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  • Springer  (27)
  • Nature Publishing Group (NPG)  (3)
  • Institute of Physics (IOP)  (2)
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  • 1
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    Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARgamma by Cdk5 (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-07-24
    Description: Obesity induced in mice by high-fat feeding activates the protein kinase Cdk5 (cyclin-dependent kinase 5) in adipose tissues. This results in phosphorylation of the nuclear receptor PPARgamma (peroxisome proliferator-activated receptor gamma), a dominant regulator of adipogenesis and fat cell gene expression, at serine 273. This modification of PPARgamma does not alter its adipogenic capacity, but leads to dysregulation of a large number of genes whose expression is altered in obesity, including a reduction in the expression of the insulin-sensitizing adipokine, adiponectin. The phosphorylation of PPARgamma by Cdk5 is blocked by anti-diabetic PPARgamma ligands, such as rosiglitazone and MRL24. This inhibition works both in vivo and in vitro, and is completely independent of classical receptor transcriptional agonism. Similarly, inhibition of PPARgamma phosphorylation in obese patients by rosiglitazone is very tightly associated with the anti-diabetic effects of this drug. All these findings strongly suggest that Cdk5-mediated phosphorylation of PPARgamma may be involved in the pathogenesis of insulin-resistance, and present an opportunity for development of an improved generation of anti-diabetic drugs through PPARgamma.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2987584/" 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/PMC2987584/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Choi, Jang Hyun -- Banks, Alexander S -- Estall, Jennifer L -- Kajimura, Shingo -- Bostrom, Pontus -- Laznik, Dina -- Ruas, Jorge L -- Chalmers, Michael J -- Kamenecka, Theodore M -- Bluher, Matthias -- Griffin, Patrick R -- Spiegelman, Bruce M -- DK087853/DK/NIDDK NIH HHS/ -- DK31405/DK/NIDDK NIH HHS/ -- K99 DK087853/DK/NIDDK NIH HHS/ -- R01 GM084041/GM/NIGMS NIH HHS/ -- R01 GM084041-03/GM/NIGMS NIH HHS/ -- R01-GM084041/GM/NIGMS NIH HHS/ -- R37 DK031405/DK/NIDDK NIH HHS/ -- R37 DK031405-30/DK/NIDDK NIH HHS/ -- S10 RR027270/RR/NCRR NIH HHS/ -- U54 MH084512/MH/NIMH NIH HHS/ -- U54 MH084512-020010/MH/NIMH NIH HHS/ -- U54-MH084512/MH/NIMH NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2010 Jul 22;466(7305):451-6. doi: 10.1038/nature09291.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cancer Biology and Division of Metabolism and Chronic Disease, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20651683" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue/drug effects/metabolism/physiopathology ; Amino Acid Sequence ; Animals ; Cell Line ; Cyclin-Dependent Kinase 5/*antagonists & inhibitors/genetics/metabolism ; Diabetes Mellitus, Experimental/complications/*drug therapy/metabolism ; Dietary Fats/pharmacology ; Humans ; Insulin/metabolism ; Ligands ; Mice ; Models, Molecular ; Obesity/chemically induced/complications/*metabolism/physiopathology ; PPAR gamma/agonists/*metabolism ; Phosphorylation/drug effects ; Phosphoserine/metabolism ; Protein Conformation ; Thiazolidinediones/*pharmacology/therapeutic use
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Antidiabetic actions of a non-agonist PPARgamma ligand blocking Cdk5-mediated phosphorylation (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-09-06
    Description: PPARgamma is the functioning receptor for the thiazolidinedione (TZD) class of antidiabetes drugs including rosiglitazone and pioglitazone. These drugs are full classical agonists for this nuclear receptor, but recent data have shown that many PPARgamma-based drugs have a separate biochemical activity, blocking the obesity-linked phosphorylation of PPARgamma by Cdk5. Here we describe novel synthetic compounds that have a unique mode of binding to PPARgamma, completely lack classical transcriptional agonism and block the Cdk5-mediated phosphorylation in cultured adipocytes and in insulin-resistant mice. Moreover, one such compound, SR1664, has potent antidiabetic activity while not causing the fluid retention and weight gain that are serious side effects of many of the PPARgamma drugs. Unlike TZDs, SR1664 also does not interfere with bone formation in culture. These data illustrate that new classes of antidiabetes drugs can be developed by specifically targeting the Cdk5-mediated phosphorylation of PPARgamma.