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  1. Expression Patterns and Potential Biological Roles of Dip2a.

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    Luqing Zhang

    Full Text Available Disconnected (disco-interacting protein 2 homolog A is a member of the DIP2 protein family encoded by Dip2a gene. Dip2a expression pattern has never been systematically studied. Functions of Dip2a in embryonic development and adult are not known. To investigate Dip2a gene expression and function in embryo and adult, a Dip2a-LacZ mouse model was generated by insertion of β-Gal cDNA after Dip2a promoter using CRISPR/Cas9 technology. Dip2a-LacZ mouse was designed to be a lacZ reporter mouse as well as a Dip2a knockout mouse. Heterozygous mice were used to study endogenous Dip2a expression and homozygotes to study DIP2A-associated structure and function. LacZ staining indicated that Dip2a is broadly expressed in neuronal, reproductive and vascular tissues, as well as in heart, kidney, liver and lung. Results demonstrate that Dip2a is expressed in ectoderm-derived tissues in developing embryos. Adult tissues showed rich staining in neurons, mesenchymal, endothelial, smooth muscle cells and cardiomyocytes by cell types. The expression pattern highly overlaps with FSTL1 and supports previous report that DIP2A to be potential receptor of FSTL1 and its protective roles of cardiomyocytes. Broad and intense embryonic and adult expression of Dip2a has implied their multiple structural and physiological roles.

  2. Caspase-14 Expression Impairs Retinal Pigment Epithelium Barrier Function: Potential Role in Diabetic Macular Edema

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    Selina Beasley

    2014-01-01

    Full Text Available We recently showed that caspase-14 is a novel molecule in retina with potential role in accelerated vascular cell death during diabetic retinopathy (DR. Here, we evaluated whether caspase-14 is implicated in retinal pigment epithelial cells (RPE dysfunction under hyperglycemia. The impact of high glucose (HG, 30 mM D-glucose on caspase-14 expression in human RPE (ARPE-19 cells was tested, which showed significant increase in caspase-14 expression compared with normal glucose (5 mM D-glucose + 25 mM L-glucose. We also evaluated the impact of modulating caspase-14 expression on RPE cells barrier function, phagocytosis, and activation of other caspases using ARPE-19 cells transfected with caspase-14 plasmid or caspase-14 siRNA. We used FITC-dextran flux assay and electric cell substrate impedance sensing (ECIS to test the changes in RPE cell barrier function. Similar to HG, caspase-14 expression in ARPE-19 cells increased FITC-dextran leakage through the confluent monolayer and decreased the transcellular electrical resistance (TER. These effects of HG were prevented by caspase-14 knockdown. Furthermore, caspase-14 knockdown prevented the HG-induced activation of caspase-1 and caspase-9, the only activated caspases by HG. Phagocytic activity was unaffected by caspase-14 expression. Our results suggest that caspase-14 contributes to RPE cell barrier disruption under hyperglycemic conditions and thus plays a role in the development of diabetic macular edema.

  3. microRNA expression and its potential role in cardioprotection by ischemic postconditioning in pigs.

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    Baars, Theodor; Skyschally, Andreas; Klein-Hitpass, Ludger; Cario, Elke; Erbel, Raimund; Heusch, Gerd; Kleinbongard, Petra

    2014-10-01

    Ischemic postconditioning (PoCo) reduces infarct size following myocardial ischemia/reperfusion. To protect, PoCo must be performed early during reperfusion, and causal cardioprotective signaling must occur then. The role of microRNA (miRNA) in PoCo is unclear. Anesthetized pigs were subjected to 60 min left anterior descending coronary artery (LAD) occlusion and 180 min reperfusion. Immediate full reperfusion (IFR, n = 5) was compared to PoCo (four cycles of 60 s/60 s reperfusion/reocclusion, n = 5). Transmural myocardial biopsies from the LAD territory were sampled at baseline, 60 min ischemia, 10 and 180 min reperfusion. RNA was isolated. The expression of 11 miRNAs, including muscle-specific (miRNA-1, -133a, -206, -208b, -214, and -499), fibrosis- (miRNA-21, -24, and -29b), neovascularization- (miRNA-92a), and inflammation-associated (miRNA-146b) candidates, was quantified using real-time PCR (RT-PCR). mRNA expression at baseline and 180 min reperfusion was quantified and validated (microarray and RT-PCR). PoCo reduced infarct size from 44.9 ± 7.7 to 34.8 ± 5.3% of the area at risk. The expression of miRNA-1, -24, -29b, -133a, -146b, -208b, and -499 was increased at 10 min reperfusion with PoCo vs. IFR; however, that of miRNA-1, -24, -208b, and -499 was already increased at 60 min ischemia and probably reflects falsely positive results. Five mRNAs were different with PoCo vs. IFR. In silico analysis identified a tentative connection between three miRNAs and five mRNAs with the biological functions "cell death", "inflammatory response" and/or "glucose metabolism". If at all, only miRNA-29b, -133a, and -146b fulfill the minimal temporal requirements for a potential causal involvement in cardioprotection by PoCo.

  4. Ion channel gene expression in lung adenocarcinoma: potential role in prognosis and diagnosis.

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    Ko, Jae-Hong; Gu, Wanjun; Lim, Inja; Bang, Hyoweon; Ko, Eun A; Zhou, Tong

    2014-01-01

    Ion channels are known to regulate cancer processes at all stages. The roles of ion channels in cancer pathology are extremely diverse. We systematically analyzed the expression patterns of ion channel genes in lung adenocarcinoma. First, we compared the expression of ion channel genes between normal and tumor tissues in patients with lung adenocarcinoma. Thirty-seven ion channel genes were identified as being differentially expressed between the two groups. Next, we investigated the prognostic power of ion channel genes in lung adenocarcinoma. We assigned a risk score to each lung adenocarcinoma patient based on the expression of the differentially expressed ion channel genes. We demonstrated that the risk score effectively predicted overall survival and recurrence-free survival in lung adenocarcinoma. We also found that the risk scores for ever-smokers were higher than those for never-smokers. Multivariate analysis indicated that the risk score was a significant prognostic factor for survival, which is independent of patient age, gender, stage, smoking history, Myc level, and EGFR/KRAS/ALK gene mutation status. Finally, we investigated the difference in ion channel gene expression between the two major subtypes of non-small cell lung cancer: adenocarcinoma and squamous-cell carcinoma. Thirty ion channel genes were identified as being differentially expressed between the two groups. We suggest that ion channel gene expression can be used to improve the subtype classification in non-small cell lung cancer at the molecular level. The findings in this study have been validated in several independent lung cancer cohorts.

  5. Thyroid Transcription Factor-1 in Orbital Adipose Tissues: Potential Role in Orbital Thyrotropin Receptor Expression

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    Bhattacharyya, Kalyan K.; Coenen, Michael J.; Bahn, Rebecca S.

    2005-01-01

    Thyroid transcription factor-1 (TTF-1) is required for maximal expression of thyrotropin receptor (TSHR) in the thyroid. Extrathyroidal TSHR expression is detectable in normal orbital adipose tissues, with increased levels found in orbital tissues from patients with Graves’ ophthalmopathy (GO), and in orbital preadipocyte cultures following differentiation. In order to determine whether TTF-1 might be involved in orbital TSHR expression, we used quantitative real-time polymerase chain reaction (PCR) to assess relative expression of this and other thyroid-associated transcription factors (TTF-2 and Pax-8) in GO orbital tissue specimens (n = 28) and cultures (n = 3), and in normal orbital tissues (n = 19) and cultures (n = 3). We detected TTF-1 and TTF-2 mRNA in GO and normal orbital tissue samples, with no difference in levels noted between the tissues. In the GO orbital cultures, TTF-1 mRNA was higher in differentiated than in control (undifferentiated) cultures (p < 0.05), while TTF-2 was unchanged. In the normal cultures, neither TTF-1 nor TTF-2 mRNA levels increased in differentiated cultures. Pax8 was undetectable in all orbital tissues and cell cultures. The presence of mRNA encoding TTF-1 in orbital tissues and cultures suggest that this transcription factor may play an important role in extrathyroidal, as it does in thyroidal, TSHR expression. PMID:15929662

