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  • 1
  • 2
    Publication Date: 2018-02-21
    Description: High mobility group box 1 (HMGB1), a chromatin-binding nuclear protein, plays a critical role in sepsis by acting as a key "late-phase" inflammatory mediator. Integrin CD11b is essential for inflammatory cell activation and migration, thus mediating inflammatory responses. However, it is unclear whether CD11b participates in the development of sepsis. In this study, we report that CD11b contributes to LPS-induced endotoxin shock and microbial sepsis, as antagonism of CD11b with the CD11b blocking Ab or CD11b inhibitor Gu-4 protects mice against LPS- and microbial sepsis-related lethality, which is associated with significantly diminished serum HMGB1 levels. Consistent with this, CD11b-deficient mice were more resistant to microbial sepsis with a much lower serum HMGB1 level compared with wild-type mice. Pharmacological blockage and genetic knockdown/knockout of CD11b in murine macrophages hampered LPS-stimulated HMGB1 nucleocytoplasmic translocation and extracellular release. Furthermore, silencing CD11b interrupted the interaction of HMGB1 with either a nuclear export factor chromosome region maintenance 1 or classical protein kinase C and inhibited classical protein kinase C–induced HMGB1 phosphorylation, the potential underlying mechanism(s) responsible for CD11b blockage-induced suppression of HMGB1 nucleocytoplasmic translocation and subsequent extracellular release. Thus, our results highlight that CD11b contributes to the development of sepsis, predominantly by facilitating nucleocytoplasmic translocation and active release of HMGB1.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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  • 3
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 371 (1994), S. 9-9 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] SIR - We wish to draw your readers' attention to the outcome of an important conference held by UNESCO and the International Council of Scientific Unions (ICSU) at the Komarov Botanical Institute in St Petersburg in December 1993. Among other things, the status and the future of botanical ...
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Thiazolidinediones are a new class of antidiabetic agent that improve insulin sensitivity and reduce plasma glucose and blood pressure in subjects with type 2 diabetes. Although these agents can bind and activate an orphan nuclear receptor, peroxisome proliferator-activated receptor gamma ...
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1437-9813
    Keywords: Key words Gastric erosions ; Drug intake ; Children ; Acute gastrointestinal bleeding ; Endoscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The authors evaluated the relationship between drug intake and upper gastrointestinal (GI) bleeding. The endoscopic files of the previous 2 years were reviewed and the incidence and age and sex distribution recorded. GI bleeding is indication for a high percentage of lower endoscopies and a low percentage of upper endoscopies. On the other hand, although rarer upper GI bleeding is more severe and frequently related to drug ingestion. About 50% of cases showed gastric erosions secondary to drug intake. A relation between gastric bleeding and paracetamol is considered, as is the possibility of preventing secondary severe bleeding by pharmacologic gastric protection in children with risk factors such as chronic use of other drugs or portal hypertension.
