Phosphotyrosine-based-phosphoproteomics scaled-down to biopsy level for analysis of individual tumor biology and treatment selection.

PubMed

Labots, Mariette; van der Mijn, Johannes C; Beekhof, Robin; Piersma, Sander R; de Goeij-de Haas, Richard R; Pham, Thang V; Knol, Jaco C; Dekker, Henk; van Grieken, Nicole C T; Verheul, Henk M W; Jiménez, Connie R

2017-06-06

Mass spectrometry-based phosphoproteomics of cancer cell and tissue lysates provides insight in aberrantly activated signaling pathways and potential drug targets. For improved understanding of individual patient's tumor biology and to allow selection of tyrosine kinase inhibitors in individual patients, phosphoproteomics of small clinical samples should be feasible and reproducible. We aimed to scale down a pTyr-phosphopeptide enrichment protocol to biopsy-level protein input and assess reproducibility and applicability to tumor needle biopsies. To this end, phosphopeptide immunoprecipitation using anti-phosphotyrosine beads was performed using 10, 5 and 1mg protein input from lysates of colorectal cancer (CRC) cell line HCT116. Multiple needle biopsies from 7 human CRC resection specimens were analyzed at the 1mg-level. The total number of phosphopeptides captured and detected by LC-MS/MS ranged from 681 at 10mg input to 471 at 1mg HCT116 protein. ID-reproducibility ranged from 60.5% at 10mg to 43.9% at 1mg. Per 1mg-level biopsy sample, >200 phosphopeptides were identified with 57% ID-reproducibility between paired tumor biopsies. Unsupervised analysis clustered biopsies from individual patients together and revealed known and potential therapeutic targets. This study demonstrates the feasibility of label-free pTyr-phosphoproteomics at the tumor biopsy level based on reproducible analyses using 1mg of protein input. The considerable number of identified phosphopeptides at this level is attributed to an effective down-scaled immuno-affinity protocol as well as to the application of ID propagation in the data processing and analysis steps. Unsupervised cluster analysis reveals patient-specific profiles. Together, these findings pave the way for clinical trials in which pTyr-phosphoproteomics will be performed on pre- and on-treatment biopsies. Such studies will improve our understanding of individual tumor biology and may enable future pTyr-phosphoproteomics

Sensitive kinase assay linked with phosphoproteomics for identifying direct kinase substrates

PubMed Central

Xue, Liang; Wang, Wen-Horng; Iliuk, Anton; Hu, Lianghai; Galan, Jacob A.; Yu, Shuai; Hans, Michael; Geahlen, Robert L.; Tao, W. Andy

2012-01-01

Our understanding of the molecular control of many disease pathologies requires the identification of direct substrates targeted by specific protein kinases. Here we describe an integrated proteomic strategy, termed kinase assay linked with phosphoproteomics, which combines a sensitive kinase reaction with endogenous kinase-dependent phosphoproteomics to identify direct substrates of protein kinases. The unique in vitro kinase reaction is carried out in a highly efficient manner using a pool of peptides derived directly from cellular kinase substrates and then dephosphorylated as substrate candidates. The resulting newly phosphorylated peptides are then isolated and identified by mass spectrometry. A further comparison of these in vitro phosphorylated peptides with phosphopeptides derived from endogenous proteins isolated from cells in which the kinase is either active or inhibited reveals new candidate protein substrates. The kinase assay linked with phosphoproteomics strategy was applied to identify unique substrates of spleen tyrosine kinase (Syk), a protein-tyrosine kinase with duel properties of an oncogene and a tumor suppressor in distinctive cell types. We identified 64 and 23 direct substrates of Syk specific to B cells and breast cancer cells, respectively. Both known and unique substrates, including multiple centrosomal substrates for Syk, were identified, supporting a unique mechanism that Syk negatively affects cell division through its centrosomal kinase activity. PMID:22451900

Quantitative phosphoproteomic analysis of porcine muscle within 24 h postmortem.

PubMed

Huang, Honggang; Larsen, Martin R; Palmisano, Giuseppe; Dai, Jie; Lametsch, René

2014-06-25

Protein phosphorylation can regulate most of the important processes in muscle, such as metabolism and contraction. The postmortem (PM) metabolism and rigor mortis have essential effects on meat quality. In order to identify and characterize the protein phosphorylation events involved in meat quality development, a quantitative mass spectrometry-based phosphoproteomic study was performed to analyze the porcine muscle within 24h PM using dimethyl labeling combined with the TiSH phosphopeptide enrichment strategy. In total 305 unique proteins were identified, including 160 phosphoproteins with 784 phosphorylation sites. Among these, 184 phosphorylation sites on 93 proteins had their phosphorylation levels significantly changed. The proteins involved in glucose metabolism and muscle contraction were the two largest clusters of phosphoproteins with significantly changed phosphorylation levels in muscle within 24 h PM. The high phosphorylation level of heat shock proteins (HSPs) in early PM may be an adaptive response to slaughter stress and protect muscle cell from apoptosis, as observed in the serine 84 of HSP27. This work indicated that PM muscle proteins underwent significant changes at the phosphorylation level but were relatively stable at the total protein level, suggesting that protein phosphorylation may have important roles in meat quality development through the regulation of proteins involved in glucose metabolism and muscle contraction, thereby affecting glycolysis and rigor mortis development in PM muscle. The manuscript describes the characterization of postmortem (PM) porcine muscle within 24 h postmortem from the perspective of protein phosphorylation using advanced phosphoproteomic techniques. In the study, the authors employed the dimethyl labeling combined with the TiSH phosphopeptide enrichment and LC-MS/MS strategy. This was the first high-throughput quantitative phosphoproteomic study in PM muscle of farm animals. In the work, both the proteome

Construction of large signaling pathways using an adaptive perturbation approach with phosphoproteomic data.

PubMed

Melas, Ioannis N; Mitsos, Alexander; Messinis, Dimitris E; Weiss, Thomas S; Rodriguez, Julio-Saez; Alexopoulos, Leonidas G

2012-04-01

Construction of large and cell-specific signaling pathways is essential to understand information processing under normal and pathological conditions. On this front, gene-based approaches offer the advantage of large pathway exploration whereas phosphoproteomic approaches offer a more reliable view of pathway activities but are applicable to small pathway sizes. In this paper, we demonstrate an experimentally adaptive approach to construct large signaling pathways from phosphoproteomic data within a 3-day time frame. Our approach--taking advantage of the fast turnaround time of the xMAP technology--is carried out in four steps: (i) screen optimal pathway inducers, (ii) select the responsive ones, (iii) combine them in a combinatorial fashion to construct a phosphoproteomic dataset, and (iv) optimize a reduced generic pathway via an Integer Linear Programming formulation. As a case study, we uncover novel players and their corresponding pathways in primary human hepatocytes by interrogating the signal transduction downstream of 81 receptors of interest and constructing a detailed model for the responsive part of the network comprising 177 species (of which 14 are measured) and 365 interactions.

Activation of Human Peripheral Blood Eosinophils by Cytokines in a Comparative Time-Course Proteomic/Phosphoproteomic Study.

PubMed

Soman, Kizhake V; Stafford, Susan J; Pazdrak, Konrad; Wu, Zheng; Luo, Xuemei; White, Wendy I; Wiktorowicz, John E; Calhoun, William J; Kurosky, Alexander

2017-08-04

Activated eosinophils contribute to airway dysfunction and tissue remodeling in asthma and thus are considered to be important factors in asthma pathology. We report here comparative proteomic and phosphoproteomic changes upon activation of eosinophils using eight cytokines individually and in selected cytokine combinations in time-course reactions. Differential protein and phosphoprotein expressions were determined by mass spectrometry after 2-dimensional gel electrophoresis (2DGE) and by LC-MS/MS. We found that each cytokine-stimulation produced significantly different changes in the eosinophil proteome and phosphoproteome, with phosphoproteomic changes being more pronounced and having an earlier onset. Furthermore, we observed that IL-5, GM-CSF, and IL-3 showed the greatest change in protein expression and phosphorylation, and this expression differed markedly from those of the other five cytokines evaluated. Comprehensive univariate and multivariate statistical analyses were employed to evaluate the comparative results. We also monitored eosinophil activation using flow cytometry (FC) analysis of CD69. In agreement with our proteomic studies, FC indicated that IL-5, GM-CSF, and IL-3 were more effective than the other five cytokines studied in stimulating a cell surface CD69 increase indicative of eosinophil activation. Moreover, selected combinations of cytokines revealed proteomic patterns with many proteins in common with single cytokine expression patterns but also showed a greater effect of the two cytokines employed, indicating a more complex signaling pathway that was reflective of a more typical inflammatory pathology.

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). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Phosphoproteomic analysis of chromoplasts from sweet orange during fruit ripening.

PubMed

Zeng, Yunliu; Pan, Zhiyong; Wang, Lun; Ding, Yuduan; Xu, Qiang; Xiao, Shunyuan; Deng, Xiuxin

2014-02-01

Like other types of plastids, chromoplasts have essential biosynthetic and metabolic activities which may be regulated via post-translational modifications, such as phosphorylation, of their resident proteins. We here report a proteome-wide mapping of in vivo phosphorylation sites in chromoplast-enriched samples prepared from sweet orange [Citrus sinensis (L.) Osbeck] at different ripening stages by titanium dioxide-based affinity chromatography for phosphoprotein enrichment with LC-MS/MS. A total of 109 plastid-localized phosphoprotein candidates were identified that correspond to 179 unique phosphorylation sites in 135 phosphopeptides. On the basis of Motif-X analysis, two distinct types of phosphorylation sites, one as proline-directed phosphorylation motif and the other as casein kinase II motif, can be generalized from these identified phosphopeptides. While most identified phosphoproteins show high homology to those already identified in plastids, approximately 22% of them are novel based on BLAST search using the public databases PhosPhAt and P(3) DB. A close comparative analysis showed that approximately 50% of the phosphoproteins identified in citrus chromoplasts find obvious counterparts in the chloroplast phosphoproteome, suggesting a rather high-level of conservation in basic metabolic activities in these two types of plastids. Not surprisingly, the phosphoproteome of citrus chromoplasts is also characterized by the lack of phosphoproteins involved in photosynthesis and by the presence of more phosphoproteins implicated in stress/redox responses. This study presents the first comprehensive phosphoproteomic analysis of chromoplasts and may help to understand how phosphorylation regulates differentiation of citrus chromoplasts during fruit ripening. © 2013 Scandinavian Plant Physiology Society.

Phosphoproteome of Pristionchus pacificus provides insights into architecture of signaling networks in nematode models.

PubMed

Borchert, Nadine; Krug, Karsten; Gnad, Florian; Sinha, Amit; Sommer, Ralf J; Macek, Boris

2012-12-01

Pristionchus pacificus is a nematode that is increasingly used as a model organism in evolutionary biology. The genome of P. pacificus differs markedly from that of C. elegans, with a high number of orphan genes that are restricted to P. pacificus and have no homologs in other species. To gain insight into the architecture of signal transduction networks in model nematodes, we performed a large-scale qualitative phosphoproteome analysis of P. pacificus. Using two-stage enrichment of phosphopeptides from a digest of P. pacificus proteins and their subsequent analysis via high accuracy MS, we detected and localized 6,809 phosphorylation events on 2,508 proteins. We compared the detected P. pacificus phosphoproteome to the recently published phosphoproteome of C. elegans. The overall numbers and functional classes of phosphoproteins were similar between the two organisms. Interestingly, the products of orphan genes were significantly underrepresented among the detected P. pacificus phosphoproteins. We defined the theoretical kinome of P. pacificus and compared it to that of C. elegans. While tyrosine kinases were slightly underrepresented in the kinome of P. pacificus, all major classes of kinases were present in both organisms. Application of our kinome annotation to a recent transcriptomic study of dauer and mixed stage populations showed that Ser/Thr and Tyr kinases show similar expression levels in P. pacificus but not in C. elegans. This study presents the first systematic comparison of phosphoproteomes and kinomes of two model nematodes and, as such, will be a useful resource for comparative studies of their signal transduction networks.

Is Phosphoproteomics Ready for Clinical Research?

PubMed Central

Iliuk, Anton B.; Tao, W. Andy

2012-01-01

Background For many diseases such as cancer where phosphorylation-dependent signaling is the foundation of disease onset and progression, single-gene testing and genomic profiling alone are not sufficient in providing most critical information. The reason for this is that in these activated pathways the signaling changes and drug resistance are often not directly correlated with changes in protein expression levels. In order to obtain the essential information needed to evaluate pathway activation or the effects of certain drugs and therapies on the molecular level, the analysis of changes in protein phosphorylation is critical. Methods Existing approaches do not differentiate clinical disease subtypes on the protein and signaling pathway level, and therefore hamper the predictive management of the disease and the selection of therapeutic targets. Conclusions The mini-review examines the impact of emerging systems biology tools and the possibility of applying phosphoproteomics to clinical research. PMID:23159844

Global Phosphoproteomics of Activated B Cells Using Complementary Metal Ion Functionalized Soluble Nanopolymers

PubMed Central

2015-01-01

Engagement of the B cell receptor for antigen (BCR) leads to immune responses through a cascade of intracellular signaling events. Most studies to date have focused on the BCR and protein tyrosine phosphorylation. Because spleen tyrosine kinase, Syk, is an upstream kinase in multiple BCR-regulated signaling pathways, it also affects many downstream events that are modulated through the phosphorylation of proteins on serine and threonine residues. Here, we report a novel phosphopeptide enrichment strategy and its application to a comprehensive quantitative phosphoproteomics analysis of Syk-dependent downstream signaling events in B cells, focusing on serine and threonine phosphorylation. Using a combination of the Syk inhibitor piceatannol, SILAC quantification, peptide fractionation, and complementary PolyMAC-Ti and PolyMAC-Zr enrichment techniques, we analyzed changes in BCR-stimulated protein phosphorylation that were dependent on the activity of Syk. We identified and quantified over 13 000 unique phosphopeptides, with a large percentage dependent on Syk activity in BCR-stimulated B cells. Our results not only confirmed many known functions of Syk, but more importantly, suggested many novel roles, including in the ubiquitin proteasome pathway, that warrant further exploration. PMID:24905233

Proteomes and Phosphoproteomes of Anther and Pollen: Availability and Progress.

PubMed

Zhang, Zaibao; Hu, Menghui; Feng, Xiaobing; Gong, Andong; Cheng, Lin; Yuan, Hongyu

2017-10-01

In flowering plants, anther development plays crucial role in sexual reproduction. Within the anther, microspore mother cells meiosis produces microspores, which further develop into pollen grains that play decisive role in plant reproduction. Previous studies on anther biology mainly focused on single gene functions relying on genetic and molecular methods. Recently, anther development has been expanded from multiple OMICS approaches like transcriptomics, proteomics/phosphoproteomics, and metabolomics. The development of proteomics techniques allowing increased proteome coverage and quantitative measurements of proteins which can characterize proteomes and their modulation during normal development, biotic and abiotic stresses in anther development. In this review, we summarize the achievements of proteomics and phosphoproteomics with anther and pollen organs from model plant and crop species (i.e. Arabidopsis, rice, tobacco). The increased proteomic information facilitated translation of information from the models to crops and thus aid in agricultural improvement. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Phosphoproteomic biomarkers predicting histologic nonalcoholic steatohepatitis and fibrosis.

PubMed

Younossi, Zobair M; Baranova, Ancha; Stepanova, Maria; Page, Sandra; Calvert, Valerie S; Afendy, Arian; Goodman, Zachary; Chandhoke, Vikas; Liotta, Lance; Petricoin, Emanuel

2010-06-04

The progression of nonalcoholic fatty liver disease (NAFLD) has been linked to deregulated exchange of the endocrine signaling between adipose and liver tissue. Proteomic assays for the phosphorylation events that characterize the activated or deactivated state of the kinase-driven signaling cascades in visceral adipose tissue (VAT) could shed light on the pathogenesis of nonalcoholic steatohepatitis (NASH) and related fibrosis. Reverse-phase protein microarrays (RPMA) were used to develop biomarkers for NASH and fibrosis using VAT collected from 167 NAFLD patients (training cohort, N = 117; testing cohort, N = 50). Three types of models were developed for NASH and advanced fibrosis: clinical models, proteomics models, and combination models. NASH was predicted by a model that included measurements of two components of the insulin signaling pathway: AKT kinase and insulin receptor substrate 1 (IRS1). The models for fibrosis were less reliable when predictions were based on phosphoproteomic, clinical, or the combination data. The best performing model relied on levels of the phosphorylation of GSK3 as well as on two subunits of cyclic AMP regulated protein kinase A (PKA). Phosphoproteomics technology could potentially be used to provide pathogenic information about NASH and NASH-related fibrosis. This information can lead to a clinically relevant diagnostic/prognostic biomarker for NASH.

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.

Exploring G protein-coupled receptor signaling networks using SILAC-based phosphoproteomics

PubMed Central

Williams, Grace R.; Bethard, Jennifer R.; Berkaw, Mary N.; Nagel, Alexis K.; Luttrell, Louis M.; Ball, Lauren E.

2015-01-01

The type 1 parathyroid hormone receptor (PTH1R) is a key regulator of calcium homeostasis and bone turnover. Here, we employed SILAC-based quantitative mass spectrometry combined with bioinformatic pathways analysis to examine global changes in protein phosphorylation following short-term stimulation of endogenously expressed PTH1R in osteoblastic cells in vitro. Following 5 min exposure to the conventional agonist, PTH(1-34), we detected significant changes in the phosphorylation of 224 distinct proteins. Kinase substrate motif enrichment demonstrated that consensus motifs for PKA and CAMK2 were the most heavily upregulated within the phosphoproteome, while consensus motifs for mitogen-activated protein kinases were strongly downregulated. Signaling pathways analysis identified ERK1/2 and AKT as important nodal kinases in the downstream network and revealed strong regulation of small GTPases involved in cytoskeletal rearrangement, cell motility, and focal adhesion complex signaling. Our data illustrate the utility of quantitative mass spectrometry in measuring dynamic changes in protein phosphorylation following GPCR activation. PMID:26160508

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].

Quantitative phosphoproteomic analysis of RIP3-dependent protein phosphorylation in the course of TNF-induced necroptosis.

PubMed

Zhong, Chuan-Qi; Li, Yuanyue; Yang, Daowei; Zhang, Na; Xu, Xiaozheng; Wu, Yaying; Chen, Jinan; Han, Jiahuai

2014-03-01

Tumor necrosis factor (TNF) induced cell death in murine fibrosarcoma L929 cells is a model system in studying programed necrosis (also known as necroptosis). Receptor interacting protein 3 (RIP3), a serine-threonine kinase, is known to play an essential role in TNF-induced necroptosis; however, the phosphorylation events initiated by RIP3 activation in necroptotic process is still largely unknown. Here, we performed a quantitative MS based analysis to compare TNF-induced changes in the global phosphoproteome of wild-type (RIP3(+/+) ) and RIP3-knockdown L929 cells at different time points after TNF treatment. A total of 8058 phosphopeptides spanning 6892 phosphorylation sites in 2762 proteins were identified in the three experiments, in which cells were treated with TNF for 0.5, 2, and 4 h. By comparing the phosphorylation sites in wild-type and RIP3-knockdown L929 cells, 174, 167, and 177 distinct phosphorylation sites were revealed to be dependent on RIP3 at the 0.5, 2, and 4 h time points after TNF treatment, respectively. Notably, most of them were not detected in a previous phosphoproteomic analysis of RIP3-dependent phosphorylation in lipopolysaccharide-stimulated peritoneal macrophages and TNF-treated murine embryonic fibroblasts (MEFs), suggesting that the data presented in this report are highly relevant to the study of TNF-induced necroptosis of L929 cells. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

PubMed Central

Adams, Nancy E.; Maurelli, Anthony T.

2015-01-01

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. PMID:25998263

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.

Phosphoproteomics and Bioinformatics Analyses of Spinal Cord Proteins in Rats with Morphine Tolerance

PubMed Central

Liaw, Wen-Jinn; Tsao, Cheng-Ming; Huang, Go-Shine; Wu, Chin-Chen; Ho, Shung-Tai; Wang, Jhi-Joung; Tao, Yuan-Xiang; Shui, Hao-Ai

2014-01-01

Introduction Morphine is the most effective pain-relieving drug, but it can cause unwanted side effects. Direct neuraxial administration of morphine to spinal cord not only can provide effective, reliable pain relief but also can prevent the development of supraspinal side effects. However, repeated neuraxial administration of morphine may still lead to morphine tolerance. Methods To better understand the mechanism that causes morphine tolerance, we induced tolerance in rats at the spinal cord level by giving them twice-daily injections of morphine (20 µg/10 µL) for 4 days. We confirmed tolerance by measuring paw withdrawal latencies and maximal possible analgesic effect of morphine on day 5. We then carried out phosphoproteomic analysis to investigate the global phosphorylation of spinal proteins associated with morphine tolerance. Finally, pull-down assays were used to identify phosphorylated types and sites of 14-3-3 proteins, and bioinformatics was applied to predict biological networks impacted by the morphine-regulated proteins. Results Our proteomics data showed that repeated morphine treatment altered phosphorylation of 10 proteins in the spinal cord. Pull-down assays identified 2 serine/threonine phosphorylated sites in 14-3-3 proteins. Bioinformatics further revealed that morphine impacted on cytoskeletal reorganization, neuroplasticity, protein folding and modulation, signal transduction and biomolecular metabolism. Conclusions Repeated morphine administration may affect multiple biological networks by altering protein phosphorylation. These data may provide insight into the mechanism that underlies the development of morphine tolerance. PMID:24392096

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chan, Chi Yuet X’avia; Gritsenko, Marina A.; Smith, Richard D.

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 phosphoproteomicsmore » in diabetes research.« less

Quantitative Phosphoproteomic Analysis of Soybean Root Hairs Inoculated with Bradyrhizobium japonicum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nguyen, Tran H.; Brechenmacher, Laurent; Aldrich, Joshua T.

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 insightmore » 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.« less

Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer.

PubMed

Francavilla, Chiara; Lupia, Michela; Tsafou, Kalliopi; Villa, Alessandra; Kowalczyk, Katarzyna; Rakownikow Jersie-Christensen, Rosa; Bertalot, Giovanni; Confalonieri, Stefano; Brunak, Søren; Jensen, Lars J; Cavallaro, Ugo; Olsen, Jesper V

2017-03-28

Our understanding of the molecular determinants of cancer is still inadequate because of cancer heterogeneity. Here, using epithelial ovarian cancer (EOC) as a model system, we analyzed a minute amount of patient-derived epithelial cells from either healthy or cancerous tissues by single-shot mass-spectrometry-based phosphoproteomics. Using a multi-disciplinary approach, we demonstrated that primary cells recapitulate tissue complexity and represent a valuable source of differentially expressed proteins and phosphorylation sites that discriminate cancer from healthy cells. Furthermore, we uncovered kinase signatures associated with EOC. In particular, CDK7 targets were characterized in both EOC primary cells and ovarian cancer cell lines. We showed that CDK7 controls cell proliferation and that pharmacological inhibition of CDK7 selectively represses EOC cell proliferation. Our approach defines the molecular landscape of EOC, paving the way for efficient therapeutic approaches for patients. Finally, we highlight the potential of phosphoproteomics to identify clinically relevant and druggable pathways in cancer. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Tissue phosphoproteomics with PolyMAC identifies potential therapeutic targets in a transgenic mouse model of HER2 positive breast cancer

PubMed Central

Searleman, Adam C.; Iliuk, Anton B.; Collier, Timothy S.; Chodosh, Lewis A.; Tao, W. Andy; Bose, Ron

2014-01-01

Altered protein phosphorylation is a feature of many human cancers that can be targeted therapeutically. Phosphopeptide enrichment is a critical step for maximizing the depth of phosphoproteome coverage by MS, but remains challenging for tissue specimens because of their high complexity. We describe the first analysis of a tissue phosphoproteome using polymer-based metal ion affinity capture (PolyMAC), a nanopolymer that has excellent yield and specificity for phosphopeptide enrichment, on a transgenic mouse model of HER2-driven breast cancer. By combining phosphotyrosine immunoprecipitation with PolyMAC, 411 unique peptides with 139 phosphotyrosine, 45 phosphoserine, and 29 phosphothreonine sites were identified from five LC-MS/MS runs. Combining reverse phase liquid chromatography fractionation at pH 8.0 with PolyMAC identified 1571 unique peptides with 1279 phosphoserine, 213 phosphothreonine, and 21 phosphotyrosine sites from eight LC-MS/MS runs. Linear motif analysis indicated that many of the phosphosites correspond to well-known phosphorylation motifs. Analysis of the tyrosine phosphoproteome with the Drug Gene Interaction database uncovered a network of potential therapeutic targets centered on Src family kinases with inhibitors that are either FDA-approved or in clinical development. These results demonstrate that PolyMAC is well suited for phosphoproteomic analysis of tissue specimens. PMID:24723360

Phosphoproteomics links glycogen synthase kinase-3 to RNA splicing.

PubMed

Khoa, Le Tran Phuc; Dou, Yali

2017-11-03

Protein kinases play essential biological roles by phosphorylating a diverse range of signaling molecules, but deciphering their direct physiological targets remains a challenge. A new study by Shinde et al. uses phosphoproteomics to identify glycogen synthase kinase-3 (GSK-3) substrates in mouse embryonic stem cells (mESCs), providing a broad profile of GSK-3 activity and defining a new role for this central kinase in regulating RNA splicing. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Quantitative Label-Free Phosphoproteomics Reveals Differentially Regulated Protein Phosphorylation Involved in West Nile Virus-Induced Host Inflammatory Response.

PubMed

Zhang, Hao; Sun, Jun; Ye, Jing; Ashraf, Usama; Chen, Zheng; Zhu, Bibo; He, Wen; Xu, Qiuping; Wei, Yanming; Chen, Huanchun; Fu, Zhen F; Liu, Rong; Cao, Shengbo

2015-12-04

West Nile virus (WNV) can cause neuro-invasive and febrile illness that may be fatal to humans. The production of inflammatory cytokines is key to mediating WNV-induced immunopathology in the central nervous system. Elucidating the host factors utilized by WNV for productive infection would provide valuable insights into the evasion strategies used by this virus. Although attempts have been made to determine these host factors, proteomic data depicting WNV-host protein interactions are limited. We applied liquid chromatography-tandem mass spectrometry for label-free, quantitative phosphoproteomics to systematically investigate the global phosphorylation events induced by WNV infection. Quantifiable changes to 1,657 phosphoproteins were found; of these, 626 were significantly upregulated and 227 were downregulated at 12 h postinfection. The phosphoproteomic data were subjected to gene ontology enrichment analysis, which returned the inflammation-related spliceosome, ErbB, mitogen-activated protein kinase, nuclear factor kappa B, and mechanistic target of rapamycin signaling pathways. We used short interfering RNAs to decrease the levels of glycogen synthase kinase-3 beta, bifunctional polynucleotide phosphatase/kinase, and retinoblastoma 1 and found that the activity of nuclear factor kappa B (p65) is significantly decreased in WNV-infected U251 cells, which in turn led to markedly reduced inflammatory cytokine production. Our results provide a better understanding of the host response to WNV infection and highlight multiple targets for the development of antiviral and anti-inflammatory therapies.

Age-Dependent Effects of Acute Alcohol Administration in the Hippocampal Phosphoproteome.

PubMed

Contreras, Ana; Morales, Lidia; Tebourbi, Ali; Miguéns, Miguel; Olmo, Nuria Del; Pérez-García, Carmen

2017-12-18

Alcohol consumption during adolescence is deleterious to the developing brain and leads to persistent deficits in adulthood. Several results provide strong evidence for ethanol-associated alterations in glutamatergic signaling and impaired synaptic plasticity in the hippocampus. Protein phosphorylation is a well-known and well-documented mechanism in memory processes, but information on phosphoprotein alterations in hippocampus after ethanol exposure is limited. This study focuses on age-related changes in the hippocampal phosphoproteome after acute alcohol administration. We have compared the phosphoprotein expression in the hippocampus of adult and adolescent Wistar rats treated with a single dose of ethanol (5 g/kg i.p.), using a proteomic approach including phosphoprotein enrichment by immobilized metal affinity chromatography (IMAC). Our proteomic analysis revealed that 13 proteins were differentially affected by age, ethanol administration, or both. Most of these proteins are involved in neuroprotection and are expressed less in young rats treated with ethanol. We conclude that acute alcohol induces important changes in the expression of phosphoproteins in the hippocampus that could increase the risk of neurodegenerative disorders, especially when the alcohol exposure begins in adolescence.

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

Unbiased phosphoproteomic method identifies the initial effects of a methacrylic acid copolymer on macrophages

PubMed Central

Chamberlain, Michael Dean; Wells, Laura A.; Lisovsky, Alexandra; Guo, Hongbo; Isserlin, Ruth; Talior-Volodarsky, Ilana; Mahou, Redouan; Emili, Andrew; Sefton, Michael V.

2015-01-01

An unbiased phosphoproteomic method was used to identify biomaterial-associated changes in the phosphorylation patterns of macrophage-like cells. The phosphorylation differences between differentiated THP1 (dTHP1) cells treated for 10, 20, or 30 min with a vascular regenerative methacrylic acid (MAA) copolymer or a control methyl methacrylate (MM) copolymer were determined by MS. There were 1,470 peptides (corresponding to 729 proteins) that were differentially phosphorylated in dTHP1 cells treated with the two materials with a greater cellular response to MAA treatment. In addition to identifying pathways (such as integrin signaling and cytoskeletal arrangement) that are well known to change with cell–material interaction, previously unidentified pathways, such as apoptosis and mRNA splicing, were also discovered. PMID:26261332

Phosphoproteome and transcription factor activity profiling identify actions of the anti-inflammatory agent UTL-5g in LPS stimulated RAW 264.7 cells including disrupting actin remodeling and STAT-3 activation.

PubMed

Carruthers, Nicholas J; Stemmer, Paul M; Chen, Ben; Valeriote, Frederick; Gao, Xiaohua; Guatam, Subhash C; Shaw, Jiajiu

2017-09-15

UTL-5g is a novel small-molecule TNF-alpha modulator. It reduces cisplatin-induced side effects by protecting kidney, liver, and platelets, thereby increasing tolerance for cisplatin. UTL-5g also reduces radiation-induced acute liver toxicity. The mechanism of action for UTL-5g is not clear at the present time. A phosphoproteomic analysis to a depth of 4943 phosphopeptides and a luminescence-based transcription factor activity assay were used to provide complementary analyses of signaling events that were disrupted by UTL-5g in RAW 264.7 cells. Transcriptional activity downstream of the interferon gamma, IL-6, type 1 Interferon, TGF-β, PKC/Ca 2+ and the glucocorticoid receptor pathways were disrupted by UTL-5g. Phosphoproteomic analysis indicated that hyperphosphorylation of proteins involved in actin remodeling was suppressed by UTL-5g (gene set analysis, FDR < 1%) as was phosphorylation of Stat3, consistent with the IL-6 results in the transcription factor assay. Neither analysis indicated that LPS-induced activation of the NF-kB, cAMP/PKA and JNK signaling pathways were affected by UTL-5g. This global characterization of UTL-5g activity in a macrophage cell line discovered that it disrupts selected aspects of LPS signaling including Stat3 activation and actin remodeling providing new insight on how UTL-5g acts to reduce cisplatin-induced side effects. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

Chen, Kai; Lv, Fan; Xu, Guofeng; Zhang, Min; Wu, Yeming; Wu, Zhixiang

2016-11-15

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.

Phosphoproteome of the Oleaginous Green Alga, Chlorella vulgaris UTEX 395, under Nitrogen-Replete and -Deplete Conditions

DOE PAGES

Guarnieri, Michael T.; Gerritsen, Alida T.; Henard, Calvin A.; ...

2018-03-06

The unicellular green alga, Chlorella vulgaris UTEX 395, represents a promising biocatalyst for renewable biofuel production due to its relatively rapid growth rate and high lipid accumulation capacity (Guarnieri et al., 2011, 2012; Gerken et al., 2013; Griffiths et al., 2014; Zuniga et al., 2016). Prior analyses have unveiled the global proteome dynamics of C. vulgaris following nitrogen depletion, which induces a high lipid accumulation phenotype (Guarnieri et al., 2011, 2013). More recently, we have reported a draft genome, genome-scale model, and nitrosoproteome for this alga (Zuniga et al., 2016; Henard et al., 2017)1 providing further insight into lipid biosynthetic-,more » nutrient response-, and post-transcriptional-regulatory mechanisms. To further our understanding of these regulatory mechanisms and expand the knowledge base surrounding this organism, comparative phosphoproteomic analyses were conducted under nitrogen-replete and -deplete conditions to identify differentially phosphorylated proteins that will aid in the evaluation of the potential role of phosphoregulation in lipogenesis.« less

Phosphoproteome of the Oleaginous Green Alga, Chlorella vulgaris UTEX 395, under Nitrogen-Replete and -Deplete Conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guarnieri, Michael T.; Gerritsen, Alida T.; Henard, Calvin A.

The unicellular green alga, Chlorella vulgaris UTEX 395, represents a promising biocatalyst for renewable biofuel production due to its relatively rapid growth rate and high lipid accumulation capacity (Guarnieri et al., 2011, 2012; Gerken et al., 2013; Griffiths et al., 2014; Zuniga et al., 2016). Prior analyses have unveiled the global proteome dynamics of C. vulgaris following nitrogen depletion, which induces a high lipid accumulation phenotype (Guarnieri et al., 2011, 2013). More recently, we have reported a draft genome, genome-scale model, and nitrosoproteome for this alga (Zuniga et al., 2016; Henard et al., 2017)1 providing further insight into lipid biosynthetic-,more » nutrient response-, and post-transcriptional-regulatory mechanisms. To further our understanding of these regulatory mechanisms and expand the knowledge base surrounding this organism, comparative phosphoproteomic analyses were conducted under nitrogen-replete and -deplete conditions to identify differentially phosphorylated proteins that will aid in the evaluation of the potential role of phosphoregulation in lipogenesis.« less

Quantitative Phosphoproteomics Dissection of Seven-transmembrane Receptor Signaling Using Full and Biased Agonists*

PubMed Central

Christensen, Gitte L.; Kelstrup, Christian D.; Lyngsø, Christina; Sarwar, Uzma; Bøgebo, Rikke; Sheikh, Søren P.; Gammeltoft, Steen; Olsen, Jesper V.; Hansen, Jakob L.

2010-01-01

Seven-transmembrane receptors (7TMRs) signal through the well described heterotrimeric G proteins but can also activate G protein-independent signaling pathways of which the impact and complexity are less understood. The angiotensin II type 1 receptor (AT1R) is a prototypical 7TMR and an important drug target in cardiovascular diseases. “Biased agonists” with intrinsic “functional selectivity” that simultaneously blocks Gαq protein activity and activates G protein-independent pathways of the AT1R confer important perspectives in treatment of cardiovascular diseases. In this study, we performed a global quantitative phosphoproteomics analysis of the AT1R signaling network. We analyzed ligand-stimulated SILAC (stable isotope labeling by amino acids in cell culture) cells by high resolution (LTQ-Orbitrap) MS and compared the phosphoproteomes of the AT1R agonist angiotensin II and the biased agonist [Sar1,Ile4,Ile8]angiotensin II (SII angiotensin II), which only activates the Gαq protein-independent signaling. We quantified more than 10,000 phosphorylation sites of which 1183 were regulated by angiotensin II or its analogue SII angiotensin II. 36% of the AT1R-regulated phosphorylations were regulated by SII angiotensin II. Analysis of phosphorylation site patterns showed a striking distinction between protein kinases activated by Gαq protein-dependent and -independent mechanisms, and we now place protein kinase D as a key protein involved in both Gαq-dependent and -independent AT1R signaling. This study provides substantial novel insight into angiotensin II signal transduction and is the first study dissecting the differences between a full agonist and a biased agonist from a 7TMR on a systems-wide scale. Importantly, it reveals a previously unappreciated diversity and quantity of Gαq protein-independent signaling and uncovers novel signaling pathways. We foresee that the amount and diversity of G protein-independent signaling may be more pronounced than

Global Phosphoproteomic Analysis of Insulin/Akt/mTORC1/S6K Signaling in Rat Hepatocytes.

PubMed

Zhang, Yuanyuan; Zhang, Yajie; Yu, Yonghao

2017-08-04

Insulin resistance is a hallmark of type 2 diabetes. Although multiple genetic and physiological factors interact to cause insulin resistance, deregulated signaling by phosphorylation is a common underlying mechanism. In particular, the specific phosphorylation-dependent regulatory mechanisms and signaling outputs of insulin are poorly understood in hepatocytes, which represents one of the most important insulin-responsive cell types. Using primary rat hepatocytes as a model system, we performed reductive dimethylation (ReDi)-based quantitative mass spectrometric analysis and characterized the phosphoproteome that is regulated by insulin as well as its key downstream kinases including Akt, mTORC1, and S6K. We identified a total of 12 294 unique, confidently localized phosphorylation sites and 3805 phosphorylated proteins in this single cell type. Detailed bioinformatic analysis on each individual data set identified both known and previously unrecognized targets of this key insulin downstream effector pathway. Furthermore, integrated analysis of the hepatic Akt/mTORC1/S6K signaling axis allowed the delineation of the substrate specificity of several close-related kinases within the insulin signaling pathway. We expect that the data sets will serve as an invaluable resource, providing the foundation for future hypothesis-driven research that helps delineate the molecular mechanisms that underlie the pathogenesis of type 2 diabetes and related metabolic syndrome.

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

Phosphoproteomic analysis of the posterior silk gland of Bombyx mori provides novel insight into phosphorylation regulating the silk production.

PubMed

Song, Jia; Che, Jiaqian; You, Zhengying; Ye, Lupeng; Li, Jisheng; Zhang, Yuyu; Qian, Qiujie; Zhong, Boxiong

2016-10-04

To understand phosphorylation event regulating silk synthesis in the posterior silk gland of Bombyx mori, phosphoproteome was profiled in a pair of near-isogenic lines, a normally cocooning strain (IC) and a nakedly pupated strain (IN) that the silk production is much lower than IC. In the posterior silk gland of the IC and IN, 714 and 658 phosphosites resided on 554 and 507 phosphopeptides from 431 and 383 phosphoproteins, were identified, respectively. Of all the phosphosites, the single phosphosite was the dominate phosphorylation form, comprising>60% of all the phosphosites in two phenotypic of silk production. All these phosphosites were classified as acidophilic and proline-directed kinase classes, and three motifs were uniquely identified in the IC. The motif S-P-P might be important for regulating phosphorylation network of silk protein synthesis. The dynamically phosphorylated proteins participated in ribosome, protein transport and energy metabolism suggest that phosphorylation may play key roles in regulating silk protein synthesis and secretion. Furthermore, fibroin heavy chain, an important component of silk protein, was specifically phosphorylated in the IC strain, suggesting its role to ensure the normal formation of silk structure and silk secretion. The data gain new understanding of the regulatory processes of silk protein synthesis and offer as starting point for further research on the silk production at phosphoproteome level. Despite the knowledge on regulation of silk protein synthesis in the posterior silk gland has gained at the gene or protein levels, how phosphorylation event influences the silk yield is largely unknown. To this end, we constructed a pair of silkworm near-isogenic lines that showed different cocooning phenotypes, and the phosphoproteome of the posterior silk gland of two isolines was compared. Here, we reported the first phosphoproteome data on the silkworm and found several key pathways related protein synthesis are

Quantitative phosphoproteome on the silkworm (Bombyx mori) cells infected with baculovirus.

PubMed

Shobahah, Jauharotus; Xue, Shengjie; Hu, Dongbing; Zhao, Cui; Wei, Ming; Quan, Yanping; Yu, Wei

2017-06-19

Bombyx mori has become an important model organism for many fundamental studies. Bombyx mori nucleopolyhedrovirus (BmNPV) is a significant pathogen to Bombyx mori, yet also an efficient vector for recombinant protein production. A previous study indicated that acetylation plays many vital roles in several cellular processes of Bombyx mori while global phosphorylation pattern upon BmNPV infection remains elusive. Employing tandem mass tag (TMT) labeling and phosphorylation affinity enrichment followed by high-resolution LC-MS/MS analysis and intensive bioinformatics analysis, the quantitative phosphoproteome in Bombyx mori cells infected by BmNPV at 24 hpi with an MOI of 10 was extensively examined. Totally, 6480 phosphorylation sites in 2112 protein groups were identified, among which 4764 sites in 1717 proteins were quantified. Among the quantified proteins, 81 up-regulated and 25 down-regulated sites were identified with significant criteria (the quantitative ratio above 1.3 was considered as up-regulation and below 0.77 was considered as down-regulation) and with significant p-value (p < 0.05). Some proteins of BmNPV were also hyperphosphorylated during infection, such as P6.9, 39 K, LEF-6, Ac58-like protein, Ac82-like protein and BRO-D. The phosphorylated proteins were primary involved in several specific functions, out of which, we focused on the binding activity, protein synthesis, viral replication and apoptosis through kinase activity.

Quantitation of the phosphoproteome using the library-assisted extracted ion chromatogram (LAXIC) strategy.

PubMed

Arrington, Justine V; Xue, Liang; Tao, W Andy

2014-01-01

Phosphorylation is a key posttranslational modification that regulates many signaling pathways, but quantifying changes in phosphorylation between samples can be challenging due to its low stoichiometry within cells. We have introduced a mass spectrometry-based label-free quantitation strategy termed LAXIC for the analysis of the phosphoproteome. This method uses a spiked-in synthetic peptide library designed to elute across the entire chromatogram for local normalization of phosphopeptides within complex samples. Normalization of phosphopeptides by library peptides that co-elute within a small time frame accounts for fluctuating ion suppression effects, allowing more accurate quantitation even when LC-MS performance varies. Here we explain the premise of LAXIC, the design of a suitable peptide library, and how the LAXIC algorithm can be implemented with software developed in-house.

Global proteome and phosphoproteome dynamics indicate novel mechanisms of vitamin C induced dormancy in Mycobacterium smegmatis.

PubMed

Albeldas, Claudia; Ganief, Naadir; Calder, Bridget; Nakedi, Kehilwe C; Garnett, Shaun; Nel, Andrew J M; Blackburn, Jonathan M; Soares, Nelson C

2018-05-30

Vitamin C has been found to affect mycobacteria in multiple ways, including increasing susceptibility to antimicrobial drugs, inducing dormancy, and having a bactericidal effect. However, the regulatory events mediating vitamin C related adaptations remain largely elusive. Ser/Thr/Tyr protein phosphorylation plays an important regulatory role in mycobacteria, contributing to environmental adaptation, including dormancy and drug resistance. This study utilised the model organism, Mycobacterium smegmatis, and TiO 2 phosphopeptide enrichment combined with mass spectrometry-based proteomics methods to elucidate the mycobacterial signalling and regulatory response to sub-lethal concentrations of vitamin C. After initial validation of peptide spectra, 224 non-redundant phosphosites in 154 proteins were retained with high confidence. Data analysis revealed that 30 peptides were differentially phosphorylated with Vitamin C treatment, including novel phosphosites found on both PknG and GarA. Of these significant proteins, we validated 11 by parallel reaction monitoring of high-confidence phosphopeptides. Interestingly, 17/30 phosphopeptides were annotated as part of transmembrane proteins, suggesting that it is likely vitamin C triggers typical signal transduction events in which the protein periplasmic domain perceives environmental signals and the cytoplasmic domain is then phosphorylated. Finally, the diverse nature of phosphorylated proteins involved in signalling, transport, and carbohydrate biosynthesis indicates the extent of such regulatory phosphorylation events. Our findings provide new mechanistic insight into a coordinated network of signalling and regulatory responses to sub-lethal vitamin C in Mycobacterium smegmatis and provide evidence that vitamin C is able to act as a novel extracellular signalling molecule. Vitamin C treatment caused changes in both the proteome and phosphoproteome associated with response to oxidative stress, a shift in metabolic

Proteomic and phosphoproteomic analysis of polyethylene glycol-induced osmotic stress in root tips of common bean (Phaseolus vulgaris L.)

PubMed Central

Horst, Walter Johannes

2013-01-01

Previous studies have shown that polyethylene glycol (PEG)-induced osmotic stress (OS) reduces cell-wall (CW) porosity and limits aluminium (Al) uptake by root tips of common bean (Phaseolus vulgaris L.). A subsequent transcriptomic study suggested that genes related to CW processes are involved in adjustment to OS. In this study, a proteomic and phosphoproteomic approach was applied to identify OS-induced protein regulation to further improve our understanding of how OS affects Al accumulation. Analysis of total soluble proteins in root tips indicated that, in total, 22 proteins were differentially regulated by OS; these proteins were functionally categorized. Seventy-seven per- cent of the total expressed proteins were involved in metabolic pathways, particularly of carbohydrate and amino acid metabolism. An analysis of the apoplastic proteome revealed that OS reduced the level of five proteins and increased that of seven proteins. Investigation of the total soluble phosphoproteome suggested that dehydrin responded to OS with an enhanced phosphorylation state without a change in abundance. A cellular immunolocalization analysis indicated that dehydrin was localized mainly in the CW. This suggests that dehydrin may play a major protective role in the OS-induced physical breakdown of the CW structure and thus maintenance of the reversibility of CW extensibility during recovery from OS. The proteomic and phosphoproteomic analyses provided novel insights into the complex mechanisms of OS-induced reduction of Al accumulation in the root tips of common bean and highlight a key role for modification of CW structure. PMID:24123251

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

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.

Rapid Phosphoproteomic Effects of Abscisic Acid (ABA) on Wild-Type and ABA Receptor-Deficient A. thaliana Mutants*

PubMed Central

Minkoff, Benjamin B.; Stecker, Kelly E.; Sussman, Michael R.

2015-01-01

Abscisic acid (ABA)1 is a plant hormone that controls many aspects of plant growth, including seed germination, stomatal aperture size, and cellular drought response. ABA interacts with a unique family of 14 receptor proteins. This interaction leads to the activation of a family of protein kinases, SnRK2s, which in turn phosphorylate substrates involved in many cellular processes. The family of receptors appears functionally redundant. To observe a measurable phenotype, four of the fourteen receptors have to be mutated to create a multilocus loss-of-function quadruple receptor (QR) mutant, which is much less sensitive to ABA than wild-type (WT) plants. Given these phenotypes, we asked whether or not a difference in ABA response between the WT and QR backgrounds would manifest on a phosphorylation level as well. We tested WT and QR mutant ABA response using isotope-assisted quantitative phosphoproteomics to determine what ABA-induced phosphorylation changes occur in WT plants within 5 min of ABA treatment and how that phosphorylation pattern is altered in the QR mutant. We found multiple ABA-induced phosphorylation changes that occur within 5 min of treatment, including three SnRK2 autophosphorylation events and phosphorylation on SnRK2 substrates. The majority of robust ABA-dependent phosphorylation changes observed were partially diminished in the QR mutant, whereas many smaller ABA-dependent phosphorylation changes observed in the WT were not responsive to ABA in the mutant. A single phosphorylation event was increased in response to ABA treatment in both the WT and QR mutant. A portion of the discovery data was validated using selected reaction monitoring-based targeted measurements on a triple quadrupole mass spectrometer. These data suggest that different subsets of phosphorylation events depend upon different subsets of the ABA receptor family to occur. Altogether, these data expand our understanding of the model by which the family of ABA receptors directs

IKAP: A heuristic framework for inference of kinase activities from Phosphoproteomics data.