  6. Potential Role of TRAIL in Metastasis of Mutant KRAS Expressing Lung Adenocarcinoma.

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    Pal, Shyama; Amin, Prayag J; Sainis, K B; Shankar, Bhavani S

    2016-12-01

    Apo2L/tumor necrosis factor (TNF)-α-related apoptosis-inducing ligand (TRAIL, TNFSF10) is an important cytokine in the tumor microenvironment and plays a major role in the balance of cell survival/death pathways. Bioinformatic analyses of 839 adenocarcinoma (AC) and 356 squamous cell lung carcinoma patient data (SCC) by cBioPortal (genomic analyses) shows that TRAIL expression leads to differential outcomes of disease free survival in AC and SCC. Oncomine datamining (transcript analyses) reveal that TRAIL is upregulated in 167 SCC as compared to 350 AC patients from six data sets. Genomic analyses using cBioPortal revealed high rates of KRAS mutation in AC accompanied by higher incidence of metastasis and increased amplifications of TRAIL gene in SCC. Bioinformatic analyses of an additional lung cancer patient database also showed that risk of disease progression was significantly increased with high TRAIL expression in AC (461 samples). In vitro studies demonstrated that TRAIL increased phosphorylation of ERK only in adenocarcinoma cell lines with mutant KRAS. This was associated with increased migration that was abrogated by MEK inhibitor PD98059. Effects of increased migration induced by TRAIL persisted even after exposure to ionizing radiation with suppression of DNA damage response. These results help understand the role of TRAIL signaling in metastasis which is essential to develop strategies to revert these signals into pro-apoptotic pathways.

  7. Identification, expression pattern, cellular location and potential role of the caveolin-1 gene from Artemia sinica.

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    Li, Xuejie; Yao, Feng; Zhang, Wei; Cheng, Cheng; Chu, Bing; Liu, Yan; Mei, Yanli; Wu, Yang; Zou, Xiangyang; Hou, Lin

    2014-05-01

    Caveolins are integral membrane proteins that serve as scaffolds to recruit numerous signaling molecules. Caveolins play an important role in membrane trafficking, signal transduction, substrate transport and endocytosis in differentiated cells. In this study, a caveolin-1 gene from Artemia sinica (As-cav-1) was successfully cloned for the first time. The full-length cDNA of As-cav-1 comprises 974 bp, with a 675 bp open reading frame (ORF) that encodes a polypeptide of 224 amino acids with a caveolin scaffolding domain (CSD) and two transmembrane domains. Multiple sequence alignment revealed that the putative As-CAV-1 protein sequence was relatively conserved across species, especially in the CSD domain. Real-time PCR revealed high levels of the As-cav-1 transcript at 0h of embryo development. Furthermore, As-cav-1 transcripts were highly upregulated under high salinity (200‰) and low temperature stresses (15°C). To further characterize As-cav-1, recombinant pET30a-cav-1 protein was expressed using a prokaryotic expression system. The recombinant protein comprised 290 amino acids with a theoretical molecular weight of 32kDa, and a predicted isoelectric point of 5.6. Western blotting of the expression levels of As-CAV-1 during different embryo development stages revealed that As-CAV-1 levels decreased gradually during development stages from 0 h to 40 h, and increased at 3d. Furthermore, western blotting showed that As-CAV-1 was upregulated to its highest expression level by low temperature stress (15°C) and high salinity. Confocal laser microscopy analysis, using antibodies generated against the recombinant As-CAV-1 protein, showed that As-CAV-1 was mostly located in the cell membrane. Our results suggested that As-cav-1 plays a vital role in protecting embryos from high salt damage and low temperature stress, especially during post-diapause embryonic development. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Expression and characterization of purinergic receptors in rat middle meningeal artery-potential role in migraine.

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    Kristian Agmund Haanes

    Full Text Available The dura mater and its vasculature have for decades been central in the hypothesis of migraine and headache pathophysiology. Although recent studies have questioned the role of the vasculature as the primary cause, dural vessel physiology is still relevant in understanding the complex pathophysiology of migraine. The aim of the present study was to isolate the middle meningeal artery (MMA from rodents and characterize their purinergic receptors using a sensitive wire myograph method and RT-PCR. The data presented herein suggest that blood flow through the MMA is, at least in part, regulated by purinergic receptors. P2X1 and P2Y6 receptors are the strongest contractile receptors and, surprisingly, ADPβS caused contraction most likely via P2Y1 or P2Y13 receptors, which is not observed in other arteries. Adenosine addition, however, caused relaxation of the MMA. The adenosine relaxation could be inhibited by SCH58261 (A2A receptor antagonist and caffeine (adenosine receptor antagonist. This gives one putative molecular mechanism for the effect of caffeine, often used as an adjuvant remedy of cranial pain. Semi-quantitative RT-PCR expression data for the receptors correlate well with the functional findings. Together these observations could be used as targets for future understanding of the in vivo role of purinergic receptors in the MMA.

  9. STIM and Orai isoform expression in pregnant human myometrium: a potential role in calcium signaling during pregnancy.

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    Evonne eChin-Smith

    2014-05-01

    Full Text Available Store-operated calcium (Ca2+ entry (SOCE can be mediated by two novel proteins, STIM/Orai. We have previously demonstrated that members of the TRPC family, putative basal and store operated calcium entry channels, are present in human myometrium and regulated by labor associated stimuli IL-1β and mechanical stretch. Although STIM and Orai isoforms (1-3 have been reported in other smooth muscle cell types, there is little known about the expression or gestational regulation of STIM and Orai expression in human myometrium. Total RNA was isolated from lower segment human myometrial biopsies obtained at caesarean section from women at the time of preterm no labor (PTNL, preterm labor (PTL, term non-labor (TNL and term with labor (TL; primary cultured human uterine smooth muscle cells, and a human myometrial cell line (hTERT-HM. STIM1-2, and Orai1-3 mRNA expression was assessed by quantitative real-time PCR. All five genes were expressed in myometrial tissue and cultured cells. Orai2 was the most abundant Orai isoform in human myometrium. Expression of STIM1-2/Orai1-3 did not alter with the onset of labor. Orai1 mRNA expression in cultured cells was enhanced by IL-1β treatment. This novel report of STIM1-2 and Orai1-3 mRNA expression in pregnant human myometrium and Orai1 regulation by IL-1β indicates a potential role for these proteins in calcium signaling in human myometrium during pregnancy.

  10. Expression and potential role of the peptide orexin-A in prostate cancer

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    Valiante, Salvatore [Department of Biology, University of Naples Federico II (Italy); Liguori, Giovanna; Tafuri, Simona [Department of Veterinary Medicine and Animal Productions, University of Naples Federico II (Italy); Pavone, Luigi Michele [Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II (Italy); Campese, Roberto [Department of Urology, “A. Cardarelli” Hospital, Naples (Italy); Monaco, Roberto [Department of Pathology, “A. Cardarelli” Hospital, Naples (Italy); Iachetta, Giuseppina; Assisi, Loredana [Department of Biology, University of Naples Federico II (Italy); Mirabella, Nicola [Department of Veterinary Medicine and Animal Productions, University of Naples Federico II (Italy); Forte, Maurizio [Institute of Genetics and Biophysics “A. Buzzati-Traverso”, CNR, Naples (Italy); Costagliola, Anna [Department of Veterinary Medicine and Animal Productions, University of Naples Federico II (Italy); Vittoria, Alfredo, E-mail: avittori@unina.it [Department of Veterinary Medicine and Animal Productions, University of Naples Federico II (Italy)

    2015-09-04

    The peptides orexin-A and orexin-B and their G protein-coupled OX1 and OX2 receptors are involved in multiple physiological processes in the central nervous system and peripheral organs. Altered expression or signaling dysregulation of orexins and their receptors have been associated with a wide range of human diseases including narcolepsy, obesity, drug addiction, and cancer. Although orexin-A, its precursor molecule prepro-orexin and OX1 receptor have been detected in the human normal and hyperplastic prostate tissues, their expression and function in the prostate cancer (PCa) remains to be addressed. Here, we demonstrate for the first time the immunohistochemical localization of orexin-A in human PCa specimens, and the expression of prepro-orexin and OX1 receptor at both protein and mRNA levels in these tissues. Orexin-A administration to the human androgen-dependent prostate carcinoma cells LNCaP up-regulates OX1 receptor expression resulting in a decrease of cell survival. Noteworthy, nanomolar concentrations of the peptide counteract the testosterone-induced nuclear translocation of the androgen receptor in the cells: the orexin-A action is prevented by the addition of the OX1 receptor antagonist SB-408124 to the test system. These findings indicate that orexin-A/OX1 receptor interaction interferes with the activity of the androgen receptor which regulates PCa onset and progression, thus suggesting that orexin-A and its receptor might represent novel therapeutic targets to challenge this aggressive cancer. - Highlights: • Orexin-A and OX1 receptor are present in human cancer prostate tissues. • Orexin-A up-regulates OX1 receptor expression in LNCaP cells. • Orexin-A inhibits testosterone-induced nuclear translocation of androgen receptor.

