The ERM-Based Self-Adaptive Agent Model

2011 ◽  
Vol 341-342 ◽  
pp. 494-498
Author(s):  
Guo Rui Huang ◽  
Fei Liu ◽  
Xu Cheng ◽  
Chao Fan Qiu
Keyword(s):  
External Environment ◽  
Dynamic Environment ◽  
Regulation Mechanism ◽  
Endocrine Regulation ◽  
Internal Environment ◽  
Agent Model ◽  
Adaptive Agent ◽  
Self Adaptive

Inspired by the mechanism of behaviour control of organisms, this paper attempts to build an underlying model of their physical and psychological activities in a dynamic environment with the purpose to achieve the self-adaption of robot behaviour in a complex, changeable environment. It designs an internal environment and emotion- & motive-generating models based upon the endocrine regulation mechanism (ERM). The robot relies upon the dynamic stability of the internal environment to accomplish its self-adaption to the external environment. The emotion-generating model is applied to in vivo and in vitro contingencies of various kinds; by releasing hormones, the emotion generated influences the robot’s in vivo and in vitro perception, and then its behavioural choice. The motive-generating model is employed to maintain the relative stability of the internal environment, and the motive generated leads to the corresponding behavioural choice directly. The experimental results prove the effectiveness of this ERM-based self-adaptive robot model.

scholarly journals Aberrantly high activation of a FoxM1–STMN1 axis contributes to progression and tumorigenesis in FoxM1-driven cancers

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Jun Liu ◽  
Jipeng Li ◽  
Ke Wang ◽  
Haiming Liu ◽  
Jianyong Sun ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Poor Prognosis ◽  
Soft Agar ◽  
Transcriptional Level ◽  
Regulation Mechanism ◽  
Strong Positive Correlation ◽  
Cell Viability Assay ◽  
High Level

AbstractFork-head box protein M1 (FoxM1) is a transcriptional factor which plays critical roles in cancer development and progression. However, the general regulatory mechanism of FoxM1 is still limited. STMN1 is a microtubule-binding protein which can inhibit the assembly of microtubule dimer or promote depolymerization of microtubules. It was reported as a major responsive factor of paclitaxel resistance for clinical chemotherapy of tumor patients. But the function of abnormally high level of STMN1 and its regulation mechanism in cancer cells remain unclear. In this study, we used public database and tissue microarrays to analyze the expression pattern of FoxM1 and STMN1 and found a strong positive correlation between FoxM1 and STMN1 in multiple types of cancer. Lentivirus-mediated FoxM1/STMN1-knockdown cell lines were established to study the function of FoxM1/STMN1 by performing cell viability assay, plate clone formation assay, soft agar assay in vitro and xenograft mouse model in vivo. Our results showed that FoxM1 promotes cell proliferation by upregulating STMN1. Further ChIP assay showed that FoxM1 upregulates STMN1 in a transcriptional level. Prognostic analysis showed that a high level of FoxM1 and STMN1 is related to poor prognosis in solid tumors. Moreover, a high co-expression of FoxM1 and STMN1 has a more significant correlation with poor prognosis. Our findings suggest that a general FoxM1-STMN1 axis contributes to cell proliferation and tumorigenesis in hepatocellular carcinoma, gastric cancer and colorectal cancer. The combination of FoxM1 and STMN1 can be a more precise biomarker for prognostic prediction.

STRETCHABLE Lab-on-Chip Device With Impedance Spectroscopy Capability for Mammalian Cell Studies

2016 ◽  
Author(s):  
Xudong Zhang ◽  
Anis Nurashikin Nordin ◽  
Fang Li ◽  
Ioana Voiculescu
Keyword(s):  
Impedance Spectroscopy ◽  
Mammalian Cells ◽  
Dynamic Environment ◽  
Cyclic Strain ◽  
Cyclic Stretch ◽  
Mechanical Stimuli ◽  
Aortic Endothelial Cells ◽  
Lab On Chip

This paper presents the fabrication and testing of electric cell-substrate impedance spectroscopy (ECIS) electrodes on a stretchable membrane. This is the first time when ECIS electrodes were fabricated on a stretchable substrate and ECIS measurements on mammalian cells exposed to cyclic strain of 10% were successfully demonstrated. A chemical was used to form strong chemical bond between gold electrodes of ECIS sensor and polymer membrane, which enable the electrodes keep good conductive ability during cyclic stretch. The stretchable membrane integrated with the ECIS sensor can simulate and replicate the dynamic environment of organism and enable the analysis of the cells activity involved in cells attachment and proliferation in vitro. Bovine aortic endothelial cells (BAEC) were used to evaluate the endothelial function influenced by mechanical stimuli in this research because they undergo in vivo cyclic physiologic elongation produced by the blood circulation in the arteries.

scholarly journals Regulation mechanism of ERM (ezrin/radixin/moesin) protein/plasma membrane association: possible involvement of phosphatidylinositol turnover and Rho-dependent signaling pathway.