PubMed

Mischnik, Marcel; Sacco, Francesca; Cox, Jürgen; Schneider, Hans-Christoph; Schäfer, Matthias; Hendlich, Manfred; Crowther, Daniel; Mann, Matthias; Klabunde, Thomas

2016-02-01

Phosphoproteomics measurements are widely applied in cellular biology to detect changes in signalling dynamics. However, due to the inherent complexity of phosphorylation patterns and the lack of knowledge on how phosphorylations are related to functions, it is often not possible to directly deduce protein activities from those measurements. Here, we present a heuristic machine learning algorithm that infers the activities of kinases from Phosphoproteomics data using kinase-target information from the PhosphoSitePlus database. By comparing the estimated kinase activity profiles to the measured phosphosite profiles, it is furthermore possible to derive the kinases that are most likely to phosphorylate the respective phosphosite. We apply our approach to published datasets of the human cell cycle generated from HeLaS3 cells, and insulin signalling dynamics in mouse hepatocytes. In the first case, we estimate the activities of 118 at six cell cycle stages and derive 94 new kinase-phosphosite links that can be validated through either database or motif information. In the second case, the activities of 143 kinases at eight time points are estimated and 49 new kinase-target links are derived. The algorithm is implemented in Matlab and be downloaded from github. It makes use of the Optimization and Statistics toolboxes. https://github.com/marcel-mischnik/IKAP.git. marcel.mischnik@gmail.com Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Phosphoproteomics Reveals Regulatory T Cell-Mediated DEF6 Dephosphorylation That Affects Cytokine Expression in Human Conventional T Cells

PubMed Central

Joshi, Rubin N.; Binai, Nadine A.; Marabita, Francesco; Sui, Zhenhua; Altman, Amnon; Heck, Albert J. R.; Tegnér, Jesper; Schmidt, Angelika

2017-01-01

Regulatory T cells (Tregs) control key events of immune tolerance, primarily by suppression of effector T cells. We previously revealed that Tregs rapidly suppress T cell receptor (TCR)-induced calcium store depletion in conventional CD4+CD25− T cells (Tcons) independently of IP3 levels, consequently inhibiting NFAT signaling and effector cytokine expression. Here, we study Treg suppression mechanisms through unbiased phosphoproteomics of primary human Tcons upon TCR stimulation and Treg-mediated suppression, respectively. Tregs induced a state of overall decreased phosphorylation as opposed to TCR stimulation. We discovered novel phosphosites (T595_S597) in the DEF6 (SLAT) protein that were phosphorylated upon TCR stimulation and conversely dephosphorylated upon coculture with Tregs. Mutation of these DEF6 phosphosites abrogated interaction of DEF6 with the IP3 receptor and affected NFAT activation and cytokine transcription in primary Tcons. This novel mechanism and phosphoproteomics data resource may aid in modifying sensitivity of Tcons to Treg-mediated suppression in autoimmune disease or cancer. PMID:28993769

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

PubMed Central

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

2016-01-01

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

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

SPECHT - single-stage phosphopeptide enrichment and stable-isotope chemical tagging: quantitative phosphoproteomics of insulin action in muscle.

PubMed

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

2015-01-30

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. Through the use of a quantitatively reproducible, proteome-wide phosphopeptide enrichment strategy, we demonstrated the feasibility of post-phosphopeptide purification chemical labeling and tagging as an enabling approach for quantitative phosphoproteomics of primary tissues. Using reductive dimethyl labeling as a generalized chemical tagging strategy, we compared the performance of post-phosphopeptide purification chemical tagging to the well established community standard, SILAC, in insulin-stimulated tissue culture cells. We then extended our method to the analysis of low-dose insulin signaling in murine muscle tissue, and report on the analytical and biological significance of our results. Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical Visualization of Phosphoproteomes on Membrane*

PubMed Central

Iliuk, Anton; Liu, X. Shawn; Xue, Liang; Liu, Xiaoqi; Tao, W. Andy

2012-01-01

With new discoveries of important roles of phosphorylation on a daily basis, phospho-specific antibodies, as the primary tool for on-membrane detection of phosphoproteins, face enormous challenges. To address an urgent need for convenient and reliable analysis of phosphorylation events, we report a novel strategy for sensitive phosphorylation analysis in the Western blotting format. The chemical reagent, which we termed pIMAGO, is based on a multifunctionalized soluble nanopolymer and is capable of selectively binding to phosphorylated residues independent of amino acid microenvironment, thus offering great promise as a universal tool in biological analyses where the site of phosphorylation is not known or its specific antibody is not available. The specificity and sensitivity of the approach was first examined using a mixture of standard proteins. The method was then applied to monitor phosphorylation changes in in vitro kinase and phosphatase assays. Finally, to demonstrate the unique ability of pIMAGO to measure endogenous phosphorylation, we used it to visualize and determine the differences in phosphorylated proteins that interact with wild-type and kinase dead mutant of Polo-like kinase 1 during mitosis, the results of which were further confirmed by a quantitative phosphoproteomics experiment. PMID:22593177

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

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.

An Integrated Phosphoproteomics Work Flow Reveals Extensive Network Regulation in Early Lysophosphatidic Acid Signaling*

PubMed Central

Schreiber, Thiemo B.; Mäusbacher, Nina; Kéri, György; Cox, Jürgen; Daub, Henrik

2010-01-01

Lysophosphatidic acid (LPA) induces a variety of cellular signaling pathways through the activation of its cognate G protein-coupled receptors. To investigate early LPA responses and assess the contribution of epidermal growth factor (EGF) receptor transactivation in LPA signaling, we performed phosphoproteomics analyses of both total cell lysate and protein kinase-enriched fractions as complementary strategies to monitor phosphorylation changes in A498 kidney carcinoma cells. Our integrated work flow enabled the identification and quantification of more than 5,300 phosphorylation sites of which 224 were consistently regulated by LPA. In addition to induced phosphorylation events, we also obtained evidence for early dephosphorylation reactions due to rapid phosphatase regulation upon LPA treatment. Phosphorylation changes induced by direct heparin-binding EGF-like growth factor-mediated EGF receptor activation were typically weaker and only detected on a subset of LPA-regulated sites, indicating signal integration among EGF receptor transactivation and other LPA-triggered pathways. Our results reveal rapid phosphoregulation of many proteins not yet implicated in G protein-coupled receptor signaling and point to various additional mechanisms by which LPA might regulate cell survival and migration as well as gene transcription on the molecular level. Moreover, our phosphoproteomics analysis of both total lysate and kinase-enriched fractions provided highly complementary parts of the LPA-regulated signaling network and thus represents a useful and generic strategy toward comprehensive signaling studies on a system-wide level. PMID:20071362

Phosphoproteomic investigation of a solvent producing bacterium Clostridium acetobutylicum.

PubMed

Bai, Xue; Ji, Zhihong

2012-07-01

In this study, we employed TiO₂ enrichment and high accuracy liquid chromatography-mass spectrometry-mass spectrometry to identify the phosphoproteome of Clostridium acetobutyicum ATCC824 in acidogenesis and solventogenesis. As many as 82 phosphopeptides in 61 proteins, with 107 phosphorylated sites on serine, threonine, or tyrosine, were identified with high confidence. We detected 52 phosphopeptides from 44 proteins in acidogenesis and 70 phosphopeptides from 51 proteins in solventogenesis, respectively. Bioinformatic analysis revealed most of the phosphoproteins located in cytoplasm and participated in carbon metabolism. Based on comparison between the two stages, we found 27 stage-specific phosphorylated proteins (10 in acidogenesis and 17 in solventogenesis), some of which were solvent production-related enzymes and metabolic regulators, showed significantly different phosphorylated status. Further analysis indicated that protein phosphorylation could be involved in the shift of stages or in solvent production pathway directly. Comparison against several other organisms revealed the evolutionary diversity among them on phosphorylation level in spite of their high homology on protein sequence level.

Proteome and phosphoproteome analysis of commensally induced dendritic cell maturation states.

PubMed

Korkmaz, Ali Giray; Popov, Todor; Peisl, Loulou; Codrea, Marius Cosmin; Nahnsen, Sven; Steimle, Alexander; Velic, Ana; Macek, Boris; von Bergen, Martin; Bernhardt, Joerg; Frick, Julia-Stefanie

2018-05-30

Dendritic cells (DCs) can shape the immune system towards an inflammatory or tolerant state depending on the bacterial antigens and the environment they encounter. In this study we provide a proteomic catalogue of differentially expressed proteins between distinct DC maturation states, brought about by bacteria that differ in their endotoxicity. To achieve this, we have performed proteomics and phosphoproteomics on murine DC cultures. Symbiont and pathobiont bacteria were used to direct dendritic cells into a semi-mature and fully-mature state, respectively. The comparison of semi-mature and fully-mature DCs revealed differential expression in 103 proteins and differential phosphorylation in 118 phosphosites, including major regulatory factors of central immune processes. Our analyses predict that these differences are mediated by upstream elements such as SOCS1, IRF3, ABCA1, TLR4, and PTGER4. Our analyses indicate that the symbiont bacterial strain affects DC proteome in a distinct way, by downregulating inflammatory proteins and activating anti-inflammatory upstream regulators. Biological significance In this study we have investigated the responses of immune cells to distinct bacterial stimuli. We have used the symbiont bacterial strain B. vulgatus and the pathobiont E. coli strain to stimulate cultured primary dendritic cells and performed a shotgun proteome analysis to investigate the protein expression and phosphorylation level differences on a genome level. We have observed expression and phosphorylation level differences in key immune regulators, transcription factors and signal transducers. Moreover, our subsequent bioinformatics analysis indicated regulation at several signaling pathways such as PPAR signaling, LXR/RXR activation and glucocorticoid signaling pathways, which are not studied in detail in an inflammation and DC maturation context. Our phosphoproteome analysis showed differential phosphorylation in 118 phosphosites including those belonging

A systematic understanding of signaling by ErbB2 in cancer using phosphoproteomics.

PubMed

Sidhanth, C; Manasa, P; Krishnapriya, S; Sneha, S; Bindhya, S; Nagare, R P; Garg, M; Ganesan, T S

2018-06-01

ErbB2 is an important receptor tyrosine kinase and a member of the ErbB family. Although it does not have a specific ligand, it transmits signals downstream by heterodimerization with other receptors in the family. It plays a major role in a variety of cellular responses like proliferation, differentiation, and adhesion. ErbB2 is amplified at the DNA level in breast cancer (20%-30%) and gastric cancer (10%-20%), and trastuzumab is effective as a therapeutic antibody. This review is a critical analysis of the currently published data on the signaling pathways of ErbB2 and the interacting proteins. It also focuses on the techniques that are currently available to evaluate the entire phosphoproteome following activation of ErbB2. Identification of new and relevant phosphoproteins can not only serve as new therapeutic targets but also as a surrogate marker in patients to assess the activity of compounds that inhibit ErbB2. Overall, such analysis will improve understanding of signaling by ErbB2.

Phosphoproteomic network analysis in the sea urchin Strongylocentrotus purpuratus reveals new candidates in egg activation.

PubMed

Guo, Hongbo; Garcia-Vedrenne, Ana Elisa; Isserlin, Ruth; Lugowski, Andrew; Morada, Anthony; Sun, Alex; Miao, Yishen; Kuzmanov, Uros; Wan, Cuihong; Ma, Hongyue; Foltz, Kathy; Emili, Andrew

2015-12-01

Fertilization triggers a dynamic symphony of molecular transformations induced by a rapid rise in intracellular calcium. Most prominent are surface alterations, metabolic activation, cytoskeletal reorganization, and cell-cycle reentry. While the activation process appears to be broadly evolutionarily conserved, and protein phosphorylation is known to play a key role, the signaling networks mediating the response to fertilization are not well described. To address this gap, we performed a time course phosphoproteomic analysis of egg activation in the sea urchin Strongylocentrotus purpuratus, a system that offers biochemical tractability coupled with exquisite synchronicity. By coupling large-scale phosphopeptide enrichment with unbiased quantitative MS, we identified striking changes in global phosphoprotein patterns at 2- and 5-min postfertilization as compared to unfertilized eggs. Overall, we mapped 8796 distinct phosphosite modifications on 2833 phosphoproteins, of which 15% were differentially regulated in early egg activation. Activated kinases were identified by phosphosite mapping, while enrichment analyses revealed conserved signaling cascades not previously associated with egg activation. This work represents the most comprehensive study of signaling associated with egg activation to date, suggesting novel mechanisms that can be experimentally tested and providing a valuable resource for the broader research community. All MS data have been deposited in the ProteomeXchange with identifier PXD002239 (http://proteomecentral.proteomexchange.org/dataset/PXD002239). © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Recent findings and technological advances in phosphoproteomics for cells and tissues.

PubMed

von Stechow, Louise; Francavilla, Chiara; Olsen, Jesper V

2015-01-01

Site-specific phosphorylation is a fast and reversible covalent post-translational modification that is tightly regulated in cells. The cellular machinery of enzymes that write, erase and read these modifications (kinases, phosphatases and phospho-binding proteins) is frequently deregulated in different diseases, including cancer. Large-scale studies of phosphoproteins - termed phosphoproteomics - strongly rely on the use of high-performance mass spectrometric instrumentation. This powerful technology has been applied to study a great number of phosphorylation-based phenotypes. Nevertheless, many technical and biological challenges have to be overcome to identify biologically relevant phosphorylation sites in cells and tissues. This review describes different technological strategies to identify and quantify phosphorylation sites with high accuracy, without significant loss of analysis speed and reproducibility in tissues and cells. Moreover, computational tools for analysis, integration and biological interpretation of phosphorylation events are discussed.

The Phosphoproteomic Response of Rice Seedlings to Cadmium Stress.

PubMed

Zhong, Min; Li, Sanfeng; Huang, Fenglin; Qiu, Jiehua; Zhang, Jian; Sheng, Zhonghua; Tang, Shaoqing; Wei, Xiangjin; Hu, Peisong

2017-09-27

The environmental damage caused by cadmium (Cd) pollution is of increasing concern in China. While the overall plant response to Cd has been investigated in some depth, the contribution (if any) of protein phosphorylation to the detoxification of Cd and the expression of tolerance is uncertain. Here, the molecular basis of the plant response has been explored in hydroponically raised rice seedlings exposed to 10 μΜ and 100 μΜ Cd 2+ stress. An analysis of the seedlings' quantitative phosphoproteome identified 2454 phosphosites, associated with 1244 proteins. A total of 482 of these proteins became differentially phosphorylated as a result of exposure to Cd stress; the number of proteins affected in this way was six times greater in the 100 μΜ Cd 2+ treatment than in the 10 μΜ treatment. A functional analysis of the differentially phosphorylated proteins implied that a significant number was involved in signaling, in stress tolerance and in the neutralization of reactive oxygen species, while there was also a marked representation of transcription factors.

The Phosphoproteomic Response of Rice Seedlings to Cadmium Stress

PubMed Central

Zhong, Min; Li, Sanfeng; Huang, Fenglin; Qiu, Jiehua; Sheng, Zhonghua; Tang, Shaoqing; Wei, Xiangjin; Hu, Peisong

2017-01-01

The environmental damage caused by cadmium (Cd) pollution is of increasing concern in China. While the overall plant response to Cd has been investigated in some depth, the contribution (if any) of protein phosphorylation to the detoxification of Cd and the expression of tolerance is uncertain. Here, the molecular basis of the plant response has been explored in hydroponically raised rice seedlings exposed to 10 μΜ and 100 μΜ Cd2+ stress. An analysis of the seedlings’ quantitative phosphoproteome identified 2454 phosphosites, associated with 1244 proteins. A total of 482 of these proteins became differentially phosphorylated as a result of exposure to Cd stress; the number of proteins affected in this way was six times greater in the 100 μΜ Cd2+ treatment than in the 10 μΜ treatment. A functional analysis of the differentially phosphorylated proteins implied that a significant number was involved in signaling, in stress tolerance and in the neutralization of reactive oxygen species, while there was also a marked representation of transcription factors. PMID:28953215

SILAC-based phosphoproteomics reveals new PP2A-Cdc55-regulated processes in budding yeast.

PubMed

Baro, Barbara; Játiva, Soraya; Calabria, Inés; Vinaixa, Judith; Bech-Serra, Joan-Josep; de LaTorre, Carolina; Rodrigues, João; Hernáez, María Luisa; Gil, Concha; Barceló-Batllori, Silvia; Larsen, Martin R; Queralt, Ethel

2018-05-01

Protein phosphatase 2A (PP2A) is a family of conserved serine/threonine phosphatases involved in several essential aspects of cell growth and proliferation. PP2ACdc55 phosphatase has been extensively related to cell cycle events in budding yeast; however, few PP2ACdc55 substrates have been identified. Here, we performed a quantitative mass spectrometry approach to reveal new substrates of PP2ACdc55 phosphatase and new PP2A-related processes in mitotic arrested cells. We identified 62 statistically significant PP2ACdc55 substrates involved mainly in actin-cytoskeleton organization. In addition, we validated new PP2ACdc55 substrates such as Slk19 and Lte1, involved in early and late anaphase pathways, and Zeo1, a component of the cell wall integrity pathway. Finally, we constructed docking models of Cdc55 and its substrate Mob1. We found that the predominant interface on Cdc55 is mediated by a protruding loop consisting of residues 84-90, thus highlighting the relevance of these aminoacids for substrate interaction. We used phosphoproteomics of Cdc55-deficient cells to uncover new PP2ACdc55 substrates and functions in mitosis. As expected, several hyperphosphorylated proteins corresponded to Cdk1-dependent substrates, although other kinases' consensus motifs were also enriched in our dataset, suggesting that PP2ACdc55 counteracts and regulates other kinases distinct from Cdk1. Indeed, Pkc1 emerged as a novel node of PP2ACdc55 regulation, highlighting a major role of PP2ACdc55 in actin cytoskeleton and cytokinesis, gene ontology terms significantly enriched in the PP2ACdc55-dependent phosphoproteome.

Parallel comparative proteomics and phosphoproteomics reveal that cattle myostatin regulates phosphorylation of key enzymes in glycogen metabolism and glycolysis pathway

PubMed Central

Yang, Shuping; Li, Xin; Liu, Xinfeng; Ding, Xiangbin; Xin, Xiangbo; Jin, Congfei; Zhang, Sheng; Li, Guangpeng; Guo, Hong

2018-01-01

MSTN-encoded myostatin is a negative regulator of skeletal muscle development. Here, we utilized the gluteus tissues from MSTN gene editing and wild type Luxi beef cattle which are native breed of cattle in China, performed tandem mass tag (TMT) -based comparative proteomics and phosphoproteomics analyses to investigate the regulatory mechanism of MSTN related to cellular metabolism and signaling pathway in muscle development. Out of 1,315 proteins, 69 differentially expressed proteins (DEPs) were found in global proteomics analysis. Meanwhile, 149 differentially changed phosphopeptides corresponding to 76 unique phosphorylated proteins (DEPPs) were detected from 2,600 identified phosphopeptides in 702 phosphorylated proteins. Bioinformatics analyses suggested that majority of DEPs and DEPPs were closely related to glycolysis, glycogenolysis, and muscle contractile fibre processes. The global discovery results were validated by Multiple Reaction Monitoring (MRM)-based targeted peptide quantitation analysis, western blotting, and muscle glycogen content measurement. Our data revealed that increase in abundance of key enzymes and phosphorylation on their regulatory sites appears responsible for the enhanced glycogenolysis and glycolysis in MSTN−/−. The elevated glycogenolysis was assocaited with an enhanced phosphorylation of Ser1018 in PHKA1, and Ser641/Ser645 in GYS1, which were regulated by upstream phosphorylated AKT-GSK3β pathway and highly consistent with the lower glycogen content in gluteus of MSTN−/−. Collectively, this study provides new insights into the regulatory mechanisms of MSTN involved in energy metabolism and muscle growth. PMID:29541418

Quantitative phosphoproteomic analysis of caprine muscle with high and low meat quality.

PubMed

Liu, Manshun; Wei, Yanchao; Li, Xin; Quek, Siew Young; Zhao, Jing; Zhong, Huazhen; Zhang, Dequan; Liu, Yongfeng

2018-07-01

During the conversion of muscle to meat, protein phosphorylation can regulate various biological processes that have important effects on meat quality. To investigate the phosphorylation pattern of protein on rigor mortis, goat longissimus thoracis and external intercostals were classified into two groups (high quality and low quality), and meat quality was evaluated according to meat quality attributes (Warner-Bratzler shear force, Color, pH and drip loss). A quantitative mass spectrometry-based phosphoproteomic study was conducted to analyze the caprine muscle at 12h postmortem applying the TiO 2 -SIMAC-HILIC (TiSH) phosphopeptide enrichment strategy. A total of 2125 phosphopeptides were identified from 750 phosphoproteins. Among them, 96 proteins had differed in phosphorylation levels. The majority of these proteins are involved in glucose metabolism and muscle contraction. The differential phosphorylation level of proteins (PFK, MYL2 and HSP27) in two groups may be the crucial factors of regulating muscle rigor mortis. This study provides a comprehensive view for the phosphorylation status of caprine muscle at rigor mortis, it also gives a better understanding of the regulation of protein phosphorylation on various biological processes that affect the final meat quality attributes. Copyright © 2018. Published by Elsevier Ltd.

Isoelectric point-based fractionation by HiRIEF coupled to LC-MS allows for in-depth quantitative analysis of the phosphoproteome.

PubMed

Panizza, Elena; Branca, Rui M M; Oliviusson, Peter; Orre, Lukas M; Lehtiö, Janne

2017-07-03

Protein phosphorylation is involved in the regulation of most eukaryotic cells functions and mass spectrometry-based analysis has made major contributions to our understanding of this regulation. However, low abundance of phosphorylated species presents a major challenge in achieving comprehensive phosphoproteome coverage and robust quantification. In this study, we developed a workflow employing titanium dioxide phospho-enrichment coupled with isobaric labeling by Tandem Mass Tags (TMT) and high-resolution isoelectric focusing (HiRIEF) fractionation to perform in-depth quantitative phosphoproteomics starting with a low sample quantity. To benchmark the workflow, we analyzed HeLa cells upon pervanadate treatment or cell cycle arrest in mitosis. Analyzing 300 µg of peptides per sample, we identified 22,712 phosphorylation sites, of which 19,075 were localized with high confidence and 1,203 are phosphorylated tyrosine residues, representing 6.3% of all detected phospho-sites. HiRIEF fractions with the most acidic isoelectric points are enriched in multiply phosphorylated peptides, which represent 18% of all the phospho-peptides detected in the pH range 2.5-3.7. Cross-referencing with the PhosphoSitePlus database reveals 1,264 phosphorylation sites that have not been previously reported and kinase association analysis suggests that a subset of these may be functional during the mitotic phase.

The beginnings of crop phosphoproteomics: exploring early warning systems of stress

PubMed Central

Rampitsch, Christof; Bykova, Natalia V.

2012-01-01

This review examines why a knowledge of plant protein phosphorylation events is important in devising strategies to protect crops from both biotic and abiotic stresses, and why proteomics should be included when studying stress pathways. Most of the achievements in elucidating phospho-signaling pathways in biotic and abiotic stress are reported from model systems: while these are discussed, this review attempts mainly to focus on work done with crops, with examples of achievements reported from rice, maize, wheat, grape, Brassica, tomato, and soy bean after cold acclimation, hormonal and oxidative hydrogen peroxide treatment, salt stress, mechanical wounding, or pathogen challenge. The challenges that remain to transfer this information into a format that can be used to protect crops against biotic and abiotic stresses are enormous. The tremendous increase in the speed and ease of DNA sequencing is poised to reveal the whole genomes of many crop species in the near future, which will facilitate phosphoproteomics and phosphogenomics research. PMID:22783265

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

In vivo phosphoproteome characterization reveals key starch granule-binding phosphoproteins involved in wheat water-deficit response.

PubMed

Chen, Guan-Xing; Zhen, Shou-Min; Liu, Yan-Lin; Yan, Xing; Zhang, Ming; Yan, Yue-Ming

2017-10-23

Drought stress during grain development causes significant yield loss in cereal production. The phosphorylated modification of starch granule-binding proteins (SGBPs) is an important mechanism regulating wheat starch biosynthesis. In this study, we performed the first proteomics and phosphoproteomics analyses of SGBPs in elite Chinese bread wheat (Triticum aestivum L.) cultivar Jingdong 17 under well-watered and water-stress conditions. Water stress treatment caused significant reductions in spike grain numbers and weight, total starch and amylopectin content, and grain yield. Two-dimensional gel electrophoresis revealed that the quantity of SGBPs was reduced significantly by water-deficit treatment. Phosphoproteome characterization of SGBPs under water-deficit treatment demonstrated a reduced level of phosphorylation of main starch synthesis enzymes, particularly for granule-bound starch synthase (GBSS I), starch synthase II-a (SS II-a), and starch synthase III (SS III). Specifically, the Ser34 site of the GBSSI protein, the Tyr358 site of SS II-a, and the Ser837 site of SS III-a exhibited significant less phosphorylation under water-deficit treatment than well-watered treatment. Furthermore, the expression levels of several key genes related with starch biosynthesis detected by qRT-PCR were decreased significantly at 15 days post-anthesis under water-deficit treatment. Immunolocalization showed a clear movement of GBSS I from the periphery to the interior of starch granules during grain development, under both water-deficit and well-watered conditions. Our results demonstrated that the reduction in gene expression or transcription level, protein expression and phosphorylation levels of starch biosynthesis related enzymes under water-deficit conditions is responsible for the significant decrease in total starch content and grain yield.

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

A Phosphoproteomic Comparison of B-RAFV600E and MKK1/2 Inhibitors in Melanoma Cells.

PubMed

Stuart, Scott A; Houel, Stephane; Lee, Thomas; Wang, Nan; Old, William M; Ahn, Natalie G

2015-06-01

Inhibitors of oncogenic B-RAF(V600E) and MKK1/2 have yielded remarkable responses in B-RAF(V600E)-positive melanoma patients. However, the efficacy of these inhibitors is limited by the inevitable onset of resistance. Despite the fact that these inhibitors target the same pathway, combination treatment with B-RAF(V600E) and MKK1/2 inhibitors has been shown to improve both response rates and progression-free survival in B-RAF(V600E) melanoma patients. To provide insight into the molecular nature of the combinatorial response, we used quantitative mass spectrometry to characterize the inhibitor-dependent phosphoproteome of human melanoma cells treated with the B-RAF(V600E) inhibitor PLX4032 (vemurafenib) or the MKK1/2 inhibitor AZD6244 (selumetinib). In three replicate experiments, we quantified changes at a total of 23,986 phosphosites on 4784 proteins. This included 1317 phosphosites that reproducibly decreased in response to at least one inhibitor. Phosphosites that responded to both inhibitors grouped into networks that included the nuclear pore complex, growth factor signaling, and transcriptional regulators. Although the majority of phosphosites were responsive to both inhibitors, we identified 16 sites that decreased only in response to PLX4032, suggesting rare instances where oncogenic B-RAF signaling occurs in an MKK1/2-independent manner. Only two phosphosites were identified that appeared to be uniquely responsive to AZD6244. When cells were treated with the combination of AZD6244 and PLX4032 at subsaturating concentrations (30 nm), responses at nearly all phosphosites were additive. We conclude that AZD6244 does not substantially widen the range of phosphosites inhibited by PLX4032 and that the benefit of the drug combination is best explained by their additive effects on suppressing ERK1/2 signaling. Comparison of our results to another recent ERK1/2 phosphoproteomics study revealed a surprising degree of variability in the sensitivity of phosphosites to

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

PubMed

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; Wu, Shih-Hsiung

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 S(88)VS(90)K 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. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Phosphoproteomic Analysis of Signaling Pathways in Head and Neck Squamous Cell Carcinoma Patient Samples

PubMed Central

Frederick, Mitchell J.; VanMeter, Amy J.; Gadhikar, Mayur A.; Henderson, Ying C.; Yao, Hui; Pickering, Curtis C.; Williams, Michelle D.; El-Naggar, Adel K.; Sandulache, Vlad; Tarco, Emily; Myers, Jeffrey N.; Clayman, Gary L.; Liotta, Lance A.; Petricoin, Emanuel F.; Calvert, Valerie S.; Fodale, Valentina; Wang, Jing; Weber, Randal S.

2011-01-01

Molecular targeted therapy represents a promising new strategy for treating cancers because many small-molecule inhibitors targeting protein kinases have recently become available. Reverse-phase protein microarrays (RPPAs) are a useful platform for identifying dysregulated signaling pathways in tumors and can provide insight into patient-specific differences. In the present study, RPPAs were used to examine 60 protein end points (predominantly phosphoproteins) in matched tumor and nonmalignant biopsy specimens from 23 patients with head and neck squamous cell carcinoma to characterize the cancer phosphoproteome. RPPA identified 18 of 60 analytes globally elevated in tumors versus healthy tissue and 17 of 60 analytes that were decreased. The most significantly elevated analytes in tumor were checkpoint kinase (Chk) 1 serine 345 (S345), Chk 2 S33/35, eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) S65, protein kinase C (PKC) ζ/ι threonine 410/412 (T410/T412), LKB1 S334, inhibitor of kappaB alpha (IκB-α) S32, eukaryotic translation initiation factor 4E (eIF4E) S209, Smad2 S465/67, insulin receptor substrate 1 (IRS-1) S612, mitogen-activated ERK kinase 1/2 (MEK1/2) S217/221, and total PKC ι. To our knowledge, this is the first report of elevated PKC ι in head and neck squamous cell carcinoma that may have significance because PKC ι is an oncogene in several other tumor types, including lung cancer. The feasibility of using RPPA for developing theranostic tests to guide personalized therapy is discussed in the context of these data. PMID:21281788

Battle through signaling between wheat and the fungal pathogen Septoria tritici revealed by proteomics and phosphoproteomics.

PubMed

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

2013-09-01

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 comprehensive

Phosphoproteomic Analysis Identifies Signaling Pathways Regulated by Curcumin in Human Colon Cancer Cells.

PubMed

Sato, Tatsuhiro; Higuchi, Yutaka; Shibagaki, Yoshio; Hattori, Seisuke

2017-09-01

Curcumin, a major polyphenol of the spice turmeric, acts as a potent chemopreventive and chemotherapeutic agent in several cancer types, including colon cancer. Although various proteins have been shown to be affected by curcumin, how curcumin exerts its anticancer activity is not fully understood. Phosphoproteomic analyses were performed using SW480 and SW620 human colon cancer cells to identify curcumin-affected signaling pathways. Curcumin inhibited the growth of the two cell lines in a dose-dependent manner. Thirty-nine curcumin-regulated phosphoproteins were identified, five of which are involved in cancer signaling pathways. Detailed analyses revealed that the mTORC1 and p53 signaling pathways are main targets of curcumin. Our results provide insight into the molecular mechanisms of the anticancer activities of curcumin and future molecular targets for its clinical application. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Temporal dynamics of the Saccharopolyspora erythraea phosphoproteome.

PubMed

Licona-Cassani, Cuauhtemoc; Lim, Sooa; Marcellin, Esteban; Nielsen, Lars K

2014-05-01

Actinomycetes undergo a dramatic reorganization of metabolic and cellular machinery during a brief period of growth arrest ("metabolic switch") preceding mycelia differentiation and the onset of secondary metabolite biosynthesis. This study explores the role of phosphorylation in coordinating the metabolic switch in the industrial actinomycete Saccharopolyspora erythraea. A total of 109 phosphopeptides from 88 proteins were detected across a 150-h fermentation using open-profile two-dimensional LC-MS proteomics and TiO(2) enrichment. Quantitative analysis of the phosphopeptides and their unphosphorylated cognates was possible for 20 pairs that also displayed constant total protein expression. Enzymes from central carbon metabolism such as putative acetyl-coenzyme A carboxylase, isocitrate lyase, and 2-oxoglutarate dehydrogenase changed dramatically in the degree of phosphorylation during the stationary phase, suggesting metabolic rearrangement for the reutilization of substrates and the production of polyketide precursors. In addition, an enzyme involved in cellular response to environmental stress, trypsin-like serine protease (SACE_6340/NC_009142_6216), decreased in phosphorylation during the growth arrest stage. More important, enzymes related to the regulation of protein synthesis underwent rapid phosphorylation changes during this stage. Whereas the degree of phosphorylation of ribonuclease Rne/Rng (SACE_1406/NC_009142_1388) increased during the metabolic switch, that of two ribosomal proteins, S6 (SACE_7351/NC_009142_7233) and S32 (SACE_6101/NC_009142_5981), dramatically decreased during this stage of the fermentation, supporting the hypothesis that ribosome subpopulations differentially regulate translation before and after the metabolic switch. Overall, we show the great potential of phosphoproteomic studies to explain microbial physiology and specifically provide evidence of dynamic protein phosphorylation events across the developmental cycle of

Temporal Dynamics of the Saccharopolyspora erythraea Phosphoproteome*

PubMed Central

Licona-Cassani, Cuauhtemoc; Lim, SooA; Marcellin, Esteban; Nielsen, Lars K.

2014-01-01

Actinomycetes undergo a dramatic reorganization of metabolic and cellular machinery during a brief period of growth arrest (“metabolic switch”) preceding mycelia differentiation and the onset of secondary metabolite biosynthesis. This study explores the role of phosphorylation in coordinating the metabolic switch in the industrial actinomycete Saccharopolyspora erythraea. A total of 109 phosphopeptides from 88 proteins were detected across a 150-h fermentation using open-profile two-dimensional LC-MS proteomics and TiO2 enrichment. Quantitative analysis of the phosphopeptides and their unphosphorylated cognates was possible for 20 pairs that also displayed constant total protein expression. Enzymes from central carbon metabolism such as putative acetyl-coenzyme A carboxylase, isocitrate lyase, and 2-oxoglutarate dehydrogenase changed dramatically in the degree of phosphorylation during the stationary phase, suggesting metabolic rearrangement for the reutilization of substrates and the production of polyketide precursors. In addition, an enzyme involved in cellular response to environmental stress, trypsin-like serine protease (SACE_6340/NC_009142_6216), decreased in phosphorylation during the growth arrest stage. More important, enzymes related to the regulation of protein synthesis underwent rapid phosphorylation changes during this stage. Whereas the degree of phosphorylation of ribonuclease Rne/Rng (SACE_1406/NC_009142_1388) increased during the metabolic switch, that of two ribosomal proteins, S6 (SACE_7351/NC_009142_7233) and S32 (SACE_6101/NC_009142_5981), dramatically decreased during this stage of the fermentation, supporting the hypothesis that ribosome subpopulations differentially regulate translation before and after the metabolic switch. Overall, we show the great potential of phosphoproteomic studies to explain microbial physiology and specifically provide evidence of dynamic protein phosphorylation events across the developmental cycle of

Deciphering the Acute Cellular Phosphoproteome Response to Irradiation with X-rays, Protons and Carbon Ions*

PubMed Central

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

2017-01-01

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 2 h 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. Because 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

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

2017-05-01

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 2 h 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. Because 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

Global protein phosphorylation dynamics during deoxynivalenol-induced ribotoxic stress response in the macrophage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pan, Xiao; Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824; Whitten, Douglas A.

Deoxynivalenol (DON), a trichothecene mycotoxin produced by Fusarium that commonly contaminates food, is capable of activating mononuclear phagocytes of the innate immune system via a process termed the ribotoxic stress response (RSR). To encapture global signaling events mediating RSR, we quantified the early temporal (≤ 30 min) phosphoproteome changes that occurred in RAW 264.7 murine macrophage during exposure to a toxicologically relevant concentration of DON (250 ng/mL). Large-scale phosphoproteomic analysis employing stable isotope labeling of amino acids in cell culture (SILAC) in conjunction with titanium dioxide chromatography revealed that DON significantly upregulated or downregulated phosphorylation of 188 proteins at bothmore » known and yet-to-be functionally characterized phosphosites. DON-induced RSR is extremely complex and goes far beyond its prior known capacity to inhibit translation and activate MAPKs. Transcriptional regulation was the main target during early DON-induced RSR, covering over 20% of the altered phosphoproteins as indicated by Gene Ontology annotation and including transcription factors/cofactors and epigenetic modulators. Other biological processes impacted included cell cycle, RNA processing, translation, ribosome biogenesis, monocyte differentiation and cytoskeleton organization. Some of these processes could be mediated by signaling networks involving MAPK-, NFκB-, AKT- and AMPK-linked pathways. Fuzzy c-means clustering revealed that DON-regulated phosphosites could be discretely classified with regard to the kinetics of phosphorylation/dephosphorylation. The cellular response networks identified provide a template for further exploration of the mechanisms of trichothecenemycotoxins and other ribotoxins, and ultimately, could contribute to improved mechanism-based human health risk assessment. - Highlights: ► Mycotoxin deoxynivalenol (DON) induces immunotoxicity via ribotoxic stress response. ► SILAC

Phosphoproteomics reveals that glycogen synthase kinase-3 phosphorylates multiple splicing factors and is associated with alternative splicing

PubMed Central

Shinde, Mansi Y.; Sidoli, Simone; Kulej, Katarzyna; Mallory, Michael J.; Radens, Caleb M.; Reicherter, Amanda L.; Myers, Rebecca L.; Barash, Yoseph; Lynch, Kristen W.; Garcia, Benjamin A.; Klein, Peter S.

2017-01-01

Glycogen synthase kinase-3 (GSK-3) is a constitutively active, ubiquitously expressed protein kinase that regulates multiple signaling pathways. In vitro kinase assays and genetic and pharmacological manipulations of GSK-3 have identified more than 100 putative GSK-3 substrates in diverse cell types. Many more have been predicted on the basis of a recurrent GSK-3 consensus motif ((pS/pT)XXX(S/T)), but this prediction has not been tested by analyzing the GSK-3 phosphoproteome. Using stable isotope labeling of amino acids in culture (SILAC) and MS techniques to analyze the repertoire of GSK-3–dependent phosphorylation in mouse embryonic stem cells (ESCs), we found that ∼2.4% of (pS/pT)XXX(S/T) sites are phosphorylated in a GSK-3–dependent manner. A comparison of WT and Gsk3a;Gsk3b knock-out (Gsk3 DKO) ESCs revealed prominent GSK-3–dependent phosphorylation of multiple splicing factors and regulators of RNA biosynthesis as well as proteins that regulate transcription, translation, and cell division. Gsk3 DKO reduced phosphorylation of the splicing factors RBM8A, SRSF9, and PSF as well as the nucleolar proteins NPM1 and PHF6, and recombinant GSK-3β phosphorylated these proteins in vitro. RNA-Seq of WT and Gsk3 DKO ESCs identified ∼190 genes that are alternatively spliced in a GSK-3–dependent manner, supporting a broad role for GSK-3 in regulating alternative splicing. The MS data also identified posttranscriptional regulation of protein abundance by GSK-3, with ∼47 proteins (1.4%) whose levels increased and ∼78 (2.4%) whose levels decreased in the absence of GSK-3. This study provides the first unbiased analysis of the GSK-3 phosphoproteome and strong evidence that GSK-3 broadly regulates alternative splicing. PMID:28916722

Human embryonic stem cell phosphoproteome revealed by electron transfer dissociation tandem mass spectrometry.

PubMed

Swaney, Danielle L; Wenger, Craig D; Thomson, James A; Coon, Joshua J

2009-01-27

Protein phosphorylation is central to the understanding of cellular signaling, and cellular signaling is suggested to play a major role in the regulation of human embryonic stem (ES) cell pluripotency. Here, we describe the use of conventional tandem mass spectrometry-based sequencing technology--collision-activated dissociation (CAD)--and the more recently developed method electron transfer dissociation (ETD) to characterize the human ES cell phosphoproteome. In total, these experiments resulted in the identification of 11,995 unique phosphopeptides, corresponding to 10,844 nonredundant phosphorylation sites, at a 1% false discovery rate (FDR). Among these phosphorylation sites are 5 localized to 2 pluripotency critical transcription factors--OCT4 and SOX2. From these experiments, we conclude that ETD identifies a larger number of unique phosphopeptides than CAD (8,087 to 3,868), more frequently localizes the phosphorylation site to a specific residue (49.8% compared with 29.6%), and sequences whole classes of phosphopeptides previously unobserved.

Human embryonic stem cell phosphoproteome revealed by electron transfer dissociation tandem mass spectrometry

PubMed Central

Swaney, Danielle L.; Wenger, Craig D.; Thomson, James A.; Coon, Joshua J.

2009-01-01

Protein phosphorylation is central to the understanding of cellular signaling, and cellular signaling is suggested to play a major role in the regulation of human embryonic stem (ES) cell pluripotency. Here, we describe the use of conventional tandem mass spectrometry-based sequencing technology—collision-activated dissociation (CAD)—and the more recently developed method electron transfer dissociation (ETD) to characterize the human ES cell phosphoproteome. In total, these experiments resulted in the identification of 11,995 unique phosphopeptides, corresponding to 10,844 nonredundant phosphorylation sites, at a 1% false discovery rate (FDR). Among these phosphorylation sites are 5 localized to 2 pluripotency critical transcription factors—OCT4 and SOX2. From these experiments, we conclude that ETD identifies a larger number of unique phosphopeptides than CAD (8,087 to 3,868), more frequently localizes the phosphorylation site to a specific residue (49.8% compared with 29.6%), and sequences whole classes of phosphopeptides previously unobserved. PMID:19144917

Quantitative Analysis of Human Pluripotency and Neural Specification by In-Depth (Phospho)Proteomic Profiling.

PubMed

Singec, Ilyas; Crain, Andrew M; Hou, Junjie; Tobe, Brian T D; Talantova, Maria; Winquist, Alicia A; Doctor, Kutbuddin S; Choy, Jennifer; Huang, Xiayu; La Monaca, Esther; Horn, David M; Wolf, Dieter A; Lipton, Stuart A; Gutierrez, Gustavo J; Brill, Laurence M; Snyder, Evan Y

2016-09-13

Controlled differentiation of human embryonic stem cells (hESCs) can be utilized for precise analysis of cell type identities during early development. We established a highly efficient neural induction strategy and an improved analytical platform, and determined proteomic and phosphoproteomic profiles of hESCs and their specified multipotent neural stem cell derivatives (hNSCs). This quantitative dataset (nearly 13,000 proteins and 60,000 phosphorylation sites) provides unique molecular insights into pluripotency and neural lineage entry. Systems-level comparative analysis of proteins (e.g., transcription factors, epigenetic regulators, kinase families), phosphorylation sites, and numerous biological pathways allowed the identification of distinct signatures in pluripotent and multipotent cells. Furthermore, as predicted by the dataset, we functionally validated an autocrine/paracrine mechanism by demonstrating that the secreted protein midkine is a regulator of neural specification. This resource is freely available to the scientific community, including a searchable website, PluriProt. Published by Elsevier Inc.

Effects of the NO/soluble guanylate cyclase/cGMP system on the functions of human platelets.

PubMed

Makhoul, Stephanie; Walter, Elena; Pagel, Oliver; Walter, Ulrich; Sickmann, Albert; Gambaryan, Stepan; Smolenski, Albert; Zahedi, René P; Jurk, Kerstin

2018-06-01

Platelets are circulating sentinels of vascular integrity and are activated, inhibited, or modulated by multiple hormones, vasoactive substances or drugs. Endothelium- or drug-derived NO strongly inhibits platelet activation via activation of the soluble guanylate cyclase (sGC) and cGMP elevation, often in synergy with cAMP-elevation by prostacyclin. However, the molecular mechanisms and diversity of cGMP effects in platelets are poorly understood and sometimes controversial. Recently, we established the quantitative human platelet proteome, the iloprost/prostacyclin/cAMP/protein kinase A (PKA)-regulated phosphoproteome, and the interactions of the ADP- and iloprost/prostacyclin-affected phosphoproteome. We also showed that the sGC stimulator riociguat is in vitro a highly specific inhibitor, via cGMP, of various functions of human platelets. Here, we review the regulatory role of the cGMP/protein kinase G (PKG) system in human platelet function, and our current approaches to establish and analyze the phosphoproteome after selective stimulation of the sGC/cGMP pathway by NO donors and riociguat. Present data indicate an extensive and diverse NO/riociguat/cGMP phosphoproteome, which has to be compared with the cAMP phosphoproteome. In particular, sGC/cGMP-regulated phosphorylation of many membrane proteins, G-proteins and their regulators, signaling molecules, protein kinases, and proteins involved in Ca 2+ regulation, suggests that the sGC/cGMP system targets multiple signaling networks rather than a limited number of PKG substrate proteins. Copyright © 2018 Elsevier Inc. All rights reserved.

Time-resolved Global and Chromatin Proteomics during Herpes Simplex Virus Type 1 (HSV-1) Infection*

PubMed Central

Kulej, Katarzyna; Avgousti, Daphne C.; Sidoli, Simone; Herrmann, Christin; Della Fera, Ashley N.; Kim, Eui Tae; Garcia, Benjamin A.; Weitzman, Matthew D.

2017-01-01

Herpes simplex virus (HSV-1) lytic infection results in global changes to the host cell proteome and the proteins associated with host chromatin. We present a system level characterization of proteome dynamics during infection by performing a multi-dimensional analysis during HSV-1 lytic infection of human foreskin fibroblast (HFF) cells. Our study includes identification and quantification of the host and viral proteomes, phosphoproteomes, chromatin bound proteomes and post-translational modifications (PTMs) on cellular histones during infection. We analyzed proteomes across six time points of virus infection (0, 3, 6, 9, 12 and 15 h post-infection) and clustered trends in abundance using fuzzy c-means. Globally, we accurately quantified more than 4000 proteins, 200 differently modified histone peptides and 9000 phosphorylation sites on cellular proteins. In addition, we identified 67 viral proteins and quantified 571 phosphorylation events (465 with high confidence site localization) on viral proteins, which is currently the most comprehensive map of HSV-1 phosphoproteome. We investigated chromatin bound proteins by proteomic analysis of the high-salt chromatin fraction and identified 510 proteins that were significantly different in abundance during infection. We found 53 histone marks significantly regulated during virus infection, including a steady increase of histone H3 acetylation (H3K9ac and H3K14ac). Our data provide a resource of unprecedented depth for human and viral proteome dynamics during infection. Collectively, our results indicate that the proteome composition of the chromatin of HFF cells is highly affected during HSV-1 infection, and that phosphorylation events are abundant on viral proteins. We propose that our epi-proteomics approach will prove to be important in the characterization of other model infectious systems that involve changes to chromatin composition. PMID:28179408

Time-resolved Global and Chromatin Proteomics during Herpes Simplex Virus Type 1 (HSV-1) Infection.

