climate covariation drives the global carbon cycle response.

  20. Compensatory water effects link yearly global land CO2 sink changes to temperature

    NASA Astrophysics Data System (ADS)

    Jung, Martin; Reichstein, Markus; Schwalm, Christopher R.; Huntingford, Chris; Sitch, Stephen; Ahlström, Anders; Arneth, Almut; Camps-Valls, Gustau; Ciais, Philippe; Friedlingstein, Pierre; Gans, Fabian; Ichii, Kazuhito; Jain, Atul K.; Kato, Etsushi; Papale, Dario; Poulter, Ben; Raduly, Botond; Rödenbeck, Christian; Tramontana, Gianluca; Viovy, Nicolas; Wang, Ying-Ping; Weber, Ulrich; Zaehle, Sönke; Zeng, Ning

    2017-01-01

    Large interannual variations in the measured growth rate of atmospheric carbon dioxide (CO2) originate primarily from fluctuations in carbon uptake by land ecosystems. It remains uncertain, however, to what extent temperature and water availability control the carbon balance of land ecosystems across spatial and temporal scales. Here we use empirical models based on eddy covariance data and process-based models to investigate the effect of changes in temperature and water availability on gross primary productivity (GPP), terrestrial ecosystem respiration (TER) and net ecosystem exchange (NEE) at local and global scales. We find that water availability is the dominant driver of the local interannual variability in GPP and TER. To a lesser extent this is true also for NEE at the local scale, but when integrated globally, temporal NEE variability is mostly driven by temperature fluctuations. We suggest that this apparent paradox can be explained by two compensatory water effects. Temporal water-driven GPP and TER variations compensate locally, dampening water-driven NEE variability. Spatial water availability anomalies also compensate, leaving a dominant temperature signal in the year-to-year fluctuations of the land carbon sink. These findings help to reconcile seemingly contradictory reports regarding the importance of temperature and water in controlling the interannual variability of the terrestrial carbon balance. Our study indicates that spatial climate covariation drives the global carbon cycle response.

  1. Braking effect of climate and topography on global change-induced upslope forest expansion

    NASA Astrophysics Data System (ADS)

    Alatalo, Juha M.; Ferrarini, Alessandro

    2017-03-01

    Forests are expected to expand into alpine areas due to global climate change. It has recently been shown that temperature alone cannot realistically explain this process and that upslope tree advance in a warmer scenario may depend on the availability of sites with adequate geomorphic/topographic characteristics. Here, we show that, besides topography (slope and aspect), climate itself can produce a braking effect on the upslope advance of subalpine forests and that tree limit is influenced by non-linear and non-monotonic contributions of the climate variables which act upon treeline upslope advance with varying relative strengths. Our results suggest that global climate change impact on the upslope advance of subalpine forests should be interpreted in a more complex way where climate can both speed up and slow down the process depending on complex patterns of contribution from each climate and non-climate variable.

  2. Global simulations of smoke from Kuwaiti oil fires and possible effects on climate

    SciTech Connect

    Glatzmaier, G.A.; Malone, R.C.; Kao, C.Y.J.

    1991-01-01

    The Los Alamos Global Climate Model has bee used to simulate the global evolution of the Kuwaiti oil fire smoke and its potential effects on the climate. The initial simulations were done shortly before the fires were lit in January 1991. They indicated that such an event would not result in a Mini Nuclear Winter'' as some people were suggesting. Further simulations during the year suggested that the smoke could be responsible for subtle regional climate changes in the spring such as a 5 degree centigrade decrease in the surface temperature in Kuwait, a 10% decrease in precipitation in Saudi Arabia and a 10% increase in precipitation in the Tibetan Plateau region. These results are in qualitative agreement with the observations this year.

  3. Braking effect of climate and topography on global change-induced upslope forest expansion.

    PubMed

    Alatalo, Juha M; Ferrarini, Alessandro

    2017-03-01

    Forests are expected to expand into alpine areas due to global climate change. It has recently been shown that temperature alone cannot realistically explain this process and that upslope tree advance in a warmer scenario may depend on the availability of sites with adequate geomorphic/topographic characteristics. Here, we show that, besides topography (slope and aspect), climate itself can produce a braking effect on the upslope advance of subalpine forests and that tree limit is influenced by non-linear and non-monotonic contributions of the climate variables which act upon treeline upslope advance with varying relative strengths. Our results suggest that global climate change impact on the upslope advance of subalpine forests should be interpreted in a more complex way where climate can both speed up and slow down the process depending on complex patterns of contribution from each climate and non-climate variable.

  4. Global simulations of smoke from Kuwaiti oil fires and possible effects on climate

    SciTech Connect

    Glatzmaier, G.A.; Malone, R.C.; Kao, C.Y.J.

    1991-12-31

    The Los Alamos Global Climate Model has bee used to simulate the global evolution of the Kuwaiti oil fire smoke and its potential effects on the climate. The initial simulations were done shortly before the fires were lit in January 1991. They indicated that such an event would not result in a ``Mini Nuclear Winter`` as some people were suggesting. Further simulations during the year suggested that the smoke could be responsible for subtle regional climate changes in the spring such as a 5 degree centigrade decrease in the surface temperature in Kuwait, a 10% decrease in precipitation in Saudi Arabia and a 10% increase in precipitation in the Tibetan Plateau region. These results are in qualitative agreement with the observations this year.

  5. How to infer the Sun's global magnetic field using the Hanle effect

    NASA Astrophysics Data System (ADS)

    Vieu, T.; Martínez González, M. J.; Pastor Yabar, A.; Asensio Ramos, A.

    2017-03-01

    We present a different approach to determine the characteristics of the global magnetic field of the Sun based on the study of the Hanle signals. The Hanle effect of a stellar dipole produces a surface asymmetric pattern of linear polarization that depends on the strength and geometry of this global field. Moreover, if the dipole is misaligned with respect to the rotation, the Hanle signals are modulated following the rotational period. We explore the possibility to retrieve those characteristics by comparing the computed theoretical signatures with actual observations. We show that this is possible, in the case of the Sr I line of the Sun, provided that the polarimetric sensitivity is of the order or below 10-5-10-6. The inference can be done either using the maps of resolved signals, in particular the spread of values obtained along different directions on the stellar disc, or using the disc-integrated signals.