  11. Expression and potential role of the peptide orexin-A in prostate cancer.

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    Valiante, Salvatore; Liguori, Giovanna; Tafuri, Simona; Pavone, Luigi Michele; Campese, Roberto; Monaco, Roberto; Iachetta, Giuseppina; Assisi, Loredana; Mirabella, Nicola; Forte, Maurizio; Costagliola, Anna; Vittoria, Alfredo

    2015-09-04

    The peptides orexin-A and orexin-B and their G protein-coupled OX1 and OX2 receptors are involved in multiple physiological processes in the central nervous system and peripheral organs. Altered expression or signaling dysregulation of orexins and their receptors have been associated with a wide range of human diseases including narcolepsy, obesity, drug addiction, and cancer. Although orexin-A, its precursor molecule prepro-orexin and OX1 receptor have been detected in the human normal and hyperplastic prostate tissues, their expression and function in the prostate cancer (PCa) remains to be addressed. Here, we demonstrate for the first time the immunohistochemical localization of orexin-A in human PCa specimens, and the expression of prepro-orexin and OX1 receptor at both protein and mRNA levels in these tissues. Orexin-A administration to the human androgen-dependent prostate carcinoma cells LNCaP up-regulates OX1 receptor expression resulting in a decrease of cell survival. Noteworthy, nanomolar concentrations of the peptide counteract the testosterone-induced nuclear translocation of the androgen receptor in the cells: the orexin-A action is prevented by the addition of the OX1 receptor antagonist SB-408124 to the test system. These findings indicate that orexin-A/OX1 receptor interaction interferes with the activity of the androgen receptor which regulates PCa onset and progression, thus suggesting that orexin-A and its receptor might represent novel therapeutic targets to challenge this aggressive cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. LncRNAs expression in preeclampsia placenta reveals the potential role of LncRNAs contributing to preeclampsia pathogenesis.

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    Xiaoju He

    Full Text Available BACKGROUND: Long non-coding RNAs (lncRNAs are an important class of pervasive genes involved in a variety of biological functions. They are aberrantly expressed in many types of diseases. In this study, we aimed to investigate the lncRNA profiles in preeclampsia. Preeclampsia has been observed in patients with molar pregnancy where a fetus is absent, which demonstrate that the placenta is sufficient to cause this condition. Thus, we analyzed the lncRNA profiles in preeclampsia placentas. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we described the lncRNA profiles in six preeclampsia placentas (T and five normal pregnancy placentas (N using microarray. With abundant and varied probes accounting for 33,045 LncRNAs in our microarray, 28,443 lncRNAs that were expressed at a specific level were detected. From the data, we found 738 lncRNAs that were differentially expressed (≥ 1.5-fold-change among preeclampsia placentas compared with controls. Coding-non-coding gene co-expression networks (CNC network were constructed based on the correlation analysis between the differentially expressed lncRNAs and mRNAs. According to the CNC network and GO analysis of differentially expressed lncRNAs/mRNAs, we selected three lncRNAs to analyze the relationship between lncRNAs and preeclampsia. LOC391533, LOC284100, and CEACAMP8 were evaluated using qPCR in 40 preeclampsia placentas and 40 controls. These results revealed that three lncRNAs were aberrantly expressed in preeclampsia placentas compared with controls. CONCLUSIONS/SIGNIFICANCE: Our study is the first study to determine the genome-wide lncRNAs expression patterns in preeclampsia placenta using microarray. These results revealed that clusters of lncRNAs were aberrantly expressed in preeclampsia placenta compared with controls, which indicated that lncRNAs differentially expressed in preeclampsia placenta might play a partial or key role in preeclampsia development. Misregulation of LOC391533, LOC

  13. Expression and Characterization of Purinergic Receptors in Rat Middle Meningeal Artery–Potential Role in Migraine

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    Haanes, Kristian Agmund; Edvinsson, Lars

    2014-01-01

    pathophysiology of migraine. The aim of the present study was to isolate the middle meningeal artery (MMA) from rodents and characterize their purinergic receptors using a sensitive wire myograph method and RT-PCR. The data presented herein suggest that blood flow through the MMA is, at least in part, regulated...... by purinergic receptors. P2X1 and P2Y6 receptors are the strongest contractile receptors and, surprisingly, ADPβS caused contraction most likely via P2Y1 or P2Y13 receptors, which is not observed in other arteries. Adenosine addition, however, caused relaxation of the MMA. The adenosine relaxation could...... with the functional findings. Together these observations could be used as targets for future understanding of the in vivo role of purinergic receptors in the MMA....

  14. Transient receptor potential vanilloid 1 expression and function in splenic dendritic cells: a potential role in immune homeostasis.

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    Assas, Bakri M; Wakid, Majed H; Zakai, Haytham A; Miyan, Jaleel A; Pennock, Joanne L

    2016-03-01

    Neuro-immune interactions, particularly those driven by neuropeptides, are increasingly implicated in immune responses. For instance, triggering calcium-channel transient receptor potential vanilloid 1 (TRPV1) on sensory nerves induces the release of calcitonin-gene-related peptide (CGRP), a neuropeptide known to moderate dendritic cell activation and T helper cell type 1 polarization. Despite observations that CGRP is not confined to the nervous system, few studies have addressed the possibility that immune cells can respond to well-documented 'neural' ligands independently of peripheral nerves. Here we have identified functionally relevant TRPV1 on primary antigen-presenting cells of the spleen and have demonstrated both calcium influx and CGRP release in three separate strains of mice using natural agonists. Furthermore, we have shown down-regulation of activation markers CD80/86 on dendritic cells, and up-regulation of interleukin-6 and interleukin-10 in response to CGRP treatment. We suggest that dendritic cell responses to neural ligands can amplify neuropeptide release, but more importantly that variability in CGRP release across individuals may have important implications for immune cell homeostasis. © 2015 John Wiley & Sons Ltd.

  15. Human Platelets Express Functional Thymic Stromal Lymphopoietin Receptors: a Potential Role in Platelet Activation in Acute Coronary Syndrome

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    Boyuan Wang

    2013-12-01

    Full Text Available Background: Thymic stromal lymphopoietin (TSLP has been shown to be expressed in various inflammatory tissues, such as human atherosclerotic plaques. Many types of myeloid cells involved in atherosclerosis, including mast cells, lymphocytes, dendritic cells and monocytes/macrophages, present TSLP receptors (TSLPR. However, it is unknown whether platelets, which also play important roles in atherothrombosis, express TSLPR. Methods and Results: We applied flow cytometry and western blotting to show that TSLPR was expressed on the surface of human platelets. Following the addition of TSLP to platelets, the expression of CD62P, CD63, PAC-1 and p-Akt as well as aggregation and ATP release were increased significantly. A TSLPR antibody and a PI3K (phosphatidylinositol 3-kinase enzyme inhibitor (LY294002 significantly inhibited the platelet activation induced by TSLP. The expression of TSLPR, CD62P and CD63 and the increment of the expression of CD62P and CD63 induced by TSLP in the acute coronary syndrome (ACS group were markedly higher than those in the control group and the stable angina pectoris (SAP group. The expression and the increment of the expression of CD62P and CD63 induced by TSLP were positively correlated with the expression of TSLPR. Conclusion: Human platelets express functional TSLPR, which can be activated by TSLP to promote platelet activation. TSLP/TSLPR functions via activating the PI3K/AKT pathway, and this signalling pathway may be one of the mechanisms involved in thrombosis in ACS. In coronary disease patients, the determination of TSLPR in platelets may help to identify the risk of ACS.