1996 ◽  
Vol 135 (1) ◽  
pp. 37-51 ◽  
Author(s):  
M Hirao ◽  
N Sato ◽  
T Kondo ◽  
S Yonemura ◽  
M Monden ◽  
...  
Keyword(s):  
Ionic Strength ◽  
Cytoplasmic Domain ◽  
Insoluble Fraction ◽  
Regulation Mechanism ◽  
Erm Proteins ◽  
Bhk Cells ◽  
High Affinity ◽  
Binding Partners

The ERM proteins, ezrin, radixin, and moesin, are involved in the actin filament/plasma membrane interaction as cross-linkers. CD44 has been identified as one of the major membrane binding partners for ERM proteins. To examine the CD44/ERM protein interaction in vitro, we produced mouse ezrin, radixin, moesin, and the glutathione-S-transferase (GST)/CD44 cytoplasmic domain fusion protein (GST-CD44cyt) by means of recombinant baculovirus infection, and constructed an in vitro assay for the binding between ERM proteins and the cytoplasmic domain of CD44. In this system, ERM proteins bound to GST-CD44cyt with high affinity (Kd of moesin was 9.3 +/- 1.6nM) at a low ionic strength, but with low affinity at a physiological ionic strength. However, in the presence of phosphoinositides (phosphatidylinositol [PI], phosphatidylinositol 4-monophosphate [4-PIP], and phosphatidylinositol 4.5-bisphosphate [4,5-PIP2]), ERM proteins bound with a relatively high affinity to GST-CD44cyt even at a physiological ionic strength: 4,5-PIP2 showed a marked effect (Kd of moesin in the presence of 4,5-PIP2 was 9.3 +/- 4.8 nM). Next, to examine the regulation mechanism of CD44/ERM interaction in vivo, we reexamined the immunoprecipitated CD44/ERM complex from BHK cells and found that it contains Rho-GDP dissociation inhibitor (GDI), a regulator of Rho GTPase. We then evaluated the involvement of Rho in the regulation of the CD44/ERM complex formation. When recombinant ERM proteins were added and incubated with lysates of cultured BHK cells followed by centrifugation, a portion of the recombinant ERM proteins was recovered in the insoluble fraction. This binding was enhanced by GTP gamma S and markedly suppressed by C3 toxin, a specific inhibitor of Rho, indicating that the GTP form of Rho in the lysate is required for this binding. A mAb specific for the cytoplasmic domain of CD44 also markedly suppressed this binding, identifying most of the binding partners for exogenous ERM proteins in the insoluble fraction as CD44. Consistent with this binding analysis, in living BHK cells treated with C3 toxin, most insoluble ERM proteins moved to soluble compartments in the cytoplasm, leaving CD44 free from ERM. These findings indicate that Rho regulates the CD44/ERM complex formation in vivo and that the phosphatidylinositol turnover may be involved in this regulation mechanism.

scholarly journals Migfilin supports hemostasis and thrombosis through regulating platelet αIIbβ3 outside-in signaling.

Haematologica ◽  
2019 ◽  
Vol 105 (11) ◽  
pp. 2608-2618
Author(s):  
Yangfan Zhou ◽  
Mengjiao Hu ◽  
Xiaoyan Chen ◽  
Shuai Wang ◽  
Jingke Li ◽  
...  
Keyword(s):  
Signaling Molecules ◽  
Dense Granule ◽  
Regulation Mechanism ◽  
Filamin A ◽  
Characteristic Functional ◽  
Integrin Αiibβ3 ◽  
Occlusion Time ◽  
Dense Granule Secretion