  6. Climate change, global warming and coral reefs: modelling the effects of temperature.

    PubMed

    Crabbe, M James C

    2008-10-01

    Climate change and global warming have severe consequences for the survival of scleractinian (reef-building) corals and their associated ecosystems. This review summarizes recent literature on the influence of temperature on coral growth, coral bleaching, and modelling the effects of high temperature on corals. Satellite-based sea surface temperature (SST) and coral bleaching information available on the internet is an important tool in monitoring and modelling coral responses to temperature. Within the narrow temperature range for coral growth, corals can respond to rate of temperature change as well as to temperature per se. We need to continue to develop models of how non-steady-state processes such as global warming and climate change will affect coral reefs.

  7. Climate change in cities due to global warming and urban effects

    NASA Astrophysics Data System (ADS)

    McCarthy, Mark P.; Best, Martin J.; Betts, Richard A.

    2010-05-01

    Urbanisation is estimated to result in 6 billion urban dwellers by 2050. Cities will be exposed to climate change from greenhouse gas induced radiative forcing, and localised effects from urbanisation such as the urban heat island. An urban land-surface model has been included in the HadAM3 Global Climate Model. It shows that regions of high population growth coincide with regions of high urban heat island potential, most notably in the Middle East, the Indian sub-continent, and East Africa. Climate change has the capacity to modify the climatic potential for urban heat islands, with increases of 30% in some locations, but a global average reduction of 6%. Warming and extreme heat events due to urbanisation and increased energy consumption are simulated to be as large as the impact of doubled CO2 in some regions, and climate change increases the disparity in extreme hot nights between rural and urban areas.

  8. Geometric effects of global lateral heterogeneity on long-period surface wave propagation

    NASA Technical Reports Server (NTRS)

    Lay, T.; Kanamori, H.

    1985-01-01

    The present investigation has the objective to document examples of anomalous long-period surface wave amplitude behavior and to provide a preliminary appraisal of the effects of global lateral heterogeneity on surface wave propagation from a ray theory perspective. Attention is given to remarkable long-period surface wave anomalies described in literature, an equidistance azimuthal plot centered on the Iranian source region, Rayleigh wave and Love wave spectra for the 256-s period arrivals for the Tabas earthquake, constrained moment tensor and fault model inversion solutions ofr Iranian earthquakes, aspects of surface wave ray tracing, and a table of Rayleigh wave amplitude anomalies for Iranian earthquakes. Surface wave ray-tracing calculations for models of global phase velocity variations proposed by Nakanishi and Anderson (1984) are found to show that large-amplitude anomalies will be observed for Love and Rayleigh waves with periods of 100-250 s.

  9. The global need for effective antibiotics-a summary of plenary presentations.

    PubMed

    Alvan, Gunnar; Edlund, Charlotta; Heddini, Andreas

    2011-04-01

    To highlight the global need for effective antibiotics and explore possible concerted actions for change, cross-cutting plenary sessions served to frame the program of the conference. These sessions contained presentations on the present state of antibacterial resistance and the availability, the use and misuse of antibiotics. A number of possible actions were discussed, such as rational use of and access to antibiotics from various perspectives. The roles of vaccines and diagnostics were touched upon and followed by in depth discussions on supply-side bottlenecks with their scientific, regulatory and financial challenges. The value chain for research and development (R&D) of antibiotics has to be reengineered if we are to realize the development of much needed new antibiotics. This challenge will require a multitude of actions, some of which are related to changing the financial realities of antibiotics and interventions by global and regional institutions.

  10. Braking effect of climate and topography on global change-induced upslope forest expansion

    NASA Astrophysics Data System (ADS)

    Alatalo, Juha M.; Ferrarini, Alessandro

    2016-08-01

    Forests are expected to expand into alpine areas due to global climate change. It has recently been shown that temperature alone cannot realistically explain this process and that upslope tree advance in a warmer scenario may depend on the availability of sites with adequate geomorphic/topographic characteristics. Here, we show that, besides topography (slope and aspect), climate itself can produce a braking effect on the upslope advance of subalpine forests and that tree limit is influenced by non-linear and non-monotonic contributions of the climate variables which act upon treeline upslope advance with varying relative strengths. Our results suggest that global climate change impact on the upslope advance of subalpine forests should be interpreted in a more complex way where climate can both speed up and slow down the process depending on complex patterns of contribution from each climate and non-climate variable.

  11. Effects of local and global context on processing sentences with subject and object relative clauses.

    PubMed

    Yang, Fang; Mo, Lun; Louwerse, Max M

    2013-06-01

    An eye tracking study investigated the effects of local and global discourse context on the processing of subject and object relative clauses, whereby the contexts favored either a subject relative clause interpretation or an object relative clause interpretation. The fixation data replicated previous studies showing that object relative clause sentences were more difficult to process than subject relative sentences. Crucially, however, the reading difficulty asymmetry between subject and object relative clause sentences disappeared when the sentences were presented with a local or a global discourse context that favored the objects in the object relative clauses. These findings demonstrate that the evidence for a syntax-based account of sentence processing is found when sentences are presented in isolation. However, if sentences are placed more naturally, in context, discourse factors outweigh the initial structural assignment.

  12. Potential effects of global environmental changes on cryptosporidiosis and giardiasis transmission.

    PubMed

    Lal, Aparna; Baker, Michael G; Hales, Simon; French, Nigel P

    2013-02-01

    Global climate change will affect the viability and spread of zoonotic parasites, while agricultural land use changes will influence infection sources and reservoirs. The health impact of these environmental changes will depend on the social, economic and physical resilience of the population. This review describes the influence of climatic variability, land-use changes, and social factors on cryptosporidiosis and giardiasis in humans. Global to public health to individual-level interventions to reduce future disease burden are highlighted. Because future environmental change is expected to have the greatest health impacts in countries with limited resources, increasing research and adaptation capabilities in these regions is emphasized. Understanding how environmental and social processes interact to influence disease transmission is essential for the development of effective strategies for disease prevention.

  13. Global Economic Effects of USA Biofuel Policy and the Potential Contribution from Advanced Biofuels

    SciTech Connect

    Gbadebo Oladosu; Keith Kline; Paul Leiby; Rocio Uria-Martinez; Maggie Davis; Mark Downing; Laurence Eaton

    2012-01-01

    This study evaluates the global economic effects of the USA renewable fuel standards (RFS2), and the potential contribution from advanced biofuels. Our simulation results imply that these mandates lead to an increase of 0.21 percent in the global gross domestic product (GDP) in 2022, including an increase of 0.8 percent in the USA and 0.02 percent in the rest of the world (ROW); relative to our baseline, no-RFS scenario. The incremental contributions to GDP from advanced biofuels in 2022 are estimated at 0.41 percent and 0.04 percent in the USA and ROW, respectively. Although production costs of advanced biofuels are higher than for conventional biofuels in our model, their economic benefits result from reductions in oil use, and their smaller impacts on food markets compared with conventional biofuels. Thus, the USA advanced biofuels targets are expected to have positive economic benefits.