  16. Regional expression of HOXA4 along the aorta and its potential role in human abdominal aortic aneurysms

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    Elmore James R

    2011-05-01

    Full Text Available Abstract Background The infrarenal abdominal aorta exhibits increased disease susceptibility relative to other aortic regions. Allograft studies exchanging thoracic and abdominal segments showed that regional susceptibility is maintained regardless of location, suggesting substantial roles for embryological origin, tissue composition and site-specific gene expression. Results We analyzed gene expression with microarrays in baboon aortas, and found that members of the HOX gene family exhibited spatial expression differences. HOXA4 was chosen for further study, since it had decreased expression in the abdominal compared to the thoracic aorta. Western blot analysis from 24 human aortas demonstrated significantly higher HOXA4 protein levels in thoracic compared to abdominal tissues (P HOXA4 transcript levels were significantly decreased in human abdominal aortic aneurysms (AAAs compared to age-matched non-aneurysmal controls (P P Conclusions Our results demonstrated spatial variation in expression of HOXA4 in human aortas that persisted into adulthood and that downregulation of HOXA4 expression was associated with AAAs, an important aortic disease of the ageing population.

  17. Expression of Aquaporins in Human Embryos and Potential Role of AQP3 and AQP7 in Preimplantation Mouse Embryo Development

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    Yun Xiong

    2013-05-01

    Full Text Available Background/Aims: Water channels, also named aquaporins (AQPs, play crucial roles in cellular water homeostasis. Methods: RT-PCR indicated the mRNA expression of AQPs 1-5, 7, 9, and 11-12, but not AQPs 0, 6, 8, and 10 in the 2∼8-cell stage human embryos. AQP3 and AQP7 were further analyzed for their mRNA expression and protein expression in the oocyte, zygote, 2-cell embryo, 4-cell embryo, 8-cell embryo, morula, and blastocyst from both human and mouse using RT-PCR and immunofluorescence, respectively. Results: AQP3 and AQP7 were detected in all these stages. Knockdown of either AQP3 or AQP7 by targeted siRNA injection into 2-cell mouse embryos significantly inhibited preimplantation embryo development. However, knockdown of AQP3 in JAr spheroid did not affect its attachment to Ishikawa cells. Conclusion: These data demonstrate that multiple aquaporins are expressed in the early stage human embryos and that AQP3 and AQP7 may play a role in preimplantation mouse embryo development.

  18. Expression of platelet derived growth factor family members and the potential role of imatinib mesylate for cervical cancer

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    Robles Elizabeth

    2006-10-01

    Full Text Available Abstract Background Despite significant achievements in the treatment of cervical cancer, it is still a deadly disease; hence newer therapeutical modalities are needed. Preliminary investigations suggest that platelet-derived growth factor (PDGF might have a role in the development of cervical cancer, therefore it is important to determine whether this growth factor pathway is functional and its targeting with imatinib mesylate leads to growth inhibition of cervical cancer cells. Results PDGF receptors (PDGFR and their ligands are frequently expressed in cervical cancer and the majority exhibited a combination of family members co-expression. A number of intronic and exonic variations but no known mutations in the coding sequence of the PDGFRα gene were found in cancer cell lines and primary tumors. Growth assays demonstrated that PDGFBB induces growth stimulation that can be blocked by imatinib and that this tyrosine kinase inhibitor on its own inhibits cell growth. These effects were associated with the phosphorylation status of the receptor. Conclusion The PDGFR system may have a role in the pathogenesis of cervical cancer as their members are frequently expressed in this tumor and cervical cancer lines are growth inhibited by the PDGFR antagonist imatinib.

  19. Effects of obesity on severity of colitis and cytokine expression in mouse mesenteric fat. Potential role of adiponectin receptor 1

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    Sideri, Aristea; Stavrakis, Dimitris; Bowe, Collin; Shih, David Q.; Fleshner, Phillip; Arsenescu, Violeta; Arsenescu, Razvan; Turner, Jerrold R.; Pothoulakis, Charalabos

    2015-01-01

    In inflammatory bowel disease (IBD), obesity is associated with worsening of the course of disease. Here, we examined the role of obesity in the development of colitis and studied mesenteric fat-epithelial cell interactions in patients with IBD. We combined the diet-induce obesity with the trinitrobenzene sulfonic acid (TNBS) colitis mouse model to create groups with obesity, colitis, and their combination. Changes in the mesenteric fat and intestine were assessed by histology, myeloperoxidase assay, and cytokine mRNA expression by real-time PCR. Medium from human mesenteric fat and cultured preadipocytes was obtained from obese patients and those with IBD. Histological analysis showed inflammatory cell infiltrate and increased histological damage in the intestine and mesenteric fat of obese mice with colitis compared with all other groups. Obesity also increased the expression of proinflammatory cytokines including IL-1β, TNF-α, monocyte chemoattractant protein 1, and keratinocyte-derived chemokine, while it decreased the TNBS-induced increases in IL-2 and IFN-γ in mesenteric adipose and intestinal tissues. Human mesenteric fat isolated from obese patients and those with and IBD demonstrated differential release of adipokines and growth factors compared with controls. Fat-conditioned media reduced adiponectin receptor 1 (AdipoR1) expression in human NCM460 colonic epithelial cells. AdipoR1 intracolonic silencing in mice exacerbated TNBS-induced colitis. In conclusion, obesity worsens the outcome of experimental colitis, and obesity- and IBD-associated changes in adipose tissue promote differential mediator release in mesenteric fat that modulates colonocyte responses and may affect the course of colitis. Our results also suggest an important role for AdipoR1 for the fat-intestinal axis in the regulation of inflammation during colitis. PMID:25591865

  20. Potential roles of abnormally expressed long noncoding RNA UCA1 and Malat-1 in metastasis of melanoma.

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    Tian, Yongjing; Zhang, Xiuying; Hao, Yinghua; Fang, Zhengyu; He, Yanling

    2014-08-01

    Melanoma is a highly aggressive skin cancer with increasing incidence worldwide. Long noncoding RNAs (lncRNAs), a group of nonprotein-coding transcripts longer than 200 nucleotides, are pervasively transcribed in the genome and are emerging as new players in tumorigenesis. The primary objective of this study was to investigate the role of six cancer-related lncRNAs in pairs of melanoma and adjacent normal tissues (ANTs). A total of 63 primary melanoma, paired ANTs, and metastatic lesions were collected in a Chinese population. Real-time PCR analysis was carried out to compare a series of cancer-related lncRNAs among primary melanoma tissues, ANTs, and metastatic lesions. In in-vitro studies, transwell migration assay was carried out to estimate the migration abilities of melanoma cells with different expression levels of urothelial carcinoma-associated 1 (UCA1) or metastasis-associated lung adenocarcinoma transcript 1 (Malat-1) lncRNAs. We found that UCA1 and Malat-1 lncRNAs were markedly more increased in melanomas than in paired ANTs (PMelanomas at later stages (stages 3-4) showed higher expression of UCA1 lncRNA than those at early stages (stages 1-2) (P=0.455). In melanomas with lymph node metastasis, the metastatic lesions had a relatively higher expression of Malat-1 lncRNA than in paired primary tumors (P=0.414). Knockdown of UCA1 or Malat-1 lncRNA could attenuate the migrational ability of melanoma cells in in-vitro studies. Increased expression of UCA1 and Malat-1 lncRNAs might have a correlation with melanoma metastasis.