PubMed

Kulej, Katarzyna; Avgousti, Daphne C; Sidoli, Simone; Herrmann, Christin; Della Fera, Ashley N; Kim, Eui Tae; Garcia, Benjamin A; Weitzman, Matthew D

2017-04-01

Herpes simplex virus (HSV-1) lytic infection results in global changes to the host cell proteome and the proteins associated with host chromatin. We present a system level characterization of proteome dynamics during infection by performing a multi-dimensional analysis during HSV-1 lytic infection of human foreskin fibroblast (HFF) cells. Our study includes identification and quantification of the host and viral proteomes, phosphoproteomes, chromatin bound proteomes and post-translational modifications (PTMs) on cellular histones during infection. We analyzed proteomes across six time points of virus infection (0, 3, 6, 9, 12 and 15 h post-infection) and clustered trends in abundance using fuzzy c-means. Globally, we accurately quantified more than 4000 proteins, 200 differently modified histone peptides and 9000 phosphorylation sites on cellular proteins. In addition, we identified 67 viral proteins and quantified 571 phosphorylation events (465 with high confidence site localization) on viral proteins, which is currently the most comprehensive map of HSV-1 phosphoproteome. We investigated chromatin bound proteins by proteomic analysis of the high-salt chromatin fraction and identified 510 proteins that were significantly different in abundance during infection. We found 53 histone marks significantly regulated during virus infection, including a steady increase of histone H3 acetylation (H3K9ac and H3K14ac). Our data provide a resource of unprecedented depth for human and viral proteome dynamics during infection. Collectively, our results indicate that the proteome composition of the chromatin of HFF cells is highly affected during HSV-1 infection, and that phosphorylation events are abundant on viral proteins. We propose that our epi-proteomics approach will prove to be important in the characterization of other model infectious systems that involve changes to chromatin composition. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Phosphoproteomics profiling suggests a role for nuclear βΙPKC in transcription processes of undifferentiated murine embryonic stem cells.

PubMed

Costa-Junior, Helio Miranda; Garavello, Nicole Milaré; Duarte, Mariana Lemos; Berti, Denise Aparecida; Glaser, Talita; de Andrade, Alexander; Labate, Carlos A; Ferreira, André Teixeira da Silva; Perales, Jonas Enrique Aguilar; Xavier-Neto, José; Krieger, José Eduardo; Schechtman, Deborah

2010-12-03

Protein kinase C (PKC) plays a key role in embryonic stem cell (ESC) proliferation, self-renewal, and differentiation. However, the function of specific PKC isoenzymes have yet to be determined. Of the PKCs expressed in undifferentiated ESCs, βIPKC was the only isoenzyme abundantly expressed in the nuclei. To investigate the role of βΙPKC in these cells, we employed a phosphoproteomics strategy and used two classical (cPKC) peptide modulators and one βIPKC-specific inhibitor peptide. We identified 13 nuclear proteins that are direct or indirect βΙPKC substrates in undifferentiated ESCs. These proteins are known to be involved in regulating transcription, splicing, and chromatin remodeling during proliferation and differentiation. Inhibiting βΙPKC had no effect on DNA synthesis in undifferentiated ESCs. However, upon differentiation, many cells seized to express βΙPKC and βΙPKC was frequently found in the cytoplasm. Taken together, our results suggest that βIPKC takes part in the processes that maintain ESCs in their undifferentiated state.

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.

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

Identification of Phosphorylated Proteins on a Global Scale.

PubMed

Iliuk, Anton

2018-05-31

Liquid chromatography (LC) coupled with tandem mass spectrometry (MS/MS) has enabled researchers to analyze complex biological samples with unprecedented depth. It facilitates the identification and quantification of modifications within thousands of proteins in a single large-scale proteomic experiment. Analysis of phosphorylation, one of the most common and important post-translational modifications, has particularly benefited from such progress in the field. Here, detailed protocols are provided for a few well-regarded, common sample preparation methods for an effective phosphoproteomic experiment. © 2018 by John Wiley & Sons, Inc. Copyright © 2018 John Wiley & Sons, Inc.

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

Phosphoproteomic insights into processes influenced by the kinase-like protein DIA1/C3orf58

PubMed Central

Hareza, Agnieszka; Bakun, Magda; Świderska, Bianka; Dudkiewicz, Małgorzata; Koscielny, Alicja; Bajur, Anna; Jaworski, Jacek

2018-01-01

Many kinases are still ‘orphans,’ which means knowledge about their substrates, and often also about the processes they regulate, is lacking. Here, DIA1/C3orf58, a member of a novel predicted kinase-like family, is shown to be present in the endoplasmic reticulum and to influence trafficking via the secretory pathway. Subsequently, DIA1 is subjected to phosphoproteomics analysis to cast light on its signalling pathways. A liquid chromatography–tandem mass spectrometry proteomic approach with phosphopeptide enrichment is applied to membrane fractions of DIA1-overexpressing and control HEK293T cells, and phosphosites dependent on the presence of DIA1 are elucidated. Most of these phosphosites belonged to CK2- and proline-directed kinase types. In parallel, the proteomics of proteins immunoprecipitated with DIA1 reported its probable interactors. This pilot study provides the basis for deeper studies of DIA1 signalling. PMID:29666759

Phosphoproteomic insights into processes influenced by the kinase-like protein DIA1/C3orf58.

PubMed

Hareza, Agnieszka; Bakun, Magda; Świderska, Bianka; Dudkiewicz, Małgorzata; Koscielny, Alicja; Bajur, Anna; Jaworski, Jacek; Dadlez, Michał; Pawłowski, Krzysztof

2018-01-01

Many kinases are still 'orphans,' which means knowledge about their substrates, and often also about the processes they regulate, is lacking. Here, DIA1/C3orf58, a member of a novel predicted kinase-like family, is shown to be present in the endoplasmic reticulum and to influence trafficking via the secretory pathway. Subsequently, DIA1 is subjected to phosphoproteomics analysis to cast light on its signalling pathways. A liquid chromatography-tandem mass spectrometry proteomic approach with phosphopeptide enrichment is applied to membrane fractions of DIA1-overexpressing and control HEK293T cells, and phosphosites dependent on the presence of DIA1 are elucidated. Most of these phosphosites belonged to CK2- and proline-directed kinase types. In parallel, the proteomics of proteins immunoprecipitated with DIA1 reported its probable interactors. This pilot study provides the basis for deeper studies of DIA1 signalling.

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

PubMed

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

2015-10-13

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. Copyright © 2015, American Association for the Advancement of Science.

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

A Library of Phosphoproteomic and Chromatin Signatures for Characterizing Cellular Responses to Drug Perturbations.

PubMed

Litichevskiy, Lev; Peckner, Ryan; Abelin, Jennifer G; Asiedu, Jacob K; Creech, Amanda L; Davis, John F; Davison, Desiree; Dunning, Caitlin M; Egertson, Jarrett D; Egri, Shawn; Gould, Joshua; Ko, Tak; Johnson, Sarah A; Lahr, David L; Lam, Daniel; Liu, Zihan; Lyons, Nicholas J; Lu, Xiaodong; MacLean, Brendan X; Mungenast, Alison E; Officer, Adam; Natoli, Ted E; Papanastasiou, Malvina; Patel, Jinal; Sharma, Vagisha; Toder, Courtney; Tubelli, Andrew A; Young, Jennie Z; Carr, Steven A; Golub, Todd R; Subramanian, Aravind; MacCoss, Michael J; Tsai, Li-Huei; Jaffe, Jacob D

2018-04-25

Although the value of proteomics has been demonstrated, cost and scale are typically prohibitive, and gene expression profiling remains dominant for characterizing cellular responses to perturbations. However, high-throughput sentinel assays provide an opportunity for proteomics to contribute at a meaningful scale. We present a systematic library resource (90 drugs × 6 cell lines) of proteomic signatures that measure changes in the reduced-representation phosphoproteome (P100) and changes in epigenetic marks on histones (GCP). A majority of these drugs elicited reproducible signatures, but notable cell line- and assay-specific differences were observed. Using the "connectivity" framework, we compared signatures across cell types and integrated data across assays, including a transcriptional assay (L1000). Consistent connectivity among cell types revealed cellular responses that transcended lineage, and consistent connectivity among assays revealed unexpected associations between drugs. We further leveraged the resource against public data to formulate hypotheses for treatment of multiple myeloma and acute lymphocytic leukemia. This resource is publicly available at https://clue.io/proteomics. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Quantitative phosphoproteomics reveals the role of protein arginine phosphorylation in the bacterial stress response.

PubMed

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

2014-02-01

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.

Quantitative cardiac phosphoproteomics profiling during ischemia-reperfusion in an immature swine model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ledee, Dolena R.; Kang, Min A.; Kajimoto, Masaki

Ischemia-reperfusion (I/R) results in altered metabolic and molecular responses, and phosphorylation is one of the most noted regulatory mechanisms mediating signaling mechanisms during physiological stresses. To expand our knowledge of the potential phosphoproteomic changes in the myocardium during I/R, we used Isobaric Tags for Relative and Absolute Quantitation-based analyses in left ventricular samples obtained from porcine hearts under control or I/R conditions. The data are available via ProteomeXchange with identifier PXD006066. We identified 1,896 phosphopeptides within left ventricular control and I/R porcine samples. Significant differential phosphorylation between control and I/R groups was discovered in 111 phosphopeptides from 86 proteins. Analysismore » of the phosphopeptides using Motif-x identified five motifs: (..R..S..), (..SP..), (..S.S..), (..S…S..), and (..S.T..). Semiquantitative immunoblots confirmed site location and directional changes in phosphorylation for phospholamban and pyruvate dehydrogenase E1, two proteins known to be altered by I/R and identified by this study. Novel phosphorylation sites associated with I/R were also identified. Functional characterization of the phosphopeptides identified by our methodology could expand our understanding of the signaling mechanisms involved during I/R damage in the heart as well as identify new areas to target therapeutic strategies.« less

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

PubMed

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

2013-07-02

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.

Mutant JAK3 phosphoproteomic profiling predicts synergism between JAK3 inhibitors and MEK/BCL2 inhibitors for the treatment of T-cell acute lymphoblastic leukemia

PubMed Central

Degryse, S; de Bock, C E; Demeyer, S; Govaerts, I; Bornschein, S; Verbeke, D; Jacobs, K; Binos, S; Skerrett-Byrne, D A; Murray, H C; Verrills, N M; Van Vlierberghe, P; Cools, J; Dun, M D

2018-01-01

Mutations in the interleukin-7 receptor (IL7R) or the Janus kinase 3 (JAK3) kinase occur frequently in T-cell acute lymphoblastic leukemia (T-ALL) and both are able to drive cellular transformation and the development of T-ALL in mouse models. However, the signal transduction pathways downstream of JAK3 mutations remain poorly characterized. Here we describe the phosphoproteome downstream of the JAK3(L857Q)/(M511I) activating mutations in transformed Ba/F3 lymphocyte cells. Signaling pathways regulated by JAK3 mutants were assessed following acute inhibition of JAK1/JAK3 using the JAK kinase inhibitors ruxolitinib or tofacitinib. Comprehensive network interrogation using the phosphoproteomic signatures identified significant changes in pathways regulating cell cycle, translation initiation, mitogen-activated protein kinase and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT signaling, RNA metabolism, as well as epigenetic and apoptotic processes. Key regulatory proteins within pathways that showed altered phosphorylation following JAK inhibition were targeted using selumetinib and trametinib (MEK), buparlisib (PI3K) and ABT-199 (BCL2), and found to be synergistic in combination with JAK kinase inhibitors in primary T-ALL samples harboring JAK3 mutations. These data provide the first detailed molecular characterization of the downstream signaling pathways regulated by JAK3 mutations and provide further understanding into the oncogenic processes regulated by constitutive kinase activation aiding in the development of improved combinatorial treatment regimens. PMID:28852199

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

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

Global anomalies and effective field theory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Golkar, Siavash; Sethi, Savdeep

2016-05-17

Here, we show that matching anomalies under large gauge transformations and large diffeomorphisms can explain the appearance and non-renormalization of couplings in effective field theory. We focus on thermal effective field theory, where we argue that the appearance of certain unusual Chern-Simons couplings is a consequence of global anomalies. As an example, we show that a mixed global anomaly in four dimensions fixes the chiral vortical effect coefficient (up to an overall additive factor). This is an experimentally measurable prediction from a global anomaly. For certain situations, we propose a simpler method for calculating global anomalies which uses correlation functionsmore » rather than eta invariants.« less

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

Differences in Beef Quality between Angus (Bos taurus taurus) and Nellore (Bos taurus indicus) Cattle through a Proteomic and Phosphoproteomic Approach.

PubMed

Rodrigues, Rafael Torres de Souza; Chizzotti, Mario Luiz; Vital, Camilo Elber; Baracat-Pereira, Maria Cristina; Barros, Edvaldo; Busato, Karina Costa; Gomes, Rafael Aparecido; Ladeira, Márcio Machado; Martins, Taiane da Silva

2017-01-01

Proteins are the major constituents of muscle and are key molecules regulating the metabolic changes during conversion of muscle to meat. Brazil is one of the largest exporters of beef and most Brazilian cattle are composed by zebu (Nellore) genotype. Bos indicus beef is generally leaner and tougher than Bos taurus such as Angus. The aim of this study was to compare the muscle proteomic and phosphoproteomic profile of Angus and Nellore. Seven animals of each breed previously subjected the same growth management were confined for 84 days. Proteins were extracted from Longissimus lumborum samples collected immediately after slaughter and separated by two-dimensional electrophoresis. Pro-Q Diamond stain was used in phosphoproteomics. Proteins identification was performed using matrix assisted laser desorption/ionization time-of-flight mass spectrometry. Tropomyosin alpha-1 chain, troponin-T, myosin light chain-1 fragment, cytoplasmic malate dehydrogenase, alpha-enolase and 78 kDa glucose-regulated protein were more abundant in Nellore, while myosin light chain 3, prohibitin, mitochondrial stress-70 protein and heat shock 70 kDa protein 6 were more abundant in Angus (P<0.05). Nellore had higher phosphorylation of myosin regulatory light chain-2, alpha actin-1, triosephosphate isomerase and 14-3-3 protein epsilon. However, Angus had greater phosphorylation of phosphoglucomutase-1 and troponin-T (P<0.05). Therefore, proteins involved in contraction and muscle organization, myofilaments expressed in fast or slow-twitch fibers and heat shock proteins localized in mitochondria or sarcoplasmic reticulum and involved in cell flux of calcium and apoptosis might be associated with differences in beef quality between Angus and Nellore. Furthermore, prohibitin appears to be a potential biomarker of intramuscular fat in cattle. Additionally, differences in phosphorylation of myofilaments and glycolytic enzymes could be involved with differences in muscle contraction force

Differences in Beef Quality between Angus (Bos taurus taurus) and Nellore (Bos taurus indicus) Cattle through a Proteomic and Phosphoproteomic Approach

PubMed Central

Chizzotti, Mario Luiz; Vital, Camilo Elber; Baracat-Pereira, Maria Cristina; Barros, Edvaldo; Busato, Karina Costa; Gomes, Rafael Aparecido; Ladeira, Márcio Machado; Martins, Taiane da Silva

2017-01-01

Proteins are the major constituents of muscle and are key molecules regulating the metabolic changes during conversion of muscle to meat. Brazil is one of the largest exporters of beef and most Brazilian cattle are composed by zebu (Nellore) genotype. Bos indicus beef is generally leaner and tougher than Bos taurus such as Angus. The aim of this study was to compare the muscle proteomic and phosphoproteomic profile of Angus and Nellore. Seven animals of each breed previously subjected the same growth management were confined for 84 days. Proteins were extracted from Longissimus lumborum samples collected immediately after slaughter and separated by two-dimensional electrophoresis. Pro-Q Diamond stain was used in phosphoproteomics. Proteins identification was performed using matrix assisted laser desorption/ionization time-of-flight mass spectrometry. Tropomyosin alpha-1 chain, troponin-T, myosin light chain-1 fragment, cytoplasmic malate dehydrogenase, alpha-enolase and 78 kDa glucose-regulated protein were more abundant in Nellore, while myosin light chain 3, prohibitin, mitochondrial stress-70 protein and heat shock 70 kDa protein 6 were more abundant in Angus (P<0.05). Nellore had higher phosphorylation of myosin regulatory light chain-2, alpha actin-1, triosephosphate isomerase and 14-3-3 protein epsilon. However, Angus had greater phosphorylation of phosphoglucomutase-1 and troponin-T (P<0.05). Therefore, proteins involved in contraction and muscle organization, myofilaments expressed in fast or slow-twitch fibers and heat shock proteins localized in mitochondria or sarcoplasmic reticulum and involved in cell flux of calcium and apoptosis might be associated with differences in beef quality between Angus and Nellore. Furthermore, prohibitin appears to be a potential biomarker of intramuscular fat in cattle. Additionally, differences in phosphorylation of myofilaments and glycolytic enzymes could be involved with differences in muscle contraction force

Quantitative analysis of the TNF-α-induced phosphoproteome reveals AEG-1/MTDH/LYRIC as an IKKβ substrate

PubMed Central

Krishnan, Ramesh K.; Nolte, Hendrik; Sun, Tianliang; Kaur, Harmandeep; Sreenivasan, Krishnamoorthy; Looso, Mario; Offermanns, Stefan; Krüger, Marcus; Swiercz, Jakub M.

2015-01-01

The inhibitor of the nuclear factor-κB (IκB) kinase (IKK) complex is a key regulator of the canonical NF-κB signalling cascade and is crucial for fundamental cellular functions, including stress and immune responses. The majority of IKK complex functions are attributed to NF-κB activation; however, there is increasing evidence for NF-κB pathway-independent signalling. Here we combine quantitative mass spectrometry with random forest bioinformatics to dissect the TNF-α-IKKβ-induced phosphoproteome in MCF-7 breast cancer cells. In total, we identify over 20,000 phosphorylation sites, of which ∼1% are regulated up on TNF-α stimulation. We identify various potential novel IKKβ substrates including kinases and regulators of cellular trafficking. Moreover, we show that one of the candidates, AEG-1/MTDH/LYRIC, is directly phosphorylated by IKKβ on serine 298. We provide evidence that IKKβ-mediated AEG-1 phosphorylation is essential for IκBα degradation as well as NF-κB-dependent gene expression and cell proliferation, which correlate with cancer patient survival in vivo. PMID:25849741

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). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The phosphoproteome of Aspergillus nidulans reveals functional association with cellular processes involved in morphology and secretion.

PubMed

Ramsubramaniam, Nikhil; Harris, Steven D; Marten, Mark R

2014-11-01

We describe the first phosphoproteome of the model filamentous fungus Aspergillus nidulans. Phosphopeptides were enriched using titanium dioxide, separated using a convenient ultra-long reverse phase gradient, and identified using a "high-high" strategy (high mass accuracy on the parent and fragment ions) with higher-energy collisional dissociation. Using this approach 1801 phosphosites, from 1637 unique phosphopeptides, were identified. Functional classification revealed phosphoproteins were overrepresented under GO categories related to fungal morphogenesis: "sites of polar growth," "vesicle mediated transport," and "cytoskeleton organization." In these same GO categories, kinase-substrate analysis of phosphoproteins revealed the majority were target substrates of CDK and CK2 kinase families, indicating these kinase families play a prominent role in fungal morphogenesis. Kinase-substrate analysis also identified 57 substrates for kinases known to regulate secretion of hydrolytic enzymes (e.g. PkaA, SchA, and An-Snf1). Altogether this data will serve as a benchmark that can be used to elucidate regulatory networks functionally associated with fungal morphogenesis and secretion. All MS data have been deposited in the ProteomeXchange with identifier PXD000715 (http://proteomecentral.proteomexchange.org/dataset/PXD000715). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparative Phosphoproteomic Analysis of the Developing Seeds in Two Indica Rice ( Oryza sativa L.) Cultivars with Different Starch Quality.

PubMed

Pang, Yuehan; Zhou, Xin; Chen, Yaling; Bao, Jinsong

2018-03-21

Protein phosphorylation plays important roles in regulation of various molecular events such as plant growth and seed development. However, its involvement in starch biosynthesis is less understood. Here, a comparative phosphoproteomic analysis of two indica rice cultivars during grain development was performed. A total of 2079 and 2434 phosphopeptides from 1273 and 1442 phosphoproteins were identified, covering 2441 and 2808 phosphosites in indica rice 9311 and Guangluai4 (GLA4), respectively. Comparative analysis identified 303 differentially phosphorylated peptides, and 120 and 258 specifically phosphorylated peptides in 9311 and GLA4, respectively. Phosphopeptides in starch biosynthesis related enzymes such as AGPase, SSIIa, SSIIIa, BEI, BEIIb, PUL, and Pho1were identified. GLA4 and 9311 had different amylose content, pasting viscosities, and gelatinization temperature, suggesting subtle difference in starch biosynthesis and regulation between GLA4 and 9311. Our study will give added impetus to further understanding the regulatory mechanism of starch biosynthesis at the phosphorylation level.

Hippocampal phosphoproteomics of F344 rats exposed to 1-bromopropane

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Zhenlie; Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550; Ichihara, Sahoko

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.more » 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

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

Opposite Electron-Transfer Dissociation and Higher-Energy Collisional Dissociation Fragmentation Characteristics of Proteolytic K/R(X)n and (X)nK/R Peptides Provide Benefits for Peptide Sequencing in Proteomics and Phosphoproteomics.

PubMed

Tsiatsiani, Liana; Giansanti, Piero; Scheltema, Richard A; van den Toorn, Henk; Overall, Christopher M; Altelaar, A F Maarten; Heck, Albert J R

2017-02-03

A key step in shotgun proteomics is the digestion of proteins into peptides amenable for mass spectrometry. Tryptic peptides can be readily sequenced and identified by collision-induced dissociation (CID) or higher-energy collisional dissociation (HCD) because the fragmentation rules are well-understood. Here, we investigate LysargiNase, a perfect trypsin mirror protease, because it cleaves equally specific at arginine and lysine residues, albeit at the N-terminal end. LysargiNase peptides are therefore practically tryptic-like in length and sequence except that following ESI, the two protons are now both positioned at the N-terminus. Here, we compare side-by-side the chromatographic separation properties, gas-phase fragmentation characteristics, and (phospho)proteome sequence coverage of tryptic (i.e., (X) n K/R) and LysargiNase (i.e., K/R(X) n ) peptides using primarily electron-transfer dissociation (ETD) and, for comparison, HCD. We find that tryptic and LysargiNase peptides fragment nearly as mirror images. For LysargiNase predominantly N-terminal peptide ions (c-ions (ETD) and b-ions (HCD)) are formed, whereas for trypsin, C-terminal fragment ions dominate (z-ions (ETD) and y-ions (HCD)) in a homologous mixture of complementary ions. Especially during ETD, LysargiNase peptides fragment into low-complexity but information-rich sequence ladders. Trypsin and LysargiNase chart distinct parts of the proteome, and therefore, the combined use of these enzymes will benefit a more in-depth and reliable analysis of (phospho)proteomes.

Dual phosphoproteomics and chemical proteomics analysis of erlotinib and gefitinib interference in acute myeloid leukemia cells.

PubMed

Weber, Christoph; Schreiber, Thiemo B; Daub, Henrik

2012-02-02

Small molecule inhibitors of protein kinases have emerged as a major class of therapeutic agents for the treatment of hematological malignancies. Both in vitro studies and patient case reports suggest therapeutic potential of the clinical kinase inhibitors erlotinib and gefitinib in acute myeloid leukemia (AML). The drugs' cellular modes of action in AML warrant further investigation as their primary therapeutic target, the epidermal growth factor receptor, is not expressed. We therefore performed SILAC-based quantitative mass spectrometry analyses to a depth of 10,975 distinct phosphorylation sites to characterize the phosphoproteome of KG1 AML cells and its regulation upon erlotinib and gefitinib treatment. Less than 50 site-specific phosphorylations changed significantly, indicating rather specific interference with AML cell signaling. Many drug-induced changes occurred within a network of tyrosine phosphorylated proteins that included Src family kinases (SFKs) and the tyrosine kinases Btk and Syk. We further performed quantitative chemical proteomics in KG1 cell extracts and identified SFKs and Btk as direct cellular targets of both erlotinib and gefitinib. Taken together, our data suggest that cellular perturbation of SFKs and/or Btk translates into rather specific signal transduction inhibition, which in turn contributes to the antileukemic activity of erlotinib and gefitinib in AML. Copyright © 2011 Elsevier B.V. All rights reserved.

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.

Quantitative Phosphoproteomics Reveals Wee1 Kinase as a Therapeutic Target in a Model of Proneural Glioblastoma.

PubMed

Lescarbeau, Rebecca S; Lei, Liang; Bakken, Katrina K; Sims, Peter A; Sarkaria, Jann N; Canoll, Peter; White, Forest M

2016-06-01

Glioblastoma (GBM) is the most common malignant primary brain cancer. With a median survival of about a year, new approaches to treating this disease are necessary. To identify signaling molecules regulating GBM progression in a genetically engineered murine model of proneural GBM, we quantified phosphotyrosine-mediated signaling using mass spectrometry. Oncogenic signals, including phosphorylated ERK MAPK, PI3K, and PDGFR, were found to be increased in the murine tumors relative to brain. Phosphorylation of CDK1 pY15, associated with the G2 arrest checkpoint, was identified as the most differentially phosphorylated site, with a 14-fold increase in phosphorylation in the tumors. To assess the role of this checkpoint as a potential therapeutic target, syngeneic primary cell lines derived from these tumors were treated with MK-1775, an inhibitor of Wee1, the kinase responsible for CDK1 Y15 phosphorylation. MK-1775 treatment led to mitotic catastrophe, as defined by increased DNA damage and cell death by apoptosis. To assess the extensibility of targeting Wee1/CDK1 in GBM, patient-derived xenograft (PDX) cell lines were also treated with MK-1775. Although the response was more heterogeneous, on-target Wee1 inhibition led to decreased CDK1 Y15 phosphorylation and increased DNA damage and apoptosis in each line. These results were also validated in vivo, where single-agent MK-1775 demonstrated an antitumor effect on a flank PDX tumor model, increasing mouse survival by 1.74-fold. This study highlights the ability of unbiased quantitative phosphoproteomics to reveal therapeutic targets in tumor models, and the potential for Wee1 inhibition as a treatment approach in preclinical models of GBM. Mol Cancer Ther; 15(6); 1332-43. ©2016 AACR. ©2016 American Association for Cancer Research.

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

2017-06-01

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 CO 2 ] 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 CO 2 on C:N:P stoichiometry are stronger than warming, (ii) combined effects of pairs of global change drivers (e.g., N addition + elevated CO 2 , warming + elevated CO 2 ) 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. © 2017 John Wiley & Sons Ltd.

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

Wide-scale quantitative phosphoproteomic analysis reveals that cold treatment of T cells closely mimics soluble antibody stimulation

PubMed Central

Ji, Qinqin; Salomon, Arthur R.

2015-01-01

The activation of T-lymphocytes through antigen-mediated T-cell receptor (TCR) clustering is vital in regulating the adaptive-immune response. Although T cell receptor signaling has been extensively studied, the fundamental mechanisms for signal initiation are not fully understood. Reduced temperature initiated some of the hallmarks of TCR signaling such as increased phosphorylation and activation on ERK and calcium release from the endoplasmic reticulum as well as coalesce T-cell membrane microdomains. The precise mechanism of TCR signaling initiation due to temperature change remains obscure. One critical question is whether signaling initiated by cold treatment of T cells differs from signaling initiated by crosslinking of the T cell receptor. To address this uncertainty, a wide-scale, quantitative mass spectrometry-based phosphoproteomic analysis was performed on T cells stimulated either by temperature shift or through crosslinking of the TCR. Careful statistical comparison between the two stimulations revealed a striking level of identity between the subset of 339 sites that changed significantly with both stimulations. This study demonstrates for the first time, at unprecedented detail, that T cell cold treatment was sufficient to initiate signaling patterns nearly identical to soluble antibody stimulation, shedding new light on the mechanism of activation of these critically important immune cells. PMID:25839225

Potential effects on health of global warming

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haines, A.; Parry, M.

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 tomore » 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.« less

Auditory global-local processing: effects of attention and musical experience.

PubMed

Ouimet, Tia; Foster, Nicholas E V; Hyde, Krista L

2012-10-01

In vision, global (whole) features are typically processed before local (detail) features ("global precedence effect"). However, the distinction between global and local processing is less clear in the auditory domain. The aims of the present study were to investigate: (i) the effects of directed versus divided attention, and (ii) the effect musical training on auditory global-local processing in 16 adult musicians and 16 non-musicians. Participants were presented with short nine-tone melodies, each comprised of three triplet sequences (three-tone units). In a "directed attention" task, participants were asked to focus on either the global or local pitch pattern and had to determine if the pitch pattern went up or down. In a "divided attention" task, participants judged whether the target pattern (up or down) was present or absent. Overall, global structure was perceived faster and more accurately than local structure. The global precedence effect was observed regardless of whether attention was directed to a specific level or divided between levels. Musicians performed more accurately than non-musicians overall, but non-musicians showed a more pronounced global advantage. This study provides evidence for an auditory global precedence effect across attention tasks, and for differences in auditory global-local processing associated with musical experience.

Stable Isotope Metabolic Labeling-based Quantitative Phosphoproteomic Analysis of Arabidopsis Mutants Reveals Ethylene-regulated Time-dependent Phosphoproteins and Putative Substrates of Constitutive Triple Response 1 Kinase*

PubMed Central

Yang, Zhu; Guo, Guangyu; Zhang, Manyu; Liu, Claire Y.; Hu, Qin; Lam, Henry; Cheng, Han; Xue, Yu; Li, Jiayang; Li, Ning

2013-01-01

Ethylene is an important plant hormone that regulates numerous cellular processes and stress responses. The mode of action of ethylene is both dose- and time-dependent. Protein phosphorylation plays a key role in ethylene signaling, which is mediated by the activities of ethylene receptors, constitutive triple response 1 (CTR1) kinase, and phosphatase. To address how ethylene alters the cellular protein phosphorylation profile in a time-dependent manner, differential and quantitative phosphoproteomics based on 15N stable isotope labeling in Arabidopsis was performed on both one-minute ethylene-treated Arabidopsis ethylene-overly-sensitive loss-of-function mutant rcn1-1, deficient in PP2A phosphatase activity, and a pair of long-term ethylene-treated wild-type and loss-of-function ethylene signaling ctr1-1 mutants, deficient in mitogen-activated kinase kinase kinase activity. In total, 1079 phosphopeptides were identified, among which 44 were novel. Several one-minute ethylene-regulated phosphoproteins were found from the rcn1-1. Bioinformatic analysis of the rcn1-1 phosphoproteome predicted nine phosphoproteins as the putative substrates for PP2A phosphatase. In addition, from CTR1 kinase-enhanced phosphosites, we also found putative CTR1 kinase substrates including plastid transcriptionally active protein and calcium-sensing receptor. These regulatory proteins are phosphorylated in the presence of ethylene. Analysis of ethylene-regulated phosphosites using the group-based prediction system with a protein–protein interaction filter revealed a total of 14 kinase–substrate relationships that may function in both CTR1 kinase- and PP2A phosphatase-mediated phosphor-relay pathways. Finally, several ethylene-regulated post-translational modification network models have been built using molecular systems biology tools. It is proposed that ethylene regulates the phosphorylation of arginine/serine-rich splicing factor 41, plasma membrane intrinsic protein 2A, light

Is manipulation of color effective in study of the global precedence effect?

PubMed

Vidal-López, Joaquín; Romera-Vivancos, Juan Antonio

2009-04-01

This article evaluates the use of color manipulation in studying the effect of global precedence and the possible involvement of the magnocellular processing system. The analysis shows variations of color used in three studies produced changes on the global precedence effect, but findings based on this technique present some methodological problems and have little theoretical support from the magnocellular processing-system perspective. For this reason, more research is required to develop knowledge about the origin of these variations in global precedence.

The effect of sadness on global-local processing.

PubMed

von Mühlenen, Adrian; Bellaera, Lauren; Singh, Amrendra; Srinivasan, Narayanan

2018-05-04

Gable and Harmon-Jones (Psychological Science, 21(2), 211-215, 2010) reported that sadness broadens attention in a global-local letter task. This finding provided the key test for their motivational intensity account, which states that the level of spatial processing is not determined by emotional valence, but by motivational intensity. However, their finding is at odds with several other studies, showing no effect, or even a narrowing effect of sadness on attention. This paper reports two attempts to replicate the broadening effect of sadness on attention. Both experiments used a global-local letter task, but differed in terms of emotion induction: Experiment 1 used the same pictures as Gable and Harmon-Jones, taken from the IAPS dataset; Experiment 2 used a sad video underlaid with sad music. Results showed a sadness-specific global advantage in the error rates, but not in the reaction times. The same null results were also found in a South-Asian sample in both experiments, showing that effects on global/local processing were not influenced by a culturally related processing bias.

The effects of variable biome distribution on global climate.

PubMed

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

1996-01-01

In projecting climatic adjustments to anthropogenically elevated atmospheric carbon dioxide, most global climate models fix biome distribution to current geographic conditions. Previous biome maps either remain unchanging or shift without taking into account climatic feedbacks such as radiation and temperature. We 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 temperature trend and order of magnitude change. The model is then used to generate an optimized future biome distribution that 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 method is to adjust biome areas subject to a constant global temperature and total surface area constraint. For regulating global temperature, oceans are found to dominate continental biomes. Algal beds are significant radiative levers as are other carbon intensive biomes including estuaries and tropical deciduous forests. To hold global temperature constant over the next 70 years this simulation requires that deserts decrease and forested areas increase. The effect of biome change on global temperature is revealed as a significant forecasting factor.

Quantitative Phosphoproteomic Analysis Provides Insight into the Response to Short-Term Drought Stress in Ammopiptanthus mongolicus Roots.

PubMed

Sun, Huigai; Xia, Bolin; Wang, Xue; Gao, Fei; Zhou, Yijun

2017-10-17

Drought is one of the major abiotic stresses that negatively affects plant growth and development. Ammopiptanthus mongolicus is an ecologically important shrub in the mid-Asia desert region and used as a model for abiotic tolerance research in trees. Protein phosphorylation participates in the regulation of various biological processes, however, phosphorylation events associated with drought stress signaling and response in plants is still limited. Here, we conducted a quantitative phosphoproteomic analysis of the response of A. mongolicus roots to short-term drought stress. Data are available via the iProx database with project ID IPX0000971000. In total, 7841 phosphorylation sites were found from the 2019 identified phosphopeptides, corresponding to 1060 phosphoproteins. Drought stress results in significant changes in the abundance of 103 phosphopeptides, corresponding to 90 differentially-phosphorylated phosphoproteins (DPPs). Motif-x analysis identified two motifs, including [pSP] and [RXXpS], from these DPPs. Functional enrichment and protein-protein interaction analysis showed that the DPPs were mainly involved in signal transduction and transcriptional regulation, osmotic adjustment, stress response and defense, RNA splicing and transport, protein synthesis, folding and degradation, and epigenetic regulation. These drought-corresponsive phosphoproteins, and the related signaling and metabolic pathways probably play important roles in drought stress signaling and response in A. mongolicus roots. Our results provide new information for understanding the molecular mechanism of the abiotic stress response in plants at the posttranslational level.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakayasu, Ernesto S.; Tempel, Rebecca; Cambronne, Xiaolu A.

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 cellularmore » 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.« less

Phosphoproteomics profiling of human skin fibroblast cells reveals pathways and proteins affected by low doses of ionizing radiation.

PubMed

Yang, Feng; Waters, Katrina M; Miller, John H; Gritsenko, Marina A; Zhao, Rui; Du, Xiuxia; Livesay, Eric A; Purvine, Samuel O; Monroe, Matthew E; Wang, Yingchun; Camp, David G; Smith, Richard D; Stenoien, David L

2010-11-30

High doses of ionizing radiation result in biological damage; however, the precise relationships between long-term health effects, including cancer, and low-dose exposures remain poorly understood and are currently extrapolated using high-dose exposure data. Identifying the signaling pathways and individual proteins affected at the post-translational level by radiation should shed valuable insight into the molecular mechanisms that regulate dose-dependent responses to radiation. We have identified 7117 unique phosphopeptides (2566 phosphoproteins) from control and irradiated (2 and 50 cGy) primary human skin fibroblasts 1 h post-exposure. Semi-quantitative label-free analyses were performed to identify phosphopeptides that are apparently altered by radiation exposure. This screen identified phosphorylation sites on proteins with known roles in radiation responses including TP53BP1 as well as previously unidentified radiation-responsive proteins such as the candidate tumor suppressor SASH1. Bioinformatic analyses suggest that low and high doses of radiation affect both overlapping and unique biological processes and suggest a role for MAP kinase and protein kinase A (PKA) signaling in the radiation response as well as differential regulation of p53 networks at low and high doses of radiation. Our results represent the most comprehensive analysis of the phosphoproteomes of human primary fibroblasts exposed to multiple doses of ionizing radiation published to date and provide a basis for the systems-level identification of biological processes, molecular pathways and individual proteins regulated in a dose dependent manner by ionizing radiation. Further study of these modified proteins and affected networks should help to define the molecular mechanisms that regulate biological responses to radiation at different radiation doses and elucidate the impact of low-dose radiation exposure on human health.

Phosphoproteomics profiling of human skin fibroblast cells reveals pathways and proteins affected by low doses of ionizing radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Feng; Waters, Katrina M.; Miller, John H.

2010-11-30

Background: High doses of ionizing radiation result in biological damage, however the precise relationships between long term health effects, including cancer, and low dose exposures remain poorly understood and are currently extrapolated using high dose exposure data. Identifying the signaling pathways and individual proteins affected at the post-translational level by radiation should shed valuable insight into the molecular mechanisms that regulate dose dependent responses to radiation. Principle Findings: We have identified 6845 unique phosphopeptides (2566 phosphoproteins) from control and irradiated (2 and 50 cGy) primary human skin fibroblasts one hour post-exposure. Dual statistical analyses based on spectral counts and peakmore » intensities identified 287 phosphopeptides (from 231 proteins) and 244 phosphopeptides (from 182 proteins) that varied significantly following exposure to 2 and 50 cGy respectively. This screen identified phosphorylation sites on proteins with known roles in radiation responses including TP53BP1 as well as previously unidentified radiation responsive proteins such as the candidate tumor suppressor SASH1. Bioinformatics analyses suggest that low and high doses of radiation affect both overlapping and unique biological processes and suggest a role of MAP kinase and protein kinase A (PKA) signaling in the radiation response as well as differential regulation of p53 networks at low and high doses of radiation. Conlcusions: Our results represent the most comprehensive analysis of the phosphoproteomes of human primary fibroblasts exposed to multiple doses of ionizing radiation published to date and provides a basis for the systems level identification of biological processes, molecular pathways and individual proteins regulated in a dose dependent manner by ionizing radiation. Further study of these modified proteins and affected networks should help to define the molecular mechanisms that regulate biological responses to radiation at

Phosphoproteomics Profiling of Human Skin Fibroblast Cells Reveals Pathways and Proteins Affected by Low Doses of Ionizing Radiation

PubMed Central

Yang, Feng; Waters, Katrina M.; Miller, John H.; Gritsenko, Marina A.; Zhao, Rui; Du, Xiuxia; Livesay, Eric A.; Purvine, Samuel O.; Monroe, Matthew E.; Wang, Yingchun; Camp, David G.; Smith, Richard D.; Stenoien, David L.

2010-01-01

Background High doses of ionizing radiation result in biological damage; however, the precise relationships between long-term health effects, including cancer, and low-dose exposures remain poorly understood and are currently extrapolated using high-dose exposure data. Identifying the signaling pathways and individual proteins affected at the post-translational level by radiation should shed valuable insight into the molecular mechanisms that regulate dose-dependent responses to radiation. Principal Findings We have identified 7117 unique phosphopeptides (2566 phosphoproteins) from control and irradiated (2 and 50 cGy) primary human skin fibroblasts 1 h post-exposure. Semi-quantitative label-free analyses were performed to identify phosphopeptides that are apparently altered by radiation exposure. This screen identified phosphorylation sites on proteins with known roles in radiation responses including TP53BP1 as well as previously unidentified radiation-responsive proteins such as the candidate tumor suppressor SASH1. Bioinformatic analyses suggest that low and high doses of radiation affect both overlapping and unique biological processes and suggest a role for MAP kinase and protein kinase A (PKA) signaling in the radiation response as well as differential regulation of p53 networks at low and high doses of radiation. Conclusions Our results represent the most comprehensive analysis of the phosphoproteomes of human primary fibroblasts exposed to multiple doses of ionizing radiation published to date and provide a basis for the systems-level identification of biological processes, molecular pathways and individual proteins regulated in a dose dependent manner by ionizing radiation. Further study of these modified proteins and affected networks should help to define the molecular mechanisms that regulate biological responses to radiation at different radiation doses and elucidate the impact of low-dose radiation exposure on human health. PMID:21152398

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

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

PubMed

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; Torregrossa, Mary M

2016-07-20

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. 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 current strategies for

State Support: A Prerequisite for Global Health Network Effectiveness

PubMed Central

Marten, Robert; Smith, Richard D.

2018-01-01

Shiffman recently summarized lessons for network effectiveness from an impressive collection of case-studies. However, in common with most global health governance analysis in recent years, Shiffman underplays the important role of states in these global networks. As the body which decides and signs international agreements, often provides the resourcing, and is responsible for implementing initiatives all contributing to the prioritization of certain issues over others, state recognition and support is a prerequisite to enabling and determining global health networks’ success. The role of states deserves greater attention, analysis and consideration. We reflect upon the underappreciated role of the state within the current discourse on global health. We present the tobacco case study to illustrate the decisive role of states in determining progress for global health networks, and highlight how states use a legitimacy loop to gain legitimacy from and provide legitimacy to global health networks. Moving forward in assessing global health networks’ effectiveness, further investigating state support as a determinant of success will be critical. Understanding how global health networks and states interact and evolve to shape and support their respective interests should be a focus for future research. PMID:29524958

Global radiative effects of solid fuel cookstove aerosol emissions

NASA Astrophysics Data System (ADS)

Huang, Yaoxian; Unger, Nadine; Storelvmo, Trude; Harper, Kandice; Zheng, Yiqi; Heyes, Chris

2018-04-01

We apply the NCAR CAM5-Chem global aerosol-climate model to quantify the net global radiative effects of black and organic carbon aerosols from global and Indian solid fuel cookstove emissions for the year 2010. Our assessment accounts for the direct radiative effects, changes to cloud albedo and lifetime (aerosol indirect effect, AIE), impacts on clouds via the vertical temperature profile (semi-direct effect, SDE) and changes in the surface albedo of snow and ice (surface albedo effect). In addition, we provide the first estimate of household solid fuel black carbon emission effects on ice clouds. Anthropogenic emissions are from the IIASA GAINS ECLIPSE V5a inventory. A global dataset of black carbon (BC) and organic aerosol (OA) measurements from surface sites and aerosol optical depth (AOD) from AERONET is used to evaluate the model skill. Compared with observations, the model successfully reproduces the spatial patterns of atmospheric BC and OA concentrations, and agrees with measurements to within a factor of 2. Globally, the simulated AOD agrees well with observations, with a normalized mean bias close to zero. However, the model tends to underestimate AOD over India and China by ˜ 19 ± 4 % but overestimate it over Africa by ˜ 25 ± 11 % (± represents modeled temporal standard deviations for n = 5 run years). Without BC serving as ice nuclei (IN), global and Indian solid fuel cookstove aerosol emissions have net global cooling radiative effects of -141 ± 4 mW m-2 and -12 ± 4 mW m-2, respectively (± represents modeled temporal standard deviations for n = 5 run years). The net radiative impacts are dominated by the AIE and SDE mechanisms, which originate from enhanced cloud condensation nuclei concentrations for the formation of liquid and mixed-phase clouds, and a suppression of convective transport of water vapor from the lower troposphere to the upper troposphere/lower stratosphere that in turn leads to reduced ice cloud formation. When BC is allowed

The effects of variable biome distribution on global climate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Noever, D.A.; Brittain, A.; Matsos, H.C.

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 anmore » 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.« less

Proteomics/phosphoproteomics of left ventricular biopsies from patients with surgical coronary revascularization and pigs with coronary occlusion/reperfusion: remote ischemic preconditioning.

PubMed

Gedik, Nilgün; Krüger, Marcus; Thielmann, Matthias; Kottenberg, Eva; Skyschally, Andreas; Frey, Ulrich H; Cario, Elke; Peters, Jürgen; Jakob, Heinz; Heusch, Gerd; Kleinbongard, Petra

2017-08-09

Remote ischemic preconditioning (RIPC) by repeated brief cycles of limb ischemia/reperfusion reduces myocardial ischemia/reperfusion injury. In left ventricular (LV) biopsies from patients undergoing coronary artery bypass grafting (CABG), only the activation of signal transducer and activator of transcription 5 was associated with RIPC's cardioprotection. We have now used an unbiased, non-hypothesis-driven proteomics and phosphoproteomics approach to analyze LV biopsies from patients undergoing CABG and from pigs undergoing coronary occlusion/reperfusion without (sham) and with RIPC. False discovery rate-based statistics identified a higher prostaglandin reductase 2 expression at early reperfusion with RIPC than with sham in patients. In pigs, the phosphorylation of 116 proteins was different between baseline and early reperfusion with RIPC and/or with sham. The identified proteins were not identical for patients and pigs, but in-silico pathway analysis of proteins with ≥2-fold higher expression/phosphorylation at early reperfusion with RIPC in comparison to sham revealed a relation to mitochondria and cytoskeleton in both species. Apart from limitations of the proteomics analysis per se, the small cohorts, the sampling/sample processing and the number of uncharacterized/unverifiable porcine proteins may have contributed to this largely unsatisfactory result.

Quantitative phosphoproteomic analysis of host responses in human lung epithelial (A549) cells during influenza virus infection.

PubMed

Dapat, Clyde; Saito, Reiko; Suzuki, Hiroshi; Horigome, Tsuneyoshi

2014-01-22

The emergence of antiviral drug-resistant influenza viruses highlights the need for alternative therapeutic strategies. Elucidation of host factors required during virus infection provides information not only on the signaling pathways involved but also on the identification of novel drug targets. RNA interference screening method had been utilized by several studies to determine these host factors; however, proteomics data on influenza host factors are currently limited. In this study, quantitative phosphoproteomic analysis of human lung cell line (A549) infected with 2009 pandemic influenza virus A (H1N1) virus was performed. Phosphopeptides were enriched from tryptic digests of total protein of infected and mock-infected cells using a titania column on an automated purification system followed by iTRAQ labeling. Identification and quantitative analysis of iTRAQ-labeled phosphopeptides were performed using LC-MS/MS. We identified 366 phosphorylation sites on 283 proteins. Of these, we detected 43 upregulated and 35 downregulated proteins during influenza virus infection. Gene ontology enrichment analysis showed that majority of the identified proteins are phosphoproteins involved in RNA processing, immune system process and response to infection. Host-virus interaction network analysis had identified 23 densely connected subnetworks. Of which, 13 subnetworks contained proteins with altered phosphorylation levels during by influenza virus infection. Our results will help to identify potential drug targets that can be pursued for influenza antiviral drug development. Copyright © 2013 Elsevier B.V. All rights reserved.

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

Proteogenomics connects somatic mutations to signalling in breast cancer.

