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1

Quantitative phosphoproteomics in fatty acid stimulated Saccharomyces cerevisiae.  

PubMed

This protocol describes the growth and stimulation, with the fatty acid oleate, of isotopically heavy and light S. cerevisiae cells. Cells are ground using a cryolysis procedure in a ball mill grinder and the resulting grindate brought into solution by urea solubilization. This procedure allows for the lysis of the cells in a metabolically inactive state, preserving phosphorylation and preventing reorientation of the phosphoproteome during cell lysis. Following reduction, alkylation, trypsin digestion of the proteins, the samples are desalted on C18 columns and the sample complexity reduced by fractionation using hydrophilic interaction chromatography (HILIC). HILIC columns preferentially retain hydrophilic molecules which is well suited for phosphoproteomics. Phosphorylated peptides tend to elute later in the chromatographic profile than the non phosphorylated counterparts. After fractionation, phosphopeptides are enriched using immobilized metal chromatography, which relies on charge-based affinities for phosphopeptide enrichment. At the end of this procedure the samples are ready to be quantitatively analyzed by mass spectrometry. PMID:19823167

Saleem, Ramsey A; Aitchison, John D

2009-01-01

2

Quantitative Phosphoproteomics of CXCL12 (SDF-1) Signaling  

PubMed Central

CXCL12 (SDF-1) is a chemokine that binds to and signals through the seven transmembrane receptor CXCR4. The CXCL12/CXCR4 signaling axis has been implicated in both cancer metastases and human immunodeficiency virus type 1 (HIV-1) infection and a more complete understanding of CXCL12/CXCR4 signaling pathways may support efforts to develop therapeutics for these diseases. Mass spectrometry-based phosphoproteomics has emerged as an important tool in studying signaling networks in an unbiased fashion. We employed stable isotope labeling with amino acids in cell culture (SILAC) quantitative phosphoproteomics to examine the CXCL12/CXCR4 signaling axis in the human lymphoblastic CEM cell line. We quantified 4,074 unique SILAC pairs from 1,673 proteins and 89 phosphopeptides were deemed CXCL12-responsive in biological replicates. Several well established CXCL12-responsive phosphosites such as AKT (pS473) and ERK2 (pY204) were confirmed in our study. We also validated two novel CXCL12-responsive phosphosites, stathmin (pS16) and AKT1S1 (pT246) by Western blot. Pathway analysis and comparisons with other phosphoproteomic datasets revealed that genes from CXCL12-responsive phosphosites are enriched for cellular pathways such as T cell activation, epidermal growth factor and mammalian target of rapamycin (mTOR) signaling, pathways which have previously been linked to CXCL12/CXCR4 signaling. Several of the novel CXCL12-responsive phosphoproteins from our study have also been implicated with cellular migration and HIV-1 infection, thus providing an attractive list of potential targets for the development of cancer metastasis and HIV-1 therapeutics and for furthering our understanding of chemokine signaling regulation by reversible phosphorylation. PMID:21949786

Wojcechowskyj, Jason A.; Lee, Jessica Y.; Seeholzer, Steven H.; Doms, Robert W.

2011-01-01

3

Quantitative Phosphoproteomics of Proteasome Inhibition in Multiple Myeloma Cells  

PubMed Central

Background The proteasome inhibitor bortezomib represents an important advance in the treatment of multiple myeloma (MM). Bortezomib inhibits the activity of the 26S proteasome and induces cell death in a variety of tumor cells; however, the mechanism of cytotoxicity is not well understood. Methodology/Principal Findings We investigated the differential phosphoproteome upon proteasome inhibition by using stable isotope labeling by amino acids in cell culture (SILAC) in combination with phosphoprotein enrichment and LC-MS/MS analysis. In total 233 phosphoproteins were identified and 72 phosphoproteins showed a 1.5-fold or greater change upon bortezomib treatment. The phosphoproteins with expression alterations encompass all major protein classes, including a large number of nucleic acid binding proteins. Site-specific phosphopeptide quantitation revealed that Ser38 phosphorylation on stathmin increased upon bortezomib treatment, suggesting new mechanisms associated to bortezomib-induced apoptosis in MM cells. Further studies demonstrated that stathmin phosphorylation profile was modified in response to bortezomib treatment and the regulation of stathmin by phosphorylation at specific Ser/Thr residues participated in the cellular response induced by bortezomib. Conclusions/Significance Our systematic profiling of phosphorylation changes in response to bortezomib treatment not only advanced the global mechanistic understanding of the action of bortezomib on myeloma cells but also identified previously uncharacterized signaling proteins in myeloma cells. PMID:20927383

Bi, Li-Jun; Tao, Sheng-Ce; Xiong, Sheng; Yin, Xin-Feng; Li, Li-Ping; Lu, Chun-Hua; Jia, Hai-Tao; He, Qing-Yu

2010-01-01

4

Quantitative Phosphoproteomics Reveals Extensive Cellular Reprogramming During HIV-1 Entry  

PubMed Central

SUMMARY Receptor engagement by HIV-1 during host cell entry activates signaling pathways that can reprogram the cell for optimal viral replication. To obtain a global view of the signaling events induced during HIV-1 entry, we conducted a quantitative phosphoproteomics screen of primary human CD4+ T cell after infection with an HIV-1 strain that engages the receptors CD4 and CXCR4. We quantified 1,757 phosphorylation sites with high stringency. The abundance of 239 phosphorylation sites from 175 genes, including several proteins in pathways known to be impacted by HIV-receptor binding, changed significantly within a minute after HIV-1 exposure. Several previously uncharacterized HIV-1 host factors were also identified and confirmed through RNAi depletion studies. Surprisingly, 5 serine/arginine-rich (SR)-proteins involved in mRNA splicing, including the splicing factor SRm300 (SRRM2) were differentially phosophorylated. Mechanistic studies with SRRM2 suggest that HIV-1 modulates host cell alternative splicing machinery during entry in order to facilitate virus replication and release. PMID:23684312

Wojcechowskyj, Jason A.; Didigu, Chuka A.; Lee, Jessica Y.; Parrish, Nicholas F.; Sinha, Rohini; Hahn, Beatrice H.; Bushman, Frederic D.; Jensen, Shane T.; Seeholzer, Steven H.; Doms, Robert W.

2014-01-01

5

Integrated Quantitative Analysis of the Phosphoproteome and Transcriptome in Tamoxifen-resistant Breast Cancer*  

PubMed Central

Quantitative phosphoproteome and transcriptome analysis of ligand-stimulated MCF-7 human breast cancer cells was performed to understand the mechanisms of tamoxifen resistance at a system level. Phosphoproteome data revealed that WT cells were more enriched with phospho-proteins than tamoxifen-resistant cells after stimulation with ligands. Surprisingly, decreased phosphorylation after ligand perturbation was more common than increased phosphorylation. In particular, 17?-estradiol induced down-regulation in WT cells at a very high rate. 17?-Estradiol and the ErbB ligand heregulin induced almost equal numbers of up-regulated phospho-proteins in WT cells. Pathway and motif activity analyses using transcriptome data additionally suggested that deregulated activation of GSK3? (glycogen-synthase kinase 3?) and MAPK1/3 signaling might be associated with altered activation of cAMP-responsive element-binding protein and AP-1 transcription factors in tamoxifen-resistant cells, and this hypothesis was validated by reporter assays. An examination of clinical samples revealed that inhibitory phosphorylation of GSK3? at serine 9 was significantly lower in tamoxifen-treated breast cancer patients that eventually had relapses, implying that activation of GSK3? may be associated with the tamoxifen-resistant phenotype. Thus, the combined phosphoproteome and transcriptome data set analyses revealed distinct signal transcription programs in tumor cells and provided a novel molecular target to understand tamoxifen resistance. PMID:21044952

Oyama, Masaaki; Nagashima, Takeshi; Suzuki, Takashi; Kozuka-Hata, Hiroko; Yumoto, Noriko; Shiraishi, Yuichi; Ikeda, Kazuhiro; Kuroki, Yoko; Gotoh, Noriko; Ishida, Takanori; Inoue, Satoshi; Kitano, Hiroaki; Okada-Hatakeyama, Mariko

2011-01-01

6

Quantitative Phospho-proteomics to Investigate the Polo-like Kinase 1-Dependent Phospho-proteome*  

PubMed Central

Polo-like kinase 1 (PLK1) is a key regulator of mitotic progression and cell division, and small molecule inhibitors of PLK1 are undergoing clinical trials to evaluate their utility in cancer therapy. Despite this importance, current knowledge about the identity of PLK1 substrates is limited. Here we present the results of a proteome-wide analysis of PLK1-regulated phosphorylation sites in mitotic human cells. We compared phosphorylation sites in HeLa cells that were or were not treated with the PLK1-inhibitor BI 4834, by labeling peptides via methyl esterification, fractionation of peptides by strong cation exchange chromatography, and phosphopeptide enrichment via immobilized metal affinity chromatography. Analysis by quantitative mass spectrometry identified 4070 unique mitotic phosphorylation sites on 2069 proteins. Of these, 401 proteins contained one or multiple phosphorylation sites whose abundance was decreased by PLK1 inhibition. These include proteins implicated in PLK1-regulated processes such as DNA damage, mitotic spindle formation, spindle assembly checkpoint signaling, and chromosome segregation, but also numerous proteins that were not suspected to be regulated by PLK1. Analysis of amino acid sequence motifs among phosphorylation sites down-regulated under PLK1 inhibition in this data set identified two potential novel variants of the PLK1 consensus motif. PMID:21857030

Grosstessner-Hain, Karin; Hegemann, Bjorn; Novatchkova, Maria; Rameseder, Jonathan; Joughin, Brian A.; Hudecz, Otto; Roitinger, Elisabeth; Pichler, Peter; Kraut, Norbert; Yaffe, Michael B.; Peters, Jan-Michael; Mechtler, Karl

2011-01-01

7

Quantitative Phosphoproteomics Analysis Reveals Broad Regulatory Role of Heparan Sulfate on Endothelial Signaling*  

PubMed Central

Heparan sulfate (HS) is a linear, abundant, highly sulfated polysaccharide that expresses in the vasculature. Recent genetic studies documented that HS critically modulates various endothelial cell functions. However, elucidation of the underlying molecular mechanism has been challenging because of the presence of a large number of HS-binding ligands found in the examined experimental conditions. In this report, we used quantitative phosphoproteomics to examine the global HS-dependent signaling by comparing wild type and HS-deficient endothelial cells that were cultured in a serum-containing medium. A total of 7222 phosphopeptides, corresponding to 1179 proteins, were identified. Functional correlation analysis identified 25 HS-dependent functional networks, and the top five are related to cell morphology, cellular assembly and organization, cellular function and maintenance, cell-to-cell communication, inflammatory response and disorder, cell growth and proliferation, cell movement, and cellular survival and death. This is consistent with cell function studies showing that HS deficiency altered endothelial cell growth and mobility. Mining for the underlying molecular mechanisms further revealed that HS modulates signaling pathways critically related to cell adhesion, migration, and coagulation, including ILK, integrin, actin cytoskeleton organization, tight junction and thrombin signaling. Intriguingly, this analysis unexpectedly determined that the top HS-dependent signaling is the IGF-1 signaling pathway, which has not been known to be modulated by HS. In-depth analysis of growth factor signaling identified 22 HS-dependent growth factor/cytokine/growth hormone signaling pathways, including those both previously known, such as HGF and VEGF, and those unknown, such as IGF-1, erythropoietin, angiopoietin/Tie, IL-17A and growth hormones. Twelve of the identified 22 growth factor/cytokine/growth hormone signaling pathways, including IGF-1 and angiopoietin/Tie signaling, were alternatively confirmed in phospho-receptor tyrosine kinase array analysis. In summary, our SILAC-based quantitative phosphoproteomic analysis confirmed previous findings and also uncovered novel HS-dependent functional networks and signaling, revealing a much broader regulatory role of HS on endothelial signaling. PMID:23649490

Qiu, Hong; Jiang, Jun-Lin; Liu, Miao; Huang, Xin; Ding, Shi-Jian; Wang, Lianchun

2013-01-01

8

Research Resource: Identification of Novel Growth Hormone-Regulated Phosphorylation Sites by Quantitative Phosphoproteomics  

PubMed Central

GH and GH receptors are expressed throughout life, and GH elicits a diverse range of responses, including growth and altered metabolism. It is therefore important to understand the full spectrum of GH signaling pathways and cellular responses. We applied mass spectrometry-based phosphoproteomics combined with stable isotope labeling with amino acids in cell culture to identify proteins rapidly phosphorylated in response to GH in 3T3-F442A preadipocytes. We identified 132 phosphosites in 95 proteins that exhibited rapid (5 or 15 min) GH-dependent statistically significant increases in phosphorylation by more than or equal to 50% and 96 phosphosites in 46 proteins that were down-regulated by GH by more than or equal to 30%. Several of the GH-stimulated phosphorylation sites were known (e.g. regulatory Thr/Tyr in Erks 1 and 2, Tyr in signal transducers and activators of transcription (Stat) 5a and 5b, Ser939 in tuberous sclerosis protein (TSC) 2 or tuberin). The remaining 126 GH-stimulated sites were not previously associated with GH. Kyoto Encyclopedia of Genes and Genomes pathway analysis of GH-stimulated sites indicated enrichment in proteins associated with the insulin and mammalian target of rapamycin (mTOR) pathways, regulation of the actin cytoskeleton, and focal adhesions. Akt/protein kinase A consensus sites (RXRXXS/T) were the most commonly phosphorylated consensus sites. Immunoblotting confirmed GH-stimulated phosphorylation of all seven novel GH-dependent sites tested [regulatory sites in proline-rich Akt substrate, 40 kDA (PRAS40), regulatory associated protein of mTOR, ATP-citrate lyase, Na+/H+ exchanger-1, N-myc downstream regulated gene 1, and Shc]). The immunoblot results suggest that many, if not most, of the GH-stimulated phosphosites identified in this large-scale quantitative phosphoproteomics analysis, including sites in multiple proteins in the Akt/ mTOR complex 1 pathway, are phosphorylated in response to GH. Their identification significantly broadens our thinking of GH-regulated cell functions. PMID:22570334

Ray, Bridgette N.; Kweon, Hye Kyong; Argetsinger, Lawrence S.; Fingar, Diane C.; Andrews, Philip C.

2012-01-01

9

QUANTITATIVE PHOSPHOPROTEOMIC ANALYSIS OF T CELL RECEPTOR SIGNALING IN DIABETES PRONE AND RESISTANT MICE  

PubMed Central

Type 1 diabetes, in human patients and NOD mice, results from immune attack on insulin-producing beta-cells of the pancreas by autoreactive T lymphocytes. In NOD mice, genetically-controlled perturbations in the signaling pathways downstream of the antigen-specific T cell receptor (TCR) may be instrumental in the altered responses of T cells, manifest as inefficient induction of apoptosis after recognition of self-antigens in the thymus, or as perturbed reactivity of mature T cells in peripheral organs. To map this signaling difference(s), we have used mass spectrometry-based quantitative phosphoproteomics to compare the activation of primary CD4+ T cells of diabetes-prone NOD and -resistant B6.H2g7 mice. Immunoprecipitation and IMAC purification of tyrosine-phosphorylated peptides, combined with a stable-isotope iTRAQ labeling, enabled us to identify and quantify over 77 phosphorylation events in 54 different proteins downstream of TCR stimulation of primary CD4+ T cells. This analysis showed a generally higher level of phosphotyrosine in activated NOD cells, as well as several phosphorylation sites that appeared to be differentially regulated in these two strains (involving TXK, CD5, PAG1, and ZAP-70). These data highlight the differences in signaling between CD4+ T cell compartments of NOD and B6g7 mice, and may underlie the dysregulation of T cells in NOD mice. PMID:20438120

Iwai, Leo K.; Benoist, Christophe; Mathis, Diane; White, Forest M

2012-01-01

10

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

PubMed

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

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

2014-02-01

11

Automated, Reproducible, Titania-Based Phosphopeptide Enrichment Strategy for Label-Free Quantitative Phosphoproteomics  

PubMed Central

An automated phosphopeptide enrichment strategy is described using titanium dioxide (TiO2)-packed, fused silica capillaries for use with liquid chromatography (LC)-mass spectrometry (MS)/MS-based, label-free proteomics workflows. To correlate an optimum peptide:TiO2 loading ratio between different particle types, the ratio of phenyl phosphate-binding capacities was used. The optimum loading for the column was then verified through replicate enrichments of a range of quantities of digested rat brain tissue cell lysate. Fractions were taken during sample loading, multiple wash steps, and the elution steps and analyzed by LC-MS/MS to gauge the efficiency and reproducibility of the enrichment. Greater than 96% of the total phosphopeptides were detected in the elution fractions, indicating efficient trapping of the phosphopeptides on the first pass of enrichment. The quantitative reproducibility of the automated setup was also improved greatly with phosphopeptide intensities from replicate enrichments exhibiting a median coefficient of variation (CV) of 5.8%, and 80% of the identified phosphopeptides had CVs below 11.1%, while maintaining >85% specificity. By providing this high degree of analytical reproducibility, this method allows for label-free phosphoproteomics over large sample sets with complex experimental designs (multiple biological conditions, multiple biological replicates, multiple time-points, etc.), including large-scale clinical cohorts. PMID:23542237

Richardson, Brenna McJury; Soderblom, Erik J.; Thompson, J. Will; Moseley, M. Arthur

2013-01-01

12

Quantitative Phosphoproteomic Profiling of Human Non-Small Cell Lung Cancer Tumors  

PubMed Central

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Within the molecular scope of NCSLC, a complex landscape of dysregulated cellular signaling has emerged, defined largely by mutations in select mediators of signal transduction, including the epidermal growth factor receptor (EGFR) and anaplastic lymphoma (ALK) kinases. Consequently, these mutant kinases become constitutively activated and targets for chemotherapeutic intervention. Encouragingly, small molecule inhibitors of these pathways have shown promise in clinical trials or are approved for clinical use. However, many protein kinases are dysregulated in NSCLC without genetic mutations. To quantify differences in tumor cell signaling that are transparent to genomic methods, we established a super-SILAC internal standard derived from NSCLC cell lines grown in vitro and labeled with heavy lysine and arginine, and deployed them in a phosphoproteomics workflow. We identified 9019 and 8753 phosphorylation sites in two separate tumors. Relative quantification of phosphopeptide abundance between tumor samples allowed for the determination of specific hubs and pathways differing between each tumor. Sites downstream of Ras showed decreased inhibitory phosphorylation (Raf/Mek) and increased activating phosphorylation (Erk1/2) in one tumor versus another. In this way, we were able to quantitatively access oncogenic kinase signaling in primary human tumors. PMID:23911959

Schweppe, Devin K.; Rigas, James R.; Gerber, Scott A.

2013-01-01

13

Quantitative phosphoproteomics using acetone-based peptide labeling: Method evaluation and application to a cardiac ischemia/reperfusion model  

PubMed Central

Mass spectrometry (MS) techniques to globally profile protein phosphorylation in cellular systems that are relevant to physiological or pathological changes have been of significant interest in biological research. In this report, an MS-based strategy utilizing an inexpensive acetone-based peptide labeling technique known as reductive alkylation by acetone (RABA) for quantitative phosphoproteomics was explored to evaluate its capacity. Since the chemistry for RABA-labeling for phosphorylation profiling had not been previously reported, it was first validated using a standard phosphoprotein and identical phosphoproteomes from cardiac tissue extracts. A workflow was then utilized to compare cardiac tissue phosphoproteomes from mouse hearts not expressing FGF2 vs. hearts expressing low molecular weight fibroblast growth factor-2 (LMW FGF2) to relate low molecular weight fibroblast growth factor-2 (LMW FGF2) mediated cardioprotective phenomena induced by ischemia/reperfusion (I/R) injury of hearts, with downstream phosphorylation changes in LMW FGF2 signaling cascades. Statistically significant phosphorylation changes were identified at 14 different sites on 10 distinct proteins including some with mechanisms already established for LMW FGF2-mediated cardioprotective signaling (e.g. connexin-43), some with new details linking LMW FGF2 to the cardioprotective mechanisms (e.g. cardiac myosin binding protein C or cMyBPC), and also several new downstream effectors not previously recognized for cardio-protective signaling by LMW FGF2. Additionally, one of the phosphopeptides, cMyBPC/pSer-282, identified was further verified with site-specific quantification using an SRM (selected reaction monitoring)-based approach that also relies on isotope labeling of a synthetic phosphopeptide with deuterated acetone as an internal standard. Overall, this study confirms that the inexpensive acetone-based peptide labeling can be used in both exploratory and targeted quantification phosphoproteomic studies to identify and verify biologically-relevant phosphorylation changes in whole tissues. PMID:24016359

Wijeratne, Aruna B.; Manning, Janet R.; Schultz, Jo El J.; Greis, Kenneth D.

2013-01-01

14

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

PubMed Central

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.—Rudrabhatla, P., Grant, P., Jaffe, H., Strong, M. J., Pant, H. C. Quantitative phosphoproteomic analysis of neuronal intermediate filament proteins (NF-M/H) in Alzheimer's disease by iTRAQ. PMID:20624930

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

2010-01-01

15

Quantitative Phosphoproteomic Analysis of Soybean Root Hairs Inoculated with Bradyrhizobium japonicum*  

PubMed Central

Root hairs are single hair-forming cells on roots that function to increase root surface area, enhancing water and nutrient uptake. In leguminous plants, root hairs also play a critical role as the site of infection by symbiotic nitrogen fixing rhizobia, leading to the formation of a novel organ, the nodule. The initial steps in the rhizobia-root hair infection process are known to involve specific receptor kinases and subsequent kinase cascades. Here, we characterize the phosphoproteome of the root hairs and the corresponding stripped roots (i.e. roots from which root hairs were removed) during rhizobial colonization and infection to gain insight into the molecular mechanism of root hair cell biology. We chose soybean (Glycine max L.), one of the most important crop plants in the legume family, for this study because of its larger root size, which permits isolation of sufficient root hair material for phosphoproteomic analysis. Phosphopeptides derived from root hairs and stripped roots, mock inoculated or inoculated with the soybean-specific rhizobium Bradyrhizobium japonicum, were labeled with the isobaric tag eight-plex iTRAQ, enriched using Ni-NTA magnetic beads and subjected to nanoRPLC-MS/MS1 analysis using HCD and decision tree guided CID/ETD strategy. A total of 1625 unique phosphopeptides, spanning 1659 nonredundant phosphorylation sites, were detected from 1126 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. PMID:22843990

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

2012-01-01

16

Quantitative Phosphoproteomic Analysis of Soybean Root Hairs Inoculated with Bradyrhizobium japonicum  

SciTech Connect

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

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

2012-11-11

17

Analysis of EGFR signaling pathway in nasopharyngeal carcinoma cells by quantitative phosphoproteomics  

Microsoft Academic Search

Background  The epidermal growth factor receptor (EGFR) is usually overexpressed in nasopharyngeal carcinoma (NPC) and is associated with\\u000a pathogenesis of NPC. However, the downstream signaling proteins of EGFR in NPC have not yet been completely understood at\\u000a the system level. The aim of this study was identify novel downstream proteins of EGFR signaling pathway in NPC cells.\\u000a \\u000a \\u000a \\u000a \\u000a Results  We analyzed EGFR-regulated phosphoproteome

Lin Ruan; Xin-Hui Li; Xun-Xun Wan; Hong Yi; Cui Li; Mao-Yu Li; Peng-Fei Zhang; Gu-Qing Zeng; Jia-Quan Qu; Qiu-Yan He; Jian-Huang Li; Yu Chen; Zhu-Chu Chen; Zhi-Qiang Xiao

2011-01-01

18

Global quantitative phosphoproteome analysis of human tumor xenografts treated with a CD44 antagonist.  

PubMed

The cell surface glycoprotein CD44 plays an important role in the development and progression of various tumor types. RG7356 is a humanized antibody targeting the constant region of CD44 that shows antitumor efficacy in mice implanted with CD44-expressing tumors such as MDA-MB-231 breast cancer cells. CD44 receptor seems to function as the main receptor for hyaluronic acid and osteopontin, serving as coreceptor for growth factor pathways like cMet, EGFR, HER-2, and VEGFR and by cytoskeletal modulation via ERM and Rho kinase signaling. To assess the direct impact of RG7356 binding to the CD44 receptor, a global mass spectrometry-based phosphoproteomics approach was applied to freshly isolated MDA-MB-231 tumor xenografts. Results from a global phosphoproteomics screen were further corroborated by Western blot and ELISA analyses of tumor lysates from CD44-expressing tumors. Short-term treatment of tumor-bearing mice with RG7356 resulted in modifications of the MAPK pathway in the responsive model, although no effects on downstream phosphorylation were observed in a nonresponsive xenograft model. Taken together, our approach augments the value of other high throughput techniques to identify biomarkers for clinical development of targeted agents. PMID:22777824

Weigand, Stefan; Herting, Frank; Maisel, Daniela; Nopora, Adam; Voss, Edgar; Schaab, Christoph; Klammer, Martin; Tebbe, Andreas

2012-09-01

19

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

PubMed

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. PMID:24291252

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

2014-01-22

20

Analysis of T4SS-induced signaling by H. pylori using quantitative phosphoproteomics  

PubMed Central

Helicobacter pylori is a Gram-negative bacterial pathogen colonizing the human stomach. Infection with H. pylori causes chronic inflammation of the gastric mucosa and may lead to peptic ulceration and/or gastric cancer. A major virulence determinant of H. pylori is the type IV secretion system (T4SS), which is used to inject the virulence factor CagA into the host cell, triggering a wide range of cellular signaling events. Here, we used a phosphoproteomic approach to investigate tyrosine signaling in response to host-pathogen interaction, using stable isotope labeling in cell culture (SILAC) of AGS cells to obtain a differential picture between multiple infection conditions. Cells were infected with wild type H. pylori P12, a P12? CagA deletion mutant, and a P12? PAI deletion mutant to compare signaling changes over time and in the absence of CagA or the T4SS. Tryptic peptides were enriched for tyrosine (Tyr) phosphopeptides and analyzed by nano-LC-Orbitrap MS. In total, 85 different phosphosites were found to be regulated following infection. The majority of phosphosites identified were kinases of the MAPK family. CagA and the T4SS were found to be key regulators of Tyr phosphosites. Our findings indicate that CagA primarily induces activation of ERK1 and integrin-linked factors, whereas the T4SS primarily modulates JNK and p38 activation. PMID:25101063

Glowinski, Frithjof; Holland, Carsten; Thiede, Bernd; Jungblut, Peter R.; Meyer, Thomas F.

2014-01-01

21

Identification of novel signaling components in N,N'-Dinitrosopiperazine-mediated metastasis of nasopharyngeal Carcinoma by quantitative phosphoproteomics  

PubMed Central

Background Nasopharyngeal carcinoma (NPC) is a highly invasive and metastatic cancer. N,N’-dinitrosopiperazine (DNP), a carcinogen with specificity for nasopharyngeal epithelium, facilitates NPC metastasis. However, the underlying mechanism is not known. Methods Quantitative phosphoproteomics, using stable isotope labeling of amino acids in cell cultures, was employed to identify phosphoproteins associated with NPC metastasis mediated by DNP. NPC cell line 6-10B, which is relatively less metastatic, was used to investigate DNP-mediated metastasis. Boyden chamber invasion assay was used to measure DNP-induced motility and invasion, and nude mice were used to verify DNP-mediated metastasis in vivo. Several different phosphoproteins detected by proteomics analysis were verified by immunoblotting. DNP-mediated metastasis facilitated by lysine-rich CEACAM1 co-isolated protein (LYRIC) phosphorylation at serine 568 was confirmed using mutations targeting the phosphorylation site of LYRIC. DNP-mediated metastasis through LYRIC phosphorylation was confirmed in the NPC cell line CNE1. DNP-mediated LYRIC phosphorylation at serine 568 was also verified in metastatic tumors of BABL/c nude mice. Results Boyden chamber invasion assay indicated that DNP mediated cell motility and invasion of NPC cell 6-10B in vitro, and experiments with nude mice indicated that DNP increased 6-10B metastasis in vivo. In the phosphoproteomics analysis, we detected 216 phosphorylation sites on 130 proteins; among these, 48 phosphorylation sites on 30 unique phosphopeptides were modulated by DNP by at least 1.5-fold. DNP mediated the expression of phosphorylated GTPase, ferritin, LYRIC, and RNA polymerase, and it decreased the expression of phosphorylated torsin-1A protein 1. Furthermore, DNP induced LYRIC phosphorylation at serine 568 to facilitate cell motility and invasion, whereas DNP-mediated motility and invasion was decreased when serine 568 in LYRIC was mutated. In another NPC cell line, CNE1, DNP also mediated cell motility and invasion followed by enhanced phosphorylation of LYRIC at serine 568. Finally, phosphorylated-LYRIC expression at serine 568 was significantly increased in metastatic tumors induced by DNP. Conclusion DNP regulates multiple signaling pathways through protein phosphorylation, including the phosphorylation of LYRIC at serine 568, and mediates NPC metastasis. These findings provide insights on the complexity and dynamics of DNP-facilitated metastasis, and may help to gain a better understanding of the mechanisms by clarifying NPC-induced metastasis. PMID:24708550

2014-01-01

22

Quantitative Phosphoproteomics of Murine Fmr1-KO Cell Lines Provides New Insights into FMRP-Dependent Signal Transduction Mechanisms.  

PubMed

Fragile X mental retardation protein (FMRP) is an RNA-binding protein that has a major effect on neuronal protein synthesis. Transcriptional silencing of the FMR1 gene leads to loss of FMRP and development of Fragile X syndrome (FXS), the most common known hereditary cause of intellectual impairment and autism. Here we utilize SILAC-based quantitative phosphoproteomics to analyze murine FMR1(-) and FMR1(+) fibroblastic cell lines derived from FMR1-KO embryos to identify proteins and phosphorylation sites dysregulated as a consequence of FMRP loss. We quantify FMRP-related changes in the levels of 5,023 proteins and 6,133 phosphorylation events and map them onto major signal transduction pathways. Our study confirms global downregulation of the MAPK/ERK pathway and decrease in phosphorylation level of ERK1/2 in the absence of FMRP, which is connected to attenuation of long-term potentiation. We detect differential expression of several key proteins from the p53 pathway, pointing to the involvement of p53 signaling in dysregulated cell cycle control in FXS. Finally, we detect differential expression and phosphorylation of proteins involved in pre-mRNA processing and nuclear transport, as well as Wnt and calcium signaling, such as PLC, PKC, NFAT, and cPLA2. We postulate that calcium homeostasis is likely affected in molecular pathogenesis of FXS. PMID:25168779

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

2014-10-01

23

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

PubMed

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. PMID:20624930

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

2010-11-01

24

Investigation of Receptor interacting protein (RIP3)-dependent Protein Phosphorylation by Quantitative Phosphoproteomics*  

PubMed Central

Receptor interacting protein 3 (RIP3) is a protein kinase that plays a key role in programmed necrosis. Despite the importance of RIP3-dependent necrosis in many pathological processes, current knowledge on the function of RIP3 is very limited. Here we present the results of a proteome-wide analysis of RIP3-regulated phosphorylation sites using cells from wildtype (RIP3+/+) and RIP3 knockout (RIP3?/?) mice. Because the activation of RIP3 requires stimulation by certain extracellular stimuli such as ligands of death receptors or Toll-like receptors, we compared the phosphorylation sites of lipopolysaccharide (LPS)-treated peritoneal macrophages from RIP3+/+ and RIP3?/? mice and the phosphorylation sites of tumor necrosis factor (TNF)-treated RIP3+/+ and RIP3?/? mouse embryonic fibroblast (MEF) cells. Stable isotope labeling by amino acids in cell culture and spike-in stable isotope labeling by amino acids in cell culture were used in the analyses of the MEFs and macrophages, respectively. Proteomic analyses using stable isotope labeling by amino acids in cell culture coupled with immobilized metal affinity chromatography-hydrophilic interaction liquid chromatography fractionation and nanoLC MS/MS identified 14,057 phosphopeptides in 4306 proteins from the macrophages and 4732 phosphopeptides in 1785 proteins from the MEFs. Analysis of amino acid sequence motifs among the phosphopeptides identified a potential motif of RIP3 phosphorylation. Among the phosphopeptides identified, 73 were found exclusively in RIP3+/+ macrophages, 121 were detected exclusively from RIP3+/+ MEFs, 286 phosphopeptides were induced more in RIP3+/+ macrophages than in RIP3?/? macrophages and 26 phosphopeptides had higher induction in RIP3+/+ MEFs than in RIP3?/? cells. Many of the RIP3 regulated phosphoproteins from the macrophages and MEF cells are functionally associated with the cell cycle; the rest, however, appear to have diverse functions in that a number of metabolism related proteins were phosphorylated in macrophages and development related phosphoproteins were induced in MEFs. The results of our phosphoproteomic analysis suggest that RIP3 might function beyond necrosis and that cell type specific function of RIP3 exists. PMID:22942356

Wu, Xiurong; Tian, Lili; Li, Jie; Zhang, Yingying; Han, Victor; Li, Yuanyue; Xu, Xiaozheng; Li, Hanjie; Chen, Xi; Chen, Jinan; Jin, Wenhai; Xie, Yongming; Han, Jiahuai; Zhong, Chuan-Qi

2012-01-01

25

Quantitative phosphoproteomic analysis reveals cAMP/vasopressin-dependent signaling pathways in native renal thick ascending limb cells  

PubMed Central

Quantitative mass spectrometry was used to identify hormone-dependent signaling pathways in renal medullary thick ascending limb (mTAL) cells via phosphoproteomic analysis. Active transport of NaCl across the mTAL epithelium is accelerated by hormones that increase cAMP levels (vasopressin, glucagon, parathyroid hormone, and calcitonin). mTAL suspensions from rat kidneys were exposed (15 min) to a mixture of these four hormones. Tryptic phosphopeptides (immobilized metal affinity chromatography-enriched) were identified and quantified by mass spectrometry (LTQ-Orbitrap) using label-free methodology. We quantified a total of 654 phosphopeptides, of which 414 were quantified in three experimental pairs (hormone vs. vehicle). Of these phosphopeptides, 82% were statistically unchanged in abundance in response to the hormone mixture. In contrast, 48 phosphopeptides were significantly increased, whereas 28 were significantly decreased. The population of up-regulated phosphopeptides was highly enriched in basophilic kinase substrate motifs (AGC or calmodulin-sensitive kinase families), whereas the down-regulated sites were dominated by “proline-directed” motifs (cyclin-dependent or MAP kinase families). Bioinformatic classification uncovered overrepresentation of transmembrane transporters, protein phosphatase regulators, and cytoskeletal binding proteins among the regulated proteins. Immunoblotting with phospho-specific antibodies confirmed cAMP/vasopressin-dependent phosphorylation at Thr96, Ser126, and Ser874 of the Na+:K+:2Cl? cotransporter NKCC2, at Ser552 of the Na+:H+ exchanger NHE3, and at Ser552 of ?-catenin. Vasopressin also increased phosphorylation of NKCC2 at both Ser126 (more than fivefold) and Ser874 (more than threefold) in rats in vivo. Both sites were phosphorylated by purified protein kinase A during in vitro assays. These results support the view that, although protein kinase A plays a central role in mTAL signaling, additional kinases, including those that target proline-directed motifs, may be involved. PMID:20713729

Gunaratne, Ruwan; Braucht, Drew W. W.; Rinschen, Markus M.; Chou, Chung-Lin; Hoffert, Jason D.; Pisitkun, Trairak; Knepper, Mark A.

2010-01-01

26

Quantitative Phosphoproteome Analysis of Lysophosphatidic Acid Induced Chemotaxis applying Dual-step ¹?O Labeling Coupled with Immobilized Metal-ion Affinity Chromatography  

SciTech Connect

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

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

2008-10-01

27

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

PubMed Central

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

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

2013-01-01

28

Global Effects of Kinase Inhibitors on Signaling Networks Revealed by Quantitative Phosphoproteomics*  

PubMed Central

Aberrant signaling causes many diseases, and manipulating signaling pathways with kinase inhibitors has emerged as a promising area of drug research. Most kinase inhibitors target the conserved ATP-binding pocket; therefore specificity is a major concern. Proteomics has previously been used to identify the direct targets of kinase inhibitors upon affinity purification from cellular extracts. Here we introduce a complementary approach to evaluate the effects of kinase inhibitors on the entire cell signaling network. We used triple labeling SILAC (stable isotope labeling by amino acids in cell culture) to compare cellular phosphorylation levels for control, epidermal growth factor stimulus, and growth factor combined with kinase inhibitors. Of thousands of phosphopeptides, less than 10% had a response pattern indicative of targets of U0126 and SB202190, two widely used MAPK inhibitors. Interestingly, 83% of the growth factor-induced phosphorylation events were affected by either or both inhibitors, showing quantitatively that early signaling processes are predominantly transmitted through the MAPK cascades. In contrast to MAPK inhibitors, dasatinib, a clinical drug directed against BCR-ABL, which is the cause of chronic myelogenous leukemia, affected nearly 1,000 phosphopeptides. In addition to the proximal effects on ABL and its immediate targets, dasatinib broadly affected the downstream MAPK pathways. Pathway mapping of regulated sites implicated a variety of cellular functions, such as chromosome remodeling, RNA splicing, and cytoskeletal organization, some of which have been described in the literature before. Our assay is streamlined and generic and could become a useful tool in kinase drug development. PMID:19651622

Pan, Cuiping; Olsen, Jesper V.; Daub, Henrik; Mann, Matthias

2009-01-01

29

Quantitative trait locus analysis of leaf dissection in tomato using Lycopersicon pennellii segmental introgression lines.  

PubMed Central

Leaves are one of the most conspicuous and important organs of all seed plants. A fundamental source of morphological diversity in leaves is the degree to which the leaf is dissected by lobes and leaflets. We used publicly available segmental introgression lines to describe the quantitative trait loci (QTL) controlling the difference in leaf dissection seen between two tomato species, Lycopersicon esculentum and L. pennellii. We define eight morphological characteristics that comprise the mature tomato leaf and describe loci that affect each of these characters. We found 30 QTL that contribute one or more of these characters. Of these 30 QTL, 22 primarily affect leaf dissection and 8 primarily affect leaf size. On the basis of which characters are affected, four classes of loci emerge that affect leaf dissection. The majority of the QTL produce phenotypes intermediate to the two parent lines, while 5 QTL result in transgression with drastically increased dissection relative to both parent lines. PMID:14668401

Holtan, Hans E E; Hake, Sarah

2003-01-01

30

Quantitative dissection of hydrogen bond-mediated proton transfer in the ketosteroid isomerase active site  

E-print Network

Quantitative dissection of hydrogen bond-mediated proton transfer in the ketosteroid isomerase for review February 1, 2013) Hydrogen bond networks are key elements of protein structure and function-depth interrogations of the proton transfer equilibrium within a hydrogen bond network formed to bound phenols

Boxer, Steven G.

31

Dissecting Dissection.  

ERIC Educational Resources Information Center

This journal features articles covering various aspects of dissection. "Biology--The Study of Life" (George Russell) offers students experiments that do not require using invasive procedures. "Animal Cruelty--Behind the Scenes" (Zoe Weil) describes sources of laboratory animals. "Doing without Dissection" (Juliana Texley) discusses objections over…

AV Magazine, 1996

1996-01-01

32

The Lottia gigantea shell matrix proteome: re-analysis including MaxQuant iBAQ quantitation and phosphoproteome analysis  

PubMed Central

Background Although the importance of proteins of the biomineral organic matrix and their posttranslational modifications for biomineralization is generally recognized, the number of published matrix proteomes is still small. This is mostly due to the lack of comprehensive sequence databases, usually derived from genomic sequencing projects. However, in-depth mass spectrometry-based proteomic analysis, which critically depends on high-quality sequence databases, is a very fast tool to identify candidates for functional biomineral matrix proteins and their posttranslational modifications. Identification of such candidate proteins is facilitated by at least approximate quantitation of the identified proteins, because the most abundant ones may also be the most interesting candidates for further functional analysis. Results Re-quantification of previously identified Lottia shell matrix proteins using the intensity-based absolute quantification (iBAQ) method as implemented in the MaxQuant identification and quantitation software showed that only 57 of the 382 accepted identifications constituted 98% of the total identified matrix proteome. This group of proteins did not contain obvious intracellular proteins, such as cytoskeletal components or ribosomal proteins, invariably identified as minor components of high-throughput biomineral matrix proteomes. Fourteen of these major proteins were phosphorylated to a variable extent. All together we identified 52 phospho sites in 20 of the 382 accepted proteins with high confidence. Conclusions We show that iBAQ quantitation may be a useful tool to narrow down the group of functional biomineral matrix protein candidates for further research in cell biology, genetics or materials research. Knowledge of posttranslational modifications in these major proteins could be a valuable addition to previously published proteomes. This is true especially for phosphorylation, because this modification was already shown to modify mineralization processes in some instances. PMID:25018669

2014-01-01

33

Quantitative Phosphoproteomics after Auxin-stimulated Lateral Root Induction Identifies an SNX1 Protein Phosphorylation Site Required for Growth*  

PubMed Central

Protein phosphorylation is instrumental to early signaling events. Studying system-wide phosphorylation in relation to processes under investigation requires a quantitative proteomics approach. In Arabidopsis, auxin application can induce pericycle cell divisions and lateral root formation. Initiation of lateral root formation requires transcriptional reprogramming following auxin-mediated degradation of transcriptional repressors. The immediate early signaling events prior to this derepression are virtually uncharacterized. To identify the signal molecules responding to auxin application, we used a lateral root-inducible system that was previously developed to trigger synchronous division of pericycle cells. To identify and quantify the early signaling events following this induction, we combined 15N-based metabolic labeling and phosphopeptide enrichment and applied a mass spectrometry-based approach. In total, 3068 phosphopeptides were identified from auxin-treated root tissue. This root proteome dataset contains largely phosphopeptides not previously reported and represents one of the largest quantitative phosphoprotein datasets from Arabidopsis to date. Key proteins responding to auxin treatment included the multidrug resistance-like and PIN2 auxin carriers, AUXIN RESPONSE FACTOR2 (ARF2), SUPPRESSOR OF AUXIN RESISTANCE 3 (SAR3), and SORTING NEXIN1 (SNX1). Mutational analysis of serine 16 of SNX1 showed that overexpression of the mutated forms of SNX1 led to retarded growth and reduction of lateral root formation due to the reduced outgrowth of the primordium, showing proof of principle for our approach. PMID:23328941

Zhang, Hongtao; Zhou, Houjiang; Berke, Lidija; Heck, Albert J. R.; Mohammed, Shabaz; Scheres, Ben; Menke, Frank L. H.

2013-01-01

34

Quantitative Tools for Dissection of Hydrogen-Producing Metabolic Networks-Final Report  

SciTech Connect

During this project we have pioneered the development of integrated experimental-computational technologies for the quantitative dissection of metabolism in hydrogen and biofuel producing microorganisms (i.e. C. acetobutylicum and various cyanobacteria species). The application of these new methodologies resulted in many significant advances in the understanding of the metabolic networks and metabolism of these organisms, and has provided new strategies to enhance their hydrogen or biofuel producing capabilities. As an example, using mass spectrometry, isotope tracers, and quantitative flux-modeling we mapped the metabolic network structure in C. acetobutylicum. This resulted in a comprehensive and quantitative understanding of central carbon metabolism that could not have been obtained using genomic data alone. We discovered that biofuel production in this bacterium, which only occurs during stationary phase, requires a global remodeling of central metabolism (involving large changes in metabolite concentrations and fluxes) that has the effect of redirecting resources (carbon and reducing power) from biomass production into solvent production. This new holistic, quantitative understanding of metabolism is now being used as the basis for metabolic engineering strategies to improve solvent production in this bacterium. In another example, making use of newly developed technologies for monitoring hydrogen and NAD(P)H levels in vivo, we dissected the metabolic pathways for photobiological hydrogen production by cyanobacteria Cyanothece sp. This investigation led to the identification of multiple targets for improving hydrogen production. Importantly, the quantitative tools and approaches that we have developed are broadly applicable and we are now using them to investigate other important biofuel producers, such as cellulolytic bacteria.

Rabinowitz, Joshua D.; Dismukes, G.Charles.; Rabitz, Herschel A.; Amador-Noguez, Daniel

2012-10-19

35

Integrated genomics and molecular breeding approaches for dissecting the complex quantitative traits in crop plants.  

PubMed

The enormous population growth, climate change and global warming are now considered major threats to agriculture and world's food security. To improve the productivity and sustainability of agriculture, the development of highyielding and durable abiotic and biotic stress-tolerant cultivars and/climate resilient crops is essential. Henceforth, understanding the molecular mechanism and dissection of complex quantitative yield and stress tolerance traits is the prime objective in current agricultural biotechnology research. In recent years, tremendous progress has been made in plant genomics and molecular breeding research pertaining to conventional and next-generation whole genome, transcriptome and epigenome sequencing efforts, generation of huge genomic, transcriptomic and epigenomic resources and development of modern genomics-assisted breeding approaches in diverse crop genotypes with contrasting yield and abiotic stress tolerance traits. Unfortunately, the detailed molecular mechanism and gene regulatory networks controlling such complex quantitative traits is not yet well understood in crop plants. Therefore, we propose an integrated strategies involving available enormous and diverse traditional and modern -omics (structural, functional, comparative and epigenomics) approaches/resources and genomics-assisted breeding methods which agricultural biotechnologist can adopt/utilize to dissect and decode the molecular and gene regulatory networks involved in the complex quantitative yield and stress tolerance traits in crop plants. This would provide clues and much needed inputs for rapid selection of novel functionally relevant molecular tags regulating such complex traits to expedite traditional and modern marker-assisted genetic enhancement studies in target crop species for developing high-yielding stress-tolerant varieties. PMID:24296899

Kujur, Alice; Saxena, Maneesha S; Bajaj, Deepak; Laxmi; Parida, Swarup K

2013-12-01

36

Phosphoproteomics Combined with Quantitative 14-3-3-affinity Capture Identifies SIRT1 and RAI as Novel Regulators of Cytosolic Double-stranded RNA Recognition Pathway.  

PubMed

Viral double-stranded RNA (dsRNA) is the most important viral structure recognized by cytosolic pattern-recognition receptors of the innate immune system, and its recognition results in the activation of signaling cascades that stimulate the production of antiviral cytokines and apoptosis of infected cells. 14-3-3 proteins are ubiquitously expressed regulatory molecules that participate in a variety of cellular processes, and 14-3-3 protein-mediated signaling pathways are activated by cytoplasmic dsRNA in human keratinocytes. However, the functional role of 14-3-3 protein-mediated interactions during viral dsRNA stimulation has remained uncharacterized. Here, we used functional proteomics to identify proteins whose phosphorylation and interaction with 14-3-3 is modulated by dsRNA and to characterize the signaling pathways activated during cytosolic dsRNA-induced innate immune response in human HaCaT keratinocytes. Phosphoproteome analysis showed that several MAPK- and immune-response-related signaling pathways were activated after dsRNA stimulation. Interactome analysis identified RelA-associated inhibitor, high-mobility group proteins, and several proteins associated with host responses to viral infection as novel 14-3-3 target proteins. Functional studies showed that RelA-associated inhibitor regulated dsRNA-induced apoptosis and TNF production. Integrated network analyses of proteomic data revealed that sirtuin1 was a central molecule regulated by 14-3-3s during dsRNA stimulation. Further experiments showed that sirtuin 1 negatively regulated dsRNA-induced NF?B transcriptional activity, suppressed expression of antiviral cytokines, and protected cells from apoptosis in dsRNA-stimulated and encephalomyocarditis-virus-infected keratinocytes. In conclusion, our data highlight the importance of 14-3-3 proteins in antiviral responses and identify RelA-associated inhibitor and sirtuin 1 as novel regulators of antiviral innate immune responses. PMID:24997996

Ohman, Tiina; Söderholm, Sandra; Hintsanen, Petteri; Välimäki, Elina; Lietzén, Niina; MacKintosh, Carol; Aittokallio, Tero; Matikainen, Sampsa; Nyman, Tuula A

2014-10-01

37

Challenges in plasma membrane phosphoproteomics  

PubMed Central

The response to extracellular stimuli often alters the phosphorylation state of plasma membrane-associated proteins. In this regard, generation of a comprehensive membrane phosphoproteome can significantly enhance signal transduction and drug mechanism studies. However, analysis of this subproteome is regarded as technically challenging, given the low abundance and insolubility of integral membrane proteins, combined with difficulties in isolating, ionizing and fragmenting phosphopeptides. In this article, we highlight recent advances in membrane and phosphoprotein enrichment techniques resulting in improved identification of these elusive peptides. We also describe the use of alternative fragmentation techniques, and assess their current and future value to the field of membrane phosphoproteomics. PMID:21819303

Orsburn, Benjamin C; Stockwin, Luke H; Newton, Dianne L

2011-01-01

38

Clinical and Technical Phosphoproteomic Research  

PubMed Central

An encouraging approach for the diagnosis and effective therapy of immunological pathologies, which would include cancer, is the identification of proteins and phosphorylated proteins. Disease proteomics, in particular, is a potentially useful method for this purpose. A key role is played by protein phosphorylation in the regulation of normal immunology disorders and targets for several new cancer drugs and drug candidates are cancer cells and protein kinases. Protein phosphorylation is a highly dynamic process. The functioning of new drugs is of major importance as is the selection of those patients who would respond best to a specific treatment regime. In all major aspects of cellular life signalling networks are key elements which play a major role in inter- and intracellular communications. They are involved in diverse processes such as cell-cycle progression, cellular metabolism, cell-cell communication and appropriate response to the cellular environment. A whole range of networks that are involved in the regulation of cell development, differentiation, proliferation, apoptosis, and immunologic responses is contained in the latter. It is so necessary to understand and monitor kinase signalling pathways in order to understand many immunology pathologies. Enrichment of phosphorylated proteins or peptides from tissue or bodily fluid samples is required. The application of technologies such as immunoproteomic techniques, phosphoenrichments and mass spectrometry (MS) is crucial for the identification and quantification of protein phosphorylation sites in order to advance in clinical research. Pharmacodynamic readouts of disease states and cellular drug responses in tumour samples will be provided as the field develops. We aim to detail the current and most useful techniques with research examples to isolate and carry out clinical phosphoproteomic studies which may be helpful for immunology and cancer research. Different phosphopeptide enrichment and quantitative techniques need to be combined to achieve good phosphopeptide recovery and good up- and-down phospho-regulation protein studies. PMID:21635771

2011-01-01

39

Development of mass spectrometry based technologies for quantitative cell signaling phosphoproteomics : the epidermal growth factor receptor family as a model system  

E-print Network

Ligand binding to cell surface receptors initiates a cascade of signaling events regulated by dynamic phosphorylation on a multitude of pathway proteins. Quantitative features, including intensity, timing, and duration of ...

Wolf Yadlin, Alejandro

2007-01-01

40

Phosphoproteome analysis of formalin-fixed and paraffin-embedded tissue sections mounted on microscope slides.  

PubMed

Formalin-fixed and paraffin-embedded (FFPE) sections mounted on microscope slides are one of the largest available resources for retrospective research on various diseases, but quantitative phosphoproteome analysis of FFPE sections has never been achieved because of the extreme difficulty of procuring sufficient phosphopeptides from the limited amounts of proteins on the slides. Here, we present the first protocol for quantitative phosphoproteome analysis of FFPE sections by utilizing phase-transfer surfactant-aided extraction/tryptic digestion of FFPE proteins followed by high-recovery phosphopeptide enrichment via lactic acid-modified titania chromatography. We established that FFPE sections retain a similar phosphoproteome to fresh tissue specimens during storage for at least 9 months, confirming the utility of our method for evaluating phosphorylation profiles in various diseases. We also verified that chemical labeling based on reductive dimethylation of amino groups was feasible for quantitative phosphoproteome analysis of FFPE samples on slides. Furthermore, we improved the LC-MS sensitivity by miniaturizing nanoLC columns to 25 ?m inner diameter. With this system, we could identify 1090 phosphopeptides from a single FFPE section obtained from a microscope slide, containing 25.2 ± 5.4 ?g of proteins. This protocol should be useful for large-scale phosphoproteome analysis of archival FFPE slides, especially scarce samples from patients with rare diseases. PMID:24328109

Wakabayashi, Masaki; Yoshihara, Hiroki; Masuda, Takeshi; Tsukahara, Mai; Sugiyama, Naoyuki; Ishihama, Yasushi

2014-02-01

41

Reconstruction of insulin signal flow from phosphoproteome and metabolome data.  