Elucidating the regulation mechanism of integrin αIIbβ3 is key to understand platelet biology and thrombotic diseases. Previous in vitro studies have implicated a role of migfilin in the support of platelet αIIbβ3 activation, however, contribution of migfilin to thrombosis and hemostasis in vivo and a detailed mechanism of migfilin in platelets are not known. In this study, with migfilin deletion (migfilin-/-) mice, we report that migfilin is a pivotal positive regulator of hemostasis and thrombosis. Migfilin-/- mice showed a nearly doubled tail-bleeding time and a prolonged occlusion time in Fecl3-induced mesenteric arteriolar thrombosis. Migfilin deficiency impedes platelet thrombi formation on collagen surface and impairs platelet aggregation and dense-granule secretion. Supported by characteristic functional readings and phosphorylation status of distinctive signaling molecules in the bidirectional signaling processes of αIIbβ3, the functional defects of migfilin-/- platelets appear to be mechanistically associated with a compromised outside-in signaling, rather than inside-out signaling. A synthesized cell-permeable migfilin peptide harboring filamin A binding sequence rescued the defective function and phosphorylation of signaling molecules of migfilin-/- platelets. Finally, migfilin does not influence the binding of filamin A and β3 subunit of αIIbβ3 in resting platelets, but hampers the re-association of filamin A and β3 during the conduct of outside-in signaling, suggesting that migfilin functions through regulating the interaction dynamics of αIIbβ3 and filamin A in platelets. Our study enhances the current understanding of platelet integrin αIIbβ3-mediated outside-in signaling and proves that migfilin is an important regulator for platelet activation, hemostasis and thrombosis.

scholarly journals MNAT1 promotes proliferation and the chemo-resistance of osteosarcoma cell to cisplatin through regulating PI3K/Akt/mTOR pathway

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Chensheng Qiu ◽  
Weiliang Su ◽  
Nana Shen ◽  
Xiaoying Qi ◽  
Xiaolin Wu ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Xenograft Model ◽  
Mtor Pathway ◽  
Regulation Mechanism ◽  
Osteosarcoma Cell ◽  
Migration Ability ◽  
Mouse Xenograft Model

Abstract Background MNAT1 (menage a trois 1, MAT1), a cyclin-dependent kinase-activating kinase (CAK) complex, highly expressed in diverse cancers and was involved in cancer molecular pathogenesis. However, its deliverance profile and biological function in osteosarcoma (OS) remain unclear. Methods The expression of MNAT1 in OS was detected by western blot (WB) and immunohistochemistry (IHC). The potential relationship between MNAT1 molecular level expression and OS clinical expectations were analyzed according to tissues microarray (TMA). Proliferation potential of OS cells was evaluated in vitro based on CCK8 and OS cells colony formation assays, while OS cells transwell and in situ tissue source wound healing assays were employed to analyze the OS cells invasion and migration ability in vitro. A nude mouse xenograft model was used to detect tumor growth in vivo. In addition, ordinary bioinformatics analysis and experimental correlation verification were performed to investigate the underlying regulation mechanism of OS by MNAT1. Results In this research, we found and confirmed that MNAT1 was markedly over-expressed in OS tissue derived in situ, also, highly MNAT1 expression was closely associated with bad clinical expectations. Functional studies had shown that MNAT1 silencing could weaken the invasion, migration and proliferation of OS cells in vitro, and inhibit OS tumor growth in vivo. Mechanism study indicated that MNAT1 contributed to the progression of OS via the PI3K/Akt/mTOR pathway. We further verified that the MNAT1 was required in the regulation of OS chemo-sensitivity to cisplatin (DDP). Conclusions Taken together, the data of the present study demonstrate a novel molecular mechanism of MNAT1 involved in the formation of DDP resistance of OS cells.

scholarly journals Upregulation of the Adhesin Gene EPA1 Mediated by PDR1 in Candida glabrata Leads to Enhanced Host Colonization

mSphere ◽  
2016 ◽  
Vol 1 (2) ◽  
Author(s):  
Luis A. Vale-Silva ◽  
Beat Moeckli ◽  
Riccardo Torelli ◽  
Brunella Posteraro ◽  
Maurizio Sanguinetti ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Epithelial Cells ◽  
Candida Glabrata ◽  
Resistance Mechanism ◽  
Cell Types ◽  
Host Cells ◽  
Regulation Mechanism ◽  
Content Type