  1. Long Non-coding RNAs Expression Profile in HepG2 Cells Reveals the Potential Role of Long Non-coding RNAs in the Cholesterol Metabolism

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    Gang Liu

    2015-01-01

    Full Text Available Background: Green tea has been shown to improve cholesterol metabolism in animal studies, but the molecular mechanisms underlying this function have not been fully understood. Long non-coding RNAs (lncRNAs have recently emerged as a major class of regulatory molecules involved in a broad range of biological processes and complex diseases. Our aim was to identify important lncRNAs that might play an important role in contributing to the benefits of epigallocatechin-3-gallate (EGCG on cholesterol metabolism. Methods: Microarrays was used to reveal the lncRNA and mRNA profiles in green tea polyphenol(--epigallocatechin gallate in cultured human liver (HepG2 hepatocytes treated with EGCG and bioinformatic analyses of the predicted target genes were performed to identify lncRNA-mRNA targeting relationships. RNA interference was used to investigate the role of lncRNAs in cholesterol metabolism. Results: The expression levels of 15 genes related to cholesterol metabolism and 285 lncRNAs were changed by EGCG treatment. Bioinformatic analysis found five matched lncRNA-mRNA pairs for five differentially expressed lncRNAs and four differentially expressed mRNA. In particular, the lncRNA AT102202 and its potential targets mRNA-3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR were identified. Using a real-time polymerase chain reaction technique, we confirmed that EGCG down-regulated mRNA expression level of the HMGCR and up-regulated expression of AT102202. After AT102202 knockdown in HepG2, we observed that the level of HMGCR expression was significantly increased relative to the scrambled small interfering RNA control (P < 0.05. Conclusions: Our results indicated that EGCG improved cholesterol metabolism and meanwhile changed the lncRNAs expression profile in HepG2 cells. LncRNAs may play an important role in the cholesterol metabolism.

  2. Long Non-coding RNAs Expression Profile in HepG2 Cells Reveals the Potential Role of Long Non-coding RNAs in the Cholesterol Metabolism

    Science.gov (United States)

    Liu, Gang; Zheng, Xinxin; Xu, Yanlu; Lu, Jie; Chen, Jingzhou; Huang, Xiaohong

    2015-01-01

    Background: Green tea has been shown to improve cholesterol metabolism in animal studies, but the molecular mechanisms underlying this function have not been fully understood. Long non-coding RNAs (lncRNAs) have recently emerged as a major class of regulatory molecules involved in a broad range of biological processes and complex diseases. Our aim was to identify important lncRNAs that might play an important role in contributing to the benefits of epigallocatechin-3-gallate (EGCG) on cholesterol metabolism. Methods: Microarrays was used to reveal the lncRNA and mRNA profiles in green tea polyphenol(-)-epigallocatechin gallate in cultured human liver (HepG2) hepatocytes treated with EGCG and bioinformatic analyses of the predicted target genes were performed to identify lncRNA-mRNA targeting relationships. RNA interference was used to investigate the role of lncRNAs in cholesterol metabolism. Results: The expression levels of 15 genes related to cholesterol metabolism and 285 lncRNAs were changed by EGCG treatment. Bioinformatic analysis found five matched lncRNA-mRNA pairs for five differentially expressed lncRNAs and four differentially expressed mRNA. In particular, the lncRNA AT102202 and its potential targets mRNA-3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) were identified. Using a real-time polymerase chain reaction technique, we confirmed that EGCG down-regulated mRNA expression level of the HMGCR and up-regulated expression of AT102202. After AT102202 knockdown in HepG2, we observed that the level of HMGCR expression was significantly increased relative to the scrambled small interfering RNA control (P < 0.05). Conclusions: Our results indicated that EGCG improved cholesterol metabolism and meanwhile changed the lncRNAs expression profile in HepG2 cells. LncRNAs may play an important role in the cholesterol metabolism. PMID:25563320

  3. Aberrant upregulation of MUC4 mucin expression in cutaneous condyloma acuminatum and squamous cell carcinoma suggests a potential role in the diagnosis and therapy of skin diseases.

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    Chakraborty, Subhankar; Swanson, Benjamin J; Bonthu, Neelima; Batra, Surinder K

    2010-07-01

    Mucins comprise a family of high-molecular-weight glycoproteins. MUC4, a large transmembrane mucin, has recently emerged as a novel marker for diagnosis, prognosis and therapy in several malignancies. However, its role in skin pathologies remains unknown. The aim of this study was to analyse the expression of MUC4 in cutaneous pathologies by immunohistochemistry for potential diagnostic, prognostic and therapeutic applications. A total of 330 tissue spots representing the normal skin, and benign and malignant cutaneous diseases, were analysed after staining with the monoclonal antibody to human MUC4 (clone 8G7). While the normal epidermis showed a negative to weak-positive expression of MUC4, its expression was significantly upregulated in squamous cell carcinomas (SCCs) where the intensity of staining correlated negatively with tumour grade and positively with age. A moderately strong MUC4 expression was also noted in 2/20 cancer adjacent normal skin and 2/21 chronically inflamed skin tissues, while 10/19 cases of vulval condyloma acuminate, 3/12 of vulval hyperplasia and 2 cases of verruca vulgaris also showed strong MUC4 positivity. Malignant melanoma, basal cell carcinoma and cutaneous cysts were negative. The results indicate that MUC4 expression is aberrantly upregulated in cutaneous SCCs, vulval condylomas and verruca vulgaris. Further, it appears that MUC4 expression in the skin may be modulated by chronic inflammation and the presence of an adjacent cutaneous malignancy in certain cases. These observations suggest a novel role for MUC4 mucin in the pathogenesis of cutaneous SCC and a possible application as a diagnostic and/or prognostic marker in cutaneous pathologies.

  4. Calcium sensing receptor expression in ovine amniotic fluid mesenchymal stem cells and the potential role of R-568 during osteogenic differentiation.

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    Pamela Di Tomo

    Full Text Available Amniotic fluid-derived stem (AFS cells have been identified as a promising source for cell therapy applications in bone traumatic and degenerative damage. Calcium Sensing Receptor (CaSR, a G protein-coupled receptor able to bind calcium ions, plays a physiological role in regulating bone metabolism. It is expressed in different kinds of cells, as well as in some stem cells. The bone CaSR could potentially be targeted by allosteric modulators, in particular by agonists such as calcimimetic R-568, which may potentially be helpful for the treatment of bone disease. The aim of our study was first to investigate the presence of CaSR in ovine Amniotic Fluid Mesenchymal Stem Cells (oAFMSCs and then the potential role of calcimimetics in in vitro osteogenesis. oAFMSCs were isolated, characterized and analyzed to examine the possible presence of CaSR by western blotting and flow cytometry analysis. Once we had demonstrated CaSR expression, we worked out that 1 µM R-568 was the optimal and effective concentration by cell viability test (MTT, cell number, Alkaline Phosphatase (ALP and Alizarin Red S (ARS assays. Interestingly, we observed that basal diffuse CaSR expression in oAFMSCs increased at the membrane when cells were treated with R-568 (1 µM, potentially resulting in activation of the receptor. This was associated with significantly increased cell mineralization (ALP and ARS staining and augmented intracellular calcium and Inositol trisphosphate (IP3 levels, thus demonstrating a potential role for calcimimetics during osteogenic differentiation. Calhex-231, a CaSR allosteric inhibitor, totally reversed R-568 induced mineralization. Taken together, our results demonstrate for the first time that CaSR is expressed in oAFMSCs and that calcimimetic R-568, possibly through CaSR activation, can significantly improve the osteogenic process. Hence, our study may provide useful information on the mechanisms regulating osteogenesis in oAFMSCs, perhaps

  5. Smoking-induced expression of the GPR15 gene indicates its potential role in chronic inflammatory pathologies.

    Science.gov (United States)

    Kõks, Gea; Uudelepp, Mari-Liis; Limbach, Maia; Peterson, Pärt; Reimann, Ene; Kõks, Sulev

    2015-11-01

    Despite the described clear epigenetic effects of smoking, the effect of smoking on genome-wide gene expression in the blood is obscure. We therefore studied the smoking-induced changes in the gene-expression profile of the peripheral blood. RNA was extracted from the whole blood of 48 individuals with a detailed smoking history (24 never-smokers, 16 smokers, and 8 ex-smokers). Gene-expression profiles were evaluated with RNA sequencing, and results were analyzed separately in 24 men and 24 women. In the male smokers, 13 genes were statistically significantly (false-discovery rate smoking with regard to chronic inflammatory diseases. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  6. A potential role for immunotherapy in thyroid cancer by enhancing NY-ESO-1 cancer antigen expression.