  14. Combined effects of global change pressures on animal-mediated pollination.

    PubMed

    González-Varo, Juan P; Biesmeijer, Jacobus C; Bommarco, Riccardo; Potts, Simon G; Schweiger, Oliver; Smith, Henrik G; Steffan-Dewenter, Ingolf; Szentgyörgyi, Hajnalka; Woyciechowski, Michał; Vilà, Montserrat

    2013-09-01

    Pollination is an essential process in the sexual reproduction of seed plants and a key ecosystem service to human welfare. Animal pollinators decline as a consequence of five major global change pressures: climate change, landscape alteration, agricultural intensification, non-native species, and spread of pathogens. These pressures, which differ in their biotic or abiotic nature and their spatiotemporal scales, can interact in nonadditive ways (synergistically or antagonistically), but are rarely considered together in studies of pollinator and/or pollination decline. Management actions aimed at buffering the impacts of a particular pressure could thereby prove ineffective if another pressure is present. Here, we focus on empirical evidence of the combined effects of global change pressures on pollination, highlighting gaps in current knowledge and future research needs.

  15. The global land shortwave cryosphere radiative effect during the MODIS era

    NASA Astrophysics Data System (ADS)

    Singh, D.; Flanner, M. G.; Perket, J.

    2015-11-01

    The shortwave cryosphere radiative effect (CrRE) is the instantaneous influence of snow and ice cover on Earth's top-of-atmosphere (TOA) solar energy budget. Here, we apply measurements from the MODerate resolution Imaging Spectroradiometer (MODIS), combined with microwave retrievals of snow presence and radiative kernels produced from four different models, to derive CrRE over global land during 2001-2013. We estimate global annual-mean land CrRE during this period of -2.6 W m-2, with variations from -2.2 to -3.0 W m-2 resulting from use of different kernels and variations of -2.4 to -2.6 W m-2 resulting from different algorithmic determinations of snow presence and surface albedo. Slightly more than half of the global land CrRE originates from perennial snow on Antarctica, whereas the majority of the northern hemispheric effect originates from seasonal snow. Consequently, the northern hemispheric land CrRE peaks at -6.0 W m-2 in April, whereas the southern hemispheric effect more closely follows the austral insolation cycle, peaking at -9.0 W m-2 in December. Mountain glaciers resolved in 0.05° MODIS data contribute about -0.037 W m-2 (1.4 %) of the global effect, with the majority (94 %) of this contribution originating from the Himalayas. Interannual trends in the global annual-mean land CrRE are not statistically significant during the MODIS era, but trends are positive (less negative) over large areas of northern Asia, especially during spring, and slightly negative over Antarctica, possibly due to increased snowfall. During a common overlap period of 2001-2008, our MODIS estimates of the northern hemispheric land CrRE are about 18 % smaller (less negative) than previous estimates derived from coarse-resolution AVHRR data, though interannual variations are well correlated (r = 0.78), indicating that these data are useful in determining longer-term trends in land CrRE.

  16. Global estimation of effective plant rooting depth: Implications for hydrological modeling

    NASA Astrophysics Data System (ADS)

    Yang, Yuting; Donohue, Randall J.; McVicar, Tim R.

    2016-10-01

    Plant rooting depth (Zr) is a key parameter in hydrological and biogeochemical models, yet the global spatial distribution of Zr is largely unknown due to the difficulties in its direct measurement. Additionally, Zr observations are usually only representative of a single plant or several plants, which can differ greatly from the effective Zr over a modeling unit (e.g., catchment or grid-box). Here, we provide a global parameterization of an analytical Zr model that balances the marginal carbon cost and benefit of deeper roots, and produce a climatological (i.e., 1982-2010 average) global Zr map. To test the Zr estimates, we apply the estimated Zr in a highly transparent hydrological model (i.e., the Budyko-Choudhury-Porporato (BCP) model) to estimate mean annual actual evapotranspiration (E) across the globe. We then compare the estimated E with both water balance-based E observations at 32 major catchments and satellite grid-box retrievals across the globe. Our results show that the BCP model, when implemented with Zr estimated herein, optimally reproduced the spatial pattern of E at both scales (i.e., R2 = 0.94, RMSD = 74 mm yr-1 for catchments, and R2 = 0.90, RMSD = 125 mm yr-1 for grid-boxes) and provides improved model outputs when compared to BCP model results from two already existing global Zr data sets. These results suggest that our Zr estimates can be effectively used in state-of-the-art hydrological models, and potentially biogeochemical models, where the determination of Zr currently largely relies on biome type-based look-up tables.

  17. Global markets and the differential effects of climate and weather on conflict

    NASA Astrophysics Data System (ADS)

    Meng, K. C.; Hsiang, S. M.; Cane, M. A.

    2011-12-01

    Both climate and weather have been attributed historically as possible drivers for violence. Previous empirical studies have either focused on isolating local idiosyncratic weather variation or have conflated weather with spatially coherent climatic changes. This paper provides the first study of the differential impacts of climate and weather variation by employing methods developed in earlier work linking the El Nino Southern Oscillation (ENSO) with the onset of civil conflicts. By separating the effects of climate from local weather, we are able to test possible mechanisms by which atmospheric changes can cause violence. It is generally difficult to separate the effect of year-to-year climate variations from other global events that might drive conflict. We avoid this problem by examining the set of tropical countries that are strongly teleconnected to ENSO. For this region, the ENSO cycle parallels the common year-to-year pattern of violence. Using ENSO, we isolate the influence of climatic changes from other global determinants of violence and compare it with the effect of local weather variations. We find that while climate affects the onset of civil conflicts in teleconnected countries, local weather has no significant effect. Productivity overall as well as across major sectors is more affected by local weather than by climatic variation. This is particularly evident in the agricultural sector where total value and cereal yield decline much greater from a 1°C increase in local temperature than a 1°C increase in ENSO. However, when examining the effect on food prices, we find that ENSO is associated with a large and statistically significant increase in cereal prices but no effect from hotter local temperatures. Altogether, this evidence points toward the ability of global and regional commodity markets to insure against the effects of local weather variation and their limitations in containing losses from aggregate shocks such as El Nino events. We posit

  18. Global, seasonal cloud variations from satellite radiance measurements. II - Cloud properties and radiative effects

    NASA Technical Reports Server (NTRS)

    Rossow, William B.; Lacis, Andrew A.