ABSTRACT Candida glabrata is an important fungal pathogen in human diseases and is also rapidly acquiring drug resistance. Drug resistance can be mediated by the transcriptional activator PDR1, and this results in the upregulation of multidrug transporters. Intriguingly, this resistance mechanism is associated in C. glabrata with increased virulence in animal models and also with increased adherence to specific host cell types. The C. glabrata adhesin gene EPA1 is a major contributor of virulence and adherence to host cells. Here, we show that EPA1 expression is controlled by PDR1 independently of subtelomeric silencing, a known EPA1 regulation mechanism. Thus, a relationship exists between PDR1, EPA1 expression, and adherence to host cells, which is critical for efficient virulence. Our results demonstrate that acquisition of drug resistance is beneficial for C. glabrata in fungus-host relationships. These findings further highlight the challenges of the therapeutic management of C. glabrata infections in human patients. Candida glabrata is the second most common Candida species causing disseminated infection, after C. albicans. C. glabrata is intrinsically less susceptible to the widely used azole antifungal drugs and quickly develops secondary resistance. Resistance typically relies on drug efflux with transporters regulated by the transcription factor Pdr1. Gain-of-function (GOF) mutations in PDR1 lead to a hyperactive state and thus efflux transporter upregulation. Our laboratory has characterized a collection of C. glabrata clinical isolates in which azole resistance was found to correlate with increased virulence in vivo. Contributing phenotypes were the evasion of adhesion and phagocytosis by macrophages and an increased adhesion to epithelial cells. These phenotypes were found to be dependent on PDR1 GOF mutation and/or C. glabrata strain background. In the search for the molecular effectors, we found that PDR1 hyperactivity leads to overexpression of specific cell wall adhesins of C. glabrata. Further study revealed that EPA1 regulation, in particular, explained the increase in adherence to epithelial cells. Deleting EPA1 eliminates the increase in adherence in an in vitro model of interaction with epithelial cells. In a murine model of urinary tract infection, PDR1 hyperactivity conferred increased ability to colonize the bladder and kidneys in an EPA1-dependent way. In conclusion, this study establishes a relationship between PDR1 and the regulation of cell wall adhesins, an important virulence attribute of C. glabrata. Furthermore, our data show that PDR1 hyperactivity mediates increased adherence to host epithelial tissues both in vitro and in vivo through upregulation of the adhesin gene EPA1. IMPORTANCE Candida glabrata is an important fungal pathogen in human diseases and is also rapidly acquiring drug resistance. Drug resistance can be mediated by the transcriptional activator PDR1, and this results in the upregulation of multidrug transporters. Intriguingly, this resistance mechanism is associated in C. glabrata with increased virulence in animal models and also with increased adherence to specific host cell types. The C. glabrata adhesin gene EPA1 is a major contributor of virulence and adherence to host cells. Here, we show that EPA1 expression is controlled by PDR1 independently of subtelomeric silencing, a known EPA1 regulation mechanism. Thus, a relationship exists between PDR1, EPA1 expression, and adherence to host cells, which is critical for efficient virulence. Our results demonstrate that acquisition of drug resistance is beneficial for C. glabrata in fungus-host relationships. These findings further highlight the challenges of the therapeutic management of C. glabrata infections in human patients.

scholarly journals The structure of a class 3 nonsymbiotic plant haemoglobin fromArabidopsis thalianareveals a novel N-terminal helical extension

2014 ◽  
Vol 70 (5) ◽  
pp. 1411-1418 ◽  
Author(s):  
Brandon J. Reeder ◽  
Michael A. Hough
Keyword(s):  
Crystal Structure ◽  
Protein Sequence ◽  
Disulfide Bonds ◽  
External Environment ◽  
Tryptophan Residue ◽  
Central Cavity ◽  
Dimer Interface ◽  
Iron Coordination

Plant nonsymbiotic haemoglobins fall into three classes, each with distinct properties but all with largely unresolved physiological functions. Here, the first crystal structure of a class 3 nonsymbiotic plant haemoglobin, that fromArabidopsis thaliana, is reported to 1.77 Å resolution. The protein forms a homodimer, with each monomer containing a two-over-two α-helical domain similar to that observed in bacterial truncated haemoglobins. A novel N-terminal extension comprising two α-helices plays a major role in the dimer interface, which occupies the periphery of the dimer–dimer face, surrounding an open central cavity. The haem pocket contains a proximal histidine ligand and an open sixth iron-coordination site with potential for a ligand, in this structure hydroxide, to form hydrogen bonds to a tyrosine or a tryptophan residue. The haem pocket appears to be unusually open to the external environment, with another cavity spanning the entrance of the two haem pockets. The final 23 residues of the C-terminal domain are disordered in the structure; however, these domains in the functional dimer are adjacent and include the only two cysteine residues in the protein sequence. It is likely that these residues form disulfide bondsin vitroand it is conceivable that this C-terminal region may act in a putative complex with a partner moleculein vivo.

