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31.
Background
The relationships between facial mimicry and subsequent psychological processes remain unclear. We hypothesized that the congruent facial muscle activity would elicit emotional experiences and that the experienced emotion would induce emotion recognition.Methodology/Principal Findings
To test this hypothesis, we re-analyzed data collected in two previous studies. We recorded facial electromyography (EMG) from the corrugator supercilii and zygomatic major and obtained ratings on scales of valence and arousal for experienced emotions (Study 1) and for experienced and recognized emotions (Study 2) while participants viewed dynamic and static facial expressions of negative and positive emotions. Path analyses showed that the facial EMG activity consistently predicted the valence ratings for the emotions experienced in response to dynamic facial expressions. The experienced valence ratings in turn predicted the recognized valence ratings in Study 2.Conclusion
These results suggest that facial mimicry influences the sharing and recognition of emotional valence in response to others'' dynamic facial expressions. 相似文献32.
Ayako Kitano Takeo Shimasaki Yuri Chikano Mitsutoshi Nakada Mayumi Hirose Tomomi Higashi Yasuhito Ishigaki Yoshio Endo Takahisa Takino Hiroshi Sato Yoshimichi Sai Ken-ichi Miyamoto Yoshiharu Motoo Kazuyuki Kawakami Toshinari Minamoto 《PloS one》2013,8(2)
Background and Purpose
The major obstacles to treatment of pancreatic cancer are the highly invasive capacity and resistance to chemo- and radiotherapy. Glycogen synthase kinase 3β (GSK3β) regulates multiple cellular pathways and is implicated in various diseases including cancer. Here we investigate a pathological role for GSK3β in the invasive and treatment resistant phenotype of pancreatic cancer.Methods
Pancreatic cancer cells were examined for GSK3β expression, phosphorylation and activity using Western blotting and in vitro kinase assay. The effects of GSK3β inhibition on cancer cell survival, proliferation, invasive ability and susceptibility to gemcitabine and radiation were examined following treatment with a pharmacological inhibitor or by RNA interference. Effects of GSK3β inhibition on cancer cell xenografts were also examined.Results
Pancreatic cancer cells showed higher expression and activity of GSK3β than non-neoplastic cells, which were associated with changes in its differential phosphorylation. Inhibition of GSK3β significantly reduced the proliferation and survival of cancer cells, sensitized them to gemcitabine and ionizing radiation, and attenuated their migration and invasion. These effects were associated with decreases in cyclin D1 expression and Rb phosphorylation. Inhibition of GSK3β also altered the subcellular localization of Rac1 and F-actin and the cellular microarchitecture, including lamellipodia. Coincident with these changes were the reduced secretion of matrix metalloproteinase-2 (MMP-2) and decreased phosphorylation of focal adhesion kinase (FAK). The effects of GSK3β inhibition on tumor invasion, susceptibility to gemcitabine, MMP-2 expression and FAK phosphorylation were observed in tumor xenografts.Conclusion
The targeting of GSK3β represents an effective strategy to overcome the dual challenges of invasiveness and treatment resistance in pancreatic cancer. 相似文献33.
Ren Matsuba Minako Imamura Yasushi Tanaka Minoru Iwata Hiroshi Hirose Kohei Kaku Hiroshi Maegawa Hirotaka Watada Kazuyuki Tobe Atsunori Kashiwagi Ryuzo Kawamori Shiro Maeda 《PloS one》2016,11(4)
AimWe performed a replication study in a Japanese population to evaluate the association between type 2 diabetes and six susceptibility loci (TMEM154, SSR1, FAF1, POU5F1, ARL15, and MPHOSPH9) originally identified by a transethnic meta-analysis of genome-wide association studies (GWAS) in 2014.MethodsWe genotyped 7,620 Japanese participants (5,817 type 2 diabetes patients and 1,803 controls) for each of the single nucleotide polymorphisms (SNPs) using a multiplex polymerase chain reaction invader assay. The association of each SNP locus with the disease was evaluated using logistic regression analysis.ResultsOf the six SNPs examined in this study, four (rs6813195 near TMEM154, rs17106184 in FAF1, rs3130501 in POU5F1 and rs4275659 near MPHOSPH9) had the same direction of effect as in the original reports, but two (rs9505118 in SSR1 and rs702634 in ARL15) had the opposite direction of effect. Among these loci, rs3130501 and rs4275659 were nominally associated with type 2 diabetes (rs3130501; p = 0.017, odds ratio [OR] = 1.113, 95% confidence interval [CI] 1.019–1.215, rs4275659; p = 0.012, OR = 1.127, 95% CI 1.026–1.238, adjusted for sex, age and body mass index), but we did not observe a significant association with type 2 diabetes for any of the six evaluated SNP loci in our Japanese population.ConclusionsOur results indicate that effects of the six SNP loci identified in the transethnic GWAS meta-analysis are not major among the Japanese, although SNPs in POU5F1 and MPHOSPH9 loci may have some effect on susceptibility to type 2 diabetes in this population. 相似文献
34.