    1990-01-01

    Cloud and surface radiative properties and their effects on the earth and surface radiation budgets are obtained based on global daily visible and IR radiance measurements. The magnitude of cloud property variations and their effects on radiation increase strongly with decreasing space/time scales. Cloud properties are systematically different between land and ocean, with ocean having larger cloud cover with somewhat larger optical thicknesses and lower cloud top altitudes. Although cloud variations appear to be the primary cause of regional radiation budget variability at 5-30 daytime scales, the effects of their seasonal variations at larger spatial scales are less important than the changes associated with changes in solar declination and atmospheric/surface temperatures. The largest seasonal variations in radiation occur in the 30-60 deg latitude band in each hemisphere. Although clouds have a net cooling effect on the global, annual mean radiation balance at both the top of the atmosphere and the surface, their net effect on regional, seasonal balances is much more varied.

  19. The Effects of Instruction with Visual Materials on the Development of Preservice Elementary Teachers' Knowledge and Attitude towards Global Warming

    ERIC Educational Resources Information Center

    Bozdogan, Aykut Emre

    2011-01-01

    This study aimed to identify the erroneous knowledge and misconceptions of preservice elementary teachers about global warming and examine the effects of instruction with visual materials on rectifying these misconceptions and fostering a positive attitude towards the issue of global warming. Having a quasi-experimental design, the study made use…

  20. Modeling the Heterogeneous Effects of GHG Mitigation Policies on Global Agriculture and Forestry

    NASA Astrophysics Data System (ADS)

    Golub, A.; Henderson, B.; Hertel, T. W.; Rose, S. K.; Sohngen, B.

    2010-12-01

    agriculture and timber products. We analyze regional changes in land use, output, competitiveness, and food consumption under climate change mitigation policy regimes which differ by participation/exclusion of agricultural sectors and non-Annex I countries, as well as policy instruments. While responsible for only a third of global GHG emissions, under the global carbon tax the land using sectors could contribute half of all economically efficient mitigation in the near term, at modest carbon prices. The imposition of a carbon tax in agriculture, however, has adverse effects on food consumption, especially in developing countries. These effects are much smaller if an agricultural producer subsidy is introduced to compensate for carbon tax the producers pay. The global forest carbon sequestration subsidy effectively controls emission leakage when the carbon tax is imposed only in Annex I regions, since the sequestration subsidy bids land away from agriculture in non-Annex I regions. Though the sequestration subsidy yields GHG abatement benefit, the policy may adversely affect food security and agricultural development in developing countries.

  1. The Effects of Chinese Dietary Trends on Global and Local Land Use

    NASA Astrophysics Data System (ADS)

    Anthony, J.

    2015-12-01

    Global land scarcity is a major concern, which, due to climate change, lifestyle changes, and population growth, will only continue to worsen. It is a major driver of global environmental degradation, famine, and sociopolitical conflicts. With some 33% of the world's dwindling supply of arable land dedicated to grossly inefficient animal husbandry or animal feed production, it is easy to see that dietary consumption patterns play an important role. Although population growth in East Asia has stagnated, changing dietary trends mean that China is now the world's largest consumers of meat, consuming 25% of global meat production, despite having less than half of the American per capita equivalent. This paper assesses changing dietary consumption patterns of Taiwan, whose current per capita meat consumption surpasses all other East Asian countries, over the past 30 years and considers the relationship this has had on overall land consumption. We then consider dietary trends of Mainland China, which shares a common cultural heritage and whose current Purchasing Power Parity (PPP) is similar to Taiwanese PPP levels in 1985. Finally we retrospectively project three alternative Taiwanese consumption patterns over the past 30 years, consider the effect of each scenario on per capita land consumption, and finally consider these results in terms of culturally analogues Mainland China.

  2. Understanding the effects of global change on ecosystems of the Sonoran Desert

    SciTech Connect

    Halvorson, W.L. )

    1993-06-01

    The Global Change program for the Sonoran Desert just began in March 1992. Currently, two projects are being directly funded by the National Park Service and we are coordinating with research of other agencies. One thrust of the program is to understand the effect of climate on species growth, abundances and distribution. This will be done using a number of methods. One is growth ring analysis of conifers on mountain ranges in and bordering the Sonoran Desert. Another study will relate the USGS Desert Laboratory data base on plant species distributions to a mesoscale climate model. Other programs that we are coordinating with include a USGS Desert Laboratory project to study long term changes in plant communities of the southwest using a comparison of photos from the early 1930s, early 1960s and early 1990s. Other agencies have active global climate research at The University of Arizona and we are working to coordinate the NPS program with these at the investigator level through participation in a university-wide Global Change Committee.

  3. Economic impact of GM crops: the global income and production effects 1996-2012.

    PubMed

    Brookes, Graham; Barfoot, Peter

    2014-01-01

    A key part of any assessment of the global value of crop biotechnology in agriculture is an examination of its economic impact at the farm level. This paper follows earlier annual studies which examined economic impacts on yields, key costs of production, direct farm income and effects, and impacts on the production base of the four main crops of soybeans, corn, cotton and canola. The commercialization of genetically modified (GM) crops has continued to occur at a rapid rate, with important changes in both the overall level of adoption and impact occurring in 2012. This annual updated analysis shows that there have been very significant net economic benefits at the farm level amounting to $18.8 billion in 2012 and $116.6 billion for the 17-year period (in nominal terms). These economic gains have been divided roughly 50% each to farmers in developed and developing countries. GM technology have also made important contributions to increasing global production levels of the four main crops, having added 122 million tonnes and 230 million tonnes respectively, to the global production of soybeans and maize since the introduction of the technology in the mid-1990s.

  4. The income and production effects of biotech crops globally 1996-2010.

    PubMed

    Brookes, Graham; Barfoot, Peter

    2012-01-01

    A critical feature in evaluating the global value of crop biotechnology in agriculture must include an assessment of its economic impact at the farm level. This paper follows earlier studies which examined economic impacts on yields, key costs of production, direct farm income, indirect (non-pecuniary) farm level income effects and impacts on the production base of the four main crops of soybeans, corn, cotton and canola. The commercialization of biotech crops is continuing to proceed rapidly, with significant changes in the overall level of adoption and impact taking place in 2010. This updated analysis shows that there have been substantial net economic benefits at the farm level amounting to $14 billion in 2010 and $78.4 billion for the 15-year period (in nominal terms). The non-pecuniary benefits associated with the use of the technology have also had a positive impact on adoption (in the US accounting for the equivalent of 22% of the total US direct farm income benefit). Biotech crops are, moreover, making important contributions to increasing global production levels of the four main crops. They have, for example, now added 97.5 million tons and 159 million tons respectively, to the global production of soybeans and corn since the introduction of the technology in the mid-1990s.