PubMed

Cellular homeostasis is regulated by signals through multiple molecular networks that include protein phosphorylation and metabolites. However, where and when the signal flows through a network and regulates homeostasis has not been explored. We have developed a reconstruction method for the signal flow based on time-course phosphoproteome and metabolome data, using multiple databases, and have applied it to acute action of insulin, an important hormone for metabolic homeostasis. An insulin signal flows through a network, through signaling pathways that involve 13 protein kinases, 26 phosphorylated metabolic enzymes, and 35 allosteric effectors, resulting in quantitative changes in 44 metabolites. Analysis of the network reveals that insulin induces phosphorylation and activation of liver-type phosphofructokinase 1, thereby controlling a key reaction in glycolysis. We thus provide a versatile method of reconstruction of signal flow through the network using phosphoproteome and metabolome data. PMID:25131207

Yugi, Katsuyuki; Kubota, Hiroyuki; Toyoshima, Yu; Noguchi, Rei; Kawata, Kentaro; Komori, Yasunori; Uda, Shinsuke; Kunida, Katsuyuki; Tomizawa, Yoko; Funato, Yosuke; Miki, Hiroaki; Matsumoto, Masaki; Nakayama, Keiichi I; Kashikura, Kasumi; Endo, Keiko; Ikeda, Kazutaka; Soga, Tomoyoshi; Kuroda, Shinya

2014-08-21

42

Phosphoproteomics and Lung Cancer Research  

PubMed Central

Massive evidence suggests that genetic abnormalities contribute to the development of lung cancer. These molecular abnormalities may serve as diagnostic, prognostic and predictive biomarkers for this deadly disease. It is imperative to search these biomarkers in different tumorigenesis pathways so as to provide the most appropriate therapy for each individual patient with lung malignancy. Phosphoproteomics is a promising technology for the identification of biomarkers and novel therapeutic targets for cancer. Thousands of proteins interact via physical and chemical association. Moreover, some proteins can covalently modify other proteins post-translationally. These post-translational modifications ultimately give rise to the emergent functions of cells in sequence, space and time. Phosphoproteomics clinical researches imply the comprehensive analysis of the proteins that are expressed in cells or tissues and can be employed at different stages. In addition, understanding the functions of phosphorylated proteins requires the study of proteomes as linked systems rather than collections of individual protein molecules. In fact, proteomics approaches coupled with affinity chromatography strategies followed by mass spectrometry have been used to elucidate relevant biological questions. This article will discuss the relevant clues of post-translational modifications, phosphorylated proteins, and useful proteomics approaches to identify molecular cancer signatures. The recent progress in phosphoproteomics research in lung cancer will be also discussed. PMID:23202899

Lopez, Elena; Cho, William C. S.

2012-01-01

43

Integrating phosphoproteomics in systems biology  

PubMed Central

Phosphorylation of serine, threonine and tyrosine plays significant roles in cellular signal transduction and in modifying multiple protein functions. Phosphoproteins are coordinated and regulated by a network of kinases, phosphatases and phospho-binding proteins, which modify the phosphorylation states, recognize unique phosphopeptides, or target proteins for degradation. Detailed and complete information on the structure and dynamics of these networks is required to better understand fundamental mechanisms of cellular processes and diseases. High-throughput technologies have been developed to investigate phosphoproteomes in model organisms and human diseases. Among them, mass spectrometry (MS)-based technologies are the major platforms and have been widely applied, which has led to explosive growth of phosphoproteomic data in recent years. New bioinformatics tools are needed to analyze and make sense of these data. Moreover, most research has focused on individual phosphoproteins and kinases. To gain a more complete knowledge of cellular processes, systems biology approaches, including pathways and networks modeling, have to be applied to integrate all components of the phosphorylation machinery, including kinases, phosphatases, their substrates, and phospho-binding proteins. This review presents the latest developments of bioinformatics methods and attempts to apply systems biology to analyze phosphoproteomics data generated by MS-based technologies. Challenges and future directions in this field will be also discussed. PMID:25349677

Liu, Yu; Chance, Mark R.

2014-01-01

44

Functional phosphoproteomic mass spectrometry-based approaches  

PubMed Central

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

2012-01-01

45

The phosphoproteome of toll-like receptor-activated macrophages  

PubMed Central

Recognition of microbial danger signals by toll-like receptors (TLR) causes re-programming of macrophages. To investigate kinase cascades triggered by the TLR4 ligand lipopolysaccharide (LPS) on systems level, we performed a global, quantitative and kinetic analysis of the phosphoproteome of primary macrophages using stable isotope labelling with amino acids in cell culture, phosphopeptide enrichment and high-resolution mass spectrometry. In parallel, nascent RNA was profiled to link transcription factor (TF) phosphorylation to TLR4-induced transcriptional activation. We reproducibly identified 1850 phosphoproteins with 6956 phosphorylation sites, two thirds of which were not reported earlier. LPS caused major dynamic changes in the phosphoproteome (24% up-regulation and 9% down-regulation). Functional bioinformatic analyses confirmed canonical players of the TLR pathway and highlighted other signalling modules (e.g. mTOR, ATM/ATR kinases) and the cytoskeleton as hotspots of LPS-regulated phosphorylation. Finally, weaving together phosphoproteome and nascent transcriptome data by in silico promoter analysis, we implicated several phosphorylated TFs in primary LPS-controlled gene expression. PMID:20531401

Weintz, Gabriele; Olsen, Jesper V; Fruhauf, Katja; Niedzielska, Magdalena; Amit, Ido; Jantsch, Jonathan; Mages, Jorg; Frech, Cornelie; Dolken, Lars; Mann, Matthias; Lang, Roland

2010-01-01

46

The calcium-dependent protein kinase 3 of toxoplasma influences basal calcium levels and functions beyond egress as revealed by quantitative phosphoproteome analysis.  

PubMed

Calcium-dependent protein kinases (CDPKs) are conserved in plants and apicomplexan parasites. In Toxoplasma gondii, TgCDPK3 regulates parasite egress from the host cell in the presence of a calcium-ionophore. The targets and the pathways that the kinase controls, however, are not known. To identify pathways regulated by TgCDPK3, we measured relative phosphorylation site usage in wild type and TgCDPK3 mutant and knock-out parasites by quantitative mass-spectrometry using stable isotope-labeling with amino acids in cell culture (SILAC). This revealed known and novel phosphorylation events on proteins predicted to play a role in host-cell egress, but also a novel function of TgCDPK3 as an upstream regulator of other calcium-dependent signaling pathways, as we also identified proteins that are differentially phosphorylated prior to egress, including proteins important for ion-homeostasis and metabolism. This observation is supported by the observation that basal calcium levels are increased in parasites where TgCDPK3 has been inactivated. Most of the differential phosphorylation observed in CDPK3 mutants is rescued by complementation of the mutants with a wild type copy of TgCDPK3. Lastly, the TgCDPK3 mutants showed hyperphosphorylation of two targets of a related calcium-dependent kinase (TgCDPK1), as well as TgCDPK1 itself, indicating that this latter kinase appears to play a role downstream of TgCDPK3 function. Overexpression of TgCDPK1 partially rescues the egress phenotype of the TgCDPK3 mutants, reinforcing this conclusion. These results show that TgCDPK3 plays a pivotal role in regulating tachyzoite functions including, but not limited to, egress. PMID:24945436

Treeck, Moritz; Sanders, John L; Gaji, Rajshekhar Y; LaFavers, Kacie A; Child, Matthew A; Arrizabalaga, Gustavo; Elias, Joshua E; Boothroyd, John C

2014-06-01

47

Dissecting Quantitative Trait Loci for Boron Efficiency across Multiple Environments in Brassica napus  

PubMed Central

High yield is the most important goal in crop breeding, and boron (B) is an essential micronutrient for plants. However, B deficiency, leading to yield decreases, is an agricultural problem worldwide. Brassica napus is one of the most sensitive crops to B deficiency, and considerable genotypic variation exists among different cultivars in response to B deficiency. To dissect the genetic basis of tolerance to B deficiency in B. napus, we carried out QTL analysis for seed yield and yield-related traits under low and normal B conditions using the double haploid population (TNDH) by two-year and the BQDH population by three-year field trials. In total, 80 putative QTLs and 42 epistatic interactions for seed yield, plant height, branch number, pod number, seed number, seed weight and B efficiency coefficient (BEC) were identified under low and normal B conditions, singly explaining 4.15–23.16% and 0.53–14.38% of the phenotypic variation. An additive effect of putative QTLs was a more important controlling factor than the additive-additive effect of epistatic interactions. Four QTL-by-environment interactions and 7 interactions between epistatic interactions and the environment contributed to 1.27–4.95% and 1.17–3.68% of the phenotypic variation, respectively. The chromosome region on A2 of SYLB-A2 for seed yield under low B condition and BEC-A2 for BEC in the two populations was equivalent to the region of a reported major QTL, BE1. The B. napus homologous genes of Bra020592 and Bra020595 mapped to the A2 region and were speculated to be candidate genes for B efficiency. These findings reveal the complex genetic basis of B efficiency in B. napus. They provide a basis for the fine mapping and cloning of the B efficiency genes and for breeding B-efficient cultivars by marker-assisted selection (MAS). PMID:23028855

Zhao, Zunkang; Wu, Likun; Nian, Fuzhao; Ding, Guangda; Shi, Taoxiong; Zhang, Didi; Shi, Lei; Xu, Fangsen; Meng, Jinling

2012-01-01

48

Phosphoproteomics for the masses  

PubMed Central

Protein phosphorylation serves as a primary mechanism of signal transduction in the cells of biological organisms. Technical advancements over the last several years in mass spectrometry now allow for the large-scale identification and quantitation of in vivo phosphorylation at unprecedented levels. These developments have occurred in the areas of sample preparation, instrumentation, quantitative methodology, and informatics so that today, ten to twenty thousand phosphorylation sites can be identified and quantified within a few weeks. With the rapid development and widespread availability of such data, its translation into biological insight and knowledge is a current obstacle. Here we present an overview of how this technology came to be and is currently applied, as well as future challenges for the field. PMID:20047291

Grimsrud, Paul A.; Swaney, Danielle L.; Wenger, Craig D.; Beauchene, Nicole A.; Coon, Joshua J.

2010-01-01

49

Chemical Visualization of Phosphoproteomes on Membrane*  

PubMed Central

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

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

2012-01-01

50

Quantitative dissection of hydrogen bond-mediated proton transfer in the ketosteroid isomerase active site  

PubMed Central

Hydrogen bond networks are key elements of protein structure and function but have been challenging to study within the complex protein environment. We have carried out in-depth interrogations of the proton transfer equilibrium within a hydrogen bond network formed to bound phenols in the active site of ketosteroid isomerase. We systematically varied the proton affinity of the phenol using differing electron-withdrawing substituents and incorporated site-specific NMR and IR probes to quantitatively map the proton and charge rearrangements within the network that accompany incremental increases in phenol proton affinity. The observed ionization changes were accurately described by a simple equilibrium proton transfer model that strongly suggests the intrinsic proton affinity of one of the Tyr residues in the network, Tyr16, does not remain constant but rather systematically increases due to weakening of the phenol–Tyr16 anion hydrogen bond with increasing phenol proton affinity. Using vibrational Stark spectroscopy, we quantified the electrostatic field changes within the surrounding active site that accompany these rearrangements within the network. We were able to model these changes accurately using continuum electrostatic calculations, suggesting a high degree of conformational restriction within the protein matrix. Our study affords direct insight into the physical and energetic properties of a hydrogen bond network within a protein interior and provides an example of a highly controlled system with minimal conformational rearrangements in which the observed physical changes can be accurately modeled by theoretical calculations. PMID:23798390

Sigala, Paul A.; Fafarman, Aaron T.; Schwans, Jason P.; Fried, Stephen D.; Fenn, Timothy D.; Caaveiro, Jose M. M.; Pybus, Brandon; Ringe, Dagmar; Petsko, Gregory A.; Boxer, Steven G.; Herschlag, Daniel

2013-01-01

51

Broader implications of SILAC-based proteomics for dissecting signaling dynamics in cancer.  

PubMed

Large-scale transcriptome and epigenome analyses have been widely utilized to discover gene alterations implicated in cancer development at the genetic level. However, mapping of signaling dynamics at the protein level is likely to be more insightful and needed to complement massive genomic data. Stable isotope labeling with amino acids in cell culture (SILAC)-based proteomic analysis represents one of the most promising comparative quantitative methods that has been extensively employed in proteomic research. This technology allows for global, robust and confident identification and quantification of signal perturbations important for the progress of human diseases, particularly malignancies. The present review summarizes the latest applications of in vitro and in vivo SILAC-based proteomics in identifying global proteome/phosphoproteome and genome-wide protein-protein interactions that contribute to oncogenesis, highlighting the recent advances in dissecting signaling dynamics in cancer. PMID:25345469

Zhang, Hua; Xu, Yichen; Papanastasopoulos, Panos; Stebbing, Justin; Giamas, Georgios

2014-12-01

52

Enrichment techniques employed in phosphoproteomics.  

PubMed

Rapid changes of protein phosphorylation play a crucial role in the regulation of many cellular processes. Being post-translationally modified, phosphoproteins are often present in quite low abundance and tend to co-exist with their unphosphorylated isoform within the cell. To make their identification more practicable, the use of enrichment protocols is often required. The enrichment strategies can be performed either at the level of phosphoproteins or at the level of phosphopeptides. Both approaches have their advantages and disadvantages. Most enriching strategies are based on chemical modifications, affinity chromatography to capture peptides and proteins containing negatively charged phosphate groups onto a positively charged matrix, or immunoprecipitation by phospho-specific antibodies.In this article, the most up-to-date enrichment techniques are discussed, taking into account their optimization, and highlighting their advantages and disadvantages. Moreover, these methods are compared to each other, revealing their complementary nature in providing comprehensive coverage of the phosphoproteome. PMID:22002794

Fíla, Jan; Honys, David

2012-09-01

53

Global Analysis of Neuronal Phosphoproteome Regulation by Chondroitin Sulfate Proteoglycans  

PubMed Central

Chondroitin sulfate proteoglycans (CSPGs) are major components of the extracellular matrix which mediate inhibition of axonal regeneration after injury to the central nervous system (CNS). Several neuronal receptors for CSPGs have recently been identified; however, the signaling pathways by which CSPGs restrict axonal growth are still largely unknown. In this study, we applied quantitative phosphoproteomics to investigate the global changes in protein phosphorylation induced by CSPGs in primary neurons. In combination with isobaric Tags for Relative and Absolute Quantitation (iTRAQ) labeling, strong cation exchange chromatography (SCX) fractionation, immobilized metal affinity chromatography (IMAC) and LC-MS/MS, we identified and quantified 2214 unique phosphopeptides corresponding to 1118 phosphoproteins, with 118 changing significantly in abundance with CSPG treatment. The proteins that were regulated by CSPGs included key components of synaptic vesicle trafficking, axon guidance mediated by semaphorins, integrin signaling, cadherin signaling and EGF receptor signaling pathways. A significant number of the regulated proteins are cytoskeletal and related proteins that have been implicated in regulating neurite growth. Another highly represented protein category regulated by CSPGs is nucleic acid binding proteins involved in RNA post-transcriptional regulation. Together, by screening the overall phosphoproteome changes induced by CSPGs, this data expand our understanding of CSPG signaling, which provides new insights into development of strategies for overcoming CSPG inhibition and promoting axonal regeneration after CNS injury. PMID:23527152

Yu, Panpan; Pisitkun, Trairak; Wang, Guanghui; Wang, Rong; Katagiri, Yasuhiro; Gucek, Marjan; Knepper, Mark A.; Geller, Herbert M.

2013-01-01

54

Phosphoproteomic Analyses Reveal Signaling Pathways That Facilitate Lytic Gammaherpesvirus Replication  

PubMed Central

Lytic gammaherpesvirus (GHV) replication facilitates the establishment of lifelong latent infection, which places the infected host at risk for numerous cancers. As obligate intracellular parasites, GHVs must control and usurp cellular signaling pathways in order to successfully replicate, disseminate to stable latency reservoirs in the host, and prevent immune-mediated clearance. To facilitate a systems-level understanding of phosphorylation-dependent signaling events directed by GHVs during lytic replication, we utilized label-free quantitative mass spectrometry to interrogate the lytic replication cycle of murine gammaherpesvirus-68 (MHV68). Compared to controls, MHV68 infection regulated by 2-fold or greater ca. 86% of identified phosphopeptides – a regulatory scale not previously observed in phosphoproteomic evaluations of discrete signal-inducing stimuli. Network analyses demonstrated that the infection-associated induction or repression of specific cellular proteins globally altered the flow of information through the host phosphoprotein network, yielding major changes to functional protein clusters and ontologically associated proteins. A series of orthogonal bioinformatics analyses revealed that MAPK and CDK-related signaling events were overrepresented in the infection-associated phosphoproteome and identified 155 host proteins, such as the transcription factor c-Jun, as putative downstream targets. Importantly, functional tests of bioinformatics-based predictions confirmed ERK1/2 and CDK1/2 as kinases that facilitate MHV68 replication and also demonstrated the importance of c-Jun. Finally, a transposon-mutant virus screen identified the MHV68 cyclin D ortholog as a viral protein that contributes to the prominent MAPK/CDK signature of the infection-associated phosphoproteome. Together, these analyses enhance an understanding of how GHVs reorganize and usurp intracellular signaling networks to facilitate infection and replication. PMID:24068923

Stahl, James A.; Chavan, Shweta S.; Sifford, Jeffrey M.; MacLeod, Veronica; Voth, Daniel E.; Edmondson, Ricky D.; Forrest, J. Craig

2013-01-01

55

Phosphoproteomic analysis: An emerging role in deciphering cellular signaling in human embryonic stem cells and their differentiated derivatives  

PubMed Central

Cellular signaling is largely controlled by protein phosphorylation. This post-translational modification (PTM) has been extensively analyzed when examining one or a few protein phosphorylation events that effect cell signaling. However, protein kinase-driven signaling networks, comprising total (phospho)proteomes, largely control cell fate. Therefore, large-scale analysis of differentially regulated protein phosphorylation is central to elucidating complex cellular events, including maintenance of pluripotency and differentiation of embryonic stem cells (ESCs). The current technology of choice for total phosphoproteome and combined total proteome plus total phosphoproteome (termed (phospho)proteome)1 analyses is multidimensional liquid chromatography- (MDLC) tandem mass spectrometry (MS/MS).Advances in the use of MDLC for separation of peptides comprising total (phospho)proteomes, phosphopeptide enrichment, separation of enriched fractions, and quantitative peptide identification by MS/MS have been rapid in recent years, as have improvements in the sensitivity, speed, and accuracy of mass spectrometers. Increasingly deep coverage of (phospho)proteomes is allowing an improved understanding of changes in protein phosphorylation networks as cells respond to stimuli and progress from one undifferentiated or differentiated state to another. Although MDLC-MS/MS studies are powerful, understanding the interpretation of the data is important, and targeted experimental pursuit of biological predictions provided by total (phospho)proteome analyses is needed.(Phospho)proteomic analyses of pluripotent stem cells are in their infancy at this time. However, such studies have already begun to contribute to an improved and accelerated understanding of basic pluripotent stem cell signaling and fate control, especially at the systems-biology level. PMID:22009073

Tobe, Brian T.D.; Hou, Junjie; Crain, Andrew M.; Singec, Ilyas; Snyder, Evan Y.; Brill, Laurence M.

2013-01-01

56

Technical phosphoproteomic and bioinformatic tools useful in cancer research  

PubMed Central

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

2011-01-01

57

Comparison of SILAC and mTRAQ quantification for phosphoproteomics on a quadrupole orbitrap mass spectrometer.  

PubMed

Advances in mass spectrometric methodology and instrumentation have promoted a continuous increase in analytical performance in the field of phosphoproteomics. Here, we employed the recently introduced quadrupole Orbitrap (Q Exactive) mass spectrometer for quantitative signaling analysis to a depth of more than 15?000 phosphorylation sites. In parallel to the commonly used SILAC approach, we evaluated the nonisobaric chemical labeling reagent mTRAQ as an alternative quantification technique. Both enabled high phosphoproteome coverage in H3122 lung cancer cells. Replicate quantifications by mTRAQ identified almost as many significant phosphorylation changes upon treatment with ALK kinase inhibitor crizotinib as found by SILAC quantification. Overall, mTRAQ was slightly less precise than SILAC as evident from a somewhat higher variance of replicate phosphosite ratios. Direct comparison of SILAC- and mTRAQ-quantified phosphosites revealed that the majority of changes were detected by either quantification techniques, but also highlighted the aspect of false negative identifications in quantitative proteomics applications. Further inspection of crizotinib-regulated phosphorylation changes unveiled interference with multiple antioncogenic mechanisms downstream of ALK fusion kinase in H3122 cells. In conclusion, our results demonstrate a strong analytical performance of the Q Exactive in global phosphoproteomics, and establish mTRAQ quantification as a useful alternative to metabolic isotope labeling. PMID:23898821

Oppermann, Felix S; Klammer, Martin; Bobe, Caroline; Cox, Jürgen; Schaab, Christoph; Tebbe, Andreas; Daub, Henrik

2013-09-01

58

Clam Dissection  

NSDL National Science Digital Library

This online slide presentation features an image rich overview of clam dissections. The 31 slides include images portraying step of a dissection as well as information about each structure and its function. This presentation may serve as an introduction to the laboratory procedure, student review, or virtual dissection.

Riedell, Kelly; District, Brookings S.

59

Phosphoproteomics characterization of novel phosphorylated sites of lens proteins from normal and cataractous human eye lenses  

PubMed Central

Purpose Post-translational modification (PTM) of lens proteins is believed to play various roles in age-related lens function and development. Among the different types of PTM, phosphorylation is most noteworthy to play a major role in the regulation of various biosignaling pathways in relation to metabolic processes and cellular functions. The present study reported the quantitative analysis of the in vivo phosphoproteomics profiles of human normal and cataractous lenses with the aim of identifying specific phosphorylation sites which may provide insights into the physiologic significance of phosphorylation in relation to cataract formation. Methods To improve detection sensitivity of low abundant proteins, we first adopted SDS-gel electrophoresis fractionation of lens extracts to identify and compare the protein compositions between normal and cataractous lenses, followed by tryptic digestion, enrichment of phosphopeptides by immobilized metal affinity chromatography (IMAC) and nano-liquid chromatography coupled tandem mass spectrometry (nanoLC-MS/MS) analysis. Results By comprehensively screening of the phosphoproteome in normal and cataractous lenses, we identified 32 phosphoproteins and 73 phosphorylated sites. The most abundantly phosphorylated proteins are two subunits of ?-crystallin, i.e., ?B1-crystallin (12%) and ?B2-crystallin (12%). Moreover, serine was found to be the most abundantly phosphorylated residue (72%) in comparison with threonine (24%) and tyrosine (4%) in the lens phosphoproteome. The quantitative analysis revealed significant and distinct changes of 19 phosphoproteins corresponding to 28 phosphorylated sites between these two types of human lenses, including 20 newly discovered novel phosphorylation sites on lens proteins. Conclusions The shotgun phosphoproteomics approach to characterize protein phosphorylation may be adapted and extended to the comprehensive analysis of other types of post-translational modification of lens proteins in vivo. The identification of these novel phosphorylation sites in lens proteins that showed differential expression in the cataractous lens may bear some unknown physiologic significance and provide insights into phosphorylation-related human eye diseases, which warrant further investigation in the future. PMID:21264232

Huang, Chun-Hao; Wang, Yi-Ting; Tsai, Chia-Feng; Chen, Yu-Ju; Lee, Jiahn-Shing

2011-01-01

60

Identification of Targets of c-Src Tyrosine Kinase by Chemical Complementation and Phosphoproteomics*  

PubMed Central

The cellular proto-oncogene c-Src is a nonreceptor tyrosine kinase involved in cell growth and cytoskeletal regulation. Despite being dysregulated in a variety of human cancers, its precise functions are not fully understood. Identification of the substrates of c-Src remains a major challenge, because there is no simple way to directly stimulate its activity. Here we combine the chemical rescue of mutant c-Src and global quantitative phosphoproteomics to obtain the first high resolution snapshot of the range of tyrosine phosphorylation events that occur in the cell immediately after specific c-Src stimulation. After enrichment by anti-phosphotyrosine antibodies, we identified 29 potential novel c-Src substrate proteins. Tyrosine phosphopeptide mapping allowed the identification of 382 nonredundant tyrosine phosphopeptides on 213 phosphoproteins. Stable isotope labeling of amino acids in cell culture-based quantitation allowed the detection of 97 nonredundant tyrosine phosphopeptides whose level of phosphorylation is increased by c-Src. A large number of previously uncharacterized c-Src putative protein targets and phosphorylation sites are presented here, a majority of which play key roles in signaling and cytoskeletal networks, particularly in cell adhesion. Integrin signaling and focal adhesion kinase signaling pathway are two of the most altered pathways upon c-Src activation through chemical rescue. In this context, our study revealed the temporal connection between c-Src activation and the GTPase Rap1, known to stimulate integrin-dependent adhesion. Chemical rescue of c-Src provided a tool to dissect the spatiotemporal mechanism of activation of the Rap1 guanine exchange factor, C3G, one of the identified potential c-Src substrates that plays a role in focal adhesion signaling. In addition to unveiling the role of c-Src in the cell and, specifically, in the Crk-C3G-Rap1 pathway, these results exemplify a strategy for obtaining a comprehensive understanding of the functions of nonreceptor tyrosine kinases with high specificity and kinetic resolution. PMID:22499769

Ferrando, Isabel Martinez; Chaerkady, Raghothama; Zhong, Jun; Molina, Henrik; Jacob, Harrys K.C.; Herbst-Robinson, Katie; Dancy, Beverley M.; Katju, Vikram; Bose, Ron; Zhang, Jin; Pandey, Akhilesh; Cole, Philip A.

2012-01-01

61

Phosphoproteomics data classify hematological cancer cell lines according to tumor type and sensitivity to kinase inhibitors  

PubMed Central

Background Tumor classification based on their predicted responses to kinase inhibitors is a major goal for advancing targeted personalized therapies. Here, we used a phosphoproteomic approach to investigate biological heterogeneity across hematological cancer cell lines including acute myeloid leukemia, lymphoma, and multiple myeloma. Results Mass spectrometry was used to quantify 2,000 phosphorylation sites across three acute myeloid leukemia, three lymphoma, and three multiple myeloma cell lines in six biological replicates. The intensities of the phosphorylation sites grouped these cancer cell lines according to their tumor type. In addition, a phosphoproteomic analysis of seven acute myeloid leukemia cell lines revealed a battery of phosphorylation sites whose combined intensities correlated with the growth-inhibitory responses to three kinase inhibitors with remarkable correlation coefficients and fold changes (> 100 between the most resistant and sensitive cells). Modeling based on regression analysis indicated that a subset of phosphorylation sites could be used to predict response to the tested drugs. Quantitative analysis of phosphorylation motifs indicated that resistant and sensitive cells differed in their patterns of kinase activities, but, interestingly, phosphorylations correlating with responses were not on members of the pathway being targeted; instead, these mainly were on parallel kinase pathways. Conclusion This study reveals that the information on kinase activation encoded in phosphoproteomics data correlates remarkably well with the phenotypic responses of cancer cells to compounds that target kinase signaling and could be useful for the identification of novel markers of resistance or sensitivity to drugs that target the signaling network. PMID:23628362

2013-01-01

62

Paper dissection  

NSDL National Science Digital Library

Students are provided with a dinosaur article from a popular magazine (e.g. Discover or Natural History) or the journal Science. Their task is to dissect the article distinguishing evidence from interpretation. They need to recognize the various hypotheses presented and also evaluate the strength of these ideas. Then during classroom discussion, they explore the implications of their dissections. For example they would address some of the following questions: Are other interpretations possible? Where have the authors over interpreted the evidence? What are the strongest interpretations? How could the ideas be further tested? What type of evidence would be sufficient to falsify or further support the interpretations of the papers?

Varricchio, David

63

Phosphoproteomic analysis of apoptotic hematopoietic stem cells from hemoglobin E/?-thalassemia  

PubMed Central

Background Hemoglobin E/?-thalassemia is particularly common in Southeast Asia and has variable symptoms ranging from mild to severe anemia. Previous investigations demonstrated the remarkable symptoms of ?-thalassemia in terms of the acceleration of apoptotic cell death. Ineffective erythropoiesis has been studied in human hematopoietic stem cells, however the distinct apoptotic mechanism was unclear. Methods The phosphoproteome of bone marrow HSCs/CD34+ cells from HbE/?-thalassemic patients was analyzed using IMAC phosphoprotein isolation followed by LC-MS/MS detection. Decyder MS software was used to quantitate differentially expressed proteins in 3 patients and 2 normal donors. The differentially expressed proteins from HSCs/CD34+ cells were compared with HbE/?-thalassemia and normal HSCs. Results A significant change in abundance of 229 phosphoproteins was demonstrated. Importantly, the analysis of the candidate proteins revealed a high abundance of proteins that are commonly found in apoptotic cells including cytochrome C, caspase 6 and apoptosis inducing factors. Moreover, in the HSCs patients a significant increase was observed in a specific type of phosphoserine/threonine binding protein, which is known to act as an important signal mediator for the regulation of cell survival and apoptosis in HbE/?-thalassemia. Conclusions Our study used a novel method to investigate proteins that influence a particular pathway in a given disease or physiological condition. Ultimately, phosphoproteome profiling in HbE/?-thalassemic stem cells is an effective method to further investigate the cell death mechanism of ineffective erythropoiesis in ?-thalassemia. Our report provides a comprehensive phosphoproteome, an important resource for the study of ineffective erythropoiesis and developing therapies for HbE/?-thalassemia. PMID:21702968

2011-01-01

64

Dissecting Light  

NSDL National Science Digital Library

White light is composed of the entire visible light spectrum, but how do you teach this to students in a hands-on way? The answer is simple: by using a spectroscope. This easy-to-make tool allows students to dissect light and in the process, develop an un

Proto, Christopher; Marek, Edmund A.

2000-04-01

65

Polyomino Dissections  

ERIC Educational Resources Information Center

One of Gardner's passions was to introduce puzzles into the classroom. From this point of view, polyomino dissections are an excellent topic. They require little background, provide training in geometric visualization, and mostly they are fun. In this article, we put together a large collection of such puzzles, introduce a new approach in solving…

Hohn, Tiina; Liu, Andy

2012-01-01

66

Parallel Proteomic and Phosphoproteomic Analyses of Successive Stages of Maize Leaf Development[C][W][OPEN  

PubMed Central

We performed large-scale, quantitative analyses of the maize (Zea mays) leaf proteome and phosphoproteome at four developmental stages. Exploiting the developmental gradient of maize leaves, we analyzed protein and phosphoprotein abundance as maize leaves transition from proliferative cell division to differentiation to cell expansion and compared these developing zones to one another and the mature leaf blade. Comparison of the proteomes and phosphoproteomes suggests a key role for posttranslational regulation in developmental transitions. Analysis of proteins with cell wall– and hormone-related functions illustrates the utility of the data set and provides further insight into maize leaf development. We compare phosphorylation sites identified here to those previously identified in Arabidopsis thaliana. We also discuss instances where comparison of phosphorylated and unmodified peptides from a particular protein indicates tissue-specific phosphorylation. For example, comparison of unmodified and phosphorylated forms of PINFORMED1 (PIN1) suggests a tissue-specific difference in phosphorylation, which correlates with changes in PIN1 polarization in epidermal cells during development. Together, our data provide insights into regulatory processes underlying maize leaf development and provide a community resource cataloging the abundance and phosphorylation status of thousands of maize proteins at four leaf developmental stages. PMID:23933881

Facette, Michelle R.; Shen, Zhouxin; Bjornsdottir, Fjola R.; Briggs, Steven P.; Smith, Laurie G.

2013-01-01

67

Dynamic Adipocyte Phosphoproteome Reveals that Akt Directly Regulates mTORC2  

PubMed Central

Summary A major challenge of the post-genomics era is to define the connectivity of protein phosphorylation networks. Here, we quantitatively delineate the insulin signaling network in adipocytes by high-resolution mass spectrometry-based proteomics. These data reveal the complexity of intracellular protein phosphorylation. We identified 37,248 phosphorylation sites on 5,705 proteins in this single-cell type, with approximately 15% responding to insulin. We integrated these large-scale phosphoproteomics data using a machine learning approach to predict physiological substrates of several diverse insulin-regulated kinases. This led to the identification of an Akt substrate, SIN1, a core component of the mTORC2 complex. The phosphorylation of SIN1 by Akt was found to regulate mTORC2 activity in response to growth factors, revealing topological insights into the Akt/mTOR signaling network. The dynamic phosphoproteome described here contains numerous phosphorylation sites on proteins involved in diverse molecular functions and should serve as a useful functional resource for cell biologists. PMID:23684622

Humphrey, Sean J.; Yang, Guang; Yang, Pengyi; Fazakerley, Daniel J.; Stockli, Jacqueline; Yang, Jean Y.; James, David E.

2013-01-01

68

Versatile nanocomposites in phosphoproteomics: a review.  

PubMed

Protein phosphorylation is one of the most important post-translational modifications. Phosphorylated peptides are present in low abundance in blood serum but play a vital role in regulatory mechanisms and may serve as casual factors in diseases. The enrichment and analysis of phosphorylated peptides directly from human serum and mapping the phosphorylation sites is a challenging task. Versatile nanocomposites of different materials have been synthesized using simple but efficient methodologies for their enrichment. The nanocomposites include magnetic, coated, embedded as well as chemically derivatized materials. Different base materials such as polymers, carbon based and metal oxides are used. The comparison of nanocomposites with respective nanoparticles provides sufficient facts about their efficiency in terms of loading capacity and capture efficiency. The cost for preparing them is low and they hold great promise to be used as chromatographic materials for phosphopeptide enrichment. This review gives an overview of different nanocomposites in phosphoproteomics, discussing the improved efficiency than the individual counterparts and highlighting their significance in phosphopeptide enrichment. PMID:22986130

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

2012-10-17

69

An Initial Characterization of the Serum Phosphoproteome  

PubMed Central

Phosphorylation is a dynamic post-translational protein modification that is the basis of a general mechanism for maintaining and regulating protein structure and function, and of course underpins key cellular processes through signal transduction. In the last several years, many studies of large-scale profiling of phosphoproteins and mapping phosphorylation sites from cultured human cells or tissues by mass spectrometry technique have been published; however, there is little information on general (or global) phosphoproteomic characterization and description of the content of phosphoprotein analytes within the circulation. Circulating phosphoproteins and phosphopeptides could represent important disease biomarkers because of their well-known importance in cellular function, and these analytes frequently are mutated and activated in human diseases such as cancer. Here we report an initial attempt to characterize the phosphoprotein content of serum. To accomplish this, we developed a method in which phosphopeptides are enriched from digested serum proteins and analyzed by LC-MS/MS using LTQ-Orbitrap (CID) and LTQ-ETD mass spectrometers. Using this approach we identified ~100 unique phosphopeptides with stringent filtering criteria and a lower than 1% false discovery rate. PMID:19824718

Zhou, Weidong; Ross, Mark M.; Tessitore, Alessandra; Ornstein, David; VanMeter, Amy; Liotta, Lance A.; Petricoin, Emanuel F.

2009-01-01

70

Evidence for a Minimal Eukaryotic Phosphoproteome?  

PubMed Central

Background Reversible phosphorylation catalysed by kinases is probably the most important regulatory mechanism in eukaryotes. Methodology/Principal Findings We studied the in vitro phosphorylation of peptide arrays exhibiting the majority of PhosphoBase-deposited protein sequences, by factors in cell lysates from representatives of various branches of the eukaryotic species. We derived a set of substrates from the PhosphoBase whose phosphorylation by cellular extracts is common to the divergent members of different kingdoms and thus may be considered a minimal eukaryotic phosphoproteome. The protein kinases (or kinome) responsible for phosphorylation of these substrates are involved in a variety of processes such as transcription, translation, and cytoskeletal reorganisation. Conclusions/Significance These results indicate that the divergence in eukaryotic kinases is not reflected at the level of substrate phosphorylation, revealing the presence of a limited common substrate space for kinases in eukaryotes and suggests the presence of a set of kinase substrates and regulatory mechanisms in an ancestral eukaryote that has since remained constant in eukaryotic life. PMID:17712425

Diks, Sander H.; Parikh, Kaushal; van der Sijde, Marijke; Joore, Jos; Ritsema, Tita; Peppelenbosch, Maikel P.

2007-01-01

71

Analysis of phosphoproteome in rice pistil.  

PubMed

As the female reproductive part of a flower, the pistil consists of the ovary, style, and stigma, and is a critical organ for the process from pollen recognition to fertilization and seed formation. Previous studies on pollen-pistil interaction mainly focused on gene expression changes with comparative transcriptomics or proteomics method. However, studies on protein PTMs are still lacking. Here we report a phosphoproteomic study on mature pistil of rice. Using IMAC enrichment, hydrophilic interaction chromatography fraction and high-accuracy MS instrument (TripleTOF 5600), 2347 of high-confidence (Ascore ? 19, p ? 0.01), phosphorylation sites corresponding to 1588 phosphoproteins were identified. Among them, 1369 phosphorylation sites within 654 phosphoproteins were newly identified; 41 serine phosphorylation motifs, which belong to three groups: proline-directed, basophilic, and acidic motifs were identified after analysis by motif-X. Two hundred and one genes whose phosphopeptides were identified here showed tissue-specific expression in pistil based on information mining of previous microarray data. All MS data have been deposited in the ProteomeXchange with identifier PXD000923 (http://proteomecentral.proteomexchange.org/dataset/PXD000923). This study will help us to understand pistil development and pollination on the posttranslational level. PMID:25074045

Wang, Kun; Zhao, Yong; Li, Ming; Gao, Feng; Yang, Ming-Kun; Wang, Xin; Li, Shaoqing; Yang, Pingfang

2014-10-01

72

Biology teachers' dissection practices and the influences that lead to their adoption: An exploratory research  

NASA Astrophysics Data System (ADS)

The lack of resolution in the on-going animal dissection debate inspired this mixed methods study to identify Connecticut secondary biology teachers' dissection practices and the influences that lead to their adoption. Qualitative findings indicate past experiences, managing objections to dissection, school culture, goals of biology teaching and ethics as major influences on dissection practices with 58.4% (n=7) of the sample dissecting and 41.6% not dissecting (n=5). Quantitative findings reveal gender, standards and curriculum, advantages of dissection and experiences as a student as major influences on dissection practices with 71.9% (n=92) of the sample dissecting and 28.1% (n=36) not dissecting. The study concludes that dissection policies are necessary and imminent in Connecticut school districts. Furthermore, it advises teacher-initiated, qualitative and quantitative assessments to expose disparities between student dissection perspectives and their own, prior to conducting dissection. Finally, it provides suggestions for addressing potential differences including administrative involvement.

Milano, Regina Nicole

73

Using phosphoproteomics to reveal signalling dynamics in plants  

E-print Network

processes, including metabolism [7,8], the cell cycle [9], stress and hormone responses [7,10­14], stomatalUsing phosphoproteomics to reveal signalling dynamics in plants Sergio de la Fuente van Bentem1 and Heribert Hirt1,2 1 Department of Plant Molecular Biology, Max F. Perutz Laboratories, University of Vienna

Hirt, Heribert

74

Evaluation and Properties of the Budding Yeast Phosphoproteome*  

PubMed Central

We have assembled a reliable phosphoproteomic data set for budding yeast Saccharomyces cerevisiae and have investigated its properties. Twelve publicly available phosphoproteome data sets were triaged to obtain a subset of high-confidence phosphorylation sites (p-sites), free of “noisy” phosphorylations. Analysis of this combined data set suggests that the inventory of phosphoproteins in yeast is close to completion, but that these proteins may have many undiscovered p-sites. Proteins involved in budding and protein kinase activity have high numbers of p-sites and are highly over-represented in the vast majority of the yeast phosphoproteome data sets. The yeast phosphoproteome is characterized by a few proteins with many p-sites and many proteins with a few p-sites. We confirm a tendency for p-sites to cluster together and find evidence that kinases may phosphorylate off-target amino acids that are within one or two residues of their cognate target. This suggests that the precise position of the phosphorylated amino acid is not a stringent requirement for regulatory fidelity. Compared with nonphosphorylated proteins, phosphoproteins are more ancient, more abundant, have longer unstructured regions, have more genetic interactions, more protein interactions, and are under tighter post-translational regulation. It appears that phosphoproteins constitute the raw material for pathway rewiring and adaptation at various evolutionary rates. PMID:22286756

Amoutzias, Grigoris D.; He, Ying; Lilley, Kathryn S.; Van de Peer, Yves; Oliver, Stephen G.

2012-01-01

75

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

PubMed Central

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 (phospho)proteomics resource for studying signaling from the point of view of both host and pathogen during a plant–pathogen interaction. PMID:23722186

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

2013-01-01

76

Phosphoproteomics Study Based on In Vivo Inhibition Reveals Sites of Calmodulin-Dependent Protein Kinase II Regulation in the Heart  

PubMed Central

Background The multifunctional Ca2+? and calmodulin?dependent protein kinase II (CaMKII) is a crucial mediator of cardiac physiology and pathology. Increased expression and activation of CaMKII has been linked to elevated risk for arrhythmic events and is a hallmark of human heart failure. A useful approach to determining CaMKII's role therein is large?scale analysis of phosphorylation events by mass spectrometry. However, current large?scale phosphoproteomics approaches have proved inadequate for high?fidelity identification of kinase?specific roles. The purpose of this study was to develop a phosphoproteomics approach to specifically identify CaMKII's downstream effects in cardiac tissue. Methods and Results To identify putative downstream CaMKII targets in cardiac tissue, animals with myocardial?delimited expression of the specific peptide inhibitor of CaMKII (AC3?I) or an inactive control (AC3?C) were compared using quantitative phosphoproteomics. The hearts were isolated after isoproterenol injection to induce CaMKII activation downstream of ??adrenergic receptor agonist stimulation. Enriched phosphopeptides from AC3?I and AC3?C mice were differentially quantified using stable isotope dimethyl labeling, strong cation exchange chromatography and high?resolution LC?MS/MS. Phosphorylation levels of several hundred sites could be profiled, including 39 phosphoproteins noticeably affected by AC3?I?mediated CaMKII inhibition. Conclusions Our data set included known CaMKII substrates, as well as several new candidate proteins involved in functions not previously implicated in CaMKII signaling. PMID:23926118

Scholten, Arjen; Preisinger, Christian; Corradini, Eleonora; Bourgonje, Vincent J.; Hennrich, Marco L.; van Veen, Toon A. B.; Swaminathan, Paari D.; Joiner, Mei-Ling; Vos, Marc A.; Anderson, Mark E.; Heck, Albert J. R.

2013-01-01

77

Proteomics and Phosphoproteomics Analysis of Human Lens Fiber Cell Membranes  

PubMed Central

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

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

2013-01-01

78

Phosphoproteome profiling of the macrophage response to different toll-like receptor ligands identifies differences in global phosphorylation dynamics.  

PubMed

Toll-like receptors (TLRs) are among the first sensors that detect infection and drive immune response. Macrophages encountering a pathogen are usually stimulated not by one TLR, but by a combination of TLRs engaged by distinct microbe ligands. To understand the integrated signaling under complex conditions, we investigated the differences in the phosphoprotein signaling cascades triggered by TLR2, TLR4, and TLR7 ligands using a single responding cell population. We performed a global, quantitative, early poststimulation kinetic analysis of the mouse macrophage phosphoproteome using stable isotope labeling with amino acids coupled to phosphopeptide enrichment and high-resolution mass spectrometry. For each TLR ligand, we found marked elevation of phosphorylation of cytoskeleton components, GTPases of the Rho family, and phospholipase C signaling pathway proteins. Phosphorylation of proteins involved in phagocytosis was only seen in response to TLR2 and TLR4 but not to TLR7 activation. Changes in the phosphorylation of proteins involved in endocytosis were delayed in response to TLR2 as compared to TLR4 ligands. These findings reveal that the phosphoproteomic response to stimulation of distinct TLRs varies both in the major modification targets and the phosphorylation dynamics. These results advance the understanding of how macrophages sense and respond to a diverse set of TLR stimuli. PMID:24941444

Sjoelund, Virginie; Smelkinson, Margery; Nita-Lazar, Aleksandra

2014-11-01

79

The Problems of Dissection.  

ERIC Educational Resources Information Center

Describes some problems of classroom dissection including the cruelty that animals destined for the laboratory suffer. Discusses the multilevel approach that the National Anti-Vivisection Society (NAVS) has developed to address the problems of animal dissection such as offering a dissection hotline, exhibiting at science teacher conferences, and…

Davis, Pat

1997-01-01

80

Phosphoproteomic analysis of chromoplasts from sweet orange during fruit ripening.  

PubMed

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. PMID:23786612

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

2014-02-01

81

Systematic Analysis of Protein Phosphorylation Networks From Phosphoproteomic Data*  

PubMed Central

In eukaryotes, hundreds of protein kinases (PKs) specifically and precisely modify thousands of substrates at specific amino acid residues to faithfully orchestrate numerous biological processes, and reversibly determine the cellular dynamics and plasticity. Although over 100,000 phosphorylation sites (p-sites) have been experimentally identified from phosphoproteomic studies, the regulatory PKs for most of these sites still remain to be characterized. Here, we present a novel software package of iGPS for the prediction of in vivo site-specific kinase-substrate relations mainly from the phosphoproteomic data. By critical evaluations and comparisons, the performance of iGPS is satisfying and better than other existed tools. Based on the prediction results, we modeled protein phosphorylation networks and observed that the eukaryotic phospho-regulation is poorly conserved at the site and substrate levels. With an integrative procedure, we conducted a large-scale phosphorylation analysis of human liver and experimentally identified 9719 p-sites in 2998 proteins. Using iGPS, we predicted a human liver protein phosphorylation networks containing 12,819 potential site-specific kinase-substrate relations among 350 PKs and 962 substrates for 2633 p-sites. Further statistical analysis and comparison revealed that 127 PKs significantly modify more or fewer p-sites in the liver protein phosphorylation networks against the whole human protein phosphorylation network. The largest data set of the human liver phosphoproteome together with computational analyses can be useful for further experimental consideration. This work contributes to the understanding of phosphorylation mechanisms at the systemic level, and provides a powerful methodology for the general analysis of in vivo post-translational modifications regulating sub-proteomes. PMID:22798277

Song, Chunxia; Ye, Mingliang; Liu, Zexian; Cheng, Han; Jiang, Xinning; Han, Guanghui; Songyang, Zhou; Tan, Yexiong; Wang, Hongyang; Ren, Jian; Xue, Yu; Zou, Hanfa

2012-01-01

82

Receptor Tyrosine Kinase Signaling Mechanisms: Devolving TrkA Responses with Phosphoproteomics  

PubMed Central

Receptor tyrosine kinases (RTKs) function through protein kinase entities located in the intracellular domain of each protomer. Following activation by ligand binding, they selectively form phosphotyrosine residues by autocatalytic modification. Some of these sites are involved in maintaining the active conformation of the kinase, while others become docking sites for various adaptor/effector/scaffold proteins, which, after complexing with the receptor, then initiate further responses through cascades of post-translational modifications and the generation of lipid second messengers. Although there is substantial overlap in the pathways and activities stimulated by this superfamily, the molecular features of the endodomains of the sub-families and the moieties that they interact with to perpetrate their signals are surprisingly distinct, which may play a significant role in the regulation and responses of the individual RTK types. Some use large scaffold proteins as the basis for most, if not all, of their signal-generating interactions, while others have numerous receptor endodomain phosphotyrosine sites that are quite overlapping in specificity. The members of the Trk family of receptors each have several tyrosine residues that are phosphorylated following stimulation, including those in the kinase activation loop, but there are only two established sites (Y490 and Y785 on TrkA) that are known to be directly involved in signal propagation. Taking advantage of this limited repertoire of docking sites, we have applied phosphoproteomic methods to dissect the signaling responses of both the native protein and derivatives that have had these two sites modified. Interestingly, a clear subset that was not dependent on either docking site was identified. A comparison with a similar set of data for EGFR indicates a considerable degree of similarity in the downstream signaling profile between these two RTKs. PMID:23266087

Bradshaw, R.A.; Chalkley, R.J.; Biarc, J.; Burlingame, A. L.

2012-01-01

83

Integrative Features of the Yeast Phosphoproteome and Protein–Protein Interaction Map  

Microsoft Academic Search

Following recent advances in high-throughput mass spectrometry (MS)–based proteomics, the numbers of identified phosphoproteins and their phosphosites have greatly increased in a wide variety of organisms. Although a critical role of phosphorylation is control of protein signaling, our understanding of the phosphoproteome remains limited. Here, we report unexpected, large-scale connections revealed between the phosphoproteome and protein interactome by integrative data-mining

Nozomu Yachie; Rintaro Saito; Naoyuki Sugiyama; Masaru Tomita; Yasushi Ishihama

2011-01-01

84

A consensus map of rapeseed (Brassica napus L.) based on diversity array technology markers: applications in genetic dissection of qualitative and quantitative traits  

PubMed Central

Background Dense consensus genetic maps based on high-throughput genotyping platforms are valuable for making genetic gains in Brassica napus through quantitative trait locus identification, efficient predictive molecular breeding, and map-based gene cloning. This report describes the construction of the first B. napus consensus map consisting of a 1,359 anchored array based genotyping platform; Diversity Arrays Technology (DArT), and non-DArT markers from six populations originating from Australia, Canada, China and Europe. We aligned the B. napus DArT sequences with genomic scaffolds from Brassica rapa and Brassica oleracea, and identified DArT loci that showed linkage with qualitative and quantitative loci associated with agronomic traits. Results The integrated consensus map covered a total of 1,987.2?cM and represented all 19 chromosomes of the A and C genomes, with an average map density of one marker per 1.46?cM, corresponding to approximately 0.88 Mbp of the haploid genome. Through in silico physical mapping 2,457 out of 3,072 (80%) DArT clones were assigned to the genomic scaffolds of B. rapa (A genome) and B. oleracea (C genome). These were used to orientate the genetic consensus map with the chromosomal sequences. The DArT markers showed linkage with previously identified non-DArT markers associated with qualitative and quantitative trait loci for plant architecture, phenological components, seed and oil quality attributes, boron efficiency, sucrose transport, male sterility, and race-specific resistance to blackleg disease. Conclusions The DArT markers provide increased marker density across the B. napus genome. Most of the DArT markers represented on the current array were sequenced and aligned with the B. rapa and B. oleracea genomes, providing insight into the Brassica A and C genomes. This information can be utilised for comparative genomics and genomic evolution studies. In summary, this consensus map can be used to (i) integrate new generation markers such as SNP arrays and next generation sequencing data; (ii) anchor physical maps to facilitate assembly of B. napus genome sequences; and (iii) identify candidate genes underlying natural genetic variation for traits of interest. PMID:23617817

2013-01-01

85

Interactive Frog Dissection  

NSDL National Science Digital Library

University of Virginia Curry School of Education's Instructional Technology Program has announced Interactive Frog Dissection. The tutorial combines text with 60 in-line color images and 17 QuickTime movies illustrating dissection procedures and internal organs. Numerous clickable image maps provide interactive practice. Research with pre-Web versions of the program suggests it is a valuable preparation tool or even a useful substitute for laboratory dissection.

86

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

PubMed Central

Plant growth adjustment during water deficit is a crucial adaptive response. The rapid fine-tuned control achieved at the post-translational level is believed to be of considerable importance for regulating early changes in plant growth reprogramming. Aiming at a better understanding of early responses to contrasting plant water statuses, we carried out a survey of the protein phosphorylation events in the growing zone of maize leaves upon a range of water regimes. In this study, the impact of mild and severe water deficits were evaluated in comparison with constant optimal watering and with recovery periods lasting 5, 10, 20, 30, 45, and 60 min. Using four biological replicates per treatment and a robust quantitative phosphoproteomic methodology based on stable-isotope labeling, we identified 3664 unique phosphorylation sites on 2496 proteins. The abundance of nearly 1250 phosphorylated peptides was reproducibly quantified and profiled with high confidence among treatments. A total of 138 phosphopeptides displayed highly significant changes according to water regimes and enabled to identify specific patterns of response to changing plant water statuses. Further quantification of protein amounts emphasized that most phosphorylation changes did not reflect protein abundance variation. During water deficit and recovery, extensive changes in phosphorylation status occurred in critical regulators directly or indirectly involved in plant growth and development. These included proteins influencing epigenetic control, gene expression, cell cycle-dependent processes and phytohormone-mediated responses. Some of the changes depended on stress intensity whereas others depended on rehydration duration, including rapid recoveries that occurred as early as 5 or 10 mins after rewatering. By combining a physiological approach and a quantitative phosphoproteomic analysis, this work provides new insights into the in vivo early phosphorylation events triggered by rapid changes in plant water status, and their possible involvement in plant growth-related processes. PMID:22787273

Bonhomme, Ludovic; Valot, Benoit; Tardieu, Francois; Zivy, Michel

2012-01-01

87

Phosphoproteome dynamics reveal novel ERK1/2 MAP kinase substrates with broad spectrum of functions  

PubMed Central

The ERK1/2 MAP kinase pathway is an evolutionarily conserved signaling module that controls many fundamental physiological processes. Deregulated activity of ERK1/2 MAP kinases is associated with developmental syndromes and several human diseases. Despite the importance of this pathway, a comprehensive picture of the natural substrate repertoire and biochemical mechanisms regulated by ERK1/2 is still lacking. In this study, we used large-scale quantitative phosphoproteomics and bioinformatics analyses to identify novel candidate ERK1/2 substrates based on their phosphorylation signature and kinetic profiles in epithelial cells. We identified a total of 7936 phosphorylation sites within 1861 proteins, of which 155 classify as candidate ERK1/2 substrates, including 128 new targets. Candidate ERK1/2 substrates are involved in diverse cellular processes including transcriptional regulation, chromatin remodeling, RNA splicing, cytoskeleton dynamics, cellular junctions and cell signaling. Detailed characterization of one newly identified substrate, the transcriptional regulator JunB, revealed that ERK1/2 phosphorylate JunB on a serine adjacent to the DNA-binding domain, resulting in increased DNA-binding affinity and transcriptional activity. Our study expands the spectrum of cellular functions controlled by ERK1/2 kinases. PMID:23712012

Courcelles, Mathieu; Fremin, Christophe; Voisin, Laure; Lemieux, Sebastien; Meloche, Sylvain; Thibault, Pierre

2013-01-01

88

Flower Dissection Lab  

NSDL National Science Digital Library

From Fairchild Tropical Botanic Garden, this site presents a simple Flower Dissection Lab using orchids and composite flowers. This pdf document contains the materials needed and instructions for the lab, as well as a worksheet for students to complete as they dissect their flower.