PubMed

Mertins, Philipp; Mani, D R; Ruggles, Kelly V; Gillette, Michael A; Clauser, Karl R; Wang, Pei; Wang, Xianlong; Qiao, Jana W; Cao, Song; Petralia, Francesca; Kawaler, Emily; Mundt, Filip; Krug, Karsten; Tu, Zhidong; Lei, Jonathan T; Gatza, Michael L; Wilkerson, Matthew; Perou, Charles M; Yellapantula, Venkata; Huang, Kuan-lin; Lin, Chenwei; McLellan, Michael D; Yan, Ping; Davies, Sherri R; Townsend, R Reid; Skates, Steven J; Wang, Jing; Zhang, Bing; Kinsinger, Christopher R; Mesri, Mehdi; Rodriguez, Henry; Ding, Li; Paulovich, Amanda G; Fenyö, David; Ellis, Matthew J; Carr, Steven A

2016-06-02

Somatic mutations have been extensively characterized in breast cancer, but the effects of these genetic alterations on the proteomic landscape remain poorly understood. Here we describe quantitative mass-spectrometry-based proteomic and phosphoproteomic analyses of 105 genomically annotated breast cancers, of which 77 provided high-quality data. Integrated analyses provided insights into the somatic cancer genome including the consequences of chromosomal loss, such as the 5q deletion characteristic of basal-like breast cancer. Interrogation of the 5q trans-effects against the Library of Integrated Network-based Cellular Signatures, connected loss of CETN3 and SKP1 to elevated expression of epidermal growth factor receptor (EGFR), and SKP1 loss also to increased SRC tyrosine kinase. Global proteomic data confirmed a stromal-enriched group of proteins in addition to basal and luminal clusters, and pathway analysis of the phosphoproteome identified a G-protein-coupled receptor cluster that was not readily identified at the mRNA level. In addition to ERBB2, other amplicon-associated highly phosphorylated kinases were identified, including CDK12, PAK1, PTK2, RIPK2 and TLK2. We demonstrate that proteogenomic analysis of breast cancer elucidates the functional consequences of somatic mutations, narrows candidate nominations for driver genes within large deletions and amplified regions, and identifies therapeutic targets.

Quantitative- and Phospho-Proteomic Analysis of the Yeast Response to the Tyrosine Kinase Inhibitor Imatinib to Pharmacoproteomics-Guided Drug Line Extension

PubMed Central

dos Santos, Sandra C.; Mira, Nuno P.; Moreira, Ana S.

2012-01-01

Abstract Imatinib mesylate (IM) is a potent tyrosine kinase inhibitor used as front-line therapy in chronic myeloid leukemia, a disease caused by the oncogenic kinase Bcr-Abl. Although the clinical success of IM set a new paradigm in molecular-targeted therapy, the emergence of IM resistance is a clinically significant problem. In an effort to obtain new insights into the mechanisms of adaptation and tolerance to IM, as well as the signaling pathways potentially affected by this drug, we performed a two-dimensional electrophoresis-based quantitative- and phospho-proteomic analysis in the eukaryotic model Saccharomyces cerevisiae. We singled out proteins that were either differentially expressed or differentially phosphorylated in response to IM, using the phosphoselective dye Pro-Q® Diamond, and identified 18 proteins in total. Ten were altered only at the content level (mostly decreased), while the remaining 8 possessed IM-repressed phosphorylation. These 18 proteins are mainly involved in cellular carbohydrate processes (glycolysis/gluconeogenesis), translation, protein folding, ion homeostasis, and nucleotide and amino acid metabolism. Remarkably, all 18 proteins have human functional homologs. A role for HSP70 proteins in the response to IM, as well as decreased glycolysis as a metabolic marker of IM action are suggested, consistent with findings from studies in human cell lines. The previously-proposed effect of IM as an inhibitor of vacuolar H+-ATPase function was supported by the identification of an underexpressed protein subunit of this complex. Taken together, these findings reinforce the role of yeast as a valuable eukaryotic model for pharmacological studies and identification of new drug targets, with potential clinical implications in drug reassignment or line extension under a personalized medicine perspective. PMID:22775238

Effective Enrichment and Mass Spectrometry Analysis of Phosphopeptides Using Mesoporous Metal Oxide Nanomaterials

PubMed Central

Nelson, Cory A.; Szczech, Jeannine R.; Dooley, Chad J.; Xu, Qingge; Lawrence, Matthew J.; Zhu, Haoyue; Jin, Song; Ge, Ying

2010-01-01

Mass spectrometry (MS)-based phosphoproteomics remains challenging due to the low abundance of phosphoproteins and substoichiometric phosphorylation. This demands better methods to effectively enrich phosphoproteins/peptides prior to MS analysis. We have previously communicated the first use of mesoporous zirconium oxide (ZrO2) nanomaterials for effective phosphopeptide enrichment. Here we present the full report including the synthesis, characterization, and application of mesoporous titanium dioxide (TiO2), ZrO2, and hafnium oxide (HfO2) in phosphopeptide enrichment and MS analysis. Mesoporous ZrO2 and HfO2 are demonstrated to be superior to TiO2 for phosphopeptide enrichment from a complex mixture with high specificity (>99%), which could almost be considered as “a purification”, mainly because of the extremely large active surface area of mesoporous nanomaterials. A single enrichment and Fourier transform MS analysis of phosphopeptides digested from a complex mixture containing 7% of α-casein identified 21 out of 22 phosphorylation sites for α-casein. Moreover, the mesoporous ZrO2 and HfO2 can be reused after a simple solution regeneration procedure with comparable enrichment performance to that of fresh materials. Mesoporous ZrO2 and HfO2 nanomaterials hold great promise for applications in MS-based phosphoproteomics. PMID:20704311

Developing Global Leaders: Building Effective Global- Intercultural Collaborative Online Learning Environments

ERIC Educational Resources Information Center

Ivy, Karen Lynne-Daniels

2017-01-01

This paper shares the findings of a study conducted on a virtual inter-cultural global leadership development learning project. Mixed Methods analysis techniques were used to examine the interviews of U.S. and Uganda youth project participants. The study, based on cultural and social constructivist learning theories, investigated the effects of…

Quantitative phosphoproteomics analysis reveals a key role of insulin growth factor 1 receptor (IGF1R) tyrosine kinase in human sperm capacitation.

PubMed

Wang, Jing; Qi, Lin; Huang, Shaoping; Zhou, Tao; Guo, Yueshuai; Wang, Gaigai; Guo, Xuejiang; Zhou, Zuomin; Sha, Jiahao

2015-04-01

One of the most important changes during sperm capacitation is the enhancement of tyrosine phosphorylation. However, the mechanisms of protein tyrosine phosphorylation during sperm capacitation are not well studied. We used label-free quantitative phosphoproteomics to investigate the overall phosphorylation events during sperm capacitation in humans and identified 231 sites with increased phosphorylation levels. Motif analysis using the NetworKIN algorithm revealed that the activity of tyrosine phosphorylation kinases insulin growth factor 1 receptor (IGF1R)/insulin receptor is significantly enriched among the up-regulated phosphorylation substrates during capacitation. Western blotting further confirmed inhibition of IGF1R with inhibitors GSK1904529A and NVP-AEW541, which inhibited the increase in tyrosine phosphorylation levels during sperm capacitation. Additionally, sperm hyperactivated motility was also inhibited by GSK1904529A and NVP-AEW541 but could be up-regulated by insulin growth factor 1, the ligand of IGF1R. Thus, the IGF1R-mediated tyrosine phosphorylation pathway may play important roles in the regulation of sperm capacitation in humans and could be a target for improvement in sperm functions in infertile men. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

CPTAC Releases Cancer Proteome Confirmatory Colon Study Data | Office of Cancer Clinical Proteomics Research

Cancer.gov

The National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) announces the release of the cancer proteome confirmatory colon study data. The goal of the study is to analyze the proteomes of approximately 100 confirmatory colon tumor patients, which includes tumor and adjacent normal samples, with liquid chromatography-tandem mass spectrometry (LC-MS/MS) global proteomic and phosphoproteomic profiling.

Selection of an Appropriate Protein Extraction Method to Study the Phosphoproteome of Maize Photosynthetic Tissue

PubMed Central

Luís, Inês M.; Alexandre, Bruno M.; Oliveira, M. Margarida

2016-01-01

Often plant tissues are recalcitrant and, due to that, methods relying on protein precipitation, such as TCA/acetone precipitation and phenol extraction, are usually the methods of choice for protein extraction in plant proteomic studies. However, the addition of precipitation steps to protein extraction methods may negatively impact protein recovery, due to problems associated with protein re-solubilization. Moreover, we show that when working with non-recalcitrant plant tissues, such as young maize leaves, protein extraction methods with precipitation steps compromise the maintenance of some labile post-translational modifications (PTMs), such as phosphorylation. Therefore, a critical issue when studying PTMs in plant proteins is to ensure that the protein extraction method is the most appropriate, both at qualitative and quantitative levels. In this work, we compared five methods for protein extraction of the C4-photosynthesis related proteins, in the tip of fully expanded third-leaves. These included: TCA/Acetone Precipitation; Phenol Extraction; TCA/Acetone Precipitation followed by Phenol Extraction; direct extraction in Lysis Buffer (a urea-based buffer); and direct extraction in Lysis Buffer followed by Cleanup with a commercial kit. Protein extraction in Lysis Buffer performed better in comparison to the other methods. It gave one of the highest protein yields, good coverage of the extracted proteome and phosphoproteome, high reproducibility, and little protein degradation. This was also the easiest and fastest method, warranting minimal sample handling. We also show that this method is adequate for the successful extraction of key enzymes of the C4-photosynthetic metabolism, such as PEPC, PPDK, PEPCK, and NADP-ME. This was confirmed by MALDI-TOF/TOF MS analysis of excised spots of 2DE analyses of the extracted protein pools. Staining for phosphorylated proteins in 2DE revealed the presence of several phosphorylated isoforms of PEPC, PPDK, and PEPCK. PMID

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)

Dynamic Interaction- and Phospho-Proteomics Reveal Lck as a Major Signaling Hub of CD147 in T Cells.

PubMed

Supper, Verena; Hartl, Ingrid; Boulègue, Cyril; Ohradanova-Repic, Anna; Stockinger, Hannes

2017-03-15

Numerous publications have addressed CD147 as a tumor marker and regulator of cytoskeleton, cell growth, stress response, or immune cell function; however, the molecular functionality of CD147 remains incompletely understood. Using affinity purification, mass spectrometry, and phosphopeptide enrichment of isotope-labeled peptides, we examined the dynamic of the CD147 microenvironment and the CD147-dependent phosphoproteome in the Jurkat T cell line upon treatment with T cell stimulating agents. We identified novel dynamic interaction partners of CD147 such as CD45, CD47, GNAI2, Lck, RAP1B, and VAT1 and, furthermore, found 76 CD147-dependent phosphorylation sites on 57 proteins. Using the STRING protein network database, a network between the CD147 microenvironment and the CD147-dependent phosphoproteins was generated and led to the identification of key signaling hubs around the G proteins RAP1B and GNB1, the kinases PKCβ, PAK2, Lck, and CDK1, and the chaperone HSPA5. Gene ontology biological process term analysis revealed that wound healing-, cytoskeleton-, immune system-, stress response-, phosphorylation- and protein modification-, defense response to virus-, and TNF production-associated terms are enriched within the microenvironment and the phosphoproteins of CD147. With the generated signaling network and gene ontology biological process term grouping, we identify potential signaling routes of CD147 affecting T cell growth and function. Copyright © 2017 by The American Association of Immunologists, Inc.

Comparative qualitative phosphoproteomics analysis identifies shared phosphorylation motifs and associated biological processes in evolutionary divergent plants.

PubMed

Al-Momani, Shireen; Qi, Da; Ren, Zhe; Jones, Andrew R

2018-06-15

Phosphorylation is one of the most prevalent post-translational modifications and plays a key role in regulating cellular processes. We carried out a bioinformatics analysis of pre-existing phosphoproteomics data, to profile two model species representing the largest subclasses in flowering plants the dicot Arabidopsis thaliana and the monocot Oryza sativa, to understand the extent to which phosphorylation signaling and function is conserved across evolutionary divergent plants. We identified 6537 phosphopeptides from 3189 phosphoproteins in Arabidopsis and 2307 phosphopeptides from 1613 phosphoproteins in rice. We identified phosphorylation motifs, finding nineteen pS motifs and two pT motifs shared in rice and Arabidopsis. The majority of shared motif-containing proteins were mapped to the same biological processes with similar patterns of fold enrichment, indicating high functional conservation. We also identified shared patterns of crosstalk between phosphoserines with enrichment for motifs pSXpS, pSXXpS and pSXXXpS, where X is any amino acid. Lastly, our results identified several pairs of motifs that are significantly enriched to co-occur in Arabidopsis proteins, indicating cross-talk between different sites, but this was not observed in rice. Our results demonstrate that there are evolutionary conserved mechanisms of phosphorylation-mediated signaling in plants, via analysis of high-throughput phosphorylation proteomics data from key monocot and dicot species: rice and Arabidposis thaliana. The results also suggest that there is increased crosstalk between phosphorylation sites in A. thaliana compared with rice. The results are important for our general understanding of cell signaling in plants, and the ability to use A. thaliana as a general model for plant biology. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Phosphoproteomics of Klebsiella pneumoniae NTUH-K2044 Reveals a Tight Link between Tyrosine Phosphorylation and Virulence*

PubMed Central

Lin, Miao-Hsia; Hsu, Tung-Li; Lin, Shu-Yu; Pan, Yi-Jiun; Jan, Jia-Tsrong; Wang, Jin-Town; Khoo, Kay-Hooi; Wu, Shih-Hsiung

2009-01-01

Encapsulated Klebsiella pneumoniae is the predominant causative agent of pyogenic liver abscess, an emerging infectious disease that often complicates metastatic meningitis or endophthalmitis. The capsular polysaccharide on K. pneumoniae surface was determined as the key to virulence. Although the regulation of capsular polysaccharide biosynthesis is largely unclear, it was found that protein-tyrosine kinases and phosphatases are involved. Therefore, the identification and characterization of such kinases, phosphatases, and their substrates would advance our knowledge of the underlying mechanism in capsule formation and could contribute to the development of new therapeutic strategies. Here, we analyzed the phosphoproteome of K. pneumoniae NTUH-K2044 with a shotgun approach and identified 117 unique phosphopeptides along with 93 in vivo phosphorylated sites corresponding to 81 proteins. Interestingly, three of the identified tyrosine phosphorylated proteins, namely protein-tyrosine kinase (Wzc), phosphomannomutase (ManB), and undecaprenyl-phosphate glycosyltransferase (WcaJ), were found to be distributed in the cps locus and thus were speculated to be involved in the converging signal transduction of capsule biosynthesis. Consequently, we decided to focus on the lesser studied ManB and WcaJ for mutation analysis. The capsular polysaccharides of WcaJ mutant (WcaJY5F) were dramatically reduced quantitatively, and the LD50 increased by 200-fold in a mouse peritonitis model compared with the wild-type strain. However, the capsular polysaccharides of ManB mutant (ManBY26F) showed no difference in quantity, and the LD50 increased by merely 6-fold in mice test. Our study provided a clear trend that WcaJ tyrosine phosphorylation can regulate the biosynthesis of capsular polysaccharides and result in the pathogenicity of K. pneumoniae NTUH-K2044. PMID:19696081

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 PM 2.5 emissions by comparing a scenario of non-EURO standards against the current estimates provided by EDGAR. We find that PM 2.5 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

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.

Comprehensive effective and efficient global public health surveillance

PubMed Central

2010-01-01

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

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

Identification of significant features by the Global Mean Rank test.

PubMed

Klammer, Martin; Dybowski, J Nikolaj; Hoffmann, Daniel; Schaab, Christoph

2014-01-01

With the introduction of omics-technologies such as transcriptomics and proteomics, numerous methods for the reliable identification of significantly regulated features (genes, proteins, etc.) have been developed. Experimental practice requires these tests to successfully deal with conditions such as small numbers of replicates, missing values, non-normally distributed expression levels, and non-identical distributions of features. With the MeanRank test we aimed at developing a test that performs robustly under these conditions, while favorably scaling with the number of replicates. The test proposed here is a global one-sample location test, which is based on the mean ranks across replicates, and internally estimates and controls the false discovery rate. Furthermore, missing data is accounted for without the need of imputation. In extensive simulations comparing MeanRank to other frequently used methods, we found that it performs well with small and large numbers of replicates, feature dependent variance between replicates, and variable regulation across features on simulation data and a recent two-color microarray spike-in dataset. The tests were then used to identify significant changes in the phosphoproteomes of cancer cells induced by the kinase inhibitors erlotinib and 3-MB-PP1 in two independently published mass spectrometry-based studies. MeanRank outperformed the other global rank-based methods applied in this study. Compared to the popular Significance Analysis of Microarrays and Linear Models for Microarray methods, MeanRank performed similar or better. Furthermore, MeanRank exhibits more consistent behavior regarding the degree of regulation and is robust against the choice of preprocessing methods. MeanRank does not require any imputation of missing values, is easy to understand, and yields results that are easy to interpret. The software implementing the algorithm is freely available for academic and commercial use.

Global alliances effect in coalition forming

NASA Astrophysics Data System (ADS)

Vinogradova, Galina; Galam, Serge

2014-11-01

Coalition forming is investigated among countries, which are coupled with short range interactions, under the influence of externally-set opposing global alliances. The model extends a recent Natural Model of coalition forming inspired from Statistical Physics, where instabilities are a consequence of decentralized maximization of the individual benefits of actors. In contrast to physics where spins can only evaluate the immediate cost/benefit of a flip of orientation, countries have a long horizon of rationality, which associates with the ability to envision a way up to a better configuration even at the cost of passing through intermediate loosing states. The stabilizing effect is produced through polarization by the global alliances of either a particular unique global interest factor or multiple simultaneous ones. This model provides a versatile theoretical tool for the analysis of real cases and design of novel strategies. Such analysis is provided for several real cases including the Eurozone. The results shed a new light on the understanding of the complex phenomena of planned stabilization in the coalition forming.

State Support: A Prerequisite for Global Health Network Effectiveness Comment on "Four Challenges that Global Health Networks Face".

PubMed

Marten, Robert; Smith, Richard D

2017-07-24

Shiffman recently summarized lessons for network effectiveness from an impressive collection of case-studies. However, in common with most global health governance analysis in recent years, Shiffman underplays the important role of states in these global networks. As the body which decides and signs international agreements, often provides the resourcing, and is responsible for implementing initiatives all contributing to the prioritization of certain issues over others, state recognition and support is a prerequisite to enabling and determining global health networks' success. The role of states deserves greater attention, analysis and consideration. We reflect upon the underappreciated role of the state within the current discourse on global health. We present the tobacco case study to illustrate the decisive role of states in determining progress for global health networks, and highlight how states use a legitimacy loop to gain legitimacy from and provide legitimacy to global health networks. Moving forward in assessing global health networks' effectiveness, further investigating state support as a determinant of success will be critical. Understanding how global health networks and states interact and evolve to shape and support their respective interests should be a focus for future research. © 2018 The Author(s); Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Quantitative phosphoproteomic analysis of neuronal intermediate filament proteins (NF-M/H) in Alzheimer's disease by iTRAQ.

PubMed

Rudrabhatla, Parvathi; Grant, Philip; Jaffe, Howard; Strong, Michael J; Pant, Harish C

2010-11-01

Aberrant hyperphosphorylation of neuronal cytoskeletal proteins is one of the major pathological hallmarks of neurodegenerative disorders such as Alzheimer disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Human NF-M/H display a large number of multiple KSP repeats in the carboxy-terminal tail domain, which are phosphorylation sites of proline-directed serine/threonine (pSer/Thr-Pro, KS/T-P) kinases. The phosphorylation sites of NF-M/H have not been characterized in AD brain. Here, we use quantitative phosphoproteomic methodology, isobaric tag for relative and absolute quantitation (iTRAQ), for the characterization of NF-M/H phosphorylation sites in AD brain. We identified 13 hyperphosphorylated sites of NF-M; 9 Lys-Ser-Pro (KSP) sites; 2 variant motifs, Glu-Ser-Pro (ESP) Ser-736 and Leu-Ser-Pro (LSP) Ser-837; and 2 non-S/T-P motifs, Ser-783 and Ser-788. All the Ser/Thr residues are phosphorylated at significantly greater abundance in AD brain compared with control brain. Ten hyperphosphorylated KSP sites have been identified on the C-terminal tail domain of NF-H, with greater abundance of phosphorylation in AD brain compared with control brain. Our data provide the direct evidence that NF-M/H are hyperphosphorylated in AD compared with control brain and suggest the role of both proline-directed and non-proline-directed protein kinases in AD. This study represents the first comprehensive iTRAQ analyses and quantification of phosphorylation sites of human NF-M and NF-H from AD brain and suggests that aberrant hyperphosphorylation of neuronal intermediate filament proteins is involved in AD.

The influence of global self-heating on the Yarkovsky and YORP effects

NASA Astrophysics Data System (ADS)

Rozitis, B.; Green, S. F.

2013-07-01

In addition to collisions and gravitational forces, there is a growing amount of evidence that photon recoil forces from the asymmetric reflection and thermal re-radiation of absorbed sunlight are primary mechanisms that are fundamental to the physical and dynamical evolution of small asteroids. The Yarkovsky effect causes orbital drift, and the Yarkovsky-O'Keefe-Radzievskii-Paddack (YORP) effect causes changes in the rotation rate and pole orientation. We present an adaptation of the Advanced Thermophysical Model to simultaneously predict the Yarkovsky and YORP effects in the presence of global self-heating that occurs within the large concavities of irregularly shaped asteroids, which has been neglected or dismissed in all previous models. It is also combined with rough surface thermal-infrared beaming effects, which have been previously shown to enhance the Yarkovsky orbital drift and dampen on average the YORP rotational acceleration by orders of several tens of per cent. Tests on all published concave shape models of near-Earth asteroids, and also on 100 Gaussian random spheres, show that the Yarkovsky effect is sensitive to shadowing and global self-heating effects at the few per cent level or less. For simplicity, Yarkovsky models can neglect these effects if the level of accuracy desired is of this order. Unlike the Yarkovsky effect, the YORP effect can be very sensitive to shadowing and global self-heating effects. Its sensitivity increases with decreasing relative strength of the YORP rotational acceleration, and does not appear to depend greatly on the degree of asteroid concavity. Global self-heating tends to produce a vertical offset in an asteroid's YORP-rotational-acceleration versus obliquity curve which is in opposite direction to that produced by shadowing effects. It also ensures that at least one critical obliquity angle exists at which zero YORP rotational acceleration occurs. Global self-heating must be included for accurate predictions of the

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.

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.

Attributional processes in the learned helplessness paradigm: behavioral effects of global attributions.

PubMed

Mikulincer, M

1986-12-01

Following the learned helplessness paradigm, I assessed in this study the effects of global and specific attributions for failure on the generalization of performance deficits in a dissimilar situation. Helplessness training consisted of experience with noncontingent failures on four cognitive discrimination problems attributed to either global or specific causes. Experiment 1 found that performance in a dissimilar situation was impaired following exposure to globally attributed failure. Experiment 2 examined the behavioral effects of the interaction between stable and global attributions of failure. Exposure to unsolvable problems resulted in reduced performance in a dissimilar situation only when failure was attributed to global and stable causes. Finally, Experiment 3 found that learned helplessness deficits were a product of the interaction of global and internal attribution. Performance deficits following unsolvable problems were recorded when failure was attributed to global and internal causes. Results were discussed in terms of the reformulated learned helplessness model.

Discontinuous pH gradient-mediated separation of TiO2-enriched phosphopeptides

PubMed Central

Park, Sung-Soo; Maudsley, Stuart

2010-01-01

Global profiling of phosphoproteomes has proven a great challenge due to the relatively low stoichiometry of protein phosphorylation and poor ionization efficiency in mass spectrometers. Effective, physiologically-relevant, phosphoproteome research relies on the efficient phosphopeptide enrichment from complex samples. Immobilized metal affinity chromatography and titanium dioxide chromatography (TOC) can greatly assist selective phosphopeptide enrichment. However, the complexity of resultant enriched samples is often still high, suggesting that further separation of enriched phosphopeptides is required. We have developed a pH-gradient elution technique for enhanced phosphopeptide identification in conjunction with TOC. Using this process, we have demonstrated its superiority to the traditional ‘one-pot’ strategies for differential protein identification. Our technique generated a highly specific separation of phosphopeptides by an applied pH-gradient between 9.2 and 11.3. The most efficient elution range for high-resolution phosphopeptide separation was between pH 9.2 and 9.4. High-resolution separation of multiply-phosphorylated peptides was primarily achieved using elution ranges > pH 9.4. Investigation of phosphopeptide sequences identified in each pH fraction indicated that phosphopeptides with phosphorylated residues proximal to acidic residues, including glutamic acid, aspartic acid, and other phosphorylated residues, were preferentially eluted at higher pH values. PMID:20946866

[Effects of globalization of structure and function of public health service in Germany].

PubMed

Bauch, J

1999-01-01

This essay discusses the effects of globalization on the German health care system. Globalization is regarded as a process to a "One-World-Society" without limits or borders to communication. Especially the economic effects of globalization are discussed, and the reduction of working places and wage levels in developed industrial societies, caused by globalization. Considering this development, it will not be possible to uphold present health care standards.

Multi-year global climatic effects of atmospheric dust from large bolide impacts

NASA Technical Reports Server (NTRS)

Thompson, Starley L.

1988-01-01

The global climatic effects of dust generated by the impact of a 10 km-diameter bolide was simulated using a one-dimensional (vertical only) globally-averaged climate model by Pollack et al. The goal of the simulation is to examine the regional climate effects, including the possibility of coastal refugia, generated by a global dust cloud in a model having realistic geographic resolution. The climate model assumes the instantaneous appearance of a global stratospheric dust cloud with initial optical depth of 10,000. The time history of optical depth decreases according to the detailed calculations of Pollack et al., reaching an optical depth of unity at day 160, and subsequently decreasing with an e-folding time of 1 year. The simulation is carried out for three years in order to examine the atmospheric effects and recovery over several seasons. The simulation does not include any effects of NOx, CO2, or wildfire smoke injections that may accompany the creation of the dust cloud. The global distribution of surface temperature changes, freezing events, precipitation and soil moisture effects and sea ice increases will be discussed.

Quantitative Phospho-proteomic Analysis of TNFα/NFκB Signaling Reveals a Role for RIPK1 Phosphorylation in Suppressing Necrotic Cell Death.

PubMed

Mohideen, Firaz; Paulo, Joao A; Ordureau, Alban; Gygi, Steve P; Harper, J Wade

2017-07-01

TNFα is a potent inducer of inflammation due to its ability to promote gene expression, in part via the NFκB pathway. Moreover, in some contexts, TNFα promotes Caspase-dependent apoptosis or RIPK1/RIPK3/MLKL-dependent necrosis. Engagement of the TNF Receptor Signaling Complex (TNF-RSC), which contains multiple kinase activities, promotes phosphorylation of several downstream components, including TAK1, IKKα/IKKβ, IκBα, and NFκB. However, immediate downstream phosphorylation events occurring in response to TNFα signaling are poorly understood at a proteome-wide level. Here we use Tandem Mass Tagging-based proteomics to quantitatively characterize acute TNFα-mediated alterations in the proteome and phosphoproteome with or without inhibition of the cIAP-dependent survival arm of the pathway with a SMAC mimetic. We identify and quantify over 8,000 phosphorylated peptides, among which are numerous known sites in the TNF-RSC, NFκB, and MAP kinase signaling systems, as well as numerous previously unrecognized phosphorylation events. Functional analysis of S320 phosphorylation in RIPK1 demonstrates a role for this event in suppressing its kinase activity, association with CASPASE-8 and FADD proteins, and subsequent necrotic cell death during inflammatory TNFα stimulation. This study provides a resource for further elucidation of TNFα-dependent signaling pathways. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

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.

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...

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,…

Phosphoproteomic Analysis Identifies Focal Adhesion Kinase 2 (FAK2) as a Potential Therapeutic Target for Tamoxifen Resistance in Breast Cancer*

PubMed Central

Wu, Xinyan; Zahari, Muhammad Saddiq; Renuse, Santosh; Nirujogi, Raja Sekhar; Kim, Min-Sik; Manda, Srikanth S.; Stearns, Vered; Gabrielson, Edward; Sukumar, Saraswati; Pandey, Akhilesh

2015-01-01

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. PMID:26330541

Indirect Effects of Global Change: From Physiological and Behavioral Mechanisms to Ecological Consequences.

PubMed

Gunderson, Alex R; Tsukimura, Brian; Stillman, Jonathon H

2017-07-01

A major focus of current ecological research is to understand how global change makes species vulnerable to extirpation. To date, mechanistic ecophysiological analyses of global change vulnerability have focused primarily on the direct effects of changing abiotic conditions on whole-organism physiological traits, such as metabolic rate, locomotor performance, cardiac function, and critical thermal limits. However, species do not live in isolation within their physical environments, and direct effects of climate change are likely to be compounded by indirect effects that result from altered interactions with other species, such as competitors and predators. The Society for Integrative and Comparative Biology 2017 Symposium "Indirect Effects of Global Change: From Physiological and Behavioral Mechanisms to Ecological Consequences" was designed to synthesize multiple approaches to investigating the indirect effects of global change by bringing together researchers that study the indirect effects of global change from multiple perspectives across habitat, type of anthropogenic change, and level of biological organization. Our goal in bringing together researchers from different backgrounds was to foster cross-disciplinary insights into the mechanistic bases and higher-order ecological consequences of indirect effects of global change, and to promote collaboration among fields. © The Author 2017. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Towards quantifying global aerosol radiative effects using lidar

NASA Astrophysics Data System (ADS)

Thorsen, T. J.

2017-12-01

Spaceborne lidar observations alleviate many of the limitations of passivesensors and have great potential to provide accurate global all-sky estimatesof the aerosol direct radiative effect (DRE). However, analysis of CALIPSOlidar observations show that CALIPSO does not detect allradiatively-significant aerosol, i.e. aerosol that directly modifies theEarth's radiation budget. We estimated that using CALIPSO observationsresults in an underestimate of the magnitude of the global mean aerosol DREby up to 54%. The CATS lidar on-board the ISS is shown to have a poorersensitivity than CALIPSO and the expected sensitivity of the upcoming ATLIDlidar on EarthCARE indicates that calculations of the aerosol DRE willcontinue to be significantly biased. Improvements to our knowledge of aerosol forcing, which contributes thelargest uncertainty to climate sensitivity, could be achieved by a futurespace-based HSRL mission. To this end, high-accuracy ground-based andairborne lidar datasets have been used to compute the detection sensitivityrequired to accurately resolve the aerosol DRE. Multiwavelength HSRLmeasurements also can retrieve vertically-resolved aerosol optical propertiesneeded for radiative transfer calculations which are not provided by currentsatellite observations. Current satellite observations also do not provideall the quantities needed to compute the aerosol direct radiative forcing,i.e. the radiative effect of just anthropogenic aerosols. A multiwavelengthHSRL allows for a more refined aerosol classification to be made enablingboth calculations of anthropogenic aerosol radiative effects and betterconstraints on global models.

From local to global measurements of nonclassical nonlinear elastic effects in geomaterials

DOE PAGES

Lott, Martin; Remillieux, Marcel C.; Le Bas, Pierre-Yves; ...

2016-09-07

Here, the equivalence between local and global measures of nonclassical nonlinear elasticity is established in a slender resonant bar. Nonlinear effects are first measured globally using nonlinear resonance ultrasound spectroscopy (NRUS), which monitors the relative shift of the resonance frequency as a function of the maximum dynamic strain in the sample. Subsequently, nonlinear effects are measured locally at various positions along the sample using dynamic acousto elasticity testing (DAET). Finally, after correcting analytically the DAET data for three-dimensional strain effects and integrating numerically these corrected data along the length of the sample, the NRUS global measures are retrieved almost exactly.

Effects of global and local contexts on chord processing: An ERP study.

PubMed

Zhang, Jingjing; Zhou, Xuefeng; Chang, Ruohan; Yang, Yufang

2018-01-31

In real life, the processing of an incoming event is continuously influenced by prior information at multiple timescales. The present study investigated how harmonic contexts at both local and global levels influence the processing of an incoming chord in an event-related potentials experiment. Chord sequences containing two phrases were presented to musically trained listeners, with the last critical chord either harmonically related or less related to its preceding context at local and/or global levels. ERPs data showed an ERAN-like effect for local context in early time window and a N5-like component for later interaction between the local context and global context. These results suggest that both the local and global contexts influence the processing of an incoming music event, and the local effect happens earlier than the global. Moreover, the interaction between the local context and global context in N5 may suggest that music syntactic integration at local level takes place prior to the integration at global level. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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.

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.

Effects of Telecoupling on Global Vegetation Dynamics

NASA Astrophysics Data System (ADS)

Viña, A.; Liu, J.

2016-12-01

With the ever increasing trend in telecoupling processes, such as international trade, all countries around the world are becoming more interdependent. However, the effects of this growing interdependence on vegetation (e.g., shifts in the geographic extent and distribution) remain unknown even though vegetation dynamics are crucially important for food production, carbon sequestration, provision of other ecosystem services, and biodiversity conservation. In this study we evaluate the effects of international trade on the spatio-temporal trajectories of vegetation at national and global scales, using vegetation index imagery collected over more than three decades by the Advanced Very High Resolution Radiometer (AVHRR) satellite sensor series together with concurrent national and international data on international trade (and its associated movement of people, goods, services and information). The spatio-temporal trajectories of vegetation are obtained using the scale of fluctuation technique, which is based on the decomposition of the AVHRR image time series to obtain information on its spatial dependence structure over time. Similar to the correlation length, the scale of fluctuation corresponds to the range over which fluctuations in the vegetation index are spatially correlated. Results indicate that global vegetation has changed drastically over the last three decades. These changes are not uniform across space, with hotspots in active trading countries. This study not only has direct implications for understanding global vegetation dynamics, but also sheds important insights on the complexity of human-nature interactions across telecoupled systems.

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.

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

PubMed

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

2013-03-01

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.

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.

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.

Global precedence effects account for individual differences in both face and object recognition performance.

PubMed

Gerlach, Christian; Starrfelt, Randi

2018-03-20

There has been an increase in studies adopting an individual difference approach to examine visual cognition and in particular in studies trying to relate face recognition performance with measures of holistic processing (the face composite effect and the part-whole effect). In the present study we examine whether global precedence effects, measured by means of non-face stimuli in Navon's paradigm, can also account for individual differences in face recognition and, if so, whether the effect is of similar magnitude for faces and objects. We find evidence that global precedence effects facilitate both face and object recognition, and to a similar extent. Our results suggest that both face and object recognition are characterized by a coarse-to-fine temporal dynamic, where global shape information is derived prior to local shape information, and that the efficiency of face and object recognition is related to the magnitude of the global precedence effect.

Nuclear phosphoproteome analysis of 3T3-L1 preadipocyte differentiation reveals system-wide phosphorylation of transcriptional regulators.

PubMed

Rabiee, Atefeh; Schwämmle, Veit; Sidoli, Simone; Dai, Jie; Rogowska-Wrzesinska, Adelina; Mandrup, Susanne; Jensen, Ole N

2017-03-01

Adipocytes (fat cells) are important endocrine and metabolic cells critical for systemic insulin sensitivity. Both adipose excess and insufficiency are associated with adverse metabolic function. Adipogenesis is the process whereby preadipocyte precursor cells differentiate into lipid-laden mature adipocytes. This process is driven by a network of transcriptional regulators (TRs). We hypothesized that protein PTMs, in particular phosphorylation, play a major role in activating and propagating signals within TR networks upon induction of adipogenesis by extracellular stimulus. We applied MS-based quantitative proteomics and phosphoproteomics to monitor the alteration of nuclear proteins during the early stages (4 h) of preadipocyte differentiation. We identified a total of 4072 proteins including 2434 phosphorylated proteins, a majority of which were assigned as regulators of gene expression. Our results demonstrate that adipogenic stimuli increase the nuclear abundance and/or the phosphorylation levels of proteins involved in gene expression, cell organization, and oxidation-reduction pathways. Furthermore, proteins acting as negative modulators involved in negative regulation of gene expression, insulin stimulated glucose uptake, and cytoskeletal organization showed a decrease in their nuclear abundance and/or phosphorylation levels during the first 4 h of adipogenesis. Among 288 identified TRs, 49 were regulated within 4 h of adipogenic stimulation including several known and many novel potential adipogenic regulators. We created a kinase-substrate database for 3T3-L1 preadipocytes by investigating the relationship between protein kinases and protein phosphorylation sites identified in our dataset. A majority of the putative protein kinases belong to the cyclin-dependent kinase family and the mitogen-activated protein kinase family including P38 and c-Jun N-terminal kinases, suggesting that these kinases act as orchestrators of early adipogenesis. © 2016 WILEY

Global health promotion: how can we strengthen governance and build effective strategies?

PubMed

Lee, Kelley

2006-12-01

This paper discusses what is meant by 'global health promotion' and the extent to which global governance architecture is emerging, enabling people to increase control over, and to improve, their health within an increasingly global context. A review of selected initiatives on breast-milk substitutes, healthy cities, tobacco control and diet and nutrition suggests that existing institutions are uneven in their capacity to tackle global health issues. The strategic building of a global approach to health promotion will draw on a broad range of governance instruments, give careful attention to implementation in the medium to longer term, reflect on the nature and appropriateness of partnerships and develop fuller understanding of effective policies for harnessing the positive influences of globalization and countering the negatives.

Estimation of the global climate effect of brown carbon

NASA Astrophysics Data System (ADS)

Zhang, A.; Wang, Y.; Zhang, Y.; Weber, R. J.; Song, Y.

2017-12-01

Carbonaceous aerosols significantly affect global radiative forcing and climate through absorption and scattering of sunlight. Black carbon (BC) and brown carbon (BrC) are light-absorbing carbonaceous aerosols. The global distribution and climate effect of BrC is uncertain. A recent study suggests that BrC absorption is comparable to BC in the upper troposphere over biomass burning region and that the resulting heating tends to stabilize the atmosphere. Yet current climate models do not include proper treatments of BrC. In this study, we derived a BrC global biomass burning emission inventory from Global Fire Emissions Database 4 (GFED4) and developed a BrC module in the Community Atmosphere Model version 5 (CAM5) of Community Earth System Model (CESM) model. The model simulations compared well to BrC observations of the Studies of Emissions, Atmospheric Composition, Clouds and Climate Coupling by Regional Surveys (SEAC4RS) and Deep Convective Clouds and Chemistry Project (DC-3) campaigns and includes BrC bleaching. Model results suggested that BrC in the upper troposphere due to convective transport is as important an absorber as BC globally. Upper tropospheric BrC radiative forcing is particularly significant over the tropics, affecting the atmosphere stability and Hadley circulation.

Changes in the Phosphoproteome and Metabolome Link Early Signaling Events to Rearrangement of Photosynthesis and Central Metabolism in Salinity and Oxidative Stress Response in Arabidopsis1

PubMed Central

Chen, Yanmei; Hoehenwarter, Wolfgang

2015-01-01

Salinity and oxidative stress are major factors affecting and limiting the productivity of agricultural crops. The molecular and biochemical processes governing the plant response to abiotic stress have often been researched in a reductionist manner. Here, we report a systemic approach combining metabolic labeling and phosphoproteomics to capture early signaling events with quantitative metabolome analysis and enzyme activity assays to determine the effects of salt and oxidative stress on plant physiology. K+ and Na+ transporters showed coordinated changes in their phosphorylation pattern, indicating the importance of dynamic ion homeostasis for adaptation to salt stress. Unique phosphorylation sites were found for Arabidopsis (Arabidopsis thaliana) SNF1 kinase homolog10 and 11, indicating their central roles in the stress-regulated responses. Seven Sucrose Non-fermenting1-Related Protein Kinase2 kinases showed varying levels of phosphorylation at multiple serine/threonine residues in their kinase domain upon stress, showing temporally distinct modulation of the various isoforms. Salinity and oxidative stress also lead to changes in protein phosphorylation of proteins central to photosynthesis, in particular the kinase State Transition Protein7 required for state transition and light-harvesting II complex proteins. Furthermore, stress-induced changes of the phosphorylation of enzymes of central metabolism were observed. The phosphorylation patterns of these proteins were concurrent with changes in enzyme activity. This was reflected by altered levels of metabolites, such as the sugars sucrose and fructose, glycolysis intermediates, and amino acids. Together, our study provides evidence for a link between early signaling in the salt and oxidative stress response that regulates the state transition of photosynthesis and the rearrangement of primary metabolism. PMID:26471895

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…

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.

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

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%.

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…

The emergence and effectiveness of global health networks: findings and future research

PubMed Central

Shiffman, Jeremy; Peter Schmitz, Hans; Berlan, David; Smith, Stephanie L; Quissell, Kathryn; Gneiting, Uwe; Pelletier, David

2016-01-01

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

Uncertainties in global aerosols and climate effects due to biofuel emissions

NASA Astrophysics Data System (ADS)

Kodros, J. K.; Scott, C. E.; Farina, S. C.; Lee, Y. H.; L'Orange, C.; Volckens, J.; Pierce, J. R.

2015-04-01

Aerosol emissions from biofuel combustion impact both health and climate; however, while reducing emissions through improvements to combustion technologies will improve health, the net effect on climate is largely unconstrained. In this study, we examine sensitivities in global aerosol concentration, direct radiative climate effect, and cloud-albedo aerosol indirect climate effect to uncertainties in biofuel emission factors, optical mixing-state, and model nucleation and background SOA. We use the Goddard Earth Observing System global chemical-transport model (GEOS-Chem) with TwO Moment Aerosol Sectional (TOMAS) microphysics. The emission factors include: amount, composition, size and hygroscopicity, as well as optical mixing-state properties. We also evaluate emissions from domestic coal use, which is not biofuel but is also frequently emitted from homes. We estimate the direct radiative effect assuming different mixing states (internal, core-shell, and external) with and without absorptive organic aerosol (brown carbon). We find the global-mean direct radiative effect of biofuel emissions ranges from -0.02 to +0.06 W m-2 across all simulation/mixing state combinations with regional effects in source regions ranging from -0.2 to +1.2 W m-2. The global-mean cloud-albedo aerosol indirect effect ranges from +0.01 to -0.02 W m-2 with regional effects in source regions ranging from -1.0 to -0.05 W m-2. The direct radiative effect is strongly dependent on uncertainties in emissions mass, composition, emissions aerosol size distributions and assumed optical mixing state, while the indirect effect is dependent on the emissions mass, emissions aerosol size distribution and the choice of model nucleation and secondary organic aerosol schemes. The sign and magnitude of these effects have a strong regional dependence. We conclude that the climate effects of biofuel aerosols are largely unconstrained, and the overall sign of the aerosol effects is unclear due to uncertainties

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.

Global shape information increases but color information decreases the composite face effect.

PubMed

Retter, Talia L; Rossion, Bruno

2015-01-01

The separation of visual shape and surface information may be useful for understanding holistic face perception--that is, the perception of a face as a single unit (Jiang, Blanz, & Rossion, 2011, Visual Cognition, 19, 1003-1034). A widely used measure of holistic face perception is the composite face effect (CFE), in which identical top face halves appear different when aligned with bottom face halves from different identities. In the present study the influences of global face shape (ie contour of the face) and color information on the CFE are investigated, with the hypothesis that global face shape supports but color impairs holistic face perception as measured in this paradigm. In experiment 1 the CFE is significantly increased when face stimuli possess natural global shape information than when cropped to a generic (ie oval) global shape; this effect is not found when the stimuli are presented inverted. In experiment 2 the CFE is significantly decreased when face stimuli are presented with color information than when presented in grayscale. These findings indicate that grayscale stimuli maintaining natural global face shape information provide the most adept measure of holistic face perception in the behavioral composite face paradigm. More generally, they show that reducing different types of information diagnostic for individual face perception can have opposite effects on the CFE, illustrating the functional dissociation between shape and surface information in face perception.

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 (PM_2.5) in the US, we conducted a comprehensive modeling effort to evaluate explicitly the effects of change...

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.

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

The Global Education Reform Movement and Its Effect on the Local African American Community

ERIC Educational Resources Information Center

Rushek, Kelli A.

2017-01-01

This conceptual research paper explores educational reformation through the theoretical work of Appadurai (1996) and Castells (2000) in the flows and connectivity of global networks. It discusses the global, national, and local effects of the neoliberal ideological reformations in education and their effects on the African American student…

Uncertainties in global aerosols and climate effects due to biofuel emissions

NASA Astrophysics Data System (ADS)

Kodros, J. K.; Scott, C. E.; Farina, S. C.; Lee, Y. H.; L'Orange, C.; Volckens, J.; Pierce, J. R.

2015-08-01

Aerosol emissions from biofuel combustion impact both health and climate; however, while reducing emissions through improvements to combustion technologies will improve health, the net effect on climate is largely unconstrained. In this study, we examine sensitivities in global aerosol concentration, direct radiative climate effect, and cloud-albedo aerosol indirect climate effect to uncertainties in biofuel emission factors, optical mixing state, and model nucleation and background secondary organic aerosol (SOA). We use the Goddard Earth Observing System global chemical-transport model (GEOS-Chem) with TwO Moment Aerosol Sectional (TOMAS) microphysics. The emission factors include amount, composition, size, and hygroscopicity, as well as optical mixing-state properties. We also evaluate emissions from domestic coal use, which is not biofuel but is also frequently emitted from homes. We estimate the direct radiative effect assuming different mixing states (homogeneous, core-shell, and external) with and without absorptive organic aerosol (brown carbon). We find the global-mean direct radiative effect of biofuel emissions ranges from -0.02 to +0.06 W m-2 across all simulation/mixing-state combinations with regional effects in source regions ranging from -0.2 to +0.8 W m-2. The global-mean cloud-albedo aerosol indirect effect (AIE) ranges from +0.01 to -0.02 W m-2 with regional effects in source regions ranging from -1.0 to -0.05 W m-2. The direct radiative effect is strongly dependent on uncertainties in emissions mass, composition, emissions aerosol size distributions, and assumed optical mixing state, while the indirect effect is dependent on the emissions mass, emissions aerosol size distribution, and the choice of model nucleation and secondary organic aerosol schemes. The sign and magnitude of these effects have a strong regional dependence. We conclude that the climate effects of biofuel aerosols are largely unconstrained, and the overall sign of the aerosol

Novel phosphorylation states of the yeast spindle pole body.