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3179551/" 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/PMC3179551/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Choi, Jang Hyun -- Banks, Alexander S -- Kamenecka, Theodore M -- Busby, Scott A -- Chalmers, Michael J -- Kumar, Naresh -- Kuruvilla, Dana S -- Shin, Youseung -- He, Yuanjun -- Bruning, John B -- Marciano, David P -- Cameron, Michael D -- Laznik, Dina -- Jurczak, Michael J -- Schurer, Stephan C -- Vidovic, Dusica -- Shulman, Gerald I -- Spiegelman, Bruce M -- Griffin, Patrick R -- 1RC4DK090861/DK/NIDDK NIH HHS/ -- DK31405/DK/NIDDK NIH HHS/ -- R01 DK040936/DK/NIDDK NIH HHS/ -- R01 GM084041/GM/NIGMS NIH HHS/ -- R01 GM084041-03/GM/NIGMS NIH HHS/ -- R01-GM084041/GM/NIGMS NIH HHS/ -- R37 DK031405/DK/NIDDK NIH HHS/ -- R37 DK031405-30/DK/NIDDK NIH HHS/ -- R37 DK031405-31/DK/NIDDK NIH HHS/ -- RC4 DK090861/DK/NIDDK NIH HHS/ -- RC4 DK090861-01/DK/NIDDK NIH HHS/ -- S10 RR027270/RR/NCRR NIH HHS/ -- U24 DK059635/DK/NIDDK NIH HHS/ -- U54 MH074404/MH/NIMH NIH HHS/ -- U54 MH074404-01/MH/NIMH NIH HHS/ -- U54-MH074404/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- England -- Nature. 2011 Sep 4;477(7365):477-81. doi: 10.1038/nature10383.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cancer Biology and Division of Metabolism and Chronic Disease, Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21892191" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3-L1 Cells ; Adipocytes/drug effects/metabolism ; Adipose Tissue, White/drug effects/metabolism ; Animals ; Biphenyl Compounds/chemistry/pharmacology ; Body Fluids/drug effects ; COS Cells ; Cercopithecus aethiops ; Cyclin-Dependent Kinase 5/*antagonists & inhibitors ; Dietary Fats/pharmacology ; Disease Models, Animal ; Dose-Response Relationship, Drug ; HEK293 Cells ; Humans ; Hypoglycemic Agents/adverse effects/chemistry/*pharmacology ; Ligands ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Models, Molecular ; Obesity/chemically induced/metabolism ; Osteogenesis/drug effects ; PPAR gamma/agonists/chemistry/*metabolism ; Phosphorylation/drug effects ; Phosphoserine/metabolism ; Thiazolidinediones/adverse effects/pharmacology ; Transcription, Genetic/drug effects ; Tumor Necrosis Factor-alpha/pharmacology ; Weight Gain/drug effects
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 3
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    A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-01-13
    Description: Exercise benefits a variety of organ systems in mammals, and some of the best-recognized effects of exercise on muscle are mediated by the transcriptional co-activator PPAR-gamma co-activator-1 alpha (PGC1-alpha). Here we show in mouse that PGC1-alpha expression in muscle stimulates an increase in expression of FNDC5, a membrane protein that is cleaved and secreted as a newly identified hormone, irisin. Irisin acts on white adipose cells in culture and in vivo to stimulate UCP1 expression and a broad program of brown-fat-like development. Irisin is induced with exercise in mice and humans, and mildly increased irisin levels in the blood cause an increase in energy expenditure in mice with no changes in movement or food intake. This results in improvements in obesity and glucose homeostasis. Irisin could be therapeutic for human metabolic disease and other disorders that are improved with exercise.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3522098/" 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/PMC3522098/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bostrom, Pontus -- Wu, Jun -- Jedrychowski, Mark P -- Korde, Anisha -- Ye, Li -- Lo, James C -- Rasbach, Kyle A -- Bostrom, Elisabeth Almer -- Choi, Jang Hyun -- Long, Jonathan Z -- Kajimura, Shingo -- Zingaretti, Maria Cristina -- Vind, Birgitte F -- Tu, Hua -- Cinti, Saverio -- Hojlund, Kurt -- Gygi, Steven P -- Spiegelman, Bruce M -- DK31405/DK/NIDDK NIH HHS/ -- DK54477/DK/NIDDK NIH HHS/ -- K99 DK087853/DK/NIDDK NIH HHS/ -- R01 DK054477/DK/NIDDK NIH HHS/ -- R01 DK061562/DK/NIDDK NIH HHS/ -- R37 DK031405/DK/NIDDK NIH HHS/ -- England -- Nature. 2012 Jan 11;481(7382):463-8. doi: 10.1038/nature10777.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22237023" target="_blank"〉PubMed〈/a〉
    Keywords: Adipocytes/cytology/drug effects/metabolism ; Adipose Tissue, Brown/*cytology/drug effects/metabolism ; Adipose Tissue, White/*cytology/drug effects/metabolism ; Animals ; Cell Respiration/drug effects ; Cells, Cultured ; Culture Media, Conditioned/pharmacology ; Energy Metabolism/drug effects/genetics/physiology ; Exercise/physiology ; Gene Expression Regulation/drug effects/genetics ; Hormones/metabolism/secretion ; Humans ; Insulin Resistance/physiology ; Intracellular Signaling Peptides and Proteins/genetics/metabolism ; Ion Channels/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Mitochondrial Proteins/metabolism ; Models, Animal ; Muscle Cells/metabolism ; Obesity/blood/chemically induced/prevention & control ; Physical Conditioning, Animal/physiology ; Plasma/chemistry ; Subcutaneous Fat/cytology/drug effects/metabolism ; *Thermogenesis/drug effects/genetics ; Trans-Activators/deficiency/genetics/*metabolism/secretion ; 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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  • 4
    Electronic Resource
    Electronic Resource
    Storm-induced fine-sediment transport, west coast of south Korea (1984)
    Springer
    Geo-marine letters 4 (1984), S. 177-180 
    Details
    ISSN: 1432-1157
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences
    Notes: Abstract Archived data, together with field observations collected between 1980 and 1982 off the west coast of Korea, suggest that the onset of winter monsoon winds in late fall initiates a residual southward flow that potentially carries large volumes of resuspended bottom sediments into the Korea Strait. During the calm conditions of summer, muds are replenished by high river discharges and reform the band of soft material, which characteristically occurs as a series of mudflats near the coast. Thus, these mudflats serve as a temporary storage facility during summer accumulation and as a source during winter erosion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02281701
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  • 5
    Electronic Resource
    Electronic Resource
    Effects of yeast extract on the production and the quality of the exopolysaccharide, zooglan, produced by Zoogloea ramigera 115SLR (1999)
    Springer
    Applied microbiology and biotechnology 51 (1999), S. 235-240 
    Details
    ISSN: 1432-0614
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Although many studies have examined the influence of culture conditions on the production and composition of polysaccharides, little is known about the factors influencing the quality of exopolysaccharides (EPS). In this work we studied the effect of yeast extract on the production, composition and molecular weight of the EPS zooglan produced by Zoogloea ramigera 115SLR. This bacterium was grown on a new completely defined synthetic medium and on a medium containing yeast extract. Growth and polysaccharide production performances were comparable on the two media with a glucose to exopolysaccharide conversion yield of 35% (g/g). The polysaccharides produced on these two media have an identical composition but a different molecular weight and molecular weight distribution. The yeast extract medium leads to a more homogeneous polysaccharide solution.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002530051387
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  • 6
    Electronic Resource
    Electronic Resource
    Efficient secretory production of alkaline phosphatase by high cell density culture of recombinant Escherichia coli using the Bacillus sp. endoxylanase signal sequence (2000)
    Springer
    Applied microbiology and biotechnology 53 (2000), S. 640-645 
    Details
    ISSN: 1432-0614
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract New secretion vectors containing the Bacillus sp. endoxylanase signal sequence were constructed for the secretory production of recombinant proteins in Escherichia coli. The E. coli alkaline phosphatase structural gene fused to the endoxylanase signal sequence was expressed from the trc promoter in various E. coli strains by induction with IPTG. Among those tested, E. coli HB101 showed the highest efficiency of secretion (up to 25.3% of total proteins). When cells were induced with 1 mM IPTG, most of the secreted alkaline phosphatase formed inclusion bodies in the periplasm. However, alkaline phosphatase could be produced as a soluble form without reduction of expression level by inducing with less (0.01 mM) IPTG, and greater than 90% of alkaline phosphatase could be recovered from the periplasm by the simple osmotic shock method. Fed-batch cultures were carried out to examine the possibility of secretory protein production at high cell density. Up to 5.2 g/l soluble alkaline phosphatase could be produced in the periplasm by the pH-stat fed-batch cultivation of E. coli HB101 harboring pTrcS1PhoA. These results demonstrate the possibility of efficient secretory production of recombinant proteins in E. coli by high cell density cultivation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002530000334
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  • 7
    Electronic Resource
    Electronic Resource
    Developmental regulation of polyamine metabolism in growth and differentiation of carrot culture (1984)
    Springer
    Planta 162 (1984), S. 532-539 
    Details
    ISSN: 1432-2048
    Keywords: Arginine decarboxylase ; Auxin in somatic embryogenesis ; Cell culture (polyamines) ; Dnucus (polyamines in embryogenesis) ; Embryogenesis somatic ; Polyamine ; S-Adenosylmethionine decarboxylase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Polyamine levels and the activities of two polyamine biosynthetic enzymes, arginine decarboxylase (EC 4.1.1.19) and S-adenosylmethionine decarboxylase (EC 4.1.1.50), were determined during somatic embryogenesis of carrot (Daucus carota L.) cell cultures. Embryogenic cultures showed severalfold increases in polyamine levels over nondifferentiating controls. A mutant cell line that failed to form embryos but grew at the same rate as the wild-type line also failed to show increases in polyamine levels, thus providing evidence that this increased polyamine content was in fact associated with the development of embryos. Furthermore, inhibition of these increases in polyamines caused by drugs inhibited embryogenesis and the effect was reversible with spermidine. The activities of arginine decarboxylase and Sadenosylmethionine decarboxylase were found to be suppressed by auxin; however, the specific effects differed between exogenous 2,4-dichlorophenoxyacetic acid and endogenous indole-3-acetic acid. The results indicate that increased polyamine levels are required for cellular differentiation and development occurring during somatic embryogenesis in carrot cell cultures.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00399919