2007-12-27

89

Phosphoproteomic studies in Arabidopsis and tobacco male gametophytes.  

PubMed

Mature pollen represents an extremely resistant quiescent structure surrounded by a tough cell wall. After its hydration on stigma papillary cells, pollen tube growth starts rapidly. Massive metabolic changes are likely to be accompanied by changes in protein phosphorylation. Protein phosphorylation belongs among the most rapid post-translational modifications. To date, only Arabidopsis thaliana and tobacco (Nicotiana tabacum) mature pollen have been subjected to phosphoproteomic studies in order to identify the phosphoproteins present. In the present mini-review, Arabidopsis and tobacco datasets were compared with each other. The representation of the O-phosphorylated amino acids was compared between these two datasets, and the putative pollen-specific or pollen-abundant phosphopeptides were highlighted. Finally, the phosphorylation sites common for both Arabidopsis and tobacco phosphoproteins are listed as well as the phosphorylation motifs identified. PMID:24646248

Fíla, Jan; ?apková, V?ra; Honys, David

2014-04-01

90

Introduction to Dissection  

NSDL National Science Digital Library

Many health science students do not enroll in undergraduate dissection-based anatomy courses during their pre-professional education. As a result, they are not familiar with dissection instruments and the mechanics of dissection, and are poorly prepared for medical, dental, and allied health science anatomy courses. Thus, the first dissections are very challenging and require extensive help from instructors. This program is designed to alleviate those deficits. It serves as an introduction to dissection in a human gross anatomy course for first-year medical and other health science students. It can be used either as a component of a structured classroom session, or, independently by individual students. The content is presented in a series of video clips arranged in two sections, each containing multiple chapters. Section #1 is a guide to the selection of proper dissection instruments. Section #2 is an overview of how to begin the first dissection in the course, including the use of dissection tools. The program is menu-driven, allowing viewing of the entire content in sequence, or, selected chapters in any order. Student and faculty surveys indicate the program prepares students well for and improves time management during the first dissections. It is available as a web-based download and as a CD-ROM. This work was supported in part by NIH P03 1B040107 and G12-RR 03034. Note: The files must be downloaded, unzipped, extracted, and saved to your local system. Download a stand-alone Flash player from Adobe.com.

Wineski, Lawrence

2007-11-20

91

Global molecular dysfunctions in gastric cancer revealed by an integrated analysis of the phosphoproteome and transcriptome  

Microsoft Academic Search

We integrated LC-MS\\/MS-based and protein antibody array-based proteomics with genomics approaches to investigate the phosphoproteome\\u000a and transcriptome of gastric cancer cell lines and endoscopic gastric biopsies from normal subjects and patients with benign\\u000a gastritis or gastric cancer. More than 3,000 non-redundant phosphorylation sites in over 1,200 proteins were identified in\\u000a gastric cancer cells. We correlated phosphoproteome data with transcriptome data

Tiannan Guo; Sze Sing Lee; Wai Har Ng; Yi Zhu; Chee Sian Gan; Jiang Zhu; Haixia Wang; Shiang Huang; Siu Kwan Sze; Oi Lian Kon

2011-01-01

92

Early Phosphoproteomic Changes in the Mouse Spleen During Deoxynivalenol-Induced Ribotoxic Stress  

PubMed Central

The trichothecene mycotoxin deoxynivalenol (DON) targets the innate immune system and is of public health significance because of its frequent presence in human and animal food. DON-induced proinflammatory gene expression and apoptosis in the lymphoid tissue have been associated with a ribotoxic stress response (RSR) that involves rapid phosphorylation of mitogen-activated protein kinases (MAPKs). To better understand the relationship between protein phosphorylation and DON’s immunotoxic effects, stable isotope dimethyl labeling–based proteomics in conjunction with titanium dioxide chromatography was employed to quantitatively profile the immediate (? 30min) phosphoproteome changes in the spleens of mice orally exposed to 5mg/kg body weight DON. A total of 90 phosphoproteins indicative of novel phosphorylation events were significantly modulated by DON. In addition to critical branches and scaffolds of MAPK signaling being affected, DON exposure also altered phosphorylation of proteins that mediate phosphatidylinositol 3-kinase/AKT pathways. Gene ontology analysis revealed that DON exposure affected biological processes such as cytoskeleton organization, regulation of apoptosis, and lymphocyte activation and development, which likely contribute to immune dysregulation associated with DON-induced RSR. Consistent with these findings, DON impacted phosphorylation of proteins within diverse immune cell populations, including monocytes, macrophages, T cells, B cells, dendritic cells, and mast cells. Fuzzy c-means clustering analysis further indicated that DON evoked several distinctive temporal profiles of regulated phosphopeptides. Overall, the findings from this investigation can serve as a template for future focused exploration and modeling of cellular responses associated with the immunotoxicity evoked by DON and other ribotoxins. PMID:23811945

Pestka, James J.

2013-01-01

93

Radiosensitization of Human Leukemic HL-60 Cells by ATR Kinase Inhibitor (VE-821): Phosphoproteomic Analysis  

PubMed Central

DNA damaging agents such as ionizing radiation or chemotherapy are frequently used in oncology. DNA damage response (DDR)—triggered by radiation-induced double strand breaks—is orchestrated mainly by three Phosphatidylinositol 3-kinase-related kinases (PIKKs): Ataxia teleangiectasia mutated (ATM), DNA-dependent protein kinase (DNA-PK) and ATM and Rad3-related kinase (ATR). Their activation promotes cell-cycle arrest and facilitates DNA damage repair, resulting in radioresistance. Recently developed specific ATR inhibitor, VE-821 (3-amino-6-(4-(methylsulfonyl)phenyl)-N-phenylpyrazine-2-carboxamide), has been reported to have a significant radio- and chemo-sensitizing effect delimited to cancer cells (largely p53-deficient) without affecting normal cells. In this study, we employed SILAC-based quantitative phosphoproteomics to describe the mechanism of the radiosensitizing effect of VE-821 in human promyelocytic leukemic cells HL-60 (p53-negative). Hydrophilic interaction liquid chromatography (HILIC)-prefractionation with TiO2-enrichment and nano-liquid chromatography—tandem mass spectrometry (LC-MS/MS) analysis revealed 9834 phosphorylation sites. Proteins with differentially up-/down-regulated phosphorylation were mostly localized in the nucleus and were involved in cellular processes such as DDR, all phases of the cell cycle, and cell division. Moreover, sequence motif analysis revealed significant changes in the activities of kinases involved in these processes. Taken together, our data indicates that ATR kinase has multiple roles in response to DNA damage throughout the cell cycle and that its inhibitor VE-821 is a potent radiosensitizing agent for p53-negative HL-60 cells. PMID:25003641

Salovska, Barbora; Fabrik, Ivo; Durisova, Kamila; Link, Marek; Vavrova, Jirina; Rezacova, Martina; Tichy, Ales

2014-01-01

94

Virtual Pig Dissection  

NSDL National Science Digital Library

Dissection can be an aspect of scientific education that can make some parties queasy, but it is a fascinating way to learn more about the different body systems, their operations, and basic animal anatomy. Entering the world of pig dissection can make budding scientists even more squeamish, but they need never fear, as this site allows these individuals the opportunity to engage in a bit of virtual pig dissection. Originally created by Professor Earl W. Fleck of Whitman CollegeâÂÂs biology department, the site lets users go inside the pig to learn about its various systems, via a set of high-quality color photographs, which can be viewed at different angles and perspectives. Of course, what would a lab be without a quiz? Rounding out the site, visitors can take short quizzes on the pigâÂÂs anatomy and such.

Fleck, Earl W.

95

Is dissection humane?  

PubMed Central

Dissection is being jeopardized in the modern medical education. It has unrelentingly faced the lashes of time and has been the scapegoat for numerous convenient curricula reforms and subjective biases. The cadaver is unparallel in establishing core knowledge among the medical community and it needs to be appreciated in a new light in the “cyber anatomy” realm of today. This article elucidates the medical and ethical validity of continuing human body dissection in medicine which outweighs all the prejudices associated with it. PMID:23908746

Hasan, Tabinda

2011-01-01

96

Alternative synthetic tools to phospho-specific antibodies for phosphoproteome analysis: progress and prospects.  

PubMed

Signal transduction cascades in living systems are often controlled via post-translational phosphorylation and dephosphorylation of proteins. These processes are catalyzed in vivo by kinase and phosphatase enzymes, which consequently play an important role in many disease states, including cancer and immune system disorders. Current techniques for studying the phosphoproteome (isotopic labeling, chromatographic techniques, and phosphospecific antibodies), although undoubtedly very powerful, have yet to provide a generic tool for phosphoproteomic analysis despite the widespread utility such a technique would have. The use of small molecule organic catalysts that can promote selective phosphate esterification could provide a useful alternative to current state-of-the-art techniques for use in, e.g., the labeling and pull-down of phosphorylated proteins. This report reviews current techniques used for phosphoproteomic analysis and the recent use of small molecule peptide-based catalysts in phosphorylation reactions, indicating possible future applications for this type of catalyst as synthetic alternatives to phosphospecific antibodies for phosphoproteome analysis. PMID:24432133

Murray, James I; Spivey, Alan C; Woscholski, Rudiger

2013-07-01

97

Video Gallery: Shark Dissection  

NSDL National Science Digital Library

This video gallery is from the Museum's Seminars on Science, a series of distance-learning courses designed to help educators meet the new national science standards. There are 16 videos each covering dissection of a different part of the dogfish shark. There is a downloadable pdf for each video.

98

Neck dissections: radical to conservative  

PubMed Central

Background Neck dissection is an important surgical procedure for the management of metastatic nodal disease in the neck. The gold standard of neck nodal management has been the radical neck dissection. Any modification in the neck dissection is always compared with this standard. Over the last few decades, in order to alleviate the morbidity of radical neck dissection, several modifications and conservative procedures have been advocated. These procedures retain certain lymphatic or non-lymphatic structures and have been shown not to compromise oncological safety. Methods A literature search of the Medline was carried out for all articles on neck dissections. The articles were systematically reviewed to analyze and trace the evolution of neck dissection. These were then categorized to address the nomenclature, management of node positive and node negative neck including those who had received chemoradiation. Results The present article discusses the neck nodal nomenclature, the radical neck dissection, its modifications and migration to more conservative procedures and possible advances in the near future. Conclusion Radical neck dissection is now replaced with modified radical neck dissections in most situations. Attempts are being made to replace modified radical neck dissections with selective neck dissections for early node positivity. Sentinel node biopsy is being studied to address the issue of node negative neck. More conservative surgeries are likely to replace the 'radical' surgeries of bygone era. This process is facilitated by earlier detection of the disease and better understanding of cancer biology. PMID:15836786

Harish, K

2005-01-01

99

Shark Dissection Webcast  

NSDL National Science Digital Library

View this Webcast dissection of four shark species conducted last August at the Birch Aquarium and narrated by Dr. Jeffrey Graham of the Scripps Institution of Oceanography. This is a rare opportunity to learn from a marine biologist as he examines the internal organs of these sharks for the audience. The site also has several short text sections offering life history and behavioral information for those users interested in learning more about sharks in general.

2001-01-01

100

Combination of Chemical Genetics and Phosphoproteomics for Kinase Signaling Analysis Enables Confident Identification of Cellular Downstream Targets*  

PubMed Central

Delineation of phosphorylation-based signaling networks requires reliable data about the underlying cellular kinase-substrate interactions. We report a chemical genetics and quantitative phosphoproteomics approach that encompasses cellular kinase activation in combination with comparative replicate mass spectrometry analyses of cells expressing either inhibitor-sensitive or resistant kinase variant. We applied this workflow to Plk1 (Polo-like kinase 1) in mitotic cells and induced cellular Plk1 activity by wash-out of the bulky kinase inhibitor 3-MB-PP1, which targets a mutant kinase version with an enlarged catalytic pocket while not interfering with wild-type Plk1. We quantified more than 20,000 distinct phosphorylation sites by SILAC, approximately half of which were measured in at least two independent experiments in cells expressing mutant and wild-type Plk1. Based on replicate phosphorylation site quantifications in both mutant and wild-type Plk1 cells, our chemical genetic proteomics concept enabled stringent comparative statistics by significance analysis of microarrays, which unveiled more than 350 cellular downstream targets of Plk1 validated by full concordance of both statistical and experimental data. Our data point to hitherto poorly characterized aspects in Plk1-controlled mitotic progression and provide a largely extended resource for functional studies. We anticipate the described strategies to be of general utility for systematic and confident identification of cellular protein kinase substrates. PMID:22199227

Oppermann, Felix S.; Grundner-Culemann, Kathrin; Kumar, Chanchal; Gruss, Oliver J.; Jallepalli, Prasad V.; Daub, Henrik

2012-01-01

101

Confident and sensitive phosphoproteomics using combinations of collision induced dissociation and electron transfer dissociation?  

PubMed Central

We present a workflow using an ETD-optimised version of Mascot Percolator and a modified version of SLoMo (turbo-SLoMo) for analysis of phosphoproteomic data. We have benchmarked this against several database searching algorithms and phosphorylation site localisation tools and show that it offers highly sensitive and confident phosphopeptide identification and site assignment with PSM-level statistics, enabling rigorous comparison of data acquisition methods. We analysed the Plasmodium falciparum schizont phosphoproteome using for the first time, a data-dependent neutral loss-triggered-ETD (DDNL) strategy and a conventional decision-tree method. At a posterior error probability threshold of 0.01, similar numbers of PSMs were identified using both methods with a 73% overlap in phosphopeptide identifications. The false discovery rate associated with spectral pairs where DDNL CID/ETD identified the same phosphopeptide was < 1%. 72% of phosphorylation site assignments using turbo-SLoMo without any score filtering, were identical and 99.8% of these cases are associated with a false localisation rate of < 5%. We show that DDNL acquisition is a useful approach for phosphoproteomics and results in an increased confidence in phosphopeptide identification without compromising sensitivity or duty cycle. Furthermore, the combination of Mascot Percolator and turbo-SLoMo represents a robust workflow for phosphoproteomic data analysis using CID and ETD fragmentation. Biological significance Protein phosphorylation is a ubiquitous post-translational modification that regulates protein function. Mass spectrometry-based approaches have revolutionised its analysis on a large-scale but phosphorylation sites are often identified by single phosphopeptides and therefore require more rigorous data analysis to unsure that sites are identified with high confidence for follow-up experiments to investigate their biological significance. The coverage and confidence of phosphoproteomic experiments can be enhanced by the use of multiple complementary fragmentation methods. Here we have benchmarked a data analysis pipeline for analysis of phosphoproteomic data generated using CID and ETD fragmentation and used it to demonstrate the utility of a data-dependent neutral loss triggered ETD fragmentation strategy for high confidence phosphopeptide identification and phosphorylation site localisation. PMID:24657495

Collins, Mark O.; Wright, James C.; Jones, Matthew; Rayner, Julian C.; Choudhary, Jyoti S.

2014-01-01

102

Identifying Drug Effects via Pathway Alterations using an Integer Linear Programming Optimization Formulation on Phosphoproteomic Data  

Microsoft Academic Search

Understanding the mechanisms of cell function and drug action is a major endeavor in the pharmaceutical industry. Drug effects are governed by the intrinsic properties of the drug (i.e., selectivity and potency) and the specific signaling transduction network of the host (i.e., normal vs. diseased cells). Here, we describe an unbiased, phosphoproteomic-based approach to identify drug effects by monitoring drug-induced

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

2009-01-01

103

Global phosphoproteomic profiling reveals distinct signatures in B-cell non-Hodgkin lymphomas.  

PubMed

Deregulation of signaling pathways controlled by protein phosphorylation underlies the pathogenesis of hematological malignancies; however, the extent to which deregulated phosphorylation may be involved in B-cell non-Hodgkin lymphoma (B-NHL) pathogenesis is largely unknown. To identify phosphorylation events important in B-NHLs, we performed mass spectrometry-based, label-free, semiquantitative phosphoproteomic profiling of 11 cell lines derived from three B-NHL categories: Burkitt lymphoma, follicular lymphoma, and mantle-cell lymphoma. In all, 6579 unique phosphopeptides, corresponding to 1701 unique phosphorylated proteins, were identified and quantified. The data are available via ProteomeXchange with identifier PXD000658. Hierarchical clustering highlighted distinct phosphoproteomic signatures associated with each lymphoma subtype. Interestingly, germinal center-derived B-NHL cell lines were characterized by phosphorylation of proteins involved in the B-cell receptor signaling. Of these proteins, phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1) was identified with the most phosphorylated tyrosine peptides in Burkitt lymphoma and follicular lymphoma. PAG1 knockdown resulted in perturbation of the tyrosine phosphosignature of B-cell receptor signaling components. Significantly, PAG1 knockdown increased cell proliferation and response to antigen stimulation of these germinal center-derived B-NHLs. These data provide a detailed annotation of phosphorylated proteins in human lymphoid cancer. Overall, our study revealed the utility of unbiased phosphoproteome interrogation in characterizing signaling networks that may provide insights into pathogenesis mechanisms in B-cell lymphomas. PMID:24667141

Rolland, Delphine; Basrur, Venkatesha; Conlon, Kevin; Wolfe, Thomas; Fermin, Damian; Nesvizhskii, Alexey I; Lim, Megan S; Elenitoba-Johnson, Kojo S J

2014-05-01

104

Predicting Kinase Activity in Angiotensin Receptor Phosphoproteomes Based on Sequence-Motifs and Interactions  

PubMed Central

Recent progress in the understanding of seven-transmembrane receptor (7TMR) signalling has promoted the development of a new generation of pathway selective ligands. The angiotensin II type I receptor (AT1aR) is one of the most studied 7TMRs with respect to selective activation of the ?-arrestin dependent signalling. Two complimentary global phosphoproteomics studies have analyzed the complex signalling induced by the AT1aR. Here we integrate the data sets from these studies and perform a joint analysis using a novel method for prediction of differential kinase activity from phosphoproteomics data. The method builds upon NetworKIN, which applies sophisticated linear motif analysis in combination with contextual network modelling to predict kinase-substrate associations with high accuracy and sensitivity. These predictions form the basis for subsequently nonparametric statistical analysis to identify likely activated kinases. This suggested that AT1aR-dependent signalling activates 48 of the 285 kinases detected in HEK293 cells. Of these, Aurora B, CLK3 and PKG1 have not previously been described in the pathway whereas others, such as PKA, PKB and PKC, are well known. In summary, we have developed a new method for kinase-centric analysis of phosphoproteomes to pinpoint differential kinase activity in large-scale data sets. PMID:24722691

B?gebo, Rikke; Horn, Heiko; Olsen, Jesper V.; Gammeltoft, Steen; Jensen, Lars J.; Hansen, Jakob L.; Christensen, Gitte L.

2014-01-01

105

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

PubMed Central

Specific oxidized phospholipids (oxPCCD36) promote platelet hyper-reactivity and thrombosis in hyperlipidemia via the scavenger receptor CD36, however the signaling pathway(s) induced in platelets by oxPCCD36 are not well defined. We have employed mass spectrometry-based tyrosine, serine, and threonine phosphoproteomics for the unbiased analysis of platelet signaling pathways induced by oxPCCD36 as well as by the strong physiological agonist thrombin. oxPCCD36 and thrombin induced differential phosphorylation of 115 proteins (162 phosphorylation sites) and 181 proteins (334 phosphorylation sites) respectively. Most of the phosphoproteome changes induced by either agonist have never been reported in platelets; thus they provide candidates in the study of platelet signaling. Bioinformatic analyses of protein phosphorylation dependent responses were used to categorize preferential motifs for (de)phosphorylation, predict pathways and kinase activity, and construct a phosphoproteome network regulating integrin activation. A putative signaling pathway involving Src-family kinases, SYK, and PLC?2 was identified in platelets activated by oxPCCD36. Subsequent ex vivo studies in human platelets demonstrated that this pathway is downstream of the scavenger receptor CD36 and is critical for platelet activation by oxPCCD36. Our results provide multiple insights into the mechanism of platelet activation and specifically in platelet regulation by oxPCCD36. PMID:24400094

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

2014-01-01

106

Tandem metal-oxide affinity chromatography for enhanced depth of phosphoproteome analysis.  

PubMed

In eukaryotic cells many diverse cellular functions are regulated by reversible protein phosphorylation. In recent years, phosphoproteomics has become a powerful tool to study protein phosphorylation because it allows unbiased localization, and site-specific quantification, of in vivo phosphorylation of hundreds of proteins in a single experiment. A common strategy to identify phosphoproteins and their phosphorylation sites from complex biological samples is the enrichment of phosphopeptides from digested cellular lysates followed by mass spectrometry. However, despite the high sensitivity of modern mass spectrometers the large dynamic range of protein abundance and the transient nature of protein phosphorylation remained major pitfalls in MS-based phosphoproteomics. Tandem metal-oxide affinity chromatography (MOAC) represents a robust and highly selective approach for the identification and site-specific quantification of low abundant phosphoproteins that is based on the successive enrichment of phosphoproteins and -peptides. This strategy combines protein extraction under denaturing conditions, phosphoprotein enrichment using Al(OH)3-based MOAC, tryptic digestion of enriched phosphoproteins followed by TiO2-based MOAC of phosphopeptides. Thus, tandem MOAC effectively targets the phosphate moiety of phosphoproteins and phosphopeptides and, thus, allows probing of the phosphoproteome to unprecedented depth. PMID:24136551

Beckers, Gerold J M; Hoehenwarter, Wolfgang; Röhrig, Horst; Conrath, Uwe; Weckwerth, Wolfram

2014-01-01

107

Searching for Novel Cdk5 Substrates in Brain by Comparative Phosphoproteomics of Wild Type and Cdk5?/? Mice  

PubMed Central

Protein phosphorylation is the most common post-translational modification that regulates several pivotal functions in cells. Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase which is mostly active in the nervous system. It regulates several biological processes such as neuronal migration, cytoskeletal dynamics, axonal guidance and synaptic plasticity among others. In search for novel substrates of Cdk5 in the brain we performed quantitative phosphoproteomics analysis, isolating phosphoproteins from whole brain derived from E18.5 Cdk5+/+ and Cdk5?/? embryos, using an Immobilized Metal-Ion Affinity Chromatography (IMAC), which specifically binds to phosphorylated proteins. The isolated phosphoproteins were eluted and isotopically labeled for relative and absolute quantitation (iTRAQ) and mass spectrometry identification. We found 40 proteins that showed decreased phosphorylation at Cdk5?/? brains. In addition, out of these 40 hypophosphorylated proteins we characterized two proteins, :MARCKS (Myristoylated Alanine-Rich protein Kinase C substrate) and Grin1 (G protein regulated inducer of neurite outgrowth 1). MARCKS is known to be phosphorylated by Cdk5 in chick neural cells while Grin1 has not been reported to be phosphorylated by Cdk5. When these proteins were overexpressed in N2A neuroblastoma cell line along with p35, serine phosphorylation in their Cdk5 motifs was found to be increased. In contrast, treatments with roscovitine, the Cdk5 inhibitor, resulted in an opposite effect on serine phosphorylation in N2A cells and primary hippocampal neurons transfected with MARCKS. In summary, the results presented here identify Grin 1 as novel Cdk5 substrate and confirm previously identified MARCKS as a a bona fide Cdk5 substrate. PMID:24658276

Contreras-Vallejos, Erick; Utreras, Elias; Borquez, Daniel A.; Prochazkova, Michaela; Terse, Anita; Jaffe, Howard; Toledo, Andrea; Arruti, Cristina; Pant, Harish C.; Kulkarni, Ashok B.; Gonzalez-Billault, Christian

2014-01-01

108

Identification of the PLK2-Dependent Phosphopeptidome by Quantitative Proteomics  

PubMed Central

Polo-like kinase 2 (PLK2) has been recently recognized as the major enzyme responsible for phosphorylation of ?-synuclein at S129 in vitro and in vivo, suggesting that this kinase may play a key role in the pathogenesis of Parkinson's disease and other synucleinopathies. Moreover PLK2 seems to be implicated in cell division, oncogenesis, and synaptic regulation of the brain. However little is known about the phosphoproteome generated by PLK2 and, consequently the overall impact of PLK2 on cellular signaling. To fill this gap we exploited an approach based on in vitro kinase assay and quantitative phosphoproteomics. A proteome-derived peptide library obtained by digestion of undifferentiated human neuroblastoma cell line was exhaustively dephosphorylated by lambda phosphatase followed by incubation with or without PLK2 recombinant kinase. Stable isotope labeling based quantitative phosphoproteomics was applied to identify the phosphosites generated by PLK2. A total of 98 unique PLK2-dependent phosphosites from 89 proteins were identified by LC-MS/MS. Analysis of the primary structure of the identified phosphosites allowed the detailed definition of the kinase specificity and the compilation of a list of potential PLK2 targets among those retrieved in PhosphositePlus, a curated database of in cell/vivo phosphorylation sites. PMID:25338102

Franchin, Cinzia; Cesaro, Luca; Pinna, Lorenzo A.; Arrigoni, Giorgio; Salvi, Mauro

2014-01-01

109

"Dissection" of a Hair Dryer  

ERIC Educational Resources Information Center

The electrical design of the common hair dryer is based almost entirely on relatively simple principles learned in introductory physics classes. Just as biology students dissect a frog to see the principles of anatomy in action, physics students can "dissect" a hair dryer to see how principles of electricity are used in a real system. They can…

Eisenstein, Stan; Simpson, Jeff

2008-01-01

110

Global Quantitative SILAC Phosphoproteomics Reveals Differential Phosphorylation Is Widespread between the Procyclic and  

E-print Network

tsetse fly. The disease is usually fatal if left untreated and is estimated to be responsible for around, then in the second stage enters the cerebral-spinal fluid and brain, resulting in coma and death. When a tsetse fly

Schnaufer, Achim

111

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

PubMed Central

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

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

112

Spontaneous Arterial Dissection.  

PubMed

There is no controlled study for the best treatment or management of cervico-cerebral artery dissection (CAD). Rationale initial empiric treatment in acute CAD to prevent secondary embolism is partial thromboplastin time (PTT)-guided anticoagulation by intravenous heparin followed by anticoagulation with warfarin. Carotid surgery for treatment of CAD is not recommended anymore with the possible exception of persisting severe stenosis of the proximal internal carotid artery (ICA). There could be use of carotid angioplasty by balloon dilatation and stenting in selected cases of severe cerebral hemodynamic impairment by bilateral CAD. Duration of secondary prophylaxis by anticoagulation is best guided by Doppler sonography follow-up, and should be continued until normalization of blood flow or until at least 1 year after the vessel is occluded. There is no evidence that pseudoaneurysms increase the risk for embolic complication, and there is no evidence for surgery or continuation of anticoagulation in patients with pseudoaneurysms. Caution should be recommended for exercises that involve excessive head movements (eg, bungee jumping, trampoline jumping, and chiropractic maneuvers). The patient should be informed that recurrent rate is low in nonfamilial cases. Doppler sonography is a low-cost and high-sensitivity method for patients at risk. PMID:11487460

Brandt, Tobias; Caplan, Louis

2001-09-01

113

Experience with parametric binary dissection  

NASA Technical Reports Server (NTRS)

Parametric Binary Dissection (PBD) is a new algorithm that can be used for partitioning graphs embedded in 2- or 3-dimensional space. It partitions explicitly on the basis of nodes + (lambda)x(edges cut), where lambda is the ratio of time to communicate over an edge to the time to compute at a node. The new algorithm is faster than the original binary dissection algorithm and attempts to obtain better partitions than the older algorithm, which only takes nodes into account. The performance of parametric dissection with plain binary dissection on 3 large unstructured 3-d meshes obtained from computational fluid dynamics and on 2 random graphs were compared. It was showm that the new algorithm can usually yield partitions that are substantially superior, but that its performance is heavily dependent on the input data.

Bokhari, Shahid H.

1993-01-01

114

Sequential phosphoproteomic enrichment through complementary metal-directed immobilized metal ion affinity chromatography.  

PubMed

Methodologies to enrich heterogeneous types of phosphopeptides are critical for comprehensive mapping of the under-explored phosphoproteome. Taking advantage of the distinct binding affinities of Ga(3+) and Fe(3+) for phosphopeptides, we designed a metal-directed immobilized metal ion affinity chromatography for the sequential enrichment of phosphopeptides. In Raji B cells, the sequential Ga(3+)-Fe(3+)-immobilized metal affinity chromatography (IMAC) strategy displayed a 1.5-3.5-fold superior phosphoproteomic coverage compared to single IMAC (Fe(3+), Ti(4+), Ga(3+), and Al(3+)). In addition, up to 92% of the 6283 phosphopeptides were uniquely enriched in either the first Ga(3+)-IMAC (41%) or second Fe(3+)-IMAC (51%). The complementary properties of Ga(3+) and Fe(3+) were further demonstrated through the exclusive enrichment of almost all of 1214 multiply phosphorylated peptides (99.4%) in the Ga(3+)-IMAC, whereas only 10% of 5069 monophosphorylated phosphopeptides were commonly enriched in both fractions. The application of sequential Ga(3+)-Fe(3+)-IMAC to human lung cancer tissue allowed the identification of 2560 unique phosphopeptides with only 8% overlap. In addition to the above-mentioned mono- and multiply phosphorylated peptides, this fractionation ability was also demonstrated on the basic and acidic phosphopeptides: acidophilic phosphorylation sites were predominately enriched in the first Ga(3+)-IMAC (72%), while Pro-directed (85%) and basophilic (79%) phosphorylation sites were enriched in the second Fe(3+)-IMAC. This strategy provided complementary mapping of different kinase substrates in multiple cellular pathways related to cancer invasion and metastasis of lung cancer. Given the fractionation ability and ease of tip preparation of this Ga(3+)-Fe(3+)-IMAC, we propose that this strategy allows more comprehensive characterization of the phosphoproteome both in vitro and in vivo. PMID:24313913

Tsai, Chia-Feng; Hsu, Chuan-Chih; Hung, Jo-Nan; Wang, Yi-Ting; Choong, Wai-Kok; Zeng, Ming-Yao; Lin, Pei-Yi; Hong, Ruo-Wei; Sung, Ting-Yi; Chen, Yu-Ju

2014-01-01

115

Phosphoproteome analysis of isoflurane-protected heart mitochondria: phosphorylation of adenine nucleotide translocator-1 on Tyr194 regulates mitochondrial function  

Microsoft Academic Search

Aims Reversible phosphorylation of mitochondrial proteins is essential in the regulation of respiratory function, energy metabolism, and mitochondrion-mediated cell death. We hypothesized that mitochon- drial protein phosphorylation plays a critical role in cardioprotection during pre and postconditioning, two of the most efficient anti-ischaemic therapies. Methods and results Using phosphoproteomic approaches, we investigated the profiles of phosphory- lated proteins in Wistar

Jianhua Feng; Min Zhu; Marcus C. Schaub; Peter Gehrig; Bernd Roschitzki; Eliana Lucchinetti; Michael Zaugg

116

Phosphoproteomic and Bioinformatic Characterization of the Signaling Alterations in Response to a PP2A Activator in Lung Cancer  

E-print Network

to a PP2A Activator in Lung Cancer Danica Wiredja1, Yu Liu1, Giridharan Gokulrangan1, Daniela Schlatzer1 cell lung cancer involves the coordinate activation of multiple oncogenic pathways, including the MAPK, the spectrum of perturbations in the phosphoproteome of cancer cells induced by these compounds is unknown

Yang, Sichun

117

Proteomic and phosphoproteomic analyses of chromatin-associated proteins from Arabidopsis thaliana.  

PubMed

The nucleus is the organelle where basically all DNA-related processes take place in eukaryotes, such as replication, transcription, and splicing as well as epigenetic regulation. The identification and description of the nuclear proteins is one of the requisites toward a comprehensive understanding of the biological functions accomplished in the nucleus. Many of the regulatory mechanisms of protein functions rely on their PTMs among which phosphorylation is probably one of the most important properties affecting enzymatic activity, interaction with other molecules, localization, or stability. So far, the nuclear and subnuclear proteome and phosphoproteome of the model plant Arabidopsis thaliana have been the subject of very few studies. In this work, we developed a purification protocol of Arabidopsis chromatin-associated proteins and performed proteomic and phosphoproteomic analyses identifying a total of 879 proteins of which 198 were phosphoproteins that were mainly involved in chromatin remodeling, transcriptional regulation, and RNA processing. From 230 precisely localized phosphorylation sites (phosphosites), 52 correspond to hitherto unidentified sites. This protocol and data thereby obtained should be a valuable resource for many domains of plant research. PMID:24889360

Bigeard, Jean; Rayapuram, Naganand; Bonhomme, Ludovic; Hirt, Heribert; Pflieger, Delphine

2014-10-01

118

Phosphoproteomic profiling reveals vasopressin-regulated phosphorylation sites in collecting duct.  

PubMed

Protein phosphorylation is an important component of vasopressin signaling in the renal collecting duct, but the database of known phosphoproteins is incomplete. We used tandem mass spectrometry to identify vasopressin-regulated phosphorylation events in isolated rat inner medullary collecting duct (IMCD) suspensions. Using multiple search algorithms to identify the phosphopeptides from spectral data, we expanded the size of the existing collecting duct phosphoproteome database from 367 to 1187 entries. Label-free quantification in vasopressin- and vehicle-treated samples detected a significant change in the phosphorylation of 29 of 530 quantified phosphopeptides. The targets include important structural, regulatory, and transporter proteins. The vasopressin-regulated sites included two known sites (Ser-486 and Ser-499) present in the urea channel UT-A1 and one previously unknown site (Ser-84) on vasopressin-sensitive urea channels UT-A1 and UT-A3. In vitro assays using synthetic peptides showed that purified protein kinase A (PKA) could phosphorylate all three sites, and immunoblotting confirmed the PKA dependence of Ser-84 and Ser-486 phosphorylation. These results expand the known list of collecting duct phosphoproteins and highlight the utility of targeted phosphoproteomic approaches. PMID:20075062

Bansal, Amar D; Hoffert, Jason D; Pisitkun, Trairak; Hwang, Shelly; Chou, Chung-Lin; Boja, Emily S; Wang, Guanghui; Knepper, Mark A

2010-02-01

119

Phosphoproteomic analysis of Rhodopseudomonas palustris reveals the role of pyruvate phosphate dikinase phosphorylation in lipid production.  

PubMed

Rhodopseudomonas palustris (R. palustris) is a purple nonsulfur anoxygenic phototrophic bacterium with metabolic versatility and is able to grow under photoheterotrophic and chemoheterotrophic states. It has uses in carbon management, carbon recycling, hydrogen generation, and lipid production; therefore, it has the potential for bioenergy production and biodegradation. This study is the first to identify the phosphoproteome of R. palustris including 100 phosphopeptides from 54 phosphoproteins and 74 phosphopeptides from 42 phosphoproteins in chemoheterotrophic and photoheterotrophic growth conditions, respectively. In the identified phosphoproteome, phosphorylation at the threonine residue, Thr487, of pyruvate phosphate dikinase (PPDK, RPA1051) was found to participate in the regulation of carbon metabolism. Here, we show that PPDK enzyme activity is higher in photoheterotrophic growth, with Thr487 phosphorylation as a possible mediator. Under the same photoheterotrophic conditions, R. palustris with overexpressed wild-type PPDK showed an enhanced accumulation of total lipids than those with mutant PPDK (T487V) form. This study reveals the role of the PPDK in the production of biodiesel material, lipid content, with threonyl-phosphorylation as one of the possible regulatory events during photoheterotrophic growth in R. palustris. PMID:23030682

Hu, Chia-Wei; Lin, Miao-Hsia; Huang, Hsuan-Cheng; Ku, Wei-Chi; Yi, Tsun-Hsuan; Tsai, Chia-Feng; Chen, Yu-Ju; Sugiyama, Naoyuki; Ishihama, Yasushi; Juan, Hsueh-Fen; Wu, Shih-Hsiung

2012-11-01

120

Cardiac phosphoproteomics during remote ischemic preconditioning: a role for the sarcomeric Z-disk proteins.  

PubMed

Remote ischemic preconditioning (RIPC) induced by brief ischemia/reperfusion cycles of remote organ (e.g., limb) is cardioprotective. The myocardial cellular changes during RIPC responsible for this phenomenon are not currently known. The aim of this work was to identify the activation by phosphorylation of cardiac proteins following RIPC. To achieve our aim we used isobaric tandem mass tagging (TMT) and reverse phase nanoliquid chromatography tandem spectrometry using a Linear Trap Quadropole (LTQ) Orbitrap Velos mass spectrometer. Male C57/Bl6 mice were anesthetized by an intraperitoneal injection of Tribromoethanol. A cuff was placed around the hind limb and inflated at 200?mmHg to prevent blood flow as confirmed by Laser Doppler Flowmetry. RIPC was induced by 4 cycles of 5?min of limb ischemia followed by 5?min of reperfusion. Hearts were extracted for phosphoproteomics. We identified approximately 30 phosphoproteins that were differentially expressed in response to RIPC protocol. The levels of several phosphoproteins in the Z-disk of the sarcomere including phospho-myozenin-2 were significantly higher than control. This study describes and validates a novel approach to monitor the changes in the cardiac phosphoproteome following the cardioprotective intervention of RIPC and prior to index ischemia. The increased level of phosphorylated sarcomeric proteins suggests they may have a role in cardiac signaling during RIPC. PMID:24795895

Abdul-Ghani, Safa; Heesom, Kate J; Angelini, Gianni D; Suleiman, M-Saadeh

2014-01-01

121

Cardiac Phosphoproteomics during Remote Ischemic Preconditioning: A Role for the Sarcomeric Z-Disk Proteins  

PubMed Central

Remote ischemic preconditioning (RIPC) induced by brief ischemia/reperfusion cycles of remote organ (e.g., limb) is cardioprotective. The myocardial cellular changes during RIPC responsible for this phenomenon are not currently known. The aim of this work was to identify the activation by phosphorylation of cardiac proteins following RIPC. To achieve our aim we used isobaric tandem mass tagging (TMT) and reverse phase nanoliquid chromatography tandem spectrometry using a Linear Trap Quadropole (LTQ) Orbitrap Velos mass spectrometer. Male C57/Bl6 mice were anesthetized by an intraperitoneal injection of Tribromoethanol. A cuff was placed around the hind limb and inflated at 200?mmHg to prevent blood flow as confirmed by Laser Doppler Flowmetry. RIPC was induced by 4 cycles of 5?min of limb ischemia followed by 5?min of reperfusion. Hearts were extracted for phosphoproteomics. We identified approximately 30 phosphoproteins that were differentially expressed in response to RIPC protocol. The levels of several phosphoproteins in the Z-disk of the sarcomere including phospho-myozenin-2 were significantly higher than control. This study describes and validates a novel approach to monitor the changes in the cardiac phosphoproteome following the cardioprotective intervention of RIPC and prior to index ischemia. The increased level of phosphorylated sarcomeric proteins suggests they may have a role in cardiac signaling during RIPC. PMID:24795895

Abdul-Ghani, Safa; Heesom, Kate J.; Angelini, Gianni D.; Suleiman, M-Saadeh

2014-01-01

122

An integrated comparative phosphoproteomic and bioinformatic approach reveals a novel class of MPM-2 motifs upregulated in EGFRvIII-expressing Glioblastoma Cells  

E-print Network

Glioblastoma (GBM, WHO grade IV) is an aggressively proliferative and invasive brain tumor that carries a poor clinical prognosis with a median survival of 9 to 12 months. In a prior phosphoproteomic study performed in the ...

Joughin, Brian A.

123

Rapid and reproducible single-stage phosphopeptide enrichment of complex peptide mixtures: application to general and phosphotyrosine-specific phosphoproteomics experiments.  

PubMed

Reversible protein phosphorylation is an essential regulatory component of virtually every cellular process and is frequently dysregulated in cancer. However, significant analytical barriers persist that hamper the routine application of phosphoproteomics in translational settings. Here, we present a straightforward and reproducible approach for the broadscale analysis of protein phosphorylation that relies on a single phosphopeptide enrichment step using titanium dioxide microspheres from whole cell lysate digests and compared it to the well-established SCX-TiO(2) workflow for phosphopeptide purification on a proteome-wide scale. We demonstrate the scaleabilty of our approach from 200 ?g to 5 mg of total NCI-H23 non-small cell lung adenocarcinoma cell lysate digest and determine its quantitative reproducibility by label-free analysis of phosphopeptide peak areas from replicate purifications (median CV: 20% RSD). Finally, we combine this approach with immunoaffinity phosphotyrosine enrichment, enabling the identification of 3168 unique nonredundant phosphotyrosine peptides in two LC-MS/MS runs from 8 mg of HeLa peptides, each with 80% phosphotyrosine selectivity, at a peptide FDR of 0.2%. Taken together, we establish and validate a robust approach for proteome-wide phosphorylation analysis in a variety of scenarios that is easy to implement in biomedical research and translational settings. PMID:21899308

Kettenbach, Arminja N; Gerber, Scott A

2011-10-15

124

Morphological Variation in Leaf Dissection of Rheum palmatum Complex (Polygonaceae)  

PubMed Central

Aims Rheum palmatum complex comprises all taxa within section Palmata in the genus Rheum, including R. officinale, R. palmatum, R. tanguticum, R. tanguticum var. liupanshanense and R. laciniatum. The identification of the taxa in section Palmata is based primarily on the degree of leaf blade dissection and the shape of the lobes; however, difficulties in species identification may arise from their significant variation. The aim of this study is to analyze the patterns of variation in leaf blade characteristics within and among populations through population-based sampling covering the entire distribution range of R. palmatum complex. Methods Samples were taken from 2340 leaves from 780 individuals and 44 populations representing the four species, and the degree of leaf blade dissection and the shape of the lobe were measured to yield a set of quantitative data. Furthermore, those data were statistically analyzed. Important Findings The statistical analysis showed that the degree of leaf blade dissection is continuous from lobed to parted, and the shape of the lobe is also continuous from broadly triangular to lanceolate both within and between populations. We suggested that taxa in section Palmata should be considered as one species. Based on the research on the R. palmatum complex, we considered that the quantitative characteristics were greatly influenced by the environment. Therefore, it is not reliable to delimitate the species according to the continuously quantitative vegetative characteristics. PMID:25349989

Wang, Xu-Mei; Hou, Xiao-Qi; Zhang, Yu-Qu; Li, Yan

2014-01-01

125

Keeping Dissection Alive for Medical Students  

NSDL National Science Digital Library

This article describes an experiential course with the goal of immersing medical students in a cadaver dissection course abroad. The course was developed because of a reduction in cadaver opportunities and a desire by medical students to gain dissection skills.

2009-11-01

126

Dissect Your Squid and Eat It Too!  

ERIC Educational Resources Information Center

Introduces a science lab activity in which students dissect fresh squids in groups of four and observe the anatomy. Parent volunteers cook the squid mantle for kids to taste. Includes directions for squid dissection. (YDS)

McGinnis, Patricia

2001-01-01

127

Animal Rights Activism Threatens Dissection.  

ERIC Educational Resources Information Center

Discussed is the movement against the use of dissections in science laboratories. Examples of protests across the United States are included. Compared is the plight of using animals in a biology classroom and the demise of the teaching of evolution in some areas. (KR)

Holden, Constance

1990-01-01

128

Dissection & Science Fairs. [Information Packet.  

ERIC Educational Resources Information Center

This collection of pamphlets and articles reprinted from other National Anti-Vivisection Society (NAVS) publications was compiled to address the issues of classroom laboratory dissection and the use of animals in science fair projects. Three of the pamphlets contained in this packet are student handbooks designed to help students of elementary,…

National Anti-Vivisection Society, Chicago, IL.

129

Traumatic bilateral vertebral artery dissection.  

PubMed

Traumatic vertebral artery dissection is not often seen by forensic pathologists, and cases investigated are scarce in the forensic literature. We present the case of a 40-year-old woman cyclist who was struck by a car while wearing a helmet, and was neurologically near normal immediately thereafter at Emergency. She presented 48 h later with acute right hemiparesis, decreasing level of consciousness, and unsteadiness. CT revealed massive cerebellar infarction. CT angiography was normal. The patient died in coma 7 days after injury and autopsy revealed bilateral edematous cerebellar infarction and bilateral vertebral artery dissection. Rotational neck injury and mural tear in the wall of the Atlantic parts of both vertebral arteries is suggested as the possible mechanism of the arterial injury. Head and neck injuries are reported as a precipitating cause of vertebral artery injury. The possible influence of trauma may be further underestimated if longer intervals between vessel dissection and ischemia occur. The current case illustrates that "talk-and-die" syndrome may be due to occult vertebral artery dissection, possibly bilateral. In forensic cases of delayed death after mild trauma to the head and neck, the vertebral arteries should be examined for the cause of death. PMID:21798679

Galtés, Ignasi; Borondo, Juan Carlos; Cos, Mònica; Subirana, Mercè; Martin-Fumadó, Carles; Martín, Carles; Castellà, Josep; Medallo, Jordi

2012-01-10

130

Acute aortic dissection related to crack cocaine  

Microsoft Academic Search

Background—Although single case reports have described acute aortic dissection in relation to cocaine use, this condition is not widely recognized, and the features of cocaine-related aortic dissection have not been defined. Methods and Results—We reviewed all available hospital charts from 1981 to 2001 with the ICD-9 diagnosis of aortic dissection. Among the 38 cases of acute aortic dissection, 14 (37%)

Priscilla Y. Hsue; Cynthia L. Salinas; Ann F. Bolger; Neal L. Benowitz; David D. Waters

2002-01-01

131

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

SciTech Connect

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

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

2013-06-05

132

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

PubMed Central

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

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

2014-01-01

133

Direct evidence of phosphorylated neuronal intermediate filament proteins in neurofibrillary tangles (NFTs): phosphoproteomics of Alzheimer's NFTs  

PubMed Central

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by brain pathology of intracellular neurofibrillary tangles (NFTs) and extracellular amyloid plaques. NFTs contain aberrantly hyperphosphorylated Tau as paired helical filaments (PHFs). Although NFs have been shown immunohistologically to be part of NFTs, there has been debate that the identity of NF proteins in NFTs is due to the cross-reactivity of phosphorylated NF antibodies with phospho-Tau. Here, we provide direct evidence on the identity of NFs in NFTs by immunochemical and mass spectrometric analysis. We have purified sarkosyl-insoluble NFTs and performed liquid chromatography/tandem mass spectrometry of NFT tryptic digests. The phosphoproteomics of NFTs clearly identified NF-M phosphopeptides SPVPKS*PVEEAK, corresponding to Ser685, and KAES*PVKEEAVAEVVTITK, corresponding to Ser736, and an NF-H phosphopeptide, EPDDAKAKEPS*KP, corresponding to Ser942. Western blotting of purified tangles with SMI31 showed a 150-kDa band corresponding to phospho-NF-M, while RT97 antibodies detected phospho-NF-H. The proteomics analysis also identified an NF-L peptide (ALYEQEIR, EAEEEKKVEGAGEEQAAAK) and another intermediate filament protein, vimentin (FADLSEAANR). Mass spectrometry revealed Tau phosphopeptides corresponding to Thr231, Ser235, Thr181, Ser184, Ser185, Thr212, Thr217, Ser396, and Ser403. And finally, phosphopeptides corresponding to MAP1B (corresponding to Ser1270, Ser1274, and Ser1779) and MAP2 (corresponding to Thr350, Ser1702, and Ser1706) were identified. In corresponding matched control preparations of PHF/NFTs, none of these phosphorylated neuronal cytoskeletal proteins were found. These studies independently demonstrate that NF proteins are an integral part of NFTs in AD brains.—Rudrabhatla, P., Jaffe, H., Pant, H. C. Direct evidence of phosphorylated neuronal intermediate filament proteins in neurofibrillary tangles (NFTs): phosphoproteomics of Alzheimer's NFTs. PMID:21828286

Rudrabhatla, Parvathi; Jaffe, Howard; Pant, Harish C.

2011-01-01

134

Identification of kinase inhibitor targets in the lung cancer microenvironment by chemical and phosphoproteomics.  

PubMed

A growing number of gene mutations, which are recognized as cancer drivers, can be successfully targeted with drugs. The redundant and dynamic nature of oncogenic signaling networks and complex interactions between cancer cells and the microenvironment, however, can cause drug resistance. While these challenges can be addressed by developing drug combinations or polypharmacology drugs, this benefits greatly from a detailed understanding of the proteome-wide target profiles. Using mass spectrometry-based chemical proteomics, we report the comprehensive characterization of the drug-protein interaction networks for the multikinase inhibitors dasatinib and sunitinib in primary lung cancer tissue specimens derived from patients. We observed in excess of 100 protein kinase targets plus various protein complexes involving, for instance, AMPK, TBK1 (sunitinib), and ILK (dasatinib). Importantly, comparison with lung cancer cell lines and mouse xenografts thereof showed that most targets were shared between cell lines and tissues. Several targets, however, were only present in tumor tissues. In xenografts, most of these proteins were of mouse origin suggesting that they originate from the tumor microenvironment. Furthermore, intersection with subsequent global phosphoproteomic analysis identified several activated signaling pathways. These included MAPK, immune, and integrin signaling, which were affected by these drugs in both cancer cells and the microenvironment. Thus, the combination of chemical and phosphoproteomics can generate a systems view of proteins, complexes, and signaling pathways that are simultaneously engaged by multitargeted drugs in cancer cells and the tumor microenvironment. This may allow for the design of novel anticancer therapies that concurrently target multiple tumor compartments. Mol Cancer Ther; 13(11); 2751-62. ©2014 AACR. PMID:25189542

Gridling, Manuela; Ficarro, Scott B; Breitwieser, Florian P; Song, Lanxi; Parapatics, Katja; Colinge, Jacques; Haura, Eric B; Marto, Jarrod A; Superti-Furga, Giulio; Bennett, Keiryn L; Rix, Uwe

2014-11-01

135

Multiplexed Detection of O-GlcNAcome, Phosphoproteome, and Whole Proteome within the Same Gel  

PubMed Central

The cellular diversity of proteins results in part from their post-translational modifications. Among all of them, the O-GlcNAcylation is an atypical glycosylation, more similar to phosphorylation than classical glycosylations. Highly dynamic, reversible, and exclusively localized on cytosolic, nuclear, and mitochondrial proteins, O-GlcNAcylation is known to regulate almost all if not all cellular processes. Fundamental for the cell life, O-GlcNAcylation abnormalities are involved in the etiology of several inherited diseases. Assessing to O-GlcNAcylation pattern will permit to get relevant data about the role of O-GlcNAcylation in cell physiology. To get understanding about the role of O-GlcNAcylation, as also considering its interplay with phosphorylation, the O-GlcNAc profiling remains a real challenge for the community of proteomists/glycoproteomists. The development of multiplexed proteomics based on fluorescent detection of proteins permits to go further in the understanding of the proteome complexity. We propose herein a multiplexed proteomic strategy to detect O-GlcNAcylated proteins, phosphoproteins, and the whole proteome within the same bidimensional gel. In particular, we investigated the phosphoproteome through the ProQ Diamond staining, while the whole proteome was visualized through Sypro Ruby staining, or after the labeling of proteins with a T-Dye fluorophore. The O-GlcNAcome was revealed by the way of the Click chemistry and the azide–alkyne cycloaddition of a fluorophore on GlcNAc moieties. This method permits, after sequential image acquisition, the direct in-gel detection of O-GlcNAcome, phosphoproteome, and whole proteome. PMID:25389416

Cieniewski-Bernard, Caroline; Dupont, Erwan; Deracinois, Barbara; Lambert, Matthias; Bastide, Bruno

2014-01-01

136

Phosphoproteome Profiling of Human Skin Fibroplast Cells in Response to Low- and High-Dose Irradiation  

SciTech Connect

The biological effect of low-dose radiation is currently not well understood. A hallmark of the response to radiation is the phosphorylation of proteins involved in DNA repair, DNA damage signaling, and cell cycle checkpoint control, which is important in prompt cellular response. The objective of the work presented here was to explore the phosphoproteome of normal human skin fibroblast (HSF) cells to reveal differences between low- and high-dose irradiation responses at the protein phosphorylation level. Several techniques —Trizol extract of proteins, methylation of the enzyme digest (peptides), enrichment of phosphopeptides with immobilized metal affinity chromatography (IMAC), nanoflow reversed-phase HPLC (nano-LC)/electrospray ionization, and tandem mass spectrometry— were combined for analysis of the HSF cell phosphoproteome following low- and high-doses of irradiation. More than 95% of the peptides identified after IMAC enrichment were phosphopeptides. Among the 493 unique phosphopeptides, 232 were singly phosphorylated, 220 were doubly phosphorylated, and 41 were triply phosphorylated, indicating the overall effectiveness of the IMAC technique to enrich both singly and multiple phosphorylated peptides. Over 700 phosphorylation sites were assigned to a total of 346 proteins, many of which are known or proposed to be highly relevant to a plethora of fundamental biological processes. The profile for proteins identified from the low-dose (2cGy) irradiated HSF cells was shown to be different from the profile obtained for proteins irradiated at the high-dose (4 Gy). This type of fundamental information regarding radiation-response to cellular events at the molecular level provides a mechanistic basis for identifying relevant molecular markers that can be used in future to better evaluate human health risks at low doses of irradiation and to develop low dose radiation counter measurements.