  5. The global income and production effects of genetically modified (GM) crops 1996-2011.

    PubMed

    Brookes, Graham; Barfoot, Peter

    2013-01-01

    A key part of any assessment of the global value of crop biotechnology in agriculture is an examination of its economic impact at the farm level. This paper follows earlier annual studies which examined economic impacts on yields, key costs of production, direct farm income and effects and impacts on the production base of the four main crops of soybeans, corn, cotton and canola. The commercialization of genetically modified (GM) crops has continued to occur at a rapid rate, with important changes in both the overall level of adoption and impact occurring in 2011. This annual updated analysis shows that there have been very significant net economic benefits at the farm level amounting to $19.8 billion in 2011 and $98.2 billion for the 16 year period (in nominal terms). The majority (51.2%) of these gains went to farmers in developing countries. GM technology have also made important contributions to increasing global production levels of the four main crops, having added 110 million tonnes and 195 million tonnes respectively, to the global production of soybeans and maize since the introduction of the technology in the mid-1990s.

  6. Rapid growth in agricultural trade: effects on global area efficiency and the role of management

    NASA Astrophysics Data System (ADS)

    Kastner, Thomas; Erb, Karl-Heinz; Haberl, Helmut

    2014-03-01

    Cropland is crucial for supplying humans with biomass products, above all, food. Globalization has led to soaring volumes of international trade, resulting in strongly increasing distances between the locations where land use takes place and where the products are consumed. Based on a dataset that allows tracing the flows of almost 450 crop and livestock products and consistently allocating them to cropland areas in over 200 nations, we analyze this rapidly growing spatial disconnect between production and consumption for the period from 1986 to 2009. At the global level, land for export production grew rapidly (by about 100 Mha), while land supplying crops for direct domestic use remained virtually unchanged. We show that international trade on average flows from high-yield to low-yield regions: compared to a hypothetical no-trade counterfactual that assumes equal consumption and yield levels, trade lowered global cropland demand by almost 90 Mha in 2008 (3-year mean). An analysis using yield gap data (which quantify the distance of prevailing yields to those attainable through the best currently available production techniques) revealed that differences in land management and in natural endowments contribute almost equally to the yield differences between exporting and importing nations. A comparison of the effect of yield differences between exporting and importing regions with the potential of closing yield gaps suggests that increasing yields holds greater potentials for reducing future cropland demand than increasing and adjusting trade volumes based on differences in current land productivity.

  7. Revisiting Aerosol Effects in Global Climate Models Using an Aerosol Lidar Simulator

    NASA Astrophysics Data System (ADS)

    Ma, P. L.; Chepfer, H.; Winker, D. M.; Ghan, S.; Rasch, P. J.

    2015-12-01

    Aerosol effects are considered a major source of uncertainty in global climate models and the direct and indirect radiative forcings have strong model dependency. These forcings are routinely evaluated (and calibrated) against observations, among them satellite retrievals are greatly used for their near-global coverage. However, the forcings calculated from model output are not directly comparable with those computed from satellite retrievals since sampling and algorithmic differences (such as cloud screening, noise reduction, and retrieval) between models and observations are not accounted for. It is our hypothesis that the conventional model validation procedures for comparing satellite observations and model simulations can mislead model development and introduce biases. Hence, we have developed an aerosol lidar simulator for global climate models that simulates the CALIOP lidar signal at 532nm. The simulator uses the same algorithms as those used to produce the "GCM-oriented CALIPSO Aerosol Product" to (1) objectively sample lidar signal profiles; and (2) derive aerosol fields (e.g., extinction profile, aerosol type, etc) from lidar signals. This allows us to sample and derive aerosol fields in the model and real atmosphere in identical ways. Using the Department of Energy's ACME model simulations, we found that the simulator-retrieved aerosol distribution and aerosol-cloud interactions are significantly different from those computed from conventional approaches, and that the model is much closer to satellite estimates than previously believed.

  8. Effects of interactive global changes on methane uptake in an annual grassland

    NASA Astrophysics Data System (ADS)

    Blankinship, Joseph C.; Brown, Jamie R.; Dijkstra, Paul; Hungate, Bruce A.

    2010-06-01

    The future size of the terrestrial methane (CH4) sink of upland soils remains uncertain, along with potential feedbacks to global warming. Much of the uncertainty lies in our lack of knowledge about potential interactive effects of multiple simultaneous global environmental changes. Field CH4 fluxes and laboratory soil CH4 consumption were measured five times during 3 consecutive years in a California annual grassland exposed to 8 years of the full factorial combination of ambient and elevated levels of precipitation, temperature, atmospheric CO2 concentration, and N deposition. Across all sampling dates and treatments, increased precipitation caused a 61% reduction in field CH4 uptake. However, this reduction depended quantitatively on other global change factors. Higher precipitation reduced CH4 uptake when temperature or N deposition (but not both) increased, and under elevated CO2 but only late in the growing season. Warming alone also decreased CH4 uptake early in the growing season, which was partly explained by a decrease in laboratory soil CH4 consumption. Atmospheric CH4 models likely need to incorporate nonadditive interactions, seasonal interactions, and interactions between methanotrophy and methanogenesis. Despite the complexity of interactions we observed in this multifactor experiment, the outcome agrees with results from single-factor experiments: an increased terrestrial CH4 sink appears less likely than a reduced one.

  9. Effects of Global Warming on Ancient Mammalian Communities and Their Environments

    PubMed Central

    DeSantis, Larisa R. G.; Feranec, Robert S.; MacFadden, Bruce J.