    Type of Medium: Electronic Resource
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  • 6
    Publication Date: 2018-09-18
    Description: Activated platelets release functional, high m.w. epidermal growth factor (HMW-EGF). In this study, we show platelets also express epidermal growth factor (EGF) receptor (EGFR) protein, but not ErbB2 or ErbB4 coreceptors, and so might respond to HMW-EGF. We found HMW-EGF stimulated platelet EGFR autophosphorylation, PI3 kinase-dependent AKT phosphorylation, and a Ca 2+ transient that were blocked by EGFR tyrosine kinase inhibition. Strong (thrombin) and weak (ADP, platelet-activating factor) G protein-coupled receptor agonists and non–G protein-coupled receptor collagen recruited EGFR tyrosine kinase activity that contributed to platelet activation because EGFR kinase inhibition reduced signal transduction and aggregation induced by each agonist. EGF stimulated ex vivo adhesion of platelets to collagen-coated microfluidic channels, whereas systemic EGF injection increased initial platelet deposition in FeCl 3 -damaged murine carotid arteries. EGFR signaling contributes to oral squamous cell carcinoma (OSCC) tumorigenesis, but the source of its ligand is not established. We find individual platelets were intercalated within OSCC tumors. A portion of these platelets expressed stimulation-dependent Bcl-3 and IL-1β and so had been activated. Stimulated platelets bound OSCC cells, and material released from stimulated platelets induced OSCC epithelial–mesenchymal transition and stimulated their migration and invasion through Matrigel barriers. Anti-EGF Ab or EGFR inhibitors abolished platelet-induced tumor cell phenotype transition, migration, and invasion; so the only factor released from activated platelets necessary for OSCC metastatic activity was HMW-EGF. These results establish HMW-EGF in platelet function and elucidate a previously unsuspected connection between activated platelets and tumorigenesis through rapid, and prolonged, autocrine-stimulated release of HMW-EGF by tumor-associated platelets.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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  • 7
    Publication Date: 2018-10-02
    Description: Intestinal alkaline SMase (Alk-SMase) cleaves phosphocholine from SM, platelet-activating factor (PAF), and lysophosphatidylcholine. We recently found that colitis-associated colon cancer was 4- to 5-fold enhanced in Alk-SMase KO mice. Here, we further studied the pathogenesis of colitis induced by dextran sulfate sodium (DSS) in WT and KO mice. Compared with WT mice, KO mice demonstrated greater body weight loss, more severe bloody diarrhea, broader inflammatory cell infiltration, and more serious epithelial injury. Higher levels of PAF and lower levels of interleukin (IL)10 were identified in KO mice 2 days after DSS treatment. A greater and progressive increase of lysophosphatidic acid (LPA) was identified. The change was associated with increased autotaxin expression in both small intestine and colon, which was identified by immunohistochemistry study, Western blot, and sandwich ELISA. The upregulation of autotaxin coincided with an early increase of PAF. IL6 and TNFα were increased in both WT and KO mice. At the later stage (day 8), significant decreases in IL6, IL10, and PAF were identified, and the decreases were greater in KO mice. In conclusion, deficiency of Alk-SMase enhances DSS-induced colitis by mechanisms related to increased autotaxin expression and LPA formation. The early increase of PAF might be a trigger for such reactions.
    Print ISSN: 0022-2275
    Electronic ISSN: 1539-7262
    Topics: Biology , Chemistry and Pharmacology , Medicine
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  • 8
    Publication Date: 2018-12-08
    Description: The central amygdala (CeA) plays a critical role in the expression of emotional behaviors, including pathologic anxiety disorders. The present study demonstrated that GABAergic inhibition in CeA was significantly increased by methyleugenol (ME), a natural constituent isolated from the essential oils of several plants. The electrophysiologic recordings showed that ME increased both tonic and miniature inhibitory postsynaptic GABAergic currents in CeA slices, especially the tonic currents, while the miniature excitatory postsynaptic currents were not affected. In the fear-induced anxiety animal model, both intraperitoneal injection or CeA-specific infusion of ME reduced the anxiety-like behaviors in mice, likely by facilitating the activation of A-type GABA receptors (GABA A Rs). These results reveal that GABA A R in the CeA can be a potential therapeutic target for the treatment of anxiety and that ME is capable of enhancing the GABAergic inhibition in CeA neurons for the inhibition of neuronal excitability.