Yang, Feng; Stenoien, David L.; Strittmatter, Eric F.; Wang, Jeng-Han; Ding, Lianghao; Lipton, Mary S.; Monroe, Matthew E.; Nicora, Carrie D.; Gritsenko, Marina A.; Tang, Keqi; Fang, Ruihua; Adkins, Joshua N.; Camp, David G.; Chen, David J.; Smith, Richard D.

2006-05-01

137

The phosphoproteome in regenerating protoplasts from Physcomitrella patens protonemata shows changes paralleling postembryonic development in higher plants  

PubMed Central

The moss Physcomitrella patens is an ideal model plant to study plant developmental processes. To better understand the mechanism of protoplast regeneration, a phosphoproteome analysis was performed. Protoplasts were prepared from protonemata. By 4 d of protoplast regeneration, the first cell divisions had ensued. Through a highly selective titanium dioxide (TiO2)-based phosphopeptide enrichment method and mass spectrometric technology, more than 300 phosphoproteins were identified as protoplast regeneration responsive. Of these, 108 phosphoproteins were present on day 4 but not in fresh protoplasts or those cultured for 2 d. These proteins are catalogued here. They were involved in cell-wall metabolism, transcription, signal transduction, cell growth/division, and cell structure. These protein functions are related to cell morphogenesis, organogenesis, and development adjustment. This study presents a comprehensive analysis of phosphoproteome involved in protoplast regeneration and indicates that the mechanism of plant protoplast regeneration is similar to that of postembryonic development. PMID:24700621

He, Yikun

2014-01-01

138

Netfrog: The Interactive Frog Dissection  

NSDL National Science Digital Library

This tutorial on frog dissection contains an introduction and sections on preparation, skin incisions, muscle incisions, and internal organs. The purpose of this lab activity is to help students learn the anatomy of a frog and provide them with a better understanding of the anatomy of vertebrate animals in general, including humans. This site provides still and motion visuals of preserved and pithed (severed spinal cord) frogs to demonstrate incisions, in addition to text.

Kinzie, Mable

139

Clinical analysis of vertebrobasilar dissection  

Microsoft Academic Search

Summary  Background. The natural history of vertebrobasilar artery dissection (VAD) is not fully known. The purpose of this study was to review\\u000a the clinical outcome of the patients with VAD, then to propose an appropriate management strategy for VAD.\\u000a \\u000a Method. From 1992 to 2004, 35 VAD patients admitted to our institutes were retrospectively reviewed. There were 28 men and 7 women,

C.-H. Kim; Y.-J. Son; S. H. Paek; M. H. Han; J. E. Kim; Y. S. Chung; B. J. Kwon; C. W. Oh; D. H. Han

2006-01-01

140

Noninvasive Detection ofVertebral Artery Dissection  

Microsoft Academic Search

Background andPurpose: We sought toidentify theuse ofduplexandtranscranial Dopplersonography inthenoninvasive diagnosis ofvertebral dissection. Methods: Tenpatients with adiagnosis ofsymptomatic vertebral artery dissection confirmed bycerebral angiography were retrospectively analyzed. Results: Computed tomographic scanning andmagnetic resonance imaging together delineated lateral medullary or cerebellar infarcts in7patients. Angiography documented a total of21vertebral artery lesions (16stenoses and5occlusions), with7of10patients havingmultiple sites ofvertebral artery dissection. Vertebral Doppler was abnormal

Michael Hoffmann; Ralph L. Sacco; Stephen Chan; P. Mohr

141

Optimal Diagnostic Imaging of Aortic Dissection  

PubMed Central

Without prompt diagnosis and treatment, aortic dissection is rapidly fatal. While standard chest radiography may give clues to the diagnosis of aortic dissection, suspected dissection can be confirmed by only 4 imaging techniques: aortography, echocardiography, computed tomography, and magnetic resonance imaging. The following review discusses each of these methods. It also explains why aortography, the previous diagnostic benchmark, has been replaced by newer techniques and why magnetic resonance imaging has become the diagnostic method of choice for imaging aortic dissection. (Texas Heart Institute Journal 1990;17:271-8) Images PMID:15227519

Wilbers, Christopher R.H.; Carrol, Clark L.; Hnilica, Mark A.

1990-01-01

142

Phosphoproteomics of collagen receptor networks reveals SHP-2 phosphorylation downstream of wild-type DDR2 and its lung cancer mutants  

PubMed Central

Collagen is an important extracellular matrix component that directs many fundamental cellular processes including differentiation, proliferation and motility. The signalling networks driving these processes are propagated by collagen receptors such as the ?1 integrins and the DDRs (discoidin domain receptors). To gain an insight into the molecular mechanisms of collagen receptor signalling, we have performed a quantitative analysis of the phosphorylation networks downstream of collagen activation of integrins and DDR2. Temporal analysis over seven time points identified 424 phosphorylated proteins. Distinct DDR2 tyrosine phosphorylation sites displayed unique temporal activation profiles in agreement with in vitro kinase data. Multiple clustering analysis of the phosphoproteomic data revealed several DDR2 candidate downstream signalling nodes, including SHP-2 (Src homology 2 domain-containing protein tyrosine phosphatase 2), NCK1 (non-catalytic region of tyrosine kinase adaptor protein 1), LYN, SHIP-2 [SH2 (Src homology 2)-domain-containing inositol phosphatase 2], PIK3C2A (phosphatidylinositol-4-phosphate 3-kinase, catalytic subunit type 2?) and PLCL2 (phospholipase C-like 2). Biochemical validation showed that SHP-2 tyrosine phosphorylation is dependent on DDR2 kinase activity. Targeted proteomic profiling of a panel of lung SCC (squamous cell carcinoma) DDR2 mutants demonstrated that SHP-2 is tyrosine-phosphorylated by the L63V and G505S mutants. In contrast, the I638F kinase domain mutant exhibited diminished DDR2 and SHP-2 tyrosine phosphorylation levels which have an inverse relationship with clonogenic potential. Taken together, the results of the present study indicate that SHP-2 is a key signalling node downstream of the DDR2 receptor which may have therapeutic implications in a subset of DDR2 mutations recently uncovered in genome-wide lung SCC sequencing screens. PMID:23822953

Iwai, Leo K.; Payne, Leo S.; Luczynski, Maciej T.; Chang, Francis; Xu, Huifang; Clinton, Ryan W.; Paul, Angela; Esposito, Edward A.; Gridley, Scott; Leitinger, Birgit; Naegle, Kristen M.; Huang, Paul H.

2013-01-01

143

Phosphoproteomic evaluation of pharmacological inhibition of leucine-rich repeat kinase 2 reveals significant off-target effects of LRRK-2-IN-1.  

PubMed

Genetic mutations in leucine-rich repeat kinase 2 (LRRK2) have been linked to autosomal dominant Parkinson's disease. The most prevalent mutation, G2019S, results in enhanced LRRK2 kinase activity that potentially contributes to the etiology of Parkinson's disease. Consequently, disease progression is potentially mediated by poorly characterized phosphorylation-dependent LRRK2 substrate pathways. To address this gap in knowledge, we transduced SH-SY5Y neuroblastoma cells with LRRK2 G2019S via adenovirus, then determined quantitative changes in the phosphoproteome upon LRRK2 kinase inhibition (LRRK2-IN-1 treatment) using stable isotope labeling of amino acids in culture combined with phosphopeptide enrichment and LC-MS/MS analysis. We identified 776 phosphorylation sites that were increased or decreased at least 50% in response to LRRK2-IN-1 treatment, including sites on proteins previously known to associate with LRRK2. Bioinformatic analysis of those phosphoproteins suggested a potential role for LRRK2 kinase activity in regulating pro-inflammatory responses and neurite morphology, among other pathways. In follow-up experiments, LRRK2-IN-1 inhibited lipopolysaccharide-induced tumor necrosis factor alpha (TNF?) and C-X-C motif chemokine 10 (CXCL10) levels in astrocytes and also enhanced multiple neurite characteristics in primary neuronal cultures. However, LRRK2-IN-1 had almost identical effects in primary glial and neuronal cultures from LRRK2 knockout mice. These data suggest LRRK2-IN-1 may inhibit pathways of perceived LRRK2 pathophysiological function independently of LRRK2 highlighting the need to use multiple pharmacological tools and genetic approaches in studies determining LRRK2 function. PMID:24117733

Luerman, Gregory C; Nguyen, Chuong; Samaroo, Harry; Loos, Paula; Xi, Hualin; Hurtado-Lorenzo, Andres; Needle, Elie; Stephen Noell, G; Galatsis, Paul; Dunlop, John; Geoghegan, Kieran F; Hirst, Warren D

2014-02-01

144

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

PubMed Central

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

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

145

Probing the phosphoproteome of HeLa cells using nanocast metal oxide microspheres for phosphopeptide enrichment.  

PubMed

Metal oxide affinity chromatography (MOAC) has become a prominent method to enrich phosphopeptides prior to their analysis by liquid chromatography-mass spectrometry. To overcome limitations in material design, we have previously reported the use of nanocasting as a means to generate metal oxide spheres with tailored properties. Here, we report on the application of two oxides, tin dioxide (stannia) and titanium dioxide (titania), for the analysis of the HeLa phosphoproteome. In combination with nanoflow LC-MS/MS analysis on a linear ion trap-Fourier transform ion cyclotron resonance instrument, we identified 619 phosphopeptides using the new stannia material, and 896 phosphopeptides using titania prepared in house. We also compared the newly developed materials to commercial titania material using an established enrichment protocol. Both titania materials yielded a comparable total number of phosphopeptides, but the overlap of the two data sets was less than one-third. Although fewer peptides were identified using stannia, the complementarity of SnO(2)-based MOAC could be shown as more than 140 phosphopeptides were exclusively identified by this material. PMID:20201521

Leitner, Alexander; Sturm, Martin; Hudecz, Otto; Mazanek, Michael; Smått, Jan-Henrik; Lindén, Mika; Lindner, Wolfgang; Mechtler, Karl

2010-04-01

146

Towards the identification of late-embryogenic-abundant phosphoproteome in Arabidopsis by 2-DE and MS.  

PubMed

Late-embryogenesis-abundant (LEA) proteins accumulate as plant seeds desiccate and also in vegetative organs during periods of stress. They are predicted to play a role in plant stress tolerance. In the present study, we have initiated the characterization of phosphorylated LEA proteins present in the Arabidopsis seed, using a strategy that combines the thermostability (solubility upon heating) of many LEA-type proteins with the use of phosphoaffinity chromatography to obtain an enriched subpopulation of phosphoproteins. The specificity and efficiency of the procedure was assessed by alkaline phosphatase treatment and by a specific stain for phosphoproteins, in addition to the immunodetection of AtRab18, a phosphorylated LEA protein present in the mature dry seed. The phosphoproteins were identified by MS either by PMF using MALDI-TOF MS after 2-DE separation, or by peptide sequencing using both capillary LC MS/MS (LC muESI-ITMS/MS) and nanoLC coupled to nanoESI-MS/MS (LC-nanoESI-Q-TOF-MS/MS). Several LEA-type and storage-like proteins were identified as components of the phosphoproteome of the Arabidopsis seed. PMID:16511814

Irar, Sami; Oliveira, Eliandre; Pagès, Montserrat; Goday, Adela

2006-04-01

147

Phosphoproteomic analysis provides novel insights into stress responses in Phaeodactylum tricornutum, a model diatom.  

PubMed

Protein phosphorylation on serine, threonine, and tyrosine (Ser/Thr/Tyr) is well established as a key regulatory posttranslational modification used in signal transduction to control cell growth, proliferation, and stress responses. However, little is known about its extent and function in diatoms. Phaeodactylum tricornutum is a unicellular marine diatom that has been used as a model organism for research on diatom molecular biology. Although more than 1000 protein kinases and phosphatases with specificity for Ser/Thr/Tyr residues have been predicted in P. tricornutum, no phosphorylation event has so far been revealed by classical biochemical approaches. Here, we performed a global phosphoproteomic analysis combining protein/peptide fractionation, TiO(2) enrichment, and LC-MS/MS analyses. In total, we identified 264 unique phosphopeptides, including 434 in vivo phosphorylated sites on 245 phosphoproteins. The phosphorylated proteins were implicated in the regulation of diverse biological processes, including signaling, metabolic pathways, and stress responses. Six identified phosphoproteins were further validated by Western blotting using phospho-specific antibodies. The functions of these proteins are discussed in the context of signal transduction networks in P. tricornutum. Our results advance the current understanding of diatom biology and will be useful for elucidating the phosphor-relay signaling networks in this model diatom. PMID:24712722

Chen, Zhuo; Yang, Ming-kun; Li, Chong-yang; Wang, Yan; Zhang, Jia; Wang, Dian-bing; Zhang, Xian-en; Ge, Feng

2014-05-01

148

Extracranial vertebral artery dissection: nine cases  

Microsoft Academic Search

Nine patients (six men, three women) with extracranial vertebral artery dissection are described. Their mean age was 39.1 years (range 17–66). In four cases dissection was “spontaneous”; in the other five cases there was a history of trivial trauma. Three patients had fibromuscular dysplasia, two were migraineurs, one had elastorrhexis. Treatment varied. Six received heparin, three acetylsalicylic acid or ticlopidine.

E. Josien

1992-01-01

149

[Dissection is still important when learning anatomy].  

PubMed

Dissection and prosection require a donation programme of cadavers for education and research. The importance of maintaining the donation programme and the significance of dissection as a teaching method when learning anatomic structures and obtaining surgical skills are evaluated. PMID:23697565

Knudsen, Britt Mejer; Søe, Niels H; Jensen, Nina Vendel; Langebæk, Rikke; Dahlin, Lars B

2013-05-20

150

Postoperative hypertension following radical neck dissection  

PubMed Central

Baroreflex failure results in wide excursions of blood pressure and heart rate. We report two cases that developed severe postoperative hypertension after radical neck dissection. Carotid sinus denervation during neck dissection may be the cause of the reflex hypertension once general anesthesia-induced vasodilatation has ended. PMID:22345960

Prakash, Smita; Rapsang, Amy; Kumar, Suresh S; Bhatia, Parminder S; Gogia, Anoop R

2012-01-01

151

Aortic arch dissection: a controversy of classification.  

PubMed

Aortic dissections originating in the ascending aorta and descending aorta have been classified as type A and type B dissections, respectively. However, dissections with intimal flap extension into the aortic arch between the innominate and left subclavian arteries are not accounted for adequately in the widely used Stanford classification. This gap has been the subject of controversy in the medical and surgical literature, and there is a tendency among many radiologists to categorize such arch dissections as type A lesions, thus making them an indication for surgery. However, the radiologic perspective is not supported by either standard dissection classification or current clinical management. In this special report, the origin of dissection classification and its evolution into current radiologic interpretation and surgical practice are reviewed. The cause for the widespread misconception about classification and treatment algorithms is identified. Institutional review board approval and waiver of informed consent were obtained as part of this HIPAA-compliant retrospective study to assess all aortic dissection studies performed at the University of Maryland Medical Center, Baltimore between 2010 and 2012 to determine the prevalence of arch dissections. Finally, a unified classification system that reconciles imaging interpretation and management implementation is proposed. PMID:24617732

Lempel, Jason K; Frazier, Aletta Ann; Jeudy, Jean; Kligerman, Seth J; Schultz, Randall; Ninalowo, Hammed A; Gozansky, Elliott K; Griffith, Bartley; White, Charles S

2014-06-01

152

Quantitative Phosphoproteomic Analysis Identifies Activation of the RET and IGF-1R/IR Signaling Pathways in Neuroblastoma  

PubMed Central

Neuroblastoma is an embryonal tumor of childhood with a heterogenous clinical presentation that reflects differences in activation of complex biological signaling pathways. Protein phosphorylation is a key component of cellular signal transduction and plays a critical role in processes that control cancer cell growth and survival. We used shotgun LC/MS to compare phosphorylation between a human MYCN amplified neuroblastoma cell line (NB10), modeling a resistant tumor, and a human neural precursor cell line (NPC), modeling a normal baseline neural crest cell. 2181 unique phosphorylation sites representing 1171 proteins and 2598 phosphopeptides were found. Protein kinases accounted for 6% of the proteome, with a predominance of tyrosine kinases, supporting their prominent role in oncogenic signaling pathways. Highly abundant receptor tyrosine kinase (RTK) phosphopeptides in the NB10 cell line relative to the NPC cell line included RET, insulin-like growth factor 1 receptor/insulin receptor (IGF-1R/IR), and fibroblast growth factor receptor 1 (FGFR1). Multiple phosphorylated peptides from downstream mediators of the PI3K/AKT/mTOR and RAS pathways were also highly abundant in NB10 relative to NPC. Our analysis highlights the importance of RET, IGF-1R/IR and FGFR1 as RTKs in neuroblastoma and suggests a methodology that can be used to identify potential novel biological therapeutic targets. Furthermore, application of this previously unexploited technology in the clinic opens the possibility of providing a new wide-scale molecular signature to assess disease progression and prognosis. PMID:24349301

DeNardo, Bradley D.; Holloway, Michael P.; Ji, Qinqin; Nguyen, Kevin T.; Cheng, Yan; Valentine, Marcus B.; Salomon, Arthur; Altura, Rachel A.

2013-01-01

153

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

PubMed Central

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) ?/? threonine 410/412 (T410/T412), LKB1 S334, inhibitor of kappaB alpha (I?B-?) 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 ?. To our knowledge, this is the first report of elevated PKC ? in head and neck squamous cell carcinoma that may have significance because PKC ? 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

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

154

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

SciTech Connect

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

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

2013-09-22

155

Direct evidence of phosphorylated neuronal intermediate filament proteins in neurofibrillary tangles (NFTs): phosphoproteomics of Alzheimer's NFTs.  

PubMed

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by brain pathology of intracellular neurofibrillary tangles (NFTs) and extracellular amyloid plaques. NFTs contain aberrantly hyperphosphorylated Tau as paired helical filaments (PHFs). Although NFs have been shown immunohistologically to be part of NFTs, there has been debate that the identity of NF proteins in NFTs is due to the cross-reactivity of phosphorylated NF antibodies with phospho-Tau. Here, we provide direct evidence on the identity of NFs in NFTs by immunochemical and mass spectrometric analysis. We have purified sarkosyl-insoluble NFTs and performed liquid chromatography/tandem mass spectrometry of NFT tryptic digests. The phosphoproteomics of NFTs clearly identified NF-M phosphopeptides SPVPKS*PVEEAK, corresponding to Ser685, and KAES*PVKEEAVAEVVTITK, corresponding to Ser736, and an NF-H phosphopeptide, EPDDAKAKEPS*KP, corresponding to Ser942. Western blotting of purified tangles with SMI31 showed a 150-kDa band corresponding to phospho-NF-M, while RT97 antibodies detected phospho-NF-H. The proteomics analysis also identified an NF-L peptide (ALYEQEIR, EAEEEKKVEGAGEEQAAAK) and another intermediate filament protein, vimentin (FADLSEAANR). Mass spectrometry revealed Tau phosphopeptides corresponding to Thr231, Ser235, Thr181, Ser184, Ser185, Thr212, Thr217, Ser396, and Ser403. And finally, phosphopeptides corresponding to MAP1B (corresponding to Ser1270, Ser1274, and Ser1779) and MAP2 (corresponding to Thr350, Ser1702, and Ser1706) were identified. In corresponding matched control preparations of PHF/NFTs, none of these phosphorylated neuronal cytoskeletal proteins were found. These studies independently demonstrate that NF proteins are an integral part of NFTs in AD brains. PMID:21828286

Rudrabhatla, Parvathi; Jaffe, Howard; Pant, Harish C

2011-11-01

156

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

PubMed

Heart damage is widely present in patients with chronic kidney disease. Salt diet is the most important environmental factor affecting development of chronic renal failure and cardiovascular diseases. The proteins involved in chronic kidney disease -induced heart damage, especially their posttranslational modifications, remain largely unknown to date. Sprague-Dawley rats underwent 5/6 nephrectomy (chronic renal failure model) or sham operation were treated for 2 weeks with a normal-(0.4% NaCl), or high-salt (4% NaCl) diet. We employed TiO2 enrichment, iTRAQ labeling and liquid-chromatography tandem mass spectrometry strategy for phosphoproteomic profiling of left ventricular free walls in these animals. A total of 1724 unique phosphopeptides representing 2551 non-redundant phosphorylation sites corresponding to 763 phosphoproteins were identified. During normal salt feeding, 89 (54%) phosphopeptides upregulated and 76 (46%) phosphopeptides downregulated in chronic renal failure rats relative to sham rats. In chronic renal failure rats, high salt intake induced upregulation of 84 (49%) phosphopeptides and downregulation of 88 (51%) phosphopeptides. Database searches revealed that most of the identified phospholproteins were important signaling molecules such as protein kinases, receptors and phosphatases. These phospholproteins were involved in energy metabolism, cell communication, cell differentiation, cell death and other biological processes. The Search Tool for the Retrieval of Interacting Genes analysis revealed functional links among 15 significantly regulated phosphoproteins in chronic renal failure rats compared to sham group, and 23 altered phosphoproteins induced by high salt intake. The altered phosphorylation levels of two proteins involved in heart damage, lamin A and phospholamban were validated. Expression of the downstream genes of these two proteins, desmin and SERCA2a, were also analyzed. PMID:24945867

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

2014-01-01

157

Alterations in the cerebellar (Phospho)proteome of a cyclic guanosine monophosphate (cGMP)-dependent protein kinase knockout mouse.  

PubMed

The cyclic nucleotide cyclic guanosine monophosphate (cGMP) plays an important role in learning and memory, but its signaling mechanisms in the mammalian brain are not fully understood. Using mass-spectrometry-based proteomics, we evaluated how the cerebellum adapts its (phospho)proteome in a knockout mouse model of cGMP-dependent protein kinase type I (cGKI). Our data reveal that a small subset of proteins in the cerebellum (?3% of the quantified proteins) became substantially differentially expressed in the absence of cGKI. More changes were observed at the phosphoproteome level, with hundreds of sites being differentially phosphorylated between wild-type and knockout cerebellum. Most of these phosphorylated sites do not represent known cGKI substrates. An integrative computational network analysis of the data indicated that the differentially expressed proteins and proteins harboring differentially phosphorylated sites largely belong to a tight network in the Purkinje cells of the cerebellum involving important cGMP/cAMP signaling nodes (e.g. PDE5 and PKARII?) and Ca(2+) signaling (e.g. SERCA3). In this way, removal of cGKI could be linked to impaired cerebellar long-term depression at Purkinje cell synapses. In addition, we were able to identify a set of novel putative (phospho)proteins to be considered in this network. Overall, our data improve our understanding of cerebellar cGKI signaling and suggest novel players in cGKI-regulated synaptic plasticity. PMID:24925903

Corradini, Eleonora; Vallur, Raghavan; Raaijmakers, Linsey M; Feil, Susanne; Feil, Robert; Heck, Albert J R; Scholten, Arjen

2014-08-01

158

From global phosphoproteomics to individual proteins: the case of translation elongation factor eEF1A.  

PubMed

Phosphoproteomics is often aimed at deciphering the modified components of signaling pathways in certain organisms, tissues and pathologies. Phosphorylation of housekeeping proteins, albeit important, usually attracts less attention. Here, we provide targeted analysis of eukaryotic translation elongation factor 1A (eEF1A), which is the main element of peptide elongation machinery. There are 97% homologous A1 and A2 isoforms of eEF1A; their expression in mammalian tissues is mutually exclusive and differentially regulated in development. The A2 isoform reveals proto-oncogenic properties and specifically interacts with some cellular proteins. Several tyrosine residues shown experimentally to be phosphorylated in eEF1A1 are hardly solution accessible, so their phosphorylation could be linked with structural rearrangement of the protein molecule. The possible role of tyrosine phosphorylation in providing the background for structural differences between the 'extended' A1 isoform and the compact oncogenic A2 isoform is discussed. The 'road map' for targeted analysis of any protein of interest using phosphoproteomics data is presented. PMID:22292825

Negrutskii, Boris; Vlasenko, Dmytro; El'skaya, Anna

2012-01-01

159

In silico analysis of phosphoproteome data suggests a rich-get-richer process of phosphosite accumulation over evolution.  

PubMed

Recent phosphoproteome analyses using mass spectrometry-based technologies have provided new insights into the extensive presence of protein phosphorylation in various species and have raised the interesting question of how this protein modification was gained evolutionarily on such a large scale. We investigated this issue by using human and mouse phosphoproteome data. We initially found that phosphoproteins followed a power-law distribution with regard to their number of phosphosites: most of the proteins included only a few phosphosites, but some included dozens of phosphosites. The power-law distribution, unlike more commonly observed distributions such as normal and log-normal distributions, is considered by the field of complex systems science to be produced by a specific rich-get-richer process called preferential attachment growth. Therefore, we explored the factors that may have promoted the rich-get-richer process during phosphosite evolution. We conducted a bioinformatics analysis to evaluate the relationship of amino acid sequences of phosphoproteins with the positions of phosphosites and found an overconcentration of phosphosites in specific regions of protein surfaces and implications that in many phosphoproteins these clusters of phosphosites are activated simultaneously. Multiple phosphosites concentrated in limited spaces on phosphoprotein surfaces may therefore function biologically as cooperative modules that are resistant to selective pressures during phosphoprotein evolution. We therefore proposed a hypothetical model by which the modularization of multiple phosphosites has been resistant to natural selection and has driven the rich-get-richer process of the evolutionary growth of phosphosite numbers. PMID:19136663

Yachie, Nozomu; Saito, Rintaro; Sugahara, Junichi; Tomita, Masaru; Ishihama, Yasushi

2009-05-01

160

Training in endoscopic submucosal dissection  

PubMed Central

Endoscopic submucosal dissection (ESD) represents an important advancement in the therapy of early neoplastic gastrointestinal lesions by providing higher en-bloc curative resection rate with lower recurrence compared to endoscopic mucosal resection (EMR) and by sparing the involved organ and protecting patient’s quality of life. Despite these advantages ESD is associated with long procedure times and a higher rate of complications, making ESD a challenging procedure which requires advanced endoscopic skills. Thus, there has been a recognized need for structured training system for ESD to enhance trainee experience and, to reduce the risks of complications and inadequate treatment. ESD has a very flat learning curve. However, we do not have uniformly accepted benchmarks for competency. Nevertheless, it appears that, in Japan, more than 30 supervised gastric ESD procedures are required to achieve technical proficiency and minimize complications. A number of training algorithms have been proposed in Japan with the aim to standardize ESD training. These algorithms cannot be directly applied in the West due to substantial differences including the availability of highly qualified mentors, the type of pathology seen, choice of devices, and trainee’s background. We propose a training algorithm for Western physicians which integrates both hands-on training courses, animal model work as well as visits to expert centers. No specific preceptor training programs have been yet developed but there is a consensus that these programs are important for permeation of ESD worldwide. PMID:23951392

Coman, Roxana M; Gotoda, Takuji; Draganov, Peter V

2013-01-01

161

Animal Rights Groups Target High School Dissection.  

ERIC Educational Resources Information Center

Two groups leading the charge against dissection are People for the Ethical Treatment of Animals (PETA) and the Student Action Corps for Animals (SACA). Protests by student and community members remain the movement's strongest weapon. (MLF)

Trotter, Andrew

1992-01-01

162

Postoperative adjuvant chemoradiotherapy in D2-dissected gastric cancer: Is radiotherapy necessary after D2-dissection?  

PubMed Central

Studies from the Far East have demonstrated that D2-dissection is superior to D0/1-dissection. The effect of postoperative chemoradiotherapy (CRT) after D2-dissection has not been accepted due to the lack of D2-dissection in Western countries, as well as the potential harmful effect of radiotherapy. In the current NCCN guideline, adjuvant chemotherapy alone is recommended in D2-dissected patients. However, three recent prospective randomized controlled trials in South Korea and China (ARTIST, NCC and Multicenter IMRT Trials) demonstrated that adjuvant CRT can be safely administered to D2-dissected patients with notable benefits. To identify the role of radiotherapy (RT) in the D2-dissected postoperative setting, clinical research attempts should include (1) identification of high-risk patients for loco-regional recurrence who might benefit from CRT; (2) modification of RT target volume based on the findings that failure patterns should be different after D1- and D2-dissection; and (3) integration of new RT techniques to decrease treatment-related toxicity. The present paper is a review of recent studies addressing these fields. Well-designed prospective randomized studies are needed to clearly define the role of adjuvant CRT in D2-dissected gastric cancer, however, future clinical studies should also focus on answering these questions. PMID:25278687

Chang, Jee Suk; Koom, Woong Sub; Lee, Youngin; Yoon, Hong In; Lee, Hyung Sik

2014-01-01

163

Managing Dissections of the Thoracic Aorta  

PubMed Central

Thoracic aortic dissection is associated with substantial morbidity and mortality, and it requires timely and accurate diagnosis and treatment. Long-term antihypertensive therapy remains critical for the treatment of this disease. Surgical intervention, although still a formidable undertaking, has evolved to better address both acute and chronic dissection, and the results have improved. Basic and clinical research, as well as technological advances, have increased our understanding of this challenging disease state. PMID:18481490

WONG, DANIEL R.; LEMAIRE, SCOTT A.; COSELLI, JOSEPH S.

2010-01-01

164

The Effect of Animal Dissections on Student Acquisition of Knowledge of and Attitudes toward the Animals Dissected.  

ERIC Educational Resources Information Center

A conflict exists over the use of animals in the classroom. One aspect of this use involved the dissection of animals. Animal protection advocates report that dissections constitute abuse of the animals dissected. The advocates state that what is learned by dissection could be more effectively learned by other means. Some science educators state…

McCollum, Terry L.

165

Predicting flow in aortic dissection: comparison of computational model with PC-MRI velocity measurements.  

PubMed

Aortic dissection is a life-threatening process in which the weakened wall develops a tear, causing separation of wall layers. The dissected layers separate the original true aortic lumen and a newly created false lumen. If untreated, the condition can be fatal. Flow rate in the false lumen is a key feature for false lumen patency, which has been regarded as one of the most important predictors of adverse early and later outcomes. Detailed flow analysis in the dissected aorta may assist vascular surgeons in making treatment decisions, but computational models to simulate flow in aortic dissections often involve several assumptions. The purpose of this study is to assess the computational models adopted in previous studies by comparison with in vivo velocity data obtained by means of phase-contrast magnetic resonance imaging (PC-MRI). Aortic dissection geometry was reconstructed from computed tomography (CT) images, while PC-MRI velocity data were used to define inflow conditions and to provide distal velocity components for comparison with the simulation results. The computational fluid dynamics (CFD) simulation incorporated a laminar-turbulent transition model, which is necessary for adequate flow simulation in aortic conditions. Velocity contours from PC-MRI and CFD in the two lumens at the distal plane were compared at four representative time points in the pulse cycle. The computational model successfully captured the complex regions of flow reversal and recirculation qualitatively, although quantitative differences exist. With a rigid wall assumption and exclusion of arch branches, the CFD model over-predicted the false lumen flow rate by 25% at peak systole. Nevertheless, an overall good agreement was achieved, confirming the physiological relevance and validity of the computational model for type B aortic dissection with a relatively stiff dissection flap. PMID:25070022

Cheng, Z; Juli, C; Wood, N B; Gibbs, R G J; Xu, X Y

2014-09-01

166

Acute type B aortic dissection: insights from the International Registry of Acute Aortic Dissection.  

PubMed

Acute type B aortic dissection comprises approximately one-third of all aortic dissection cases. Although this catastrophic cardiovascular condition was first described in the medical literature over two centuries ago, data on the optimal diagnostic and treatment modalities for type B dissection was slow to evolve throughout the latter half of the twentieth century, even as newer diagnostic techniques and management strategies became commonplace. To further elucidate contemporary practice patterns and outcomes of aortic dissection, the International Registry of Acute Aortic Dissection (IRAD) was established in 1996. Over the past two decades, IRAD publications have steadily increased our knowledge and understanding about aortic dissection. Specifically in recent years, analyses of IRAD data have gone beyond simply characterizing the patient with acute type B aortic dissection and have attempted to identify the means by which the outcome of such a patient could be improved. Thus, we present herein three areas in which IRAD data has recently advanced our understanding of acute type B aortic dissection: temporal classification especially for the subacute time period, risk stratification for identifying complicated cases, and thoracic endovascular aortic repair (TEVAR). PMID:25133099

Patel, Akshar Y; Eagle, Kim A; Vaishnava, Prashant

2014-07-01

167

A phosphoproteomics approach to identify candidate kinase inhibitor pathway targets in lymphoma-like primary cell lines.  

PubMed

Mass spectrometry-based technologies are increasingly utilized in drug discovery. Phosphoproteomics in particular has allowed for the efficient surveying of phosphotyrosine signaling pathways involved in various diseases states, most prominently in cancer. We describe a phosphotyrosine-based proteomics screening approach to identify signaling pathways and tyrosine kinase inhibitor targets in highly tumorigenic human lymphoma-like primary cells. We identified several receptor tyrosine kinase pathways and validated SRC family kinases (SFKs) as potential drug targets for targeted selection of small molecule inhibitors. BMS-354825 (dasatinib) and SKI-606 (bosutinib), second and third generation clinical SFK/ABL inhibitors, were found to be potent cytotoxic agents against tumorigenic cells with low toxicity to normal pediatric stem cells. Both SFK inhibitors reduced ERK1/2 and AKT phosphorylation and induced apoptosis. This study supports the adaptation of high-end mass spectrometry techniques for the efficient identification of candidate tyrosine kinases as novel therapeutic targets in primary cancer cell lines. PMID:23701117

Vojvodic, Miliana; Hansford, Loen M; Morozova, Olena; Blakely, Kim M; Taylor, Paul; Fathers, Kelly E; Moffat, Jason; Marra, Marco; Smith, Kristen M; Moran, Michael F; Kaplan, David R

2013-12-01

168

Quantitative genetics in the age of omics  

Microsoft Academic Search

The use of natural variation in the genetic dissection of quantitative traits has a long-standing tradition. Recent advances in high-throughput technologies for the quantification of biological molecules have shifted the focus in quantitative genetics from single traits to comprehensive large-scale analyses. So-called omic technologies now enable geneticists to take a look in the black box that translates genetic information into

Joost JB Keurentjes; Maarten Koornneef; Dick Vreugdenhil

2008-01-01

169

Carotid and vertebral artery dissection syndromes  

PubMed Central

Cervicocerebral arterial dissections (CAD) are an important cause of strokes in younger patients accounting for nearly 20% of strokes in patients under the age of 45 years. Extracranial internal carotid artery dissections comprise 70%–80% and extracranial vertebral dissections account for about 15% of all CAD. Aetiopathogenesis of CAD is incompletely understood, though trauma, respiratory infections, and underlying arteriopathy are considered important. A typical picture of local pain, headache, and ipsilateral Horner's syndrome followed after several hours by cerebral or retinal ischaemia is rare. Doppler ultrasound, MRI/MRA, and CT angiography are useful non-invasive diagnostic tests. The treatment of extracranial CAD is mainly medical using anticoagulants or antiplatelet agents although controlled studies to show their effectiveness are lacking. The prognosis of extracranial CAD is generally much better than that of the intracranial CAD. Recurrences are rare in CAD. PMID:15937204

Thanvi, B; Munshi, S; Dawson, S; Robinson, T

2005-01-01

170

Scope on Safety: Dissection--Don't cut out safety  

NSDL National Science Digital Library

In June 2005, the NSTA Board of Directors adopted a revised position statement, Responsible Use of Live Animals and Dissection in the Science Classroom. Under the "Dissection" section, NSTA calls for more research to determine the effectiveness of animal dissection activities and alternatives, and the extent to which these activities should be integrated into the science curriculum. Until research indicates the effectiveness of alternatives to dissection, many teachers will continue including dissections in their classrooms. Those that do need to make sure they are addressing related safety issues to ensure a successful learning experience. This month's Scope on Safety features NSTA's safety recommendations for safe and ethical dissection practices.

Roy, Ken

2007-02-01

171

The nature of dissection: Exploring student conceptions  

NASA Astrophysics Data System (ADS)

The model of conceptual change in science describes the process of learning as a complete restructuring of knowledge, when learners discover or are shown more plausible, intelligent alternatives to existing conceptions. Emotions have been acknowledged as part of a learner's conceptual ecology, but the effects of emotions on learning have yet to be described. This research was conducted to examine the role that emotions have on learning for thirteen high school students, as they dissected cats in a Human Anatomy and Physiology class. The project also investigated whether a student's emotional reactions may be used to develop a sense of connectedness with the nonhuman world, which is defined as ecological literacy. This study utilized a grounded theory approach, in which student responses to interviews were the primary source of data. Interviews were transcribed, and responses were coded according to a constant comparative method of analysis. Responses were compared with the four conditions necessary for conceptual change to occur, and also to five principles of ecological literacy. Students who had negative reactions to dissection participated less in the activity, and demonstrated less conceptual change. Two female students showed the strongest emotional reactions to dissection, and also the lowest amount of conceptual change. One male student also had strong negative reactions to death, and showed no conceptual change. The dissection experiences of the students in this study did not generally reflect ecological principles. The two students whose emotional reactions to dissection were the most negative demonstrated the highest degree of ecological literacy. These results provide empirical evidence of the effects that emotions have on learning, and also supports the opinions of educators who do not favor dissection, because it does not teach students to respect all forms of life.

York, Katharine

172

Surgical treatment of acute ascending aortic dissection.  

PubMed Central

Since adopting a policy of immediate operation on patients with acute dissection of the ascending aorta, 42 men and 6 women (ages 18-67 years) have been managed surgically. Thirty-two patients had graft replacement of the ascending aorta and resuspension of the incompetent aortic valve. One of these had a coronary graft. There were five deaths in this group. Eight patients required aortic valve replacement because of a diseased aortic valve as well as grafting of the ascending aorta, with one death. Three patients had resuspension of the aortic valve and primary repair of their dissection without mortality. Two patients were managed successfully with an intraluminal prosthesis and resuspension of the aortic valve. Another patient had successful repair with a valved conduit and reimplantation of the coronaries. Two patients dissected 4 and 6 years after aortic valve replacement and neither survived operative repair. Of the surviving patients, one required dialysis, one a femoral-femoral bypass graft, and one an axillo-femoral bypass graft. One patient required a pacemaker for heart block, and two underwent successful repair of suture line aneurysms, both occurring three years after operation. On the basis of this experience, prompt surgical intervention for acute ascending aortic dissection is the treatment of choice. A variety of techniques are available to repair the dissected aorta. Long-term results for resuspension of the aortic valve in acute ascending aortic dissection have been excellent and emphasize that valve replacement should be reserved for those patients found at operation to have a primary abnormality of the aortic valve. PMID:6222709

Wolfe, W G; Oldham, H N; Rankin, J S; Moran, J F

1983-01-01

173

Intracranial Vertebral Artery Dissections: Evolving Perspectives  

PubMed Central

Summary Intracranial vertebral artery dissection (VAD) represents the underlying etiology in a significant percentage of posterior circulation ischemic strokes and subarachnoid hemorrhages. These lesions are particularly challenging in their diagnosis, management, and in the prediction of long-term outcome. Advances in the understanding of underlying processes leading to dissection, as well as the evolution of modern imaging techniques are discussed. The data pertaining to medical management of intracranial VADs, with emphasis on anticoagulants and antiplatelet agents, is reviewed. Surgical intervention is discussed, including, the selection of operative candidates, open and endovascular procedures, and potential complications. The evolution of endovascular technology and techniques is highlighted. PMID:23217643

Ali, M.S.; Amenta, P.S.; Starke, R.M.; Jabbour, P.M.; Gonzalez, L.F.; Tjoumakaris, S.I.; Flanders, A.E.; Rosenwasser, R.H.; Dumont, A.S.

2012-01-01

174

Comparative Phosphoproteome Analysis of the Developing Grains in Bread Wheat (Triticum aestivum L.) under Well-Watered and Water-Deficit Conditions.  

PubMed

Wheat (Triticum aestivum), one of the most important cereal crops, is often threatened by drought. In this study, water deficit significantly reduced the height of plants and yield of grains. To explore further the effect of drought stress on the development and yield of grains, we first performed a large scale phosphoproteome analysis of developing grains in wheat. A total of 590 unique phosphopeptides, representing 471 phosphoproteins, were identified under well-watered conditions. Motif-X analysis showed that four motifs were enriched, including [sP], [Rxxs], [sDxE], and [sxD]. Through comparative phosphoproteome analysis between well-watered and water-deficit conditions, we found that 63 unique phosphopeptides, corresponding to 61 phosphoproteins, showed significant changes in phosphorylation level (?2-fold intensities). Functional analysis suggested that some of these proteins may be involved in signal transduction, embryo and endosperm development of grains, and drought response and defense under water-deficit conditions. Moreover, we also found that some chaperones may play important roles in protein refolding or degradation when the plant is subjected to water stress. These results provide a detailed insight into the stress response and defense mechanisms of developmental grains at the phosphoproteome level. They also suggested some potential candidates for further study of transgenosis and drought stress as well as incorporation into molecular breeding for drought resistance. PMID:25145454

Zhang, Ming; Ma, Cao-Ying; Lv, Dong-Wen; Zhen, Shou-Min; Li, Xiao-Hui; Yan, Yue-Ming

2014-10-01

175

Conservative Management of Chronic Aortic Dissection with Underlying Aortic Aneurysm  

PubMed Central

Aortic dissection is one of the most common aortic emergencies affecting around 2000 Americans each year. It usually presents in the acute state but in a small percentage of patients aortic dissections go unnoticed and these patients survive without any adequate therapy. With recent advances in medical care and diagnostic technologies, aortic dissection can be successfully managed through surgical or medical options, consequently increasing the related survival rate. However, little is known about the optimal long-term management of patients suffering from chronic aortic dissection. The purpose of the present report is to review aortic dissection, namely its pathology and the current diagnostic tools available, and to discuss the management options for chronic aortic dissection. We report a patient in which chronic aortic dissection presented with recurring episodes of vomiting and also discuss the management plan of our patient who had a chronic aortic dissection as well as an underlying aortic aneurysm. PMID:24179638

Yusuf Beebeejaun, Mohammad; Malec, Aleksandra; Gupta, Ravi

2013-01-01

176

A COMPARATIVE PRIMATE ANATOMY Dissection Manual  

E-print Network

is used as a reference species against which we compared the anatomy of the non-human primates. It alsoA COMPARATIVE PRIMATE ANATOMY Dissection Manual Edited by: Rebecca Rogers Ackermann Version 1 Anatomy taught jointly by Professors J Cheverud, G Conroy, and J Phillips-Conroy, at Washington University

Ackermann, Rebecca Rogers

177

Chemistry & Biology Chemical Dissection of the Link  

E-print Network

for dynamic intracellular protein O-glycosylation. We have used galacto-streptozotocin to chemically dissect for streptozotocin, suggesting the need for using more specific inhibitors to study protein O proteins in higher eukaryotes (Zachara and Hart, 2006; Hart et al., 2007). O-GlcNAcylation has been shown

van Aalten, Daan

178

Dissecting the pressure field in tidal flow  

E-print Network

amplitude [N x 107 ] phase relative to the velocity [deg] power [W x107 ] 1 2 3 4 tidal excursion parameterDissecting the pressure field in tidal flow past a headland: When is form drag "real?" Sally Warner waves eddies H L LHH H L L LH #12;Numerical model Gaussian-shaped headland Barotropic tidal velocity D L

Warner, Sally

179

Dissecting the pressure field in tidal flow  

E-print Network

Dissecting the pressure field in tidal flow past a headland: When is form drag "real?" Sally Warner of oscillating flow H L HL velocity form drag power average power floodslack work done on system #12;0 0 0 0 90 180 270 360 90 180 270 360 0 degrees Drag of oscillating flow H L HL velocity form drag power average

Warner, Sally

180

Squid Dissection: From Pen to Ink.  

ERIC Educational Resources Information Center

Introduces students to dissection, which is an important part of scientific discovery. Students not only gain an understanding of the anatomy of a squid, but also develop a sense of responsibility and respect for the animal that they are using as a learning tool. (Author/SOE)

Brown, Cindy; Kisiel, Jim

2003-01-01

181

Spontaneous bilateral carotid artery dissection following cervical manipulation.  

PubMed

We report an autopsy case of a bilateral carotid artery dissection, following cervical manipulation by a chiropractor. To establish the etiology of a cervical artery dissection is important in view of possible legal implications and to exclude hereditary disorders, since cervical artery dissection has been linked to several arteriopathies. The underlying arteriopathy in the presented case was an idiopathic cystic medial degeneration. This report emphasizes the role of the pathologist in defining the underlying arteriopathy in carotid artery dissection. PMID:22633562

Carprieaux, Marilyn; Michotte, Alex; Van Varenbergh, Dirk; Marichal, Miriam Pipeleers

2012-09-01

182

MRI in spontaneous dissection of vertebral and carotid arteries  

Microsoft Academic Search

Fifteen patients were observed between 1987 and 1990: there were six with angiographically confirmed vertebral artery dissection, and 9 with carotid artery dissection. Results showed concordance of MRI and angiographic findings, in all cases but one. The dissected portion consistently showed a semilunar hyperintensity narrowing the residual eccentric signal void of the lumen when the artery was not completely occluded.

F. Gelbert; E. Assouline; J. E. Hodes; D. Reizine; F. Woimant; B. George; M. Hagueneau; J. J. Merland

1991-01-01

183

Spontaneous dissecting aneurysm of the extracranial vertebral artery (20 cases)  

Microsoft Academic Search

Spontaneous dissecting aneurysm of the vertebral artery is an infrequent cause of vertebro basilar ischemic strokes. Previously reported cases concern essentially occlusion of the basilar artery. Only 14 cases of spontaneous dissecting aneurysm concern the extracranial vertebral artery among these eight were angiographically documented. In this study based upon 15 patients (20 dissecting aneurysms), the authors discuss etiological factors, such

J. Chiras; S. Marciano; J. Vega Molina; J. Touboul; B. Poirier; J. Bories

1985-01-01

184

A Novel Approach to the Dissection of the Human Knee  

NSDL National Science Digital Library

This article describes an alternate technique to dissecting the human knee in a cadaver lab. The purpose behind the procedure is to allow for maximal visualization of intra-articular structures that are typically removed early in dissection. This technique modernizes the dissection to allow for students to visualize structures that they would see during a knee replacement surgery.

Michael Schumaker (Youngstown Orthopedics)

2009-02-01

185

A case report on asymptomatic ascending aortic dissection  

PubMed Central

Aortic dissection is a relatively rare but dreadful illness, often presenting with tearing chest pain and acute hemodynamic compromise. Early and accurate diagnosis and treatment are essential for survival. In the present review, a rare case of an asymptomatic ascending aortic dissection is reported. The general clinical manifestations, diagnosis and management of aortic dissection will also be reviewed. PMID:22477421

Cohen, Ronny; Mena, Derrick; Carbajal-Mendoza, Roger; Arole, Olugbenga; Mejia, Jose O

2008-01-01

186

Which Comes First: The Use of Computer Simulation of Frog Dissection or Conventional Dissection as Academic Exercise?  

ERIC Educational Resources Information Center

Science educators and school administrators are reexamining the educational value of animal dissection in the nation's schools and are focusing on simulation as an instructional alternative. One implication of the debate is that simulations can lead to equivalent learning to hands-on dissection. The second implication is whether dissection is…

Akpan, Joseph; Strayer, Jeremy

2010-01-01

187

Student attitudes toward cadaveric dissection at a UK medical school.  

PubMed

A more humanistic approach toward dissection has emerged. However, student attitudes toward this approach are unknown and the influences on such attitudes are little understood. One hundred and fifty-six first-year medical students participated in a study examining firstly, attitudes toward the process of dissection and the personhood of the cadaver and secondly, the extent to which gender, anxiety, exposure to dissection, bereavement and prior experience of a dead body influenced these attitudes. Attitudes toward dissection were assessed by of levels of agreement toward eleven statements and by selection of adjectives describing possible feelings toward dissection. Students were asked about recent bereavement, whether they had seen a dead body prior to starting their course and exposure to dissection when completing the questionnaire. Validated instruments were used to measure disposition toward generalized anxiety (Hospital Anxiety and Depression Scale) and toward death anxiety (Collett-Lester Death Anxiety Scale). Between 60% and 94% of students held positive attitudes toward the process of dissection and over 70% of students selected 2 or fewer negative adjectives. Students' attitudes toward the personhood of the cadaver were more disparate. Disposition toward anxiety (particularly death anxiety), and exposure to dissection, influenced attitudes. Female gender and recent bereavement exerted a negative influence. Students with higher levels of anxiety experienced more negative feelings and those recently bereaved were less enthusiastic about dissection. Anticipation of dissection may be worse than reality. Sensitive preparation of students prior to entering the dissecting room for the first time may be beneficial. PMID:21656918

Quince, Thelma A; Barclay, Stephen I G; Spear, Michelle; Parker, Richard A; Wood, Diana F

2011-01-01

188

Endovascular Treatment of Huge Dissecting Aneurysms Involving the Basilar Artery  

PubMed Central

Summary Dissecting aneurysms involving the basilar artery (BA) are lesions with significant morbidity and mortality. Their management is controversial and often difficult. There is no generally approved strategy. Two cases of huge dissections involving the BA presented with subarachnoid hemorrhage in one case and mass effect in both cases. The dissection of case 1 involved the upper two thirds of the BA distal to the anterior inferior cerebellar arteries (AICA). Another dissection of case 2 involved the bilateral vertebral arteries (VA) distal to bilateral PICA and extended to upper third of the BA. After making a basket with coils inside the pseudoaneursym, proximal dissection was totally occluded in case 1. Dissection on the bilateral VA distal to the bilateral PICA and proximal BA was occluded in case 2 with a small residual dissection on the left VA. Case 1 had an excellent recovery with a durable image and clinical result. But recanalization and regrowth occurred in case 2, which might have originated from the residual dissection on the left VA, induced acute mass effect and sudden coma six weeks after the initial treatment. The residual and regrown dissection had to be occluded in a second intervention. The patient died two days later. BA occlusion is safe and efficient for dissections involving the BA as in our case and the literature. Proximal occlusion might be enough for huge and long lesions like ours. It seems that completely dense packing of proximal dissection is the key point to prevent recanalization. PMID:20566106

Yang, X.; Mu, S.; Lv, M.; Li, L.; Wu, Z.

2007-01-01

189

Medical management in type B aortic dissection  

PubMed Central

Medical management is generally the preferred treatment for uncomplicated type B acute aortic dissection cases. It is often centered on the use of antihypertensive agents, which alleviates hemodynamic stress on the damaged aortic wall. Methods of medical management and drug selection are still based mainly on personal experience, expert opinion and historical observational studies as randomized controlled studies are lacking. Guidelines from European (ESC), American (ACC/AHA) and Asian (Japan) societies in the last decade have made recommendations on use of medications, but also reaffirmed the lack of evidence for therapeutic approaches and targeted medical management. More recent evidence suggests that there may be type-selective benefits for antihypertensive medications. Here, we will discuss the present understanding of medical management of acute aortic dissection. PMID:25133106

Eagle, Kim A.; Bossone, Eduardo; Ballotta, Andrea; Froehlich, James B.; Isselbacher, Eric M.

2014-01-01

190

Complex intimal flaps in acute aortic dissection  

Microsoft Academic Search

A 43-year-old man was emergently admitted and diagnosed as acute aortic dissection (Stanford type A). While being prepared\\u000a for emergent operation he fell into hemodynamic hazard with repeated ventricular fibrillation and loss of consciousness. Massive\\u000a aortic regurgitation and coronary disturbance due to a back-and-forth movement of an intimal flap through the aortic valve\\u000a were the causes of the cardiogenic catastrophy.

Shinji Akishima; Junichi Sakurai; Tomoaki Jikuya

2003-01-01

191

Block data distribution for parallel nested dissection  

SciTech Connect

In this paper, we consider the problem of data partitioning for block sparse Cholesky factorization on distributed memory MIMD computers. We propose a preprocessing algorithm which computes and distributes a column block partition based on an initial partition induced by a nested dissection ordering. This preprocessing algorithm works by optimizing load balancing under precedence constraints and communication traffic. It can be performed in linear time and space complexities.

Charrier, P.; Facq, L.; Roman, J. [Universite Bordeaux, Talence (France)

1995-12-01

192

"Ostrich sign" indicates bilateral vertebral artery dissection.  