    2009-01-01

    Background Current global warming affects the composition and dynamics of mammalian communities and can increase extinction risk; however, long-term effects of warming on mammals are less understood. Dietary reconstructions inferred from stable isotopes of fossil herbivorous mammalian tooth enamel document environmental and climatic changes in ancient ecosystems, including C3/C4 transitions and relative seasonality. Methodology/Principal Findings Here, we use stable carbon and oxygen isotopes preserved in fossil teeth to document the magnitude of mammalian dietary shifts and ancient floral change during geologically documented glacial and interglacial periods during the Pliocene (∼1.9 million years ago) and Pleistocene (∼1.3 million years ago) in Florida. Stable isotope data demonstrate increased aridity, increased C4 grass consumption, inter-faunal dietary partitioning, increased isotopic niche breadth of mixed feeders, niche partitioning of phylogenetically similar taxa, and differences in relative seasonality with warming. Conclusion/Significance Our data show that global warming resulted in dramatic vegetation and dietary changes even at lower latitudes (∼28°N). Our results also question the use of models that predict the long term decline and extinction of species based on the assumption that niches are conserved over time. These findings have immediate relevance to clarifying possible biotic responses to current global warming in modern ecosystems. PMID:19492043

  10. Effects of Chemical Aging on Global Secondary Organic Aerosol using the Volatility Basis Set Approach

    NASA Astrophysics Data System (ADS)

    Park, R.; Jo, D.; Kim, M.; Spracklen, D. V.; Hodzic, A.

    2014-12-01

    Organic aerosol (OA) constitutes significant mass fractions (20-90%) of total dry fine aerosols in the atmosphere. However, global models of OA have shown large discrepancies when compared to the observations because of the limited capability to simulate secondary OA (SOA). For reducing the discrepancies between observations and models, recent studies have shown that chemical aging reactions in the atmosphere are important because they can lead to decreases in organic volatility, resulting in increase of SOA mass yields. To efficiently simulate chemical aging of SOA in the atmosphere, we implemented the volatility basis set approach in a global 3-D chemical transport model (GEOS-Chem). We present full-year simulations and their comparisons with multiple observations - global aerosol mass spectrometer dataset, the Interagency Monitoring of Protected Visual Environments from the United States, the European Monitoring and Evaluation Programme dataset and water-soluble organic carbon observation data collected over East Asia. Using different input parameters in the model, we also explore the uncertainty of the SOA simulation for which we use an observational constraint to find the optimized values with which the model reduces the discrepancy from the observations. Finally, we estimate the effect of OA on climate using our best simulation results.

  11. Effect of Age on Variability in the Production of Text-Based Global Inferences

    PubMed Central

    Williams, Lynne J.; Dunlop, Joseph P.; Abdi, Hervé

    2012-01-01

    As we age, our differences in cognitive skills become more visible, an effect especially true for memory and problem solving skills (i.e., fluid intelligence). However, by contrast with fluid intelligence, few studies have examined variability in measures that rely on one’s world knowledge (i.e., crystallized intelligence). The current study investigated whether age increased the variability in text based global inference generation–a measure of crystallized intelligence. Global inference generation requires the integration of textual information and world knowledge and can be expressed as a gist or lesson. Variability in generating two global inferences for a single text was examined in young-old (62 to 69 years), middle-old (70 to 76 years) and old-old (77 to 94 years) adults. The older two groups showed greater variability, with the middle elderly group being most variable. These findings suggest that variability may be a characteristic of both fluid and crystallized intelligence in aging. PMID:22590523

  12. Effect of chronic heroin and cocaine administration on global DNA methylation in brain and liver.

    PubMed

    Fragou, Domniki; Zanos, Panos; Kouidou, Sofia; Njau, Samuel; Kitchen, Ian; Bailey, Alexis; Kovatsi, Leda

    2013-04-26

    Drug abuse is associated with epigenetic changes, such as histone modifications and DNA methylation. The purpose of the present study was to examine the effect of chronic cocaine and heroin administration on global DNA methylation in brain and liver. Male, 8 week old, C57BL/6J mice received heroin in a chronic 'intermittent' escalating dose paradigm, or cocaine in a chronic escalating dose 'binge' paradigm, which mimic the human pattern of opioid or cocaine abuse respectively. Following sacrifice, livers and brains were removed and DNA was extracted from them. The extracted DNA was hydrolyzed and 2'-deoxycytidine and 5-methyl-2'-deoxycytidine were determined by HPLC-UV. The % 5-methyl-2'-deoxycytidine content of DNA was significantly higher in the brain compared to the liver. There were no differences between the control animals and the cocaine or heroin treated animals in neither of the tissues examined, which is surprising since cocaine administration induced gross morphological changes in the liver. Moreover, there was no difference in the % 5-methyl-2'-deoxycytidine content of DNA between the cocaine and the heroin treated animals. The global DNA methylation status in the brain and liver of mice chronically treated with cocaine or heroin remains unaffected, but this finding cannot exclude the existence of anatomical region or gene-specific methylation differences. This is the first time that global DNA methylation in the liver and whole brain has been studied following chronic cocaine or heroin treatment.

  13. The effect of density stratification on the prediction of global storm surges

    NASA Astrophysics Data System (ADS)

    Kodaira, Tsubasa; Thompson, Keith R.; Bernier, Natacha B.

    2016-12-01

    With the long-term goal of developing an operational forecast system for total water level, we conduct a hindcast study of global storm surges for Fall 2014 using a baroclinic ocean model based on the NEMO framework. The model has 19 vertical levels, a horizontal resolution of 1/12°, and is forced by hourly forecasts of atmospheric wind and air pressure. Our first objective is to evaluate the model's ability to predict hourly sea levels recorded by a global array of 257 tide gauges. It is shown that the model can provide reasonable predictions of surges for the whole test period at tide gauges with relatively large tidal residuals (i.e., gauges where the standard deviation of observed sea level, after removal of the tide, exceeds 5 cm). Our second objective is to quantify the effect of density stratification on the prediction of global surges. It is found that the inclusion of density stratification increases the overall predictive skill at almost all tide gauges. The increase in skill for the instantaneous peak surge is smaller. The location for which the increase in overall skill is largest (east coast of South Africa) is discussed in detail and physical reasons for the improvement are given.