    Print ISSN: 0022-3565
    Electronic ISSN: 1521-0103
    Topics: Medicine
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  • 9
    Publication Date: 2011-07-12
    Description: Potato (Solanum tuberosum L.) is the world's most important non-grain food crop and is central to global food security. It is clonally propagated, highly heterozygous, autotetraploid, and suffers acute inbreeding depression. Here we use a homozygous doubled-monoploid potato clone to sequence and assemble 86% of the 844-megabase genome. We predict 39,031 protein-coding genes and present evidence for at least two genome duplication events indicative of a palaeopolyploid origin. As the first genome sequence of an asterid, the potato genome reveals 2,642 genes specific to this large angiosperm clade. We also sequenced a heterozygous diploid clone and show that gene presence/absence variants and other potentially deleterious mutations occur frequently and are a likely cause of inbreeding depression. Gene family expansion, tissue-specific expression and recruitment of genes to new pathways contributed to the evolution of tuber development. The potato genome sequence provides a platform for genetic improvement of this vital crop.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Potato Genome Sequencing Consortium -- Xu, Xun -- Pan, Shengkai -- Cheng, Shifeng -- Zhang, Bo -- Mu, Desheng -- Ni, Peixiang -- Zhang, Gengyun -- Yang, Shuang -- Li, Ruiqiang -- Wang, Jun -- Orjeda, Gisella -- Guzman, Frank -- Torres, Michael -- Lozano, Roberto -- Ponce, Olga -- Martinez, Diana -- De la Cruz, German -- Chakrabarti, S K -- Patil, Virupaksh U -- Skryabin, Konstantin G -- Kuznetsov, Boris B -- Ravin, Nikolai V -- Kolganova, Tatjana V -- Beletsky, Alexey V -- Mardanov, Andrei V -- Di Genova, Alex -- Bolser, Daniel M -- Martin, David M A -- Li, Guangcun -- Yang, Yu -- Kuang, Hanhui -- Hu, Qun -- Xiong, Xingyao -- Bishop, Gerard J -- Sagredo, Boris -- Mejia, Nilo -- Zagorski, Wlodzimierz -- Gromadka, Robert -- Gawor, Jan -- Szczesny, Pawel -- Huang, Sanwen -- Zhang, Zhonghua -- Liang, Chunbo -- He, Jun -- Li, Ying -- He, Ying -- Xu, Jianfei -- Zhang, Youjun -- Xie, Binyan -- Du, Yongchen -- Qu, Dongyu -- Bonierbale, Merideth -- Ghislain, Marc -- Herrera, Maria del Rosario -- Giuliano, Giovanni -- Pietrella, Marco -- Perrotta, Gaetano -- Facella, Paolo -- O'Brien, Kimberly -- Feingold, Sergio E -- Barreiro, Leandro E -- Massa, Gabriela A -- Diambra, Luis -- Whitty, Brett R -- Vaillancourt, Brieanne -- Lin, Haining -- Massa, Alicia N -- Geoffroy, Michael -- Lundback, Steven -- DellaPenna, Dean -- Buell, C Robin -- Sharma, Sanjeev Kumar -- Marshall, David F -- Waugh, Robbie -- Bryan, Glenn J -- Destefanis, Marialaura -- Nagy, Istvan -- Milbourne, Dan -- Thomson, Susan J -- Fiers, Mark -- Jacobs, Jeanne M E -- Nielsen, Kare L -- Sonderkaer, Mads -- Iovene, Marina -- Torres, Giovana A -- Jiang, Jiming -- Veilleux, Richard E -- Bachem, Christian W B -- de Boer, Jan -- Borm, Theo -- Kloosterman, Bjorn -- van Eck, Herman -- Datema, Erwin -- Hekkert, Bas te Lintel -- Goverse, Aska -- van Ham, Roeland C H J -- Visser, Richard G F -- BB/F012640/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/F012640/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- WT 083481/Wellcome Trust/United Kingdom -- England -- Nature. 2011 Jul 10;475(7355):189-95. doi: 10.1038/nature10158.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉BGI-Shenzhen, Chinese Ministry of Agricultural, Key Lab of Genomics, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21743474" target="_blank"〉PubMed〈/a〉