PubMed

Vertebral artery dissections (VADs) comprise about 2% of ischemic strokes and can be associated with trauma, chiropractic manipulation, motor vehicle collisions, whiplash, amusement park rides, golfing, and other motion-induced injuries to the neck. We present a case of bilateral extracranial VAD as a complication of conducting an orchestra. To our knowledge, this has not been documented in the literature. Conceivably, vigorous neck twisting in an inexperienced, amateur conductor may place excessive rotational forces upon mobile portions of the verterbral arteries, tear the intima, deposit subintimal blood that extends longitudinally, and cause neck pain and/or posterior fossa ischemic symptoms. Magnetic resonance angiography examinations of axially oriented slices of bilateral VADs resemble the face of an ostrich. This observation is similar to the "puppy sign," in which bilateral internal carotid artery dissections resemble the face of a dog. Craniocervical dissections of either the carotid or vertebral arteries have the potential to form an aneurysm, cause artery-to-artery embolism, or completely occlude the parent artery, resulting in an ischemic stroke. Because bilateral VADs in axial magnetic resonance angiographic sections stand out like the eyes of an ostrich, and because the fast identification of VADs is so critical, we eponymize this image the "ostrich sign." PMID:21440457

Rose, David Z; Husain, M Rizwan

2012-11-01

193

Hybrid Strategy for Residual Arch and Thoracic Aortic Dissection following Acute Type A Aortic Dissection Repair  

PubMed Central

Progressive dilatation of the false lumen in the arch and descending aorta has been encountered in one-third of survivors as a late sequelae following repair of ascending aortic dissection. Conventional treatment for the same requiring cardiopulmonary bypass and deep hypothermic circulatory arrest is associated with high morbidity and mortality especially in the elderly cohort of patients. Herein we report a case of symptomatic progressive aneurysmal dilatation of residual arch and descending thoracic aortic dissection following repair of type A aortic dissection, successfully treated by total arch debranching and ascending aortic prosthesis to bicarotid and left subclavian bypass followed by staged retrograde aortic stent-graft deployment. This case report with relevant review of the literature highlights this clinical entity and the present evidence on its appropriate management strategies. Close surveillance is mandatory following surgical repair of type A aortic dissection and hybrid endovascular procedures seem to be the most dependable modality for salvage of patients detected to have progression of residual arch dissection. PMID:24716088

Agrawal, Vivek; Parameshwarappa, Shashidhar Kallappa; Savlania, Ajay; Kumar, Santhosh; Madathipat, Unnikrishnan

2014-01-01

194

Optimization of enrichment conditions on TiO2 chromatography using glycerol as an additive reagent for effective phosphoproteomic analysis.  

PubMed

Metal oxide affinity chromatography (MOAC) represented by titanium dioxide (TiO2) chromatography has been used for phosphopeptide enrichment from cell lysate digests prior to mass spectrometry. For in-depth phosphoproteomic analysis, it is important for MOAC to achieve high phosphopeptide enrichment efficiency by optimizing purification conditions. However, there are some differences in phosphopeptide selectivity and specificity enriched by various TiO2 materials and procedures. Here, we report that binding/wash buffers containing polyhydric alcohols, such as glycerol, markedly improve phosphopeptide selectivity from complex peptide mixtures. In addition, the elution conditions combined with secondary amines, such as bis-Tris propane, made it possible to recover phosphopeptides with highly hydrophobic properties and/or longer peptide lengths. To assess the practical applicability of our improved method, we confirmed using PC3 prostate cancer cells. By combining the hydrophilic interaction chromatography (HILIC) with the optimized TiO2 enrichment method prior to LC-MS/MS analysis, over 8300 phosphorylation sites and 2600 phosphoproteins were identified. Additionally, some dephosphorylations of those were identified by treatment with dasatinib for a kinase inhibitor. These results indicate that our method is applicable to understanding the profiling of kinase inhibitors such as anticancer compounds, which will be useful for drug discovery and development. PMID:24245541

Fukuda, Isao; Hirabayashi-Ishioka, Yoshino; Sakikawa, Ikue; Ota, Takeshi; Yokoyama, Mari; Uchiumi, Takaoki; Morita, Atsushi

2013-12-01

195

Proteomic and phospho-proteomic profile of human platelets in basal, resting state: insights into integrin signaling.  

PubMed

During atherogenesis and vascular inflammation quiescent platelets are activated to increase the surface expression and ligand affinity of the integrin alphaIIbbeta3 via inside-out signaling. Diverse signals such as thrombin, ADP and epinephrine transduce signals through their respective GPCRs to activate protein kinases that ultimately lead to the phosphorylation of the cytoplasmic tail of the integrin alphaIIbbeta3 and augment its function. The signaling pathways that transmit signals from the GPCR to the cytosolic domain of the integrin are not well defined. In an effort to better understand these pathways, we employed a combination of proteomic profiling and computational analyses of isolated human platelets. We analyzed ten independent human samples and identified a total of 1507 unique proteins in platelets. This is the most comprehensive platelet proteome assembled to date and includes 190 membrane-associated and 262 phosphorylated proteins, which were identified via independent proteomic and phospho-proteomic profiling. We used this proteomic dataset to create a platelet protein-protein interaction (PPI) network and applied novel contextual information about the phosphorylation step to introduce limited directionality in the PPI graph. This newly developed contextual PPI network computationally recapitulated an integrin signaling pathway. Most importantly, our approach not only provided insights into the mechanism of integrin alphaIIbbeta3 activation in resting platelets but also provides an improved model for analysis and discovery of PPI dynamics and signaling pathways in the future. PMID:19859549

Qureshi, Amir H; Chaoji, Vineet; Maiguel, Dony; Faridi, Mohd Hafeez; Barth, Constantinos J; Salem, Saeed M; Singhal, Mudita; Stoub, Darren; Krastins, Bryan; Ogihara, Mitsunori; Zaki, Mohammed J; Gupta, Vineet

2009-01-01

196

Gene expression in acute Stanford type A dissection: a comparative microarray study  

PubMed Central

Background We compared gene expression profiles in acutely dissected aorta with those in normal control aorta. Materials and methods Ascending aorta specimen from patients with an acute Stanford A-dissection were taken during surgery and compared with those from normal ascending aorta from multiorgan donors using the BD Atlas™ Human1.2 Array I, BD Atlas™ Human Cardiovascular Array and the Affymetrix HG-U133A GeneChip®. For analysis only genes with strong signals of more than 70 percent of the mean signal of all spots on the array were accepted as being expressed. Quantitative real-time polymerase chain reaction (RT-PCR) was used to confirm regulation of expression of a subset of 24 genes known to be involved in aortic structure and function. Results According to our definition expression profiling of aorta tissue specimens revealed an expression of 19.1% to 23.5% of the genes listed on the arrays. Of those 15.7% to 28.9% were differently expressed in dissected and control aorta specimens. Several genes that encode for extracellular matrix components such as collagen IV ?2 and -?5, collagen VI ?3, collagen XIV ?1, collagen XVIII ?1 and elastin were down-regulated in aortic dissection, whereas levels of matrix metalloproteinases-11, -14 and -19 were increased. Some genes coding for cell to cell adhesion, cell to matrix signaling (e.g., polycystin1 and -2), cytoskeleton, as well as several myofibrillar genes (e.g., ?-actinin, tropomyosin, gelsolin) were found to be down-regulated. Not surprisingly, some genes associated with chronic inflammation such as interleukin -2, -6 and -8, were up-regulated in dissection. Conclusion Our results demonstrate the complexity of the dissecting process on a molecular level. Genes coding for the integrity and strength of the aortic wall were down-regulated whereas components of inflammatory response were up-regulated. Altered patterns of gene expression indicate a pre-existing structural failure, which is probably a consequence of insufficient remodeling of the aortic wall resulting in further aortic dissection. PMID:16824202

Weis-Muller, Barbara Theresia; Modlich, Olga; Drobinskaya, Irina; Unay, Derya; Huber, Rita; Bojar, Hans; Schipke, Jochen D; Feindt, Peter; Gams, Emmeran; Muller, Wolfram; Goecke, Timm; Sandmann, Wilhelm

2006-01-01

197

Effectiveness of a new inflatable balloon device for gluing dissected layers in an experimental model of aortic dissection  

PubMed Central

OBJECTIVES: In the surgical treatment of acute aortic dissection, tissue glues are widely used to reinforce the adhesion between the dissected aortic layers. A new inflatable balloon device was developed to compress the dissected aortic wall during gluing to increase adhesion between the dissected layers. The present study used an ex vivo experimental animal model to test the hypothesis that this device is effective when gluing the true and false channels of dissected aortas. METHODS: In the ex vivo experimental model, aortic dissection was simulated surgically on 12 fresh bovine aorta samples. In six samples (group I), the inflatable balloon device was inserted into the aorta to reinforce and fuse the dissected layers during gluing. The other six fresh bovine aortic samples (group II) were compressed between the surgeon’s fingers during gluing. Aortic samples were evaluated and compared macroscopically and histologically. RESULTS: In group I, adhesion between the dissected layers was easily achieved during gluing. All false cavities were perfectly closed, with no deleterious effects related to the device. In group II, the adhesion between the dissected layers was not complete and some false cavities remained patent. CONCLUSIONS: The inflatable balloon device can increase the adhesive effect of tissue glues via homogenous compression of the dissected aortic layers. In addition, the balloon can prevent distal embolization of the glue. PMID:23940445

Colak, Necmettin; Nazli, Yunus; Alpay, Mehmet Fatih; Akkaya, Ismail Olgun; Aksoy, Omer Nuri; Akgedik, Sukran; Cakir, Omer

2013-01-01

198

Metabolic Signature of Electrosurgical Liver Dissection  

PubMed Central

Background and Aims High frequency electrosurgery has a key role in the broadening application of liver surgery. Its molecular signature, i.e. the metabolites evolving from electrocauterization which may inhibit hepatic wound healing, have not been systematically studied. Methods Human liver samples were thus obtained during surgery before and after electrosurgical dissection and subjected to a two-stage metabolomic screening experiment (discovery sample: N?=?18, replication sample: N?=?20) using gas chromatography/mass spectrometry. Results In a set of 208 chemically defined metabolites, electrosurgical dissection lead to a distinct metabolic signature resulting in a separation in the first two dimensions of a principal components analysis. Six metabolites including glycolic acid, azelaic acid, 2-n-pentylfuran, dihydroactinidiolide, 2-butenal and n-pentanal were consistently increased after electrosurgery meeting the discovery (p<2.0×10?4) and the replication thresholds (p<3.5×10?3). Azelaic acid, a lipid peroxidation product from the fragmentation of abundant sn-2 linoleoyl residues, was most abundant and increased 8.1-fold after electrosurgical liver dissection (preplication?=?1.6×10?4). The corresponding phospholipid hexadecyl azelaoyl glycerophosphocholine inhibited wound healing and tissue remodelling in scratch- and proliferation assays of hepatic stellate cells and cholangiocytes, and caused apoptosis dose-dependently in vitro, which may explain in part the tissue damage due to electrosurgery. Conclusion Hepatic electrosurgery generates a metabolic signature with characteristic lipid peroxidation products. Among these, azelaic acid shows a dose-dependent toxicity in liver cells and inhibits wound healing. These observations potentially pave the way for pharmacological intervention prior liver surgery to modify the metabolic response and prevent postoperative complications. PMID:24058442

von Schonfels, Witigo; von Kampen, Oliver; Patsenker, Eleonora; Stickel, Felix; Schniewind, Bodo; Hinz, Sebastian; Ahrens, Markus; Balschun, Katharina; Egberts, Jan-Hendrik; Richter, Klaus; Landrock, Andreas; Sipos, Bence; Will, Olga; Huebbe, Patrizia; Schreiber, Stefan; Nothnagel, Michael; Rocken, Christoph; Rimbach, Gerald; Becker, Thomas

2013-01-01

199

MRI and MR angiography of vertebral artery dissection  

Microsoft Academic Search

A review of 4,500 angiograms yielded 11 patients with dissection of the vertebral arteries who had MRI and (in 4 patients)\\u000a MR angiography (MRA) in the acute phase of stroke. One patient with incidental discovery at arteriography of asymptomatic\\u000a vertebral artery dissection and two patients with acute strokes with MRI and MRA findings consistent with vertebral artery\\u000a dissection were included.

M. Mascalchi; M. C. Bianchi; S. Mangiafico; G. Ferrito; M. Puglioli; E. Marin; S. Mugnai; R. Canapicchi; N. Quilici; D. Inzitari

1997-01-01

200

Iatrogenic left main artery dissection: A catastrophic complication  

PubMed Central

Iatrogenic left main artery (LM) dissection is a catastrophic complication of coronary angiography and angioplasty that requires prompt management using stenting. Although LM dissection can be prevented, it cannot always be avoided and has a reported incidence rate of 0.02%. In the present report, a case of iatrogenic LM dissection that was successfully treated with multiple stents is presented and followed by a brief review of the literature. PMID:23592948

Namazi, Mohammad Hassan; Rostami, Reza Tajik; Mohammadi, Afsaneh; Amini, Abdol Latifi; Safi, Morteza; Saadat, Habibollah; Vakili, Hosein; Motamedi, Mohammad Reza; Movahed, Mohammad Reza

2012-01-01

201

Ascending aorta dissection associated with bicuspid aortic valve  

Microsoft Academic Search

Aortic dissection etiology involve many factors that are difficult to identify clearly. We report a 47-year-old man who underwent\\u000a a Bentall operation with reattachment of bypass grafts for a dissecting aneurysm (De Bakey type II) 4 years after combined\\u000a triple coronary artery bypass grafting and mitral valve replacement. This case appeared to be associated with factors leading\\u000a to dissecting aneurysm

Atsushi Morishita; Tadayuki Shimakura; Masaki Nonoyama; Taiichi Takasaki; Masataka Yoda

2001-01-01

202

Unexpected limited chronic dissection of the ascending aorta  

PubMed Central

We report a rare case of a limited chronic dissection of the ascending aorta that was accidentally discovered at operation performed for severe aortic stenosis and moderate to severe dilatation of the ascending aorta. Preoperative investigations such as transoesophageal echocardiography and cardiac catheterization missed the diagnosis of dissection. Intraoperative findings included a 3.5 cm eccentric bulge of the ascending aorta and a 5 mm circular shaped intimal tear comunicating with a limited hematoma or small dissection of the media layer. (The rarety of the report is that the chronic dissection is limited to a small area (approximatively 3.5 × 2.5 cm) of the ascending aorta). PMID:18638403

Venturini, Andrea; Zoffoli, Giampaolo; Mangino, Domenico; Ascione, Raimondo; Terrini, Alberto; Asta, Angiolino; Angelini, Gianni; Polesel, Elvio

2008-01-01

203

Orientation to dissection: Assisting students through the transition.  

PubMed

Human dissection continues to be strongly argued for teaching human anatomy to medical students and is technically and emotionally demanding. An orientation to dissection and the laboratory are provided for students before beginning their work because students' and families' reactions to dissection are often complex. This study explored medical students' experiences of attending an orientation to human dissection and the anatomy laboratory. Students' reactions, feelings, and thoughts were enquired about 1 year after beginning dissection at the University of Auckland, New Zealand. Qualitative research methods, specifically one-on-one semistructured interview were utilized. Third-year medical students self-selected into the study and were interviewed 1 year after entering the laboratory. Transcribed audiotapes of the interviews were analyzed for themes across the interviews. One year after dissection students have vivid memories with differing ways of viewing the body that may help or hinder with dissection. The themes presented include orientation, student anticipation, psychological approach to the body, normalizing-continuing disquiet, and social reference. The orientation eases student entry into the laboratory. There can be ongoing feelings of ambivalence regards the body for some students. Novel findings include that students not only have their own feelings to deal with but also those of friends and family who question them and may feel uncomfortable with the idea of them dissecting. Even one year after beginning dissection, students may emotionally struggle with their work and may require further support, including how they talk about sensitive topics with other people. PMID:21815220

Lamdin, R; Weller, J; Kerse, N

2012-03-01

204

Molecular Mechanisms of Thoracic Aortic Dissection  

PubMed Central

Thoracic aortic dissection (TAD) is a highly lethal vascular disease. In many patients with TAD, the aorta progressively dilates and ultimately ruptures. Dissection formation, progression, and rupture cannot be reliably prevented pharmacologically because the molecular mechanisms of aortic wall degeneration are poorly understood. The key histopathologic feature of TAD is medial degeneration, a process characterized by smooth muscle cell depletion and extracellular matrix degradation. These structural changes have a profound impact on the functional properties of the aortic wall and can result from excessive protease-mediated destruction of the extracellular matrix, altered signaling pathways, and altered gene expression. Review of the literature reveals differences in the processes that lead to ascending versus descending and sporadic versus hereditary TAD. These differences add to the complexity of this disease. Although tremendous progress has been made in diagnosing and treating TAD, a better understanding of the molecular, cellular, and genetic mechanisms that cause this disease is necessary to developing more effective preventative and therapeutic treatment strategies. PMID:23856125

Wu, Darrell; Shen, Ying H.; Russell, Ludivine; Coselli, Joseph S.; LeMaire, Scott A.

2013-01-01

205

Genetics and phosphoproteomics reveal a protein phosphorylation network in the abscisic acid signaling pathway in Arabidopsis thaliana.  

PubMed

Abscisic acid (ABA) is a phytohormone that regulates diverse plant processes, including seed germination and the response to dehydration. In Arabidopsis thaliana, protein kinases of the SNF1-related protein kinase 2 (SnRK2) family are believed to transmit ABA- or dehydration-induced signals through phosphorylation of downstream substrates. By mass spectrometry, we identified proteins that were phosphorylated in Arabidopsis wild-type plants, but not in mutants lacking all three members of the SnRK2 family (srk2dei), treated with ABA or subjected to dehydration stress. The number of differentially phosphorylated peptides was greater in srk2dei plants treated with ABA than in the ones subjected to dehydration, suggesting that SnRK2 was mainly involved in ABA signaling rather than dehydration. We identified 35 peptides that were differentially phosphorylated in wild-type but not in srk2dei plants treated with ABA. Biochemical and genetic studies of candidate SnRK2-regulated phosphoproteins showed that SnRK2 promoted the ABA-induced activation of the mitogen-activated protein kinases AtMPK1 and AtMPK2; that SnRK2 mediated phosphorylation of Ser(45) in a bZIP transcription factor, AREB1 (ABA-responsive element binding protein 1), and stimulated ABA-responsive gene expression; and that a previously unknown protein, SnRK2-substrate 1 (SNS1), was phosphorylated in vivo by ABA-activated SnRK2s. Reverse genetic analysis revealed that SNS1 inhibited ABA responses in Arabidopsis. Thus, by integrating genetics with phosphoproteomics, we identified multiple components of the ABA-responsive protein phosphorylation network. PMID:23572148

Umezawa, Taishi; Sugiyama, Naoyuki; Takahashi, Fuminori; Anderson, Jeffrey C; Ishihama, Yasushi; Peck, Scott C; Shinozaki, Kazuo

2013-04-01

206

Phosphoproteome analysis of an early onset mouse model (TgCRND8) of Alzheimer's disease reveals temporal changes in neuronal and glia signaling pathways.  

PubMed

Sustained exposure to soluble amyloid ? (A?42 ) oligomers is predicted to impair synaptic function in the hippocampal-entorhinal circuit, signaling synaptic loss and precipitating cognitive impairment in Alzheimer's disease. Regional changes in overall patterns of protein phosphorylation are likely crucial to promote transition from a presymptomatic to a symptomatic state in response to accumulating A?42. Here, we used unbiased proteomic approaches to compare the phosphoproteome of presymptomatic and symptomatic TgCRND8 mice and identify network disruptions in signaling pathways implicated in the manifestation of behavioral indices of learning and memory impairment. Phosphopeptide enrichment with triple isotopic dimethylation labeling combined with online multidimensional separation and MS was used to profile phosphoproteome changes in 2- and 6-month-old TgCRND8 mice and congenic littermate controls. We identified 1026 phosphopeptides representing 1168 phosphorylation sites from 476 unique proteins. Of these, 595 phosphopeptides from 293 unique proteins were reliably quantified and 139 phosphopeptides were found to change significantly in the hippocampus of TgCRND8 mice following conversion from a presymptomatic to a symptomatic state. PMID:23335269

Wang, Fangjun; Blanchard, Alexandre P; Elisma, Fred; Granger, Matthew; Xu, Hongbin; Bennett, Steffany A L; Figeys, Daniel; Zou, Hanfa

2013-04-01

207

The Effect of a Prior Dissection Simulation on Middle School Students' Dissection Performance and Understanding of the Anatomy and Morphology of the Frog.  

ERIC Educational Resources Information Center

Reports on a study that examined the prior use of simulation on frog dissection in improving students' actual dissection performance and learning of frog anatomy and morphology. Finds that students who performed the simulation before dissection performed significantly better than students who performed dissection before using the simulation or…

Akpan, Joseph Paul; Andre, Thomas

1999-01-01

208

Cerebral Dissecting Aneurysms in Patients with Essential Thrombocythemia  

PubMed Central

The etiologies of intracranial artery dissection are various, the exogenous as well as inherited connective tissue disorders. We report on a patient who presented with diffuse subarachnoid hemorrhage who had been suffered from essential thrombocythemia. He was diagnosed to multiple dissecting aneurysms of left superior cerebellar artery, left posterior inferior cerebellar artery and right pericallosal artery and treated with endovascular coil embolization. PMID:25368771

Baek, Jin Wook

2014-01-01

209

Dissection Videos Do Not Improve Anatomy Examination Scores  

ERIC Educational Resources Information Center

In this quasi-experimental study, we describe the effect of showing dissection videos on first-year medical students' performance in terms of test scores during a gross anatomy course. We also surveyed students' perception regarding the showing of dissection videos. Two hundred eighty-seven first-year medical students at Rawalpindi Medical College…

Mahmud, Waqas; Hyder, Omar; Butt, Jamaal; Aftab, Arsalan

2011-01-01

210

Geographic Dissection of the Twitter Network Juhi Kulshrestha Farshad Kooti  

E-print Network

Geographic Dissection of the Twitter Network Juhi Kulshrestha Farshad Kooti Max Planck Institute interactions occur online via social net- working sites like Twitter and Facebook, users can in- teract in online social networks? In this paper, we attempt to address this question by dissecting the Twitter so

Gummadi, Krishna P.

211

A Modified Dissection Method to Preserve Neck Structures  

ERIC Educational Resources Information Center

The neck is not only one of the more challenging anatomical regions to dissect but also has important application to clinical conditions, diseases, and procedures. In this study, we describe two simple modifications for dissection of the neck that (1) aid in the identification and preservation of the cutaneous branches of the cervical plexus and…

Hankin, Mark H.; Stoller, Jeremy L.

2009-01-01

212

Student Attitudes toward Cadaveric Dissection at a UK Medical School  

ERIC Educational Resources Information Center

A more humanistic approach toward dissection has emerged. However, student attitudes toward this approach are unknown and the influences on such attitudes are little understood. One hundred and fifty-six first-year medical students participated in a study examining firstly, attitudes toward the process of dissection and the personhood of the…

Quince, Thelma A.; Barclay, Stephen I. G.; Spear, Michelle; Parker, Richard A.; Wood, Diana F.

2011-01-01

213

Supraomohyoid neck dissection in cancer of the oral cavity  

Microsoft Academic Search

Background: In oral cavity cancer, supraomohyoid neck dissection (SOHND) is becoming more popular for patients with N0 and N1 disease in the neck. The aim of this study was to assess the value of this surgical procedure.Methods: The study included 237 previously untreated patients with oral cavity cancer. The neck treatment consisted of SOHND or functional neck dissection (FND). One

Claire Majoufre; Alain Faucher; Carine Laroche; Camille De Bonfils; François Siberchicot; Jean-Louis Renaud-Salis; Jacques Pinsolle

1999-01-01

214

Student Attitudes Toward Cadaveric Dissection at a UK Medical School  

NSDL National Science Digital Library

This article describes a survey conducted among first year medical students examining two main questions. One, attitudes toward the process of dissection and the personhood of the cadaver Two, the extent to which gender, anxiety, exposure to dissection, bereavement and prior experience of a dead body influenced these attitudes. Outcomes and suggestions on how to respond to first year dissectors are provided.

Thelma Quince (University of Cambridge Department of Public Health and Primary Care)

2011-06-08

215

Coronary artery dissection following blunt chest trauma: a case report  

PubMed Central

Coronary artery dissection following blunt chest trauma is rare. We report the case of a 43-year-old woman who was admitted with a subacute inferior myocardial infarction due to dissection of the right coronary artery. Ten days earlier, she had sustained a minimal chest trauma. The literature is reviewed and management is discussed. ImagesFigure 1Figure 2

Swinkels, B.M.; Hoedemaker, G.; Peters, R.H.J.

2005-01-01

216

Signal transduction in cerebral arteries after subarachnoid hemorrhage--a phosphoproteomic approach  

PubMed Central

After subarachnoid hemorrhage (SAH), pathologic changes in cerebral arteries contribute to delayed cerebral ischemia and poor outcome. We hypothesize such changes are triggered by early intracellular signals, targeting of which may prevent SAH-induced vasculopathy. We performed an unbiased quantitative analysis of early SAH-induced phosphorylations in cerebral arteries and evaluated identified signaling components as targets for prevention of delayed vasculopathy and ischemia. Labeled phosphopeptides from rat cerebral arteries were quantified by high-resolution tandem mass spectrometry. Selected SAH-induced phosphorylations were validated by immunoblotting and monitored over a 24-hour time course post SAH. Moreover, inhibition of key phosphoproteins was performed. Major SAH-induced phosphorylations were observed on focal adhesion complexes, extracellular regulated kinase 1/2 (ERK1/2), calcium calmodulin-dependent kinase II, signal transducer and activator of transcription (STAT3) and c-Jun, the latter two downstream of ERK1/2. Inhibition of ERK1/2 6-hour post SAH prevented increases in cerebrovascular constrictor receptors, matrix metalloprotease-9, wall thickness, and improved neurologic outcome. STAT3 inhibition partially mimicked these effects. The study shows that quantitative mass spectrometry is a strong approach to study in vivo vascular signaling. Moreover, it shows that targeting of ERK1/2 prevents delayed pathologic changes in cerebral arteries and improves outcome, and identifies SAH-induced signaling components downstream and upstream of ERK1/2. PMID:23715060

Parker, Benjamin L; Larsen, Martin R?ssel; Edvinsson, Lars IH; Povlsen, Gro Klitgaard

2013-01-01

217

Traditional versus Computer-Based Dissections in Enhancing Learning in a Tertiary Setting: A Student Perspective.  

ERIC Educational Resources Information Center

Describes a study that investigates both the use and usefulness of laboratory dissections and computer-based dissections in a tertiary, first-year human biology course. Explores attitudes toward dissection. (DDR)

Franklin, Sue; Peat, Mary; Lewis, Alison

2002-01-01

218

78 FR 6838 - Certain Balloon Dissection Devices and Products Containing Same; Institution of Investigation  

Federal Register 2010, 2011, 2012, 2013

...337-TA-865] Certain Balloon Dissection Devices and Products...importation of certain dissection balloons and products containing the...importation of certain dissection balloons and products containing the...Geisingen, Germany; Pajunk Medical Systems L.P., 6611...

2013-01-31

219

Pancreatic dissection in the procedure of pancreaticoduodenectomy (with videos).  

PubMed

The procedure of pancreaticoduodenectomy consists of three parts: resection, lymph node dissection, and reconstruction. A transection of the pancreas is commonly performed after a maneuver of the pancreatic head, exposing of the portal vein or lymph node dissection, and it should be confirmed as a safe method for pancreatic transection for decreasing the incidence of pancreatic fistula. However, there are only a few clinical trials with high levels of evidence for pancreatic surgery. In this report, we discuss the following issues: dissection of peripancreatic tissue, exposing the portal vein, pancreatic transection, dissection of the right hemicircle of the peri-superior mesenteric artery including plexus and lymph nodes, and dissection of the pancreatic parenchyma. PMID:22076671

Yamaue, Hiroki; Tani, Masaji; Kawai, Manabu; Hirono, Seiko; Okada, Ken-ichi; Miyazawa, Motoki

2012-03-01

220

Open surgical repair for chronic type B aortic dissection: a systematic review  

PubMed Central

Background The treatment of chronic type B aortic dissection (CBAD) remains complicated. Thoracic endovascular aortic repair (TEVAR) has supplanted open surgical repair (OSR) as the preferred surgical treatment for CBAD. Despite TEVAR’s superior short-term results, much less is understood about its long-term outcomes. As much of the understanding of OSR originates from historical report, contemporary series, with modern surgical techniques and technologies, may present an alternative to TEVAR. The present systematic review will assess the short- and long-term outcomes of historic and contemporary series of OSR for CBAD. Methods Electronic searches were performed using six databases from their inception to March 2014. Relevant studies with OSRs for chronic type B dissection were identified. Data were extracted by two independent reviewers and analyzed according to predefined clinical endpoints. Studies were sub-classified into the pre-endovascular (historic series) and endovascular era (contemporary series) depending on whether the majority of cases were performed after 1999. Results Nineteen studies were identified for inclusion for quantitative analysis. Pooled short-term mortality was 11.1% overall, and 7.5% in the nine contemporary studies. Stroke, spinal cord ischemia, renal dysfunction, and reoperation for bleeding were 5.9%, 4.9%, 8.1%, and 8.1%, respectively, for the contemporary series. Absolute late reintervention was identified in 13.3% of patients overall, and in 11.3% of patients in the contemporary series. Aggregated survival at 1-, 3-, 5-, and 10-years of all patients were 82.1%, 74.1%, 66.3%, and 50.8%, respectively. Conclusions OSR for chronic type B dissection in the contemporary era offers acceptable results. Management approaches should be considered carefully, taking into account both short-term and long-term complications. More research is required to clarify specific indications for OSR and TEVAR in chronic type B dissections. PMID:25133097

Tian, David H.; De Silva, Ramesh P.; Wang, Tom

2014-01-01

221

PBS Learning Media: Cow's Eye Dissection  

NSDL National Science Digital Library

This video-based interactive activity gives users a close-up and fascinating view of the anatomy of a real cow eye as it is dissected by a teenage narrator. You'll get a view of the cornea, watch light refract through the extracted lens, see the retina from the inside, and more. The Flash movies are divided into 12 segments which may be stopped/started interactively. Each segment contains text information with vocabulary definitions in hover-over format. The resource also provides a diagram of the eye and detailed illustrations of how the eye refracts light and sends messages to the optic nerve. PBS Learning Media is a growing collection of 10,000+ free educational resources compiled by researchers and experienced teachers to promote the use of digital resources in the classroom.

2009-06-12

222

Endoscopic submucosal dissection for colorectal neoplasms  

PubMed Central

Endoscopic submucosal dissection (ESD) is an established therapeutic technique for the treatment of gastrointestinal neoplasms. Because it is typically completed as en bloc resection, this technique provides a complete specimen for precise pathological evaluation. On the other hand, ESD is not as widely applied in treating colorectal neoplasms as with gastric cancers, due to its technical difficulty, longer procedure time, and increased risk of perforation. However, some devices that facilitate ESD and improve the safety of the procedure have been recently reported, and the use of the technique has gradually spread worldwide. Endoscopists who begin to perform ESD need to recognize the indications of ESD, the technical issue involved in this procedure, and its associated complications. This review outlines the methods and certain types of devices used for colorectal ESD. PMID:25333002

Takamaru, Hiroyuki; Mori, Genki; Yamada, Masayoshi; Kinjo, Yuzuru; So, Eriko; Abe, Seiichiro; Otake, Yosuke; Nakajima, Takeshi; Matsuda, Takahisa; Saito, Yutaka

2014-01-01

223

Vertebral artery dissection associated with viral meningitis  

PubMed Central

Background Vertebral artery dissection (VAD) is often associated with trauma or occurs spontaneously, inevitably causing some neurological deficits. Even though acute infection can be related to the development of spontaneous VAD (sVAD), VAD associated with viral meningitis has never been reported in the literature. Case presentation A 42-year-old man with fever, sore throat, and runny nose developed sudden onset of occipital headache, vertigo, transient confusion, diplopia, and ataxia. Brain stem encephalitis was diagnosed initially because the cerebrospinal fluid (CSF) study showed inflammatory changes. However, subsequent diffusion-weighted (DWI) magnetic resonance imaging of his brain demonstrated left lateral medullary infarction, and the digital subtraction angiography (DSA) confirmed VAD involving left V4 segment of the artery. Consequently, the patient was diagnosed as VAD accompanied by viral meningitis. Conclusion This case suggests that viral meningitis might lead to inflammatory injury of the vertebral arterial wall, even sVAD with multiple neurological symptoms. PMID:22909191

2012-01-01

224

The Effects of Computer Animated Dissection versus Preserved Animal Dissection on the Student Achievement in a High School Biology Class.  

ERIC Educational Resources Information Center

The purpose of this study was to examine the effectiveness of computer-animated dissection techniques versus the effectiveness of traditional dissection techniques as related to student achievement. The sample used was 104 general biology students from a small, rural high school in Northeast Tennessee. Random selection was used to separate the…

Kariuki, Patrick; Paulson, Ronda

225

On Quantitizing  

PubMed Central

Quantitizing, commonly understood to refer to the numerical translation, transformation, or conversion of qualitative data, has become a staple of mixed methods research. Typically glossed are the foundational assumptions, judgments, and compromises involved in converting disparate data sets into each other and whether such conversions advance inquiry. Among these assumptions are that qualitative and quantitative data constitute two kinds of data, that quantitizing constitutes a unidirectional process essentially different from qualitizing, and that counting is an unambiguous process. Among the judgments are deciding what and how to count. Among the compromises are balancing numerical precision with narrative complexity. The standpoints of “conditional complementarity,” “critical remediation,” and “analytic alternation” clarify the added value of converting qualitative data into quantitative form. PMID:19865603

Sandelowski, Margarete; Voils, Corrine I.; Knafl, George

2009-01-01

226

[Aortic dissection and carotid arteries dissection complicated by ischaemic stroke in a patient with cystic medial necrosis].  

PubMed

We present a case of a 62-year-old man who was admitted in grave condition to the Institute of Psychiatry and Neurology because of ischaemic stroke. Neurological examination re- vealed left-sided pyramidal hemiparesis. Computed tomography (CT) showed the ischaemic focus in the right cerebral hemisphere. Clinical examination and ultrasound examination revealed dissection of the aortic arch and extracranial arteries. Aortic dissection was confirmed in echocardiography and chest CT. The patient remained comatose and died after 7 days. Post-mortem examination identified dissection of the aortic arch, brachiocephalic truncus, common carotid arteries, internal carotid arteries and dissection extending along the whole aorta into both iliac arteries. This examination also showed a massive haemopericardium and a scar in the heart muscle after myocardial infarction. Microscopic examination identified cystic medial necrosis. This type of dissection is very rarely described. PMID:20054762

Jachi?ska, Katarzyna; Lipczy?ska-?ojkowska, Wanda; Kuran, W?odzimierz; Rozenfeld, Anna; Grochowska, Elzbieta; Szpak, Grazyna M; Lenart, Janusz

2009-01-01

227

Level V in therapeutic neck dissections for papillary thyroid carcinoma.  

PubMed

Neck dissection for papillary thyroid carcinoma (PTC) is the standard of care for patients with clinical evidence of regional metastases. However, the extent of neck dissection is debatable. The purpose of the current study was to develop evidence-based recommendations for when to include level V, or 1 of its sublevels, among patients with PTC undergoing neck dissection. A literature review of all studies evaluating the occurrence of metastases in level V in patients with regional metastases from PTC undergoing neck dissection was performed. Occurrence of metastases at level V is low in most series (5% to 10%), although a wide range was noticed. In cases in which metastases were found at level V, they occurred almost exclusively at sublevel VB. Sublevel VA was rarely, if ever, involved with metastatic lymph nodes. However, only recently have investigators begun to specify which sublevels of level V are at risk. Therapeutic dissection of level V is indicated when there is clinical evidence of disease involving this zone. Elective dissection of sublevel VB is indicated when there is involvement of level IV, or possibly multiple nodes at levels II and III. Under these circumstances, dissection of sublevel VB is indicated but sublevel VA may be spared. PMID:22287259

Khafif, Avi; Medina, Jesus E; Robbins, K Thomas; Silver, Carl E; Weber, Randal S; Rinaldo, Alessandra; Owen, Randall P; Shaha, Ashok R; Ferlito, Alfio

2013-04-01

228

Dissection and Downstream Analysis of Zebra Finch Embryos at Early Stages of Development  

PubMed Central

The zebra finch (Taeniopygiaguttata) has become an increasingly important model organism in many areas of research including toxicology1,2, behavior3, and memory and learning4,5,6. As the only songbird with a sequenced genome, the zebra finch has great potential for use in developmental studies; however, the early stages of zebra finch development have not been well studied. Lack of research in zebra finch development can be attributed to the difficulty of dissecting the small egg and embryo. The following dissection method minimizes embryonic tissue damage, which allows for investigation of morphology and gene expression at all stages of embryonic development. This permits both bright field and fluorescence quality imaging of embryos, use in molecular procedures such as in situ hybridization (ISH), cell proliferation assays, and RNA extraction for quantitative assays such as quantitative real-time PCR (qtRT-PCR). This technique allows investigators to study early stages of development that were previously difficult to access. PMID:24999108

Murray, Jessica R.; Stanciauskas, Monika E.; Aralere, Tejas S.; Saha, Margaret S.

2014-01-01

229

Aortic dissection one year after aortic valve replacement.  

PubMed

Acute aortic dissection after aortic valve replacement is rare. A 57-year-old man presented with an acute type A aortic dissection 1 year after aortic valve replacement, which originated from the previous aortotomy site. He underwent a Bentall procedure. Postoperatively, he developed complete heart block requiring permanent pacemaker implantation. During aortic valve replacement, risk factors for aortic dissection (diameter of the aorta and fragility and thinness of the aortic wall) should be assessed. Prophylactic aortic root replacement should be undertaken if the aortic root is more than 45?mm in diameter. PMID:24887849

Behranwala, Ali Asgar; Handa, Shyam R; Mehta, Nihar P

2014-11-01

230

Neck dissection with cervical sensory preservation in thyroid cancer  

PubMed Central

Thyroid cancer is the most common endocrine malignancy. Recently, controversy has focused on the management of lymph node metastases, which represent approximately 90% of disease recurrences and may require considerable time, effort, and resources to diagnose and treat. Neck dissections play an essential role in the management of head and neck cancer. A modified radical neck dissection (MND) refers to resection of the lymph nodes in levels II through V and often including the central nodes in level VI. When performing modified neck dissection, we recommend to protect more reserved cervical plexus. The purpose is to better protect patient’s neck skin feeling. PMID:25083485

Xue, Shuai; Wang, Peisong

2013-01-01

231

Traumatic carotid artery dissection caused by bungee jumping.  

PubMed

Bungee jumping is a popular recreational activity in which participant experiences transient freefall while connected to a bungee cord. The rapid freefall and the resultant rebound force created by the bungee cord can result in a variety of bodily injuries. We report herein a case of traumatic carotid artery dissection caused by bungee jumping. The symptoms related to carotid artery dissection were successfully treated with anticoagulation. The etiology of carotid dissection related to bungee jumping is discussed. Physicians should be cognizant of this potential injury due to the force created by the freefall and rebound motion associated in this recreational sport. PMID:17980290

Zhou, Wei; Huynh, Tam T; Kougias, Panagiotis; El Sayed, Hosam F; Lin, Peter H

2007-11-01

232

Cervical artery dissection goes frequently undiagnosed.  

PubMed

Cervical artery dissection (CeAD) is a frequent cause of stroke among young patients. It is unclear how many CeADs occur asymptomatically or cause subtle and unspecific clinical symptoms. We hypothesize that CeAD remains often unrecognized. Accordingly, the incidence of CeAD might be higher and the stroke risk lower than generally assumed. Lack of CeAD-indicating clinical symptoms is regarded as the main cause of missed diagnoses. We further hypothesize that underrepresentation of asymptomatic and oligosymptomatic patients in CeAD studies may have biased the association between ischemia and local symptoms in CeAD patients as well as the associations of CeAD with risk factors or co-morbidities. We finally hypothesize that symptomatic CeAD may be preceded by an initial asymptomatic phase. According to this final hypothesis, the time of onset of CeAD should be considered uncertain. The issue of unrecognized CeAD is relevant, as it may affect the associations between CeAD and putative risk factors. Furthermore, the existence of clinically silent CeADs may explain why recurrent and familial CeAD have been rarely observed. PMID:23562286

Grond-Ginsbach, Caspar; Metso, Tiina M; Metso, Antti J; Pezzini, Alessandro; Tatlisumak, Turgut; Hakimi, Maani; Grau, Armin J; Kloss, Manja; Lichy, Christoph

2013-06-01

233

On Quantitizing  

ERIC Educational Resources Information Center

"Quantitizing", commonly understood to refer to the numerical translation, transformation, or conversion of qualitative data, has become a staple of mixed methods research. Typically glossed are the foundational assumptions, judgments, and compromises involved in converting disparate data sets into each other and whether such conversions advance…

Sandelowski, Margarete; Voils, Corrine I.; Knafl, George

2009-01-01

234

Endovascular treatment of acute type B dissection complicating aortic coarctation.  

PubMed

Surgical treatment poses a high risk to patients with concomitant aortic coarctation and dissection, and an interventional approach could be an alternative. We describe the case of a 52-year-old man with a long history of untreated hypertension and aortic coarctation who emergently presented at our institution with an acute Stanford type B dissection. The patient's elevated serum creatinine level, perfusion deficit in the right lower limb, and hypertension did not respond to medical therapy, and he did not consent to surgery. By endovascular means, we used a self-expandable stent-graft to cover the entry point of the dissection; then, we deployed a balloon-expandable bare-metal stent to correct residual stenosis. To our knowledge, this is the first report of the endovascular treatment of aortic coarctation complicated by type B dissection. PMID:23678217

Kassaian, Seyed Ebrahim; Abbasi, Kyomars; Mousavi, Mehdi; Sahebjam, Mohammad

2013-01-01

235

Radical lymph node dissection for gallbladder cancer: indications and limitations.  

PubMed

Radical lymph node dissection provides survival benefit for patients with pT2 or more advanced gallbladder carcinoma tumors only if potentially curative resection is feasible; it must always be considered when planning a resection or re-resection for robust patients with pT2 or more advanced gallbladder carcinoma tumors. The degree of radical lymphadenectomy depends on clinically assessed nodal status: portal lymph node dissection is limited to cN0 disease; extended portal nodal dissection is indicated for cN0 and a modest degree of cN1 disease; peripancreatic lymph node dissection with pancreaticoduodenectomy is indicated for selected cases of evident peripancreatic nodal disease and/or direct organ involvement. Extended resection with extensive lymphadenectomy should be limited to expert surgeons because it may cause serious morbidity and mortality. PMID:17336245

Shirai, Yoshio; Wakai, Toshifumi; Hatakeyama, Katsuyoshi

2007-01-01

236

Blunt scissors stromal dissection technique for deep anterior lamellar keratoplasty  

PubMed Central

Objective We describe a modified technique for performing lamellar dissection in deep anterior lamellar keratoplasty after failure to achieve a “big bubble” detachment of Descemet’s membrane (DM) with deep intrastromal pneumatic injection. Methods The technique utilizes blunt lamellar dissection with blunt-tipped corneal mini scissors as an alternative to a crescent blade, which can be difficult for surgeons to master and is associated with a high risk of perforation. Results Other techniques of blunt dissection, such as the Melles technique, cannot be utilized after failure to achieve a big bubble, as emphysema in the stroma prevents visualization of the spatula. In contrast, our blunt scissors lamellar dissection technique takes advantage of the emphysema and microdetachments of DM created by the pneumatic injection. Conclusion This technique provides deep anterior lamellar keratoplasty surgeons with a simple, alternative method of baring DM or achieving a pre-DM plane with minimal residual stroma, after failure to achieve a big bubble. PMID:25258506

Anwar, Didar S; Kruger, Matthew M; Mootha, V Vinod

2014-01-01

237

Dissection Videos Do Not Improve Anatomy Examination Scores  

NSDL National Science Digital Library

This article describes the effect and student perception of showing dissection videos on first-year medical students' performance in terms of test scores during a gross anatomy course. The article describes the methods and outcomes.

Waqas Mahmud (Rawalpindi Medical College Anatomy); Omar Hyder (Rawalpindi Medical College Obstetrics and Gynecology); Jamaal Butt (Rawalpindi Medical College Anatomy); Arsalan Aftab (Rawalpindi Medical College Anatomy)

2011-01-03

238

Comparative N-Glycoproteomic and Phosphoproteomic Profiling of Human Placental Plasma Membrane between Normal and Preeclampsia Pregnancies with High-Resolution Mass Spectrometry  

PubMed Central

Preeclampsia is a serious complication of pregnancy, which affects 2–8% of all pregnancies and is one of the leading causes of maternal and perinatal mortality and morbidity worldwide. To better understand the molecular mechanisms involved in pathological development of placenta in preeclampsia, we used high-resolution LC-MS/MS technologies to construct a comparative N-glycoproteomic and phosphoproteomic profiling of human placental plasma membrane in normal and preeclamptic pregnancies. A total of 1027 N-glyco- and 2094 phospho- sites were detected in human placental plasma membrane, and 5 N-glyco- and 38 phospho- proteins, respectively, with differentially expression were definitively identified between control and preeclamptic placental plasma membrane. Further bioinformatics analysis indicated that these differentially expressed proteins correlate with several specific cellular processes occurring during pathological changes of preeclamptic placental plasma membrane. PMID:24260401

Wang, Fuqiang; Wang, Ling; Shi, Zhonghua; Liang, Gaolin

2013-01-01

239

Robust, Quantitative, Labelfree Phosphoproteomics Platform: Automated Enrichment and 2DLC/MS/MS Brenna M. Richardson, Erik J. Soderblom, J. Will Thompson, M. Arthur Moseley  

E-print Network

variation was approximately cut by more than half by using an automated enrichment setup and Glycolic Acid frame. By adjusting the fractionation to compensate for the more acidic nature of phosphopeptides, a 3 acid · Formic acid added to fraction collection vials prior to enrichment · Dry down

Richardson, David

240

Reassessment of the coronal incision and subgaleal dissection for foreheadplasty.  

PubMed

Thirty years ago, the aging upper face was generally ignored by surgeons performing facial rejuvenation surgery. Ultimately, the coronal incision forehead lift technique became an accepted procedure, with most surgeons raising the forehead flap at the subgaleal plane. These surgeons found the subgaleal plane to be the "natural" or most accessible dissection plane to use, and it continues to be the most commonly used dissection plane for foreheadplasty today. However, some surgeons have begun to advocate using the subperiosteal plane, and controversy surrounds the question of which dissection plane is more surgically sound for raising a forehead flap. On the basis of 25 fresh cadaver dissections and more than 20 years of clinical experience with foreheadplasty, the author concludes that dissection done at the subperiosteal rather than the subgaleal plane provides greater benefit to the patient. Although both subgaleal and subperiosteal planes can provide relative ease of dissection, elevation of the forehead flap at the subperiosteal plane can maximally preserve blood supply for the forehead flap and predictably preserve long-term frontoparietal scalp sensation. The deep division of the supraorbital nerve, which provides sensation to the frontoparietal scalp, is placed at risk for transection with subgaleal elevation of the forehead flap. The skin incision approach chosen for the forehead flap can also affect postoperative frontoparietal scalp sensation. The deep division of the supraorbital nerve will always be transected by a coronal incision approach for forehead flap elevation, with dissection done at either the subgaleal or the subperiosteal level. Only limited scalp incisions placed to avoid the course of the deep division of the supraorbital nerve can avoid transecting this nerve, and only subperiosteal dissection of the forehead flap can predictably preserve this nerve while elevating the forehead flap. PMID:9703089

Knize, D M

1998-08-01

241

Surgery for aortic dissection associated with congenital bicuspid aortic valve  

Microsoft Academic Search

Congenital bicuspid aortic valve is a relatively rare malformation. It is reported that the presence of this anomaly predisposes\\u000a the patient to the development of dissecting aortic aneurysms. Between 1981 and October 1997, 7 patients with aortic dissection\\u000a associated with congenital bicuspid aortic valve underwent surgical treatment at our institution. The patients consisted of\\u000a six males and one female. The

Motomi Ando; Yutaka Okita; Ritsu Matsukawa; Shinichi Takamoto

1998-01-01

242

Spontaneous vertebral dissection: Clinical, conventional angiographic, CT, and MR findings  

SciTech Connect

The purpose of this study was to determine if typical clinical and neuroradiologic patterns exist in patients with spontaneous vertebral artery (VA) dissection. The medical records and neuroradiologic examinations of 14 patients with spontaneous VA dissection were reviewed. The medical records were examined to exclude patients with a history of trauma and to record evidence of a nontratimatic precipitating event ({open_quotes}trivial trauma{close_quotes}) and presence of possible risk factors such as hypertension. All patients under-went conventional angiography, 13 either CT or MRI (II both CT and MRI), and 3 MRA. Conventional arteriograrris were evaluated for dissection site, evidence of fibromuscular dysplasia, luminal stenosis or occlusion, and pseudoaneurysm formation, CT examinations for the presence of infarction or subarachnoid hemorrhage, MR examinations for the presence of infarction or arterial signal abnormality, and MR angiograms for abnormality of the arterial signal column. Seven patients had precipitating events within 24 h of onset of symptoms that may have been causative of dissection and five had hypertension. At catheter angiography, two patients had dissections in two arteries (both VAs in one patient, VA and internal carotid artery in one patient), giving a total of 15 VAs with dissection. Dissection sites included V1 in four patients, V2 in one patient, V3 in three patients, V4 in six patients, and both V3 and V4 in one patient. Luminal stenosis was present in 13 VAs, occlusion in 2, pseudoaneurysm in 1, and evidence of fibromuscular dysplasia in 1. Posterior circulation infarcts were found on CT or MR in five patients. Subarachnoid hemorrhage was found on CT in two patients and by lumbar puncture alone in two patients. Abnormal periarterial signal on MRI was seen in three patients. MRA demonstrated absent VA signal in one patient, pseudoaneurysm in one, and a false-negative examination in one.

Provenzale, J.M.; Morgenlander, J.C. [Duke Univ. Medical Center, Durham, NC (United States)] [Duke Univ. Medical Center, Durham, NC (United States); Gress, D. [Univ. of California, San Francisco, CA (United States)] [Univ. of California, San Francisco, CA (United States)

1996-03-01

243

Unraveling pancreatic islet biology by quantitative proteomics  

SciTech Connect

The pancreatic islets of Langerhans play a critical role in maintaining blood glucose homeostasis by secreting insulin and several other important peptide hormones. Impaired insulin secretion due to islet dysfunction is linked to the pathogenesis underlying both Type 1 and Type 2 diabetes. Over the past 5 years, emerging proteomic technologies have been applied to dissect the signaling pathways that regulate islet functions and gain an understanding of the mechanisms of islet dysfunction relevant to diabetes. Herein, we briefly review some of the recent quantitative proteomic studies involving pancreatic islets geared towards gaining a better understanding of islet biology relevant to metabolic diseases.

Zhou, Jianying; Dann, Geoffrey P.; Liew, Chong W.; Smith, Richard D.; Kulkarni, Rohit N.; Qian, Weijun

2011-08-01

244

3D segmentation of the true and false lumens on CT aortic dissection images  

NASA Astrophysics Data System (ADS)

Our works are related to aortic dissections which are a medical emergency and can quickly lead to death. In this paper, we want to retrieve in CT images the false and the true lumens which are aortic dissection features. Our aim is to provide a 3D view of the lumens that we can difficultly obtain either by volume rendering or by another visualization tool which only directly gives the outer contour of the aorta; or by other segmentation methods because they mainly directly segment either only the outer contour of the aorta or other connected arteries and organs both. In our work, we need to segment the two lumens separately; this segmentation will allow us to: distinguish them automatically, facilitate the landing of the aortic prosthesis, propose a virtual 3d navigation and do quantitative analysis. We chose to segment these data by using a deformable model based on the fast marching method. In the classical fast marching approach, a speed function is used to control the front propagation of a deforming curve. The speed function is only based on the image gradient. In our CT images, due to the low resolution, with the fast marching the front propagates from a lumen to the other; therefore, the gradient data is insufficient to have accurate segmentation results. In the paper, we have adapted the fast marching method more particularly by modifying the speed function and we succeed in segmenting the two lumens separately.

Fetnaci, Nawel; ?ubniewski, Pawe?; Miguel, Bruno; Lohou, Christophe

2013-03-01

245

Computed Tomography of Aortic Wall Calcifications in Aortic Dissection Patients  

PubMed Central

Objectives To investigate the frequency of aortic calcifications at the outer edge of the false lumen and the frequency of fully circular aortic calcifications in a consecutive series of patients with aortic dissection who underwent contrast-enhanced CT. Methods The study population compromised of 69 consecutive subjects aged 60 years and older with a contrast-enhanced CT scan demonstrating an aortic dissection. All CT scans were evaluated for the frequency of aortic calcifications at the outer edge of the false lumen and the frequency of fully circular aortic calcifications by two experienced observers. Between observer reliability was evaluated by using Cohen’s Kappa. Differences between groups were tested using unpaired T test and Chi-square test. Results Presumed media calcifications were observed in 22 (32%) patients of 60 years and older and were found more frequently in chronic aortic dissection (N?=?12/23, 52%) than in acute aortic dissection (N?=?10/46, 22%). Conclusion As the intima has been torn away by the aortic dissection it is highly likely that CT scans can visualize the calcifications in the tunica media of the aorta. PMID:25003993

de Jong, Pim A.; Hellings, Willem E.; Takx, Richard A. P.; Isgum, Ivana; van Herwaarden, Joost A.; Mali, Willem P. Th. M.

