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521.
Fokko J. Bosker†‡ Joost H. A. Folgering‡ Anatoliy V. Gladkevich† Anne Schmidt§ Marieke C. G. van der Hart†‡ Jeffrey Sprouse§ Johan A. den Boer† Ben H. C. Westerink‡ Thomas I. F. H. Cremers†‡ 《Journal of neurochemistry》2009,108(5):1126-1135
Both microdialysis and electrophysiology were used to investigate whether another serotonin (5‐HT) receptor subtype next to the 5‐HT1A autoreceptor is involved in the acute effects of a selective serotonin reuptake inhibitor on 5‐HT neuronal activity. On the basis of a previous study, we decided to investigate the involvement of the 5‐HT7 receptors. Experiments were performed with the specific 5‐HT7 antagonist SB 258741 and the putative 5‐HT7 agonist AS19. In this study WAY 100.635 was used to block 5‐HT1A receptors. Systemic administration of SB 258741 significantly reduced the effect of combined selective serotonin reuptake inhibitor and WAY 100.635 administration on extracellular 5‐HT in the ventral hippocampus as well as 5‐HT neuronal firing in the dorsal raphe nucleus. In the microdialysis study, co‐administration of AS19 and WAY 100.635 showed a biphasic effect on extracellular 5‐HT in ventral hippocampus, hinting at opposed 5‐HT7 receptor mediated effects. In the electrophysiological experiments, systemic administration of AS19 alone displayed a bell‐shaped dose–effect curve: moderately increasing 5‐HT neuronal firing at lower doses while decreasing it at higher doses. SB 258741 was capable of blocking the effect of AS19 at a low dose. This is consistent with the pharmacological profile of AS19, displaying high affinity for 5‐HT7 receptors and moderate affinity for 5‐HT1A receptors. The data are in support of an excitatory effect of selective serotonin reuptake inhibitors on 5‐HT neuronal activity mediated by 5‐HT7 receptors. It can be speculated, that the restoration of 5‐HT neuronal firing upon chronic antidepressant treatment, which is generally attributed to desensitization of 5‐HT1A receptors alone, in fact results from a shift in balance between 5‐HT1A and 5‐HT7 receptor function. 相似文献
522.
Bokhoven M Stephen SL Knight S Gevers EF Robinson IC Takeuchi Y Collins MK 《Journal of virology》2009,83(1):283-294
523.
Emmani B.M. Nascimento Marieke Snel Bruno Guigas Gerard C.M. van der Zon Jan Kriek J. Antonie Maassen Ingrid M. Jazet Michaela Diamant D. Margriet Ouwens 《Cellular signalling》2010,22(6):961-967
Type 2 diabetes is associated with alterations in protein kinase B (PKB/Akt) and mammalian target of rapamycin complex 1 (mTORC1) signalling. The proline-rich Akt substrate of 40-kDa (PRAS40) is a component of mTORC1, which has a regulatory function at the intersection of the PKB/Akt and mTORC1 signalling pathway. Phosphorylation of PRAS40-Thr246 by PKB/Akt, and PRAS40-Ser183 and PRAS40-Ser221 by mTORC1 results in dissociation from mTORC1, and its binding to 14-3-3 proteins. Although all phosphorylation sites within PRAS40 have been implicated in 14-3-3 binding, substitution of Thr246 by Ala alone is sufficient to abolish 14-3-3 binding under conditions of intact mTORC1 signalling. This suggests that phosphorylation of PRAS40-Thr246 may facilitate efficient phosphorylation of PRAS40 on its mTORC1-dependent sites. In the present study, we investigated the mechanism of PRAS40-Ser183 phosphorylation in response to insulin. Insulin promoted PRAS40-Ser183 phosphorylation after a euglycaemic–hyperinsulinaemic clamp in human skeletal muscle. The insulin-induced PRAS40-Ser183 phosphorylation was further evidenced in vivo in rat skeletal and cardiac muscle, and in vitro in A14 fibroblasts, 3T3L1 adipocytes and L6 myotubes. Inhibition of mTORC1 by rapamycin or amino acid deprivation partially abrogated insulin-mediated PRAS40-Ser183 phosphorylation in cultured cell lines. However, lowering insulin-induced PRAS40-Thr246 phosphorylation using wortmannin or palmitate in cell lines, or by feeding rats a high-fat diet, completely abolished insulin-mediated PRAS40-Ser183 phosphorylation. In addition, replacement of Thr246 by Ala reduced insulin-mediated PRAS40-Ser183 phosphorylation. We conclude that PRAS40-Ser183 is a component of insulin action, and that efficient phosphorylation of PRAS40-Ser183 by mTORC1 requires the phosphorylation of PRAS40-Thr246 by PKB/Akt. 相似文献
524.
