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- Abbas, Abdul-Karim, 1959, et al.
(författare)
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Persistent LTP without triggered protein synthesis.
- 2009
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Ingår i: Neuroscience research. - : Elsevier BV. - 0168-0102. ; 63:1, s. 59-65
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Tidskriftsartikel (refereegranskat)abstract
- Protein synthesis is believed to be involved in stabilizing synaptic plasticity. Effects lasting longer than about 2-3h are considered to require synthesis of new proteins, implying a functional separation between early (E) and late (L) components. However, the issue of constitutive vs. new protein synthesis is still unclear, especially in young animals. Here, we examined the effects of two protein synthesis inhibitors, anisomycin and emetine, on long-term-potentiation (LTP) in CA1 area of hippocampal slices from 12- to 20-day-old rats. Either drug was applied from -30 min to +30 min with respect to LTP induction, a time window previously reported to be critical. However, the LTP remained stable under the entire recording period of 4h (anisomycin), or 8h (emetine). Proper preparation of emetine solution was evidenced by the fact that, in separate experiments, prolonged treatment with emetine gradually blocked baseline responses. Although no corresponding effect was observed with anisomycin, the drug was judged to be potent by its ability to inhibit yeast growth. The ability of anisomycin to inhibit protein synthesis was further confirmed by radiolabeling experiments assessing the degree of leucine incorporation. Our data suggest that LTP up to at least 8h is not dependent on triggered protein synthesis but can be attained by utilizing proteins already available at induction time.
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| 4. |
- Li, Rui, 1975, et al.
(författare)
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Characterization of NMDA induced depression in rat hippocampus: involvement of AMPA and NMDA receptors.
- 2004
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Ingår i: Neuroscience letters. - : Elsevier BV. - 0304-3940. ; 357:2, s. 87-90
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Tidskriftsartikel (refereegranskat)abstract
- The involvement of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) vs. N-methyl-d-aspartate (NMDA) receptor mediated changes in NMDA-induced long-term depression (LTD) was assessed by monitoring isolated AMPA, isolated NMDA and composite field excitatory postsynaptic potentials (EPSP) in the CA1 area of acute rat hippocampal slices. Application of NMDA (20-50 microM) for 3-5 min led to LTD of both AMPA and NMDA receptor mediated EPSPs with near equal changes of the responses. However, AMPA EPSPs displayed a faster initial recovery than NMDA EPSPs. In addition, during the first 15-25 min after NMDA application, there was a superimposed potentiation of the later, but not early, part of AMPA EPSPs, implying a prolongation of waveform. In contrast, the NMDA EPSP waveform remained unaltered throughout the experiments. While it has been maintained that NMDA-induced depression is equivalent to stimulus-induced LTD, our results reveal additional complexity, suggesting a multitude of changes, most likely at the postsynaptic receptor level.
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- Chen, Tian-Jiao, et al.
(författare)
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Genetic and environmental influences on the relationship between ADHD symptoms and internalizing problems : A Chinese twin study
- 2016
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Ingår i: American Journal of Medical Genetics Part B. - Hoboken, USA : John Wiley & Sons. - 1552-4841 .- 1552-485X. ; 171:7, s. 931-937
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Tidskriftsartikel (refereegranskat)abstract
- Several twin studies have investigated the overlap between attention deficit hyperactivity disorder (ADHD) and externalizing problems; however, limited information is known regarding the genetic and environmental contribution to the overlap between ADHD and internalizing problems. This study examined the genetic and environmental influences on the variation in and covariation between ADHD symptoms and internalizing problems by using the Child Behavior Checklist (CBCL). We investigated 1,316 child and adolescent twins, including 780 monozygotic twins and 536 dizygotic twins, aged 6 years to 18 years from the Chinese Child and Adolescent Twin Registry. ADHD symptoms and internalizing problems were quantified through parent rating by using the Attention Problems Scale and other three scales, which include Anxious/Depressed, Withdrawn, and Somatic Complaints of CBCL. Genetic and environmental susceptibilities common to ADHD symptoms and internalizing problems were examined through bivariate twin modeling. Results showed that genetic factors substantially influenced the ADHD symptoms with a heritability of 72%. Modest genetic influences and substantial shared environmental influences (20-77%) were observed in the three internalizing problem scales. Common genetic and shared environmental influences were essential for the overlap between ADHD and the three internalizing problems respectively. Approximately one-fifth of the genetic variance of ADHD symptoms was shared with anxiety/depression. In conclusion, substantial genetic and shared environmental influences on ADHD symptoms and internalizing problems were observed in Chinese children and adolescents. Our finding supports a common etiology between ADHD and internalizing problems. This finding can also help explain the co-existence of these behavior problems. © 2015 Wiley Periodicals, Inc.
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- Garcia-Salcedo, Raúl, et al.