2014-01-01

246

A Second-Generation Device for Automated Training and Quantitative Behavior Analyses of Molecularly-Tractable Model Organisms  

Microsoft Academic Search

A deep understanding of cognitive processes requires functional, quantitative analyses of the steps leading from genetics and the development of nervous system structure to behavior. Molecularly-tractable model systems such as Xenopus laevis and planaria offer an unprecedented opportunity to dissect the mechanisms determining the complex structure of the brain and CNS. A standardized platform that facilitated quantitative analysis of behavior

Douglas Blackiston; Tal Shomrat; Cindy L. Nicolas; Christopher Granata; Michael Levin

2010-01-01

247

The birth and evolution of neuroscience through cadaveric dissection.  

PubMed

Although interest in the art of dissection and vivisection has waxed and waned throughout the ages, the past century has seen it accepted as commonplace in medical schools across the country. No other practice in medicine has contributed more to the understanding of neuroanatomy and the neurosciences as dissection of the human cadaver, the origins of which are widely documented to have been in Alexandrian Greece. This article chronicles the fascinating and often controversial use of dissection and vivisection in these fields through the ages, beginning with Herophilus of Alexandria, among the first systematic dissectors in the history of Western medicine. The authors comment on its role in the development of modern neurosurgery and conclude with remarks about use of this educational tool today in the United States. PMID:20657312

Moon, Karam; Filis, Andreas K; Cohen, Alan R

2010-09-01

248

Digital dissection system for medical school anatomy training  

NASA Astrophysics Data System (ADS)

As technology advances, new and innovative ways of viewing and visualizing the human body are developed. Medicine has benefited greatly from imaging modalities that provide ways for us to visualize anatomy that cannot be seen without invasive procedures. As long as medical procedures include invasive operations, students of anatomy will benefit from the cadaveric dissection experience. Teaching proper technique for dissection of human cadavers is a challenging task for anatomy educators. Traditional methods, which have not changed significantly for centuries, include the use of textbooks and pictures to show students what a particular dissection specimen should look like. The ability to properly carry out such highly visual and interactive procedures is significantly constrained by these methods. The student receives a single view and has no idea how the procedure was carried out. The Department of Anatomy at Mayo Medical School recently built a new, state-of-the-art teaching laboratory, including data ports and power sources above each dissection table. This feature allows students to access the Mayo intranet from a computer mounted on each table. The vision of the Department of Anatomy is to replace all paper-based resources in the laboratory (dissection manuals, anatomic atlases, etc.) with a more dynamic medium that will direct students in dissection and in learning human anatomy. Part of that vision includes the use of interactive 3-D visualization technology. The Biomedical Imaging Resource (BIR) at Mayo Clinic has developed, in collaboration with the Department of Anatomy, a system for the control and capture of high resolution digital photographic sequences which can be used to create 3-D interactive visualizations of specimen dissections. The primary components of the system include a Kodak DC290 digital camera, a motorized controller rig from Kaidan, a PC, and custom software to synchronize and control the components. For each dissection procedure, the images are captured automatically, and then processed to generate a Quicktime VR sequence, which permits users to view an object from multiple angles by rotating it on the screen. This provides 3-D visualizations of anatomy for students without the need for special '3-D glasses' that would be impractical to use in a laboratory setting. In addition, a digital video camera may be mounted on the rig for capturing video recordings of selected dissection procedures being carried out by expert anatomists for playback by the students. Anatomists from the Department of Anatomy at Mayo have captured several sets of dissection sequences and processed them into Quicktime VR sequences. The students are able to look at these specimens from multiple angles using this VR technology. In addition, the student may zoom in to obtain high-resolution close-up views of the specimen. They may interactively view the specimen at varying stages of dissection, providing a way to quickly and intuitively navigate through the layers of tissue. Electronic media has begun to impact all areas of education, but a 3-D interactive visualization of specimen dissections in the laboratory environment is a unique and powerful means of teaching anatomy. When fully implemented, anatomy education will be enhanced significantly by comparison to traditional methods.

Augustine, Kurt E.; Pawlina, Wojciech; Carmichael, Stephen W.; Korinek, Mark J.; Schroeder, Kathryn K.; Segovis, Colin M.; Robb, Richard A.

2003-05-01

249

Acute dissection of the left anterior descending after contusio cordis.  

PubMed

Traumatic coronary artery dissection after blunt chest trauma is extremely rare. The diagnosis is often delayed and some are only diagnosed postmortem. We report a case of acute dissection of the left anterior descending (LAD) after contusio cordis that presented at our institution. In our case we performed the off pump coronary artery bypass operation (OPCAB) procedure with left internal mammary artery (LIMA) on LAD by a partial lower sternotomy approach. There were no operative or perioperative complications and the patient was discharged from hospital 6 days postoperatively. OPCAB operation through the partial lower sternotomy is a safe and effective technique for the treatment of patients with acute dissection of a coronary artery after blunt chest trauma. PMID:21460781

Monsefi, N; Moritz, A; Dzemali, O

2011-04-01

250

Spontaneous coronary artery dissection in a patient with bacterial meningitis.  

PubMed

A 40-year-old man was admitted to our hospital because of the acute onset of fever and headache, which were attributed to bacterial meningitis. Antibiotic treatment was initiated and his condition gradually improved. On day 5 after admission, immediately after masturbation, he developed abrupt onset of severe chest pain and cold sweat and the ECG suggested acute anterior myocardial infarction. Immediate coronary angiography revealed spontaneous dissection of the left anterior descending artery. After conservative management, his cardiac function improved. Acute coronary syndrome may be rarely caused by spontaneous coronary artery dissection. Sepsis was considered as a probable trigger for spontaneous coronary artery dissection, possibly through vascular damage from increased nitric oxide and sympathetic nervous over-activation. PMID:24194165

Kinoshita, Kensuke; Tsunoda, Yoshiya; Watanabe, Shigeyuki; Tokuda, Yasuharu

2013-01-01

251

Quantitative Literacy  

NSDL National Science Digital Library

This resource guide from the Middle School Portal 2 project, written specifically for teachers, provides links to exemplary resources including background information, lessons, career information, and related national science education standards.On this wiki page, you will find online lessons, activities, and projects that allow students a range of real-world contexts. The Content Collections section contains sites that offer sets of problems and illustrations that connect middle school math to down-to-earth settings. The Interdisciplinary Lessons and Activities section offers activities and projects ready for interdisciplinary teaching. Each of the following sections focuses on a math topic: Data Analysis and Display, Probability, Measurement, Number and Operations. The resources offer mathematics in settings that deliberately cross over into other areas of the curriculum. Finally, for teachers looking for support in teaching quantitative literacy, a new approach for us all, Background Information for Teachers presents a select set of professional resources.

Herrera, Terese

2009-04-01

252

Adjustable dissection and surgical table as an aid to teaching.  

PubMed

An adjustable dissection and surgical table for teaching residents, fellows, staff, and other medical and allied health personnel about anatomy and simulated techniques of surgery in the laboratory setting is described. The table can be attached to a standard House-Urban temporal bone dissection bench. The temporal bone laboratory can thus serve a dual purpose in teaching ear and soft tissue anatomy and surgical techniques of the head and neck. In this setting such a dual purpose laboratory can often include basic and clinical research activities as a third function. PMID:3339939

Work, W P

1988-02-01

253

Questionable necessity to remove the submandibular gland in neck dissection.  

PubMed

Saliva is of major importance in taste, speech, swallowing, and protection against dental caries. Neck dissection surgery and/or radiotherapy may impair the function of the submandibular glands. Over the years, there has been a trend toward more conservative approaches to neck dissection. Metastasis to the submandibular gland itself is extremely rare and if removal of the lymph nodes of sublevel IB is imperative, it seems feasible to preserve the submandibular gland, unless it is involved by direct tumor extension of the primary tumor or the adjacent metastatic lymph nodes. Clinical studies to validate this concept are needed. PMID:20629090

Takes, Robert P; Robbins, K Thomas; Woolgar, Julia A; Rinaldo, Alessandra; Silver, Carl E; Olofsson, Jan; Ferlito, Alfio

2011-05-01

254

Isolated Unilateral Hypoglossal Nerve Palsy Due to Vertebral Artery Dissection  

PubMed Central

We report the case of a patient with unilateral tongue weakness secondary to an isolated lower motor neuron hypoglossal nerve palsy that was caused by a right vertebral artery dissection in the lower neck. The patient had a boggy tongue with a deviation to the right side but an otherwise normal neurological examination. Magnetic resonance angiography showed a narrow lumen of the right vertebral artery in the neck. After initially treating the patient with aspirin in the emergency room and later with warfarin for three months, there was complete recanalization of the right vertebral artery. Only one other case of vertebral artery dissection and twelfth nerve palsy has been reported before. PMID:22031481

Mahadevappa, Karthik; Chacko, Thomas; Nair, Anil K.

2012-01-01

255

Infective Left Atrial Dissecting Flap after Cardiac Surgery  

PubMed Central

Left atrial dissection (LatD), defined as the forced separation of the left atrial (LA) wall layers by blood, is a rare and severe complication of cardiac surgery. It is most frequently associated with atrioventricular junction injuries. We report a case of infected LatD after coronary artery bypass graft, mitral valve replacement, aortic valve replacement and ascending aortic root replacement. The patient was presented with septicemia and disseminated intravascular coagulation. To the best of our knowledge, this is the first case report of LA dissecting flap concomitant with attached infective vegetations identified by transesophageal echocardiography. PMID:25309695

Tabiban, Sasan; Ghaemian, Ali; Bagheri, Babak; Shokri, Mojtaba

2014-01-01

256

Concomitant Reconstruction of Arch Vessels during Repair of Aortic Dissection  

PubMed Central

Surgery for acute aortic dissection is challenging, especially in cases of cerebral malperfusion. Should we perform only the aortic repair, or should we also reconstruct the arch vessels when they are severely affected by the disease process? Here we present a case of acute aortic dissection with multiple tears that involved the brachiocephalic artery and caused cerebral and right upper-extremity malperfusion. The patient successfully underwent complete replacement of the brachiocephalic artery and the aortic arch during deep hypothermic circulatory arrest, with antegrade cerebral protection. We have found this technique to be safe and reproducible for use in this group of patients. PMID:25120398

Nezic, Dusko; Vukovic, Petar; Jovanovic, Marko; Lozuk, Branko; Jagodic, Sinisa; Djukanovic, Bosko

2014-01-01

257

Genetic dissection of NK cell responses  

PubMed Central

The association of Natural Killer (NK) cell deficiencies with disease susceptibility has established a central role for NK cells in host defence. In this context, genetic approaches have been pivotal in elucidating and characterizing the molecular mechanisms underlying NK cell function. To this end, homozygosity mapping and linkage analysis in humans have identified mutations that impact NK cell function and cause life-threatening diseases. However, several critical restrictions accompany genetic studies in humans. Studying NK cell pathophysiology in a mouse model has therefore proven a useful tool. The relevance of the mouse model is underscored by the similarities that exist between cell-structure-sensing receptors and the downstream signaling that leads to NK cell activation. In this review, we provide an overview of how human and mouse quantitative trait locis (QTLs) have facilitated the identification of genes that modulate NK cell development, recognition, and killing of target cells. PMID:23346087

Moussa, Peter; Marton, Jennifer; Vidal, Silvia M.; Fodil-Cornu, Nassima

2012-01-01

258

Dissecting cell death with proteomic scalpels.  

PubMed

Programmed cell deaths (PCD), including apoptosis, autophagy and programmed necrosis, are genetically determined, complex processes in multi-cellular organisms. Problems with the regulation of PCD have been implicated in a number of diseases including myocardial infarction, cancer and autoimmune disease. As a result, the investigation on PCD regulation has stirred considerable interest. In the past decades, many PCD-involved proteins had been identified as being modulated by post-translational mechanisms, including post-translational modification, protein-protein interactions and protein cleavage, which fall precisely within the range of proteomic analysis. Contemporary quantitative proteomics, interactomics, PTMomics, degradomics, chemical proteomics and pharmacoproteomics have been quickly applied in the field of PCD research, and possess the potential to be the driving forces of the field. This review attempts to highlight some of the major achievements in the application of proteomics in PCD research to trigger further thinking and application. PMID:22247084

Wang, Li-Shun; Xia, Li; Shen, Shao-Min; Zheng, Ying; Yu, Yun; Chen, Guo-Qiang

2012-02-01

259

Genetic dissection of a model complex trait using the Drosophila Synthetic Population Resource.  

PubMed

Genetic dissection of complex, polygenic trait variation is a key goal of medical and evolutionary genetics. Attempts to identify genetic variants underlying complex traits have been plagued by low mapping resolution in traditional linkage studies, and an inability to identify variants that cumulatively explain the bulk of standing genetic variation in genome-wide association studies (GWAS). Thus, much of the heritability remains unexplained for most complex traits. Here we describe a novel, freely available resource for the Drosophila community consisting of two sets of recombinant inbred lines (RILs), each derived from an advanced generation cross between a different set of eight highly inbred, completely resequenced founders. The Drosophila Synthetic Population Resource (DSPR) has been designed to combine the high mapping resolution offered by multiple generations of recombination, with the high statistical power afforded by a linkage-based design. Here, we detail the properties of the mapping panel of >1600 genotyped RILs, and provide an empirical demonstration of the utility of the approach by genetically dissecting alcohol dehydrogenase (ADH) enzyme activity. We confirm that a large fraction of the variation in this classic quantitative trait is due to allelic variation at the Adh locus, and additionally identify several previously unknown modest-effect trans-acting QTL (quantitative trait loci). Using a unique property of multiparental linkage mapping designs, for each QTL we highlight a relatively small set of candidate causative variants for follow-up work. The DSPR represents an important step toward the ultimate goal of a complete understanding of the genetics of complex traits in the Drosophila model system. PMID:22496517

King, Elizabeth G; Merkes, Chris M; McNeil, Casey L; Hoofer, Steven R; Sen, Saunak; Broman, Karl W; Long, Anthony D; Macdonald, Stuart J

2012-08-01

260

78 FR 17429 - Certain Balloon Dissection Devices and Products Containing Same; Commission Determination Not To...  

Federal Register 2010, 2011, 2012, 2013

...337-TA-865] Certain Balloon Dissection Devices and Products...after importation of certain balloon dissection devices and products...Geisingen, Germany; and Pajunk Medical Systems LP of Norcross, Georgia...Medizintechnologie and Pajunk Medical Systems LP filed a motion...

2013-03-21

261

Evaluation of MorphologyNet as a Virtual Dissection Experience  

Microsoft Academic Search

As technological developments in the field of medical imaging increase at an exponential rate, literally hundreds of researchers and clinicians are generating three- dimensional visualizations of anatomical structures for use in research and disease diagnosis. But virtual dissection experiences (VDEs) can also be valuable for and appealing to the current video-game generation of K-16 students, and may well stimulate student

Jennifer Leopold; Anne Maglia

262

Rectilinear Glass-Cut Dissections of Rectangles to Squares  

E-print Network

Rectilinear Glass-Cut Dissections of Rectangles to Squares Jurek Czyzowicz§ czyzowic is made using only rectilinear glass-cuts, i.e., vertical or horizontal straight-line cuts separating pieces into two. 1 Introduction A glass-cut of a rectangle is a cut by a straight-line segment

Urrutia, Jorge

263

Dissecting Oxygenic Photosynthesis: The Evolution of the "Z"-Scheme  

E-print Network

11CHAPTER Dissecting Oxygenic Photosynthesis: The Evolution of the "Z"-Scheme for Thylakoid and two photosystems are involved in oxygenic photosynthesis. This is then followed by the discovery Drop in Photosynthesis; Two Light Reactions; Two Photosystems; Z-Scheme of Photosynthesis #12

Govindjee

264

Fibromuscular Dysplasia May Herald Symptomatic Recurrence of Cervical Artery Dissection  

Microsoft Academic Search

Background: The prevalence of fibromuscular dysplasia (FMD) in patients with cervical artery dissection (CAD) is unknown. Our objectives were to assess the risk of CAD recurring as a stroke or a transient ischemic attack and the association of these events with FMD. Methods: We prospectively included and followed 103 consecutive patients who had been admitted for a CAD. The median

J. M. de Bray; G. Marc; V. Pautot; B. Vielle; A. Pasco; P. Lhoste; F. Dubas

2007-01-01

265

Stanford type A aortic dissection. A new surgical approach.  

PubMed Central

We describe a new surgical technique adopted for the repair of Stanford type A aortic dissection. In order to minimize the risk of malperfusion caused by retrograde flow during cardiopulmonary bypass, we avoid femoral artery cannulation. On the hypothesis that it is best not to interfere with the hemodynamics of the dissection, we cannulate the dissected ascending aorta, in either the true or false lumen. We here report 2 cases of successful surgical treatment of Stanford type A aortic dissection. In both cases, the false lumen was cannulated under deep hypothermic circulatory arrest, without clamping the aorta. While the patient was cooling, a 10-mm GORE-TEX side arm was sutured to a Dacron graft prosthesis. Repair of the aortic arch was carried out 1st. The aortic cannula was inserted into the GORE-TEX side arm, the tubular prosthesis was cross-clamped, and cardiopulmonary bypass was reinstituted. After this, the aortic bulb was repaired as usual and the tubular prosthesis was sutured to the bulb. No postoperative cerebral complication occurred. Our experience must be confirmed by more cases and a longer follow up. Images PMID:9566066

Lijoi, A; Scarano, F; Dottori, V; Parodi, E; Casali, G; Bartolozzi, F

1998-01-01

266

Prototyping Dissection Puzzles with Layered Manufacturing Carlo H. Squin  

E-print Network

Deposition Modeling (FDM) machine. 2. Helicoidal Dissections In the fall of 2011, I decided to experiment be used to train students' spatial understanding and to teach geometrical modeling as well as some used as class exercises in a graduate course on computer-aided solid modeling: Helicoidal sectioning

Sequin, Carlo H.

267

The Effect of Ultrasound Dissection in Thyroid Surgery  

Microsoft Academic Search

Background: One of the most important aspects of thyroid surgery is hemostasis. The ultrasonically activated scalpel is described as a very useful instrument in thyroid surgery for the dissection and sealing of vessels. Our study compares the short-term results of endocrine surgery, with and without the use of ultrasonic devices. Methods: In a prospectively randomized trial, 96 patients with endemic

K. Witzel; B. H. A. von Rahden; H. J. Stein

2009-01-01

268

Gastric Wall Dissection as a Complication of Percutaneous Gastrostomy  

SciTech Connect

A percutaneous gastrostomy (PG) was complicated by gastric wall dissection and partial tube malposition. It occurred after tangential puncture along the greater curvature of the stomach which was performed in order to avoid an enlarged left lobe of the liver. To prevent this complication we recommend not using hydrophilic guidewires during PG.

Reimer, Wolfgang; Farres, Maria Teresa; Lammer, Johannes [Department of Radiology, Division of Angiography and Interventional Radiology, University of Vienna, AKH, Waehringer Guertel 18-20, A-1090 Vienna (Austria)

1996-04-15

269

Photoreceptor degeneration: genetic and mechanistic dissection of a complex trait  

Microsoft Academic Search

The retina provides exquisitely sensitive vision that relies on the integrity of a uniquely vulnerable cell, the photoreceptor (PR). The genetic and mechanistic causes of retinal degeneration due to PR cell death — which occurs in conditions such as retinitis pigmentosa and age-related macular degeneration — are being successfully dissected. Over one hundred loci, some containing common variants but most

Christina F. Chakarova; Mai M. Abd El-Aziz; Alan F. Wright; Shomi S. Bhattacharya

2010-01-01

270

Using Small Molecules To Dissect Mechanisms of Microbial Pathogenesis  

E-print Network

Using Small Molecules To Dissect Mechanisms of Microbial Pathogenesis Aaron W. Puri and Matthew of the infection cycle, small molecules that modulate or monitor enzyme activity levels are ideal tools for study- proaches to study pathogenesis. In addition to being used to perturb protein function, small molecule

Bogyo, Matthew

271

The Influence of Emotion on Students' Performance in Dissection Exercises  

ERIC Educational Resources Information Center

This paper investigates the issue of how emotions such as disgust influence students' self-efficacy belief in terms of mastering a dissection task and also how these affect their interest in the biology of the heart. Following models of intrinsic motivation and the development of motivation, we expected disgust to negatively impact on students'…

Holstermann, Nina; Grube, Dietmar; Bogeholz, Susanne

2009-01-01

272

Mutations in myosin light chain kinase cause familial aortic dissections.  

PubMed

Mutations in smooth muscle cell (SMC)-specific isoforms of ?-actin and ?-myosin heavy chain, two major components of the SMC contractile unit, cause familial thoracic aortic aneurysms leading to acute aortic dissections (FTAAD). To investigate whether mutations in the kinase that controls SMC contractile function (myosin light chain kinase [MYLK]) cause FTAAD, we sequenced MYLK by using DNA from 193 affected probands from unrelated FTAAD families. One nonsense and four missense variants were identified in MYLK and were not present in matched controls. Two variants, p.R1480X (c.4438C>T) and p.S1759P (c.5275T>C), segregated with aortic dissections in two families with a maximum LOD score of 2.1, providing evidence of linkage of these rare variants to the disease (p = 0.0009). Both families demonstrated a similar phenotype characterized by presentation with an acute aortic dissection with little to no enlargement of the aorta. The p.R1480X mutation leads to a truncated protein lacking the kinase and calmodulin binding domains, and p.S1759P alters amino acids in the ?-helix of the calmodulin binding sequence, which disrupts kinase binding to calmodulin and reduces kinase activity in vitro. Furthermore, mice with SMC-specific knockdown of Mylk demonstrate altered gene expression and pathology consistent with medial degeneration of the aorta. Thus, genetic and functional studies support the conclusion that heterozygous loss-of-function mutations in MYLK are associated with aortic dissections. PMID:21055718

Wang, Li; Guo, Dong-chuan; Cao, Jiumei; Gong, Limin; Kamm, Kristine E; Regalado, Ellen; Li, Li; Shete, Sanjay; He, Wei-Qi; Zhu, Min-Sheng; Offermanns, Stephan; Gilchrist, Dawna; Elefteriades, John; Stull, James T; Milewicz, Dianna M

2010-11-12

273

Mutations in Myosin Light Chain Kinase Cause Familial Aortic Dissections  

PubMed Central

Mutations in smooth muscle cell (SMC)-specific isoforms of ?-actin and ?-myosin heavy chain, two major components of the SMC contractile unit, cause familial thoracic aortic aneurysms leading to acute aortic dissections (FTAAD). To investigate whether mutations in the kinase that controls SMC contractile function (myosin light chain kinase [MYLK]) cause FTAAD, we sequenced MYLK by using DNA from 193 affected probands from unrelated FTAAD families. One nonsense and four missense variants were identified in MYLK and were not present in matched controls. Two variants, p.R1480X (c.4438C>T) and p.S1759P (c.5275T>C), segregated with aortic dissections in two families with a maximum LOD score of 2.1, providing evidence of linkage of these rare variants to the disease (p = 0.0009). Both families demonstrated a similar phenotype characterized by presentation with an acute aortic dissection with little to no enlargement of the aorta. The p.R1480X mutation leads to a truncated protein lacking the kinase and calmodulin binding domains, and p.S1759P alters amino acids in the ?-helix of the calmodulin binding sequence, which disrupts kinase binding to calmodulin and reduces kinase activity in vitro. Furthermore, mice with SMC-specific knockdown of Mylk demonstrate altered gene expression and pathology consistent with medial degeneration of the aorta. Thus, genetic and functional studies support the conclusion that heterozygous loss-of-function mutations in MYLK are associated with aortic dissections. PMID:21055718

Wang, Li; Guo, Dong-chuan; Cao, Jiumei; Gong, Limin; Kamm, Kristine E.; Regalado, Ellen; Li, Li; Shete, Sanjay; He, Wei-Qi; Zhu, Min-Sheng; Offermanns, Stephan; Gilchrist, Dawna; Elefteriades, John; Stull, James T.; Milewicz, Dianna M.

2010-01-01

274

Alternative paratracheal lymph node dissection in left-sided hilar lung cancer patients: comparing the number of lymph nodes dissected to the number of lymph nodes dissected in right-sided mediastinal dissections  

Microsoft Academic Search

Objective: Removing or sampling lymph nodes from the bilateral paratracheal area through a left thoracotomy is not a standard procedure in patients with lung cancer. The aim of this study was to evaluate the feasibility of a technique without ductus arteriosus division and mobilization of the aortic arch and to compare the number of lymph nodes resected in left-sided dissections

Alper Toker; Serhan Tanju; Sedat Ziyade; Serkan Kaya; Suat Erus; Berker Ozkan; Dilek Yilmazbayhan

2011-01-01

275

Digital dissection system for medical school anatomy training  

Microsoft Academic Search

As technology advances, new and innovative ways of viewing and visualizing the human body are developed. Medicine has benefited greatly from imaging modalities that provide ways for us to visualize anatomy that cannot be seen without invasive procedures. As long as medical procedures include invasive operations, students of anatomy will benefit from the cadaveric dissection experience. Teaching proper technique for

Kurt E. Augustine; Wojciech Pawlina; Stephen W. Carmichael; Mark J. Korinek; Kathryn K. Schroeder; Colin M. Segovis; Richard A. Robb

2003-01-01

276

Kendall Hunt Dissection of a Squid: Part 2  

NSDL National Science Digital Library

The purpose of this 9-minute video is to illustrate notable anatomical structures of the market squid (Loligo opalescens) to prepare teachers to lead a dissection of this species; however, this video is not meant to be viewed by students. Presented as a workshop at the NMEA Annual Conference, July 2010.

2012-01-01

277

Cancer Cell Dissecting the Unique Role of the Retinoblastoma  

E-print Network

Cancer Cell Article Dissecting the Unique Role of the Retinoblastoma Tumor Suppressor during-cycle control. However, cancer-associated mutations are almost exclusively found in RB, implying that RB has for cancer development; hence, the roles and regulation of RB have been intensively studied (reviewed

278

Neurovascular Bundle Decompression without Excessive Dissection for Tarsal Tunnel Syndrome.  

PubMed

Tarsal tunnel syndrome (TTS) is an entrapment neuropathy of the posterior tibial nerve and its branches in the tarsal tunnel. We present our less invasive surgical treatment of TTS in 69 patients (116 feet) and their clinical outcomes. The mean follow-up period was 64.6 months. With the patient under local anesthesia we use a microscope to perform sharp dissection of the flexor retinaculum and remove the connective tissues surrounding the posterior tibial nerve and vessels. To prevent postoperative adhesion and delayed neuropathy, decompression is performed to achieve symptom improvement without excessive dissection. Decompression is considered complete when the patient reports intraoperative symptom abatement and arterial pulsation is sufficient. The sensation of numbness and/or pain and of foreign substance adhesion was reduced in 92% and 95% of our patients, respectively. In self-assessments, 47 patients (68%) reported the treatment outcome as satisfactory, 15 (22%) as acceptable, and 7 (10%) were dissatisfied. Of 116 feet, 4 (3%) required re-operation, initial decompression was insufficient in 2 feet and further decompression was performed; in the other 2 feet improvement was achieved by decompression of the distal tarsal tunnel. Our surgical method involves neurovascular bundle decompression to obtain sufficient arterial pulsation. As we use local anesthesia, we can confirm symptom improvement intraoperatively, thereby avoiding unnecessary excessive dissection. Our method is simple, safe, and without detailed nerve dissection and it prevents postoperative adhesion. PMID:25367582

Kim, Kyongsong; Isu, Toyohiko; Morimoto, Daijiro; Sasamori, Toru; Sugawara, Atsushi; Chiba, Yasuhiro; Isobe, Masahiro; Kobayashi, Shiro; Morita, Akio

2014-11-15

279

External iliac artery dissection causing early renal transplant dysfunction.  

PubMed

External iliac artery dissection after kidney transplantation is a rare, catastrophic but potentially reversible complication. Treatment which may save both the transplant and the patient requires clinical suspicion, timely imaging, and prompt intervention. This case report describes successful diagnosis of this complication and surgical intervention which saved the kidney and safeguarded blood supply to the patient's leg. PMID:24695666

Lee, Gwyn; Barlow, Adam; Doughman, Tahir; Nicholson, Michael L

2014-01-01

280

Marquette University Gross Dissection Workshop - Upper & Lower Extremity  

NSDL National Science Digital Library

This website provides information regarding Marquette University's Gross Dissection of the Extremities workshop. The focus of the course is an intensive anatomy and kinesiology review. Even years this course focus on the lower extremity and the odd years the focus is on the upper extremity.

Marquette University (Marquette University)

2012-07-24

281

Dissection of Conformational Conversion Events during Prion Amyloid Fibril  

E-print Network

Dissection of Conformational Conversion Events during Prion Amyloid Fibril Formation Using Hydrogen A molecular understanding of prion diseases requires an understanding of the mechanism of amyloid fibril formation by the prion protein. In particular, it is necessary to define the sequence of the structural

282

Dissection of the Hyperadhesive Phenotype of Airway Eosinophils in Asthma  

E-print Network

Dissection of the Hyperadhesive Phenotype of Airway Eosinophils in Asthma Steven R. Barthel, Nizar, and Department of Medicine, University of Wisconsin­Madison, Madison, Wisconsin Asthma is characterized. Keywords: adhesion molecules; cell trafficking; eosinophils; human Asthma is an inflammatory syndrome

Mosher, Deane F.

283

There Is More to the Dissection of a Pig's Heart  

ERIC Educational Resources Information Center

The dissection of the mammalian heart in secondary biology classes need not be restricted to revealing the internal structure of the heart and its function. It could also be used to demonstrate other important aspects of blood circulation, including the blood supply to the heart itself as well as the causes and effects of coronary heart disease.…

Lee, Yeung Chung

2004-01-01

284

A Novel Approach to the Dissection of the Human Knee  

ERIC Educational Resources Information Center

The knee is one of the most frequently injured joints of the human body with injuries affecting the general population and the athletic population of many age groups. Dissection procedures for the knee joint typically do not allow unobstructed visualization of the anterior cruciate or posterior cruciate ligaments without sacrificing the collateral…

Clemente, F. Richard; Fabrizio, Philip A.; Shumaker, Michael

2009-01-01

285

[Leg Swelling following Inguinal and Ilioinguinal Dissection of Melanoma Metastases.  

PubMed

Background: With respect to survival and local disease control, the adequate extent of lymph node dissection for melanoma metastasis to the groin is controversial. Since the methods for accurate quantification of leg oedemas are not well standardised, it remains also unclear whether the iliac part of a radical ilioinguinal lymph node dissection contributes to postoperative lymphoedema. Patients and Methods: Using a questionnaire and clinical examinations, we prospectively studied 65?persons for the presence of leg swellings (11?with inguinal lymph node dissection (sCLND), 23?with ilioinguinal dissection (rCLND), and 31 without nodal surgery and without signs of venous insufficiency). Exact volumetry of the legs was performed using the Image 3 D method. Results: The mean interval between the lymphadenectomy and the examination for swellings was 24?±?30?months. Compared with sCLND, the amount of postoperative drainage fluid was significantly higher after rCLND (1960?±?1390 mL versus (vs.) 898?±?578 mL). Patients with rCLND perceived more frequently leg swellings (83 % vs. 55 %, p?= 0.09), however, also 23 % of the control persons perceived leg swellings. Clinical signs of swelling were found slightly more frequently in the rCLND group (52 % vs. 45 %). After rCLND, the gain in volume of the ipsilateral thigh was significantly higher than after sCLND (7.01?±?4.83 % vs. 1.29?±?6.12 %, p?= 0.01). Patients with rCLND more frequently needed manual lymph drainage (70 % vs. 45 %). In the control persons, the volumes of the right (mostly dominant) and the left legs did not differ significantly. Conclusions: Our results suggest that the iliac part of an ilioinguinal lymph node dissection significantly contributes to lymphoedema. Because of the multitude of reasons for swellings of the lower leg, volumetry of the thigh seems to be most adequate for quantifying the amount of postoperative lymphoedema. PMID:22511022

Pratsch, A L; Kretschmer, L

2012-04-17

286

The First Cut Is the Deepest: Reflections on the State of Animal Dissection in Biology Education  

ERIC Educational Resources Information Center

In biology education, the study of structure has traditionally involved the use of dissection. Animal-rights campaigners have caused biology educators and learners to question the necessity of dissections. This study reviews the research evidence for the efficacy of alternatives to dissection and then turns to research evidence on attitudes to…

De Villiers, Rian; Monk, Martin

2005-01-01

287

Spontaneous coronary dissection associated with sleep deprivation presenting with acute myocardial infarction  

Microsoft Academic Search

Spontaneous coronary dissection is a rare cause of myocardial ischemia, myocardial infarction and sudden cardiac death. Idiopathic spontaneous coronary artery dissection (SCAD) occurs in patient without risk factors for coronary artery disease and without underlying pregnancy. We describe a case of idiopathic spontaneous coronary dissection after sleep deprivation presenting with acute myocardial infarction. A 40 year old woman presented to

Soon Yong Suh; Jin Won Kim; Cheol Ung Choi; Eung Ju Kim; Seung-Woon Rha; Chang Gyu Park; Hong Seog Seo; Dong Joo Oh

2007-01-01

288

A Comparison of V-Frog[C] to Physical Frog Dissection  

ERIC Educational Resources Information Center

The purpose of the present study was to examine and compare the effectiveness of virtual frog dissection using V-Frog[C] and physical frog dissection on learning, retention, and affect. Subjects were secondary students enrolled in year-long life science classes in a suburban high school (N=102). Virtual dissections were done with V-Frog[C], a…

Lalley, James P.; Piotrowski, Phillip S.; Battaglia, Barbara; Brophy, Keith; Chugh, Kevin

2010-01-01

289

Conservative treatment of iatrogenic left main coronary artery dissection: report of two cases.  

PubMed

Revascularization treatment is mostly recommended for iatrogenic left main coronary artery dissection because of potential for catastrophic sequel, even in case of initial TIMI 3 flow and hemodynamic stability. However, conservative treatment seems to be feasible in asymptomatic and hemodinamically stable patient with low-grade dissection. We report two cases of iatrogenic left main coronary dissection managed conservatively. PMID:24400208

Celik, Murat; Yuksel, Uygar Cagdas; Yalcinkaya, Emre; Gokoglan, Yalcin; Iyisoy, Atila

2013-12-01

290

Conservative treatment of iatrogenic left main coronary artery dissection: report of two cases  

PubMed Central

Revascularization treatment is mostly recommended for iatrogenic left main coronary artery dissection because of potential for catastrophic sequel, even in case of initial TIMI 3 flow and hemodynamic stability. However, conservative treatment seems to be feasible in asymptomatic and hemodinamically stable patient with low-grade dissection. We report two cases of iatrogenic left main coronary dissection managed conservatively. PMID:24400208

Yuksel, Uygar Cagdas; Yalcinkaya, Emre; Gokoglan, Yalcin; Iyisoy, Atila

2013-01-01

291

Biology Teachers' Dissection Practices and the Influences that Lead to Their Adoption: An Exploratory Research  

ERIC Educational Resources Information Center

The lack of resolution in the on-going animal dissection debate inspired this mixed methods study to identify Connecticut secondary biology teachers' dissection practices and the influences that lead to their adoption. Qualitative findings indicate past experiences, managing objections to dissection, school culture, goals of biology teaching and…

Milano, Regina Nicole

2010-01-01

292

An Investigative Alternative to Single-Species Dissection in the Introductory Biology Laboratory  

ERIC Educational Resources Information Center

Dissections of single species (e.g., fetal pig) are a common student learning activity in introductory biology courses. Such dissections demonstrate location of anatomical parts and provide dissection practice but provide less opportunity for student critical thinking, numeracy and demonstration of the scientific method. A comparative anatomy lab…

Carlin, Joel L.

2010-01-01

293

Perceived Disgust and Personal Experiences are Associated with Acceptance of Dissections in Schools  

ERIC Educational Resources Information Center

Animal dissections are essential parts of anatomy/zoology courses, but their effectiveness is influenced by student attitudes and emotions. Here we examined attitudes toward dissections in 397 prospective biology teachers enrolling two Slovak universities. Perceived disgust of dissections negatively correlated with other attitudes toward…

Fancovicova, Jana; Prokop, Pavol; Leskova, Andrea

2013-01-01

294

Increased Carotid Artery Stiffness Without Atherosclerotic Change in Patients With Aortic Dissection  

Microsoft Academic Search

The arterial properties and pathogenesis of aortic dissection remain obscure. To examine the arterial properties of patients with aortic dissection, the authors studied the ultrasonographic characteristics of the carotid artery in patients with an aortic dissection (AD, n=86), and compared these findings with data of patients suffering from arteriosclerosis obliterans (ASO, n=151), coronary artery disease (CAD, n=163), and with healthy

Shinji Makita; Atsushi Ohira; Yujiro Naganuma; Yoshiteru Moriai; Hiroyuki Niinuma; Akihiko Abiko; Katsuhiko Hiramori

2006-01-01

295

Facile synthesis of Fe3O4@mesoporous TiO2 microspheres for selective enrichment of phosphopeptides for phosphoproteomics analysis.  

PubMed

Protein phosphorylation is one of the most important post-translational modifications. Due to the dynamic nature and low stoichiometry of the protein phosphorylation, enrichment of phosphopeptides from proteolytic mixtures is necessary prior to their characterization by mass spectrometry. In this work, we synthesized Fe3O4@mesoporous TiO2 magnetic microspheres with core-shell structure and large surface area for selective enrichment of phosphopeptides. To demonstrate its ability for selective enrichment of phosphopeptides, we applied Fe3O4@mesoporous TiO2 magnetic microspheres to isolation and enrichment of the phosphopeptides from tryptic digestion of standard proteins and real samples, and then the enriched peptides were analyzed by matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) or liquid chromatography coupled to electrospray ionization mass spectrometry (LC-ESI-MS). Due to that the as-made Fe3O4@mesoporous TiO2 microspheres have large surface area, good dispersivity and biocompatibility, they have been demonstrated as a powerful tool for phosphoproteomics research. PMID:23597982

Lu, Jin; Wang, Mengyi; Deng, Chunhui; Zhang, Xiangmin

2013-02-15

296

Phosphoproteomic Analysis Reveals the Effects of PilF Phosphorylation on Type IV Pilus and Biofilm Formation in Thermus thermophilus HB27*  

PubMed Central

Thermus thermophilus HB27 is an extremely thermophilic eubacteria with a high frequency of natural competence. This organism is therefore often used as a thermophilic model to investigate the molecular basis of type IV pili–mediated functions, such as the uptake of free DNA, adhesion, twitching motility, and biofilm formation, in hot environments. In this study, the phosphoproteome of T. thermophilus HB27 was analyzed via a shotgun approach and high-accuracy mass spectrometry. Ninety-three unique phosphopeptides, including 67 in vivo phosphorylated sites on 53 phosphoproteins, were identified. The distribution of Ser/Thr/Tyr phosphorylation sites was 57%/36%/7%. The phosphoproteins were mostly involved in central metabolic pathways and protein/cell envelope biosynthesis. According to this analysis, the ATPase motor PilF, a type IV pili–related component, was first found to be phosphorylated on Thr-368 and Ser-372. Through the point mutation of PilF, mimic phosphorylated mutants T368D and S372E resulted in nonpiliated and nontwitching phenotypes, whereas nonphosphorylated mutants T368V and S372A displayed piliation and twitching motility. In addition, mimic phosphorylated mutants showed elevated biofilm-forming abilities with a higher initial attachment rate, caused by increasing exopolysaccharide production. In summary, the phosphorylation of PilF might regulate the pili and biofilm formation associated with exopolysaccharide production. PMID:23828892

Wu, Wan-Ling; Liao, Jiahn-Haur; Lin, Guang-Huey; Lin, Miao-Hsia; Chang, Ying-Che; Liang, Suh-Yuen; Yang, Feng-Ling; Khoo, Kay-Hooi; Wu, Shih-Hsiung

2013-01-01

297

Sequential enrichment with titania-coated magnetic mesoporous hollow silica microspheres and zirconium arsenate-modified magnetic nanoparticles for the study of phosphoproteome of HL60 cells.  

PubMed

As one of the most important types of post-translational modifications, reversible phosphorylation of proteins plays crucial roles in a large number of biological processes. However, owing to the relatively low abundance and dynamic nature of phosphorylation and the presence of the unphosphorylated peptides in large excess, phosphopeptide enrichment is indispensable in large-scale phosphoproteomic analysis. Metal oxides including titanium dioxide have become prominent affinity materials to enrich phosphopeptides prior to their analysis using liquid chromatography-mass spectrometry (LC-MS). In the current study, we established a novel strategy, which encompassed strong cation exchange chromatography, sequential enrichment of phosphopeptides using titania-coated magnetic mesoporous hollow silica microspheres (TiO2/MHMSS) and zirconium arsenate-modified magnetic nanoparticles (ZrAs-Fe3O4@SiO2), and LC-MS/MS analysis, for the proteome-wide identification of phosphosites of proteins in HL60 cells. In total, we were able to identify 11,579 unique phosphorylation sites in 3432 unique proteins. Additionally, our results suggested that TiO2/MHMSS and ZrAs-Fe3O4@SiO2 are complementary in phosphopeptide enrichment, where the two types of materials displayed preferential binding of peptides carrying multiple and single phosphorylation sites, respectively. PMID:25262027

Yu, Qiong-Wei; Li, Xiao-Shui; Xiao, Yongsheng; Guo, Lei; Zhang, Fan; Cai, Qian; Feng, Yu-Qi; Yuan, Bi-Feng; Wang, Yinsheng

2014-10-24

298

Tissue Quality Assessment Using a Novel Direct Elasticity Assessment Device (The E-Finger): A Cadaveric Study of Prostatectomy Dissection  

PubMed Central

Introduction Minimally invasive radical prostatectomy (RP) (robotic and laparoscopic), have brought improvements in the outcomes of RP due to improved views and increased degrees of freedom of surgical devices. Robotic and laparoscopic surgeries do not incorporate haptic feedback, which may result in complications secondary to inadequate tissue dissection (causing positive surgical margins, rhabdosphincter damage, etc). We developed a micro-engineered device (6 mm2 sized) [E-finger]) capable of quantitative elasticity assessment, with amplitude ratio, mean ratio and phase lag representing this. The aim was to assess the utility of the device in differentiating peri-prostatic tissue types in order to guide prostate dissection. Material and Methods Two embalmed and 2 fresh frozen cadavers were used in the study. Baseline elasticity values were assessed in bladder, prostate and rhabdosphincter of pre-dissected embalmed cadavers using the micro-engineered device. A measurement grid was created to span from the bladder, across the prostate and onto the rhabdosphincter of fresh frozen cadavers to enable a systematic quantitative elasticity assessment of the entire area by 2 independent assessors. Tissue was sectioned along each row of elasticity measurement points, and stained with haematoxylin and eosin (H&E). Image analysis was performed with Image Pro Premier to determine the histology at each measurement point. Results Statistically significant differences in elasticity were identified between bladder, prostate and sphincter in both embalmed and fresh frozen cadavers (p?=?<0.001). Intra-class correlation (ICC) reliability tests showed good reliability (average ICC?=?0.851). Sensitivity and specificity for tissue identification was 77% and 70% respectively to a resolution of 6 mm2. Conclusions This cadaveric study has evaluated the ability of our elasticity assessment device to differentiate bladder, prostate and rhabdosphincter to a resolution of 6 mm2. The results provide useful data for which to continue to examine the use of elasticity assessment devices for tissue quality assessment with the aim of giving haptic feedback to surgeons performing complex surgery. PMID:25384014

Good, Daniel W.; Khan, Ashfaq; Hammer, Steven; Scanlan, Paul; Shu, Wenmiao; Phipps, Simon; Parson, Simon H.; Stewart, Grant D.; Reuben, Robert; McNeill, S. Alan

2014-01-01

299

Bare Stent Implantation in Iatrogenic Dissecting Pseudoaneurysm of the Superior Mesenteric Artery  

SciTech Connect

Iatrogenic arterial dissection leading to the development of dissecting pseudoaneurysms of the superior mesenteric artery (SMA) is a rare complication of angiography. Surgical and endovascular treatment options exist for this important condition. We report a case of bare stent implantation in dissecting pseudoaneurysm of the SMA that developed after angiography in a patient with acute mesenteric ischemia. Although it is rarely published, iatrogenic arterial dissection causing pseudoaneurysm can occur after diagnostic and interventional angiography. Bare stent implantation in dissecting pseudoaneurysm of the SMA could be an advantageous endovascular treatment option in selected cases due its to potential preservation of important side branches of the SMA.

Kutlu, Ramazan [Inonu University School of Medicine, Department of Radiology (Turkey)], E-mail: rkutlu@inonu.edu.tr; Ara, Cengiz [Inonu University School of Medicine, Department of General Surgery (Turkey); Sarac, Kaya [Inonu University School of Medicine, Department of Radiology (Turkey)

2007-02-15

300

Fundamentals of quantitative research  

Microsoft Academic Search

The main purpose of this article is to introduce some important fundamental concepts of quantitative research to readers especially novice researchers. It comprises types of research, definitions of quantitative research, different types and assumptions of quantitative research, when to use and not to use quantitative methods, advantages, common approaches and samples of quantitative research, and common misconceptions. Besides, a set

Suphat Sukamolson

301

Quantitative Analysis of Signaling Networks across Differentially Embedded Tumors Highlights Interpatient Heterogeneity in Human Glioblastoma.  

PubMed

Glioblastoma multiforme (GBM) is the most aggressive malignant primary brain tumor, with a dismal mean survival even with the current standard of care. Although in vitro cell systems can provide mechanistic insight into the regulatory networks governing GBM cell proliferation and migration, clinical samples provide a more physiologically relevant view of oncogenic signaling networks. However, clinical samples are not widely available and may be embedded for histopathologic analysis. With the goal of accurately identifying activated signaling networks in GBM tumor samples, we investigated the impact of embedding in optimal cutting temperature (OCT) compound followed by flash freezing in LN2 vs immediate flash freezing (iFF) in LN2 on protein expression and phosphorylation-mediated signaling networks. Quantitative proteomic and phosphoproteomic analysis of 8 pairs of tumor specimens revealed minimal impact of the different sample processing strategies and highlighted the large interpatient heterogeneity present in these tumors. Correlation analyses of the differentially processed tumor sections identified activated signaling networks present in selected tumors and revealed the differential expression of transcription, translation, and degradation associated proteins. This study demonstrates the capability of quantitative mass spectrometry for identification of in vivo oncogenic signaling networks from human tumor specimens that were either OCT-embedded or immediately flash-frozen. PMID:24927040

Johnson, Hannah; White, Forest M

2014-11-01

302

Quantitative Trait Loci Mapping in Five New Large Recombinant Inbred Line Populations of Arabidopsis thaliana Genotyped With Consensus Single-Nucleotide Polymorphism Markers  

Microsoft Academic Search

Quantitative approaches conducted in a single mapping population are limited by the extent of genetic variation distinguishing the parental genotypes. To overcome this limitation and allow a more complete dissection of the genetic architecture of complex traits, we built an integrated set of 15 new large Arabidopsis thaliana recombinant inbred line (RIL) populations optimized for quantitative trait loci (QTL) mapping,

Matthieu Simon; Olivier Loudet; Stephanie Durand; Aurelie Berard; Dominique Brunel; F.-X. Sennesal; M. Durand-Tardif; G. Pelletier; C. Camilleri

2008-01-01

303

High-energy drinks may provoke aortic dissection.  

PubMed

High-energy drinks have become extremely popular after Red Bull's promotion at 1987 in Austria and 1997 in the United States. Since then, we witnessed spectacular increase in different brands, caffeine content and market consumption all over the world. However, there are no reports published in the scientific literature related with detrimental side effects after heavy consumption of high-energy drinks. We report a series of three high-risk cardiovascular patients who had aortic dissection (De Bakey type I and II) following significant consumption of high-energy drinks. All of them required emergency surgical procedure and were remaining stable after surgery. We propose that uncontrolled consumption of high-energy drinks, especially in patients with underlying heart disease, could provoke potentially lethal cardiovascular events as well as acute aortic dissection. PMID:23914511

Jonjev, Zivojin S; Bala, Gustav

2013-05-01

304

Bilateral Carotid Artery Dissection after High Impact Road Traffic Accident  

PubMed Central

A 58 year old man was involved in a high impact road traffic incident and was admitted for observation. Asymptomatic for the first 24 hours, he collapsed with symptoms and signs consistent with a cerebrovascular accident. Computed tomography angiogram (CTA) and Magnetic resonance angiogram (MRA) demonstrated bilateral internal carotid artery dissections and a left middle cerebral artery infarct. It was not considered appropriate to attempt stenting or other revascularistation. The patient was treated with heparin prior to starting warfarin. He made a partial recovery and was discharged to a rehabilitation facility. This case is a reminder of carotid dissection as an uncommon but serious complication of high speed motor vehicle accident, which may be silent initially. Literature Review suggests risk stratification before relevant radiological screening at risk patients. Significant advances in CTA have made it the diagnostic tool of choice, but ultrasound is an important screening tool. PMID:22470607

Srivastava, Ankur; Bradley, Marcus; Kelly, Michael

2008-01-01

305

Description, dissection, and subsampling of Apollo 14 core sample 14230  

NASA Technical Reports Server (NTRS)

Core sample 14230, collected at Triplet Crater near the Fra Mauro landing site of the Apollo 14 mission, was dissected in greater detail than any previous core. Sediment from the actual lunar surface was missing, and 6.7 grams of sediment were removed from the base of the core for a portion of the biotest prime sample. Upper and lower portions of the original 70.7-gram core (12.5 centimeters long) were fractured excessively but not mixed stratigraphically. Three major morphologic units and 11 subdivisions were recognized. Dissection provided 55 subsamples in addition to three others made by removing longitudinal sections of the core impregnated with n-butyl methacrylate for use as a permanent documentary record and for studies requiring particles of known orientation.

Fryxell, R.; Heiken, G.

1971-01-01

306

Management of Acute Aortic Syndrome and Chronic Aortic Dissection  

SciTech Connect

Acute aortic syndrome (AAS) describes several life-threatening aortic pathologies. These include intramural hematoma, penetrating aortic ulcer, and acute aortic dissection (AAD). Advances in both imaging and endovascular treatment have led to an increase in diagnosis and improved management of these often catastrophic pathologies. Patients, who were previously consigned to medical management or high-risk open surgical repair, can now be offered minimally invasive solutions with reduced morbidity and mortality. Information from the International Registry of Acute Aortic Dissection (IRAD) database demonstrates how in selected patients with complicated AAD the 30-day mortality from open surgery is 17% and endovascular stenting is 6%. Despite these improvements in perioperative deaths, the risks of stroke and paraplegia remain with endovascular treatment (combined outcome risk 4%). The pathophysiology of each aspect of AAS is described. The best imaging techniques and the evolving role of endovascular techniques in the definitive management of AAS are discussed incorporating strategies to reduce perioperative morbidity.

Nordon, Ian M., E-mail: inordon@sgul.ac.uk; Hinchliffe, Robert J.; Loftus, Ian M.; Morgan, Robert A.; Thompson, Matt M. [St George's Hospital, St. George's Vascular Institute, St. James' Wing (United Kingdom)

2011-10-15

307

A quantum informational approach for dissecting chemical reactions  

E-print Network

We present a conceptionally different approach to dissect bond-formation processes in metal-driven catalysis using concepts from quantum information theory. Our method uses the entanglement and correlation among molecular orbitals to analyze changes in electronic structure that accompany chemical processes. As a proof-of-principle example, the evolution of nickel-ethene bond-formation is dissected which allows us to monitor the interplay of back-bonding and $\\pi$-donation along the reaction coordinate. Furthermore, the reaction pathway of nickel-ethene complexation is analyzed using quantum chemistry methods revealing the presence of a transition state. Our study supports the crucial role of metal-to-ligand back-donation in the bond-forming process of nickel-ethene.

Duperrouzel, Corinne; Boguslawski, Katharina; Barcza, Gergerly; Legeza, Örs; Ayers, Paul W

2014-01-01

308

A proposed dissection procedure for vertebral arteries in forensic pathology.  