Keisuke Iida Yamato Tsushima Yue Ma Shadi Sedghi Masoud Mai Sakuma Tomomi Yokoyama Wataru Yoshida Kazunori Ikebukuro Kazuo Nagasawa 《Bioorganic & medicinal chemistry》2019,27(8):1742-1746
G-quadruplexes (G4s) are non-B DNA structures present in guanine-rich regions of gene regulatory areas, promoters and CpG islands, but their occurrence and functions remain incompletely understood. Thus, methodology to identify G4 sequences is needed. Here, we describe the synthesis of a novel cyclic hepta-oxazole compound, L1Bio-7OTD (1), bearing a biotin affinity-tag as a tool to pull down G4 structures from mixtures of G4-forming and non G4-forming DNA sequences. We confirmed that it could pull down G4s associated with telomeres, bcl-2 gene, and c-kit gene. 相似文献
35.
Shun Nanjyo Kenji Ohgane Hiromasa Yoshioka Makoto Makishima Yuichi Hashimoto Tomomi Noguchi-Yachide 《Bioorganic & medicinal chemistry》2019,27(10):1952-1961
Selective estrogen receptor (ER) down-regulators (SERDs) are pure ER antagonists that also induce ER degradation upon binding to the receptor. Although SERDs have been developed for the treatment of ER-positive breast cancers for nearly a decade, their precise mechanism(s) of action and structure-activity relationship are still unclear. Generally, Western blotting is used to examine the effects of SERDs on ER protein levels, but the methodology is low-throughput and not quantitative. Here, we describe a quantitative, high-throughput, luciferase-based assay for the evaluation of SERDs activity. For this purpose, we established stable recombinant HEK-293 cell lines expressing ERα fused with emerald luciferase. We also designed and synthesized new diphenylmethane derivatives as candidate SERDs, and evaluated their SERDs activity using the developed system in order to examine their structure-activity relationship, taking EC50 as a measure of potency, and Emax as a measure of efficacy. 相似文献
36.
Brown NM Martin SM Maurice N Kuwana T Knudson CM 《The Journal of biological chemistry》2007,282(4):2144-2155
Cytokine deprivation has been classically used to study molecular processes of apoptosis. Following interleukin (IL)-3 withdrawal in FL5.12 cells, Bax undergoes a conformational change that results in its mitochondria targeting, cytochrome c release, activation of caspase-9, and apoptosis. Cells overexpressing Casp9DN (dominant negative caspase-9) or treated with the caspase inhibitor Q-VD-OPh increased viability but failed to increase clonogenic survival. We find that caspase-inhibited cells had a significant fraction of viable cells (herein termed "rescued" cells) that failed to initiate cell division after IL-3 add back. The "rescued" cells had reduced mitochondrial potential, stained for active Bax, and had reduced staining with dihydroethidium, an agent sensitive to superoxide levels. Readdition of IL-3 after deprivation demonstrated that Bax activation was reversed, whereas altered 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide and dihydroethidium staining persisted for days. Furthermore, the "rescued" cells were resistant to rotenone, an inhibitor of mitochondrial respiration. The cells were highly sensitive to 2-deoxyglucose, an inhibitor of glycolysis and proposed anti-cancer agent. We conclude that the inhibition of caspase-9 allows cells to retain viability, but cells have prolonged mitochondrial dysfunction and enter a unique nondividing state that shares some properties with malignant cells. 相似文献
37.
Yamato M Shiba T Yoshida M Ide T Seri N Kudou W Kinugawa S Tsutsui H 《The FEBS journal》2007,274(15):3855-3863
Plasma concentrations of free fatty acids are increased in metabolic syndrome, and the increased fatty acids may cause cellular damage via the induction of oxidative stress. The present study was designed to determine whether the increase in fatty acids can modify the free sulfhydryl group in position 34 of albumin (Cys34) and enhance the redox-cycling activity of the copper-albumin complex in high-fat diet-induced obese mice. The mice were fed with commercial normal diet or high-fat diet and water ad libitum for 3 months. The high-fat diet-fed mice developed obesity, hyperlipemia, and hyperglycemia. The plasma fatty acid/albumin ratio also significantly increased in high-fat diet-fed mice. The increased fatty acid/albumin ratio was associated with conformational changes in albumin and the oxidation of sulfhydryl groups. Moreover, an ascorbic acid radical, an index of redox-cycling activity of the copper-albumin complex, was detected only in the plasma from obese mice, whereas the plasma concentrations of ascorbic acid were not altered. Plasma thiobarbituric acid reactive substances were significantly increased in the high-fat diet group. These results indicate that the increased plasma fatty acids in the high-fat diet group resulted in the activated redox cycling of the copper-albumin complex and excessive lipid peroxidation. 相似文献
38.