  14. Global MHD simulations of Mercury's magnetosphere with coupled planetary interior: Induction effect of the planetary conducting core on the global interaction

    NASA Astrophysics Data System (ADS)

    Jia, Xianzhe; Slavin, James A.; Gombosi, Tamas I.; Daldorff, Lars K. S.; Toth, Gabor; Holst, Bart

    2015-06-01

    Mercury's comparatively weak intrinsic magnetic field and its close proximity to the Sun lead to a magnetosphere that undergoes more direct space-weathering interactions than other planets. A unique aspect of Mercury's interaction system arises from the large ratio of the scale of the planet to the scale of the magnetosphere and the presence of a large-size core composed of highly conducting material. Consequently, there is strong feedback between the planetary interior and the magnetosphere, especially under conditions of strong external forcing. Understanding the coupled solar wind-magnetosphere-interior interaction at Mercury requires not only analysis of observations but also a modeling framework that is both comprehensive and inclusive. We have developed a new global MHD model for Mercury in which the planetary interior is modeled as layers of different electrical conductivities that electromagnetically couple to the surrounding plasma environment. This new modeling capability allows us to characterize the dynamical response of Mercury to time-varying external conditions in a self-consistent manner. Comparison of our model results with observations by the MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft shows that the model provides a reasonably good representation of the global magnetosphere. To demonstrate the capability to model induction effects, we have performed idealized simulations in which Mercury's magnetosphere is impacted by a solar wind pressure enhancement. Our results show that due to the induction effect, Mercury's core exerts strong global influences on the way Mercury responds to changes in the external environment, including modifying the global magnetospheric structure and affecting the extent to which the solar wind directly impacts the surface. The global MHD model presented here represents a crucial step toward establishing a modeling framework that enables self-consistent characterization of Mercury

  15. Integration of Extended MHD and Kinetic Effects in Global Magnetosphere Models

    NASA Astrophysics Data System (ADS)

    Germaschewski, K.; Wang, L.; Maynard, K. R. M.; Raeder, J.; Bhattacharjee, A.

    2015-12-01

    Computational models of Earth's geospace environment are an important tool to investigate the science of the coupled solar-wind -- magnetosphere -- ionosphere system, complementing satellite and ground observations with a global perspective. They are also crucial in understanding and predicting space weather, in particular under extreme conditions. Traditionally, global models have employed the one-fluid MHD approximation, which captures large-scale dynamics quite well. However, in Earth's nearly collisionless plasma environment it breaks down on small scales, where ion and electron dynamics and kinetic effects become important, and greatly change the reconnection dynamics. A number of approaches have recently been taken to advance global modeling, e.g., including multiple ion species, adding Hall physics in a Generalized Ohm's Law, embedding local PIC simulations into a larger fluid domain and also some work on simulating the entire system with hybrid or fully kinetic models, the latter however being to computationally expensive to be run at realistic parameters. We will present an alternate approach, ie., a multi-fluid moment model that is derived rigorously from the Vlasov-Maxwell system. The advantage is that the computational cost remains managable, as we are still solving fluid equations. While the evolution equation for each moment is exact, it depends on the next higher-order moment, so that truncating the hiearchy and closing the system to capture the essential kinetic physics is crucial. We implement 5-moment (density, momentum, scalar pressure) and 10-moment (includes pressure tensor) versions of the model, and use local approximations for the heat flux to close the system. We test these closures by local simulations where we can compare directly to PIC / hybrid codes, and employ them in global simulations using the next-generation OpenGGCM to contrast them to MHD / Hall-MHD results and compare with observations.

  16. Direct effect of aerosol optical properties on global dimming and brightening

    NASA Astrophysics Data System (ADS)

    Kudo, R.; Uchiyama, A.

    2011-12-01

    Surface solar radiation observed at numerous locations has decreased from the 1960s to the 1980s (Global dimming), thereafter increased (Global brightening). The dimming and brightening is considered to be due to the changes in both clouds and aerosols. Aerosols have a direct impact on the surface solar radiation by scattering and absorption. The impact is determined by three parameters: optical depth (AOD), single scattering albedo (SSA), and asymmetry factor, but the effect of asymmetry factor is rather smaller than the others. Therefore, the long-term changes in AOD and SSA are necessary to evaluate the aerosol impact on the global dimming and brightening. We have developed the method to estimate AOD and SSA from the hourly accumulated direct and diffuse irradiances measured by the ground-based broadband radiometers. In the estimation, the real part of the refractive index is fixed, and the size distribution is defined by the Junge distribution with a fixed shaping constant. Using the developed method, the measurements from 1975 to 2008 at 14 sites in Japan were analyzed. Consequently, a decrease of AOD by 0.02 and an increase of SSA by 0.2 during the period were seen. The surface solar radiation under the clear sky conditions, which was calculated from the estimated aerosol optical properties, was increased by 5% due to the changes in AOD and SSA; the influence of SSA was dominant. We also investigate the cloud impact on the surface solar radiation which was simply defined as the difference between the surface solar radiation under the cloudy sky conditions and under the clear sky conditions; the cloud impact had no statistically significant trends. The brightening in Japan may be due to the changes in aerosol optical properties, especially SSA. Our developed method can be applied to measurements at other sites around the world and would be helpful to understand the causes of the global dimming and brightening.

  17. Muon g-2 estimates: can one trust effective Lagrangians and global fits?

    NASA Astrophysics Data System (ADS)

    Benayoun, M.; David, P.; DelBuono, L.; Jegerlehner, F.

    2015-12-01

    Previous studies have shown that the Hidden Local Symmetry (HLS) model, supplied with appropriate symmetry breaking mechanisms, provides an effective Lagrangian (Broken Hidden Local Symmetry, BHLS) which encompasses a large number of processes within a unified framework. Based on it, a global fit procedure allows for a simultaneous description of the e^+ e^- annihilation into six final states—π ^+π ^-, π ^0γ , η γ , π ^+π ^-π ^0, K^+K^-, K_L K_S—and includes the dipion spectrum in the τ decay and some more light meson decay partial widths. The contribution to the muon anomalous magnetic moment a_{μ }^{th} of these annihilation channels over the range of validity of the HLS model (up to 1.05 GeV) is found much improved in comparison to the standard approach of integrating the measured spectra directly. However, because most spectra for the annihilation process e^+e^- → π ^+π ^- undergo overall scale uncertainties which dominate the other sources, one may suspect some bias in the dipion contribution to a_{μ }^{th}, which could question the reliability of the global fit method. However, an iterated global fit algorithm, shown to lead to unbiased results by a Monte Carlo study, is defined and applied successfully to the e^+e^- → π ^+π ^- data samples from CMD2, SND, KLOE, BaBar, and BESSIII. The iterated fit solution is shown to further improve the prediction for a_{μ }, which we find to deviate from its experimental value above the 4σ level. The contribution to a_{μ } of the π ^+π ^- intermediate state up to 1.05 GeV has an uncertainty about 3 times smaller than the corresponding usual estimate. Therefore, global fit techniques are shown to work and lead to improved unbiased results.