scholarly journals SUV39H1-DNMT3A-mediated epigenetic regulation of Tim-3 and galectin-9 in the cervical cancer

2020 ◽  
Author(s):  
Li Zhang ◽  
Sijuan Tian ◽  
Minyi Zhao ◽  
Ting Yang ◽  
Shimin Quan ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Lines ◽  
Epigenetic Regulation ◽  
Promoter Region ◽  
Expression System ◽  
Methylation Status ◽  
Regulation Mechanism ◽  
Cellular Expression

Abstract Background: Methylation of histone 3 at lysine 9 (H3K9) and DNA methylation are epigenetic marks correlated with genes silencing. The tumor microenvironment significantly influences therapeutic responses and clinical outcomes. The epigenetic-regulation mechanism of the costimulatory factors Tim-3 and galectin-9 in cervical cancer remains unknown. Methods: The methylation status of HAVCR2 and LGALS9 were detected by MS-PCR in cervical cancer tissues and cell lines. The underlying molecular mechanism of SUV39H1-DNMT3A-Tim-3/galectin-9 regulation was elucidated using cervical cancer cell lines containing siRNA or/and over-expression system. Confirmation of the regulation of DNMT3A by SUV39H1 used ChIP-qPCR.Results: SUV39H1 up-regulates H3K9me3 expression at the DNMT3A promoter region, which in turn induced expression of DNMT3A in cervical cancer. In addition, the mechanistic studies indicate that DNMT3A mediates the epigenetic modulation of the HAVCR2 and LGALS9 genes by directly binding to their promoter regions in vitro. Moreover, in an in vivo assay, the expression profile of SUV39H1 up-regulates the level of H3K9me3 at the DNMT3A promoter region was found to correlate with Tim-3 and galectin-9 cellular expression level. Conclusion: These results indicate that SUV39H1-DNMT3A is a crucial Tim-3 and galectin-9 regulatory axis in cervical cancer.

scholarly journals Transcriptional Difference between SARS-COV-2 and other Human Coronaviruses Revealed by Sub-genomic RNA Profiling

2020 ◽  
Author(s):  
Lin Lv ◽  
Xiaoqing Xie ◽  
Qiyu Gong ◽  
Ru Feng ◽  
Xiaokui Guo ◽  
...  
Keyword(s):  
Regulation Mechanism ◽  
List Type ◽  
Genomic Rna ◽  
Human Patient ◽  
Spike Gene ◽  
Rna Profiling ◽  
Order Of Magnitude ◽  
Human Coronaviruses

AbstractSARS-COV-2 and all other coronaviruses express its 3 prime genes by forming sub-genomic RNA. As the genome of these virus exist in RNA form, only by profiling the relative abundance of these sgRNAs, can the viral transcriptome be revealed. Utilizing publically available meta-transcriptomic data generated from patient samples, we were able to infer the viral transcriptome in vivo, which is distinct from the in vitro one derived from cell culture. Inter-sample diversity was also observed and a sample specific transcript was identified. By doing the same analysis to MERS and SARS data, we were able to compare the three in terms of transcription. Among the differences, SARS-COV-2 has significantly elevated expression of the Spike gene, which may contribute to its high transmissibility.HighlightsThe in vivo transcriptome of SARS-CoV-2 revealed by sgRNA profiling, for 25 patient samples around the globe.The Spike protein expression is an order of magnitude higher in SARS-CoV-2 than MERS-CoV or SARS-CoV, possibly contributing to the virus’ elevated transmissibility.The in vivo SARS-CoV-2 transcriptomes, as inferred from human patient data was distinct from the in vitro one derived from cell line culture, all the accessory genes were up-regulated in vivo, suggesting intricate expression regulation mechanism for the small viral genome.

Sign in / Sign up

Export Citation Format

Share Document