PubMed

Vertebral artery removing constitutes a significant forensic pathology challenge. Dissection techniques during head-neck autopsy are based on anterior approach, a difficult method, which is unable to assess the transverse part of the artery. This work presents an original and simple method for dissecting vertebral arteries by a posterior approach, opening the vertebroarterial canal through the spinal canal without any special equipment. Once the spinal cord is removed, the transversarium foramens are opened by an internal cut at the pedicle and an external cut at the transverse process. This enables us to visualize vertebral arteries in its entirety. The method improves both the examination of the upper extracranial segment of the vertebral artery and the neuropathological study when arterial injury is suspected. Applying this method routinely is both feasible and useful in suspected cases of vertebral artery trauma and could contribute to assess more precisely the actual incidence of this injury. PMID:21827482

Galtés, Ignasi; Rodríguez-Baeza, Alfonso; Subirana, Mercè; Barbería, Eneko; Castellà, Josep; Medallo, Jordi

2012-01-01

309

Age-dependent differences in cervical artery dissection.  

PubMed

The goal of this work was to explore age-dependent differences in cervical artery dissection (CeAD). This study is based on the Cervical Artery Dissection and Ischemic Stroke Patients population comprising 983 consecutive CeAD patients and 658 control patients with a non-CeAD ischemic stroke (IS), frequency-matched for age and gender. Patients were divided into three age categories: ?33 (for CeAD, n = 150), 34-54 (n = 688), and ?55 (n = 145) years, and the youngest and oldest groups were compared. The youngest patients were mostly women and the oldest men. The frequency of internal carotid artery dissection (ICAD) versus vertebral artery dissection (VAD) increased with age from 44 to 75 %. This age-related shift remained significant after adjustment for sex. The frequency of a transient ischemic event as the CeAD symptom declined from 33 % in the youngest age group, to 19 % in the oldest. Vascular risk factors increased in frequency with advancing age in both groups, but for hypertension the increase was steeper for non-CeAD IS patients. For CeAD patients, but not for patients with non-CeAD IS, preceding infection was more common in the oldest group. The youngest non-CeAD IS patients had better functional outcome (modified Rankin Scale 0-1) than the oldest, while the similar trend was not statistically significant among CeAD patients. Younger age seems to be associated with VAD and female gender, and older age with ICAD and male gender. Age-related changes in the frequencies of hypertension and recent infection were different between the CeAD and non-CeAD IS groups. Age does not seem to be an important outcome predictor in CeAD strokes. PMID:22527225

Metso, Tiina M; Debette, Stéphanie; Grond-Ginsbach, Caspar; Engelter, Stefan T; Leys, Didier; Brandt, Tobias; Pezzini, Alessandro; Bersano, Anna; Kloss, Manja; Thijs, Vincent; Lyrer, Philippe A; Tatlisumak, Turgut; Metso, Antti J

2012-10-01

310

[Four cases of dissecting aneurysm of the aorta].  

PubMed

Four cases of dissecting aneurysm of the aorta are described. Attention is drawn to the difficulties of clinical diagnosis, the results of which will often be expressed in wide differences of prognosis and sometimes of treatment pattern, including surgical correction in suitable cases. A summary account of the literature data is used in expressing some views on the clinical and aetiopathogenetic position in the light of recent knowledge. PMID:17340830

Micheletti, P C; Tortarolo, E; Cardellino, G

1969-09-01

311

Science Sampler: Frog dissection--An alternative model  

NSDL National Science Digital Library

Local dollar stores can be a treasure-trove of inexpensive items that are ideal for hands-on activities in the science classroom. This article describes one such activity in which a model frog that costs less than a dollar was used to allow students to perform a simulated dissection. It was designed as a teacher-directed activity in order for students to practice reading, following complex directions, and using critical-thinking skills.

Sanders, June

2007-02-01

312

Modeling Plaque Fissuring and Dissection during Balloon Angioplasty Intervention  

Microsoft Academic Search

Balloon angioplasty intervention is traumatic to arterial tissue. Fracture mechanisms such as plaque fissuring and\\/or dissection\\u000a occur and constitute major contributions to the lumen enlargement. However, these types of mechanically-based traumatization\\u000a of arterial tissue are also contributing factors to both acute procedural complications and chronic restenosis of the treatment\\u000a site. We propose physical and finite element models, which are generally

T. Christian Gasser; Gerhard A. Holzapfel

2007-01-01

313

Laparoscopic gastrectomy with lymph node dissection for gastric cancer  

Microsoft Academic Search

Since 1991, laparoscopic surgery has been adopted for the treatment of gastric cancer, and it has been performed worldwide,\\u000a especially in Japan and Korea. We reviewed the English-language literature to clarify the current status of and problems associated\\u000a with laparoscopic gastrectomy with lymph node dissection as treatment for gastric cancer. In Japan, early-stage gastric cancer\\u000a (T1\\/T2, N0) is considered the

Norio Shiraishi; Kazuhiro Yasuda; Seigo Kitano

2006-01-01

314

Are all hands-on activities equally effective? Effect of using plastic models, organ dissections, and virtual dissections on student learning and perceptions.  

PubMed

This study investigated the impact of three commonly used cardiovascular model-assisted activities on student learning and student attitudes and perspectives about science. College students enrolled in a Human Anatomy and Physiology course were randomly assigned to one of three experimental groups (organ dissections, virtual dissections, or plastic models). Each group received a 15-min lecture followed by a 45-min activity with one of the treatments. Immediately after the lesson and then 2 mo later, students were tested on anatomy and physiology knowledge and completed an attitude survey. Students who used plastic models achieved significantly higher overall scores on both the initial and followup exams than students who performed organ or virtual dissections. On the initial exam, students in the plastic model and organ dissection treatments scored higher on anatomy questions than students who performed virtual dissections. Students in the plastic model group scored higher than students who performed organ dissections on physiology questions. On the followup exam, when asked anatomy questions, students in the plastic model group scored higher than dissection students and virtual dissection students. On attitude surveys, organ dissections had higher perceived value and were requested for inclusion in curricula twice as often as any other activity. Students who performed organ dissections were more likely than the other treatment groups to agree with the statement that "science is fun," suggesting that organ dissections may promote positive attitudes toward science. The findings of this study provide evidence for the importance of multiple types of hands-on activities in anatomy laboratory courses. PMID:24585474

Lombardi, Sara A; Hicks, Reimi E; Thompson, Katerina V; Marbach-Ad, Gili

2014-03-01

315

[CT analysis of aortic cobwebs in aortic dissection].  

PubMed

Contrast-enhanced CT images in patients with acute or chronic aortic dissection were evaluated for the purpose of determining the clinical usefulness of "aortic cobwebs", which were originally reported by Williams et al. as an anatomical marker of the false lumen. Aortic cobwebs were detected in 13 of 44 cases (30%), demonstrating as low density structures in the false lumen continuing from the intimal flap. The aortic cobwebs were mainly linear in shape, and the size ranged from 5 x 1 to 15 x 3 mm (mean: 9 x 2 mm). Aortic cobwebs were more frequently demonstrated in chronic than in acute cases, and were more often detected in the abdominal aorta. Follow-up CT examinations of the cobwebs revealed no interval change in six cases, disappearance in three cases and thickening in one case. There was no significant correlation between the sequential changes in the cobwebs and dilatation or thrombus formation in the false lumen. Aortic cobwebs seem to represent partially residual bands of the aortic media incompletely sheared from the aortic wall during the initial processes of aortic dissection. These structures are considered to be a reliable anatomic marker and to be useful for CT identification of the false lumen in aortic dissection. PMID:7617466

Hayashi, H; Onda, M; Takagi, R; Kawamata, H; Watari, J; Ichikawa, T; Kumazaki, T

1995-05-01

316

Magnetic resonance imaging of suspected cervicocranial arterial dissections.  

PubMed

The authors propose that the optimal screening protocol for evaluation of suspected cervicocranial arterial dissections is magnetic resonance imaging (MRI) that includes three components: 1) contrast-enhanced three-dimensional time-of-flight magnetic resonance angiography (MRA) through the superior mediastinum, neck, and skull base; 2) three-dimensional multiple overlapping thin-section acquisition MRA of the skull base and Circle of Willis region; and 3) axial non-contrast, non-fat-suppressed T1-weighted, fat-suppressed T1-weighted, and T2-weighted spin-echo MRI from the level of the aortic arch through the level of the circle of Willis. MRA permits visualization of vascular luminal narrowing or obliteration, which can suggest vascular dissection but can also be caused by congenital variation, dysplasia, intraluminal thrombus, vasospasm, or extramural compression by tumor. By directly visualizing the blood vessel wall, axial T1-weighted and T2-weighted spin-echo MRI can identify the intramural hemorrhage of vascular dissection. This protocol is designed to maximize the sensitivity of a noninvasive technique and may eliminate the need for conventional endovascular angiography. PMID:15662248

Shah, Gaurang V; Quint, Douglas J; Trobe, Jonathan D

2004-12-01

317

Endovascular Treatment of Iatrogenic and Traumatic Carotid Artery Dissection  

SciTech Connect

This paper reports on the early and midterm results of endovascular treatment of acute carotid artery dissections, its specific problems, and its limitations. We encountered seven patients with symptomatic extracranial carotid artery dissection, three cases of which occurred after carotid endarterectomy, two after carotid angioplasty and stenting, and two after trauma. Balloon-expandable and self-expanding stents were placed using a transfemoral approach. Success in restoring the carotid lumen was achieved in all patients. No procedure-related complications occurred. All patients experienced significant clinical improvement while in the hospital and achieved complete long-term recovery. At follow-up (mean, 22.4 months), good luminal patency of the stented segments was observed. In conclusion, in this small series, primary stent-supported angioplasty seems to be a safe and effective strategy in the treatment of selected patients having acute traumatic extracranial carotid artery dissection, with excellent early and midterm results. Larger series and longer-term follow-up are required before definitive recommendations can be made.

Schulte, Stefan; Donas, Konstantinos P., E-mail: k.donas@gmx.at; Pitoulias, Georgios A.; Horsch, Svante [Hospital Porz am Rhein, Academic Teaching Hospital of the University of Cologne, Department of Vascular Surgery (Germany)

2008-09-15

318

Saphenous Vein Sparing Superficial Inguinal Dissection in Lower Extremity Melanoma  

PubMed Central

Aim. The classic inguinal lymph node dissection is the main step for the regional control of the lower extremity melanoma, but this surgical procedure is associated with significant postoperative morbidity. The permanent lymphedema is the most devastating long-term complication leading to a significant decrease in the patient's quality of life. In this study we present our experience with modified, saphenous vein sparing, inguinal lymph node dissections for patients with melanoma of the lower extremity. Methods. Twenty one patients (10 women, 11 men) who underwent saphenous vein sparing superficial inguinal lymph node dissection for the melanoma of lower extremity were included in this study. The effects of saphenous vein sparing on postoperative complications were evaluated. Results. We have observed the decreased rate of long-term lymphedema in patients undergoing inguinal lymphadenectomy for the lower extremity melanoma. Conclusion. The inguinal lymphadenectomy with saphenous vein preservation in lower extremity melanoma patients seems to be an oncologically safe procedure and it may offer reduced long-term morbidity. PMID:25126426

Ozturk, Muhammed Besir; Akan, Arzu; Ozkaya, Ozay; Egemen, Onur; Oreroglu, Ali R?za; Akan, Mithat

2014-01-01

319

Talking about Death: Implementing Peer Discussion as a Coping Mechanism to Overcome Fears about Dissection, Death, and Dying  

ERIC Educational Resources Information Center

Many studies have reported on the perceptions of medical students toward dissection. It is important to understand the feelings and symptoms experienced during dissection so that they can be adequately handled. Prior to dissection, first year students are given lectures on aspects of dissection, death and dying, and death rituals in various…

Kotze, Sanet Henriet; Mole, Calvin Gerald

2013-01-01

320

Are All Hands-On Activities Equally Effective? Effect of Using Plastic Models, Organ Dissections, and Virtual Dissections on Student Learning and Perceptions  

ERIC Educational Resources Information Center

This study investigated the impact of three commonly used cardiovascular model-assisted activities on student learning and student attitudes and perspectives about science. College students enrolled in a Human Anatomy and Physiology course were randomly assigned to one of three experimental groups (organ dissections, virtual dissections, or…

Lombardi, Sara A.; Hicks, Reimi E.; Thompson, Katerina V.; Marbach-Ad, Gili

2014-01-01

321

Use of multimedia technology to provide solutions to existing curriculum problems: Virtual frog dissection  

NASA Astrophysics Data System (ADS)

The objective of this research was to determine whether currently available multimedia technology can resolve existing problems in the K--12 science curriculum. There are several practical and ethical problems relating to the classroom use of animal dissection and this led to the selection of hands-on frog dissection as the curriculum activity where the use of multimedia was investigated. The major finding was that multimedia-based virtual dissection was more effective than hands-on dissection in helping students learn about frog anatomy. Moreover, this result was achieved when the time available for the virtual dissection was approximately 44% less than that available for hands-on dissection. Examination of possible relationships between student characteristics and achievement revealed that students' attitudes to educational uses of animal dissection and their computer experience were positively correlated with their achievement scores. No relationships were found between either student gender or dissection experience and achievement test outcomes. Students rated virtual dissection as the easier of the two types of dissection, though they gave equivalent ratings for their enjoyment of virtual and hands-on dissection. Despite favorable feedback on the virtual dissection, a significant majority of students stated that they felt they would be "missing-out" on a valuable experience if they were not given the opportunity to perform a hands-on frog dissection. Comparing how students spent their time during each type of dissection showed that students spent a significantly larger proportion of their time On-Task when using the multimedia-based virtual dissection. In particular, the average increase in the proportion of time spent on activities directly related to the subject matter was over 36%. Time spent On-Task had a significant positive relationship with achievement for hands-on dissection. It may play a similar role for achievement with virtual dissection, but the small deviation in time On-Task data for virtual dissection prevented confirming this intuition. The teacher who participated in the research found that the use of a multimedia, inquiry-based computer application did limit his insight into students' classroom progress. However, he did not feel this to be a problem, nor did it in any way reduce his control over class activities.

Youngblut, Christine

322

Phosphoproteome and proteome analyses reveal low-phosphate mediated plasticity of root developmental and metabolic regulation in maize (Zea mays L.).  

PubMed

Phosphate (Pi) deficiency has become a significant challenge to worldwide agriculture due to the depletion of accessible rock phosphate that is the major source of cheap Pi fertilizers. Previous research has identified a number of diverse adaptive responses to Pi starvation in the roots of higher plants. In this study, we found that accelerated axile root elongation of Pi-deprived maize plants resulted from enhanced cell proliferation. Comparative phosphoproteome and proteome profiles of maize axile roots were conducted in four stages in response to Pi deficiency by multiplex staining of high-resolution two dimensional gel separated proteins. Pro-Q DPS stained gels revealed that 6% of phosphoprotein spots displayed changes in phosphorylation state following low-Pi treatment. These proteins were involved in a large number of metabolic and cellular pathways including carbon metabolism and signal transduction. Changes in protein abundance of a number of enzymes indicated that low-Pi induced a number of carbon flux modifications in metabolic processes including sucrose breakdown and other downstream sugar metabolic pathways. A few key metabolic enzymes, including sucrose synthase (EC 2.4.1.13) and malate dehydrogenase (EC 1.1.1.37), and several signaling components involved in protein kinase or phosphatase cascades, auxin signaling and 14-3-3 proteins displayed low-Pi responsive changes in phosphorylation state or protein abundance. A variety of key enzymes and signaling components identified as potential targets for phosphorylation provide novel clues for comprehensive understanding of Pi regulation in plants. Protein phosphorylation, coordinating with changes in protein abundance, is required for maize root metabolic regulation and developmental acclimation to Pi starvation. PMID:25190054

Li, Kunpeng; Xu, Changzheng; Fan, Wenming; Zhang, Hongli; Hou, Jiajia; Yang, Aifang; Zhang, Kewei

2014-10-01

323

Phosphoproteomic identification of targets of the Arabidopsis sucrose nonfermenting-like kinase SnRK2.8 reveals a connection to metabolic processes  

PubMed Central

SnRK2.8 is a member of the sucrose nonfermenting-related kinase family that is down-regulated when plants are deprived of nutrients and growth is reduced. When this kinase is over expressed in Arabidopsis, the plants grow larger. To understand how this kinase modulates growth, we identified some of the proteins that are phosphorylated by this kinase. A new phosphoproteomic method was used in which total protein from plants overexpressing the kinase was compared with total protein from plants in which the kinase was inactivated. Protein profiles were compared on two-dimensional gels following staining by a dye that recognizes phosphorylated amino acids. Candidate target proteins were confirmed with in vitro phosphorylation assays, using the kinase and target proteins that were purified from Escherichia coli. Seven target proteins were confirmed as being phosphorylated by SnRK2.8. Certain targets, such as 14-3-3 proteins, regulate as yet unidentified proteins, whereas other targets, such as glyoxalase I and ribose 5-phosphate isomerase, detoxify byproducts from glycolysis and catalyze one of the final steps in carbon fixation, respectively. Also, adenosine kinase and 60S ribosomal protein were confirmed as targets of SnRK2.8. Using mass spectrometry, we identified phosphorylated residues in the SnRK2.8, the 14-3-3?, and the 14-3-3?. These data show that the expression of SnRK2.8 is correlated with plant growth, which may in part be due to the phosphorylation of enzymes involved in metabolic processes. PMID:17404219

Shin, Ryoung; Alvarez, Sophie; Burch, Adrien Y.; Jez, Joseph M.; Schachtman, Daniel P.

2007-01-01

324

Recurrent aortic dissection presenting with repeated transient ischemic attacks: a novel pathophysiology and successful endovascular treatment.  

PubMed

Aortic dissection is the most common and the most lethal event that can involve the aorta. Typically, aortic dissection presents with sharp, tearing, or ripping pain. Alternatively, the patients may suffer from possible extension of the dissecting aneurysm into the supra-aortic vessels resulting in syncope in 9.4 % of patients cerebrovascular accidents in 4.7 %. We present a case of recurrent aortic dissection, which presented with recurrent transient ischemic attacks (TIAs). The etiology of the neurological symptoms was attributed to a steal phenomenon. The right subclavian artery was supplied by retrograde flow from the right internal carotid artery through the false lumen of the dissection. To prevent further hemodynamic TIAs, we successfully occluded the proximal part of the false lumen of the dissection responsible for the steal phenomenon. PMID:23307261

Elshikh, S; Schumacher, M; Dohmen, A; Weber, J

2013-12-01

325

Multidetector computed tomography angiography: Application in vertebral artery dissection  

PubMed Central

Background and Purpose: Multidetector computed tomography angiography (MDCTA) is a minimally invasive radiological technique providing high-resolution images of the arterial wall and angiographic images of the lumen. We studied the radiological features of vertebral artery dissection (VAD) in a consecutive series of patients investigated for acute stroke and subarachnoid hemorrhage (SAH) in order to confirm and define the diagnostic features of VAD on MDCTA. Patients and Methods: Review of patients identified prospectively over a 4-year period with VAD assessed by MDCTA was conducted. Radiological features of VAD on MDCTA were reanalyzed utilising previously reported criteria for VAD. Results: Thirty-five patients (25 males, mean age 49.6 years) with a total of 45 dissected vertebral arteries were reviewed. MDCTA features of VAD included increased wall thickness in 44/45 (97.7%) arteries and increased total vessel diameter in 42/45 arteries (93.3%). All dissected arteries had either lumen stenosis (21/45) or associated segmental occlusion (24/45). An intimal flap was detected in 6/45 (13.3 %) vessels. Twenty-five patients had follow-up imaging, 14/32 vessels returned to normal, 4 showed improvement in stenosis but did not return to normal and 14 demonstrated no change. The majority of non-occluded vessels became normal or displayed improved patency. Only 4/17 occluded arteries demonstrated re-establishment of flow. No adverse effects were recorded. Conclusions: MDCTA is a safe and reliable technique for the diagnosis of VAD. Increased wall thickness (97.7%) and increased vessel wall diameter (93.3%) were the most frequently observed features. PMID:21633613

Teasdale, Evelyn; Zampakis, Peter; Santosh, Celestine; Razvi, Saif

2011-01-01

326

Follicle trauma and the role of the dissecting microscope in hair transplantation. A multicenter study.  

PubMed

Use of the dissecting stereomicroscope during hair transplant graft dissection has been advocated as a means of reducing hair follicle transection and improving graft growth. The study evaluated the prevalence of hair follicle transection in grafts prepared with and without the dissecting stereomicroscope. Approximately half as much transection (10% vs 20%, p < 0.05) was noted in grafts prepared with microscopes, suggesting their use may be associated with less hair follicle trauma and improved hair growth. PMID:10327300

Cooley, J E; Vogel, J E

1999-04-01

327

Dissecting aneurysms of the vertebrobasilar system. A comprehensive review on natural history and treatment options  

Microsoft Academic Search

Vertebral artery dissection has been recognized as an uncommon cause of ischemic stroke. However, it is less well known as\\u000a a cause of subarachnoid hemorrhage. Even if dissecting aneurysms of the vertebral artery are rare, their importance arise\\u000a from their high morbidity and mortality with rebleeding occurring more often than in cases of saccular aneurysms. Dissecting\\u000a aneurysms of the vertebrobasilar

Jorge Arturo Santos-Franco; Marco Zenteno; Angel Lee

2008-01-01

328

In utero release of constriction amniotic bands via blunt dissection.  

PubMed

Therapeutic techniques for in utero release of amniotic bands have relied on transecting instruments. We present an additional technique, blunt dissection, to release a constriction band in utero. The lower extremity that had detectable abnormalities during prenatal ultrasound had improved outcome after blunt in utero release of the amniotic band compared to the contralateral (control) leg. These findings support two conjectures: first, the degree of band adherence to the fetus is an important factor influencing the surgical approach to in utero lysis of the bands; second, that in utero release of constriction bands can result in improvement in outcome. PMID:22017664

Assaf, Raymen; Llanes, Arlyn; Chmait, Ramen

2012-02-01

329

Coronary angiogram classification of spontaneous coronary artery dissection.  

PubMed

Spontaneous coronary artery dissection (SCAD) is under-diagnosed and the true prevalence is underestimated. Unfortunately, SCAD is frequently missed on coronary angiogram since the arterial wall is not imaged with this test. Optical coherence tomography or intravascular ultrasound should be the true gold-standard to diagnose SCAD. Given the elusive angiographic diagnosis of SCAD and the lack of familiarity with angiographic variants of SCAD, a diagnostic algorithm and angiographic classification for SCAD is proposed in this article. © 2013 Wiley Periodicals, Inc. PMID:24227590

Saw, Jacqueline

2014-12-01

330

Aortic intramural hematoma progressing rapidly to aortic dissection.  

PubMed

A 73-year-old man presented with intermittent chest pain radiating to the back, which had started 12 hours earlier. On the day after emergency consultation, a thoracic scan showed an acute aortic intramural hematoma starting at the sinotubular junction with an ascending aorta diameter of 5.7 cm. One hour after the initial scan, the patient had acute chest pain followed by a loss of consciousness. A second scan was obtained 2 hours after the initial scan and showed a type A aortic dissection that extended from the sinotubular junction to the descending aorta. PMID:25154802

Dionne, Pierre Olivier; Perrault, Louis P

2014-10-01

331

Ruptured Valsalva Sinus Aneurysm to Pericardium Simulated Aortic Root Dissection  

PubMed Central

Ruptured valsalva sinus aneurysm to pericardium is a rare condition. Here, we described a case presented with tamponade. Initially, hemopericardium was partially drained and then, imaging evaluations were done. Transesophageal echocardiography showed limited dissection of aortic sinus and CT angiography of the ascending aorta showed deformed dilated right coronary sinus. Besides, surgery showed that windsock tract of the right coronary sinus had ruptured into the pericardium with avulsed right coronary aortic cusp. This case indicated a rare cause of cardiac tamponade and insufficiency of imaging modalities for making an accurate diagnosis. PMID:24936486

Davarpasand, Tahereh; Hosseinsabet, Ali; Abassi, Kumars; Arzhan, Sorya

2014-01-01

332

Models and approaches to dissect host-symbiont specificity.  

PubMed

Animals are symbiotic superorganisms, composed of eukaryotic cells and specific microbial residents that perform essential functions for their host. As humans, we are beginning to appreciate the diversity and function of our own microbiota, but model systems are leading the field in illustrating the molecular mechanisms that allow specific relationships to be recapitulated during each host generation. This review focuses on models in which genetic screens, coupled with genomics, imaging, phylogenetics and population biology, have begun to allow a remarkably detailed investigation into the molecular dissection of the evolution of host specificity in animal symbionts. PMID:20729086

Mandel, Mark J

2010-11-01

333

Ruptured valsalva sinus aneurysm to pericardium simulated aortic root dissection.  

PubMed

Ruptured valsalva sinus aneurysm to pericardium is a rare condition. Here, we described a case presented with tamponade. Initially, hemopericardium was partially drained and then, imaging evaluations were done. Transesophageal echocardiography showed limited dissection of aortic sinus and CT angiography of the ascending aorta showed deformed dilated right coronary sinus. Besides, surgery showed that windsock tract of the right coronary sinus had ruptured into the pericardium with avulsed right coronary aortic cusp. This case indicated a rare cause of cardiac tamponade and insufficiency of imaging modalities for making an accurate diagnosis. PMID:24936486

Davarpasand, Tahereh; Hosseinsabet, Ali; Abassi, Kumars; Arzhan, Sorya

2014-04-01

334

Dissecting inhibitory brain circuits with genetically-targeted technologies  

PubMed Central

The evolution of genetically targeted tools has begun to allow us to dissect anatomically and functionally heterogeneous interneurons, and to probe circuit function from synapses to behavior. Over the last decade, these tools have been used widely to visualize neurons in a cell type-specific manner, and engage them to activate and inactivate with exquisite precision. In this process, we have expanded our understanding of interneuron diversity, their functional connectivity, and how selective inhibitory circuits contribute to behavior. Here we discuss the relative assets of genetically encoded fluorescent proteins (FPs), viral tracing methods, optogenetics, chemical genetics, and biosensors in the study of inhibitory interneurons and their respective circuits. PMID:25368555

Murphey, Dona K.; Herman, Alexander M.; Arenkiel, Benjamin R.

2014-01-01

335

A Case of Acute Aortic Dissection Presenting with Chest Pain Relieved by Sublingual Nitroglycerin  

PubMed Central

Acute aortic dissection is an uncommon disorder which can have fatal results in the event of treatment delay or misdiagnosis. This case examines a 77-year-old woman presenting with chest pain relieved by nitroglycerin. She was referred to the emergency room with clinical suspicion of acute coronary syndrome (ACS). However, she was later diagnosed with acute aortic dissection and an emergency operation was performed with successful recovery. Aortic dissection may manifest in various ways depending on the site involved and may mimic other disorders such as ACS or pulmonary embolism. Therefore, clinicians must always be aware of aortic dissection and its different clinical manifestations must be understood. PMID:24340165

Kim, Hyun Joo; Lee, Hyun-Ki

2013-01-01

336

Application of blunt dissection in ESD of a gastric submucosal tumor  

PubMed Central

We performed endoscopic submucosal dissection of a gastric fundus tumor. It was difficult to strip the tumor completely due to space limitation, and we used blunt dissection to remove the tumor quickly and safely. Firstly, the basal area of the 2.5 cm submucosal tumor located in the gastric fundus was cut open, and the mucosa was dissected. The tumor was difficult to peel, therefore, a snare was used and the tumor was pulled and tightened slightly. Short electronic coagulation was used during the procedure. The tumor was then bluntly dissected. This method ensured rapid and complete removal of the tumor. PMID:24914398

Wen, Zong-Quan; Wu, Guang-Yao; Yu, Shao-Ping; Lin, Xiao-Dong; Li, Song-Hu; Huang, Xian-Guang; Zhang, Fu; Zeng, Xiao-Yu; Huang, Hai-Yan; Li, Ai-Mei

2014-01-01

337

Isolated spontaneous dissection of the celiac trunk in a patient with bicuspid aortic valve.  

PubMed

Isolated spontaneous dissection of celiac trunk is a rare entity. The spontaneous dissection of the visceral artery occurs without aortic dissection. The most consistent presenting symptom is acute onset abdominal pain. Complications consist of ischemia, aneurysm formation, and rupture. We report an exceptional case of an isolated spontaneous dissection of the celiac trunk which occurred in a 49 year old male with a previously undiagnosed bicuspid aortic valve (BAV). We also describe the classical appearance in different imaging modalities with a particular emphasis on multidetector computed tomography, and discuss the clinical manifestation and its relationship to BAV. PMID:20539840

Zeina, Abdel-Rauf; Nachtigal, Alicia; Troitsa, Anton; Admon, Gil; Avshovich, Nina

2010-01-01

338

Nanometer-Scale Dissection of Chromosomes by Atomic Force Microscopy Combined with Heat-Denaturing Treatment  

NASA Astrophysics Data System (ADS)

We have developed a method for dissecting chromosome fragments with a size of a few hundred nanometers by atomic force microscopy (AFM). By using this method, we demonstrated reproducible dissections of silkworm chromosomes in the pachytene phase. The dissected fragments were successfully recovered on the cantilever tips, as confirmed by fluorescent microscopy using fluorescent stained chromosomes. To recover dissected chromosome fragments from a larger chromosome, such as the human metaphase chromosome of a somatic cell, heat denaturation was found to be effective. Further improvements in this method may lead to a novel tool for isolating valuable genes and/or investigating local genome structures in the near future.

Tsukamoto, Kazumi; Kuwazaki, Seigo; Yamamoto, Kimiko; Shichiri, Motoharu; Yoshino, Tomoyuki; Ohtani, Toshio; Sugiyama, Shigeru

2006-03-01

339

Cell-type Specific Optogenetic Mice for Dissecting Neural Circuitry Function  

E-print Network

Optogenetic methods have emerged as powerful tools for dissecting neural circuit connectivity, function, and dysfunction. We used a Bacterial Artificial Chromosome (BAC) transgenic strategy to express Channelrhodopsin2 ...

Zhao, Shengli

340

Vertebral Dissecting Aneurysm Treated with Wingspan Stent Deployment and Detachable Coils  

PubMed Central

Summary We describe the first documented endovascular treatment of vertebral dissecting aneurysm using a Wingspan stent and detachable coils. A 54-year-old man presented with a nonruptured vertebral dissecting aneurysm. Because of the dissecting nature of the vertebral aneurysms, a 3x15-mm Wingspan stent was placed in the left vertebral artery. One month later, several detachable coils were introduced into the aneurysm. Six-month follow-up angiogram confirmed the obliteration. Vertebral dissecting aneurysm can be treated with Wingspan stent placement and detachable coils. PMID:20465940

Lv, M.; Lv, X.; Li, Y.; Yang, X.; Wu, Z.

2009-01-01

341

Non Linear Programming (NLP) formulation for quantitative modeling of protein signal transduction pathways.  

PubMed

Modeling of signal transduction pathways plays a major role in understanding cells' function and predicting cellular response. Mathematical formalisms based on a logic formalism are relatively simple but can describe how signals propagate from one protein to the next and have led to the construction of models that simulate the cells response to environmental or other perturbations. Constrained fuzzy logic was recently introduced to train models to cell specific data to result in quantitative pathway models of the specific cellular behavior. There are two major issues in this pathway optimization: i) excessive CPU time requirements and ii) loosely constrained optimization problem due to lack of data with respect to large signaling pathways. Herein, we address both issues: the former by reformulating the pathway optimization as a regular nonlinear optimization problem; and the latter by enhanced algorithms to pre/post-process the signaling network to remove parts that cannot be identified given the experimental conditions. As a case study, we tackle the construction of cell type specific pathways in normal and transformed hepatocytes using medium and large-scale functional phosphoproteomic datasets. The proposed Non Linear Programming (NLP) formulation allows for fast optimization of signaling topologies by combining the versatile nature of logic modeling with state of the art optimization algorithms. PMID:23226239

Mitsos, Alexander; Melas, Ioannis N; Morris, Melody K; Saez-Rodriguez, Julio; Lauffenburger, Douglas A; Alexopoulos, Leonidas G

2012-01-01

342

Non Linear Programming (NLP) Formulation for Quantitative Modeling of Protein Signal Transduction Pathways  

PubMed Central

Modeling of signal transduction pathways plays a major role in understanding cells' function and predicting cellular response. Mathematical formalisms based on a logic formalism are relatively simple but can describe how signals propagate from one protein to the next and have led to the construction of models that simulate the cells response to environmental or other perturbations. Constrained fuzzy logic was recently introduced to train models to cell specific data to result in quantitative pathway models of the specific cellular behavior. There are two major issues in this pathway optimization: i) excessive CPU time requirements and ii) loosely constrained optimization problem due to lack of data with respect to large signaling pathways. Herein, we address both issues: the former by reformulating the pathway optimization as a regular nonlinear optimization problem; and the latter by enhanced algorithms to pre/post-process the signaling network to remove parts that cannot be identified given the experimental conditions. As a case study, we tackle the construction of cell type specific pathways in normal and transformed hepatocytes using medium and large-scale functional phosphoproteomic datasets. The proposed Non Linear Programming (NLP) formulation allows for fast optimization of signaling topologies by combining the versatile nature of logic modeling with state of the art optimization algorithms. PMID:23226239

Morris, Melody K.; Saez-Rodriguez, Julio; Lauffenburger, Douglas A.; Alexopoulos, Leonidas G.

2012-01-01

343

Subretinal Perfluorocarbon Liquid for Dissection of Proliferative Vitreoretinopathy  

PubMed Central

Proliferative vitreoretinopathy (PVR) is a frequent condition following complex retinal detachments or trauma, and subretinal PVR is a common cause of retinal redetachment. Subretinal PVR removal is challenging and may require creating multiple or large retinotomies, making manipulation of the retina difficult and sometimes hazardous. We propose a novel surgical technique that may facilitate subretinal removal of PVR. After peripheral retinotomy of 180 degrees or greater, perfluorocarbon liquid (PFCL) is carefully introduced into the subretinal space as a single bubble which provides space to perform the maneuvers. The PFCL serves as a second hand which folds the retina over, thereby allowing better visualization for safer and easier subretinal PVR removal. PFCL in then removed by direct aspiration as a single bubble while still under balanced salt solution, taking advantage of its high surface tension which prevents leaving bubbles behind. The described technique allows adequate exposure of the subretinal space for proper dissection of difficult-to-reach subretinal PVR. We applied this technique in five patients with chronic retinal detachment, extensive subretinal PVR and poor visual potential. The utilization of subretinal PFCL can assist dissection of subretinal PVR and may be useful in eyes with complicated retinal detachment and poor visual prognosis. PMID:23502847

Dalma-Weiszhausz, Jose; Franco-Cardenas, Valentina; Dalma, Alejandro

2012-01-01

344

Predicting aortic enlargement in type B aortic dissection  

PubMed Central

Patients with uncomplicated acute type B aortic dissection (ABAD) can generally be treated with conservative medical management. However, these patients may develop aortic enlargement during follow-up, with the risk of rupture. Several predictors have been studied in recent years to identify ABAD patients at high risk of aortic enlargement, who may benefit from early surgical or endovascular intervention. This study reviewed and summarized the current available literature on prognostic variables related to aortic enlargement during follow-up in uncomplicated ABAD patients. It revealed multiple factors affecting aortic expansion including demographic, clinical, pharmacologic and radiologic variables. Such predictors may be used to identify those ABAD patients at higher risk for aortic enlargement who may benefit from closer radiologic surveillance or early endovascular intervention. This approach deserves even more consideration because a significant number of patients develop aneurysmal degeneration along the dissected segments during follow-up, and may lose the opportunity for endovascular treatment if not identified at an early stage. PMID:24967168

Jonker, Frederik H. W.; van Bogerijen, Guido H. W.; Tolenaar, Jip L.; Moll, Frans L.; Czerny, Martin; Patel, Himanshu J.

2014-01-01

345

Virtual Temporal Bone Dissection System: Development and Testing  

PubMed Central

Objectives/Hypothesis The objective of this project was to develop a virtual temporal bone dissection system that would provide an enhanced educational experience for the training of otologic surgeons. Study Design A randomized, controlled, multi-institutional single blinded validation study. Methods The project encompassed 4 areas of emphasis: structural data acquisition, integration of the system, dissemination of the system, and validation. Results Structural acquisition was performed on multiple imaging platforms. Integration achieved a cost effective system. Dissemination was achieved on different levels including casual interest, downloading of software, and full involvement in development and validation studies. A validation study was performed at 8 different training institutions across the country using a two arm, randomized trial where study subjects were randomized to a two-week practice session using either the virtual temporal bone or standard cadaveric temporal bones. Eighty subjects were enrolled and randomized to one of the two treatment arms, 65 completed the study. There was no difference between the two groups using a blinded rating tool to assess performance after training. Conclusions 1. A virtual temporal bone dissection system has been developed and compared to cadaveric temporal bones for practice using a multi-center trial. 2. There is no statistical difference seen between practice on the current simulator when compared to practice on human cadaveric temporal bones. 3. Further refinements in structural acquisition and interface design have been identified which can be implemented prior to full incorporation into training programs and use for objective skills assessment. PMID:22294268

Wiet, Gregory J.; Stredney, Don; Kerwin, Thomas; Hittle, Bradley; Fernandez, Soledad A.; Welling, D. Bradley

2012-01-01

346

Combined subgaleal/myocutaneous technique for temporalis muscle dissection.  

PubMed

Background?The frontal branch of the facial nerve (FBFN) is the most susceptible neural structure to injury during frontotemporal craniotomies. The balance between adequate temporalis muscle mobilization and frontal branch protection with minimal anatomical alteration is the philosophy behind our approach to temporalis muscle dissection. Objective?To describe a combined subgaleal/myocutaneous technique for dissection and mobilization of the temporalis muscle in anterolateral cranial approaches. Methods?Interdisciplinary literature review of the anatomical course of the FBFN was performed. Retrospective analysis of anterolateral craniotomies performed at our institution in which the combined subgaleal/myocutaneous (CSGMC) technique was performed. Results?A total of 71 cases of anterolateral craniotomies (excluding full variant orbitozygomatic) were performed with the successful application of a CSGMC technique (36 pterional, 31 orbitopterional, and 4 fronto-orbital). Partial frontalis weakness was transient in one case. Conclusion?The CSGMC technique provides sufficient protection for the FBFN and allows for adequate mobilization for a variety of skull base exposures while minimally violating myofascial anatomy. This is the first reported technique that allows both adequate temporalis muscle mobilization with performance of the one-piece orbitofrontal and orbitopterional approaches, without disruption of the superficial/deep temporalis fascia and fat-pad complex. PMID:24294555

Youssef, A Samy; Ahmadian, Amir; Ramos, Edwin; Vale, Fernando; van Loveren, Harry R

2012-12-01

347

Genetic basis of thoracic aortic aneurysms and aortic dissections.  

PubMed

Ascending thoracic aortic aneurysms leading to type A dissections (TAAD) can occur in association with a genetic syndrome, such as Marfan syndrome (MFS), or as an autosomal dominant disorder in the absence of syndromic features, termed familial TAAD. Familial TAAD demonstrates genetic heterogeneity, and linkage studies have identified three TAAD loci at 5q13-14 (TAAD1), 11q23 (FAA1), and 3p24-25 (TAAD2). The underlying genetic heterogeneity of TAAD is reflected in the phenotypic variation associated with familial TAAD with respect to age of onset, progression, penetrance, and association with additional cardiac and vascular features. Recently, mutations in the TGFBR2 gene have been identified as the cause of disease linked to the TAAD2 locus, supporting the hypothesis that dysregulation of TGFbeta signaling is a mechanism leading to aneurysms and dissections. The recent identification of the TGFbeta pathway as a key target in the molecular pathogenesis of TAAD has opened new avenues for future genetic and therapeutic research. PMID:16273536

Pannu, Hariyadarshi; Tran-Fadulu, Van; Milewicz, Dianna M

2005-11-15

348

Popliteal lymph node dissection for metastases of cutaneous malignant melanoma  

PubMed Central

Popliteal lymph node dissection is performed when grossly metastatic nodal disease is encountered in the popliteal fossa or after microscopic metastasis is found in interval sentinel nodes during clinical staging of cutaneous malignant melanoma. Initially, an S-shaped incision is made to gain access to the popliteal fossa. A careful en bloc removal of fat tissue and lymph nodes is made to preserve and avoid the injury of peroneal and tibial nerves as well as popliteal vessels, following the previous recommendations. This rare surgical procedure was successfully employed in a patient with cutaneous malignant melanoma and nodal metastases at the popliteal fossa. The technique described by Karakousis was reproduced in a step-by-step fashion to allow anatomical identification of the neurovascular structures and radical resection with no post-operative morbidity and prompt recovery. Popliteal lymph node dissection is a rarely performed operative procedure. Following a lymphoscintigraphic examination of the popliteal nodal station, surgeons can be asked to explore the popliteal fossa. Detailed familiarity of the operative procedure is necessary, however, to avoid complications. PMID:24886058

2014-01-01

349

Towards a fast implementation of spectral nested dissection  

NASA Technical Reports Server (NTRS)

We describe the spectral nested dissection (SND) algorithm, a new algorithm for computing orderings appropriate for parallel factorization of sparse, symmetric matrices. The algorithm makes use of spectral properties of the Laplacian matrix associated with the given matrix to compute separators. We evaluate the quality of the spectral orderings with respect to several measures: fill, elimination tree height, height and weight balances of elimination trees, and clique tree heights. We use some very large structural analysis problems as test cases and demonstrate on these real applications (such as the Space Shuttle Solid Rocket Booster) that spectral orderings compare quite favorably with commonly used orderings, outperforming them by a wide margin for some of these measures. The only disadvantage of SND is its relatively long execution time. We will present some recent efforts to improve the execution time using both a multilevel and a hybrid approach. We use SND in computing a multifrontal numerical factorization with the different orderings on an eight processor Cray Y-MP and show its effectiveness. We believe that spectral nested dissection is a major breakthrough in terms of generating efficient sparse orderings for parallel machines.

Pothen, Alex; Simon, Horst D.; Wang, Lie; Barnard, Stephen T.

1992-01-01

350

Mutations in TGFBR2 gene cause spontaneous cervical artery dissection.  

PubMed

Mutations in the genes encoding transforming growth factor ? receptors 1 and 2 (TGFBR1 and TGFBR2) have recently been associated with hereditary connective tissue disorders with widespread vascular involvement, including arterial dissection. To determine whether mutations in these genes cause spontaneous cervical artery dissection (sCAD), all coding exons of TGFBR1 and TGFBR2 were sequenced in 56 consecutive patients with sCAD. Novel TGFBR2 disease causing mutations were found in two patients. The two mutations were the pK327R substitution affecting the kinase domain of TGFBR2 and the pC138R substitution falling in the extracellular domain of the protein, involved in TGF? binding and signalling. No TGFBR1 mutation was found. The findings indicate that TGFBR2 gene mutations are responsible for sCAD in 3.6% (95% CI 0.0 to 8.4) of cases, have implications in understanding the role of TGF? signalling in the pathogenesis of sCAD and emphasise the importance of considering molecular characterisation of the TGFBR2 gene in these patients, regardless of the presence of clinical features suggestive of hereditary connective tissue disorders. PMID:21270064

Pezzini, Alessandro; Drera, Bruno; Del Zotto, Elisabetta; Ritelli, Marco; Carletti, Monica; Tomelleri, Gianpaolo; Bovi, Paolo; Giossi, Alessia; Volonghi, Irene; Costa, Paolo; Magoni, Mauro; Padovani, Alessandro; Barlati, Sergio; Colombi, Marina

2011-12-01

351

Evaluating the promiscuous nature of tyrosine kinase inhibitors assessed in A431 epidermoid carcinoma cells by both chemical- and phosphoproteomics.  

PubMed

Deregulation of protein tyrosine kinase signaling has been linked to many diseases, most notably cancer. As a consequence, small molecule inhibitors of protein tyrosine kinases may provide powerful strategies for treatment. Following the successful introduction of imatinib in the treatment of chronic myelogenous leukemia, such drugs are also now evaluated for other types of cancer. However, many developed kinase inhibitors are not very target-specific and therefore may induce side effects. The importance of such side effects is certainly cell-proteome dependent. Understanding the all-inclusive action of a tyrosine kinase inhibitor on each individual cell-type entails the identification of potential targets, combined with monitoring the downstream effects revealing the signaling networks involved. Here, we explored a multilevel quantitative mass spectrometry-based proteomic strategy to identify the direct targets and downstream signaling effect of four tyrosine kinase inhibitors (imatinib, dasatinib, bosutinib, and nilotinib) in epidermoid carcinoma cells, as a model system for skin-cancer. More than 25 tyrosine kinases showed affinity to the drugs, with imatinib and nilotinib displaying a high specificity, especially when compared to dasatinib and bosutinib. Consequently, the latter two drugs showed a larger effect on downstream phosphotyrosine signaling. Many of the proteins affected are key regulators in cell adhesion and invasion. Our data represents a multiplexed view on the promiscuous action of certain tyrosine kinase inhibitors that needs to be taking into consideration prior to the application of these drugs in the treatment of different forms of cancer. PMID:24804581

Giansanti, Piero; Preisinger, Christian; Huber, Kilian V M; Gridling, Manuela; Superti-Furga, Giulio; Bennett, Keiryn L; Heck, Albert J R

2014-07-18

352

Dissection of a Krox20 positive feedback loop driving cell fate choices in hindbrain patterning  

PubMed Central

Although feedback loops are essential in development, their molecular implementation and precise functions remain elusive. Using enhancer knockout in mice, we demonstrate that a direct, positive autoregulatory loop amplifies and maintains the expression of Krox20, a transcription factor governing vertebrate hindbrain segmentation. By combining quantitative data collected in the zebrafish with biophysical modelling that accounts for the intrinsic stochastic molecular dynamics, we dissect the loop at the molecular level. We find that it underpins a bistable switch that turns a transient input signal into cell fate commitment, as we observe in single cell analyses. The stochasticity of the activation process leads to a graded input–output response until saturation is reached. Consequently, the duration and strength of the input signal controls the size of the hindbrain segments by modulating the distribution between the two cell fates. Moreover, segment formation is buffered from severe variations in input level. Finally, the progressive extinction of Krox20 expression involves a destabilization of the loop by repressor molecules. These mechanisms are of general significance for cell type specification and tissue patterning. PMID:24061538

Bouchoucha, Yassine X; Reingruber, Jurgen; Labalette, Charlotte; Wassef, Michel A; Thierion, Elodie; Desmarquet-Trin Dinh, Carole; Holcman, David; Gilardi-Hebenstreit, Pascale; Charnay, Patrick

2013-01-01

353

Characterization and genetic dissection of resistance to spotted alfalfa aphid (Therioaphis trifolii) in Medicago truncatula  

PubMed Central

Aphids cause significant yield losses in agricultural crops worldwide. Medicago truncatula, a model legume, cultivated pasture species in Australia and close relative of alfalfa (Medicago sativa), was used to study the defence response against Therioaphis trifolii f. maculate [spotted alfalfa aphid (SAA)]. Aphid performance and plant damage were compared among three accessions. A20 is highly susceptible, A17 has moderate resistance, and Jester is strongly resistant. Subsequent analyses using A17 and A20, reciprocal F1s and an A17×A20 recombinant inbred line (RIL) population revealed that this moderate resistance is phloem mediated and involves antibiosis and tolerance but not antixenosis. Electrical penetration graph analysis also identified a novel waveform termed extended potential drop, which occurred following SAA infestation of M. truncatula. Genetic dissection using the RIL population revealed three quantitative trait loci on chromosomes 3, 6, and 7 involved in distinct modes of aphid defence including antibiosis and tolerance. An antibiosis locus resides on linkage group 3 (LG3) and is derived from A17, whereas a plant tolerance and antibiosis locus resides on LG6 and is derived from A20, which exhibits strong temporary tolerance. The loci identified reside in regions harbouring classical resistance genes, and introgression of these loci in current medic cultivars may help provide durable resistance to SAA, while elucidation of their molecular mechanisms may provide valuable insight into other aphid–plant interactions. PMID:24058162

Kamphuis, Lars G.; Lichtenzveig, Judith; Peng, Kefan; Guo, Su-Min; Klingler, John P.

2013-01-01

354

Toward Quantitative "In Vivo Biochemistry" with Fluorescence Fluctuation Spectroscopy  

PubMed Central

Quantitative description of protein dynamics and interactions in vivo with temporal and spatial resolution is a key step in dissecting molecular mechanisms in cell biology. Fluorescence fluctuation spectroscopy (FFS) has recently emerged as a powerful in vivo tool for assessing molecular concentration and movement and formation of hetero- and homo-oligomeric complexes. This article discusses point FFS-based analysis methods that have proven useful to cell biologists, focusing on the kinds of information they provide, their pros and cons, and the basic instrumentation required. Along the way, we describe briefly a few recent examples where these analyses have helped address important biological questions. PMID:21160072

2010-01-01

355

Dissecting yield-associated loci in super hybrid rice by resequencing recombinant inbred lines and improving parental genome sequences.  

PubMed

The growing world population and shrinkage of arable land demand yield improvement of rice, one of the most important staple crops. To elucidate the genetic basis of yield and uncover its associated loci in rice, we resequenced the core recombinant inbred lines of Liang-You-Pei-Jiu, the widely cultivated super hybrid rice, and constructed a high-resolution linkage map. We detected 43 yield-associated quantitative trait loci, of which 20 are unique. Based on the high-density physical map, the genome sequences of paternal variety 93-11 and maternal cultivar PA64s of Liang-You-Pei-Jiu were significantly improved. The large recombinant inbred line population combined with plentiful high-quality single nucleotide polymorphisms and insertions/deletions between parental genomes allowed us to fine-map two quantitative trait loci, qSN8 and qSPB1, and to identify days to heading8 and lax panicle1 as candidate genes, respectively. The quantitative trait locus qSN8 was further confirmed to be days to heading8 by a complementation test. Our study provided an ideal platform for molecular breeding by targeting and dissecting yield-associated loci in rice. PMID:23940322

Gao, Zhen-Yu; Zhao, Shan-Cen; He, Wei-Ming; Guo, Long-Biao; Peng, You-Lin; Wang, Jin-Jin; Guo, Xiao-Sen; Zhang, Xue-Mei; Rao, Yu-Chun; Zhang, Chi; Dong, Guo-Jun; Zheng, Feng-Ya; Lu, Chang-Xin; Hu, Jiang; Zhou, Qing; Liu, Hui-Juan; Wu, Hai-Yang; Xu, Jie; Ni, Pei-Xiang; Zeng, Da-Li; Liu, Deng-Hui; Tian, Peng; Gong, Li-Hui; Ye, Chen; Zhang, Guang-Heng; Wang, Jian; Tian, Fu-Kuan; Xue, Da-Wei; Liao, Yi; Zhu, Li; Chen, Ming-Sheng; Li, Jia-Yang; Cheng, Shi-Hua; Zhang, Geng-Yun; Wang, Jun; Qian, Qian

2013-08-27

356

Dissection of the extracranial vertebral artery: report of four cases and review of the literature  

Microsoft Academic Search

Four cases of cervical vertebral artery (VA) dissection are reported. In three patients VA dissection was associated with neck trauma. All patients were young or middle-aged (range 27 to 49 years). In two there was a history of migraine. Pain preceded neurological symptoms from hours to six weeks. Three patients had neurological deficits including elements of the lateral medullary syndrome,

P Hinse; A Thie; L Lachenmayer

1991-01-01

357

Structural Dissection of a Highly Knotted Peptide Reveals Minimal Motif with Antimicrobial Activity*S  

E-print Network

that understanding the structural features responsible for the activity of these natural products (11­14) may provideStructural Dissection of a Highly Knotted Peptide Reveals Minimal Motif with Antimicrobial Activity in nature. We have undertaken the structural dissection of a highly knotted, cysteine-rich plant thionin

Pompeu Fabra, Universitat

358

Adaptive techniques for real-time haptic and visual simulation of bone dissection  

Microsoft Academic Search

Bone dissection is an important component of many sur- gical procedures. In this paper, we discuss adaptive tech- niques for providing real-time haptic and visual feedback during a virtual bone dissection simulation. The simulator is being developed as a component of a training system for temporal bone surgery. We harness the difference in com- plexity and frequency requirements of the

Marco Agus; Andrea Giachetti; Enrico Gobbetti; Gianluigi Zanetti; Antonio Zorcolo

2003-01-01

359

The Specific Relationship between Disgust and Interest: Relevance during Biology Class Dissections and Gender Differences  

ERIC Educational Resources Information Center

This investigation examined trajectories of interest and disgust related to a biology dissection class. Three hundred and two secondary students completed ratings of disgust sensitivity and individual interest in the topic of the heart approximately one week before a dissection class. States of disgust and interest were recorded before, during,…

Holstermann, Nina; Ainley, Mary; Grube, Dietmar; Roick, Thorsten; Bogeholz, Susanne

2012-01-01

360

Traumatic dissection of the internal carotid artery: simultaneous infarct of optic nerve and brain  

PubMed Central

Key Clinical Message Traumatic intracranial internal carotid artery dissection is a rare but significant cause of stroke in patients in their forties, leading to high morbidity and mortality. Simultaneous ischemic stroke and optic nerve infarction can occur. Clinical suspicion of dissection is determining in the acute management. PMID:25356244

Correa, Edgar; Martinez, Braulio

2014-01-01

361

Spontaneous coronary artery dissection associated with cocaine use: A case report and brief review  

Microsoft Academic Search

Isolated, spontaneous dissection of the coronary arteries in the absence of trauma is an unusual but well-documented occurrence. Fewer than 50 cases have been reported in males in the English language literature, and only one case, nonfatal, was associated with cocaine use. We present the second overall and the first fatal case of cocaine-associated spontaneous coronary artery dissection and a

Jon R. Steinhauer; James B. Caulfield

2001-01-01

362

Can the principles of evidence-based medicine be applied to the treatment of aortic dissections?  