PubMed

Fong, Kimberly K; Zelter, Alex; Graczyk, Beth; Hoyt, Jill M; Riffle, Michael; Johnson, Richard; MacCoss, Michael J; Davis, Trisha N

2018-06-14

Phosphorylation regulates yeast spindle pole body (SPB) duplication and separation and likely regulates microtubule nucleation. We report a phosphoproteomic analysis using tandem mass spectrometry of enriched Saccharomyces cerevisiae SPBs for two cell cycle arrests, G1/S and the mitotic checkpoint, expanding on previously reported phosphoproteomic data sets. We present a novel phosphoproteomic state of SPBs arrested in G1/S by a cdc4-1 temperature sensitive mutation, with particular focus on phosphorylation events on the γ-tubulin small complex (γ-TuSC). The cdc4-1 arrest is the earliest arrest at which microtubule nucleation has occurred at the newly duplicated SPB. Several novel phosphorylation sites were identified in G1/S and during mitosis on the microtubule nucleating γ-TuSC. These sites were analyzed in vivo by fluorescence microscopy and were shown to be required for proper regulation of spindle length. Additionally, in vivo analysis of two mitotic sites in Spc97 found that phosphorylation of at least one of these sites is required for progression through the cell cycle. This phosphoproteomic data set not only broadens the scope of the phosphoproteome of SPBs, it also identifies several γ-TuSC phosphorylation sites that influence microtubule formation. © 2018. Published by The Company of Biologists Ltd.

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.

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

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…

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.

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

Quantification of effective plant rooting depth: advancing global hydrological modelling

NASA Astrophysics Data System (ADS)

Yang, Y.; Donohue, R. J.; McVicar, T.

2017-12-01

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. Moreover, Zr observations are usually only representative of a single plant or several plants, which can differ greatly from the effective Zr over a modelling 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 and provides improved model outputs when compared to BCP model results from two already existing global Zr datasets. 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.

Vacuum-polarization effects in global monopole space-times

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mazzitelli, F.D.; Lousto, C.O.

1991-01-15

The gravitational effect produced by a global monopole may be approximated by a solid deficit angle. As a consequence, the energy-momentum tensor of a quantum field will have a nonzero vacuum expectation value. Here we study this vacuum-polarization effect'' around the monopole. We find explicit expressions for both {l angle}{phi}{sup 2}{r angle}{sub ren} and {l angle}{ital T}{sub {mu}{nu}}{r angle}{sub ren} for a massless scalar field. The back reaction of the quantum field on the monopole metric is also investigated.

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;

Quantitative Phosphoproteomics Unravels Biased Phosphorylation of Serotonin 2A Receptor at Ser280 by Hallucinogenic versus Nonhallucinogenic Agonists*

PubMed Central

Karaki, Samah; Becamel, Carine; Murat, Samy; Mannoury la Cour, Clotilde; Millan, Mark J.; Prézeau, Laurent; Bockaert, Joël; Marin, Philippe; Vandermoere, Franck

2014-01-01

The serotonin 5-HT2A receptor is a primary target of psychedelic hallucinogens such as lysergic acid diethylamine, mescaline, and psilocybin, which reproduce some of the core symptoms of schizophrenia. An incompletely resolved paradox is that only some 5-HT2A receptor agonists exhibit hallucinogenic activity, whereas structurally related agonists with comparable affinity and activity lack such a psychoactive activity. Using a strategy combining stable isotope labeling by amino acids in cell culture with enrichment in phosphorylated peptides by means of hydrophilic interaction liquid chromatography followed by immobilized metal affinity chromatography, we compared the phosphoproteome in HEK-293 cells transiently expressing the 5-HT2A receptor and exposed to either vehicle or the synthetic hallucinogen 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI) or the nonhallucinogenic 5-HT2A agonist lisuride. Among the 5995 identified phosphorylated peptides, 16 sites were differentially phosphorylated upon exposure of cells to DOI versus lisuride. These include a serine (Ser280) located in the third intracellular loop of the 5-HT2A receptor, a region important for its desensitization. The specific phosphorylation of Ser280 by hallucinogens was further validated by quantitative mass spectrometry analysis of immunopurified receptor digests and by Western blotting using a phosphosite specific antibody. The administration of DOI, but not of lisuride, to mice, enhanced the phosphorylation of 5-HT2A receptors at Ser280 in the prefrontal cortex. Moreover, hallucinogens induced a less pronounced desensitization of receptor-operated signaling in HEK-293 cells and neurons than did nonhallucinogenic agonists. The mutation of Ser280 to aspartic acid (to mimic phosphorylation) reduced receptor desensitization by nonhallucinogenic agonists, whereas its mutation to alanine increased the ability of hallucinogens to desensitize the receptor. This study reveals a biased phosphorylation of

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…

The Climate Effects of Deforestation the Amazon Rainforest under Global Warming Conditions

NASA Astrophysics Data System (ADS)

Werth, D.; Avissar, R.

2006-12-01

Replacement of tropical rainforests has been observed to have a strong drying effect in Amazon simulations, with effects reaching high into the atmospheric column and into the midlatitudes. The drying effects of deforestation, however, can be moderated by the effects of global warming, which should accelerate the hydrologic cycle of the Amazon. The effects of a prescribed, time-varying Amazon deforestation done in conjunction with a steady, moderate increase in CO2 concentrations are determined using a climate model. The model agrees with previous studies when each forcing is applied individually - compared to a control run, Amazon deforestation decreases the local precipitation and global warming increases it. When both are applied, however, the precipitation and other hydrologic variables decrease, but to a lesser extent than when deforestation alone was applied. In effect, the two effects act opposite to one another and bring the simulated climate closer to that of the control.

Effect of surface tension on global modes of confined wake flows

NASA Astrophysics Data System (ADS)

Tammisola, Outi; Lundell, Fredrik; Söderberg, L. Daniel

2011-01-01

Many wake flows are susceptible to self-sustained oscillations, such as the well-known von Kármán vortex street behind a cylinder that makes a rope beat against a flagpole at a distinct frequency on a windy day. One appropriate method to study these global instabilities numerically is to look at the growth rates of the linear temporal global modes. If all growth rates for all modes are negative for a certain flow field then a self-sustained oscillation should not occur. On the other hand, if one growth rate for one mode is slightly positive, the oscillation will approximately obtain the frequency and shape of this global mode. In our study, we first introduce surface tension between two fluids to the wake-flow problem. Then we investigate its effects on the global linear instability of a spatially developing wake with two co-flowing immiscible fluids. The inlet profile consists of two uniform layers, which makes the problem easily parametrizable. The fluids are assumed to have the same density and viscosity, with the result that the interface position becomes dynamically important solely through the action of surface tension. Two wakes with different parameter values and surface tension are studied in detail. The results show that surface tension has a strong influence on the oscillation frequency, growth rate, and shape of the global mode(s). Finally, we make an attempt to confirm and explain the surface-tension effect based on a local stability analysis of the same flow field in the streamwise position of maximum reverse flow.

Proteome and phosphoproteome analysis of honeybee (Apis mellifera) venom collected from electrical stimulation and manual extraction of the venom gland

PubMed Central

2013-01-01

Background Honeybee venom is a complicated defensive toxin that has a wide range of pharmacologically active compounds. Some of these compounds are useful for human therapeutics. There are two major forms of honeybee venom used in pharmacological applications: manually (or reservoir disrupting) extracted glandular venom (GV), and venom extracted through the use of electrical stimulation (ESV). A proteome comparison of these two venom forms and an understanding of the phosphorylation status of ESV, are still very limited. Here, the proteomes of GV and ESV were compared using both gel-based and gel-free proteomics approaches and the phosphoproteome of ESV was determined through the use of TiO2 enrichment. Results Of the 43 proteins identified in GV, < 40% were venom toxins, and > 60% of the proteins were non-toxic proteins resulting from contamination by gland tissue damage during extraction and bee death. Of the 17 proteins identified in ESV, 14 proteins (>80%) were venom toxic proteins and most of them were found in higher abundance than in GV. Moreover, two novel proteins (dehydrogenase/reductase SDR family member 11-like and histone H2B.3-like) and three novel phosphorylation sites (icarapin (S43), phospholipase A-2 (T145), and apamin (T23)) were identified. Conclusions Our data demonstrate that venom extracted manually is different from venom extracted using ESV, and these differences may be important in their use as pharmacological agents. ESV may be more efficient than GV as a potential pharmacological source because of its higher venom protein content, production efficiency, and without the need to kill honeybee. The three newly identified phosphorylated venom proteins in ESV may elicit a different immune response through the specific recognition of antigenic determinants. The two novel venom proteins extend our proteome coverage of honeybee venom. PMID:24199871

Global Change Could Amplify Fire Effects on Soil Greenhouse Gas Emissions

PubMed Central

Niboyet, Audrey; Brown, Jamie R.; Dijkstra, Paul; Blankinship, Joseph C.; Leadley, Paul W.; Le Roux, Xavier; Barthes, Laure; Barnard, Romain L.; Field, Christopher B.; Hungate, Bruce A.

2011-01-01

Background Little is known about the combined impacts of global environmental changes and ecological disturbances on ecosystem functioning, even though such combined impacts might play critical roles in shaping ecosystem processes that can in turn feed back to climate change, such as soil emissions of greenhouse gases. Methodology/Principal Findings We took advantage of an accidental, low-severity wildfire that burned part of a long-term global change experiment to investigate the interactive effects of a fire disturbance and increases in CO2 concentration, precipitation and nitrogen supply on soil nitrous oxide (N2O) emissions in a grassland ecosystem. We examined the responses of soil N2O emissions, as well as the responses of the two main microbial processes contributing to soil N2O production – nitrification and denitrification – and of their main drivers. We show that the fire disturbance greatly increased soil N2O emissions over a three-year period, and that elevated CO2 and enhanced nitrogen supply amplified fire effects on soil N2O emissions: emissions increased by a factor of two with fire alone and by a factor of six under the combined influence of fire, elevated CO2 and nitrogen. We also provide evidence that this response was caused by increased microbial denitrification, resulting from increased soil moisture and soil carbon and nitrogen availability in the burned and fertilized plots. Conclusions/Significance Our results indicate that the combined effects of fire and global environmental changes can exceed their effects in isolation, thereby creating unexpected feedbacks to soil greenhouse gas emissions. These findings highlight the need to further explore the impacts of ecological disturbances on ecosystem functioning in the context of global change if we wish to be able to model future soil greenhouse gas emissions with greater confidence. PMID:21687708

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

NASA Astrophysics Data System (ADS)

Varma, Keisha; Linn, Marcia C.

2012-08-01

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 conclusions about how individual variables effect changes in the Earth's temperature. They also carry out inquiry activities to make connections between scientific processes, the socio-scientific issues, and ideas presented in the media. Results show that participating in the unit increases students' understanding of the science. We discuss how students integrate their ideas about global climate change as a result of using virtual experiments that allow them to explore meaningful complexities of the climate system.

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

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.

Effectiveness of forest management strategies to mitigate effects of global change in Siberia

Treesearch

Eric Gustafson; Anatoly Shvidenko; Robert Scheller; Brian Sturtevant

2011-01-01

Siberian forest ecosystems are experiencing multiple global changes. Climate change produces direct (temperature and precipitation) and indirect (altered fire regimes and increase in cold-limited insect outbreaks) effects. Although much of Siberia has not yet been subject to timber harvest, the frontier of timber cutting is advancing steadily across the region. We...

Improved global simulation of groundwater-ecosystem interactions via tight coupling of a dynamic global ecosystem model and a global hydrological model

NASA Astrophysics Data System (ADS)

Braakhekke, Maarten; Rebel, Karin; Dekker, Stefan; Smith, Benjamin; Sutanudjaja, Edwin; van Beek, Rens; van Kampenhout, Leo; Wassen, Martin

2017-04-01

In up to 30% of the global land surface ecosystems are potentially influenced by the presence of a shallow groundwater table. In these regions upward water flux by capillary rise increases soil moisture availability in the root zone, which has a strong effect on evapotranspiration, vegetation dynamics, and fluxes of carbon and nitrogen. Most global hydrological models and several land surface models simulate groundwater table dynamics and their effects on land surface processes. However, these models typically have relatively simplistic representation of vegetation and do not consider changes in vegetation type and structure. Dynamic global vegetation models (DGVMs), describe land surface from an ecological perspective, combining detailed description of vegetation dynamics and structure, and biogeochemical processes and are thus more appropriate to simulate the ecological and biogeochemical effects of groundwater interactions. However, currently virtually all DGVMs ignore these effects, assuming that water tables are too deep to affect soil moisture in the root zone. We have implemented a tight coupling between the dynamic global ecosystem model LPJ-GUESS and the global hydrological model PCR-GLOBWB, which explicitly simulates groundwater dynamics. This coupled model allows us to explicitly account for groundwater effects on terrestrial ecosystem processes at global scale. Results of global simulations indicate that groundwater strongly influences fluxes of water, carbon and nitrogen, in many regions, adding up to a considerable effect at the global scale.

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

Quantitative and Functional Phosphoproteomic Analysis Reveals that Ethylene Regulates Water Transport via the C-Terminal Phosphorylation of Aquaporin PIP2;1 in Arabidopsis.

PubMed

Qing, Dongjin; Yang, Zhu; Li, Mingzhe; Wong, Wai Shing; Guo, Guangyu; Liu, Shichang; Guo, Hongwei; Li, Ning

2016-01-04

Ethylene participates in the regulation of numerous cellular events and biological processes, including water loss, during leaf and flower petal wilting. The diverse ethylene responses may be regulated via dynamic interplays between protein phosphorylation/dephosphorylation and ubiquitin/26S proteasome-mediated protein degradation and protease cleavage. To address how ethylene alters protein phosphorylation through multi-furcated signaling pathways, we performed a (15)N stable isotope labelling-based, differential, and quantitative phosphoproteomics study on air- and ethylene-treated ethylene-insensitive Arabidopsis double loss-of-function mutant ein3-1/eil1-1. Among 535 non-redundant phosphopeptides identified, two and four phosphopeptides were up- and downregulated by ethylene, respectively. Ethylene-regulated phosphorylation of aquaporin PIP2;1 is positively correlated with the water flux rate and water loss in leaf. Genetic studies in combination with quantitative proteomics, immunoblot analysis, protoplast swelling/shrinking experiments, and leaf water loss assays on the transgenic plants expressing both the wild-type and S280A/S283A-mutated PIP2;1 in the both Col-0 and ein3eil1 genetic backgrounds suggest that ethylene increases water transport rate in Arabidopsis cells by enhancing S280/S283 phosphorylation at the C terminus of PIP2;1. Unknown kinase and/or phosphatase activities may participate in the initial up-regulation independent of the cellular functions of EIN3/EIL1. This finding contributes to our understanding of ethylene-regulated leaf wilting that is commonly observed during post-harvest storage of plant organs. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

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…

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…

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

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

Globalization and Health

PubMed Central

Martin, Greg

2005-01-01

This debut editorial of Globalization and Health introduces the journal, briefly delineating its goals and objectives and outlines its scope of subject matter. 'Open Access' publishing is expected to become an increasingly important format for peer reviewed academic journals and that Globalization and Health is 'Open Access' is appropriate. The rationale behind starting a journal dedicated to globalization and health is three fold: Firstly: Globalization is reshaping the social geography within which we might strive to create health or prevent disease. The determinants of health – be they a SARS virus or a predilection for fatty foods – have joined us in our global mobility. Driven by economic liberalization and changing technologies, the phenomenon of 'access' is likely to dominate to an increasing extent the unfolding experience of human disease and wellbeing. Secondly: Understanding globalization as a subject matter itself needs certain benchmarks and barometers of its successes and failings. Health is one such barometer. It is a marker of social infrastructure and social welfare and as such can be used to either sound an alarm or give a victory cheer as our interconnectedness hurts and heals the populations we serve. And lastly: In as much as globalization can have an effect on health, it is also true that health and disease has an effect on globalization as exemplified by the existence of quarantine laws and the devastating economic effects of the AIDS pandemic. A balanced view would propose that the effects of globalization on health (and health systems) are neither universally good nor bad, but rather context specific. If the dialogue pertaining to globalization is to be directed or biased in any direction, then it must be this: that we consider the poor first. PMID:15847699

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.

Quantifying spatially and temporally explicit CO 2 fertilization effects on global terrestrial ecosystem carbon dynamics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Shaoqing; Zhuang, Qianlai; Chen, Min

Current terrestrial ecosystem models are usually driven with global average annual atmospheric carbon dioxide (CO 2) concentration data at the global scale. However, high-precision CO 2 measurement from eddy flux towers showed that seasonal, spatial surface atmospheric CO 2 concentration differences were as large as 35 ppmv and the site-level tests indicated that the CO 2 variation exhibited different effects on plant photosynthesis. Here we used a process-based ecosystem model driven with two spatially and temporally explicit CO 2 data sets to analyze the atmospheric CO 2 fertilization effects on the global carbon dynamics of terrestrial ecosystems from 2003 tomore » 2010. Our results demonstrated that CO 2 seasonal variation had a negative effect on plant carbon assimilation, while CO2 spatial variation exhibited a positive impact. When both CO 2 seasonal and spatial effects were considered, global gross primary production and net ecosystem production were 1.7 Pg C•yr –1 and 0.08 Pg C•yr –1 higher than the simulation using uniformly distributed CO 2 data set and the difference was significant in tropical and temperate evergreen broadleaf forest regions. Moreover, this study suggests that the CO 2 observation network should be expanded so that the realistic CO 2 variation can be incorporated into the land surface models to adequately account for CO 2 fertilization effects on global terrestrial ecosystem carbon dynamics.« less

Quantifying spatially and temporally explicit CO 2 fertilization effects on global terrestrial ecosystem carbon dynamics

DOE PAGES

Liu, Shaoqing; Zhuang, Qianlai; Chen, Min; ...

2016-07-25

Current terrestrial ecosystem models are usually driven with global average annual atmospheric carbon dioxide (CO 2) concentration data at the global scale. However, high-precision CO 2 measurement from eddy flux towers showed that seasonal, spatial surface atmospheric CO 2 concentration differences were as large as 35 ppmv and the site-level tests indicated that the CO 2 variation exhibited different effects on plant photosynthesis. Here we used a process-based ecosystem model driven with two spatially and temporally explicit CO 2 data sets to analyze the atmospheric CO 2 fertilization effects on the global carbon dynamics of terrestrial ecosystems from 2003 tomore » 2010. Our results demonstrated that CO 2 seasonal variation had a negative effect on plant carbon assimilation, while CO2 spatial variation exhibited a positive impact. When both CO 2 seasonal and spatial effects were considered, global gross primary production and net ecosystem production were 1.7 Pg C•yr –1 and 0.08 Pg C•yr –1 higher than the simulation using uniformly distributed CO 2 data set and the difference was significant in tropical and temperate evergreen broadleaf forest regions. Moreover, this study suggests that the CO 2 observation network should be expanded so that the realistic CO 2 variation can be incorporated into the land surface models to adequately account for CO 2 fertilization effects on global terrestrial ecosystem carbon dynamics.« less

Growth-rate dependent global effects on gene expression in bacteria

PubMed Central

Klumpp, Stefan; Zhang, Zhongge; Hwa, Terence

2010-01-01

Summary Bacterial gene expression depends not only on specific regulations but also directly on bacterial growth, because important global parameters such as the abundance of RNA polymerases and ribosomes are all growth-rate dependent. Understanding these global effects is necessary for a quantitative understanding of gene regulation and for the robust design of synthetic genetic circuits. The observed growth-rate dependence of constitutive gene expression can be explained by a simple model using the measured growth-rate dependence of the relevant cellular parameters. More complex growth dependences for genetic circuits involving activators, repressors and feedback control were analyzed, and salient features were verified experimentally using synthetic circuits. The results suggest a novel feedback mechanism mediated by general growth-dependent effects and not requiring explicit gene regulation, if the expressed protein affects cell growth. This mechanism can lead to growth bistability and promote the acquisition of important physiological functions such as antibiotic resistance and tolerance (persistence). PMID:20064380

Global Atmospheric Aerosol Modeling

NASA Technical Reports Server (NTRS)

Hendricks, Johannes; Aquila, Valentina; Righi, Mattia

2012-01-01

Global aerosol models are used to study the distribution and properties of atmospheric aerosol particles as well as their effects on clouds, atmospheric chemistry, radiation, and climate. The present article provides an overview of the basic concepts of global atmospheric aerosol modeling and shows some examples from a global aerosol simulation. Particular emphasis is placed on the simulation of aerosol particles and their effects within global climate models.

Successful conservation of global waterbird populations depends on effective governance

NASA Astrophysics Data System (ADS)

Amano, Tatsuya; Székely, Tamás; Sandel, Brody; Nagy, Szabolcs; Mundkur, Taej; Langendoen, Tom; Blanco, Daniel; Soykan, Candan U.; Sutherland, William J.

2018-01-01

Understanding global patterns of biodiversity change is crucial for conservation research, policies and practices. However, for most ecosystems, the lack of systematically collected data at a global level limits our understanding of biodiversity changes and their local-scale drivers. Here we address this challenge by focusing on wetlands, which are among the most biodiverse and productive of any environments and which provide essential ecosystem services, but are also amongst the most seriously threatened ecosystems. Using birds as an indicator taxon of wetland biodiversity, we model time-series abundance data for 461 waterbird species at 25,769 survey sites across the globe. We show that the strongest predictor of changes in waterbird abundance, and of conservation efforts having beneficial effects, is the effective governance of a country. In areas in which governance is on average less effective, such as western and central Asia, sub-Saharan Africa and South America, waterbird declines are particularly pronounced; a higher protected area coverage of wetland environments facilitates waterbird increases, but only in countries with more effective governance. Our findings highlight that sociopolitical instability can lead to biodiversity loss and undermine the benefit of existing conservation efforts, such as the expansion of protected area coverage. Furthermore, data deficiencies in areas with less effective governance could lead to underestimations of the extent of the current biodiversity crisis.

Successful conservation of global waterbird populations depends on effective governance.

PubMed

Amano, Tatsuya; Székely, Tamás; Sandel, Brody; Nagy, Szabolcs; Mundkur, Taej; Langendoen, Tom; Blanco, Daniel; Soykan, Candan U; Sutherland, William J

2018-01-11

Understanding global patterns of biodiversity change is crucial for conservation research, policies and practices. However, for most ecosystems, the lack of systematically collected data at a global level limits our understanding of biodiversity changes and their local-scale drivers. Here we address this challenge by focusing on wetlands, which are among the most biodiverse and productive of any environments and which provide essential ecosystem services, but are also amongst the most seriously threatened ecosystems. Using birds as an indicator taxon of wetland biodiversity, we model time-series abundance data for 461 waterbird species at 25,769 survey sites across the globe. We show that the strongest predictor of changes in waterbird abundance, and of conservation efforts having beneficial effects, is the effective governance of a country. In areas in which governance is on average less effective, such as western and central Asia, sub-Saharan Africa and South America, waterbird declines are particularly pronounced; a higher protected area coverage of wetland environments facilitates waterbird increases, but only in countries with more effective governance. Our findings highlight that sociopolitical instability can lead to biodiversity loss and undermine the benefit of existing conservation efforts, such as the expansion of protected area coverage. Furthermore, data deficiencies in areas with less effective governance could lead to underestimations of the extent of the current biodiversity crisis.

Effect of limb cooling on peripheral and global oxygen consumption in neonates

PubMed Central

Hassan, I; Wickramasinghe, Y; Spencer, S

2003-01-01

Aim: To evaluate peripheral oxygen consumption (VO2) measurements using near infrared spectroscopy (NIRS) with arterial occlusion in healthy term neonates by studying the effect of limb cooling on peripheral and global VO2. Subjects and methods: Twenty two healthy term neonates were studied. Peripheral VO2 was measured by NIRS using arterial occlusion and measurement of the oxyhaemoglobin (HbO2) decrement slope. Global VO2 was measured by open circuit calorimetry. Global and peripheral VO2 was measured in each neonate before and after limb cooling. Results: In 10 neonates, a fall in forearm temperature of 2.2°C (mild cooling) decreased forearm VO2 by 19.6% (p < 0.01). Global VO2 did not change. In 12 neonates, a fall in forearm temperature of 4°C (moderate cooling) decreased forearm VO2 by 34.7% (p < 0.01). Global VO2 increased by 17.6% (p < 0.05). Conclusions: The NIRS arterial occlusion method is able to measure changes in peripheral VO2 induced by limb cooling. The changes are more pronounced with moderate limb cooling when a concomitant rise in global VO2 is observed. Change in peripheral temperature must be taken into consideration in the interpretation of peripheral VO2 measurements in neonates. PMID:12598504

Effect of limb cooling on peripheral and global oxygen consumption in neonates.

PubMed

Hassan, I A-A; Wickramasinghe, Y A; Spencer, S A

2003-03-01

To evaluate peripheral oxygen consumption (VO(2)) measurements using near infrared spectroscopy (NIRS) with arterial occlusion in healthy term neonates by studying the effect of limb cooling on peripheral and global VO(2). Twenty two healthy term neonates were studied. Peripheral VO(2) was measured by NIRS using arterial occlusion and measurement of the oxyhaemoglobin (HbO(2)) decrement slope. Global VO(2) was measured by open circuit calorimetry. Global and peripheral VO(2) was measured in each neonate before and after limb cooling. In 10 neonates, a fall in forearm temperature of 2.2 degrees C (mild cooling) decreased forearm VO(2) by 19.6% (p < 0.01). Global VO(2) did not change. In 12 neonates, a fall in forearm temperature of 4 degrees C (moderate cooling) decreased forearm VO(2) by 34.7% (p < 0.01). Global VO(2) increased by 17.6% (p < 0.05). The NIRS arterial occlusion method is able to measure changes in peripheral VO(2) induced by limb cooling. The changes are more pronounced with moderate limb cooling when a concomitant rise in global VO(2) is observed. Change in peripheral temperature must be taken into consideration in the interpretation of peripheral VO(2) measurements in neonates.

The effect of giving global coronary risk information to adults: a systematic review.

PubMed

Sheridan, Stacey L; Viera, Anthony J; Krantz, Mori J; Ice, Christa L; Steinman, Lesley E; Peters, Karen E; Kopin, Laurie A; Lungelow, Danielle

2010-02-08

Global coronary heart disease (CHD) risk estimation (ie, a quantitative estimate of a patient's chances of CHD calculated by combining risk factors in an empirical equation) is recommended as a starting point for primary prevention efforts in all US adults. Whether it improves outcomes is currently unknown. To assess the effect of providing global CHD risk information to adults, we performed a systematic evidence review. We searched MEDLINE for the years 1980 to 2008, Psych Info, CINAHL, and the Cochrane Database and included English-language articles that met prespecified inclusion criteria. Two reviewers independently reviewed titles, abstracts, and articles for inclusion and assessed study quality. We identified 20 articles, reporting on 18 unique fair or good quality studies (including 14 randomized controlled studies). These showed that global CHD risk information alone or with accompanying education increased the accuracy of perceived risk and probably increased intent to start therapy. Studies with repeated risk information or risk information and repeated doses of counseling showed small significant reductions in predicted CHD risk (absolute differences, -0.2% to -2% over 10 years in studies using risk estimates derived from Framingham equations). Studies providing global risk information at only 1 point in time seemed ineffective. Global CHD risk information seems to improve the accuracy of risk perception and may increase intent to initiate CHD prevention among individuals at moderate to high risk. The effect of global risk presentation on more distal outcomes is less clear and seems to be related to the intensity of accompanying interventions.

Global phosphorylation analysis of beta-arrestin-mediated signaling downstream of a seven transmembrane receptor (7TMR).

PubMed

Xiao, Kunhong; Sun, Jinpeng; Kim, Jihee; Rajagopal, Sudarshan; Zhai, Bo; Villén, Judit; Haas, Wilhelm; Kovacs, Jeffrey J; Shukla, Arun K; Hara, Makoto R; Hernandez, Marylens; Lachmann, Alexander; Zhao, Shan; Lin, Yuan; Cheng, Yishan; Mizuno, Kensaku; Ma'ayan, Avi; Gygi, Steven P; Lefkowitz, Robert J

2010-08-24

beta-Arrestin-mediated signaling downstream of seven transmembrane receptors (7TMRs) is a relatively new paradigm for signaling by these receptors. We examined changes in protein phosphorylation occurring when HEK293 cells expressing the angiotensin II type 1A receptor (AT1aR) were stimulated with the beta-arrestin-biased ligand Sar(1), Ile(4), Ile(8)-angiotensin (SII), a ligand previously found to signal through beta-arrestin-dependent, G protein-independent mechanisms. Using a phospho-antibody array containing 46 antibodies against signaling molecules, we found that phosphorylation of 35 proteins increased upon SII stimulation. These SII-mediated phosphorylation events were abrogated after depletion of beta-arrestin 2 through siRNA-mediated knockdown. We also performed an MS-based quantitative phosphoproteome analysis after SII stimulation using a strategy of stable isotope labeling of amino acids in cell culture (SILAC). We identified 1,555 phosphoproteins (4,552 unique phosphopeptides), of which 171 proteins (222 phosphopeptides) showed increased phosphorylation, and 53 (66 phosphopeptides) showed decreased phosphorylation upon SII stimulation of the AT1aR. This study identified 38 protein kinases and three phosphatases whose phosphorylation status changed upon SII treatment. Using computational approaches, we performed system-based analyses examining the beta-arrestin-mediated phosphoproteome including construction of a kinase-substrate network for beta-arrestin-mediated AT1aR signaling. Our analysis demonstrates that beta-arrestin-dependent signaling processes are more diverse than previously appreciated. Notably, our analysis identifies an AT1aR-mediated cytoskeletal reorganization network whereby beta-arrestin regulates phosphorylation of several key proteins, including cofilin and slingshot. This study provides a system-based view of beta-arrestin-mediated phosphorylation events downstream of a 7TMR and opens avenues for research in a rapidly evolving area

Separating direct and indirect effects of global change: a population dynamic modeling approach using readily available field data.

PubMed

Farrer, Emily C; Ashton, Isabel W; Knape, Jonas; Suding, Katharine N

2014-04-01

Two sources of complexity make predicting plant community response to global change particularly challenging. First, realistic global change scenarios involve multiple drivers of environmental change that can interact with one another to produce non-additive effects. Second, in addition to these direct effects, global change drivers can indirectly affect plants by modifying species interactions. In order to tackle both of these challenges, we propose a novel population modeling approach, requiring only measurements of abundance and climate over time. To demonstrate the applicability of this approach, we model population dynamics of eight abundant plant species in a multifactorial global change experiment in alpine tundra where we manipulated nitrogen, precipitation, and temperature over 7 years. We test whether indirect and interactive effects are important to population dynamics and whether explicitly incorporating species interactions can change predictions when models are forecast under future climate change scenarios. For three of the eight species, population dynamics were best explained by direct effect models, for one species neither direct nor indirect effects were important, and for the other four species indirect effects mattered. Overall, global change had negative effects on species population growth, although species responded to different global change drivers, and single-factor effects were slightly more common than interactive direct effects. When the fitted population dynamic models were extrapolated under changing climatic conditions to the end of the century, forecasts of community dynamics and diversity loss were largely similar using direct effect models that do not explicitly incorporate species interactions or best-fit models; however, inclusion of species interactions was important in refining the predictions for two of the species. The modeling approach proposed here is a powerful way of analyzing readily available datasets which should be

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.

Aerosol Indirect Effects on Cirrus Clouds in Global Aerosol-Climate Models

NASA Astrophysics Data System (ADS)

Liu, X.; Zhang, K.; Wang, Y.; Neubauer, D.; Lohmann, U.; Ferrachat, S.; Zhou, C.; Penner, J.; Barahona, D.; Shi, X.

2015-12-01

Cirrus clouds play an important role in regulating the Earth's radiative budget and water vapor distribution in the upper troposphere. Aerosols can act as solution droplets or ice nuclei that promote ice nucleation in cirrus clouds. Anthropogenic emissions from fossil fuel and biomass burning activities have substantially perturbed and enhanced concentrations of aerosol particles in the atmosphere. Global aerosol-climate models (GCMs) have now been used to quantify the radiative forcing and effects of aerosols on cirrus clouds (IPCC AR5). However, the estimate uncertainty is very large due to the different representation of ice cloud formation and evolution processes in GCMs. In addition, large discrepancies have been found between model simulations in terms of the spatial distribution of ice-nucleating aerosols, relative humidity, and temperature fluctuations, which contribute to different estimates of the aerosol indirect effect through cirrus clouds. In this presentation, four GCMs with the start-of-the art representations of cloud microphysics and aerosol-cloud interactions are used to estimate the aerosol indirect effects on cirrus clouds and to identify the causes of the discrepancies. The estimated global and annual mean anthropogenic aerosol indirect effect through cirrus clouds ranges from 0.1 W m-2 to 0.3 W m-2 in terms of the top-of-the-atmosphere (TOA) net radiation flux, and 0.5-0.6 W m-2 for the TOA longwave flux. Despite the good agreement on global mean, large discrepancies are found at the regional scale. The physics behind the aerosol indirect effect is dramatically different. Our analysis suggests that burden of ice-nucleating aerosols in the upper troposphere, ice nucleation frequency, and relative role of ice formation processes (i.e., homogeneous versus heterogeneous nucleation) play key roles in determining the characteristics of the simulated aerosol indirect effects. In addition to the indirect effect estimate, we also use field campaign

USGS global change research

USGS Publications Warehouse

,

1995-01-01

The Earth's global environment--its interrelated climate, land, oceans, fresh water, atmospheric and ecological systems-has changed continually throughout Earth history. Human activities are having ever-increasing effects on these systems. Sustaining our environment as population and demands for resources increase requires a sound understanding of the causes and cycles of natural change and the effects of human activities on the Earth's environmental systems. The U.S. Global Change Research Program was authorized by Congress in 1989 to provide the scientific understanding necessary to develop national and international policies concerning global environmental issues, particularly global climate change. The program addresses questions such as: what factors determine global climate; have humans already begun to change the global climate; will the climate of the future be very different; what will be the effects of climate change; and how much confidence do we have in our predictions? Through understanding, we can improve our capability to predict change, reduce the adverse effects of human activities, and plan strategies for adapting to natural and human-induced environmental change.

Globalizing Globalization: The Neo-Institutional Concept of a World Culture

ERIC Educational Resources Information Center

Trohler, Daniel

2009-01-01

In this paper, the author focuses on how globalization and education are addressed in research. More precisely, he concentrates on only one dominant approach to analyzing globalization and its effects on education and also the educational role within globalization. His thesis is that, with the background of Max Weber's Protestant ethic thesis,…

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.

Diverse Responses of Global Vegetation to Climate Changes: Spatial Patterns and Time-lag Effects

NASA Astrophysics Data System (ADS)

Wu, D.; Zhao, X.; Zhou, T.; Huang, K.; Xu, W.

2014-12-01

Global climate changes have enormous influences on vegetation growth, meanwhile, response of vegetation to climate express space diversity and time-lag effects, which account for spatial-temporal disparities of climate change and spatial heterogeneity of ecosystem. Revelation of this phenomenon will help us further understanding the impact of climate change on vegetation. Assessment and forecast of global environmental change can be also improved under further climate change. Here we present space diversity and time-lag effects patterns of global vegetation respond to three climate factors (temperature, precipitation and solar radiation) based on quantitative analysis of satellite data (NDVI) and Climate data (Climate Research Unit). We assessed the time-lag effects of global vegetation to main climate factors based on the great correlation fitness between NDVI and the three climate factors respectively among 0-12 months' temporal lags. On this basis, integrated response model of NDVI and the three climate factors was built to analyze contribution of different climate factors to vegetation growth with multiple regression model and partial correlation model. In the result, different vegetation types have distinct temporal lags to the three climate factors. For the precipitation, temporal lags of grasslands are the shortest while the evergreen broad-leaf forests are the longest, which means that grasslands are more sensitive to precipitation than evergreen broad-leaf forests. Analysis of different climate factors' contribution to vegetation reveal that vegetation are dominated by temperature in the high northern latitudes; they are mainly restricted by precipitation in arid and semi-arid areas (Australia, Western America); in humid areas of low and intermediate latitudes (Amazon, Eastern America), vegetation are mainly influenced by solar radiation. Our results reveal the time-lag effects and major driving factors of global vegetation growth and explain the

A global estimate of the full oceanic 13C Suess effect since the preindustrial

NASA Astrophysics Data System (ADS)

Eide, Marie; Olsen, Are; Ninnemann, Ulysses S.; Eldevik, Tor

2017-03-01

We present the first estimate of the full global ocean 13C Suess effect since preindustrial times, based on observations. This has been derived by first using the method of Olsen and Ninnemann (2010) to calculate 13C Suess effect estimates on sections spanning the world ocean, which were next mapped on a global 1° × 1° grid. We find a strong 13C Suess effect in the upper 1000 m of all basins, with strongest decrease in the subtropical gyres of the Northern Hemisphere, where δ13C of dissolved inorganic carbon has decreased by more than 0.8‰ since the industrial revolution. At greater depths, a significant 13C Suess effect can only be detected in the northern parts of the North Atlantic Ocean. The relationship between the 13C Suess effect and the concentration of anthropogenic carbon varies strongly between water masses, reflecting the degree to which source waters are equilibrated with the atmospheric 13C Suess effect before sinking. Finally, we estimate a global ocean inventory of anthropogenic CO2 of 92 ± 46 Gt C. This provides an estimate that is almost independent of and consistent, within the uncertainties, with previous estimates.

Mesoscale Effects on Carbon Export: A Global Perspective

NASA Astrophysics Data System (ADS)

Harrison, Cheryl S.; Long, Matthew C.; Lovenduski, Nicole S.; Moore, Jefferson K.

2018-04-01

Carbon export from the surface to the deep ocean is a primary control on global carbon budgets and is mediated by plankton that are sensitive to physical forcing. Earth system models generally do not resolve ocean mesoscale circulation (O(10-100) km), scales that strongly affect transport of nutrients and plankton. The role of mesoscale circulation in modulating export is evaluated by comparing global ocean simulations conducted at 1° and 0.1° horizontal resolution. Mesoscale resolution produces a small reduction in globally integrated export production (<2%) however, the impact on local export production can be large (±50%), with compensating effects in different ocean basins. With mesoscale resolution, improved representation of coastal jets block off-shelf transport, leading to lower export in regions where shelf-derived nutrients fuel production. Export is further reduced in these regions by resolution of mesoscale turbulence, which restricts the spatial area of production. Maximum mixed layer depths are narrower and deeper across the Subantarctic at higher resolution, driving locally stronger nutrient entrainment and enhanced summer export production. In energetic regions with seasonal blooms, such as the Subantarctic and North Pacific, internally generated mesoscale variability drives substantial interannual variation in local export production. These results suggest that biogeochemical tracer dynamics show different sensitivities to transport biases than temperature and salinity, which should be considered in the formulation and validation of physical parameterizations. Efforts to compare estimates of export production from observations and models should account for large variability in space and time expected for regions strongly affected by mesoscale circulation.

Global change effects on humid tropical forests: Evidence for biogeochemical and biodiversity shifts at an ecosystem scale

NASA Astrophysics Data System (ADS)

Cusack, Daniela F.; Karpman, Jason; Ashdown, Daniel; Cao, Qian; Ciochina, Mark; Halterman, Sarah; Lydon, Scott; Neupane, Avishesh

2016-09-01

Government and international agencies have highlighted the need to focus global change research efforts on tropical ecosystems. However, no recent comprehensive review exists synthesizing humid tropical forest responses across global change factors, including warming, decreased precipitation, carbon dioxide fertilization, nitrogen deposition, and land use/land cover changes. This paper assesses research across spatial and temporal scales for the tropics, including modeling, field, and controlled laboratory studies. The review aims to (1) provide a broad understanding of how a suite of global change factors are altering humid tropical forest ecosystem properties and biogeochemical processes; (2) assess spatial variability in responses to global change factors among humid tropical regions; (3) synthesize results from across humid tropical regions to identify emergent trends in ecosystem responses; (4) identify research and management priorities for the humid tropics in the context of global change. Ecosystem responses covered here include plant growth, carbon storage, nutrient cycling, biodiversity, and disturbance regime shifts. The review demonstrates overall negative effects of global change on all ecosystem properties, with the greatest uncertainty and variability in nutrient cycling responses. Generally, all global change factors reviewed, except for carbon dioxide fertilization, demonstrate great potential to trigger positive feedbacks to global warming via greenhouse gas emissions and biogeophysical changes that cause regional warming. This assessment demonstrates that effects of decreased rainfall and deforestation on tropical forests are relatively well understood, whereas the potential effects of warming, carbon dioxide fertilization, nitrogen deposition, and plant species invasions require more cross-site, mechanistic research to predict tropical forest responses at regional and global scales.

Effect of dark matter halo on global spiral modes in a collisionless galactic disk

NASA Astrophysics Data System (ADS)

Ghosh, Soumavo; Saini, Tarun Deep; Jog, Chanda J.

2017-07-01

Low surface brightness (LSB) galaxies are dominated by dark matter halo from the innermost radii; hence they are ideal candidates to investigate the influence of dark matter on different dynamical aspects of spiral galaxies. Here, we study the effect of dark matter halo on grand-design, m = 2 , spiral modes in a galactic disk, treated as a collisionless system, by carrying out a global modal analysis within the WKB approximation. First, we study a superthin, LSB galaxy UGC 7321 and show that it does not support discrete global spiral modes when modeled as a disk-alone system or as a disk plus dark matter system. Even a moderate increase in the stellar central surface density does not yield any global spiral modes. This naturally explains the observed lack of strong large-scale spiral structure in LSBs. An earlier work (Ghosh et al., 2016) where the galactic disk was treated as a fluid system for simplicity had shown that the dominant halo could not arrest global modes. We found that this difference arises due to the different dispersion relation used in the two cases and which plays a crucial role in the search for global spiral modes. Thus the correct treatment of stars as a collisionless system as done here results in the suppression of global spiral modes, in agreement with the observations. We performed a similar modal analysis for the Galaxy, and found that the dark matter halo has a negligible effect on large-scale spiral structure.

Peer acceptance protects global self-esteem from negative effects of low closeness to parents during adolescence and early adulthood.

PubMed

Birkeland, Marianne Skogbrott; Breivik, Kyrre; Wold, Bente

2014-01-01

Having a distant relationship with parents seems to increase the risk of developing a more negative global self-esteem. This article describes a longitudinal study of 1,090 Norwegian adolescents from the age of 13-23 (54 % males) that explored whether peer acceptance can act as a moderator and protect global self-esteem against the negative effects of experiencing low closeness in relationships with parents. A quadratic latent growth curve for global self-esteem with closeness to parents and peer acceptance as time-varying covariates was modeled, taking partial measurement invariance in global self-esteem into account. Peer acceptance was found to have a general protective effect on global self-esteem for all adolescents. In addition, at most ages, peer acceptance was found to have a protective-stabilizing effect on the relationship between closeness to parents and global self-esteem. This indicates that peer acceptance can be an especially valuable source of global self-esteem when closeness to parents is low.

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

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

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

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

PubMed

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

2017-01-20

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 (β freq.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).

Monitoring the Effects of the Global Crisis on Education Provision

ERIC Educational Resources Information Center

Chang, Gwang-Chol

2010-01-01

This paper summarizes the experience and findings from the monitoring work carried out by UNESCO throughout 2009 to examine and assess the possible effects of the global financial and economic crisis on education provision in its Member States. The findings showed that although it was too early to ascertain the full extent of the impact of the…

Effects of Global Budgeting on the Distribution of Dentists and Use of Dental Care in Taiwan

PubMed Central

Hsueh, Ya-Seng A; Lee, Shoou-Yih D; Huang, Yu-Tung A

2004-01-01

Objective To examine the effects of global budgeting on the distribution of dentists and the use and cost of dental care in Taiwan. Data Sources (1) Monthly dental claim data from January 1996 to December 2001 for the entire insured population in Taiwan. (2) The 1996–2001 population information for the cities, counties and townships in Taiwan, abstracted from the Taiwan-Fukien Demographic Fact Book. Study Design Longitudinal, using the autocorrelation model. Principal Findings Results indicated decline in dental care utilization, particularly after the implementation of dental global budgeting. With few exceptions, dental global budgeting did not improve the distribution of dental care and dentist supply. Conclusions The experience of the dental global budget program in Taiwan suggested that dental global budgeting might contain dental care utilization and that several conditions might have to be met in order for the reimbursement system to have effective redistributive impact on dental care and dentist supply. PMID:15544648

Effects of bt crops on arthropod natual enemies: a global synthesis

USDA-ARS?s Scientific Manuscript database

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...

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

Proteomic Analysis to Identify Functional Molecules in Drug Resistance Caused by E-Cadherin Knockdown in 3D-Cultured Colorectal Cancer Models

DTIC Science & Technology

2014-09-01

total number of 538 phosphopeptides were identified, among which 350 phosphopeptides had been identified with the first round of TiO2 enrichment and 430...year research and the collection of proteomic and phosphoproteomic data is still in process. PRODUCTS Manuscripts: Yue XS , Hummon AB. Combining...of IMAC and TiO2 enrichment methods to increase phosphoproteomic identifications, manuscript in preparation. Yue XS , Hummon AB. Proteomic and

Cost-effective priorities for global mammal conservation.

PubMed

Carwardine, Josie; Wilson, Kerrie A; Ceballos, Gerardo; Ehrlich, Paul R; Naidoo, Robin; Iwamura, Takuya; Hajkowicz, Stefan A; Possingham, Hugh P

2008-08-12

Global biodiversity priority setting underpins the strategic allocation of conservation funds. In identifying the first comprehensive set of global priority areas for mammals, Ceballos et al. [Ceballos G, Ehrlich PR, Soberón J, Salazar I, Fay JP (2005) Science 309:603-607] found much potential for conflict between conservation and agricultural human activity. This is not surprising because, like other global priority-setting approaches, they set priorities without socioeconomic objectives. Here we present a priority-setting framework that seeks to minimize the conflicts and opportunity costs of meeting conservation goals. We use it to derive a new set of priority areas for investment in mammal conservation based on (i) agricultural opportunity cost and biodiversity importance, (ii) current levels of international funding, and (iii) degree of threat. Our approach achieves the same biodiversity outcomes as Ceballos et al.'s while reducing the opportunity costs and conflicts with agricultural human activity by up to 50%. We uncover shortfalls in the allocation of conservation funds in many threatened priority areas, highlighting a global conservation challenge.

Global Warming: Understanding and Teaching the Forecast.

ERIC Educational Resources Information Center

Andrews, Bill

1995-01-01

A resource for teaching about the consequences of global warming. Discusses feedback from the temperature increase, changes in the global precipitation pattern, effects on agriculture, weather extremes, effects on forests, effects on biodiversity, effects on sea levels, and actions which will help the global community cope with global warming. (LZ)

Ice Cloud Properties And Their Radiative Effects: Global Observations And Modeling

NASA Astrophysics Data System (ADS)

Hong, Yulan

Ice clouds are crucial to the Earth's radiation balance. They cool the Earth-atmosphere system by reflecting solar radiation back to space and warm it by blocking outgoing thermal radiation. However, there is a lack of an observation-based climatology of ice cloud properties and their radiative effects. Two active sensors, the CloudSat radar and the CALIPSO lidar, for the first time provide vertically resolved ice cloud data on a global scale. Using synergistic signals of these two sensors, it is possible to obtain both optically thin and thick ice clouds as the radar excels in probing thick clouds while the lidar is better to detect the thin ones. First, based on the CloudSat radar and CALIPSO lidar measurements, we have derived a climatology of ice cloud properties. Ice clouds cover around 50% of the Earth surface, and their global-mean optical depth, ice water path, and effective radius are approximately 2 (unitless), 109 g m. {-2} and 48 \\mum, respectively. Ice cloud occurrence frequency not only depends on regions and seasons, but also on the types of ice clouds as defined by optical depth (tau) values. Optically thin ice clouds (tau < 3) are most frequently observed in the tropics around 15 km and in the midlatitudes below 5 km, while the thicker clouds (tau > 3) occur frequently in the tropical convective areas and along the midlatitude storm tracks. Using ice retrievals derived from combined radar-lidar measurements, we conducted radiative transfer modeling to study ice cloud radiative effects. The combined effects of ice clouds warm the earth-atmosphere system by approximately 5 W m-2, contributed by a longwave warming effect of about 21.8 W m-2 and a shortwave cooling effect of approximately -16.7 W m-2. Seasonal variations of ice cloud radiative effects are evident in the midlatitudes where the net effect changes from warming during winter to cooling during summer, and the net warming effect occurs year-round in the tropics (˜ 10 W m-2). Ice cloud

Feeling global, acting ethically: global identification and fairtrade consumption.