    Science.gov (United States)

    Gunda, Viswanath; Frederick, Dennie T; Bernasconi, Maria J; Wargo, Jennifer A; Parangi, Sareh

    2014-08-01

    NY-ESO-1 is one of the most immunogenic members of the cancer/testis antigen family and its levels can be increased after exposure to demethylating and deacetylating agents. This cytoplasmic antigen can serve as a potent target for cancer immunotherapy and yet has not been well studied in differentiated thyroid cancer cells. We studied the baseline expression of NY-ESO-1 messenger RNA and protein before and after exposure to 5-aza-2'-deoxycytidine (DAC) (72 hours) in a panel of thyroid cancer cell lines using quantitative polymerase chain reaction and Western blot. HLA-A2+, NY-ESO-1+ thyroid cell lines were then co-cultured with peripheral blood lymphocytes transduced with NY-ESO-1 specific T-cell receptor (TCR) and assayed for interferon-gamma and Granzyme-B release in the medium. SCID mice injected orthotopically with BCPAP cells were treated with DAC to evaluate for NY-ESO-1 gene expression in vivo. None of the thyroid cancer cell lines showed baseline expression of NY-ESO-1. Three cell lines, BCPAP, TPC-1, and 8505c, showed an increase in NY-ESO-1 gene expression with DAC treatment and were found to be HLA-A2 positive. DAC-treated target BCPAP and TPC-1 tumor cells with up-regulated NY-ESO-1 levels were able to mount an appropriate interferon-gamma and Granzyme-B response upon co-culture with the NY-ESO-1-TCR-transduced peripheral blood lymphocytes. In vivo DAC treatment was able to increase NY-ESO-1 expression in an orthotopic mouse model with BCPAP cells. Our data suggest that many differentiated thyroid cancer cells can be pressed to express immune antigens, which can then be utilized in TCR-based immunotherapeutic interventions.

  7. LncRNAs Expression in Preeclampsia Placenta Reveals the Potential Role of LncRNAs Contributing to Preeclampsia Pathogenesis

    OpenAIRE

    He, Xiaoju; He, Yinyan; Xi, Binrong; Zheng, Jiusheng; Zeng, Xiaoming; Cai, Qinhua; OuYang, Yu; Wang, Chen; Zhou, Xiaofei; Huang, Huiying; Deng, Wei; Xin, Siming; Huang, Qixiang; Liu, Huai

    2013-01-01

    BACKGROUND: Long non-coding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. They are aberrantly expressed in many types of diseases. In this study, we aimed to investigate the lncRNA profiles in preeclampsia. Preeclampsia has been observed in patients with molar pregnancy where a fetus is absent, which demonstrate that the placenta is sufficient to cause this condition. Thus, we analyzed the lncRNA profiles in preeclampsia placentas. MET...

  8. Antagonistic dark/light-induced SigB/SigD, group 2 sigma factors, expression through redox potential and their roles in cyanobacteria.

    Science.gov (United States)

    Imamura, Sousuke; Asayama, Munehiko; Takahashi, Hiroyuki; Tanaka, Kan; Takahashi, Hideo; Shirai, Makoto

    2003-11-20

    The expression of group 2 sigma factors is characterized in a cyanobacterium Synechocystis sp. PCC 6803 grown in culture, changing light conditions (white, red and blue light, and darkness), or the presence of drugs (rifampicin, chloramphenicol, DCMU, and DBMIB), and the roles of these sigma factors are elucidated. The expression of dark/light-induced SigB/SigD was accelerated under opposite redox (oxidation/reduction) states in an electron transport chain of photosynthesis. Expression of the dark-induced lrtA and light-induced psbA2/3 transcript was significantly reduced in the sigB and sigD knockout strains, respectively. Abundant amounts of sigB transcript and protein were observed in the sigC knockout strain, implying that SigC represses SigB expression under light. These findings clearly showed that SigB/SigD with another group 2 sigma, SigC, contribute to transcription for a subset of dark/light-responsive genes in the cyanobacterium. A possible model for SigB/SigD is presented and the potential ability for promoter recognition is also discussed.

  9. HIF-1α and GLUT-1 Expression in Atypical Endometrial Hyperplasia, Type I and II Endometrial Carcinoma: A Potential Role in Pathogenesis.

    Science.gov (United States)

    Al-Sharaky, Dalia Rifaat; Abdou, Asmaa Gaber; Wahed, Moshira Mohammed Abdel; Kassem, Hend Abdou

    2016-05-01

    potential role in carcinogenesis of EC. HIF-1α may promote GLUT-1 expression in EC especially surrounding areas of necrosis. The differences between type I and type II EC regarding HIF-1α and GLUT-1 expression may confirm the differences in their aetiopathogenesis.

  10. LncRNAs expression in adjuvant-induced arthritis rats reveals the potential role of LncRNAs contributing to rheumatoid arthritis pathogenesis.

    Science.gov (United States)

    Jiang, Hui; Qin, Xiu-Juan; Li, Wei-Ping; Ma, Rong; Wang, Ting; Li, Zhu-Qing

    2016-11-15

    Long non-coding RNAs (LncRNAs) are an important class of widespread molecules involved in diverse biological functions, which are exceptionally expressed in numerous types of diseases. Currently, limited study on LncRNA in rheumatoid arthritis (RA) is available. In this study, we aimed to identify the specifically expressed LncRNA that are relevant to adjuvant-induced arthritis (AA) in rats, and to explore the possible molecular mechanisms of RA pathogenesis. To identify LncRNAs specifically expressed in rheumatoid arthritis, the expression of LncRNAs in synoviums of rats from the model group (n=3) was compared with that in the control group (n=3) using Arraystar Rat LncRNA/mRNA microarray and real-time polymerase chain reaction (RT-PCR). Up to 260 LncRNAs were found to be differentially expressed (≥1.5-fold-change) in the synoviums between AA model and the normal rats (170 up-regulated and 90 down-regulated LncRNAs in AA rats compared with normal rats). Coding-non-coding gene co-expression networks (CNC network) were drawn based on the correlation analysis between the differentially expressed LncRNAs and mRNAs. Six LncRNAs, XR_008357, U75927, MRAK046251, XR_006457, DQ266363 and MRAK003448, were selected to analyze the relationship between LncRNAs and RA via the CNC network and GO analysis. Real-time PCR result confirmed that the six LncRNAs were specifically expressed in the AA rats. These results revealed that clusters of LncRNAs were uniquely expressed in AA rats compared with controls, which manifests that these differentially expressed LncRNAs in AA rats might play a vital role in RA development. Up-regulation or down-regulation of the six LncRNAs might contribute to the molecular mechanism underlying RA. To sum up, our study provides potential targets for treatment of RA and novel profound understanding of the pathogenesis of RA. Copyright © 2016. Published by Elsevier B.V.

  11. Differential gene expression and transport functionality in the bundle sheath versus mesophyll - a potential role in leaf mineral homeostasis.