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  • 8
    Electronic Resource
    Electronic Resource
    Effect of nutrient deficiency on accumulation and relative molecular weight of poly-β-hydroxybutyric acid by methylotrophic bacterium, Pseudomonas 135 (1992)
    Springer
    Applied microbiology and biotechnology 37 (1992), S. 702-706 
    Details
    ISSN: 1432-0614
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Summary Pseudomonas 135, a facultative methylotroph, was cultivated on methanol as a sole carbon and energy source for the accumulation of poly-β-hydroxybutyric acid (PHB). The cells grew fairly well on minimal synthetic medium containing 0.5% (v/v) of methanol at pH 7.0 and 30° C. The maximum specific growth rate was determined to be 0.26–0.28 h−1 with a growth yield of 0.38 in the optimized growth medium. For stimulation of PHB accumulation in the cells, deficiency of nutrients such as NH inf4 sup+ , Mg2+ and PO inf4 sup3− was crucial even though cell growth was significantly suppressed. The PHB content of a 40-h culture was determined to be 37% of the total cell mass in NH inf4 sup+ -limited medium, 42.5% on Mg2+-deficient medium, and 34.5% on PO inf4 sup3− -deficient medium. The maximum content of PHB in the cells could reach 55% in NH inf4 sup+ -limited fed-batch culture. The average relative molecular eight determined by gel permeation chromatography was 3.7 × 105 in NH inf4 sup+ -limited culture, 2.5 × 105 in Mg2+-deficientmedium, and 3.1 × 105 in PO inf4 sup3− -deficient medium. Polydispersity determined in each culture was relatively high (about 10–11). The solid PHB had a melting temperature of 173° C.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00174831
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  • 9
    Electronic Resource
    Electronic Resource
    High molecular weight syndiotacticity-rich poly(vinyl alcohol) gel in aging process (2000)
    Springer
    Colloid & polymer science 278 (2000), S. 1198-1204 
    Details
    ISSN: 1435-1536
    Keywords: Key words Aging ; Poly(vinyl alcohol) ; Gel ; Syndiotacticity ; High molecular weight
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The properties of the aged gels of high molecular weight syndiotacticity-rich poly(vinyl alcohol)s (HMW S-PVAs) with different syndiotactic diad (s-diad) contents were investigated. HMW S-PVA gels with s-diad content of 61.5% and 58.2% showed the rapid increases of the syneresis and the turbidity from the early stage of aging time, which is ascribable to the phase separation, while that with s-diad content of 55.7% did not. From the morphological study, it was confirmed that the phase separation in HMW S-PVA gel with s-diad content of 61.5% occurred without the liquid-liquid phase separation in sol state, whereas both the liquid-liquid phase separation in sol state and the subsequent phase separation in gel state occurred in the case of HMW S-PVA gel with s-diad content of 58.2%. On the other hand, HMW S-PVA gel with s-diad content of 55.7% showed neither the liquid-liquid phase separation in sol state nor the phase separation in gel state in the long period of time. It was also confirmed from wide angle X-ray diffractogram that the crystallization was accompanied by the phase separation in gel state in the aging process of PVA gel. However, the crystallization was hindered by the fast network formation at the initial stage of time. Later the syndiotacticity promoted the crystallization. The tensile modulus of HMW S-PVA gel with higher syndiotacticity increased more significantly with time.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003960000387
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  • 10
    Electronic Resource
    Electronic Resource
    Tolerance Optimization for Mechanisms with Lubricated Joints (1998)
    Springer
    Multibody system dynamics 2 (1998), S. 145-168 
    Details
    ISSN: 1573-272X
    Keywords: tolerance ; clearance ; optimization ; mechanical error ; mechanism ; lubricated joint
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract This paper addresses an analytical approach to tolerance optimization for planar mechanisms with lubricated joints based on mechanical error analysis. The mobility method is applied to consider the lubrication effects at joints and planar mechanisms are stochastically defined by using the clearance vector model for mechanical error analysis. The uncertainties considered in the analysis are tolerances on link lengths and radial clearances and these are selected as design variables. To show the validity of the proposed method for mechanical error analysis, it is applied to two examples, and the results obtained are compared with those of Monte Carlo simulations. Based on the mechanical error analysis, tolerance optimizations are applied to the examples.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009785211763
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