PubMed

Reese, Gerhard; Kohlmann, Fabienne

2015-01-01

Global identification has become a popular construct in recent psychological debate as it relates to harmonious intergroup relations and a caring for all humanity. Based on social identity theorizing, the current research tests whether global identification can also predict consumer choices, at the expense of lower personal benefit. Importantly, we assumed that concerns about global injustice represent a crucial component of that relation. We predicted that participants who identified strongly with all humanity would rather choose a Fairtrade product alternative over a conventional one, compared with low identifiers. In addition, we assumed that this effect be mediated by perceived global injustice. Both predictions were confirmed in a consumer choice study (N = 68). Overall, global identification and globally relevant consumer behavior seem meaningfully interconnected, and we discuss these findings with regard to recent theoretical developments in Fairtrade consumption research.

Vacuum polarization effects on flat branes due to a global monopole

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bezerra de Mello, E.R.

2006-05-15

In this paper we analyze the vacuum polarization effects associated with a massless scalar field in the higher-dimensional spacetime. Specifically we calculate the renormalized vacuum expectation value of the square of the field, <{phi}{sup 2}(x)>{sub Ren}, induced by a global monopole in the 'braneworld' scenario. In this context the global monopole lives in a n=3-dimensional submanifold of the higher-dimensional (bulk) spacetime, and our universe is represented by a transverse flat (p-1)-dimensional brane. In order to develop this analysis we calculate the general Green function admitting that the scalar field propagates in the bulk. Also a general curvature coupling parameter betweenmore » the field and the geometry is assumed. We explicitly show that the vacuum polarization effects depend crucially on the values attributed to p. We also investigate the general structure of the renormalized vacuum expectation value of the energy-momentum tensor, {sub Ren}, for p=3.« less

Anti-correlated Networks, Global Signal Regression, and the Effects of Caffeine in Resting-State Functional MRI

PubMed Central

Wong, Chi Wah; Olafsson, Valur; Tal, Omer; Liu, Thomas T.

2012-01-01

Resting-state functional connectivity magnetic resonance imaging is proving to be an essential tool for the characterization of functional networks in the brain. Two of the major networks that have been identified are the default mode network (DMN) and the task positive network (TPN). Although prior work indicates that these two networks are anti-correlated, the findings are controversial because the anti-correlations are often found only after the application of a pre-processing step, known as global signal regression, that can produce artifactual anti-correlations. In this paper, we show that, for subjects studied in an eyes-closed rest state, caffeine can significantly enhance the detection of anti-correlations between the DMN and TPN without the need for global signal regression. In line with these findings, we find that caffeine also leads to widespread decreases in connectivity and global signal amplitude. Using a recently introduced geometric model of global signal effects, we demonstrate that these decreases are consistent with the removal of an additive global signal confound. In contrast to the effects observed in the eyes-closed rest state, caffeine did not lead to significant changes in global functional connectivity in the eyes-open rest state. PMID:22743194

Visuospatial working memory in children with autism: the effect of a semantic global organization.

PubMed

Mammarella, Irene C; Giofrè, David; Caviola, Sara; Cornoldi, Cesare; Hamilton, Colin

2014-06-01

It has been reported that individuals with Autism Spectrum Disorders (ASD) perceive visual scenes as a sparse set of details rather than as a congruent and meaningful unit, failing in the extraction of the global configuration of the scene. In the present study, children with ASD were compared with typically developing (TD) children, in a visuospatial working memory task, the Visual Patterns Test (VPT). The VPT array was manipulated to vary the semantic affordance of the pattern, high semantic (global) vs. low semantic; temporal parameters were also manipulated within the change detection protocol. Overall, there was no main effect associated with Group, however there was a significant effect associated with Semantics, which was further qualified by an interaction between the Group and Semantic factors; there was only a significant effect of semantics in the TD group. The findings are discussed in light of the weak central coherence theory where the ASD group are unable to make use of long term memory semantics in order to construct global representations of the array. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Heart of Great Teaching: Pearson Global Survey of Educator Effectiveness

ERIC Educational Resources Information Center

McKnight, Katherine; Graybeal, John; Yarbro, Jessica; Graybeal, Lacey

2016-01-01

To contribute to the global discussion about what makes an effective teacher, Pearson surveyed students ages 15-19, teachers, principals, education researchers, education policymakers, and parents of school-aged children in 23 countries (Canada, U.S., Mexico, Brazil, Argentina, Finland, Germany, Poland, England, Morocco, Egypt, South Africa,…

A Study of Aerosol Direct Radiative Effect and Its Impacts on Global Terrestrial Ecosystem Cycles

NASA Astrophysics Data System (ADS)

Zhang, J.; Shao, S.; Zhou, L.

2017-12-01

Aerosols can absorb and scatter solar radiation, thus cause the total solar radiation reaching the surface to drop and the fraction of diffuse radiation to increase, which influence the surface radiation budget. The global surface radiation with and without consideration of aerosols are calculated by the Fu-Liou atmospheric radiative transfer model based on the MODIS aerosol products, CERES cloud products and other remote sensing data. The aerosol direct radiative effect is calculated based on the two scenarios of aerosols. Our calculation showed that in 2007, aerosols decreased the global total radiation by 9.16 W m-2 on average. Large decrease generally occurred in places with high AOD. As for the diffuse radiation, aerosol-induced changes were either positive or negative. Large increase generally occurred in places with high surface albedo, while large decrease generally occurred in places with high cloud fraction. The global aerosol-induced diffuse radiation change averaged 8.17 W m-2 in 2007. The aerosol direct radiative effect causes the photosynthetic active radiation to increase, and its influences on the global carbon cycle of terrestrial ecosystem are studied by using the Community Land Model (CLM). Calculations show that the aerosol direct radiative effects caused the global averages of terrestrial gross primary productivity (GPP), net primary productivity (NPP), heterotrophic respiration (RH), autotrophic respiration (RA), and net ecosystem productivity (Reco) to increase in 2007, with significant spatial variations however. The global average changes of GPP, NPP, NEP, RA, RH and Reco in 2007 were +6.47 gC m-2, +2.23 gC m-2, +0.34 gC m-2, +4.24 gC m-2, +1.89 gC m-2, +6.13 gC m-2, respectively. Examinations of the carbon fluxes show that the aerosol direct radiative effects influence the terrestrial ecosystem carbon cycles via the following two approaches: First, the diffuse fertilization effect, i.e. more diffuse radiation absorbed by vegetation shade

On Effective Radiative Forcing of Partial Internally and Externally Mixed Aerosols and Their Effects on Global Climate

NASA Astrophysics Data System (ADS)

Zhou, Chen; Zhang, Hua; Zhao, Shuyun; Li, Jiangnan

2018-01-01

The total effective radiative forcing (ERF) due to partial internally mixed (PIM) and externally mixed (EM) anthropogenic aerosols, as well as their climatic effects since the year of 1850, was evaluated and compared using the aerosol-climate online coupled model of BCC_AGCM2.0_CUACE/Aero. The influences of internal mixing (IM) on aerosol hygroscopicity parameter, optical properties, and concentration were considered. Generally, IM could markedly weaken the negative ERF and cooling effects of anthropogenic aerosols. The global annual mean ERF of EM anthropogenic aerosols from 1850 to 2010 was -1.87 W m-2, of which the aerosol-radiation interactive ERF (ERFari) and aerosol-cloud interactive ERF (ERFaci) were -0.49 and -1.38 W m-2, respectively. The global annual mean ERF due to PIM anthropogenic aerosols from 1850 to 2010 was -1.23 W m-2, with ERFari and ERFaci of -0.23 and -1.01 W m-2, respectively. The global annual mean surface temperature and water evaporation and precipitation were reduced by 1.74 K and 0.14 mm d-1 for EM scheme and 1.28 K and 0.11 mm d-1 for PIM scheme, respectively. However, the relative humidity near the surface was slightly increased for both mixing cases. The Intertropical Convergence Zone was southwardly shifted for both EM and PIM cases but was less southwardly shifted in PIM scheme due to the less reduction in atmospheric temperature in the midlatitude and low latitude of the Northern Hemisphere.

Simulating the effects of climate and agricultural management practices on global crop yield

NASA Astrophysics Data System (ADS)

Deryng, D.; Sacks, W. J.; Barford, C. C.; Ramankutty, N.

2011-06-01

Climate change is expected to significantly impact global food production, and it is important to understand the potential geographic distribution of yield losses and the means to alleviate them. This study presents a new global crop model, PEGASUS 1.0 (Predicting Ecosystem Goods And Services Using Scenarios) that integrates, in addition to climate, the effect of planting dates and cultivar choices, irrigation, and fertilizer application on crop yield for maize, soybean, and spring wheat. PEGASUS combines carbon dynamics for crops with a surface energy and soil water balance model. It also benefits from the recent development of a suite of global data sets and analyses that serve as model inputs or as calibration data. These include data on crop planting and harvesting dates, crop-specific irrigated areas, a global analysis of yield gaps, and harvested area and yield of major crops. Model results for present-day climate and farm management compare reasonably well with global data. Simulated planting and harvesting dates are within the range of crop calendar observations in more than 75% of the total crop-harvested areas. Correlation of simulated and observed crop yields indicates a weighted coefficient of determination, with the weighting based on crop-harvested area, of 0.81 for maize, 0.66 for soybean, and 0.45 for spring wheat. We found that changes in temperature and precipitation as predicted by global climate models for the 2050s lead to a global yield reduction if planting and harvesting dates remain unchanged. However, adapting planting dates and cultivar choices increases yield in temperate regions and avoids 7-18% of global losses.

Global effects of interactions on galaxy evolution

NASA Technical Reports Server (NTRS)

Kennicutt, Robert C., Jr.

1990-01-01

Recent observations of the evolutionary properties of paired and interacting galaxies are reviewed, with special emphasis on their global emission properties and star formation rates. Data at several wavelengths provide strong confirmation of the hypothesis, proposed originally by Larson and Tinsley, that interactions trigger global bursts of star formation in galaxies. The nature and properties of the starbursts, and their overall role in galactic evolution are also discussed.

Anti-correlated networks, global signal regression, and the effects of caffeine in resting-state functional MRI.

PubMed

Wong, Chi Wah; Olafsson, Valur; Tal, Omer; Liu, Thomas T

2012-10-15

Resting-state functional connectivity magnetic resonance imaging is proving to be an essential tool for the characterization of functional networks in the brain. Two of the major networks that have been identified are the default mode network (DMN) and the task positive network (TPN). Although prior work indicates that these two networks are anti-correlated, the findings are controversial because the anti-correlations are often found only after the application of a pre-processing step, known as global signal regression, that can produce artifactual anti-correlations. In this paper, we show that, for subjects studied in an eyes-closed rest state, caffeine can significantly enhance the detection of anti-correlations between the DMN and TPN without the need for global signal regression. In line with these findings, we find that caffeine also leads to widespread decreases in connectivity and global signal amplitude. Using a recently introduced geometric model of global signal effects, we demonstrate that these decreases are consistent with the removal of an additive global signal confound. In contrast to the effects observed in the eyes-closed rest state, caffeine did not lead to significant changes in global functional connectivity in the eyes-open rest state. Copyright © 2012 Elsevier Inc. All rights reserved.

Making sense of the global health crisis: policy narratives, conflict, and global health governance.

PubMed

Ney, Steven

2012-04-01

Health has become a policy issue of global concern. Worried that the unstructured, polycentric, and pluralist nature of global health governance is undermining the ability to serve emergent global public health interests, some commentators are calling for a more systematic institutional response to the "global health crisis." Yet global health is a complex and uncertain policy issue. This article uses narrative analysis to explore how actors deal with these complexities and how uncertainties affect global health governance. By comparing three narratives in terms of their basic assumptions, the way they define problems as well as the solutions they propose, the analysis shows how the unstructured pluralism of global health policy making creates a wide scope of policy conflict over the global health crisis. This wide scope of conflict enables effective policy-oriented learning about global health issues. The article also shows how exclusionary patterns of cooperation and competition are emerging in health policy making at the global level. These patterns threaten effective learning by risking both polarization of the policy debate and unanticipated consequences of health policy. Avoiding these pitfalls, the analysis suggests, means creating global health governance regimes that promote openness and responsiveness in deliberation about the global health crisis.

Global synthesis of the documented and projected effects of climate change on inland fishes

USGS Publications Warehouse

Myers, Bonnie; Lynch, Abigail; Bunnell, David; Chu, Cindy; Falke, Jeffrey A.; Kovach, Ryan; Krabbenhoft, Trevor J.; Kwak, Thomas J.; Paukert, Craig P.

2017-01-01

Although climate change is an important factor affecting inland fishes globally, a comprehensive review of how climate change has impacted and will continue to impact inland fishes worldwide does not currently exist. We conducted an extensive, systematic primary literature review to identify English-language, peer-reviewed journal publications with projected and documented examples of climate change impacts on inland fishes globally. Since the mid-1980s, scientists have projected the effects of climate change on inland fishes, and more recently, documentation of climate change impacts on inland fishes has increased. Of the thousands of title and abstracts reviewed, we selected 624 publications for a full text review: 63 of these publications documented an effect of climate change on inland fishes, while 116 publications projected inland fishes’ response to future climate change. Documented and projected impacts of climate change varied, but several trends emerged including differences between documented and projected impacts of climate change on salmonid abundance (P = 0.0002). Salmonid abundance decreased in 89.5% of documented effects compared to 35.7% of projected effects, where variable effects were more commonly reported (64.3%). Studies focused on responses of salmonids (61% of total) to climate change in North America and Europe, highlighting major gaps in the literature for taxonomic groups and geographic focus. Elucidating global patterns and identifying knowledge gaps of climate change effects on inland fishes will help managers better anticipate local changes in fish populations and assemblages, resulting in better development of management plans, particularly in systems with little information on climate change effects on fish.

Negative health system effects of Global Fund's investments in AIDS, tuberculosis and malaria from 2002 to 2009: systematic review.

PubMed

Car, Josip; Paljärvi, Tapio; Car, Mate; Kazeem, Ayodele; Majeed, Azeem; Atun, Rifat

2012-10-01

By using the Global Fund as a case example, we aim to critically evaluate the evidence generated from 2002 to 2009 for potential negative health system effects of Global Health Initiatives (GHI). Systematic review of research literature. Developing Countries. All interventions potentially affecting health systems that were funded by the Global Fund. Negative health system effects of Global Fund investments as reported by study authors. We identified 24 studies commenting on adverse effects on health systems arising from Global Fund investments. Sixteen were quantitative studies, six were qualitative and two used both quantitative and qualitative methods, but none explicitly stated that the studies were originally designed to capture or to assess health system effects (positive or negative). Only seemingly anecdotal evidence or authors' perceptions/interpretations of circumstances could be extracted from the included studies. This study shows that much of the currently available evidence generated between 2002 and 2009 on GHIs potential negative health system effects is not of the quality expected or needed to best serve the academic or broader community. The majority of the reviewed research did not fulfil the requirements of rigorous scientific evidence.

Ownership strategies of multinational corporations: Towards designing effective global networks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Raghunathan, S.P.

1992-01-01

The thesis of this research is that MNCs, attempting to implement different international strategies in response to several environmental factors, let their global networks evolve. The ownership structure of the network is therefore a function of the international strategy and environment of a firm. A particular strategy (configuration/coordination), given a certain environment, may be effective if associated with the appropriate structure. This study is based on a survey of 318 US manufacturing-sector MNCs using a questionnaire. The ownership structure of an MNC network was identified by studying the nature of ownership - method and form - of overseas subsidiaries. Usingmore » network theoretic methods, ownership structure was empirically related to international environment, strategy, and performance. Results of this study throw light on the design of global networks and enable a general theory of the design of MNCs to be eventually developed.« less

Effects of Age and Attention on Auditory Global-Local Processing in Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Foster, Nicholas E. V.; Ouimet, Tia; Tryfon, Ana; Doyle-Thomas, Krissy; Anagnostou, Evdokia; Hyde, Krista L.

2016-01-01

In vision, typically-developing (TD) individuals perceive "global" (whole) before "local" (detailed) features, whereas individuals with autism spectrum disorder (ASD) exhibit a local bias. However, auditory global-local distinctions are less clear in ASD, particularly in terms of age and attention effects. To these aims, here…

An Exploratory Study of Chinese University Undergraduates' Global Competence: Effects of Internationalisation at Home and Motivation

ERIC Educational Resources Information Center

Meng, Qian; Zhu, Chang; Cao, Chun

2017-01-01

Global competence is categorised into three dimensions: knowledge, skills/experience and attitudes. This study aims to investigate the global competence discrepancies of Chinese undergraduates in universities and regions of different development levels, as well as the effects of internationalisation efforts at home and students' motivation on…

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

Global cancer research initiative

PubMed Central

Love, Richard R

2010-01-01

Cancer is an increasing problem for low- and middle-income countries undergoing an epidemiologic transition from dominantly acute communicable disease to more frequent chronic disease with increased public health successes in the former domain. Progress against cancer in high-income countries has been modest and has come at enormous expense. There are several well-conceived global policy and planning initiatives which, with adequate political will, can favorably impact the growing global cancer challenges. Most financial resources for cancer, however, are spent on diagnosis and management of patients with disease in circumstances where specific knowledge about effective approaches is significantly limited, and the majority of interventions, other than surgery, are not cost-effective in resource-limited countries by global standards. In summary, how to intervene effectively on a global scale for the majority of citizens who develop cancer is poorly defined. In contrast to technology-transfer approaches, markedly increased clinical research activities are more likely to benefit cancer sufferers. In these contexts, a global cancer research initiative is proposed, and mechanisms for realizing such an effort are suggested. PMID:21188101

Quantitative Analysis of Tissue Samples by Combining iTRAQ Isobaric Labeling with Selected/Multiple Reaction Monitoring (SRM/MRM).

PubMed

Narumi, Ryohei; Tomonaga, Takeshi

2016-01-01

Mass spectrometry-based phosphoproteomics is an indispensible technique used in the discovery and quantification of phosphorylation events on proteins in biological samples. The application of this technique to tissue samples is especially useful for the discovery of biomarkers as well as biological studies. We herein describe the application of a large-scale phosphoproteome analysis and SRM/MRM-based quantitation to develop a strategy for the systematic discovery and validation of biomarkers using tissue samples.

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.

Local and global dynamical effects of dark energy

NASA Astrophysics Data System (ADS)

Chernin, A. D.

Local expansion flows of galaxies were discovered by Lemaitre and Hubble in 1927-29 at distances of less than 25-30 Mpc. The global expansion of the Universe as a whole was predicted theoretically by Friedmann in 1922-24 and discovered in the 1990s in observations at truly cosmological distances of more than 1 000 Mpc. On all these spatial scales, the flows follow a (nearly) linear velocity-distance relation, known now as Hubble's law. This similarity of local and global phenomena is due to the universal dark energy antigravity which dominates the cosmic dynamics on both local and global spatial scales.

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

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…

A global analysis of the urban heat island effect based on multisensor satellite data

NASA Astrophysics Data System (ADS)

Xiao, J.; Frolking, S. E.; Milliman, T. E.; Schneider, A.; Friedl, M. A.

2017-12-01

Human population is rapidly urbanizing. In much of the world, cities are prone to hotter weather than surrounding rural areas - so-called `urban heat islands' - and this effect can have mortal consequences during heat waves. During the daytime, when the surface energy balance is driven by incoming solar radiation, the magnitude of urban warming is strongly influenced by surface albedo and the capacity to evaporate water (i.e., there is a strong relationship between vegetated land fraction and the ratio of sensible to latent heat loss or Bowen ratio). At nighttime, urban cooling is often inhibited by the thermal inertia of the built environment and anthropogenic heat exhaust from building and transportation energy use. We evaluated a suite of global remote sensing data sets representing a range of urban characteristics against MODIS-derived land-surface temperature differences between urban and surrounding rural areas. We included two new urban datasets in this analysis - MODIS-derived change in global urban extent and global urban microwave backscatter - along with several MODIS standard products and DMSP/OLS nighttime lights time series data. The global analysis spanned a range of urban characteristics that likely influence the magnitude of daytime and/or nighttime urban heat islands - urban size, population density, building density, state of development, impervious fraction, eco-climatic setting. Specifically, we developed new satellite datasets and synthesizing these with existing satellite data into a global database of urban land surface parameters, used two MODIS land surface temperature products to generate time series of daytime and nighttime urban heat island effects for 30 large cities across the globe, and empirically analyzed these data to determine specifically which remote sensing-based characterizations of global urban areas have explanatory power with regard to both daytime and nighttime urban heat islands.

Global-change effects on early-stage decomposition processes in tidal wetlands - implications from a global survey using standardized litter

NASA Astrophysics Data System (ADS)

Mueller, Peter; Schile-Beers, Lisa M.; Mozdzer, Thomas J.; Chmura, Gail L.; Dinter, Thomas; Kuzyakov, Yakov; de Groot, Alma V.; Esselink, Peter; Smit, Christian; D'Alpaos, Andrea; Ibáñez, Carles; Lazarus, Magdalena; Neumeier, Urs; Johnson, Beverly J.; Baldwin, Andrew H.; Yarwood, Stephanie A.; Montemayor, Diana I.; Yang, Zaichao; Wu, Jihua; Jensen, Kai; Nolte, Stefanie

2018-05-01

Tidal wetlands, such as tidal marshes and mangroves, are hotspots for carbon sequestration. The preservation of organic matter (OM) is a critical process by which tidal wetlands exert influence over the global carbon cycle and at the same time gain elevation to keep pace with sea-level rise (SLR). The present study assessed the effects of temperature and relative sea level on the decomposition rate and stabilization of OM in tidal wetlands worldwide, utilizing commercially available standardized litter. While effects on decomposition rate per se were minor, we show strong negative effects of temperature and relative sea level on stabilization, as based on the fraction of labile, rapidly hydrolyzable OM that becomes stabilized during deployment. Across study sites, OM stabilization was 29 % lower in low, more frequently flooded vs. high, less frequently flooded zones. Stabilization declined by ˜ 75 % over the studied temperature gradient from 10.9 to 28.5 °C. Additionally, data from the Plum Island long-term ecological research site in Massachusetts, USA, show a pronounced reduction in OM stabilization by > 70 % in response to simulated coastal eutrophication, confirming the potentially high sensitivity of OM stabilization to global change. We therefore provide evidence that rising temperature, accelerated SLR, and coastal eutrophication may decrease the future capacity of tidal wetlands to sequester carbon by affecting the initial transformations of recent OM inputs to soil OM.

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.

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.

Measuring the extent and effectiveness of protected areas as an indicator for meeting global biodiversity targets

PubMed Central

Chape, S; Harrison, J; Spalding, M; Lysenko, I

2005-01-01

There are now over 100 000 protected areas worldwide, covering over 12% of the Earth's land surface. These areas represent one of the most significant human resource use allocations on the planet. The importance of protected areas is reflected in their widely accepted role as an indicator for global targets and environmental assessments. However, measuring the number and extent of protected areas only provides a unidimensional indicator of political commitment to biodiversity conservation. Data on the geographic location and spatial extent of protected areas will not provide information on a key determinant for meeting global biodiversity targets: ‘effectiveness’ in conserving biodiversity. Although tools are being devised to assess management effectiveness, there is no globally accepted metric. Nevertheless, the numerical, spatial and geographic attributes of protected areas can be further enhanced by investigation of the biodiversity coverage of these protected areas, using species, habitats or biogeographic classifications. This paper reviews the current global extent of protected areas in terms of geopolitical and habitat coverage, and considers their value as a global indicator of conservation action or response. The paper discusses the role of the World Database on Protected Areas and collection and quality control issues, and identifies areas for improvement, including how conservation effectiveness indicators may be included in the database to improve the value of protected areas data as an indicator for meeting global biodiversity targets. PMID:15814356

Global Distribution of Cloud Droplet Number Concentration, Autoconversion Rate, and Aerosol Indirect Effect Under Diabatic Droplet Activation

NASA Technical Reports Server (NTRS)

Barahona, Donifan; Sotiropoulou, Rafaella; Nenes, Athanasios

2011-01-01

This study presents a global assessment of the sensitivity of droplet number to diabatic activation (i.e., including effects from entrainment of dry air) and its first-order tendency on indirect forcing and autoconversion. Simulations were carried out with the NASA Global Modeling Initiative (GMI) atmospheric and transport model using climatological metereorological fields derived from the former NASA Data Assimilation Office (DAO), the NASA Finite volume GCM (FVGCM) and the Goddard Institute for Space Studies version II (GISS) GCM. Cloud droplet number concentration (CDNC) is calculated using a physically based prognostic parameterization that explicitly includes entrainment effects on droplet formation. Diabatic activation results in lower CDNC, compared to adiabatic treatment of the process. The largest decrease in CDNC (by up to 75 percent) was found in the tropics and in zones of moderate CCN concentration. This leads to a global mean effective radius increase between 0.2-0.5 micrometers (up to 3.5 micrometers over the tropics), a global mean autoconversion rate increase by a factor of 1.1 to 1.7 (up to a factor of 4 in the tropics), and a 0.2-0.4 W m(exp -2) decrease in indirect forcing. The spatial patterns of entrainment effects on droplet activation tend to reduce biases in effective radius (particularly in the tropics) when compared to satellite retrievals. Considering the diabatic nature of ambient clouds, entrainment effects on CDNC need to be considered in GCM studies of the aerosol indirect effect.

Cosmic-Ray Reaction and Greenhouse Effect of Halogenated Molecules: Culprits for Atmospheric Ozone Depletion and Global Climate Change

NASA Astrophysics Data System (ADS)

Lu, Q.-B.

2013-07-01

This study is focused on the effects of cosmic rays (solar activity) and halogen-containing molecules (mainly chlorofluorocarbons — CFCs) on atmospheric ozone depletion and global climate change. Brief reviews are first given on the cosmic-ray-driven electron-induced-reaction (CRE) theory for O3 depletion and the warming theory of halogenated molecules for climate change. Then natural and anthropogenic contributions to these phenomena are examined in detail and separated well through in-depth statistical analyses of comprehensive measured datasets of quantities, including cosmic rays (CRs), total solar irradiance, sunspot number, halogenated gases (CFCs, CCl4 and HCFCs), CO2, total O3, lower stratospheric temperatures and global surface temperatures. For O3 depletion, it is shown that an analytical equation derived from the CRE theory reproduces well 11-year cyclic variations of both polar O3 loss and stratospheric cooling, and new statistical analyses of the CRE equation with observed data of total O3 and stratospheric temperature give high linear correlation coefficients ≥ 0.92. After the removal of the CR effect, a pronounced recovery by 20 25 % of the Antarctic O3 hole is found, while no recovery of O3 loss in mid-latitudes has been observed. These results show both the correctness and dominance of the CRE mechanism and the success of the Montreal Protocol. For global climate change, in-depth analyses of the observed data clearly show that the solar effect and human-made halogenated gases played the dominant role in Earth's climate change prior to and after 1970, respectively. Remarkably, a statistical analysis gives a nearly zero correlation coefficient (R = -0.05) between corrected global surface temperature data by removing the solar effect and CO2 concentration during 1850-1970. In striking contrast, a nearly perfect linear correlation with coefficients as high as 0.96-0.97 is found between corrected or uncorrected global surface temperature and total

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…

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.

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.

Global assessment of the effect of climate change on ammonia emissions from seabirds

NASA Astrophysics Data System (ADS)

Riddick, Stuart N.; Dragosits, Ulrike; Blackall, Trevor D.; Tomlinson, Sam J.; Daunt, Francis; Wanless, Sarah; Hallsworth, Stephen; Braban, Christine F.; Tang, Y. Sim; Sutton, Mark A.

2018-07-01

Seabird colonies alter the biogeochemistry of nearby ecosystems, while the associated emissions of ammonia (NH3) may cause acidification and eutrophication of finely balanced biomes. To examine the possible effects of future climate change on the magnitude and distribution of seabird NH3 emissions globally, a global seabird database was used as input to the GUANO model, a dynamic mass-flow process-based model that simulates NH3 losses from seabird colonies at an hourly resolution in relation to environmental conditions. Ammonia emissions calculated by the GUANO model were in close agreement with measured NH3 emissions across a wide range of climates. For the year 2010, the total global seabird NH3 emission is estimated at 82 [37-127] Gg year-1. This is less than previously estimated using a simple temperature-dependent empirical model, mainly due to inclusion of nitrogen wash-off from colonies during precipitation events in the GUANO model. High precipitation, especially between 40° and 60° S, results in total emissions for the penguin species that are 82% smaller than previously estimated, while for species found in dry tropical areas, emissions are 83-133% larger. Application of temperature anomalies for several IPCC scenarios for 2099 in the GUANO model indicated a predicted net increase in global seabird NH3 emissions of 27% (B1 scenario) and 39% (A2 scenario), compared with the 2010 estimates. At individual colonies, the net change was the result of influences of temperature, precipitation and relative humidity change, with smaller effects of wind-speed changes. The largest increases in NH3 emissions (mean: 60% [486 to -50] increase; A2 scenario for 2099 compared with 2010) were found for colonies 40°S to 65°N, and may lead to increased plant growth and decreased biodiversity by eliminating nitrogen sensitive plant species. Only 7% of the seabird colonies assessed globally (mainly limited to the sub-polar Southern Ocean) were estimated to experience a

Global characteristics of zonal flows due to the effect of finite bandwidth in drift wave turbulence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uzawa, K.; Li Jiquan; Kishimoto, Y.

2009-04-15

The spectral effect of the zonal flow (ZF) on its generation is investigated based on the Charney-Hasegawa-Mima turbulence model. It is found that the effect of finite ZF bandwidth qualitatively changes the characteristics of ZF instability. A spatially localized (namely, global) nonlinear ZF state with an enhanced, unique growth rate for all spectral components is created under a given turbulent fluctuation. It is identified that such state originates from the successive cross couplings among Fourier components of the ZF and turbulence spectra through the sideband modulation. Furthermore, it is observed that the growth rate of the global ZF is determinedmore » not only by the spectral distribution and amplitudes of turbulent pumps as usual, but also statistically by the turbulence structure, namely, their probabilistic initial phase factors. A ten-wave coupling model of the ZF modulation instability involving the essential effect of the ZF spectrum is developed to clarify the basic features of the global nonlinear ZF state.« less

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

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.

Parallel Transport with Sheath and Collisional Effects in Global Electrostatic Turbulent Transport in FRCs

NASA Astrophysics Data System (ADS)

Bao, Jian; Lau, Calvin; Kuley, Animesh; Lin, Zhihong; Fulton, Daniel; Tajima, Toshiki; Tri Alpha Energy, Inc. Team

2017-10-01

Collisional and turbulent transport in a field reversed configuration (FRC) is studied in global particle simulation by using GTC (gyrokinetic toroidal code). The global FRC geometry is incorporated in GTC by using a field-aligned mesh in cylindrical coordinates, which enables global simulation coupling core and scrape-off layer (SOL) across the separatrix. Furthermore, fully kinetic ions are implemented in GTC to treat magnetic-null point in FRC core. Both global simulation coupling core and SOL regions and independent SOL region simulation have been carried out to study turbulence. In this work, the ``logical sheath boundary condition'' is implemented to study parallel transport in the SOL. This method helps to relax time and spatial steps without resolving electron plasma frequency and Debye length, which enables turbulent transports simulation with sheath effects. We will study collisional and turbulent SOL parallel transport with mirror geometry and sheath boundary condition in C2-W divertor.

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.

Effects of Global Cerebral Ischemia in the Pregnant Rat

PubMed Central

Spencer, Sarah J.; Galic, Michael A.; Tsutsui, Mio; Pittman, Quentin J.; Mouihate, Abdeslam

2012-01-01

Background and Purpose Stroke during pregnancy is an emerging concern. Although females undergo many physiological, endocrine, and neurological alterations during pregnancy, the consequences of such changes on outcome after stroke are unclear. It is predicted that increases in steroid hormones observed during pregnancy may confer protective effects against the neurological and pathological sequelae of stroke. Methods We therefore investigated behavioral and histological consequences of a global cerebral ischemia (2-vessel occlusion; 2VO), and how these outcomes correlated with pregnancy-related changes in hormones in Sprague-Dawley rats. Results After the 2VO, pregnant rats exhibited poorer memory in a contextual fear conditioning test of learning and memory than sham-treated controls, whereas nonpregnant rats did not. They also showed enhanced CA1 hippocampal neuronal injury. This susceptibility to damage is despite significant pregnancy-associated hypothermia and is probably not associated with alterations in 17β-estradiol or corticosterone levels. Conclusion These findings are the first to show enhanced neuronal damage in pregnant animals after global cerebral ischemia. They also suggest that the mechanism may be independent of changes in estrogen, corticosterone, and body temperature. PMID:18239170

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.

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

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.

The challenge of sustaining effectiveness over time: the case of the global network to stop tuberculosis

PubMed Central

Quissell, Kathryn; Walt, Gill

2016-01-01

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. PMID

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.

ISO-9000: Effects on the Global Marketplace and Contract Relations With the U.S. Department of Defense

DTIC Science & Technology

1998-12-01

is affecting business procedures both internally (operations) and externally ( global marketing ). A methndology for determining current opinions and...perceptions of certified companies and the effects that lS0-9000 has had on global marketing of products. The range of data were analyzed and

75 FR 64351 - The Economic Effects of Significant U.S. Import Restraints: Seventh Update; Special Topic: Global...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-19

.... Import Restraints: Seventh Update; Special Topic: Global Supply Chains AGENCY: United States... effects analysis similar to that included in prior reports, include an overview of global supply chains... firm supplying the information. By order of the Commission. Issued: October 14, 2010. William R. Bishop...

Effects of global change during the 21st century on the 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.; Galloway, J. N.

2015-01-01

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, estimated to be 193 Tg N yr-1 in 2010 which is approximately equal to the sum of biological N fixation in terrestrial and marine ecosystems. According to current trajectories, 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 surface temperature of 5 °C even 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 132 Tg N yr-1. Another major change is the effect of changes in aerosol composition combined with changes in temperature. 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 and human health effects globally as well as eutrophication and climate effects. The volatility of NH4NO3 and rapid dry deposition of the vapour phase dissociation products, HNO3 and NH3, is estimated to be reducing the transport

Space sensors for global change

DOE Office of Scientific and Technical Information (OSTI.GOV)

Canavan, G.H.

1994-02-15

Satellite measurements should contribute to a fuller understanding of the physical processes behind the radiation budget, exchange processes, and global change. Climate engineering requires global observation for early indications of predicted effects, which puts a premium on affordable, distributed constellations of satellites with effective, affordable sensors. Defense has a requirement for continuous global surveillance for warning of aggression, which could evolve from advanced sensors and satellites in development. Many climate engineering needs match those of defense technologies.

Effects of global warming on ancient mammalian communities and their environments.

PubMed

DeSantis, Larisa R G; Feranec, Robert S; MacFadden, Bruce J

2009-06-03

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 C(3)/C(4) transitions and relative seasonality. 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 (approximately 1.9 million years ago) and Pleistocene (approximately 1.3 million years ago) in Florida. Stable isotope data demonstrate increased aridity, increased C(4) 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. Our data show that global warming resulted in dramatic vegetation and dietary changes even at lower latitudes (approximately 28 degrees 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.

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

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

Effect of ice-albedo feedback on global sensitivity in a one-dimensional radiative-convective climate model

NASA Technical Reports Server (NTRS)

Wang, W.-C.; Stone, P. H.

1980-01-01

The feedback between the ice albedo and temperature is included in a one-dimensional radiative-convective climate model. The effect of this feedback on global sensitivity to changes in solar constant is studied for the current climate conditions. This ice-albedo feedback amplifies global sensitivity by 26 and 39%, respectively, for assumptions of fixed cloud altitude and fixed cloud temperature. The global sensitivity is not affected significantly if the latitudinal variations of mean solar zenith angle and cloud cover are included in the global model. The differences in global sensitivity between one-dimensional radiative-convective models and energy balance models are examined. It is shown that the models are in close agreement when the same feedback mechanisms are included. The one-dimensional radiative-convective model with ice-albedo feedback included is used to compute the equilibrium ice line as a function of solar constant.

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.

Global climate change and vector-borne diseases

USGS Publications Warehouse

Ginsberg, H.S.

2002-01-01

Global warming will have different effects on different diseases because of the complex and idiosynchratic interactions between vectors, hosts, and pathogens that influence transmission dynamics of each pathogen. Human activities, including urbanization, rapid global travel, and vector management, have profound effects on disease transmission that can operate on more rapid time scales than does global climate change. The general concern about global warming encouraging the spread of tropical diseases is legitimate, but the effects vary among diseases, and the ecological implications are difficult to predict.

Effect of age on variability in the production of text-based global inferences.

PubMed

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.

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

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.

Global atmospheric changes.

PubMed

Piver, W T

1991-12-01

Increasing concentrations of CO2 and other greenhouse gases in the atmosphere can be directly related to global warming. In terms of human health, because a major cause of increasing atmospheric concentrations of CO2 is the increased combustion of fossil fuels, global warming also may result in increases in air pollutants, acid deposition, and exposure to ultraviolet (UV) radiation. To understand better the impacts of global warming phenomena on human health, this review emphasizes the processes that are responsible for the greenhouse effect, air pollution, acid deposition, and increased exposure to UV radiation.

Global Salmonidae introductions reveal stronger ecological effects of changing intraspecific compared to interspecific diversity.

PubMed

Buoro, Mathieu; Olden, Julian D; Cucherousset, Julien

2016-11-01

The introduction of organisms within the native range of wild conspecifics is a widespread phenomenon and locally modifies patterns in intraspecific diversity. However, our knowledge of the resulting ecological effects, as opposed to those caused by invasion-induced changes in interspecific diversity, is still limited. Here, we investigated the ecological effects of native and non-native invaders across levels of biological organisations and recipient organisms using the global and long history introductions of salmonids. Our meta-analysis demonstrated that the global effects of native species introductions exceeded those induced by non-native invaders. The impacts of native invaders were primarily manifested at the individual level on wild conspecifics, but remained largely unexplored on other native organisms and at the community and ecosystem levels. Overlooked and poorly appreciated, quantifying the impacts of native invaders has important implications because human-assisted introductions of domesticated organisms are ubiquitous and likely to proliferate in the future. © 2016 John Wiley & Sons Ltd/CNRS.

Global / globalizing cities.

PubMed

Yeoh, B S

1999-01-01

Along with the rise in research on globalization, the concept of globalization has become a subject to a more critical scrutiny. While majority agree that it represents a serious challenge to the state-centrist assumptions of most previous social science, doubts about its newness, inevitability and epoch-making qualities are also being raised. Others argue that the globalization literature neglects issues of social regulation by the nation-state, while some critics view it as a discourse drawn upon to legitimize particular political and economic agendas. Debates focus on metropolitan manifestations and impacts. Moving from this background, the paper presents three sociospatial urban configurations that have emerged in the literature. Alongside attempts at identifying globalizing cities and transnational urban networks as new theoretical subjects, another significant vein in the literature focuses on the complex forces of globalization and the production of new urban spaces in these cities. In addition, economic conceptions of globalization is now being pushed beyond adding sociocultural or sociopolitical dimensions and argue instead for the need to theorize globalization as a discursive formation. The global city as a discursive category conjures up imaginary concepts of high modernity, megadevelopment, 21st century urbanity. However, it is noted that the way forward is to focus on the distinctive ways in which urban actors engage in specific processes of economic and social reflexivity. There exists an urgent task for theorizations of the global city, which weave together historical, economic, cultural, sociopolitical and discursive dimensions.

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

Local Versus Global Effects of Isoflurane Anesthesia on Visual Processing in the Fly Brain.

PubMed

Cohen, Dror; Zalucki, Oressia H; van Swinderen, Bruno; Tsuchiya, Naotsugu

2016-01-01

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.

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.

Nonbinding Legal Instruments in Governance for Global Health: Lessons from the Global AIDS Reporting Mechanism.

PubMed

Taylor, Allyn; Alfvén, Tobias; Hougendobler, Daniel; Buse, Kent

2014-01-01

Recent debate over World Health Organization reform has included unprecedented attention to international lawmaking as a future priority function of the Organization. However, the debate is largely focused on the codification of new binding legal instruments. Drawing upon lessons from the success of the Global AIDS Reporting Mechanism, established pursuant to the United Nations' Declaration of Commitment on HIV/AIDS, we argue that effective global health governance requires consideration of a broad range of instruments, both binding and nonbinding. A detailed examination of the Global AIDS Reporting Mechanism reveals that the choice of the nonbinding format makes an important contribution to its effectiveness. For instance, the flexibility and adaptability of the nonbinding format have allowed the global community to: (1) undertake commitments in a timely manner; (2) adapt and experiment in the face of a dynamic pandemic; and (3) grant civil society an unparalleled role in monitoring and reporting on state implementation of global commitments. UNAIDS' institutional support has also played a vital role in ensuring the continuing effectiveness of the Global AIDS Reporting Mechanism. Overall, the experience of the Global AIDS Reporting Mechanism evidences that, at times, nimbler nonbinding instruments can offer benefits over slower, more rigid binding legal approaches to governance, but depend critically, like all instruments, on the perceived legitimacy thereof. © 2014 American Society of Law, Medicine & Ethics, Inc.

[Cost-effectiveness analysis and diet quality index applied to the WHO Global Strategy].

PubMed

Machado, Flávia Mori Sarti; Simões, Arlete Naresse

2008-02-01

To test the use of cost-effectiveness analysis as a decision making tool in the production of meals for the inclusion of the recommendations published in the World Health Organization's Global Strategy. Five alternative options for breakfast menu were assessed previously to their adoption in a food service at a university in the state of Sao Paulo, Southeastern Brazil, in 2006. Costs of the different options were based on market prices of food items (direct cost). Health benefits were estimated based on adaptation of the Diet Quality Index (DQI). Cost-effectiveness ratios were estimated by dividing benefits by costs and incremental cost-effectiveness ratios were estimated as cost differential per unit of additional benefit. The meal choice was based on health benefit units associated to direct production cost as well as incremental effectiveness per unit of differential cost. The analysis showed the most simple option with the addition of a fruit (DQI = 64 / cost = R$ 1.58) as the best alternative. Higher effectiveness was seen in the options with a fruit portion (DQI1=64 / DQI3=58 / DQI5=72) compared to the others (DQI2=48 / DQI4=58). The estimate of cost-effectiveness ratio allowed to identifying the best breakfast option based on cost-effectiveness analysis and Diet Quality Index. These instruments allow easy application easiness and objective evaluation which are key to the process of inclusion of public or private institutions under the Global Strategy directives.

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

Relationship between Attitudes of Multicultural Education and Perceptions Regarding Cultural Effect of Globalization

ERIC Educational Resources Information Center

Bagceli Kahraman, Pinar; Onur Sezer, Gonul

2017-01-01

Purpose: This research aims to determine the relationship between the perceptions of teacher candidates towards the cultural effect of globalization and their attitudes towards multicultural education. Research Methods: The sample group consisted of 213 teacher candidates. In the study's personal information form, the scale of attitude towards…

An effective drift correction for dynamical downscaling of decadal global climate predictions

NASA Astrophysics Data System (ADS)

Paeth, Heiko; Li, Jingmin; Pollinger, Felix; Müller, Wolfgang A.; Pohlmann, Holger; Feldmann, Hendrik; Panitz, Hans-Jürgen

2018-04-01

Initialized decadal climate predictions with coupled climate models are often marked by substantial climate drifts that emanate from a mismatch between the climatology of the coupled model system and the data set used for initialization. While such drifts may be easily removed from the prediction system when analyzing individual variables, a major problem prevails for multivariate issues and, especially, when the output of the global prediction system shall be used for dynamical downscaling. In this study, we present a statistical approach to remove climate drifts in a multivariate context and demonstrate the effect of this drift correction on regional climate model simulations over the Euro-Atlantic sector. The statistical approach is based on an empirical orthogonal function (EOF) analysis adapted to a very large data matrix. The climate drift emerges as a dramatic cooling trend in North Atlantic sea surface temperatures (SSTs) and is captured by the leading EOF of the multivariate output from the global prediction system, accounting for 7.7% of total variability. The SST cooling pattern also imposes drifts in various atmospheric variables and levels. The removal of the first EOF effectuates the drift correction while retaining other components of intra-annual, inter-annual and decadal variability. In the regional climate model, the multivariate drift correction of the input data removes the cooling trends in most western European land regions and systematically reduces the discrepancy between the output of the regional climate model and observational data. In contrast, removing the drift only in the SST field from the global model has hardly any positive effect on the regional climate model.

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. �

Stability of strong species interactions resist the synergistic effects of local and global pollution in kelp forests.

PubMed

Falkenberg, Laura J; Russell, Bayden D; Connell, Sean D

2012-01-01

Foundation species, such as kelp, exert disproportionately strong community effects and persist, in part, by dominating taxa that inhibit their regeneration. Human activities which benefit their competitors, however, may reduce stability of communities, increasing the probability of phase-shifts. We tested whether a foundation species (kelp) would continue to inhibit a key competitor (turf-forming algae) under moderately increased local (nutrient) and near-future forecasted global pollution (CO(2)). Our results reveal that in the absence of kelp, local and global pollutants combined to cause the greatest cover and mass of turfs, a synergistic response whereby turfs increased more than would be predicted by adding the independent effects of treatments (kelp absence, elevated nutrients, forecasted CO(2)). The positive effects of nutrient and CO(2) enrichment on turfs were, however, inhibited by the presence of kelp, indicating the competitive effect of kelp was stronger than synergistic effects of moderate enrichment of local and global pollutants. Quantification of physicochemical parameters within experimental mesocosms suggests turf inhibition was likely due to an effect of kelp on physical (i.e. shading) rather than chemical conditions. Such results indicate that while forecasted climates may increase the probability of phase-shifts, maintenance of intact populations of foundation species could enable the continued strength of interactions and persistence of communities.

Globalization, culture and psychology.

PubMed

Melluish, Steve

2014-10-01

This article outlines the cultural and psychological effects of globalization. It looks at the impact of globalization on identity; ideas of privacy and intimacy; the way we understand and perceive psychological distress; and the development of the profession of psychology around the world. The article takes a critical perspective on globalization, seeing it as aligned with the spread of neoliberal capitalism, a tendency towards cultural homogenization, the imposition of dominant 'global north' ideas and the resultant growing inequalities in health and well-being. However, it also argues that the increased interconnectedness created by globalization allows for greater acknowledgement of our common humanity and for collective efforts to be developed to tackle what are increasingly global problems. This requires the development of more nuanced understandings of cultural differences and of indigenous psychologies.