Microsoft Academic Search

Surgical treatment of patients with acute type A aortic dissections has improved early survival from 10–20 to approximately 80%. Data supporting several other treatment recommendations in patients with aortic dissection, however, are less convincing. We hypothesized that applying strict principles of evidence-based medicine would invalidate most of the recommendations in these published papers. We conducted a literature search asking three

Truls Myrmel; David T. M. Lai; D. Craig Miller

2004-01-01

363

GCSE Students' Attitudes to Dissection and Using Animals in Research and Product Testing.  

ERIC Educational Resources Information Center

Questionnaires from students passing the General Certificate of Secondary Education (GCSE) that explored attitudes to dissection and using animals in product testing administered to (n=469) students ages 14-15 showed a high level of support for peers who object to dissection, although objectors are likely to be met with derogatory comments,…

Lock, Roger

1995-01-01

364

Syncope and cardiovocal syndrome as the result of a spontaneous innominate artery dissection.  

PubMed

Dissection of the innominate artery is extremely rare and is associated with a high in-hospital mortality rate. We present the case of a 44-year-old man who presented with syncope and cardiovocal syndrome as the result of a spontaneous innominate artery dissection with an extension to the right common carotid. PMID:19571766

Lampropoulos, Stelios; Theofilogiannakos, Efstratios K; Gkontopoulos, Argiris; Kadoglou, Nikos P; Mamalis, Vassilis; Kontaki, Theodosia; Kottas, George

2009-10-01

365

Alpha1Antitrypsin Deficiency-Associated Cervical Artery Dissection: Report of Three Cases  

Microsoft Academic Search

The pathogenesis of cervical artery dissection is poorly understood. Deficiency of the elastase inhibitor alpha-1-antitrypsin may represent a predisposing condition. Biochemical and genetic analyses in a series of 12 consecutive patients with spontaneous dissection of the neck vessels showed 3 cases associated to alpha-1-antitrypsin deficiency, in combination with transient precipitating factors. A disequilibrium between proteolytic enzymes and protease inhibitors may

Alessandro Pezzini; Mauro Magoni; Luciano Corda; Lara Pini; Daniela Medicina; Mario Crispino; Marco Pavia; Alessandro Padovani; Vittorio Grassi

2002-01-01

366

Successful treatment of acute dissection of the donor aorta after orthotopic heart transplantation  

Microsoft Academic Search

Acute aortic dissection is one of the rare aortic complications that occur after orthotopic heart transplantation. We report the second case of successful surgical treatment of aortic dissection confined to the donor aorta in a recipient of an orthotopic cardiac allograft. A 68-year-old patient was admitted with chest pain and shortness of breath 7 years after orthotopic heart transplantation. He

Ali Kubilay Korkut; Francis Wellens; Luc Foubert; Marc Goethals

2003-01-01

367

Medical Students' Reactions to Anatomic Dissection and the Phenomenon of Cadaver Naming  

ERIC Educational Resources Information Center

The teaching of gross anatomy has, for centuries, relied on the dissection of human cadavers, and this formative experience is known to evoke strong emotional responses. The authors hypothesized that the phenomenon of cadaver naming is a coping mechanism used by medical students and that it correlates with other attitudes about dissection and body…

Williams, Austin D.; Greenwald, Emily E.; Soricelli, Rhonda L.; DePace, Dennis M.

2014-01-01

368

Perceptions of dissection by students in one medical school: beyond learning about anatomy. A qualitative study  

Microsoft Academic Search

INTRODUCTION The practice of dissection, as part of undergraduate medical education, has recently resurfaced in the public eye. This paper focuses on a number of important learning outcomes that were reported by Year 1-5 medical students in a British medical school, during the dissection sessions in the first 2 years of their training, as part of a wider qualitative research

Heidi K Lempp

2005-01-01

369

Surgical treatment of superior mesenteric artery dissecting aneurysm and simultaneous celiac artery compression  

Microsoft Academic Search

Spontaneous dissections of visceral arteries are rare, but when they do occur, they most commonly involve the superior mesenteric artery (SMA). We present a case of intestinal ischemia caused by a spontaneous dissection of the SMA in a patient with simultaneous celiac artery occlusion. The patient was a 45-year-old woman who presented with intestinal angina of sudden onset. Arteriography revealed

Maurice M. Solis; Tim J. Ranval; David R. McFarland

1993-01-01

370

Numerical simulation of arterial dissection during balloon angioplasty of atherosclerotic coronary arteries  

E-print Network

1 Numerical simulation of arterial dissection during balloon angioplasty of atherosclerotic, published in "Journal of Biomechanics 47, 4 (2014) pages 878-889" #12;2 Abstract Balloon angioplasty-onset complications such as restenosis. Keywords balloon angioplasty, coronary artery, arterial dissection, cohesive

Boyer, Edmond

371

Extracapsular dissection of the parapharyngeal space for a pleomorphic adenoma: a 10-year review.  

PubMed

Pleomorphic adenomas of the parapharyngeal space are difficult to remove with a margin of normal tissue. We reviewed 29 cases of extracapsular dissection of a parapharyngeal pleomorphic adenoma and found that extracapsular dissection does not increase the probability of recurrence of the tumour. PMID:24768035

Guo, Yuxing; Guo, Chuanbin; Zhang, Lei; Yu, Guangyan

2014-07-01

372

The discovery of the body: human dissection and its cultural contexts in ancient Greece.  

PubMed Central

In the first half of the third century B.C, two Greeks, Herophilus of Chalcedon and his younger contemporary Erasistratus of Ceos, became the first and last ancient scientists to perform systematic dissections of human cadavers. In all probability, they also conducted vivisections of condemned criminals. Their anatomical and physiological discoveries were extraordinary. The uniqueness of these events presents an intriguing historical puzzle. Animals had been dissected by Aristotle in the preceding century (and partly dissected by other Greeks in earlier centuries), and, later, Galen (second century A.D.) and others again systematically dissected numerous animals. But no ancient scientists ever seem to have resumed systematic human dissection. This paper explores, first, the cultural factors--including traditional Greek attitudes to the corpse and to the skin, also as manifested in Greek sacred laws--that may have prevented systematic human dissection during almost all of Greek antiquity, from the Pre-Socratic philosopher-scientists of the sixth and fifth centuries B.C. to distinguished Greek physicians of the later Roman Empire. Second, the exceptional constellation of cultural, political, and social circumstances in early Alexandria that might have emboldened Herophilus to overcome the pressures of cultural traditions and to initiate systematic human dissection, is analyzed. Finally, the paper explores possible reasons for the mysteriously abrupt disappearance of systematic human dissection from Greek science after the death of Erasistratus and Herophilus. PMID:1285450

von Staden, H.

1992-01-01

373

Computed tomography manifestation of a triple-barreled aortic dissection: the Mercedes-Benz mark sign.  

PubMed

Computed tomographic (CT) findings of a rare case of triple-barreled aortic dissection was described. CT demonstrated the extent of dissection, a communication between two channels, and three lumens separated by the intimal flap and a thin undetached tunica media, resembling a Mercedes-Benz mark. PMID:3168525

Shin, M S; Zorn, G L; Ho, K J

1988-04-01

374

Positive and negative motivational gradients during first use of the dissecting room  

Microsoft Academic Search

Immediately after their first use of the dissecting room, 45 preclinical medical students rated their enthusiasm and reluctance at seven points along a time sequence encompassing their experience from the night before to the completion of their first dissection. A second group of 42 preclinical medical students carried out the same ratings in real time. A naive group of 24

John Gaskell

1985-01-01

375

Dissecting and recording from the C. Elegans neuromuscular junction.  

PubMed

Neurotransmission is the process by which neurons transfer information via chemical signals to their post-synaptic targets, on a rapid time scale. This complex process requires the coordinated activity of many pre- and post-synaptic proteins to ensure appropriate synaptic connectivity, conduction of electrical signals, targeting and priming of secretory vesicles, calcium sensing, vesicle fusion, localization and function of postsynaptic receptors and finally, recycling mechanisms. As neuroscientists it is our goal to elucidate which proteins function in each of these steps and understand their mechanisms of action. Electrophysiological recordings from synapses provide a quantifiable read out of the underlying electrical events that occur during synaptic transmission. By combining this technique with the powerful array of molecular and genetic tools available to manipulate synaptic proteins in C. elegans, we can analyze the resulting functional changes in synaptic transmission. The C. elegans NMJs formed between motor neurons and body wall muscles control locomotion, therefore, mutants with uncoordinated locomotory phenotypes (known as unc s) often perturb synaptic transmission at these synapses (1). Since unc mutants are maintained on a rich supply of a bacterial food source, they remain viable as long as they retain some pharyngeal pumping ability to ingest food. This, together with the fact that C. elegans exist as hermaphrodites, allows them to pass on mutant progeny without the need for elaborate mating behaviors. These attributes, coupled with our recent ability to record from the worms NMJs (2 3) make this an excellent model organism in which to address precisely how unc mutants impact neurotransmission. The dissection method involves immobilizing adult worms using a cyanoacrylic glue in order to make an incision in the worm cuticle exposing the NMJs. Since C. elegans adults are only 1 mm in length the dissection is performed with the use of a dissecting microscope and requires excellent hand-eye coordination. NMJ recordings are made by whole-cell voltage clamping individual body wall muscle cells and neurotransmitter release can be evoked using a variety of stimulation protocols including electrical stimulation, light-activated channel-rhodopsin-mediated depolarization (4) and hyperosmotic saline, all of which will be briefly described. PMID:19488020

Richmond, Janet

2009-01-01

376

Nonsyndromic genetic predisposition to aortic dissection: a newly recognized, diagnosable, and preventable occurrence in families.  

PubMed

The major diseases affecting the aorta are aortic aneurysms and dissections, with patients with acute dissections often presenting in the emergency department (ED). Recent studies demonstrate a strong genetic predisposition to thoracic aortic aneurysms and dissections, independent of syndromes traditionally considered to predispose to aortic disease (such as Marfan syndrome). Nonsyndromic familial thoracic aortic aneurysms and dissections are inherited in families as an autosomal dominant disorder and a variable age of onset of the aortic disease. The case reported here illustrates the critical importance of obtaining a family history of thoracic aortic aneurysms and dissections, along with unexplained sudden death, when assessing an individual with chest pain in the ED, regardless of age and in the absence of a known genetic syndrome. PMID:14707946

Hasham, Sumera N; Lewin, Matthew R; Tran, Van T; Pannu, Hariyadarshi; Muilenburg, Ann; Willing, Marcia; Milewicz, Dianna M

2004-01-01

377

Dynamic aortic obstruction in a patient with acute type B dissection.  

PubMed

There are at least 7000 aortic dissections diagnosed in the United States each year. Type B dissections accounted for 38% of cases enrolled in the prospective International Registry of Aortic Dissection. We report a case of a 48-year-old hypertensive woman with an acute type B aortic dissection causing significant dynamic obstruction of the aorta. Intravascular ultrasound of her aorta revealed a mobile intimal flap nearly obliterating the true lumen with each systolic contraction. Simultaneous pressure tracings obtained from her ascending aorta and femoral artery demonstrated a systolic pressure gradient in excess of 100 mm Hg. The patient developed progressive renal failure and ultimately underwent successful operative replacement of the proximal descending thoracic aorta with a Dacron graft. In this case presentation, we highlight the unusual physiology exemplified by this case and explore contemporary management strategies for complicated type B aortic dissection, including surgery and catheter-based techniques. PMID:16628024

Mega, Jessica L; Opotowsky, Alexander R; Curillova, Zelmira; O'Gara, Patrick T

2006-01-01

378

Tenascin C protects aorta from acute dissection in mice  

NASA Astrophysics Data System (ADS)

Acute aortic dissection (AAD) is caused by the disruption of intimomedial layer of the aortic walls, which is immediately life-threatening. Although recent studies indicate the importance of proinflammatory response in pathogenesis of AAD, the mechanism to keep the destructive inflammatory response in check is unknown. Here, we report that induction of tenascin-C (TNC) is a stress-evoked protective mechanism against the acute hemodynamic and humoral stress in aorta. Periaortic application of CaCl2 caused stiffening of abdominal aorta, which augmented the hemodynamic stress and TNC induction in suprarenal aorta by angiotensin II infusion. Deletion of Tnc gene rendered mice susceptible to AAD development upon the aortic stress, which was accompanied by impaired TGF? signaling, insufficient induction of extracellular matrix proteins and exaggerated proinflammatory response. Thus, TNC works as a stress-evoked molecular damper to maintain the aortic integrity under the acute stress.

Kimura, Taizo; Shiraishi, Kozoh; Furusho, Aya; Ito, Sohei; Hirakata, Saki; Nishida, Norifumi; Yoshimura, Koichi; Imanaka-Yoshida, Kyoko; Yoshida, Toshimichi; Ikeda, Yasuhiro; Miyamoto, Takanobu; Ueno, Takafumi; Hamano, Kimikazu; Hiroe, Michiaki; Aonuma, Kazutaka; Matsuzaki, Masunori; Imaizumi, Tsutomu; Aoki, Hiroki

2014-02-01

379

Desirable training of endoscopic submucosal dissection: further spread worldwide  

PubMed Central

Endoscopic submucosal dissection (ESD) is an excellent treatment because of its high curative resection rate and low local recurrence rate. However, its technical difficulty prevents from its permeation worldwide. For further permeation of ESD, the establishment of an appropriate training system is essential. In Japan, trainee endoscopists who have had prerequisites for ESD, that is to say, basic knowledge and skills, start ESD in accordance with a stepwise training system under close supervision by experts. The trainers select an appropriate lesion in human for each step of developments in ESD techniques. In Western countries there are few ESD experts at present, so an ex vivo animal model training must play a major role in the training system. It is desirable that these training systems should be constructed by some authorized organizations such as Japan Gastroenterological Endoscopy Society (JGES).

Fujishiro, Mitsuhiro; Kodashima, Shinya; Niimi, Keiko; Ono, Satoshi; Yamamichi, Nobutake; Koike, Kazuhiko

2014-01-01

380

Dissecting the role of milk components on gut microbiota composition.  

PubMed

The composition of human milk is tailored to contribute to the development of the gastrointestinal (GI) tract of newborns and infants. Importantly, human milk contains the antimicrobial compounds lysozyme and lactoferrin that are thought to contribute to the formation of a health-promoting microbiota. As these protective factors are lacking in the milk of dairy animals, we genetically engineered goats expressing human lysozyme in their milk and have recently reported a new animal model to dissect out the role of milk components on gut microbiota formation. Using the pig as a more human-relevant animal model, we demonstrated that consumption of lysozyme-rich milk enriched the abundance of bacteria associated with GI health and decreased those associated with disease, much like human milk. This work demonstrated that the pig is a valid animal model for gut microbiome studies on the effects of dietary components on microbiota composition, host-microbe interactions and state of the intestine. PMID:23235404

Maga, Elizabeth A; Weimer, Bart C; Murray, James D

2013-01-01

381

Complications Related to Gastric Endoscopic Submucosal Dissection and Their Managements  

PubMed Central

Endoscopic submucosal dissection (ESD) for early gastric cancer is a well-established procedure with the advantage of resection in an en bloc fashion, regardless of the size, shape, coexisting ulcer, and location of the lesion. However, gastric ESD is a more difficult and meticulous technique, and also requires a longer procedure time, than conventional endoscopic mucosal resection. These factors naturally increase the risk of various complications. The two most common complications accompanying gastric ESD are bleeding and perforation. These complications are known to occur both intraoperatively and postoperatively. However, there are other rare but serious complications related to gastric ESD, including aspiration pneumonia, stenosis, venous thromboembolism, and air embolism. Endoscopists should have sufficient knowledge about such complications and be prepared to deal with them appropriately, as successful management of complications is necessary for the successful completion of the entire ESD procedure.

Saito, Itaru; Tsuji, Yosuke; Sakaguchi, Yoshiki; Niimi, Keiko; Ono, Satoshi; Kodashima, Shinya; Yamamichi, Nobutake; Koike, Kazuhiko

2014-01-01

382

Dissecting teleost B cell differentiation using transcription factors.  

PubMed

B cell developmental pathways in teleost fishes are poorly understood. In the absence of serological reagents, an alternative approach to dissecting teleost B cell development is to use transcription factors that are differentially expressed during B cell development. This review discusses the structure and function of six transcription factors that play essential roles during teleost B cell development: Ikaros, E2A, EBF, Pax5, Blimp1, and XbpI. Research on alternative splicing of both the Ikaros and Pax5 genes in rainbow trout is presented, including their functional significance. An application is discussed that should aid in elucidating teleost B cell development and activation, by using transcription factors as developmental markers in flow cytometric analysis. Possible future studies in teleost B cell development are suggested in the context of gene regulation. Lastly, broader impacts and practical applications are discussed. PMID:21251922

Zwollo, Patty

2011-09-01

383

Tenascin C protects aorta from acute dissection in mice  

PubMed Central

Acute aortic dissection (AAD) is caused by the disruption of intimomedial layer of the aortic walls, which is immediately life-threatening. Although recent studies indicate the importance of proinflammatory response in pathogenesis of AAD, the mechanism to keep the destructive inflammatory response in check is unknown. Here, we report that induction of tenascin-C (TNC) is a stress-evoked protective mechanism against the acute hemodynamic and humoral stress in aorta. Periaortic application of CaCl2 caused stiffening of abdominal aorta, which augmented the hemodynamic stress and TNC induction in suprarenal aorta by angiotensin II infusion. Deletion of Tnc gene rendered mice susceptible to AAD development upon the aortic stress, which was accompanied by impaired TGF? signaling, insufficient induction of extracellular matrix proteins and exaggerated proinflammatory response. Thus, TNC works as a stress-evoked molecular damper to maintain the aortic integrity under the acute stress. PMID:24514259

Kimura, Taizo; Shiraishi, Kozoh; Furusho, Aya; Ito, Sohei; Hirakata, Saki; Nishida, Norifumi; Yoshimura, Koichi; Imanaka-Yoshida, Kyoko; Yoshida, Toshimichi; Ikeda, Yasuhiro; Miyamoto, Takanobu; Ueno, Takafumi; Hamano, Kimikazu; Hiroe, Michiaki; Aonuma, Kazutaka; Matsuzaki, Masunori; Imaizumi, Tsutomu; Aoki, Hiroki

2014-01-01

384

Recommended sedation and intraprocedural monitoring for gastric endoscopic submucosal dissection.  

PubMed

Endoscopic submucosal dissection is associated with a longer treatment time and a higher risk of patient discomfort than conventional procedures. Adequate, safe sedation is therefore essential. Sedation can cause adverse effects such as hypoxemia and hypotension, requiring continuous intraoperative and postoperative monitoring of blood pressure, use of the electrocardiogram, and arterial blood oxygen saturation by pulse oximetry. A physician and a nurse solely responsible for sedating and monitoring the patient should be present during treatment.A combination of benzodiazepines and analgesics are generally used for sedation, but new sedatives such as propofol and dexmedetomidine hydrochloride are expected to be useful agents. Endoscopists should become more familiar with sedatives, analgesics, and emergency procedures in the future. PMID:23406354

Sasaki, Tohru; Tanabe, Satoshi; Ishido, Kenji; Azuma, Mizutomo; Katada, Chikatoshi; Higuchi, Katsuhiko; Koizumi, Wasaburo

2013-03-01

385

Open fenestration for complicated acute aortic B dissection  

PubMed Central

Acute type B aortic dissection (ABAD) is a serious cardiovascular emergency in which morbidity and mortality are often related to the presence of complications at clinical presentation. Visceral, renal, and limb ischemia occur in up to 30% of patients with ABAD and are associated with higher in-hospital mortality. The aim of the open fenestration is to resolve the malperfusion by creating a single aortic lumen at the suprarenal or infrarenal level. This surgical procedure is less invasive than total aortic replacement, thus not requiring extracorporeal support and allowing preservation of the intercostal arteries, which results in decreased risk of paraplegia. Surgical aortic fenestration represents an effective and durable option for treating ischemic complications of ABAD, particularly for patients with no aortic dilatation. In the current endovascular era, this open technique serves as an alternative option in case of contraindications or failure of endovascular management of complicated ABAD. PMID:25133107

Segreti, Sara; Grassi, Viviana; Lomazzi, Chiara; Cova, Marta; Piffaretti, Gabriele; Rampoldi, Vincenzo

2014-01-01

386

Management Strategy of Isolated Spontaneous Dissection of the Superior Mesenteric Artery  

PubMed Central

Objective: Isolated spontaneous dissection of the superior mesenteric artery (SMA) is very rare among of the visceral artery dissection and its treatment is not established. In this paper we present our experiences and consider the treatment of isolated SMA dissection. Methods: A retrospective review of our cases from 2005 was performed. Clinical symptoms, radiologic findings and results were evaluated. There were 14 cases of visceral artery dissection, in which all cases were with SMA dissection. There were 12 males and 2 females with a mean age of 57 years (range 41–78 years). Results: We categorized SMA dissection into the six types according to the Sakamoto’s and Zerbib’s classification. One patient with type VI underwent emergent endovascular surgery with stent. One patient with type VI received thrombectomy and intimectomy with open surgery. One patient with type II underwent aneurysmectomy due to enlarged dissected SMA 3 months later from onset. The other eleven patients were managed conservatively. At follow-up, the diameter of SMA did not enlarged and the length of the dissection significantly decreased to 20.7 ± 15.7 mm from 38.0 ± 15.1 mm at onset (p <0.01). After treatment, imaging indicated the following changes in classification: type I, one patient; type II, 4 patients; type IV, 4 patients; complete remodeling, one patient, all without any event during the follow-up period of 5–82 months. Conclusion: Most patients with isolated visceral artery dissection occurred in superior mesenteric artery and can be treated conservatively; however, endovascular or surgical procedures including laparotomy are indicated when there is suspicion of severe mesenteric ischemia. Because the dissection configuration will change, long term follow-up is necessary. (*English translation of Jpn J Vasc Surg 2013; 22: 695-701)

Takase, Shinya; Seto, Yuki; Yokoyama, Hitoshi; Gotoh, Mitsukazu; Kogure, Michihiko; Midorikawa, Hirofumi; Saito, Tomiyoshi; Maehara, Kazuhira

2014-01-01

387

Acute Aortic Dissections with Pregnancy in Women with ACTA2 Mutations  

PubMed Central

Mutations in ACTA2 predispose to thoracic aortic aneurysms and dissections as well as coronary artery and cerebrovascular disease. Here we examined the risk of aortic dissections, stroke and myocardial infarct with pregnancy in women with ACTA2 mutations. Of the 53 women who had a total of 137 pregnancies, eight had aortic dissections in the third trimester or the postpartum period (6% of pregnancies). One woman also had a myocardial infarct that occurred during pregnancy that was independent of her aortic dissection. Compared to the population-based frequency of peripartum aortic dissections of 0.6%, the rate of peripartum aortic dissections in women with ACTA2 mutations is much higher (8 out of 39; 20%). Six of these dissections initiated in the ascending aorta (Stanford type A), three of which were fatal. Three women had ascending aortic dissections at diameters less that 5.0 cm (range 3.8 to 4.7 cm). Aortic pathology showed mild to moderate medial degeneration of the aorta in three women. Of note, five of the women had hypertension either during or before the pregnancy. In summary, the majority of women with ACTA2 mutations did not have aortic or other vascular complications with pregnancy. However, these findings show that pregnancy is associated with significant risk for aortic dissections in women in whom diagnosis of ACTA2 mutation has not been made. Women with ACTA2 mutations who are planning to get pregnant should be counseled about this risk of aortic dissections, and proper clinical management should be initiated to reduce this risk. PMID:24243736

Regalado, Ellen S.; Guo, Dong-chuan; Estrera, Anthony L.; Buja, L. Maximilian; Milewicz, Dianna M.

2014-01-01

388

Imaging Characteristics of Symptomatic Vertebral Artery Dissection: A Systematic Review  

PubMed Central

Background Vertebral artery dissection (VAD) is an important cause of stroke in the young. VAD can present with a range of imaging findings. We sought to summarize the diagnostic value of various imaging findings in patients with symptomatic VAD. Methods We conducted a systematic review of observational studies, searching electronic databases (MEDLINE, EMBASE) for English-language manuscripts with >5 subjects with clinical or radiological features of VAD. Two independent reviewers selected studies for inclusion; a third adjudicated differences. Studies were assessed for methodological quality and imaging data were abstracted. Pooled proportions were calculated. Results Of 3996 citations, we screened 511 manuscripts and selected 75 studies describing 1,972 VAD patients. Most studies utilized conventional angiography or magnetic resonance angiography (MRA) to diagnose VAD; CT angiography (CTA) and Doppler ultrasonography were described less frequently. Imaging findings reported were vertebral artery stenosis (51%), string and pearls (48%), arterial dilation (37%), arterial occlusion (36%), and pseudoaneurysm, double lumen, and intimal flap (22% each). In cases where conventional angiography was the reference standard, CTA was more sensitive (100%) than either MRA (77%) or Doppler ultrasonography (71%) (p=0.001). Conclusions Imaging findings vary widely in patients with VAD, with no single radiographic sign present in the majority of VAD patients. Non-specific radiographic signs predominate. CTA probably has greater sensitivity for dissection than MRA or ultrasound relative to conventional angiography. Higher quality studies on imaging techniques and radiographic criteria in subjects with VAD are needed. Future studies should compare imaging techniques in well-defined, undifferentiated populations of clinical VAD suspects. PMID:22931729

Gottesman, Rebecca F.; Sharma, Priti; Robinson, Karen A.; Arnan, Martinson; Tsui, Megan; Saber-Tehrani, Ali; Newman-Toker, David E.

2013-01-01

389

Murine Model of Surgically Induced Acute Aortic Dissection Type A  

PubMed Central

Objectives This study aimed at developing a murine model of surgically induced acute aortic dissection type A (AAD) for investigation of the formation and progression of AAD, and to test whether this system could be used for biomarker discovery. Methods Adult fibrillin-1 deficient, Fbn1C1039G/+ mice and wild-type mice were anesthetized, ventilated and the ascending aorta exposed via hemisternotomy. We hypothesized that AAD could be induced either by injecting autologous blood into the aortic wall or by injury to the wall with aortic clamping. Echocardiography was done preoperatively, and serum samples collected before and 30 minutes after surgery, and analyzed by ELISA. Results Echocardiography revealed larger aortic root diameters in Fbn1C1039G/+ compared with wild-type mice (P=0.001). Histology showed that aortic clamp injury but not injection of blood leads to large intimal tears, disruption of aortic wall structures and localized dissection of the aortic media in Fbn1C1039G/+ mice. AAD developed in 4 out of 5 Fbn1C1039G/+ mice versus 0 out of 5 wild-type mice after aortic clamping (P<0.01). Elastin staining showed higher elastic fiber fragmentation and disarray in Fbn1C1039G/+ compared with wild-type mice. ELISA analysis revealed elevated circulating TGF?1 concentrations after inducing AAD in Fbn1C1039G/+ mice (P=0.02, 150±61 ng/ml vs. 456±97 ng/ml), but not in wild-type or sham-operated mice. Conclusions Aortic clamp injury can induce AAD in Fbn1C1039G/+, but not in wild-type mice. This murine model of surgically induced AAD is highly reproducible and non-lethal in the short-term. Using this system, we revealed that circulating TGF?1 is a promising biomarker for AAD. PMID:19910001

Matt, Peter; Huso, David L.; Habashi, Jennifer; Holm, Tammy; Doyle, Jeff; Schoenhoff, Florian; Liu, Guosheng; Black, James; Van Eyk, Jennifer E.; Dietz, Harry C.

2010-01-01

390

Students as teachers in an anatomy dissection course.  

PubMed

One way to improve students' learning outcomes and well-being is to change teaching practices to allow students to become more active participants. We used an anatomy dissection course to test a cooperative group work method in which first-year veterinary students took turns leading their peer group and were each responsible for teaching the anatomy of a particular topographic region. The important blood vessels, lymphatic system, and nerves of each region of the body were covered. Students felt that exploration of the entire topographic region helped them to acquire a comprehensive understanding of the respiratory apparatus and the cardiovascular and nervous systems. Assigning individual tasks to each group member resulted in sharing the workload equally. Open-ended comments revealed that support from other group members was important for the students' learning experience, but the results also offered insight into a lack of constructive criticism. While teaching was considered challenging, and even a stress factor that hindered learning for some students, group work was generally held to be supportive of learning. The results suggest that more thorough instruction of students in their group work and in their individual tasks is required. Some students experienced difficulty in expressing their concerns openly and in seeking guidance from teachers, demonstrating the need for further investigation regarding students' self-regulation skills. Comments from the open-ended responses suggest that use of a cooperative learning method in anatomy dissection courses not only deepens student understanding of a subject but also offers first-year students an opportunity to practice the generic skills that will be needed in their future profession. PMID:24219999

Salomäki, Tiina; Laakkonen, Juha; Ruohoniemi, Mirja

2014-01-01

391

Talking about death: implementing peer discussion as a coping mechanism to overcome fears about dissection, death, and dying.  

PubMed

Many studies have reported on the perceptions of medical students toward dissection. It is important to understand the feelings and symptoms experienced during dissection so that they can be adequately handled. Prior to dissection, first year students are given lectures on aspects of dissection, death and dying, and death rituals in various cultures. Two separate questionnaires, one given during the first week of dissection and another given one month into the program were then completed anonymously by dissection groups. The questions were designed to be open-ended, thereby encouraging group discussion amongst students. The questionnaires were used to determine the perception of students to dissection and to discover if these perceptions change during the dissection program. The first questionnaire revealed that students do experience fears and anxiety prior to and at the beginning of dissection; however, most of these fears dissipated by the time of the second questionnaire. One month into dissection students cited talking to peers as their main coping mechanism and fewer students mentioned emotional detachment from their cadaver as a coping mechanism, as was the case in the first questionnaire. Dissection was perceived as a positive experience by our student cohort and most students cited the main advantage of dissection as the ability to visualize organs in three dimensions. The comprehensive answers received from the students indicated that thorough discussion of feelings amongst peers occurred, introducing students to an important coping mechanism at an early stage of their learning. PMID:23208957

Kotzé, Sanet Henriët; Mole, Calvin Gerald

2013-01-01

392

Virtual, on-line, frog dissection vs. conventional laboratory dissection: A comparison of student achievement and teacher perceptions among honors, general ability, and foundations-level high school biology classes  

NASA Astrophysics Data System (ADS)

Dissecting animal specimens has long been a tradition in biology classes. Objections by students, based on religious or ethical grounds, have been raised regarding the dissections of animals in classroom laboratories. A number of states now have legal proceedings or statewide policies requiring that alternatives to the actual dissection of laboratory animal specimens be permitted in their school districts. Alternatives to actual dissections have been developed in recent years. For a variety of reasons, performing an actual or conventional animal dissection may not be a desirable option. The purpose of this study was to investigate how a virtual On-line frog dissection compares with an actual laboratory dissection. What were the perceptions of the teacher's using it? How does student achievement compare among three the different ability levels on a pre and posttest regarding basic frog anatomy? Is a virtual On-line dissection a suitable alternative for students who, for whatever reason, do not participate in the actual laboratory experience? The subjects consisted of 218 biology students among three different ability levels, in a Northeastern suburban high school. Approximately half of the student groups participated in a virtual On-line dissection, the other half in an actual laboratory dissection. A pretest of basic frog anatomy was administered to the students two days before and the posttest one day after their dissection experience. Data were analyzed using matched pairs t-Tests, Analysis of Variance, Tukey HSD, and Squared Curvilinear Coefficients. Survey questionnaires were administered to the teachers after the dissection experiences were completed. There were no significant differences found in achievement between the virtual and conventional dissection groups. There were significant differences found in achievement score means among the three ability levels. There was no significant interaction between gender and achievement. Perceptions of the teacher's facilitating the two instructional methods varied. The main area of agreement among them was that a virtual On-line frog dissection was a viable alternative for students who objected to doing a conventional dissection.

Kopec, Ronald H.

2002-09-01

393

Multislice CT virtual intravascular endoscopy of aortic dissection: A pictorial essay  

PubMed Central

AIM: To present our experience of using 3D virtual intravascular endoscopy (VIE) to characterize and evaluate the intraluminal appearances of aortic dissection. METHODS: Ten patients with known aortic dissection underwent dual-source computed tomography angiography and were included in the study. In addition to 2D axial and multiplanar reformatted images as well as 3D reconstructions, VIE images were created in each patient to demonstrate intraluminal views of the aorta and its branches, origin of artery branches and artery branch involvement by aortic dissection. RESULTS: Stanford A dissection was found in 8 patients and B dissection in the remaining 2 patients. VIE images were successfully generated in all of the patients with excellent visualization of the normal anatomical structures, intimal flap and intimal entrance tear, communication between true and false lumens, as well as assessment of the extent of aortic dissection. CONCLUSION: Our preliminary experience suggests that VIE could be used as a complementary tool to assist radiologists accurately evaluate aortic dissection so that better patient management can be achieved. PMID:21179312

Sun, Zhonghua; Cao, Yan

2010-01-01

394

Triple Plane Dissection in Open Primary Rhinoplasty in Middle Eastern Noses  

PubMed Central

Objective: Rhinoplasty started as a closed technique and then the open technique gained popularity. Open technique gave surgeons the opportunity to visualize and manipulate the cartilaginous skeleton at the tip of the nose precisely. The dissection planes in open rhinoplasty technique may be subcutaneous, submuscular (under the superficial musculoaponeurotic system), or subpericondrial subperiosteal. Each plane has advantages and disadvantages. The aim of this study was to combine planes to get the maximal benefit of each plane. Method: The study was performed on 38 Middle Eastern patients, among whom 23 were females and 15 were males. All patients presented for primary rhinoplasty. They were divided into 5 groups on the basis of their skin thickness. Dissection started subcutaneous at the area of the lower lateral cartilages and then shifted subsuperficial musculoaponeurotic system over the upper lateral cartilages and ended subperiosteal over the bony skeleton. Results: This triple plane of dissection gave acceptable results without any complication. Subcutaneous dissection allowed thinning of the thick sebaceous skin at the tip and alar region, subsuperficial musculoaponeurotic system dissection allowed direct exposure of the upper lateral cartilage without thinning skin at an area where it is thin, and subperiosteal dissection helped masking any bony irregularities resulted from osteotomies. Conclusion: The triple plane dissection in open primary rhinoplasty in Middle Eastern patients maximized the advantages of each plane and minimized the disadvantages and resulted in safe cosmetic results. PMID:23967367

Elshahat, Ahmed

2013-01-01

395

A Simple and Safe Technique for Manipulation of Retrosternal Dissection in the Nuss Procedure  

PubMed Central

Objective: The Nuss procedure has become the first choice for repairing the pectus excavatum because of the advantages of the technique including minimal invasiveness and short operative duration. Although this technique appears simple and easy, life-threatening complications during dissection such as intraoperative cardiac perforation have been reported. We developed a new approach for safer dissection of retrosternal space. Methods: We use a dissector that is commonly used for laparoscopic operation, instead of the Nuss introducer. The dissector goes through the same skin incision where the Nuss bar will be inserted. The major difference is the position of dissector insertion, which is set up more dorsally than usual, and the use of a laparoscopic dissector instead of the Nuss introducer. In this new approach, the direction of dissection is from dorsal toward the anterior thoracic wall, which allows us to visually follow the tip of the dissector throughout the surgery. Moreover using the dissector that has better manipulation capability enables us the fine dissection and also is able to precisely determine both the layer and the area of the dissection level. Results: We have treated more than 150 patients using this technique without any complications since 2008. In all the cases, safer dissection of the retrosternal space was performed with good results. Conclusion: We believe every surgeon can easily apply this procedure to patients with pectus excavatum, and this procedure can reduce the stress during the dissection. PMID:24570769

Noguchi, Masahiko; Kondoh, Shoji; Fujita, Kenya

2014-01-01

396

Endoscopic submucosal tunnel dissection salvage technique for ulcerative early gastric cancer.  

PubMed

Endoscopic submucosal dissection is an effective treatment modality for early gastric cancer (EGC), though the submucosal fibrosis found in ulcerative EGC is an obstacle for successful treatment. This report presents two cases of ulcerative EGC in two males, 73- and 80-year-old, with severe fibrosis. As endoscopic ultrasonography suggested that the EGCs had invaded the submucosal layer, the endoscopic submucosal tunnel dissection salvage technique was utilized for complete resection of the lesions. Although surgical gastrectomy was originally scheduled, the two patients had severe coronary heart disease, and surgeries were refused because of the risks associated with their heart conditions. The endoscopic submucosal tunnel dissection salvage technique procedures described in these cases were performed under conscious sedation, and were completed within 30 min. The complete en bloc resection of EGC using endoscopic submucosal tunnel dissection salvage technique was possible with a free resection margin, and no other complications were noted during the procedure. This is the first known report concerning the use of the endoscopic submucosal tunnel dissection salvage technique salvage technique for treatment of ulcerative EGC. We demonstrate that endoscopic submucosal tunnel dissection salvage technique it is a feasible method showing several advantages over endoscopic submucosal dissection for cases of EGC with fibrosis. PMID:25083097

Choi, Hyuk Soon; Chun, Hoon Jai; Seo, Min Ho; Kim, Eun Sun; Keum, Bora; Seo, Yeon Seok; Jeen, Yoon Tae; Lee, Hong Sik; Um, Soon Ho; Kim, Chang Duck; Ryu, Ho Sang

2014-07-21

397

[Hybrid operative intervention for DeBakey type III aortic dissection with the relay stent graft].  

PubMed

Determining the exact incidence of aortic dissection is highly conjectural because many cases of the disease remain undiagnosed. According to the autopsy findings, the incidence rate of the pathology concerned varies within the range from 0.2 to 0.8%. In clinical practice, aortic dissection is the cause of sudden death in 1.1% of the patients involved. However, aortic dissection should by no means be considered a rare disease. According to Borst et ah, ruptures in thoracic-portion aortic dissections are encountered 2-3 times more often than tears occurring in abdominal aortic aneurysms. The prognosis for patients presenting with a chronic aortic dissection is unfavourable. The commonest complications of the natural course of the disease include the development of a secondary dissection, formation of an aneurysm, progression of aortic regurgitation and circulatory insufficiency, occlusion of the aortic branches, and a late aortic rupture being the immediate cause of death in 30% of patients suffering from chronic dissection. With the recent advent of stent grafts, there appeared a possibility in the majority of cases involving a chronic type B dissection by the Stanford classification to substantially avoid an otherwise inevitably traumatic and typically prolonged reconstructive operation. Unfortunately, in some patients, owing to anatomical peculiarities, it is not always possible to deploy an endograft, thus requiring a major surgical intervention to perform instead. The authors describe herein a case of endovascular prosthetic reconstruction of the aortic arch and the descending portion in a patient who was found to have a type III aortic dissection according to the DeBakey classification and treated with the Relay stent graft. PMID:20635727

Cherniavski?, A M; Karpenko, A A; Cherniavski?, M A; Starodubtsev, V B; Edemski?, A G

2010-01-01

398

Familial Thoracic Aortic Aneurysms and Dissections: Identification of a Novel Locus for Stable Aneurysms with a Low Risk for Progression to Aortic Dissection  

PubMed Central

Background Thoracic aortic aneurysms leading to acute aortic dissections (TAAD) are the major diseases that affect the thoracic aorta. Approximately 20% of patients with TAAD have a family history of TAAD, and these patients present younger with more rapidly enlarging aneurysms than patients without a family history of aortic disease. Methods and Results A large family with multiple members with TAAD inherited in an autosomal dominant manner was identified. The ascending aortic aneurysms were associated with slow enlargement, a low risk of dissection, and decreased penetrance in women. Genome-wide linkage analysis was performed and a novel locus on chromosome 12 was identified for the mutant gene causing disease in this family. Of the 12 male members who carry the disease-linked microsatellite haplotype, nine had ascending aortic aneurysms with an average diameter of 4.7 cm and average age of 55 years (age range, 32-76) at the time of diagnosis; only one individual had progressed to acute aortic dissection and no other members with aortic dissections were identified. Women harboring the disease-linked haplotype did not have thoracic aortic disease, including an 84 year old woman. Sequencing of 9 genes within the critical interval at the chromosome 12 locus did not identify the mutant gene. Conclusion Mapping a locus for ascending thoracic aortic aneurysms associated with a low risk of aortic dissection supports our hypothesis that genes leading to familial disease can be associated with less aggressive thoracic aortic disease. PMID:21163914

Guo, Dong-Chuan; Regalado, Ellen S.; Minn, Charles; Tran-Fadulu, Van; Coney, Joshua; Cao, Jiumei; Wang, Min; Yu, Robert K.; Estrera, Anthony L.; Safi, Hazim J.; Shete, Sanjay S.; Milewicz, Dianna M.

2013-01-01

399

Iatrogenic aortic dissection during left subclavian artery stenting: immediate detection by calcium sign under fluoroscope.  

PubMed

Calcified aorta with acute iatrogenic aortic dissection is a potential but rarely reported complication of subclavian or innominate artery intervention. We report a patient who developed aortic dissection during stenting for left subclavian artery. A newly developed "calcium sign," signifying displacement of the intimal calcification from the outer soft-tissue margin and which is traditionally recognized on chest radiograph, was detected by real-time fluoroscopy and served as the diagnostic clue. Type B aortic dissection was further confirmed by chest computed tomography. PMID:20532777

Wang, Yi-Chih; Hwang, Juey-Jen; Lai, Ling-Ping; Tseng, Chuen-Den

2011-02-01

400

Pipeline endovascular reconstruction of traumatic dissecting aneurysms of the intracranial internal carotid artery.  

PubMed

A 22-year-old woman was involved in a motor vehicle collision resulting in multiple facial fractures and extensive internal carotid artery (ICA) injury including a right carotid-cavernous fistula, complex dissection flap and dissecting aneurysms. Endovascular coil embolization was initially performed to treat the cavernous carotid fistula and then again on two separate occasions to treat expanding dissecting aneurysms. Parent vessel reconstruction of the right ICA was subsequently performed with the Pipeline embolization device, resulting in complete anatomical restoration of this vessel. PMID:24353328

Prasad, Vikram; Gandhi, Dheeraj; Jindal, Gaurav

2014-12-01

401

Determinants of Early and Late Outcome after Surgery for TypeA Aortic Dissection  

Microsoft Academic Search

  The aim of this study was to identify the\\u000a most important variables associated with early and late mortality in\\u000a patients operated on for type A aortic dissection over a 15-year\\u000a period. From January 1984 to March 1999, 110 patients underwent surgery\\u000a for type A aortic dissection. The 88.1% of patients had an acute type\\u000a A dissection (AD) and 11.8% had

2001-01-01

402

Acute gallbladder necrosis in a patient with acute type B aortic dissection.  

PubMed

Although vascular complications induced by acute aortic dissection are varied and common, gallbladder necrosis induced by acute aortic dissection is rare. We experienced the case of a 42-year-old woman who suffered from acute gallbladder necrosis that occurred the following day after the onset of acute type B aortic dissection. Contrasted computed tomography, which showed the thickened wall of the gallbladder and the pericholecystic fluid, as well as the occluded celiac artery, was an effective diagnostic procedure. We performed cholecystectomy and revascularization of the celiac artery using autologous saphenous vein. Her postoperative course was uneventful, and she was discharged after 20 postoperative days. PMID:24386028

Ito, Toshiro; Yasuda, Naomi; Kuroda, Yohsuke; Sugawara, Motoshi; Koyanagi, Tetsuya; Higami, Tetsuya

2013-01-01

403

Acute Gallbladder Necrosis in a Patient with Acute Type B Aortic Dissection  

PubMed Central

Although vascular complications induced by acute aortic dissection are varied and common, gallbladder necrosis induced by acute aortic dissection is rare. We experienced the case of a 42-year-old woman who suffered from acute gallbladder necrosis that occurred the following day after the onset of acute type B aortic dissection. Contrasted computed tomography, which showed the thickened wall of the gallbladder and the pericholecystic fluid, as well as the occluded celiac artery, was an effective diagnostic procedure. We performed cholecystectomy and revascularization of the celiac artery using autologous saphenous vein. Her postoperative course was uneventful, and she was discharged after 20 postoperative days. PMID:24386028

2013-01-01

404

Quantitative nuclear hepatology  

SciTech Connect

This is the first in a series of four Continuing Education articles on quantitative imaging techniques. After studying this article, the reader should be able to: 1) compare the radiopharmaceuticals available for hepatobiliary imaging; 2) discuss quantitation of hepatobiliary studies; and 3) discuss the clinical applications of these techniques.

Gilbert, S.A.; Brown, P.H.; Krishnamurthy, G.T.

1987-03-01

405

Modern quantitative schlieren techniques  

Microsoft Academic Search

Schlieren optical techniques have traditionally been used to qualitatively visualize refractive flowfields in transparent media. Modern schlieren optics, however, are increasingly focused on obtaining quantitative information such as temperature and density fields in a flow -- once the sole purview of interferometry -- without the need for coherent illumination. Quantitative data are obtained from schlieren images by integrating the measured

Michael Hargather; Gary Settles

2010-01-01

406

Systematic dissection of regulatory motifs in 2000 predicted human enhancers using a massively parallel reporter assay.  

PubMed

Genome-wide chromatin annotations have permitted the mapping of putative regulatory elements across multiple human cell types. However, their experimental dissection by directed regulatory motif disruption has remained unfeasible at the genome scale. Here, we use a massively parallel reporter assay (MPRA) to measure the transcriptional levels induced by 145-bp DNA segments centered on evolutionarily conserved regulatory motif instances within enhancer chromatin states. We select five predicted activators (HNF1, HNF4, FOXA, GATA, NFE2L2) and two predicted repressors (GFI1, ZFP161) and measure reporter expression in erythroleukemia (K562) and liver carcinoma (HepG2) cell lines. We test 2104 wild-type sequences and 3314 engineered enhancer variants containing targeted motif disruptions, each using 10 barcode tags and two replicates. The resulting data strongly confirm the enhancer activity and cell-type specificity of enhancer chromatin states, the ability of 145-bp segments to recapitulate both, the necessary role of regulatory motifs in enhancer function, and the complementary roles of activator and repressor motifs. We find statistically robust evidence that (1) disrupting the predicted activator motifs abolishes enhancer function, while silent or motif-improving changes maintain enhancer activity; (2) evolutionary conservation, nucleosome exclusion, binding of other factors, and strength of the motif match are predictive of enhancer activity; (3) scrambling repressor motifs leads to aberrant reporter expression in cell lines where the enhancers are usually inactive. Our results suggest a general strategy for deciphering cis-regulatory elements by systematic large-scale manipulation and provide quantitative enhancer activity measurements across thousands of constructs that can be mined to develop predictive models of gene expression. PMID:23512712

Kheradpour, Pouya; Ernst, Jason; Melnikov, Alexandre; Rogov, Peter; Wang, Li; Zhang, Xiaolan; Alston, Jessica; Mikkelsen, Tarjei S; Kellis, Manolis

2013-05-01

407

Systematic dissection of regulatory motifs in 2000 predicted human enhancers using a massively parallel reporter assay  

PubMed Central

Genome-wide chromatin annotations have permitted the mapping of putative regulatory elements across multiple human cell types. However, their experimental dissection by directed regulatory motif disruption has remained unfeasible at the genome scale. Here, we use a massively parallel reporter assay (MPRA) to measure the transcriptional levels induced by 145-bp DNA segments centered on evolutionarily conserved regulatory motif instances within enhancer chromatin states. We select five predicted activators (HNF1, HNF4, FOXA, GATA, NFE2L2) and two predicted repressors (GFI1, ZFP161) and measure reporter expression in erythroleukemia (K562) and liver carcinoma (HepG2) cell lines. We test 2104 wild-type sequences and 3314 engineered enhancer variants containing targeted motif disruptions, each using 10 barcode tags and two replicates. The resulting data strongly confirm the enhancer activity and cell-type specificity of enhancer chromatin states, the ability of 145-bp segments to recapitulate both, the necessary role of regulatory motifs in enhancer function, and the complementary roles of activator and repressor motifs. We find statistically robust evidence that (1) disrupting the predicted activator motifs abolishes enhancer function, while silent or motif-improving changes maintain enhancer activity; (2) evolutionary conservation, nucleosome exclusion, binding of other factors, and strength of the motif match are predictive of enhancer activity; (3) scrambling repressor motifs leads to aberrant reporter expression in cell lines where the enhancers are usually inactive. Our results suggest a general strategy for deciphering cis-regulatory elements by systematic large-scale manipulation and provide quantitative enhancer activity measurements across thousands of constructs that can be mined to develop predictive models of gene expression. PMID:23512712

Kheradpour, Pouya; Ernst, Jason; Melnikov, Alexandre; Rogov, Peter; Wang, Li; Zhang, Xiaolan; Alston, Jessica; Mikkelsen, Tarjei S.; Kellis, Manolis

2013-01-01

408

A new order of D2 lymphadenectomy in laparoscopic gastrectomy for cancer: live anatomy-based dissection.  

PubMed

It was the aim of this study to develop a methodology for dissection in laparoscopic distal gastrectomy with D2 lymphadenectomy (D2 LDG) for gastric cancer. One-hundred and thirty-two patients with distal gastric cancer underwent D2 LDG with a novel sequence of lymph node dissection between August 2004 and June 2008. Live anatomy in each step was observed simultaneously to ensure and confirm the newly developed methodology. Dissections in LDG were standardized as sequential steps: Dividing the gastrocolic ligament and getting access to the prepancreatic space--lymph node dissection in the lower left area--lymph node dissection in the lower right area--lymph node dissection in the upper right area--lymph nodes dissection centrally--lymph node dissection between liver and stomach. All dissections were successfully performed in peripancreatic spaces and their extensions. Gastric vessels were located by special landmarks, traced along vascular trunks and bifurcations, and identified by fine dissection technique in vaginavasorum. Sequential dissection around the pancreas was an effective method for D2 LDG. It was ensured by anatomical knowledge in each step: Vessels and fascial spaces around a central landmark, the pancreas. PMID:21091070

Li, Guo-Xin; Zhang, Ce; Yu, Jiang; Wang, Ya-Nan; Hu, Yan-Feng

2010-12-01

409

A large QTL for fear and anxiety mapped using an F2 cross can be dissected into multiple smaller QTLs  

PubMed Central

Using chromosome substitution strains (CSS), we previously identified a large quantitative trait locus (QTL) for conditioned fear (CF) on mouse chromosome 10. Here, we used an F2 cross between CSS-10 and C57BL/6J (B6) to localize that QTL to distal chromosome 10. That QTL accounted for all of the difference between CSS-10 and B6. We then produced congenic strains to fine-map that interval. We identified two congenic strains that captured some or all of the QTL. The larger congenic strain (Line 1; 122.387121 – 129.068 Mb; build 37) appeared to account for all of the difference between CSS-10 and B6. The smaller congenic strain (Line 2; 127.277–129.068 Mb) was intermediate between CSS-10 and B6. We used haplotype mapping followed by qPCR to identify one gene that was differentially expressed in both lines relative to B6 (Rnf41) and one that was differentially expressed between only Line 1 and B6 (Shmt2). These cis-eQTLs may cause the behavioral QTLs; however, further studies are required to validate these candidate genes. More generally, our observation that a large QTL mapped using CSS and F2 crosses can be dissected into multiple smaller QTLs demonstrates a weaknesses of two-stage approaches that seek to use coarse mapping to identify large regions followed by fine-mapping. Indeed, additional dissection of these congenic strains might result in further subdivision of these QTL regions. Despite these limitations we have successfully fine mapped two QTLs to small regions and identified putative candidate genes, demonstrating that the congenic approach can be effective for fine mapping QTLs. PMID:23876074

Parker, Clarissa C.; Sokoloff, Greta; Leung, Emily; Kirkpatrick, Stacey L.; Palmer, Abraham A.

2013-01-01

410

Dissecting impulsivity and its relationships to drug addictions.  

PubMed

Addictions are often characterized as forms of impulsive behavior. That said, it is often noted that impulsivity is a multidimensional construct, spanning several psychological domains. This review describes the relationship between varieties of impulsivity and addiction-related behaviors, the nature of the causal relationship between the two, and the underlying neurobiological mechanisms that promote impulsive behaviors. We conclude that the available data strongly support the notion that impulsivity is both a risk factor for, and a consequence of, drug and alcohol consumption. While the evidence indicating that subtypes of impulsive behavior are uniquely informative-either biologically or with respect to their relationships to addictions-is convincing, multiple lines of study link distinct subtypes of impulsivity to low dopamine D2 receptor function and perturbed serotonergic transmission, revealing shared mechanisms between the subtypes. Therefore, a common biological framework involving monoaminergic transmitters in key frontostriatal circuits may link multiple forms of impulsivity to drug self-administration and addiction-related behaviors. Further dissection of these relationships is needed before the next phase of genetic and genomic discovery will be able to reveal the biological sources of the vulnerability for addiction indexed by impulsivity. PMID:24654857

Jentsch, J David; Ashenhurst, James R; Cervantes,