Background and AimsMangrove plants are mostly found in tropical and sub-tropical tidal flats, and their limited distribution may be related to their responses to growth temperatures. However, the mechanisms underlying these responses have not been clarified. Here, we measured the dependencies of the growth parameters and respiration rates of leaves and roots on growth temperatures in typical mangrove species.MethodsWe grew two typical species of Indo-Pacific mangroves, Bruguiera gymnorrhiza and Rhizophora stylosa, at four different temperatures (15, 20, 25 and 30 °C) by irrigating with fresh water containing nutrients, and we measured growth parameters, chemical composition, and leaf and root O2 respiration rates. We then estimated the construction costs of leaves and roots and the respiration rates required for maintenance and growth.Key ResultsThe relative growth rates of both species increased with growth temperature due to changes in physiological parameters such as net assimilation rate and respiration rate rather than to changes in structural parameters such as leaf area ratio. Both species required a threshold temperature for growth (12.2 °C in B. gymnorrhiza and 18.1 °C in R. stylosa). At the low growth temperature, root nitrogen uptake rate was lower in R. stylosa than in B. gymnorrhiza, leading to a slower growth rate in R. stylosa. This indicates that R. stylosa is more sensitive than B. gymnorrhiza to low temperature.ConclusionsOur results suggest that the mangrove species require a certain warm temperature to ensure respiration rates sufficient for maintenance and growth, particularly in roots. The underground temperature probably limits their growth under the low-temperature condition. The lower sensitivity of B. gymnorrhiza to low temperature shows its potential to adapt to a wider habitat temperature range than R. stylosa. These growth and respiratory features may explain the distribution patterns of the two mangrove species. 相似文献
39.
Downregulation of the voltage-dependent calcium channel (VDCC) beta-subunit mRNAs in pancreatic islets of type 2 diabetic rats 总被引:1,自引:0,他引:1
Iwashima Y Abiko A Ushikubi F Hata A Kaku K Sano H Eto M 《Biochemical and biophysical research communications》2001,280(3):923-932
The present study was undertaken to determine whether altered expression of the VDCC beta-subunits in pancreatic beta-cells could play a role in the changes in beta-cell sensitivity to glucose that occur with diabetes. Application of competitive RT-PCR procedure revealed that in normal Wistar rats, LETO and prediabetic OLETF rats, the beta(2)-subunit mRNA levels were 60-200-fold greater than the levels for the beta(3)-subunit. These findings suggest that the beta(2)-subunit as well as the beta-cell type VDCC1 alpha(1)-subunit may be the predominant form of the VDCC expressed in pancreatic beta-cells. The levels of mRNA encoding the beta-subunits and the beta-cell type alpha(1)-subunit as well as insulin were significantly reduced in diabetic rats. Perfusion experiments revealed that diabetic rats showed the higher basal insulin secretion and profoundly impaired insulin secretory responses to glucose compared with non-diabetic rats. Alternatively, impaired insulin secretory responses to glucose in high dose glucose-infused rats were recovered partly with the elevation of mRNA levels of the VDCC beta(2)- and beta(3)-subunits as well as the alpha(1)-subunit by the treatment with diazoxide. Thus, considering the possibility that the most striking effect of the VDCC alpha(1) beta-subunit coexpression in pancreatic beta-cells might occur on activation kinetics like the skeletal muscle, the impairment of further activation of the VDCCs to acute glucose challenge caused by the reduced expressions of the alpha(1) beta-subunits mRNAs in type 2 diabetic animals might be at least partly associated with the alterations in beta-cell sensitivity to glucose. 相似文献
40.
In myocardial cells (MCs), endothelin-1 (ET-1) exerts various effects such as hypertrophy, and causes cellular injury. Long-term treatment with an endothelin-A (ETA) receptor antagonist improves the survival of rats with heart failure, suggesting that myocardial endothelin system contributes to the progression of heart failure. p38 mitogen-activated kinase (MAPK) is a member of the MAPK family and activated by several forms of environmental stresses. We show here the effect of ET-1 on p38 MAPK activation and the role of ET-1-activated p38 MAPK on morphological changes in MCs. ET-1-stimulated p38 MAPK phosphorylation was detectable within 2 min and maximal at 5 min and was concentration dependent. The maximum effect was obtained at 10 nM. An ETA receptor antagonist, BQ-123, but not an endothelin-B receptor antagonist, BQ-788, inhibited these reactions. A p38 MAPK inhibitor, SB203580, failed to inhibit the morphological changes associated with ET-1-induced myocardial cell hypertrophy. These results indicate that p38 MAPK is activated by ET-1 but does not contribute to the development of ET-1-induced myocardial cell hypertrophy. 相似文献