Hepatic signaling by the mechanistic target of rapamycin complex 2 (mTORC2)

PubMed Central

Lamming, Dudley W.; Demirkan, Gokhan; Boylan, Joan M.; Mihaylova, Maria M.; Peng, Tao; Ferreira, Jonathan; Neretti, Nicola; Salomon, Arthur; Sabatini, David M.; Gruppuso, Philip A.

2014-01-01

The mechanistic target of rapamycin (mTOR) exists in two complexes that regulate diverse cellular processes. mTOR complex 1 (mTORC1), the canonical target of rapamycin, has been well studied, whereas the physiological role of mTORC2 remains relatively uncharacterized. In mice in which the mTORC2 component Rictor is deleted in liver [Rictor-knockout (RKO) mice], we used genomic and phosphoproteomic analyses to characterize the role of hepatic mTORC2 in vivo. Overnight food withdrawal followed by refeeding was used to activate mTOR signaling. Rapamycin was administered before refeeding to specify mTORC2-mediated events. Hepatic mTORC2 regulated a complex gene expression and post-translational network that affects intermediary metabolism, ribosomal biogenesis, and proteasomal biogenesis. Nearly all changes in genes related to intermediary metabolic regulation were replicated in cultured fetal hepatocytes, indicating a cell-autonomous effect of mTORC2 signaling. Phosphoproteomic profiling identified mTORC2-related signaling to 144 proteins, among which were metabolic enzymes and regulators. A reduction of p38 MAPK signaling in the RKO mice represents a link between our phosphoproteomic and gene expression results. We conclude that hepatic mTORC2 exerts a broad spectrum of biological effects under physiological conditions. Our findings provide a context for the development of targeted therapies to modulate mTORC2 signaling.—Lamming, D. W., Demirkan, G., Boylan, J. M., Mihaylova, M. M., Peng, T., Ferreira, J., Neretti, N., Salomon, A., Sabatini, D. M., Gruppuso, P. A. Hepatic signaling by the mechanistic target of rapamycin complex 2 (mTORC2). PMID:24072782

Biogeochemical effects of global change on U.S. National Parks

USGS Publications Warehouse

Herrmann, R.; Stottlemyer, R.; Zak, J.C.; Edmonds, R.L.; Van Miegroet, H.

2000-01-01

Federal parks and other public lands have unique mandates and rules regulating their use and conservation. Because of variation in their response to local, regional, and global-scale disturbance, development of mitigation strategies requires substantial research in the context of long-term inventory and monitoring. In 1982, the National Park Service began long-term, watershed-level studies in a series of national parks. The objective was to provide a more comprehensive database against which the effects of global change and other issues could be quantified. A subset of five sites in North Carolina, Texas, Washington, Michigan, and Alaska, is examined here. During the last 50 years, temperatures have declined at the southern sites and increased at the northern sites with the greatest increase in Alaska. Only the most southern site has shown an increase in precipitation amount. The net effect of these trends, especially for the most northern and southern sites, would likely be an increase in the growing season and especially the time soil processes could continue without moisture or temperature limitations. During the last 18 years, there were few trends in atmospheric ion inputs. The most evident was the decline in SO42- deposition. There were no significant relationships between ion input and stream water output. This finding suggests other factors as modification of precipitation or canopy throughfall by soil processes, hydrologic flow path, and snowmelt rates are major processes regulating stream water chemical outputs.

Top-down constraints on disturbance dynamics in the terrestrial carbon cycle: effects at global and regional scales

NASA Astrophysics Data System (ADS)

Bloom, A. A.; Exbrayat, J. F.; van der Velde, I.; Peters, W.; Williams, M.

2014-12-01

Large uncertainties preside over terrestrial carbon flux estimates on a global scale. In particular, the strongly coupled dynamics between net ecosystem productivity and disturbance C losses are poorly constrained. To gain an improved understanding of ecosystem C dynamics from regional to global scale, we apply a Markov Chain Monte Carlo based model-data-fusion approach into the CArbon DAta-MOdel fraMework (CARDAMOM). We assimilate MODIS LAI and burned area, plant-trait data, and use the Harmonized World Soil Database (HWSD) and maps of above ground biomass as prior knowledge for initial conditions. We optimize model parameters based on (a) globally spanning observations and (b) ecological and dynamic constraints that force single parameter values and parameter inter-dependencies to be representative of real world processes. We determine the spatial and temporal dynamics of major terrestrial C fluxes and model parameter values on a global scale (GPP = 123 +/- 8 Pg C yr-1 & NEE = -1.8 +/- 2.7 Pg C yr-1). We further show that the incorporation of disturbance fluxes, and accounting for their instantaneous or delayed effect, is of critical importance in constraining global C cycle dynamics, particularly in the tropics. In a higher resolution case study centred on the Amazon Basin we show how fires not only trigger large instantaneous emissions of burned matter, but also how they are responsible for a sustained reduction of up to 50% in plant uptake following the depletion of biomass stocks. The combination of these two fire-induced effects leads to a 1 g C m-2 d-1reduction in the strength of the net terrestrial carbon sink. Through our simulations at regional and global scale, we advocate the need to assimilate disturbance metrics in global terrestrial carbon cycle models to bridge the gap between globally spanning terrestrial carbon cycle data and the full dynamics of the ecosystem C cycle. Disturbances are especially important because their quick occurrence may have

Mere exposure effect can be elicited in transient global amnesia.

PubMed

Marin-Garcia, Eugenia; Ruiz-Vargas, Jose M; Kapur, Narinder

2013-01-01

Transient global amnesia (TGA) is one of the most severe forms of anterograde amnesia seen in clinical practice, yet patients may show evidence of spared learning during the amnesic episode. The scope of spared learning in such a severe form of amnesia remains uncertain, and it is also unclear whether findings from single-case studies hold up in group studies of TGA patients. In this group study, we found evidence that extended the domain of spared learning in TGA to include the mere exposure effect, whereby enhanced preference is primed by prior exposure to stimuli. We demonstrate this effect during an acute episode in a group of TGA patients, where they showed enhanced preference for previously exposed faces, despite markedly impaired performance on standard anterograde memory tests.

Volcanism, global catastrophe and mass mortality

NASA Technical Reports Server (NTRS)

Francis, P. W.; Burke, K.

1988-01-01

The effects of very large volcanic eruptions are well documented in many studies, mostly based on observations made on three historic eruptions, Laki 1783; Tambora 1815 and Krakatau 1883. Such eruptions have effects that are catastrophic locally and measurable globally, but it is not clear that even the largest volcanic eruptions have had global catastrophic effects, nor caused mass extinctions. Two different types of volcanic eruption were considered as likely to have the most serious widespread effects: large silicic explosive eruptions producing hundreds or thousands of cubic kilometers of pyroclastic materials, and effusive basaltic eruptions producing of approximately 100 cubic kilometers of lava. In both cases, the global effects are climatic, and attributable to production of stratospheric aerosols. Other possibilities need to be explored. Recent research on global change has emphasized the extreme sensitivity of the links between oceanic circulation, atmospheric circulation and climate. In particular, it was argued that the pattern of ocean current circulation (which strongly influences climate) is unstable; it may rapidly flip from one pattern to a different one, with global climatic consequences. If volcanism has been a factor in global environmental change and a cause of mass extinctions, it seems most likely that it has done so by providing a trigger to other processes, for example by driving oceanic circulation from one mode to another.

Global Effects of Superparameterization on Hydrothermal Land-Atmosphere Coupling on Multiple Timescales

NASA Astrophysics Data System (ADS)

Qin, Hongchen; Pritchard, Michael S.; Kooperman, Gabriel J.; Parishani, Hossein

2018-02-01

Many conventional General Circulation Models (GCMs) in the Global Land-Atmosphere Coupling Experiment (GLACE) tend to produce what is now recognized as overly strong land-atmosphere (L-A) coupling. We investigate the effects of cloud Superparameterization (SP) on L-A coupling on timescales beyond diurnal where it has been recently shown to have a favorable muting effect hydrologically. Using the Community Atmosphere Model v3.5 (CAM3.5) and its Superparameterized counterpart SPCAM3.5, we conducted soil moisture interference experiments following the GLACE and Atmospheric Model Intercomparison Project (AMIP) protocols. The results show that, on weekly-to-subseasonal timescales, SP also mutes hydrologic L-A coupling. This is detectable globally, and happens through the evapotranspiration-precipitation segment. But on seasonal timescales, SP does not exhibit detectable effects on hydrologic L-A coupling. Two robust regional effects of SP on thermal L-A coupling have also been explored. Over the Arabian Peninsula, SP reduces thermal L-A coupling through a straightforward control by mean rainfall reduction. More counterintuitively, over the Southwestern US and Northern Mexico, SP enhances the thermal L-A coupling in a way that is independent of rainfall and soil moisture. This signal is associated with a systematic and previously unrecognized effect of SP that produces an amplified Bowen ratio, and is detectable in multiple SP model versions and experiment designs. In addition to amplifying the present-day Bowen ratio, SP is found to amplify the climate sensitivity of Bowen ratio as well, which likely plays a role in influencing climate change predictions at the L-A interface.

Global change-driven effects on dissolved organic matter composition: Implications for food webs of northern lakes.

PubMed

Creed, Irena F; Bergström, Ann-Kristin; Trick, Charles G; Grimm, Nancy B; Hessen, Dag O; Karlsson, Jan; Kidd, Karen A; Kritzberg, Emma; McKnight, Diane M; Freeman, Erika C; Senar, Oscar E; Andersson, Agneta; Ask, Jenny; Berggren, Martin; Cherif, Mehdi; Giesler, Reiner; Hotchkiss, Erin R; Kortelainen, Pirkko; Palta, Monica M; Vrede, Tobias; Weyhenmeyer, Gesa A

2018-03-15

Northern ecosystems are experiencing some of the most dramatic impacts of global change on Earth. Rising temperatures, hydrological intensification, changes in atmospheric acid deposition and associated acidification recovery, and changes in vegetative cover are resulting in fundamental changes in terrestrial-aquatic biogeochemical linkages. The effects of global change are readily observed in alterations in the supply of dissolved organic matter (DOM)-the messenger between terrestrial and lake ecosystems-with potentially profound effects on the structure and function of lakes. Northern terrestrial ecosystems contain substantial stores of organic matter and filter or funnel DOM, affecting the timing and magnitude of DOM delivery to surface waters. This terrestrial DOM is processed in streams, rivers, and lakes, ultimately shifting its composition, stoichiometry, and bioavailability. Here, we explore the potential consequences of these global change-driven effects for lake food webs at northern latitudes. Notably, we provide evidence that increased allochthonous DOM supply to lakes is overwhelming increased autochthonous DOM supply that potentially results from earlier ice-out and a longer growing season. Furthermore, we assess the potential implications of this shift for the nutritional quality of autotrophs in terms of their stoichiometry, fatty acid composition, toxin production, and methylmercury concentration, and therefore, contaminant transfer through the food web. We conclude that global change in northern regions leads not only to reduced primary productivity but also to nutritionally poorer lake food webs, with discernible consequences for the trophic web to fish and humans. © 2018 John Wiley & Sons Ltd.

A global analysis of the asymmetric effect of ENSO on extreme precipitation

NASA Astrophysics Data System (ADS)

Sun, Xun; Renard, Benjamin; Thyer, Mark; Westra, Seth; Lang, Michel

2015-11-01

The global and regional influence of the El Niño-Southern Oscillation (ENSO) phenomenon on extreme precipitation was analyzed using a global database comprising over 7000 high quality observation sites. To better quantify possible changes in relatively rare design-relevant precipitation quantiles (e.g. the 1 in 10 year event), a Bayesian regional extreme value model was used, which employed the Southern Oscillation Index (SOI) - a measure of ENSO - as a covariate. Regions found to be influenced by ENSO include parts of North and South America, southern and eastern Asia, South Africa, Australia and Europe. The season experiencing the greatest ENSO effect varies regionally, but in most of the ENSO-affected regions the strongest effect happens in boreal winter, during which time the 10-year precipitation for |SOI| = 20 (corresponding to either a strong El Niño or La Niña episode) can be up to 50% higher or lower than for SOI = 0 (a neutral phase). Importantly, the effect of ENSO on extreme precipitation is asymmetric, with most parts of the world experiencing a significant effect only for a single ENSO phase. This finding has important implications on the current understanding of how ENSO influences extreme precipitation, and will enable a more rigorous theoretical foundation for providing quantitative extreme precipitation intensity predictions at seasonal timescales. We anticipate that incorporating asymmetric impacts of ENSO on extreme precipitation will help lead to better-informed climate-adaptive design of flood-sensitive infrastructure.

Global network centrality of university rankings

NASA Astrophysics Data System (ADS)

Guo, Weisi; Del Vecchio, Marco; Pogrebna, Ganna

2017-10-01

Universities and higher education institutions form an integral part of the national infrastructure and prestige. As academic research benefits increasingly from international exchange and cooperation, many universities have increased investment in improving and enabling their global connectivity. Yet, the relationship of university performance and its global physical connectedness has not been explored in detail. We conduct, to our knowledge, the first large-scale data-driven analysis into whether there is a correlation between university relative ranking performance and its global connectivity via the air transport network. The results show that local access to global hubs (as measured by air transport network betweenness) strongly and positively correlates with the ranking growth (statistical significance in different models ranges between 5% and 1% level). We also found that the local airport's aggregate flight paths (degree) and capacity (weighted degree) has no effect on university ranking, further showing that global connectivity distance is more important than the capacity of flight connections. We also examined the effect of local city economic development as a confounding variable and no effect was observed suggesting that access to global transportation hubs outweighs economic performance as a determinant of university ranking. The impact of this research is that we have determined the importance of the centrality of global connectivity and, hence, established initial evidence for further exploring potential connections between university ranking and regional investment policies on improving global connectivity.

Global self-esteem and method effects: competing factor structures, longitudinal invariance, and response styles in adolescents.

PubMed

Urbán, Róbert; Szigeti, Réka; Kökönyei, Gyöngyi; Demetrovics, Zsolt

2014-06-01

The Rosenberg Self-Esteem Scale (RSES) is a widely used measure for assessing self-esteem, but its factor structure is debated. Our goals were to compare 10 alternative models for the RSES and to quantify and predict the method effects. This sample involves two waves (N =2,513 9th-grade and 2,370 10th-grade students) from five waves of a school-based longitudinal study. The RSES was administered in each wave. The global self-esteem factor with two latent method factors yielded the best fit to the data. The global factor explained a large amount of the common variance (61% and 46%); however, a relatively large proportion of the common variance was attributed to the negative method factor (34 % and 41%), and a small proportion of the common variance was explained by the positive method factor (5% and 13%). We conceptualized the method effect as a response style and found that being a girl and having a higher number of depressive symptoms were associated with both low self-esteem and negative response style, as measured by the negative method factor. Our study supported the one global self-esteem construct and quantified the method effects in adolescents.

Global self-esteem and method effects: competing factor structures, longitudinal invariance and response styles in adolescents

PubMed Central

Urbán, Róbert; Szigeti, Réka; Kökönyei, Gyöngyi; Demetrovics, Zsolt

2013-01-01

The Rosenberg Self-Esteem Scale (RSES) is a widely used measure for assessing self-esteem, but its factor structure is debated. Our goals were to compare 10 alternative models for RSES; and to quantify and predict the method effects. This sample involves two waves (N=2513 ninth-grade and 2370 tenth-grade students) from five waves of a school-based longitudinal study. RSES was administered in each wave. The global self-esteem factor with two latent method factors yielded the best fit to the data. The global factor explained large amount of the common variance (61% and 46%); however, a relatively large proportion of the common variance was attributed to the negative method factor (34 % and 41%), and a small proportion of the common variance was explained by the positive method factor (5% and 13%). We conceptualized the method effect as a response style, and found that being a girl and having higher number of depressive symptoms were associated with both low self-esteem and negative response style measured by the negative method factor. Our study supported the one global self-esteem construct and quantified the method effects in adolescents. PMID:24061931

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.

Identification of BCAP-{sub L} as a negative regulator of the TLR signaling-induced production of IL-6 and IL-10 in macrophages by tyrosine phosphoproteomics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsumura, Takayuki; Department of Life Science and Medical Bio-Science, Waseda University, Shinjuku-ku, Tokyo 162-8480; Oyama, Masaaki

2010-09-17

Research highlights: {yields} Twenty five tyrosine-phosphorylated proteins in LPS-stimulated macrophages were determined. {yields} BCAP is a novel tyrosine-phosphorylated protein in LPS-stimulated macrophages. {yields} BCAP-{sub L} inhibits IL-6 and IL-10 production in LPS-stimulated macrophages. -- Abstract: Toll-like receptor (TLR) signaling in macrophages is essential for anti-pathogen responses such as cytokine production and antigen presentation. Although numerous reports suggest that protein tyrosine kinases (PTKs) are involved in cytokine induction in response to lipopolysaccharides (LPS; TLR4 ligand) in macrophages, the PTK-mediated signal transduction pathway has yet to be analyzed in detail. Here, we carried out a comprehensive and quantitative dynamic tyrosine phosphoproteomic analysismore » on the TLR4-mediated host defense system in RAW264.7 macrophages using stable isotope labeling by amino acids in cell culture (SILAC). We determined the temporal profiles of 25 proteins based on SILAC-encoded peptide(s). Of these, we focused on the tyrosine phosphorylation of B-cell adaptor for phosphatidylinositol 3-kinase (BCAP) because the function of BCAP remains unknown in TLR signaling in macrophages. Furthermore, Bcap has two distinct transcripts, a full-length (Bcap-{sub L}) and an alternatively initiated or spliced (Bcap-{sub S}) mRNA, and little is known about the differential functions of the BCAP-{sub L} and BCAP-{sub S} proteins. Our study showed, for the first time, that RNAi-mediated selective depletion of BCAP-{sub L} enhanced IL-6 and IL-10 production but not TNF-{alpha} production in TLR ligand-stimulated macrophages. We propose that BCAP-{sub L} (but not BCAP-{sub S}) is a negative regulator of the TLR-mediated host defense system in macrophages.« less

Compensatory Water Effects Link Yearly Global Land CO2 Sink Changes to Temperature

NASA Technical Reports Server (NTRS)

Jung, Martin; Reichstein, Markus; Tramontana, Gianluca; Viovy, Nicolas; Schwalm, Christopher R.; Wang, Ying-Ping; Weber, Ulrich; Weber, Ulrich; Zaehle, Soenke; Zeng, Ning;

The effects of global awareness on the spreading of epidemics in multiplex networks

NASA Astrophysics Data System (ADS)

Zang, Haijuan

2018-02-01

It is increasingly recognized that understanding the complex interplay patterns between epidemic spreading and human behavioral is a key component of successful infection control efforts. In particular, individuals can obtain the information about epidemics and respond by altering their behaviors, which can affect the spreading dynamics as well. Besides, because the existence of herd-like behaviors, individuals are very easy to be influenced by the global awareness information. Here, in this paper, we propose a global awareness controlled spreading model (GACS) to explore the interplay between the coupled dynamical processes. Using the global microscopic Markov chain approach, we obtain the analytical results for the epidemic thresholds, which shows a high accuracy by comparison with lots of Monte Carlo simulations. Furthermore, considering other classical models used to describe the coupled dynamical processes, including the local awareness controlled contagion spreading (LACS) model, Susceptible-Infected-Susceptible-Unaware-Aware-Unaware (SIS-UAU) model and the single layer occasion, we make a detailed comparisons between the GACS with them. Although the comparisons and results depend on the parameters each model has, the GACS model always shows a strong restrain effects on epidemic spreading process. Our results give us a better understanding of the coupled dynamical processes and highlights the importance of considering the spreading of global awareness in the control of epidemics.

Learning to Plunder: Global Education, Global Inequality and the Global City

ERIC Educational Resources Information Center

Tannock, Stuart

2010-01-01

Most research and policy discussions of education in the global city have focused on the ways in which globalization and the emergence of global or globalizing cities can create social, economic and educational inequality locally, within the global city itself. Global cities, however, are, by definition, powerful places, where the core…

Energy, atmospheric chemistry, and global climate

NASA Technical Reports Server (NTRS)

Levine, Joel S.

1991-01-01

Global atmospheric changes due to ozone destruction and the greenhouse effect are discussed. The work of the Intergovernmental Panel on Climate Change is reviewed, including its judgements regarding global warming and its recommendations for improving predictive capability. The chemistry of ozone destruction and the global atmospheric budget of nitrous oxide are reviewed, and the global sources of nitrous oxide are described.

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.

Global network centrality of university rankings

PubMed Central

Del Vecchio, Marco; Pogrebna, Ganna

2017-01-01

Universities and higher education institutions form an integral part of the national infrastructure and prestige. As academic research benefits increasingly from international exchange and cooperation, many universities have increased investment in improving and enabling their global connectivity. Yet, the relationship of university performance and its global physical connectedness has not been explored in detail. We conduct, to our knowledge, the first large-scale data-driven analysis into whether there is a correlation between university relative ranking performance and its global connectivity via the air transport network. The results show that local access to global hubs (as measured by air transport network betweenness) strongly and positively correlates with the ranking growth (statistical significance in different models ranges between 5% and 1% level). We also found that the local airport’s aggregate flight paths (degree) and capacity (weighted degree) has no effect on university ranking, further showing that global connectivity distance is more important than the capacity of flight connections. We also examined the effect of local city economic development as a confounding variable and no effect was observed suggesting that access to global transportation hubs outweighs economic performance as a determinant of university ranking. The impact of this research is that we have determined the importance of the centrality of global connectivity and, hence, established initial evidence for further exploring potential connections between university ranking and regional investment policies on improving global connectivity. PMID:29134105

The effects of Global Fund financing on health governance in Brazil.

PubMed

Gómez, Eduardo J; Atun, Rifat

2012-07-16

The impact of donors, such as national government (bi-lateral), private sector, and individual financial (philanthropic) contributions, on domestic health policies of developing nations has been the subject of scholarly discourse. Little is known, however, about the impact of global financial initiatives, such as the Global Fund to Fight AIDS, Tuberculosis, and Malaria, on policies and health governance of countries receiving funding from such initiatives. This study employs a qualitative methodological design based on a single case study: Brazil. Analysis at national, inter-governmental and community levels is based on in-depth interviews with the Global Fund and the Brazilian Ministry of Health and civil societal activists. Primary research is complemented with information from printed media, reports, journal articles, and books, which were used to deepen our analysis while providing supporting evidence. Our analysis suggests that in Brazil, Global Fund financing has helped to positively transform health governance at three tiers of analysis: the national-level, inter-governmental-level, and community-level. At the national-level, Global Fund financing has helped to increased political attention and commitment to relatively neglected diseases, such as tuberculosis, while harmonizing intra-bureaucratic relationships; at the inter-governmental-level, Global Fund financing has motivated the National Tuberculosis Programme to strengthen its ties with state and municipal health departments, and non-governmental organisations (NGOs); while at the community-level, the Global Fund's financing of civil societal institutions has encouraged the emergence of new civic movements, participation, and the creation of new municipal participatory institutions designed to monitor the disbursement of funds for Global Fund grants. Global Fund financing can help deepen health governance at multiple levels. Future work will need to explore how the financing of civil society by the

Quantifying the Effects of Historical Land Cover Conversion Uncertainty on Global Carbon and Climate Estimates

NASA Astrophysics Data System (ADS)

Di Vittorio, A. V.; Mao, J.; Shi, X.; Chini, L.; Hurtt, G.; Collins, W. D.

2018-01-01

Previous studies have examined land use change as a driver of global change, but the translation of land use change into land cover conversion has been largely unconstrained. Here we quantify the effects of land cover conversion uncertainty on the global carbon and climate system using the integrated Earth System Model. Our experiments use identical land use change data and vary land cover conversions to quantify associated uncertainty in carbon and climate estimates. Land cover conversion uncertainty is large, constitutes a 5 ppmv range in estimated atmospheric CO2 in 2004, and generates carbon uncertainty that is equivalent to 80% of the net effects of CO2 and climate and 124% of the effects of nitrogen deposition during 1850-2004. Additionally, land cover uncertainty generates differences in local surface temperature of over 1°C. We conclude that future studies addressing land use, carbon, and climate need to constrain and reduce land cover conversion uncertainties.

Quantifying the Effects of Historical Land Cover Conversion Uncertainty on Global Carbon and Climate Estimates

DOE PAGES

Di Vittorio, A. V.; Mao, J.; Shi, X.; ...

2018-01-03

Previous studies have examined land use change as a driver of global change, but the translation of land use change into land cover conversion has been largely unconstrained. In this paper, we quantify the effects of land cover conversion uncertainty on the global carbon and climate system using the integrated Earth System Model. Our experiments use identical land use change data and vary land cover conversions to quantify associated uncertainty in carbon and climate estimates. Land cover conversion uncertainty is large, constitutes a 5 ppmv range in estimated atmospheric CO 2 in 2004, and generates carbon uncertainty that is equivalentmore » to 80% of the net effects of CO 2 and climate and 124% of the effects of nitrogen deposition during 1850–2004. Additionally, land cover uncertainty generates differences in local surface temperature of over 1°C. Finally, we conclude that future studies addressing land use, carbon, and climate need to constrain and reduce land cover conversion uncertainties.« less

Quantifying the Effects of Historical Land Cover Conversion Uncertainty on Global Carbon and Climate Estimates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Di Vittorio, A. V.; Mao, J.; Shi, X.

Previous studies have examined land use change as a driver of global change, but the translation of land use change into land cover conversion has been largely unconstrained. In this paper, we quantify the effects of land cover conversion uncertainty on the global carbon and climate system using the integrated Earth System Model. Our experiments use identical land use change data and vary land cover conversions to quantify associated uncertainty in carbon and climate estimates. Land cover conversion uncertainty is large, constitutes a 5 ppmv range in estimated atmospheric CO 2 in 2004, and generates carbon uncertainty that is equivalentmore » to 80% of the net effects of CO 2 and climate and 124% of the effects of nitrogen deposition during 1850–2004. Additionally, land cover uncertainty generates differences in local surface temperature of over 1°C. Finally, we conclude that future studies addressing land use, carbon, and climate need to constrain and reduce land cover conversion uncertainties.« less

Non-communicable diseases and global health governance: enhancing global processes to improve health development.

PubMed

Magnusson, Roger S

2007-05-22

This paper assesses progress in the development of a global framework for responding to non-communicable diseases, as reflected in the policies and initiatives of the World Health Organization (WHO), World Bank and the UN: the institutions most capable of shaping a coherent global policy. Responding to the global burden of chronic disease requires a strategic assessment of the global processes that are likely to be most effective in generating commitment to policy change at country level, and in influencing industry behaviour. WHO has adopted a legal process with tobacco (the WHO Framework Convention on Tobacco Control), but a non-legal, advocacy-based approach with diet and physical activity (the Global Strategy on Diet, Physical Activity and Health). The paper assesses the merits of the Millennium Development Goals (MDGs) and the FCTC as distinct global processes for advancing health development, before considering what lessons might be learned for enhancing the implementation of the Global Strategy on Diet. While global partnerships, economic incentives, and international legal instruments could each contribute to a more effective global response to chronic diseases, the paper makes a special case for the development of international legal standards in select areas of diet and nutrition, as a strategy for ensuring that the health of future generations does not become dependent on corporate charity and voluntary commitments. A broader frame of reference for lifestyle-related chronic diseases is needed: one that draws together WHO's work in tobacco, nutrition and physical activity, and that envisages selective use of international legal obligations, non-binding recommendations, advocacy and policy advice as tools of choice for promoting different elements of the strategy.

Non-communicable diseases and global health governance: enhancing global processes to improve health development

PubMed Central

Magnusson, Roger S

2007-01-01

This paper assesses progress in the development of a global framework for responding to non-communicable diseases, as reflected in the policies and initiatives of the World Health Organization (WHO), World Bank and the UN: the institutions most capable of shaping a coherent global policy. Responding to the global burden of chronic disease requires a strategic assessment of the global processes that are likely to be most effective in generating commitment to policy change at country level, and in influencing industry behaviour. WHO has adopted a legal process with tobacco (the WHO Framework Convention on Tobacco Control), but a non-legal, advocacy-based approach with diet and physical activity (the Global Strategy on Diet, Physical Activity and Health). The paper assesses the merits of the Millennium Development Goals (MDGs) and the FCTC as distinct global processes for advancing health development, before considering what lessons might be learned for enhancing the implementation of the Global Strategy on Diet. While global partnerships, economic incentives, and international legal instruments could each contribute to a more effective global response to chronic diseases, the paper makes a special case for the development of international legal standards in select areas of diet and nutrition, as a strategy for ensuring that the health of future generations does not become dependent on corporate charity and voluntary commitments. A broader frame of reference for lifestyle-related chronic diseases is needed: one that draws together WHO's work in tobacco, nutrition and physical activity, and that envisages selective use of international legal obligations, non-binding recommendations, advocacy and policy advice as tools of choice for promoting different elements of the strategy. PMID:17519005

Globalization and social determinants of health: The role of the global marketplace (part 2 of 3)

PubMed Central

Labonté, Ronald; Schrecker, Ted

2007-01-01

Globalization is a key context for the study of social determinants of health (SDH): broadly stated, SDH are the conditions in which people live and work, and that affect their opportunities to lead healthy lives. In the first article in this three part series, we described the origins of the series in work conducted for the Globalization Knowledge Network of the World Health Organization's Commission on Social Determinants of Health and in the Commission's specific concern with health equity. We identified and defended a definition of globalization that gives primacy to the drivers and effects of transnational economic integration, and addressed a number of important conceptual and methodological issues in studying globalization's effects on SDH and their distribution, emphasizing the need for transdisciplinary approaches that reflect the complexity of the topic. In this second article, we identify and describe several, often interacting clusters of pathways leading from globalization to changes in SDH that are relevant to health equity. These involve: trade liberalization; the global reorganization of production and labour markets; debt crises and economic restructuring; financial liberalization; urban settings; influences that operate by way of the physical environment; and health systems changed by the global marketplace. PMID:17578569

Globalization and social determinants of health: The role of the global marketplace (part 2 of 3).

PubMed

Labonté, Ronald; Schrecker, Ted

2007-06-19

Globalization is a key context for the study of social determinants of health (SDH): broadly stated, SDH are the conditions in which people live and work, and that affect their opportunities to lead healthy lives. In the first article in this three part series, we described the origins of the series in work conducted for the Globalization Knowledge Network of the World Health Organization's Commission on Social Determinants of Health and in the Commission's specific concern with health equity. We identified and defended a definition of globalization that gives primacy to the drivers and effects of transnational economic integration, and addressed a number of important conceptual and methodological issues in studying globalization's effects on SDH and their distribution, emphasizing the need for transdisciplinary approaches that reflect the complexity of the topic. In this second article, we identify and describe several, often interacting clusters of pathways leading from globalization to changes in SDH that are relevant to health equity. These involve: trade liberalization; the global reorganization of production and labour markets; debt crises and economic restructuring; financial liberalization; urban settings; influences that operate by way of the physical environment; and health systems changed by the global marketplace.

Tobacco industry globalization and global health governance: towards an interdisciplinary research agenda

PubMed Central

Lee, Kelley; Eckhardt, Jappe; Holden, Chris

2016-01-01

Shifting patterns of tobacco production and consumption, and the resultant disease burden worldwide since the late twentieth century, prompted efforts to strengthen global health governance through adoption of the Framework Convention on Tobacco Control. While the treaty is rightfully considered an important achievement, to address a neglected public health issue through collective action, evidence suggests that tobacco industry globalization continues apace. In this article, we provide a systematic review of the public health literature and reveal definitional and measurement imprecision, ahistorical timeframes, transnational tobacco companies and the state as the primary units and levels of analysis, and a strong emphasis on agency as opposed to structural power. Drawing on the study of globalization in international political economy and business studies, we identify opportunities to expand analysis along each of these dimensions. We conclude that this expanded and interdisciplinary research agenda provides the potential for fuller understanding of the dual and dynamic relationship between the tobacco industry and globalization. Deeper analysis of how the industry has adapted to globalization over time, as well as how the industry has influenced the nature and trajectory of globalization, is essential for building effective global governance responses. This article is published as part of a thematic collection dedicated to global governance. PMID:28458910

Tobacco industry globalization and global health governance: towards an interdisciplinary research agenda.

PubMed

Lee, Kelley; Eckhardt, Jappe; Holden, Chris

2016-01-01

Shifting patterns of tobacco production and consumption, and the resultant disease burden worldwide since the late twentieth century, prompted efforts to strengthen global health governance through adoption of the Framework Convention on Tobacco Control. While the treaty is rightfully considered an important achievement, to address a neglected public health issue through collective action, evidence suggests that tobacco industry globalization continues apace. In this article, we provide a systematic review of the public health literature and reveal definitional and measurement imprecision, ahistorical timeframes, transnational tobacco companies and the state as the primary units and levels of analysis, and a strong emphasis on agency as opposed to structural power. Drawing on the study of globalization in international political economy and business studies, we identify opportunities to expand analysis along each of these dimensions. We conclude that this expanded and interdisciplinary research agenda provides the potential for fuller understanding of the dual and dynamic relationship between the tobacco industry and globalization. Deeper analysis of how the industry has adapted to globalization over time, as well as how the industry has influenced the nature and trajectory of globalization, is essential for building effective global governance responses. This article is published as part of a thematic collection dedicated to global governance.

Radiative effects of global MODIS cloud regimes

PubMed Central

Oreopoulos, Lazaros; Cho, Nayeong; Lee, Dongmin; Kato, Seiji

2018-01-01

We update previously published MODIS global cloud regimes (CRs) using the latest MODIS cloud retrievals in the Collection 6 dataset. We implement a slightly different derivation method, investigate the composition of the regimes, and then proceed to examine several aspects of CR radiative appearance with the aid of various radiative flux datasets. Our results clearly show the CRs are radiatively distinct in terms of shortwave, longwave and their combined (total) cloud radiative effect. We show that we can clearly distinguish regimes based on whether they radiatively cool or warm the atmosphere, and thanks to radiative heating profiles to discern the vertical distribution of cooling and warming. Terra and Aqua comparisons provide information about the degree to which morning and afternoon occurrences of regimes affect the symmetry of CR radiative contribution. We examine how the radiative discrepancies among multiple irradiance datasets suffering from imperfect spatiotemporal matching depend on CR, and whether they are therefore related to the complexity of cloud structure, its interpretation by different observational systems, and its subsequent representation in radiative transfer calculations. PMID:29619289

Radiative effects of global MODIS cloud regimes.

PubMed

Oreopoulos, Lazaros; Cho, Nayeong; Lee, Dongmin; Kato, Seiji

2016-03-16

We update previously published MODIS global cloud regimes (CRs) using the latest MODIS cloud retrievals in the Collection 6 dataset. We implement a slightly different derivation method, investigate the composition of the regimes, and then proceed to examine several aspects of CR radiative appearance with the aid of various radiative flux datasets. Our results clearly show the CRs are radiatively distinct in terms of shortwave, longwave and their combined (total) cloud radiative effect. We show that we can clearly distinguish regimes based on whether they radiatively cool or warm the atmosphere, and thanks to radiative heating profiles to discern the vertical distribution of cooling and warming. Terra and Aqua comparisons provide information about the degree to which morning and afternoon occurrences of regimes affect the symmetry of CR radiative contribution. We examine how the radiative discrepancies among multiple irradiance datasets suffering from imperfect spatiotemporal matching depend on CR, and whether they are therefore related to the complexity of cloud structure, its interpretation by different observational systems, and its subsequent representation in radiative transfer calculations.

Radiative Effects of Global MODIS Cloud Regimes

NASA Technical Reports Server (NTRS)

Oraiopoulos, Lazaros; Cho, Nayeong; Lee, Dong Min; Kato, Seiji

2016-01-01

We update previously published MODIS global cloud regimes (CRs) using the latest MODIS cloud retrievals in the Collection 6 dataset. We implement a slightly different derivation method, investigate the composition of the regimes, and then proceed to examine several aspects of CR radiative appearance with the aid of various radiative flux datasets. Our results clearly show the CRs are radiatively distinct in terms of shortwave, longwave and their combined (total) cloud radiative effect. We show that we can clearly distinguish regimes based on whether they radiatively cool or warm the atmosphere, and thanks to radiative heating profiles to discern the vertical distribution of cooling and warming. Terra and Aqua comparisons provide information about the degree to which morning and afternoon occurrences of regimes affect the symmetry of CR radiative contribution. We examine how the radiative discrepancies among multiple irradiance datasets suffering from imperfect spatiotemporal matching depend on CR, and whether they are therefore related to the complexity of cloud structure, its interpretation by different observational systems, and its subsequent representation in radiative transfer calculations.

Ozone, Climate, and Global Atmospheric Change.

ERIC Educational Resources Information Center

Levine, Joel S.

1992-01-01

Presents an overview of global atmospheric problems relating to ozone depletion and global warming. Provides background information on the composition of the earth's atmosphere and origin of atmospheric ozone. Describes causes, effects, and evidence of ozone depletion and the greenhouse effect. A vignette provides a summary of a 1991 assessment of…

From a United Nations Study: The Climatic and Other Global Effects of Nuclear War.

ERIC Educational Resources Information Center

Environment, 1988

1988-01-01

Presents excerpts from the first chapter of a report presented to the General Assembly of the United Nations during the Special Session on Disarmament. Discussed are key scientific issues regarding the global effects of nuclear war, and the findings and conclusions presented in the report. (CW)

Studying the physical basis of global warming: thermal effects of the interaction between radiation and matter and greenhouse effect

NASA Astrophysics Data System (ADS)

Besson, Ugo; De Ambrosis, Anna; Mascheretti, Paolo

2010-03-01

We present a teaching module dealing with the thermal effects of interaction between radiation and matter, the infrared emission of bodies and the greenhouse effect devoted to university level and teacher education. The module stresses the dependence of the optical properties of materials (transparency, absorptivity and emissivity) on radiation frequency, as a result of interaction between matter and radiation. Multiple experiences are suggested to favour a progressive construction of knowledge on the physical aspects necessary to understand the greenhouse effect and global warming. Some results obtained with university students are briefly reported.

Does Globalization Affect Human Well-Being?

ERIC Educational Resources Information Center

Tsai, Ming-Chang

2007-01-01

The prevailing theorizing of globalization's influence of human well-being suggests to assess both the favorable and unfavorable outcomes. This study formulates a dialectical model, adopts a comprehensive globalization measure and uses a three-wave panel data during 1980-2000 to empirically test direct and indirect effects of global flows' human…

The effects of Global Fund financing on health governance in Brazil

PubMed Central

2012-01-01

Objectives The impact of donors, such as national government (bi-lateral), private sector, and individual financial (philanthropic) contributions, on domestic health policies of developing nations has been the subject of scholarly discourse. Little is known, however, about the impact of global financial initiatives, such as the Global Fund to Fight AIDS, Tuberculosis, and Malaria, on policies and health governance of countries receiving funding from such initiatives. Methods This study employs a qualitative methodological design based on a single case study: Brazil. Analysis at national, inter-governmental and community levels is based on in-depth interviews with the Global Fund and the Brazilian Ministry of Health and civil societal activists. Primary research is complemented with information from printed media, reports, journal articles, and books, which were used to deepen our analysis while providing supporting evidence. Results Our analysis suggests that in Brazil, Global Fund financing has helped to positively transform health governance at three tiers of analysis: the national-level, inter-governmental-level, and community-level. At the national-level, Global Fund financing has helped to increased political attention and commitment to relatively neglected diseases, such as tuberculosis, while harmonizing intra-bureaucratic relationships; at the inter-governmental-level, Global Fund financing has motivated the National Tuberculosis Programme to strengthen its ties with state and municipal health departments, and non-governmental organisations (NGOs); while at the community-level, the Global Fund’s financing of civil societal institutions has encouraged the emergence of new civic movements, participation, and the creation of new municipal participatory institutions designed to monitor the disbursement of funds for Global Fund grants. Conclusions Global Fund financing can help deepen health governance at multiple levels. Future work will need to explore how

Processionary Moths and Associated Urtication Risk: Global Change-Driven Effects.

PubMed

Battisti, Andrea; Larsson, Stig; Roques, Alain

2017-01-31

Processionary moths carry urticating setae, which cause health problems in humans and other warm-blooded animals. The pine processionary moth Thaumetopoea pityocampa has responded to global change (climate warming and increased global trade) by extending its distribution range. The subfamily Thaumetopoeinae consists of approximately 100 species. An important question is whether other processionary moth species will similarly respond to these specific dimensions of global change and thus introduce health hazards into new areas. We describe, for the first time, how setae are distributed on different life stages (adult, larva) of major groups within the subfamily. Using the available data, we conclude that there is little evidence that processionary moths as a group will behave like T. pityocampa and expand their distributional range. The health problems caused by setae strongly relate to population density, which may, or may not, be connected to global change.

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.

Switching between global and local levels: the level repetition effect and its hemispheric asymmetry

PubMed Central

Kéïta, Luc; Bedoin, Nathalie; Burack, Jacob A.; Lepore, Franco

2014-01-01

The global level of hierarchical stimuli (Navon’s stimuli) is typically processed quicker and better than the local level; further differential hemispheric dominance is described for local (left hemisphere, LH) and global (right hemisphere, RH) processing. However, neuroimaging and behavioral data indicate that stimulus category (letter or object) could modulate the hemispheric asymmetry for the local level processing. Besides, when the targets are unpredictably displayed at the global or local level, the participant has to switch between levels, and the magnitude of the switch cost increases with the number of repeated-level trials preceding the switch. The hemispheric asymmetries associated with level switching is an unresolved issue. LH areas may be involved in carrying over the target level information in case of level repetition. These areas may also largely participate in the processing of level-changed trials. Here we hypothesized that RH areas underly the inhibitory mechanism performed on the irrelevant level, as one of the components of the level switching process. In an experiment using a within-subject design, hierarchical stimuli were briefly presented either to the right or to the left visual field. 32 adults were instructed to identify the target at the global or local level. We assessed a possible RH dominance for the non-target level inhibition by varying the attentional demands through the manipulation of level repetitions (two or gour repeated-level trials before the switch). The behavioral data confirmed a LH specialization only for the local level processing of letter-based stimuli, and detrimental effect of increased level repetitions before a switch. Further, data provides evidence for a RH advantage in inhibiting the non-target level. Taken together, the data supports the notion of the existence of multiple mechanisms underlying level-switch effects. PMID:24723903

GLOBAL CHANGE RESEARCH NEWS #18: SYMPOSIUM SESSION ON "GLOBAL ATMOSPHERIC CHANGE"

EPA Science Inventory

A session on "Understanding and Managing Effects of Global Atmospheric Change" will be held at the Fifth Symposium of the U.S. EPA National Health and Environmental Effects Research Laboratory. The Symposium topic is "Indicators in Health and Ecological Risk Assessment." The s...

Three-Dimensional (3-D) Printing: A Cost-Effective Solution for Improving Global Accessibility to Prostheses.

PubMed

Silva, Kyle; Rand, Stephanie; Cancel, David; Chen, Yuxi; Kathirithamby, Rani; Stern, Michelle

2015-12-01

The lack of access to prostheses is a global problem, partially caused by the high cost associated with the current manufacturing process. Three-dimensional printing is gaining use in the medical field, and one such area is prosthetics. In addition to using cost-effective materials, this technology allows for rapid prototyping, making it an efficient solution for the development of affordable prostheses. If the rehabilitation medicine community embraces this novel technology, we can help alleviate the global disparity of access to prostheses. Copyright © 2015 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Global aerosol effects on convective clouds

NASA Astrophysics Data System (ADS)

Wagner, Till; Stier, Philip

2013-04-01

Atmospheric aerosols affect cloud properties, and thereby the radiation balance of the planet and the water cycle. The influence of aerosols on clouds is dominated by increase of cloud droplet and ice crystal numbers (CDNC/ICNC) due to enhanced aerosols acting as cloud condensation and ice nuclei. In deep convective clouds this increase in CDNC/ICNC is hypothesised to increase precipitation because of cloud invigoration through enhanced freezing and associated increased latent heat release caused by delayed warm rain formation. Satellite studies robustly show an increase of cloud top height (CTH) and precipitation with increasing aerosol optical depth (AOD, as proxy for aerosol amount). To represent aerosol effects and study their influence on convective clouds in the global climate aerosol model ECHAM-HAM, we substitute the standard convection parameterisation, which uses one mean convective cloud for each grid column, with the convective cloud field model (CCFM), which simulates a spectrum of convective clouds, each with distinct values of radius, mixing ratios, vertical velocity, height and en/detrainment. Aerosol activation and droplet nucleation in convective updrafts at cloud base is the primary driver for microphysical aerosol effects. To produce realistic estimates for vertical velocity at cloud base we use an entraining dry parcel sub cloud model which is triggered by perturbations of sensible and latent heat at the surface. Aerosol activation at cloud base is modelled with a mechanistic, Köhler theory based, scheme, which couples the aerosols to the convective microphysics. Comparison of relationships between CTH and AOD, and precipitation and AOD produced by this novel model and satellite based estimates show general agreement. Through model experiments and analysis of the model cloud processes we are able to investigate the main drivers for the relationship between CTH / precipitation and AOD.

Where theory and practice of global health intersect: the developmental history of a Canadian global health initiative.

PubMed

Daibes, Ibrahim; Sridharan, Sanjeev

2014-01-01

This paper examines the scope of practice of global health, drawing on the practical experience of a global health initiative of the Government of Canada--the Teasdale-Corti Global Health Research Partnership Program. A number of challenges in the practical application of theoretical definitions and understandings of global health are addressed. These challenges are grouped under five areas that form essential characteristics of global health: equity and egalitarian North-South partnerships, interdisciplinary scope, focus on upstream determinants of health, global conceptualization, and global health as an area of both research and practice. Information in this paper is based on the results of an external evaluation of the program, which involved analysis of project proposals and technical reports, surveys with grantees and interviews with grantees and program designers, as well as case studies of three projects and a review of relevant literature. The philosophy and recent definitions of global health represent a significant and important departure from the international health paradigm. However, the practical applicability of this maturing area of research and practice still faces significant systemic and structural impediments that, if not acknowledged and addressed, will continue to undermine the development of global health as an effective means to addressing health inequities globally and to better understanding, and acting upon, upstream determinants of health toward health for all. While it strives to redress global inequities, global health continues to be a construct that is promoted, studied, and dictated mostly by Northern institutions and scholars. Until practical mechanisms are put in place for truly egalitarian partnerships between North and South for both the study and practice of global health, the emerging philosophy of global health cannot be effectively put into practice.