    Science.gov (United States)

    Wigoda, Noa; Pasmanik-Chor, Metsada; Yang, Tianyuan; Yu, Ling; Moshelion, Menachem; Moran, Nava

    2017-06-01

    Under fluctuating ambient conditions, the ability of plants to maintain hydromineral homeostasis requires the tight control of long distance transport. This includes the control of radial transport within leaves, from veins to mesophyll. The bundle sheath is a structure that tightly wraps around leaf vasculature. It has been suggested to act as a selective barrier in the context of radial transport. This suggestion is based on recent physiological transport assays of bundle sheath cells (BSCs), as well as the anatomy of these cells.We hypothesized that the unique transport functionality of BSCs is apparent in their transcriptome. To test this, we compared the transcriptomes of individually hand-picked protoplasts of GFP-labeled BSCs and non-labeled mesophyll cells (MCs) from the leaves of Arabidopsis thaliana. Of the 90 genes differentially expressed between BSCs and MCs, 45% are membrane related and 20% transport related, a prominent example being the proton pump AHA2. Electrophysiological assays showed that the major AKT2-like membrane K+ conductances of BSCs and MCs had different voltage dependency ranges. Taken together, these differences may cause simultaneous but oppositely directed transmembrane K+ fluxes in BSCs and MCs, in otherwise similar conditions. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  12. Microarray Expression Profile Analysis of Long Non-Coding RNAs in Umbilical Cord Plasma Reveals their Potential Role in Gestational Diabetes-Induced Macrosomia

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    Zhonghua Shi

    2015-05-01

    Full Text Available Background: Fetal macrosomia and its associated complications are the most frequent and serious morbidities for infants associated with gestational diabetes mellitus (GDM. The associations between long non-coding RNAs (lncRNAs and macrosomia have been rarely reported; therefore, we investigated the umbilical cord lncRNA profiles in GDM macrosomia. Method: Thirty pairs of GDM macrosomia and normal controls were divided into three subgroups randomly, and the umbilical cord vein blood from each subgroup was mixed, and hybridized to a microarray containing probes representing 33,000 lncRNA genes. Quantitative real-time polymerase chain reaction (qPCR was used to validate selected differentially expressed lncRNAs. The gene ontology (GO, pathway and network analysis were performed. Result: The microarray identified 8814 lncRNAs that were expressed in the umbilical cord blood, of which 349 were significantly upregulated and 892 were significantly downregulated (fold-change ≥ 2.0 in GDM group. The highest enriched GOs targeted by downregulated transcripts were biological regulation. Pathway analysis indicated that nine pathways corresponded to downregulated transcripts. Conclusions: Certain lncRNAs that were aberrantly expressed in the umbilical cord blood from GDM macrosomia might play a partial or key role in GDM macrosomia development. This study provided potential targets for treatment of macrosomia and novel insights into macrosomia biology.

  13. Microarray Expression Profile Analysis of Long Non-Coding RNAs in Umbilical Cord Plasma Reveals their Potential Role in Gestational Diabetes-Induced Macrosomia.

    Science.gov (United States)

    Shi, Zhonghua; Zhao, Chun; Long, Wei; Ding, Hongjuan; Shen, Rong

    2015-01-01

    Fetal macrosomia and its associated complications are the most frequent and serious morbidities for infants associated with gestational diabetes mellitus (GDM). The associations between long non-coding RNAs (lncRNAs) and macrosomia have been rarely reported; therefore, we investigated the umbilical cord lncRNA profiles in GDM macrosomia. Thirty pairs of GDM macrosomia and normal controls were divided into three subgroups randomly, and the umbilical cord vein blood from each subgroup was mixed, and hybridized to a microarray containing probes representing 33,000 lncRNA genes. Quantitative real-time polymerase chain reaction (qPCR) was used to validate selected differentially expressed lncRNAs. The gene ontology (GO), pathway and network analysis were performed. The microarray identified 8814 lncRNAs that were expressed in the umbilical cord blood, of which 349 were significantly upregulated and 892 were significantly downregulated (fold-change ≥ 2.0) in GDM group. The highest enriched GOs targeted by downregulated transcripts were biological regulation. Pathway analysis indicated that nine pathways corresponded to downregulated transcripts. Certain lncRNAs that were aberrantly expressed in the umbilical cord blood from GDM macrosomia might play a partial or key role in GDM macrosomia development. This study provided potential targets for treatment of macrosomia and novel insights into macrosomia biology. © 2015 S. Karger AG, Basel.

  14. Gene expression profile of patients with Mayer-Rokitansky-Küster-Hauser syndrome: new insights into the potential role of developmental pathways.

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    Cristina Nodale

    Full Text Available Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS is a rare disease characterized by congenital aplasia of uterus and vagina. Although many studies have investigated several candidate genes, up to now none of them seem to be responsible for the aetiology of the syndrome. In our study, we identified differences in gene expression profile of in vitro cultured vaginal tissue of MRHKS patients using whole-genome microarray analysis. A group of eight out of sixteen MRKHS patients that underwent reconstruction of neovagina with an autologous in vitro cultured vaginal tissue were subjected to microarray analysis and compared with five healthy controls. Results obtained by array were confirmed by qRT-PCR and further extended to other eight MRKHS patients. Gene profiling of MRKHS patients delineated 275 differentially expressed genes, of which 133 downregulated and 142 upregulated. We selected six deregulated genes (MUC1, HOXC8, HOXB2, HOXB5, JAG1 and DLL1 on the basis of their fold change, their differential expression in most patients and their relevant role in embryological development. All patients showed upregulation of MUC1, while HOXB2 and HOXB5 were downregulated, as well as Notch ligands JAG1 and DLL1 in the majority of them. Interestingly, HOXC8 was significantly upregulated in 47% of patients, with a differential expression only in MRKHS type I patients. Taken together, our results highlighted the dysregulation of developmental genes, thus suggesting a potential alteration of networks involved in the formation of the female reproductive tract and providing a useful clue for understanding the pathophysiology of MRKHS.

  15. The potential role of Brachyury in inducing epithelial-to-mesenchymal transition (EMT) and HIF-1α expression in breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Shao, Chao [Department of Mammary Surgery, Zhongshan Hospital of Sun Yat-sen University, Zhongshan, 528403 (China); Zhang, Jingjing, E-mail: jingjingzhangzs@163.com [Department of Cancer Radiotherapy, Zhongshan Hospital of Sun Yat-sen University, Zhongshan, 528403 (China); Fu, Jianhua [Department of Thoracic Surgery, Cancer Center, Zhongshan Hospital of Sun Yat-sen University, Zhongshan, 528403 (China); Ling, Feihai, E-mail: feihailingfhl@163.com [Department of Mammary Surgery, Zhongshan Hospital of Sun Yat-sen University, Zhongshan, 528403 (China)

    2015-11-27

    One of transcription factors of the T-box family, Brachyury has been implicated in tumorigenesis of many types of cancers, regulating cancer cell proliferation, metastasis, invasion and epithelial-to-mesenchymal transition (EMT). However, the role of Brachyury in breast cancer cells has been scarcely reported. The present study aimed to investigate the expression and role of Brachyury in breast cancer. Brachyury expression was analyzed by qRT-PCR and Western blot. The correlations between Brachyury expression and clinicopathological factors of breast cancer were determined. Involvement of EMT stimulation and hypoxia-inducible factor-1α (HIF-1α) expression induction by Brachyury was also evaluated. Moreover, the effect of Brachyury on tumor growth and metastasis in vivo was examined in a breast tumor xenograft model. Brachyury expression was enhanced in primary breast cancer tissues and Brachyury expression was correlated with tumor stage and lymph node metastasis. Hypoxia enhanced Brachyury expression, the silencing of which blocked the modulation effect of hypoxia on E-cadherin and vimentin expression. Brachyury significantly augmented HIF-1alpha expression via PTEN/Akt signaling as well as accelerated cell proliferation and migration in vitro. Additionally, Brachyury accelerated breast tumor xenograft growth and increased lung metastasis in nude mice. In summary, our data confirmed that Brachyury might contribute to hypoxia-induced EMT of breast cancer and trigger HIF-1alpha expression via PTEN/Akt signaling. - Highlights: • Brachyury expression was correlated with tumor stage and lymph node metastasis. • Hypoxia enhanced Brachyury expression, which contributes to hypoxia-induced EMT. • Brachyury significantly augmented HIF-1alpha expression via PTEN/Akt signaling. • Brachyury accelerated tumor xenograft growth and increased lung metastasis.

  16. The bovine paranasal sinuses: Bacterial flora, epithelial expression of nitric oxide and potential role in the in-herd persistence of respiratory disease pathogens.