(författare)
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Glucose de-repression by yeast AMP-activated protein kinase SNF1 is controlled via at least two independent steps
- 2014
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Ingår i: Febs Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 281:7, s. 1901-1917
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Tidskriftsartikel (refereegranskat)abstract
- The AMP-activated protein kinase, AMPK, controls energy homeostasis in eukaryotic cells but little is known about the mechanisms governing the dynamics of its activation/deactivation. The yeast AMPK, SNF1, is activated in response to glucose depletion and mediates glucose de-repression by inactivating the transcriptional repressor Mig1. Here we show that overexpression of the Snf1-activating kinase Sak1 results, in the presence of glucose, in constitutive Snf1 activation without alleviating glucose repression. Co-overexpression of the regulatory subunit Reg1 of the Glc-Reg1 phosphatase complex partly restores glucose regulation of Snf1. We generated a set of 24 kinetic mathematical models based on dynamic data of Snf1 pathway activation and deactivation. The models that reproduced our experimental observations best featured (a) glucose regulation of both Snf1 phosphorylation and dephosphorylation, (b) determination of the Mig1 phosphorylation status in the absence of glucose by Snf1 activity only and (c) a regulatory step directing active Snf1 to Mig1 under glucose limitation. Hence it appears that glucose de-repression via Snf1-Mig1 is regulated by glucose via at least two independent steps: the control of activation of the Snf1 kinase and directing active Snf1 to inactivating its target Mig1.
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| 8. |
- Schmidt, G. W., et al.
(författare)
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Mig1 localization exhibits biphasic behavior which is controlled by both metabolic and regulatory roles of the sugar kinases
- 2020
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Ingår i: Molecular Genetics and Genomics. - : Springer Science and Business Media LLC. - 1617-4615 .- 1617-4623. ; 295, s. 1489-1500
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Tidskriftsartikel (refereegranskat)abstract
- Glucose, fructose and mannose are the preferred carbon/energy sources for the yeastSaccharomyces cerevisiae. Absence of preferred energy sources activates glucose derepression, which is regulated by the kinase Snf1. Snf1 phosphorylates the transcriptional repressor Mig1, which results in its exit from the nucleus and subsequent derepression of genes. In contrast, Snf1 is inactive when preferred carbon sources are available, which leads to dephosphorylation of Mig1 and its translocation to the nucleus where Mig1 acts as a transcription repressor. Here we revisit the role of the three hexose kinases, Hxk1, Hxk2 and Glk1, in glucose de/repression. We demonstrate that all three sugar kinases initially affect Mig1 nuclear localization upon addition of glucose, fructose and mannose. This initial import of Mig1 into the nucleus was temporary; for continuous nucleocytoplasmic shuttling of Mig1, Hxk2 is required in the presence of glucose and mannose and in the presence of fructose Hxk2 or Hxk1 is required. Our data suggest that Mig1 import following exposure to preferred energy sources is controlled via two different pathways, where (1) the initial import is regulated by signals derived from metabolism and (2) continuous shuttling is regulated by the Hxk2 and Hxk1 proteins. Mig1 nucleocytoplasmic shuttling appears to be important for the maintenance of the repressed state in which Hxk1/2 seems to play an essential role.
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| 9. |
- Tian, Ye, 1975, et al.
(författare)
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Gis4, a new component of the ion homeostasis system in the yeast Saccharomyces cerevisiae
- 2006
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Ingår i: Eukaryotic Cell. - 1535-9778 .- 1535-9786. ; 5:10, s. 1611-1621
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Tidskriftsartikel (refereegranskat)abstract
- Gis4 is a new component of the system required for acquisition of salt tolerance in Saccharomyces cerevisiae. The gis4 Delta mutant is sensitive to Na+ and Li+ ions but not to osmotic stress. Genetic evidence suggests that Gis4 mediates its function in salt tolerance, at least partly, together with the Snf1 protein kinase and in parallel with the calcineurin protein phosphatase. When exposed to salt stress, mutants lacking gis4 Delta display a defect in maintaining low intracellular levels of Na+ and Li+ ions and exporting those ions from the cell. This defect is due to diminished expression of the ENA1 gene, which encodes the Na+ and Li+ export pump. The protein sequence of Gis4 is poorly conserved and does not reveal any hints to its molecular function. Gis4 is enriched at the cell surface, probably due to C-terminal farnesylation. The CAAX box at the C terminus is required for cell surface localization but does not seem to be strictly essential for the function of Gis4 in salt tolerance. Gis4 and Snf1 seem to share functions in the control of ion homeostasis and ENA1 expression but not in glucose derepression, the best known role of Snf1. Together with additional evidence that links Gis4 genetically and physically to Snf1, it appears that Gis4 may function in a pathway in which Snf1 plays a specific role in controlling ion homeostasis. Hence, it appears that the conserved Snf1 kinase plays roles in different pathways controlling nutrient as well as stress response.
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| 10. |
- Tian, Ye, 1975, et al.
(författare)
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The mammalian AMP-activated protein kinase complex mediates glucose regulation of gene expression in the yeast Saccharomyces cerevisiae
- 2014
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Ingår i: FEBS Letters. - : Wiley. - 1873-3468 .- 0014-5793. ; 588:12, s. 2070-2077
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Tidskriftsartikel (refereegranskat)abstract
- The AMP-activated protein kinase (AMPK) controls energy homeostasis in eukaryotic cells. Here we expressed hetero-trimeric mammalian AMPK complexes in a Saccharomyces cerevisiae mutant lacking all five genes encoding yeast AMPK/SNF1 components. Certain mammalian complexes complemented the growth defect of the yeast mutant on non-fermentable carbon sources. Phosphorylation of the AMPK alpha 1-subunit was glucose-regulated, albeit not by the G1c7-Reg1/2 phosphatase, which performs this function on yeast AMPK/SNFl. AMPK could take over SNF1 function in glucose derepression. While indirectly acting anti-diabetic drugs had no effect on AMPK in yeast, compound 991 stimulated alpha 1-subunit phosphorylation. Our results demonstrate a remarkable functional conservation of AMPK and that glucose regulation of AMPK may not be mediated by regulatory features of a specific phosphatase. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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