  18. Global and Regional Decreases in Tropospheric Oxidants from Photochemical Effects of Aerosols

    NASA Technical Reports Server (NTRS)

    Martin, Randall V.; Jacob, Daniel J.; Yantosca, Robert M.; Chin, Mian; Ginoux, Paul

    2003-01-01

    We evaluate the sensitivity of tropospheric OH, O3, and O3 precursors to photochemical effects of aerosols not usually included in global models: (1) aerosol scattering and absorption of ultraviolet radiation and (2) reactive uptake of HO', NO2, and NO3. Our approach is to couple a global 3-D model of tropospheric chemistry (GEOS- CHEM) with aerosol fields from a global 3-D aerosol model (GOCART). Reactive uptake by aerosols is computed using reaction probabilities from a recent review (gamma(sub HO2) = 0.2, gamma(sub NO2) = 10(exp -4), gamma(sub NO3) = l0(exp -3). Aerosols decrease the O3 - O((sup 1)D) photolysis frequency by 5-20% at the surface throughout the Northern Hemisphere (largely due to mineral dust) and by a factor of 2 in biomass burning regions (largely due to black carbon). Aerosol uptake of HO2 accounts for 10-40% of total HOx radical ((triple bonds)OH + peroxy) loss in the boundary layer over polluted continental regions (largely due to sulfate and organic carbon) and for more than 70% over tropical biomass burning regions (largely due to organic carbon). Uptake of NO2 and NO3 accounts for 10-20% of total HNO3 production over biomass burning regions and less elsewhere. Annual mean OH concentrations decrease by 9% globally and by 5-35% in the boundary layer over the Northern Hemisphere. Simulated CO increases by 5- 15 ppbv in the remote Northern Hemisphere, improving agreement with observations. Simulated boundary layer O3 decreases by 15- 45 ppbv over India during the biomass burning season in March and by 5-9 ppbv over northern Europe in August, again improving comparison with observations. We find that particulate matter controls would increase surface O3 over Europe and other industrial regions.

  19. New Regional and Global HFC Projections and Effects of National Regulations and Montreal Protocol Amendment Proposals

    NASA Astrophysics Data System (ADS)

    Velders, G. J. M.

    2015-12-01

    Hydrofluorocarbons (HFCs) are used as substitutes for ozone-depleting substances that are being phased out globally under Montreal Protocol regulations. New global scenarios of HFC emissions reach 4.0-5.3 GtCO2-eq yr-1 in 2050, which corresponds to a projected growth from 2015 to 2050 which is 9% to 29% of that for CO2 over the same time period. New baseline scenarios are formulated for 10 HFC compounds, 11 geographic regions, and 13 use categories. These projections are the first to comprehensively assess production and consumption of individual HFCs in multiple use sectors and geographic regions with emission estimates constrained by atmospheric observations. In 2050, in percent of global HFC emissions, China (~30%), India and the rest of Asia (~25%), Middle East and northern Africa (~10%), and USA (~10%) are the principal source regions; and refrigeration and stationary air conditioning are the major use sectors. National regulations to limit HFC use have been adopted recently in the European Union, Japan and USA, and four proposals have been submitted in 2015 to amend the Montreal Protocol to substantially reduce growth in HFC use. Calculated baseline emissions are reduced by 90% in 2050 by implementing the North America Montreal Protocol amendment proposal. Global adoption of technologies required to meet national regulations would be sufficient to reduce 2050 baseline HFC consumption by more than 50% of that achieved with the North America proposal for most developed and developing countries. The new HFC scenarios and effects of national regulations and Montreal Protocol amendment proposals will be presented.

  20. Influence of Ice Particle Surface Roughening on the Global Cloud Radiative Effect

    NASA Technical Reports Server (NTRS)

    Yi, Bingqi; Yang, Ping; Baum, Bryan A.; LEcuyer, Tristan; Oreopoulos, Lazaros; Mlawer, Eli J.; Heymsfield, Andrew J.; Liou, Kuo-Nan

    2013-01-01

    Ice clouds influence the climate system by changing the radiation budget and large-scale circulation. Therefore, climate models need to have an accurate representation of ice clouds and their radiative effects. In this paper, new broadband parameterizations for ice cloud bulk scattering properties are developed for severely roughened ice particles. The parameterizations are based on a general habit mixture that includes nine habits (droxtals, hollow/solid columns, plates, solid/hollow bullet rosettes, aggregate of solid columns, and small/large aggregates of plates). The scattering properties for these individual habits incorporate recent advances in light-scattering computations. The influence of ice particle surface roughness on the ice cloud radiative effect is determined through simulations with the Fu-Liou and the GCM version of the Rapid Radiative Transfer Model (RRTMG) codes and the National Center for Atmospheric Research Community Atmosphere Model (CAM, version 5.1). The differences in shortwave (SW) and longwave (LW) radiative effect at both the top of the atmosphere and the surface are determined for smooth and severely roughened ice particles. While the influence of particle roughening on the single-scattering properties is negligible in the LW, the results indicate that ice crystal roughness can change the SW forcing locally by more than 10 W m(exp -2) over a range of effective diameters. The global-averaged SW cloud radiative effect due to ice particle surface roughness is estimated to be roughly 1-2 W m(exp -2). The CAM results indicate that ice particle roughening can result in a large regional SW radiative effect and a small but nonnegligible increase in the global LW cloud radiative effect.

  1. Phosphoproteomic Analysis of KSHV-Infected Cells Reveals Roles of ORF45-Activated RSK during Lytic Replication

    PubMed Central

    Avey, Denis; Tepper, Sarah; Li, Wenwei; Turpin, Zachary; Zhu, Fanxiu

    2015-01-01

    Kaposi’s Sarcoma-Associated Herpesvirus (KSHV) is an oncogenic virus which has adapted unique mechanisms to modulate the cellular microenvironment of its human host. The pathogenesis of KSHV is intimately linked to its manipulation of cellular signaling pathways, including the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway. We have previously shown that KSHV ORF45 contributes to the sustained activation of both ERK and p90 ribosomal S6 kinase (RSK, a major functional mediator of ERK/MAPK signaling) during KSHV lytic replication. ORF45-activated RSK is required for optimal KSHV lytic gene expression and progeny virion production, though the underlying mechanisms downstream of this activation are still unclear. We hypothesized that the activation of RSK by ORF45 causes differential phosphorylation of cellular and viral substrates, affecting biological processes essential for efficient KSHV lytic replication. Accordingly, we observed widespread and significant differences in protein phosphorylation upon induction of lytic replication. Mass-spectrometry-based