A Study of Global Health Elective Outcomes

PubMed Central

Russ, Christiana M.; Tran, Tony; Silverman, Melanie; Palfrey, Judith

2017-01-01

Background and Objectives: To identify the effects of global health electives over a decade in a pediatric residency program. Methods: This was an anonymous email survey of the Boston Combined Residency alumni funded for global health electives from 2002 to 2011. A test for trend in binomial proportions and logistic regression were used to document associations between elective and participant characteristics and the effects of the electives. Qualitative data were also analyzed. Results: Of the 104 alumni with available email addresses, 69 (66%) responded, describing 94 electives. Elective products included 27 curricula developed, 11 conference presentations, and 7 academic publications. Thirty-two (46%) alumni continued global health work. Previous experience, previous travel to the site, number of global electives, and cumulative global elective time were associated with postresidency work in global health or with the underserved. Conclusions: Resident global electives resulted in significant scholarship and teaching and contributed to long-term career trajectories. PMID:28229096

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. Published by Oxford University Press on behalf of the Annals of Botany Company.

Local food web management increases resilience and buffers against global change effects on freshwaters

NASA Astrophysics Data System (ADS)

Urrutia-Cordero, Pablo; Ekvall, Mattias K.; Hansson, Lars-Anders

2016-07-01

A major challenge for ecological research is to identify ways to improve resilience to climate-induced changes in order to secure the ecosystem functions of natural systems, as well as ecosystem services for human welfare. With respect to aquatic ecosystems, interactions between climate warming and the elevated runoff of humic substances (brownification) may strongly affect ecosystem functions and services. However, we hitherto lack the adaptive management tools needed to counteract such global-scale effects on freshwater ecosystems. Here we show, both experimentally and using monitoring data, that predicted climatic warming and brownification will reduce freshwater quality by exacerbating cyanobacterial growth and toxin levels. Furthermore, in a model based on long-term data from a natural system, we demonstrate that food web management has the potential to increase the resilience of freshwater systems against the growth of harmful cyanobacteria, and thereby that local efforts offer an opportunity to secure our water resources against some of the negative impacts of climate warming and brownification. This allows for novel policy action at a local scale to counteract effects of global-scale environmental change, thereby providing a buffer period and a safer operating space until climate mitigation strategies are effectively established.

Effects of finite coverage on global polarization observables in heavy ion collisions

NASA Astrophysics Data System (ADS)

Lan, Shaowei; Lin, Zi-Wei; Shi, Shusu; Sun, Xu

2018-05-01

In non-central relativistic heavy ion collisions, the created matter possesses a large initial orbital angular momentum. Particles produced in the collisions could be polarized globally in the direction of the orbital angular momentum due to spin-orbit coupling. Recently, the STAR experiment has presented polarization signals for Λ hyperons and possible spin alignment signals for ϕ mesons. Here we discuss the effects of finite coverage on these observables. The results from a multi-phase transport and a toy model both indicate that a pseudorapidity coverage narrower than | η | < ∼ 1 will generate a larger value for the extracted ϕ-meson ρ00 parameter; thus a finite coverage can lead to an artificial deviation of ρ00 from 1/3. We also show that a finite η and pT coverage affect the extracted pH parameter for Λ hyperons when the real pH value is non-zero. Therefore proper corrections are necessary to reliably quantify the global polarization with experimental observables.

Effects of local and global network connectivity on synergistic epidemics

NASA Astrophysics Data System (ADS)

Broder-Rodgers, David; Pérez-Reche, Francisco J.; Taraskin, Sergei N.

2015-12-01

Epidemics in networks can be affected by cooperation in transmission of infection and also connectivity between nodes. An interplay between these two properties and their influence on epidemic spread are addressed in the paper. A particular type of cooperative effects (called synergy effects) is considered, where the transmission rate between a pair of nodes depends on the number of infected neighbors. The connectivity effects are studied by constructing networks of different topology, starting with lattices with only local connectivity and then with networks that have both local and global connectivity obtained by random bond-rewiring to nodes within a certain distance. The susceptible-infected-removed epidemics were found to exhibit several interesting effects: (i) for epidemics with strong constructive synergy spreading in networks with high local connectivity, the bond rewiring has a negative role in epidemic spread, i.e., it reduces invasion probability; (ii) in contrast, for epidemics with destructive or weak constructive synergy spreading on networks of arbitrary local connectivity, rewiring helps epidemics to spread; (iii) and, finally, rewiring always enhances the spread of epidemics, independent of synergy, if the local connectivity is low.

Effects of local and global network connectivity on synergistic epidemics.

PubMed

Broder-Rodgers, David; Pérez-Reche, Francisco J; Taraskin, Sergei N

2015-12-01

Epidemics in networks can be affected by cooperation in transmission of infection and also connectivity between nodes. An interplay between these two properties and their influence on epidemic spread are addressed in the paper. A particular type of cooperative effects (called synergy effects) is considered, where the transmission rate between a pair of nodes depends on the number of infected neighbors. The connectivity effects are studied by constructing networks of different topology, starting with lattices with only local connectivity and then with networks that have both local and global connectivity obtained by random bond-rewiring to nodes within a certain distance. The susceptible-infected-removed epidemics were found to exhibit several interesting effects: (i) for epidemics with strong constructive synergy spreading in networks with high local connectivity, the bond rewiring has a negative role in epidemic spread, i.e., it reduces invasion probability; (ii) in contrast, for epidemics with destructive or weak constructive synergy spreading on networks of arbitrary local connectivity, rewiring helps epidemics to spread; (iii) and, finally, rewiring always enhances the spread of epidemics, independent of synergy, if the local connectivity is low.

[The globalization of health].

PubMed

Franco, A

2003-01-01

In this article diverse aspects of the relationship between health and globalization are explored. Different dimensions of globalization (economic, technological, cultural and political) are considered. Aspects of its effects on health (epidemiological, ethical and environmental), as well as its relationship with public health, power distribution and equity are discussed. Data that demonstrate the globalization of risks and of diseases, due to the current model of international relations and geographical mobility, are analyzed. The article defends the globalization of health and integrates renewed concepts and scientific advances in public health with politics, social strategies and new organizational forms of the practice of public health. Finally, we discuss the opportunities that have been provided by globalization since the middle of the last century for redefining world government and for developing local movements, based on solidarity and a new concept of politics, which could favor the universalization of health.

The Global Public Health Intelligence Network and early warning outbreak detection: a Canadian contribution to global public health.

PubMed

Mykhalovskiy, Eric; Weir, Lorna

2006-01-01

The recent SARS epidemic has renewed widespread concerns about the global transmission of infectious diseases. In this commentary, we explore novel approaches to global infectious disease surveillance through a focus on an important Canadian contribution to the area--the Global Public Health Intelligence Network (GPHIN). GPHIN is a cutting-edge initiative that draws on the capacity of the Internet and newly available 24/7 global news coverage of health events to create a unique form of early warning outbreak detection. This commentary outlines the operation and development of GPHIN and compares it to ProMED-mail, another Internet-based approach to global health surveillance. We argue that GPHIN has created an important shift in the relationship of public health and news information. By exiting the pyramid of official reporting, GPHIN has created a new monitoring technique that has disrupted national boundaries of outbreak notification, while creating new possibilities for global outbreak response. By incorporating news within the emerging apparatus of global infectious disease surveillance, GPHIN has effectively responded to the global media's challenge to official country reporting of outbreak and enhanced the effectiveness and credibility of international public health.

Global warming effects: future feasibility of current cooling equipment for animal houses

NASA Astrophysics Data System (ADS)

Valiño, V.; Perdigones, A.; García, J. L.; de La Plaza, S.

2009-04-01

Interest in global warming effects on the agricultural systems is currently high, especially in areas which are likely to be more affected by this temperature rising, i.e. the Mediterranean area (IPCC, 2008). According to this report, the model projections of surface warming predict a temperature increase between 0.5°C to 1.5°C in the European area by the period 2020-2029. The aim of the present work was to assess the future consequences of the global warming effect on the feasibility of the cooling equipment in animal houses. Several equipment combinations were compared by means of modelling the inside climate in fattening pig houses, including forced ventilation and cooling pad. The modelling was carried out for six different European locations: Spain, Greece, Italy, The Netherlands, Germany and the United Kingdom, for the today conditions; secondly, the global warming effect in the inside climate was considered in a second set of simulations, and a mean temperature rising of 2°C was taken into account. Climate data. The six European locations were: Madrid (Spain); Aliartos (Greece); Bedford (The United Kingdom); Schipol (The Netherlands); Milan (Italy); and Stuttgart (Germany). From every location, the available climate data were monthly mean temperature (To; °C); monthly mean relative humidity (HRo, %) and monthly mean solar irradiation on horizontal surface (So; W m-2). From these monthly values, hourly means were calculated resulting in 24 data for a typical day, each month. Climate model. In this study, cooling strategies resulted from the combination of natural ventilation, mechanical ventilation and cooling pads. The climate model was developed taking into account the following energy fluxes: solar radiation, ventilation (Seginer, 2002), animal heat losses (Blanes and Pedersen, 2005), and loss of energy due to the cooling pads (Seginer, 2002). Results for the present work, show a comparative scene of the inside climate by using different cooling

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…

Global Public Leadership in a Technological Era

ERIC Educational Resources Information Center

Masciulli, Joseph

2011-01-01

Good (ethical and effective) global public leadership--by national politicians, intergovernmental and nongovernmental international organizational leaders, multinational corporate leaders, and technoscientists--will make a significant positive difference in our global system's capacity to solve contemporary and futuristic global problems. High…

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.

[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.

The Effectiveness of learning materials based on multiple intelligence on the understanding of global warming

NASA Astrophysics Data System (ADS)

Liliawati, W.; Purwanto; Zulfikar, A.; Kamal, R. N.

2018-05-01

This study aims to examine the effectiveness of the use of teaching materials based on multiple intelligences on the understanding of high school students’ material on the theme of global warming. The research method used is static-group pretest-posttest design. Participants of the study were 60 high school students of XI class in one of the high schools in Bandung. Participants were divided into two classes of 30 students each for the experimental class and control class. The experimental class uses compound-based teaching materials while the experimental class does not use a compound intelligence-based teaching material. The instrument used is a test of understanding of the concept of global warming with multiple choices form amounted to 15 questions and 5 essay items. The test is given before and after it is applied to both classes. Data analysis using N-gain and effect size. The results obtained that the N-gain for both classes is in the medium category and the effectiveness of the use of teaching materials based on the results of effect-size test results obtained in the high category.

'Home made' model to study the greenhouse effect and global warming

NASA Astrophysics Data System (ADS)

Onorato, P.; Mascheretti, P.; DeAmbrosis, A.

2011-03-01

In this paper a simplified two-parameter model of the greenhouse effect on the Earth is developed, starting from the well known two-layer model. It allows both the analysis of the temperatures of the inner planets, by focusing on the role of the greenhouse effect, and a comparison between the temperatures the planets should have in the absence of greenhouse effect and their actual ones. It may also be used to predict the average temperature of the Earth surface in the future, depending on the variations of the concentration of greenhouse gases in the atmosphere due to human activities. This model can promote an elementary understanding of global warming since it allows a simple formalization of the energy balance for the Earth in the stationary condition, in the presence of greenhouse gases. For these reasons it can be introduced in courses for undergraduate physics students and for teacher preparation.

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.

Global warming and effects on the Arctic fox.

PubMed

Fuglei, Eva; Ims, Rolf Anker

2008-01-01

We predict the effect of global warming on the arctic fox, the only endemic terrestrial predatory mammals in the arctic region. We emphasize the difference between coastal and inland arctic fox populations. Inland foxes rely on peak abundance of lemming prey to sustain viable populations. In the short-term, warmer winters result in missed lemming peak years and reduced opportunities for successful arctic fox breeding. In the long-term, however, warmer climate will increase plant productivity and more herbivore prey for competitive dominant predators moving in from the south. The red fox has already intruded the arctic region and caused a retreat of the southern limit of arctic fox distribution range. Coastal arctic foxes, which rely on the richer and temporally stable marine subsidies, will be less prone to climate-induced resource limitations. Indeed, arctic islands, becoming protected from southern species invasions as the extent of sea ice is decreasing, may become the last refuges for coastal populations of Arctic foxes.

The effects of household management practices on the global warming potential of urban lawns.

PubMed

Gu, Chuanhui; Crane, John; Hornberger, George; Carrico, Amanda

2015-03-15

Nitrous oxide (N2O) emissions are an important component of the greenhouse gas (GHG) budget for urban turfgrasses. A biogeochemical model DNDC successfully captured the magnitudes and patterns of N2O emissions observed at an urban turfgrass system at the Richland Creek Watershed in Nashville, TN. The model was then used to study the long-term (i.e. 75 years) impacts of lawn management practice (LMP) on soil organic carbon sequestration rate (dSOC), soil N2O emissions, and net Global Warming Potentials (net GWPs). The model simulated N2O emissions and net GWP from the three management intensity levels over 75 years ranged from 0.75 to 3.57 kg N ha(-1)yr(-1) and 697 to 2443 kg CO2-eq ha(-1)yr(-1), respectively, which suggested that turfgrasses act as a net carbon emitter. Reduction of fertilization is most effective to mitigate the global warming potentials of turfgrasses. Compared to the baseline scenario, halving fertilization rate and clipping recycle as an alternative to synthetic fertilizer can reduce net GWPs by 17% and 12%, respectively. In addition, reducing irrigation and mowing are also effective in lowering net GWPs. The minimum-maintenance LMP without irrigation and fertilization can reduce annual N2O emissions and net GWPs by approximately 53% and 70%, respectively, with the price of gradual depletion of soil organic carbon, when compared to the intensive-maintenance LMP. A lawn age-dependent best management practice is recommended: a high dose fertilizer input at the initial stage of lawn establishment to enhance SOC sequestration, followed by decreasing fertilization rate when the lawn ages to minimize N2O emissions. A minimum-maintained LMP with clipping recycling, and minimum irrigation and mowing, is recommended to mitigate global warming effects from urban turfgrass systems. Among all practices, clipping recycle may be a relatively malleable behavior and, therefore, a good target for interventions seeking to reduce the environmental impacts of lawn

The effects of 1.5 and 2 degrees of global warming on Africa in the CORDEX ensemble

NASA Astrophysics Data System (ADS)

Nikulin, Grigory; Lennard, Chris; Dosio, Alessandro; Kjellström, Erik; Chen, Youmin; Hänsler, Andreas; Kupiainen, Marco; Laprise, René; Mariotti, Laura; Fox Maule, Cathrine; van Meijgaard, Erik; Panitz, Hans-Jürgen; Scinocca, John F.; Somot, Samuel

2018-06-01

There is a general lack of information about the potential effects of 1.5, 2 or more degrees of global warming on the regional climates within Africa, and most studies that address this use data from coarse resolution global models. Using a large ensemble of CORDEX Africa simulations, we present a pan-African overview of the effects of 1.5 and 2 °C global warming levels (GWLs) on the African climate. The CORDEX simulations, consistent with their driving global models, show a robust regional warming exceeding the mean global one over most of Africa. The highest increase in annual mean temperature is found over the subtropics and the smallest one over many coastal regions. Projected changes in annual mean precipitation have a tendency to wetter conditions in some parts of Africa (e.g. central/eastern Sahel and eastern Africa) at both GWLs, but models’ agreement on the sign of change is low. In contrast to mean precipitation, there is a consistent increase in daily precipitation intensity of wet days over a large fraction of tropical Africa emerging already at 1.5 °C GWL and strengthening at 2 °C. A consistent difference between 2 °C and 1.5 °C warmings is also found for projected changes in annual mean temperature and daily precipitation intensity. Our study indicates that a 0.5 °C further warming (from 1.5 °C–2 °C) can indeed produce a robust change in some aspects of the African climate and its extremes.

Integrating global health with medical education.

PubMed

Aulakh, Alex; Tweed, Sam; Moore, Jolene; Graham, Wendy

2017-04-01

Globalisation has implications for the next generation of doctors, and thus for medical education. Increasingly, global health is being taught in medical schools, although its incorporation into an already full curriculum presents challenges. Global health was introduced into the MBChB curriculum at the University of Aberdeen through a student-selected component (SSC) as part of an existing medical humanities block. The Global Health and Humanities (GHH) module was first delivered in the autumn of 2013 and will shortly enter its third year. This student-led study used quantitative and qualitative methods to assess the module's appropriateness and effectiveness for strengthening learning on global health, consisting of online surveys for course participants and semi-structured interviews with faculty members. Integrating global health into the undergraduate medical curriculum by way of an SSC was regarded by teaching staff as an effective and realistic approach. A recognised strength of delivering global health as part of the medical humanities block was the opportunity to expose students to the social determinants of health through interdisciplinary teaching. Participating students all agreed that the learning approach strengthened both their knowledge of global health and a range of generic skills. SSCs are, by definition, self-selecting, and will have a tendency to attract students already with an interest in a topic - here global health. A wide range of learning opportunities is needed to integrate global health throughout medical curricula, and to reach all students. © 2016 John Wiley & Sons Ltd.

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...

A global network topology of stock markets: Transmitters and receivers of spillover effects

NASA Astrophysics Data System (ADS)

Shahzad, Syed Jawad Hussain; Hernandez, Jose Areola; Rehman, Mobeen Ur; Al-Yahyaee, Khamis Hamed; Zakaria, Muhammad

2018-02-01

This paper applies a bivariate cross-quantilogram approach to examine the spillover network structure in the stock markets of 58 countries according to bearish, normal and bullish market scenarios. Our aim is to identify the strongest interdependencies, the directionality of the spillover risk effects, and to detect those equity markets with the potential to cause global systemic risk. The results highlight the role of the US and Canadian equity markets as major spillover transmitters, while the stock markets of Romania, Taiwan and Mexico act mainly as spillover receivers. Particularly strong spillovers are observed from the Canadian and US equity markets towards the Irish market, and from the Brazilian equity market towards the Kenyan equivalent. The equity market networks suggest that only the US equity market can trigger systemic risk on a global scale. Implications of the results are discussed.

Unexpected Events Induce Motor Slowing via a Brain Mechanism for Action-Stopping with Global Suppressive Effects

PubMed Central

Aron, Adam R.

2013-01-01

When an unexpected event occurs in everyday life (e.g., a car honking), one experiences a slowing down of ongoing action (e.g., of walking into the street). Motor slowing following unexpected events is a ubiquitous phenomenon, both in laboratory experiments as well as such everyday situations, yet the underlying mechanism is unknown. We hypothesized that unexpected events recruit the same inhibition network in the brain as does complete cancellation of an action (i.e., action-stopping). Using electroencephalography and independent component analysis in humans, we show that a brain signature of successful outright action-stopping also exhibits activity following unexpected events, and more so in blocks with greater motor slowing. Further, using transcranial magnetic stimulation to measure corticospinal excitability, we show that an unexpected event has a global motor suppressive effect, just like outright action-stopping. Thus, unexpected events recruit a common mechanism with outright action-stopping, moreover with global suppressive effects. These findings imply that we can now leverage the considerable extant knowledge of the neural architecture and functional properties of the stopping system to better understand the processing of unexpected events, including perhaps how they induce distraction via global suppression. PMID:24259571

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…

Global Methane Initiative

EPA Pesticide Factsheets

The Global Methane Initiative promotes cost-effective, near-term methane recovery through partnerships between developed and developing countries, with participation from the private sector, development banks, and nongovernmental organizations.

Global Health and Foreign Policy

PubMed Central

Feldbaum, Harley; Lee, Kelley; Michaud, Joshua

2010-01-01

Health has long been intertwined with the foreign policies of states. In recent years, however, global health issues have risen to the highest levels of international politics and have become accepted as legitimate issues in foreign policy. This elevated political priority is in many ways a welcome development for proponents of global health, and it has resulted in increased funding for and attention to select global health issues. However, there has been less examination of the tensions that characterize the relationship between global health and foreign policy and of the potential effects of linking global health efforts with the foreign-policy interests of states. In this paper, the authors review the relationship between global health and foreign policy by examining the roles of health across 4 major components of foreign policy: aid, trade, diplomacy, and national security. For each of these aspects of foreign policy, the authors review current and historical issues and discuss how foreign-policy interests have aided or impeded global health efforts. The increasing relevance of global health to foreign policy holds both opportunities and dangers for global efforts to improve health. PMID:20423936

Global health and foreign policy.

PubMed

Feldbaum, Harley; Lee, Kelley; Michaud, Joshua

2010-01-01

Health has long been intertwined with the foreign policies of states. In recent years, however, global health issues have risen to the highest levels of international politics and have become accepted as legitimate issues in foreign policy. This elevated political priority is in many ways a welcome development for proponents of global health, and it has resulted in increased funding for and attention to select global health issues. However, there has been less examination of the tensions that characterize the relationship between global health and foreign policy and of the potential effects of linking global health efforts with the foreign-policy interests of states. In this paper, the authors review the relationship between global health and foreign policy by examining the roles of health across 4 major components of foreign policy: aid, trade, diplomacy, and national security. For each of these aspects of foreign policy, the authors review current and historical issues and discuss how foreign-policy interests have aided or impeded global health efforts. The increasing relevance of global health to foreign policy holds both opportunities and dangers for global efforts to improve health.

Global Energy Issues and Alternate Fueling

NASA Technical Reports Server (NTRS)

Hendricks, Robert C.

2007-01-01

This viewgraph presentation describes world energy issues and alternate fueling effects on aircraft design. The contents include: 1) US Uses about 100 Quad/year (1 Q = 10(exp 15) Btu) World Energy Use: about 433 Q/yr; 2) US Renewable Energy about 6%; 3) Nuclear Could Grow: Has Legacy Problems; 4) Energy Sources Primarily NonRenewable Hydrocarbon; 5) Notes; 6) Alternate Fuels Effect Aircraft Design; 7) Conventional-Biomass Issue - Food or Fuel; 8) Alternate fuels must be environmentally benign; 9) World Carbon (CO2) Emissions Problem; 10) Jim Hansen s Global Warming Warnings; 11) Gas Hydrates (Clathrates), Solar & Biomass Locations; 12) Global Energy Sector Response; 13) Alternative Renewables; 14) Stratospheric Sulfur Injection Global Cooling Switch; 15) Potential Global Energy Sector Response; and 16) New Sealing and Fluid Flow Challenges.

Molecular Dynamics Pinpoint the Global Fluorine Effect in Balanoid Binding to PKCε and PKA.

PubMed

Hardianto, Ari; Liu, Fei; Ranganathan, Shoba

2018-02-26

(-)-Balanol is an adenosine triphosphate mimic that inhibits protein kinase C (PKC) isozymes and cAMP-dependent protein kinase (PKA) with limited selectivity. While PKA is known as a tumor promoter, PKC isozymes can be tumor promoters or suppressors. In particular, PKCε is frequently involved in tumorigenesis and a potential target for anticancer drugs. We recently reported that stereospecific fluorination of balanol yielded a balanoid with enhanced selectivity for PKCε over other PKC isozymes and PKA, although the global fluorine effect behind the selectivity enhancement is not fully understood. Interestingly, in contrast to PKA, PKCε is more sensitive to this fluorine effect. Here we investigate the global fluorine effect on the different binding responses of PKCε and PKA to balanoids using molecular dynamics (MD) simulations. For the first time to the best of our knowledge, we found that a structurally equivalent residue in each kinase, Thr184 in PKA and Ala549 in PKCε, is essential for the different binding responses. Furthermore, the study revealed that the invariant Lys, Lys73 in PKA and Lys437 in PKCε, already known to have a crucial role in the catalytic activity of kinases, serves as the main anchor for balanol binding. Overall, while Thr184 in PKA attenuates the effect of fluorination, Ala549 permits remote response of PKCε to fluorine substitution, with implications for rational design of future balanol-based PKCε inhibitors.

Effects of Drake Passage on a strongly eddying global ocean

NASA Astrophysics Data System (ADS)

Viebahn, Jan; von der Heydt, Anna S.; Dijkstra, Henk A.

2015-04-01

During the past 65 Million (Ma) years, Earth's climate has undergone a major change from warm 'greenhouse' to colder 'icehouse' conditions with extensive ice sheets in the polar regions of both hemispheres. The Eocene-Oligocene (~34 Ma) and Oligocene-Miocene (~23 Ma) boundaries reflect major transitions in Cenozoic global climate change. Proposed mechanisms of these transitions include reorganization of ocean circulation due to critical gateway opening/deepening, changes in atmospheric CO2-concentration, and feedback mechanisms related to land-ice formation. Drake Passage (DP) is an intensively studied gateway because it plays a central role in closing the transport pathways of heat and chemicals in the ocean. The climate response to a closed DP has been explored with a variety of general circulation models, however, all of these models employ low model-grid resolutions such that the effects of subgrid-scale fluctuations ('eddies') are parameterized. We present results of the first high-resolution (0.1° horizontally) realistic global ocean model simulation with a closed DP in which the eddy field is largely resolved. The simulation extends over more than 200 years such that the strong transient adjustment process is passed and a near-equilibrium ocean state is reached. The effects of DP are diagnosed by comparing with both an open DP high-resolution control simulation (of same length) and corresponding low-resolution simulations. By focussing on the heat/tracer transports we demonstrate that the results are twofold: Considering spatially integrated transports the overall response to a closed DP is well captured by low-resolution simulations. However, looking at the actual spatial distributions drastic differences appear between far-scattered high-resolution and laminar-uniform low-resolution fields. We conclude that sparse and highly localized tracer proxy observations have to be interpreted carefully with the help of high-resolution model simulations.

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.

Global biosurveillance: enabling science and technology. Workshop background and motivation: international scientific engagement for global security

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cui, Helen H

2011-01-18

Through discussion the conference aims to: (1) Identify core components of a comprehensive global biosurveillance capability; (2) Determine the scientific and technical bases to support such a program; (3) Explore the improvement in biosurveillance to enhance regional and global disease outbreak prediction; (4) Recommend an engagement approach to establishing an effective international community and regional or global network; (5) Propose implementation strategies and the measures of effectiveness; and (6) Identify the challenges that must be overcome in the next 3-5 years in order to establish an initial global biosurveillance capability that will have significant positive impact on BioNP as wellmore » as public health and/or agriculture. There is also a look back at the First Biothreat Nonproliferation Conference from December 2007. Whereas the first conference was an opportunity for problem solving to enhance and identify new paradigms for biothreat nonproliferation, this conference is moving towards integrated comprehensive global biosurveillance. Main reasons for global biosurveillance are: (1) Rapid assessment of unusual disease outbreak; (2) Early warning of emerging, re-emerging and engineered biothreat enabling reduced morbidity and mortality; (3) Enhanced crop and livestock management; (4) Increase understanding of host-pathogen interactions and epidemiology; (5) Enhanced international transparency for infectious disease research supporting BWC goals; and (6) Greater sharing of technology and knowledge to improve global health.« less

Globalization and economic growth: empirical evidence on the role of complementarities.

PubMed

Samimi, Parisa; Jenatabadi, Hashem Salarzadeh

2014-01-01

This study was carried out to investigate the effect of economic globalization on economic growth in OIC countries. Furthermore, the study examined the effect of complementary policies on the growth effect of globalization. It also investigated whether the growth effect of globalization depends on the income level of countries. Utilizing the generalized method of moments (GMM) estimator within the framework of a dynamic panel data approach, we provide evidence which suggests that economic globalization has statistically significant impact on economic growth in OIC countries. The results indicate that this positive effect is increased in the countries with better-educated workers and well-developed financial systems. Our finding shows that the effect of economic globalization also depends on the country's level of income. High and middle-income countries benefit from globalization whereas low-income countries do not gain from it. In fact, the countries should receive the appropriate income level to be benefited from globalization. Economic globalization not only directly promotes growth but also indirectly does so via complementary reforms.

Globalization and Economic Growth: Empirical Evidence on the Role of Complementarities

PubMed Central

Samimi, Parisa; Jenatabadi, Hashem Salarzadeh

2014-01-01

This study was carried out to investigate the effect of economic globalization on economic growth in OIC countries. Furthermore, the study examined the effect of complementary policies on the growth effect of globalization. It also investigated whether the growth effect of globalization depends on the income level of countries. Utilizing the generalized method of moments (GMM) estimator within the framework of a dynamic panel data approach, we provide evidence which suggests that economic globalization has statistically significant impact on economic growth in OIC countries. The results indicate that this positive effect is increased in the countries with better-educated workers and well-developed financial systems. Our finding shows that the effect of economic globalization also depends on the country’s level of income. High and middle-income countries benefit from globalization whereas low-income countries do not gain from it. In fact, the countries should receive the appropriate income level to be benefited from globalization. Economic globalization not only directly promotes growth but also indirectly does so via complementary reforms. PMID:24721896

Understanding the Role and Impact of Effective Country and Community Leadership in Progress Toward the Global Plan.

PubMed

Lyons, Charles; Pillay, Yogan

2017-05-01

Individual leadership and leaders have played pivotal roles in the history of efforts to end the AIDS epidemic. The goal of this article is to reflect on and understand how leadership and leaders have impacted and enabled the success of the Global Plan Towards the Elimination of New HIV Infections among Children by 2015 and Keeping their Mothers Alive (Global Plan). To accomplish this goal, multiple interviews were conducted with individuals in positions of leadership who had been identified as people whose actions drove progress. Interviewees were selected from all levels of traditional hierarchies and sectors to provide a more complete account and representation of leadership, with a particular emphasis on the community, district, and country levels. The leaders interviewed provide insight into their work, motivations, and approaches to effective leadership. Through their experiences, they shed light on the strategies they used to drive changes in policy, programs, practice, and communities that allowed for progress toward the goals of the Global Plan. Leaders also identify future challenges and areas of improvement in the effort to end the AIDS epidemic that they feel require leadership and urgent action. In conclusion, this article identifies common characteristics of effective leadership and reflects on the experiences of individuals who are leaders in the effort to end the AIDS epidemic, and how their lessons learned can be applied to help realize future global public health goals.

Kinome-wide Decoding of Network-Attacking Mutations Rewiring Cancer Signaling

PubMed Central

Creixell, Pau; Schoof, Erwin M.; Simpson, Craig D.; Longden, James; Miller, Chad J.; Lou, Hua Jane; Perryman, Lara; Cox, Thomas R.; Zivanovic, Nevena; Palmeri, Antonio; Wesolowska-Andersen, Agata; Helmer-Citterich, Manuela; Ferkinghoff-Borg, Jesper; Itamochi, Hiroaki; Bodenmiller, Bernd; Erler, Janine T.; Turk, Benjamin E.; Linding, Rune

2015-01-01

Summary Cancer cells acquire pathological phenotypes through accumulation of mutations that perturb signaling networks. However, global analysis of these events is currently limited. Here, we identify six types of network-attacking mutations (NAMs), including changes in kinase and SH2 modulation, network rewiring, and the genesis and extinction of phosphorylation sites. We developed a computational platform (ReKINect) to identify NAMs and systematically interpreted the exomes and quantitative (phospho-)proteomes of five ovarian cancer cell lines and the global cancer genome repository. We identified and experimentally validated several NAMs, including PKCγ M501I and PKD1 D665N, which encode specificity switches analogous to the appearance of kinases de novo within the kinome. We discover mutant molecular logic gates, a drift toward phospho-threonine signaling, weakening of phosphorylation motifs, and kinase-inactivating hotspots in cancer. Our method pinpoints functional NAMs, scales with the complexity of cancer genomes and cell signaling, and may enhance our capability to therapeutically target tumor-specific networks. PMID:26388441

Bringing Globalization into the Classroom

ERIC Educational Resources Information Center

Billings, Nancy Carter

2006-01-01

Some of the most effective resources for bringing the concept of globalization into the classroom is through the personal and professional experiences of the classroom teacher, the personal experiences of students from diverse cultures, the inclusion of curriculum activities with a global context, and the involvement of guest speakers with global…

Acute effects of a large bolide impact simulated by a global atmospheric circulation model

NASA Technical Reports Server (NTRS)

Thompson, Starley L.; Crutzen, P. J.

1988-01-01

The goal is to use a global three-dimensional atmospheric circulation model developed for studies of atmospheric effects of nuclear war to examine the time evolution of atmospheric effects from a large bolide impact. The model allows for dust and NOx injection, atmospheric transport by winds, removal by precipitation, radiative transfer effects, stratospheric ozone chemistry, and nitric acid formation and deposition on a simulated Earth having realistic geography. Researchers assume a modest 2 km-diameter impactor of the type that could have formed the 32 km-diameter impact structure found near Manson, Iowa and dated at roughly 66 Ma. Such an impact would have created on the order of 5 x 10 to the 10th power metric tons of atmospheric dust (about 0.01 g cm(-2) if spread globally) and 1 x 10 to the 37th power molecules of NO, or two orders of magnitude more stratospheric NO than might be produced in a large nuclear war. Researchers ignore potential injections of CO2 and wildfire smoke, and assume the direct heating of the atmosphere by impact ejecta on a regional scale is not large compared to absorption of solar energy by dust. Researchers assume an impact site at 45 N in the interior of present day North America.

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…

Variability and trends in global drought

USGS Publications Warehouse

McCabe, Gregory J.; Wolock, David M.

2015-01-01

Monthly precipitation (P) and potential evapotranspiration (PET) from the CRUTS3.1 data set are used to compute monthly P minus PET (PMPE) for the land areas of the globe. The percent of the global land area with annual sums of PMPE less than zero are used as an index of global drought (%drought) for 1901 through 2009. Results indicate that for the past century %drought has not changed, even though global PET and temperature (T) have increased. Although annual global PET and T have increased, annual global P also has increased and has mitigated the effects of increased PET on %drought.

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.

Polycentrism in Global Health Governance Scholarship

PubMed Central

Tosun, Jale

2018-01-01

Drawing on an in-depth analysis of eight global health networks, a recent essay in this journal argued that global health networks face four challenges to their effectiveness: problem definition, positioning, coalition-building, and governance. While sharing the argument of the essay concerned, in this commentary, we argue that these analytical concepts can be used to explicate a concept that has implicitly been used in global health governance scholarship for quite a few years. While already prominent in the discussion of climate change governance, for instance, global health governance scholarship could make progress by looking at global health governance as being polycentric. Concisely, polycentric forms of governance mix scales, mechanisms, and actors. Drawing on the essay, we propose a polycentric approach to the study of global health governance that incorporates coalitionbuilding tactics, internal governance and global political priority as explanatory factors. PMID:29325406

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…

A novel dysregulated pathway-identification analysis based on global influence of within-pathway effects and crosstalk between pathways

PubMed Central

Han, Junwei; Li, Chunquan; Yang, Haixiu; Xu, Yanjun; Zhang, Chunlong; Ma, Jiquan; Shi, Xinrui; Liu, Wei; Shang, Desi; Yao, Qianlan; Zhang, Yunpeng; Su, Fei; Feng, Li; Li, Xia

2015-01-01

Identifying dysregulated pathways from high-throughput experimental data in order to infer underlying biological insights is an important task. Current pathway-identification methods focus on single pathways in isolation; however, consideration of crosstalk between pathways could improve our understanding of alterations in biological states. We propose a novel method of pathway analysis based on global influence (PAGI) to identify dysregulated pathways, by considering both within-pathway effects and crosstalk between pathways. We constructed a global gene–gene network based on the relationships among genes extracted from a pathway database. We then evaluated the extent of differential expression for each gene, and mapped them to the global network. The random walk with restart algorithm was used to calculate the extent of genes affected by global influence. Finally, we used cumulative distribution functions to determine the significance values of the dysregulated pathways. We applied the PAGI method to five cancer microarray datasets, and compared our results with gene set enrichment analysis and five other methods. Based on these analyses, we demonstrated that PAGI can effectively identify dysregulated pathways associated with cancer, with strong reproducibility and robustness. We implemented PAGI using the freely available R-based and Web-based tools (http://bioinfo.hrbmu.edu.cn/PAGI). PMID:25551156

Global Repetition Influences Contextual Cueing

PubMed Central

Zang, Xuelian; Zinchenko, Artyom; Jia, Lina; Li, Hong

2018-01-01

Our visual system has a striking ability to improve visual search based on the learning of repeated ambient regularities, an effect named contextual cueing. Whereas most of the previous studies investigated contextual cueing effect with the same number of repeated and non-repeated search displays per block, the current study focused on whether a global repetition frequency formed by different presentation ratios between the repeated and non-repeated configurations influence contextual cueing effect. Specifically, the number of repeated and non-repeated displays presented in each block was manipulated: 12:12, 20:4, 4:20, and 4:4 in Experiments 1–4, respectively. The results revealed a significant contextual cueing effect when the global repetition frequency is high (≥1:1 ratio) in Experiments 1, 2, and 4, given that processing of repeated displays was expedited relative to non-repeated displays. Nevertheless, the contextual cueing effect reduced to a non-significant level when the repetition frequency reduced to 4:20 in Experiment 3. These results suggested that the presentation frequency of repeated relative to the non-repeated displays could influence the strength of contextual cueing. In other words, global repetition statistics could be a crucial factor to mediate contextual cueing effect. PMID:29636716

Global Repetition Influences Contextual Cueing.

PubMed

Zang, Xuelian; Zinchenko, Artyom; Jia, Lina; Assumpção, Leonardo; Li, Hong

2018-01-01

Our visual system has a striking ability to improve visual search based on the learning of repeated ambient regularities, an effect named contextual cueing. Whereas most of the previous studies investigated contextual cueing effect with the same number of repeated and non-repeated search displays per block, the current study focused on whether a global repetition frequency formed by different presentation ratios between the repeated and non-repeated configurations influence contextual cueing effect. Specifically, the number of repeated and non-repeated displays presented in each block was manipulated: 12:12, 20:4, 4:20, and 4:4 in Experiments 1-4, respectively. The results revealed a significant contextual cueing effect when the global repetition frequency is high (≥1:1 ratio) in Experiments 1, 2, and 4, given that processing of repeated displays was expedited relative to non-repeated displays. Nevertheless, the contextual cueing effect reduced to a non-significant level when the repetition frequency reduced to 4:20 in Experiment 3. These results suggested that the presentation frequency of repeated relative to the non-repeated displays could influence the strength of contextual cueing. In other words, global repetition statistics could be a crucial factor to mediate contextual cueing effect.

Global Patch Matching

NASA Astrophysics Data System (ADS)

Huang, X.; Hu, K.; Ling, X.; Zhang, Y.; Lu, Z.; Zhou, G.

2017-09-01

This paper introduces a novel global patch matching method that focuses on how to remove fronto-parallel bias and obtain continuous smooth surfaces with assuming that the scenes covered by stereos are piecewise continuous. Firstly, simple linear iterative cluster method (SLIC) is used to segment the base image into a series of patches. Then, a global energy function, which consists of a data term and a smoothness term, is built on the patches. The data term is the second-order Taylor expansion of correlation coefficients, and the smoothness term is built by combing connectivity constraints and the coplanarity constraints are combined to construct the smoothness term. Finally, the global energy function can be built by combining the data term and the smoothness term. We rewrite the global energy function in a quadratic matrix function, and use least square methods to obtain the optimal solution. Experiments on Adirondack stereo and Motorcycle stereo of Middlebury benchmark show that the proposed method can remove fronto-parallel bias effectively, and produce continuous smooth surfaces.

Globalization and health: a framework for analysis and action.

PubMed Central

Woodward, D.; Drager, N.; Beaglehole, R.; Lipson, D.

2001-01-01

Globalization is a key challenge to public health, especially in developing countries, but the linkages between globalization and health are complex. Although a growing amount of literature has appeared on the subject, it is piecemeal, and suffers from a lack of an agreed framework for assessing the direct and indirect health effects of different aspects of globalization. This paper presents a conceptual framework for the linkages between economic globalization and health, with the intention that it will serve as a basis for synthesizing existing relevant literature, identifying gaps in knowledge, and ultimately developing national and international policies more favourable to health. The framework encompasses both the indirect effects on health, operating through the national economy, household economies and health-related sectors such as water, sanitation and education, as well as more direct effects on population-level and individual risk factors for health and on the health care system. Proposed also is a set of broad objectives for a programme of action to optimize the health effects of economic globalization. The paper concludes by identifying priorities for research corresponding with the five linkages identified as critical to the effects of globalization on health. PMID:11584737

Global Warming: How Much and Why?

ERIC Educational Resources Information Center

Lanouette, William

1990-01-01

Summarizes the history of the study of global warming and includes a discussion of the role of gases, like carbon dioxide, methane, and chlorofluorocarbon (CFC). Discusses modern research on the global warming, including computer modelling and the super-greenhouse effect. (YP)

Historical effects of CO2 and climate trends on global crop water demand

NASA Astrophysics Data System (ADS)

Urban, Daniel W.; Sheffield, Justin; Lobell, David B.

2017-12-01

A critical question for agricultural production and food security is how water demand for staple crops will respond to climate and carbon dioxide (CO2) changes1, especially in light of the expected increases in extreme heat exposure2. To quantify the trade-offs between the effects of climate and CO2 on water demand, we use a `sink-strength' model of demand3,4 which relies on the vapour-pressure deficit (VPD), incident radiation and the efficiencies of canopy-radiation use and canopy transpiration; the latter two are both dependent on CO2. This model is applied to a global data set of gridded monthly weather data over the cropping regions of maize, soybean, wheat and rice during the years 1948-2013. We find that this approach agrees well with Penman-Monteith potential evapotranspiration (PM) for the C3 crops of soybean, wheat and rice, where the competing CO2 effects largely cancel each other out, but that water demand in maize is significantly overstated by a demand measure that does not include CO2, such as the PM. We find the largest changes in wheat, for which water demand has increased since 1981 over 86% of the global cropping area and by 2.3-3.6 percentage points per decade in different regions.

The global climate change effect on the Altai region's climate in the first half of XXI century

NASA Astrophysics Data System (ADS)

Lagutin, Anatoly A.; Volkov, Nikolai V.; Makushev, Konstantin M.; Mordvin, Egor Yu.

2017-11-01

We investigate an effect of global climate system change on climate of Altai region. It is shown that a data of the RegCM4 regional climate model, obtained for contemporary and future periods, within an approach which is based on standard Euclidean distance, allows to define specific zones in which climate change is forecasted. Such zones have been defined for the Altai region territory within the framework of global radiative forcing scenarios RCP 4.5 and RCP 8.5 for the middle of XXI century.

Aerosol effects on cloud water amounts were successfully simulated by a global cloud-system resolving model.

PubMed

Sato, Yousuke; Goto, Daisuke; Michibata, Takuro; Suzuki, Kentaroh; Takemura, Toshihiko; Tomita, Hirofumi; Nakajima, Teruyuki

2018-03-07

Aerosols affect climate by modifying cloud properties through their role as cloud condensation nuclei or ice nuclei, called aerosol-cloud interactions. In most global climate models (GCMs), the aerosol-cloud interactions are represented by empirical parameterisations, in which the mass of cloud liquid water (LWP) is assumed to increase monotonically with increasing aerosol loading. Recent satellite observations, however, have yielded contradictory results: LWP can decrease with increasing aerosol loading. This difference implies that GCMs overestimate the aerosol effect, but the reasons for the difference are not obvious. Here, we reproduce satellite-observed LWP responses using a global simulation with explicit representations of cloud microphysics, instead of the parameterisations. Our analyses reveal that the decrease in LWP originates from the response of evaporation and condensation processes to aerosol perturbations, which are not represented in GCMs. The explicit representation of cloud microphysics in global scale modelling reduces the uncertainty of climate prediction.

The Global Signal in fMRI: Nuisance or Information?

PubMed Central

Nalci, Alican; Falahpour, Maryam

2017-01-01

The global signal is widely used as a regressor or normalization factor for removing the effects of global variations in the analysis of functional magnetic resonance imaging (fMRI) studies. However, there is considerable controversy over its use because of the potential bias that can be introduced when it is applied to the analysis of both task-related and resting-state fMRI studies. In this paper we take a closer look at the global signal, examining in detail the various sources that can contribute to the signal. For the most part, the global signal has been treated as a nuisance term, but there is growing evidence that it may also contain valuable information. We also examine the various ways that the global signal has been used in the analysis of fMRI data, including global signal regression, global signal subtraction, and global signal normalization. Furthermore, we describe new ways for understanding the effects of global signal regression and its relation to the other approaches. PMID:28213118

Global land use change, economic globalization, and the looming land scarcity.

PubMed

Lambin, Eric F; Meyfroidt, Patrick

2011-03-01

A central challenge for sustainability is how to preserve forest ecosystems and the services that they provide us while enhancing food production. This challenge for developing countries confronts the force of economic globalization, which seeks cropland that is shrinking in availability and triggers deforestation. Four mechanisms-the displacement, rebound, cascade, and remittance effects-that are amplified by economic globalization accelerate land conversion. A few developing countries have managed a land use transition over the recent decades that simultaneously increased their forest cover and agricultural production. These countries have relied on various mixes of agricultural intensification, land use zoning, forest protection, increased reliance on imported food and wood products, the creation of off-farm jobs, foreign capital investments, and remittances. Sound policies and innovations can therefore reconcile forest preservation with food production. Globalization can be harnessed to increase land use efficiency rather than leading to uncontrolled land use expansion. To do so, land systems should be understood and modeled as open systems with large flows of goods, people, and capital that connect local land use with global-scale factors.

Global spatiotemporal distribution of soil respiration modeled using a global database

NASA Astrophysics Data System (ADS)

Hashimoto, S.; Carvalhais, N.; Ito, A.; Migliavacca, M.; Nishina, K.; Reichstein, M.

2015-07-01

The flux of carbon dioxide from the soil to the atmosphere (soil respiration) is one of the major fluxes in the global carbon cycle. At present, the accumulated field observation data cover a wide range of geographical locations and climate conditions. However, there are still large uncertainties in the magnitude and spatiotemporal variation of global soil respiration. Using a global soil respiration data set, we developed a climate-driven model of soil respiration by modifying and updating Raich's model, and the global spatiotemporal distribution of soil respiration was examined using this model. The model was applied at a spatial resolution of 0.5°and a monthly time step. Soil respiration was divided into the heterotrophic and autotrophic components of respiration using an empirical model. The estimated mean annual global soil respiration was 91 Pg C yr-1 (between 1965 and 2012; Monte Carlo 95 % confidence interval: 87-95 Pg C yr-1) and increased at the rate of 0.09 Pg C yr-2. The contribution of soil respiration from boreal regions to the total increase in global soil respiration was on the same order of magnitude as that of tropical and temperate regions, despite a lower absolute magnitude of soil respiration in boreal regions. The estimated annual global heterotrophic respiration and global autotrophic respiration were 51 and 40 Pg C yr-1, respectively. The global soil respiration responded to the increase in air temperature at the rate of 3.3 Pg C yr-1 °C-1, and Q10 = 1.4. Our study scaled up observed soil respiration values from field measurements to estimate global soil respiration and provide a data-oriented estimate of global soil respiration. The estimates are based on a semi-empirical model parameterized with over one thousand data points. Our analysis indicates that the climate controls on soil respiration may translate into an increasing trend in global soil respiration and our analysis emphasizes the relevance of the soil carbon flux from soil to

Global Warming.

ERIC Educational Resources Information Center

Hileman, Bette

1989-01-01

States the foundations of the theory of global warming. Describes methodologies used to measure the changes in the atmosphere. Discusses steps currently being taken in the United States and the world to slow the warming trend. Recognizes many sources for the warming and the possible effects on the earth. (MVL)

Functional Proteomics Identifies Acinus L as a Direct Insulin- and Amino Acid-Dependent Mammalian Target of Rapamycin Complex 1 (mTORC1) Substrate*