    Keywords: Evolution, Molecular ; Gene Duplication ; Gene Expression Regulation, Plant ; Genes, Plant/genetics ; Genetic Variation ; Genome, Plant/*genetics ; *Genomics ; Haplotypes/genetics ; Heterozygote ; Homozygote ; Immunity, Innate ; Inbreeding ; Molecular Sequence Annotation ; Molecular Sequence Data ; Plant Diseases/genetics ; Ploidies ; Solanum tuberosum/*genetics/physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2012-04-13
    Description: In the fasted state, increases in circulating glucagon promote hepatic glucose production through induction of the gluconeogenic program. Triggering of the cyclic AMP pathway increases gluconeogenic gene expression via the de-phosphorylation of the CREB co-activator CRTC2 (ref. 1). Glucagon promotes CRTC2 dephosphorylation in part through the protein kinase A (PKA)-mediated inhibition of the CRTC2 kinase SIK2. A number of Ser/Thr phosphatases seem to be capable of dephosphorylating CRTC2 (refs 2, 3), but the mechanisms by which hormonal cues regulate these enzymes remain unclear. Here we show in mice that glucagon stimulates CRTC2 dephosphorylation in hepatocytes by mobilizing intracellular calcium stores and activating the calcium/calmodulin-dependent Ser/Thr-phosphatase calcineurin (also known as PP3CA). Glucagon increased cytosolic calcium concentration through the PKA-mediated phosphorylation of inositol-1,4,5-trisphosphate receptors (InsP(3)Rs), which associate with CRTC2. After their activation, InsP(3)Rs enhanced gluconeogenic gene expression by promoting the calcineurin-mediated dephosphorylation of CRTC2. During feeding, increases in insulin signalling reduced CRTC2 activity via the AKT-mediated inactivation of InsP(3)Rs. InsP(3)R activity was increased in diabetes, leading to upregulation of the gluconeogenic program. As hepatic downregulation of InsP(3)Rs and calcineurin improved circulating glucose levels in insulin resistance, these results demonstrate how interactions between cAMP and calcium pathways at the level of the InsP(3)R modulate hepatic glucose production under fasting conditions and in diabetes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3343222/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3343222/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Yiguo -- Li, Gang -- Goode, Jason -- Paz, Jose C -- Ouyang, Kunfu -- Screaton, Robert -- Fischer, Wolfgang H -- Chen, Ju -- Tabas, Ira -- Montminy, Marc -- HL087123/HL/NHLBI NIH HHS/ -- P01 HL087123/HL/NHLBI NIH HHS/ -- P01 HL087123-05/HL/NHLBI NIH HHS/ -- R01 DK049777/DK/NIDDK NIH HHS/ -- R01 DK049777-19/DK/NIDDK NIH HHS/ -- R01 DK091618/DK/NIDDK NIH HHS/ -- R01 DK091618-02/DK/NIDDK NIH HHS/ -- R01-DK049777/DK/NIDDK NIH HHS/ -- R01-DK083834/DK/NIDDK NIH HHS/ -- R01-DK091618/DK/NIDDK NIH HHS/ -- R37 DK083834/DK/NIDDK NIH HHS/ -- R37 DK083834-29/DK/NIDDK NIH HHS/ -- T32 GM008666/GM/NIGMS NIH HHS/ -- England -- Nature. 2012 Apr 8;485(7396):128-32. doi: 10.1038/nature10988.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22495310" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood Glucose/*metabolism ; Calcineurin/metabolism ; Calcium/metabolism ; Calcium Signaling ; Cells, Cultured ; Cyclic AMP/metabolism ; Diabetes Mellitus/blood/genetics/*metabolism ; Fasting/blood/*metabolism ; Gene Expression Regulation/drug effects ; Glucagon/pharmacology ; *Gluconeogenesis/genetics ; HEK293 Cells ; Hepatocytes/metabolism ; Humans ; Inositol 1,4,5-Trisphosphate Receptors/*metabolism ; Insulin Resistance ; Liver/cytology/*metabolism ; Mice ; Phosphorylation/drug effects ; Trans-Activators/metabolism ; Transcription Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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