Oligonucleotide-mediated gene targeting is emerging as a powerful tool for the introduction of subtle gene modifications in mouse embryonic stem (ES) cells and the generation of mutant mice. However, its efficacy is strongly suppressed by DNA mismatch repair (MMR). Here we report a simple and rapid procedure for the generation of mouse mutants using transient down regulation of the central MMR protein MSH2 by RNA interference. We demonstrate that under this condition, unmodified single-stranded DNA oligonucleotides can be used to substitute single or several nucleotides. In particular, simultaneous substitution of four adjacent nucleotides was highly efficient, providing the opportunity to substitute virtually any given codon. We have used this method to create a codon substitution (N750F) in the Rb gene of mouse ES cells and show that the oligonucleotide-modified Rb allele can be transmitted through the germ line of mice. 相似文献
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527.
Werner L. Vos Marieke Schor Artur Baumgaertner D. Peter Tieleman Marcus A. Hemminga 《European biophysics journal : EBJ》2010,39(2):229-239
Computer simulations were carried out of a number of AEDANS-labeled single cysteine mutants of a small reference membrane
protein, M13 major coat protein, covering 60% of its primary sequence. M13 major coat protein is a single membrane-spanning,
α-helical membrane protein with a relatively large water-exposed region in the N-terminus. In 10-ns molecular dynamics simulations,
we analyze the behavior of the AEDANS label and the native tryptophan, which were used as acceptor and donor in previous FRET
experiments. The results indicate that AEDANS is a relatively inert environmental probe that can move unhindered through the
lipid membrane when attached to a membrane protein. 相似文献
528.
Bogdan Petre Philip Kragel Lauren Y. Atlas Stephan Geuter Marieke Jepma Leonie Koban Anjali Krishnan Marina Lopez-Sola Elizabeth A. Reynolds Losin Mathieu Roy Choong-Wan Woo Tor D. Wager 《PLoS biology》2022,20(5)
Information is coded in the brain at multiple anatomical scales: locally, distributed across regions and networks, and globally. For pain, the scale of representation has not been formally tested, and quantitative comparisons of pain representations across regions and networks are lacking. In this multistudy analysis of 376 participants across 11 studies, we compared multivariate predictive models to investigate the spatial scale and location of evoked heat pain intensity representation. We compared models based on (a) a single most pain-predictive region or resting-state network; (b) pain-associated cortical–subcortical systems developed from prior literature (“multisystem models”); and (c) a model spanning the full brain. We estimated model accuracy using leave-one-study-out cross-validation (CV; 7 studies) and subsequently validated in 4 independent holdout studies. All spatial scales conveyed information about pain intensity, but distributed, multisystem models predicted pain 20% more accurately than any individual region or network and were more generalizable to multimodal pain (thermal, visceral, and mechanical) and specific to pain. Full brain models showed no predictive advantage over multisystem models. These findings show that multiple cortical and subcortical systems are needed to decode pain intensity, especially heat pain, and that representation of pain experience may not be circumscribed by any elementary region or canonical network. Finally, the learner generalization methods we employ provide a blueprint for evaluating the spatial scale of information in other domains.Is pain represented by a single brain area or network, spanning multiple systems or distributed throughout the brain? fMRI brain decoding in a large multi-study dataset shows that multiple cortical and subcortical systems are needed to decode pain intensity; the approach is novel and can characterize scale of representation across diverse brain processes. 相似文献
529.
Margaret A. Scull William M. Schneider Brenna R. Flatley Robert Hayden Canny Fung Christopher T. Jones Marieke van de Belt Fran?ois Penin Charles M. Rice 《PLoS pathogens》2015,11(11)
The hepatitis C virus (HCV) p7 protein is required for infectious virus production via its role in assembly and ion channel activity. Although NMR structures of p7 have been reported, the location of secondary structural elements and orientation of the p7 transmembrane domains differ among models. Furthermore, the p7 structure-function relationship remains unclear. Here, extensive mutagenesis, coupled with infectious virus production phenotyping and molecular modeling, demonstrates that the N-terminal helical region plays a previously underappreciated yet critical functional role, especially with respect to E2/p7 cleavage efficiency. Interrogation of specific N-terminal helix residues identified as having p7-specific defects and predicted to point toward the channel pore, in a context of independent E2/p7 cleavage, further supports p7 as a structurally plastic, minimalist ion channel. Together, our findings indicate that the p7 N-terminal helical region is critical for E2/p7 processing, protein-protein interactions, ion channel activity, and infectious HCV production. 相似文献
530.
Martijn Dorenbosch Marieke C. Verweij Ivan Nagelkerken Narriman Jiddawi Gerard van der Velde 《Environmental Biology of Fishes》2004,70(3):203-209
We studied daily tidal movements of tagged juvenile Lutjanus fulviflamma and Lutjanus ehrenbergii between two adjacent habitats, a subtidal channel and shallow tidal notches in the fossil reef terrace, in a shallow marine bay on Zanzibar Island (Tanzania). Due to a large tidal range, the notches were dry at low-tide and were only accessible to the snappers at high-tide. Of the resighted individuals, 48% showed clear movement between the two habitats, orientated in a direction perpendicular to the tidal currents. Individuals resighted more than once showed site fidelity, indicating homing in both the channel and the notches. We suggest that a significant part of this population of juvenile snappers may move from a low-tide resting habitat to a high-tide resting habitat during the daytime, perhaps to avoid predation by larger predators that may enter the channel at high-tide. 相似文献