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    Gerard M Murray

    Full Text Available The bovine paranasal sinuses are a group of complex cavernous air-filled spaces, lined by respiratory epithelium, the exact function of which is unclear. While lesions affecting these sinuses are occasionally reported in cattle, their microbial flora has not been defined. Furthermore, given that the various bacterial and viral pathogens causing bovine respiratory disease (BRD persist within herds, we speculated that the paranasal sinuses may serve as a refuge for such infectious agents. The paranasal sinuses of clinically normal cattle (n = 99 and of cattle submitted for post-mortem examination (PME: n = 34 were examined by microbial culture, PCR and serology to include bacterial and viral pathogens typically associated with BRD: Mycoplasma bovis, Histophilus somni, Mannheimia haemolytica and Pasteurella multocida, bovine respiratory syncytial virus (BRSV and bovine parainfluenza-3 virus (BPIV-3. Overall, the paranasal sinuses were either predominantly sterile or did not contain detectable microbes (83.5%: 94.9% of clinically normal and 50.0% of cattle submitted for PME. Bacteria, including BRD causing pathogens, were identified in relatively small numbers of cattle (<10%. While serology indicated widespread exposure of both clinically normal and cattle submitted for PME to BPIV-3 and BRSV (seroprevalences of 91.6% and 84.7%, respectively, PCR identified BPIV-3 in only one animal. To further explore these findings we investigated the potential role of the antimicrobial molecule nitric oxide (NO within paranasal sinus epithelium using immunohistochemistry. Expression of the enzyme responsible for NO synthesis, inducible nitric oxide synthase (iNOS, was detected to varying degrees in 76.5% of a sub-sample of animals suggesting production of this compound plays a similar protective role in the bovine sinus as it does in humans.

  17. Cloning, expression pattern, and potential role of apoptosis inhibitor 5 in the termination of embryonic diapause and early embryo development of Artemia sinica.

    Science.gov (United States)

    Zhang, Shuang; Yao, Feng; Jing, Ting; Zhang, Mengchen; Zhao, Wei; Zou, Xiangyang; Sui, Linlin; Hou, Lin

    2017-09-10

    During the embryonic development of Artemia sinica, the diapause phenomenon can be induced by high salinity or low temperature conditions. The diapause embryo at the gastrula stage is maintained under the threat of apoptosis to guarantee the embryo's normal development. In this process, apoptosis inhibitor proteins play vital roles in protecting embryos against apoptosis. Apoptosis inhibitor5 (API5) plays a pivotal role in regulating the cell cycle and preventing programmed cell death after growth factor starvation. In the present study, we cloned the full-length cDNA representing the api5 gene from A. sinica (As-api5), which encodes a 372-amino acid protein. In situ hybridization experiments revealed that As-api5 expression is not tissue or organ specific. Quantitative real-time PCR analyses of the developmental expression of As-api5 showed that it reached its highest level at 10h, after which its expression decreased. High salinity and low temperature treatments increased the expression of As-api5. Western blotting was used to assess the abundance of As-API5 and related proteins (As-CyclinA, As-CyclinE, As-E2F1, As-CDK2, As-APAF1, and As-Caspase9). Downregulation of As-api5 expression using a short interfering RNA resulted in increased mortality and embryo malformation of A. sinica. Taken together, the results indicated that API5 plays a crucial role in embryonic diapause termination and early embryo development of A. sinica. Copyright © 2017. Published by Elsevier B.V.

  18. The miRNAome of Catharanthus roseus: identification, expression analysis, and potential roles of microRNAs in regulation of terpenoid indole alkaloid biosynthesis

    Science.gov (United States)

    Shen, Ethan M.; Singh, Sanjay K.; Ghosh, Jayadri S.; Patra, Barunava; Paul, Priyanka; Yuan, Ling; Pattanaik, Sitakanta

    2017-01-01

    MicroRNAs (miRNAs) regulate numerous crucial biological processes in plants. However, information is limited on their involvement in the biosynthesis of specialized metabolites in plants, including Catharanthus roseus that produces a number of pharmaceutically valuable, bioactive terpenoid indole alkaloids (TIAs). Using small RNA-sequencing, we identified 181 conserved and 173 novel miRNAs (cro-miRNAs) in C. roseus seedlings. Genome-wide expression analysis revealed that a set of cro-miRNAs are differentially regulated in response to methyl jasmonate (MeJA). In silico target prediction identified 519 potential cro-miRNA targets that include several auxin response factors (ARFs). The presence of cleaved transcripts of miRNA-targeted ARFs in C. roseus cells was confirmed by Poly(A) Polymerase-Mediated Rapid Amplification of cDNA Ends (PPM-RACE). We showed that auxin (indole acetic acid, IAA) repressed the expression of key TIA pathway genes in C. roseus seedlings. Moreover, we demonstrated that a miRNA-regulated ARF, CrARF16, binds to the promoters of key TIA pathway genes and repress their expression. The C. roseus miRNAome reported here provides a comprehensive account of the cro-miRNA populations, as well as their abundance and expression profiles in response to MeJA. In addition, our findings underscore the importance of miRNAs in posttranscriptional control of the biosynthesis of specialized metabolites. PMID:28223695

  19. Decidual Macrophages Are Significantly Increased in Spontaneous Miscarriages and Over-Express FasL: A Potential Role for Macrophages in Trophoblast Apoptosis

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    Antonis Makrigiannakis

    2012-07-01

    Full Text Available Decidual macrophages (DM are the second most abundant population in the fetal-maternal interface. Their role has been so far identified as being local immuno-modulators favoring the maternal tolerance to the fetus. Herein we investigated tissue samples from 11 cases of spontaneous miscarriages and from 9 cases of elective terminations of pregnancy. Using immunohistochemistry and dual immunofluorescence we have demonstrated that in spontaneous miscarriages the DM are significantly increased. Additionally, we noted a significant up-regulation of macrophage FasL expression. Our results further support a dual role for DM during pregnancy and miscarriages. We hypothesize that the baseline DM population in normal pregnancy is in line with an M2 phenotype supporting the ongoing gestation. In contrast, during spontaneous miscarriages, the increased FasL-expressing population could be a part of an M1 phenotype participating in Fas/FasL-related apoptosis. Our results highlight a new aspect of macrophage biology in pregnancy physiology and pathophysiology. Further studies with larger samples are needed to verify the current results and evaluate their clinical impact.

  20. Evolution and expression analysis reveal the potential role of the HD-Zip gene family in regulation of embryo abortion in grapes (Vitis vinifera L.).

    Science.gov (United States)

    Li, Zhiqian; Zhang, Chen; Guo, Yurui; Niu, Weili; Wang, Yuejin; Xu, Yan

    2017-09-21

    The HD-Zip family has a diversity of functions during plant development. In this study, we identify 33 HD-Zip transcription factors in grape and detect their expressions in ovules and somatic embryos, as well as in various vegetative organs. A genome-wide survey for HD-Zip transcription factors in Vitis was conducted based on the 12 X grape genome (V. vinifera L.). A total of 33 members were identified and classified into four subfamilies (I-IV) based on phylogeny analysis with Arabidopsis, rice and maize. VvHDZs in the same subfamily have similar protein motifs and intron/exon structures. An evaluation of duplication events suggests several HD-Zip genes arose before the divergence of the grape and Arabidopsis lineages. The 33 members of HD-Zip were differentially expressed in ovules of the stenospermic grape, Thompson Seedless and of the seeded grape, Pinot noir. Most have higher expressions during ovule abortion in Thompson Seedless. In addition, transcripts of the HD-Zip family were also detected in somatic embryogenesis of Thompson Seedless and in different vegetative organs of Thompson Seedless at varying levels. Additionally, VvHDZ28 is located in the nucleus and had transcriptional activity consistent with the typical features of the HD-Zip family. Our results provide a foundation for future grape HD-Zip gene function research. The identification and expression profiles of the HD-Zip transcription factors in grape, reveal their diverse roles during ovule abortion and organ development. Our results lay a foundation for functional analysis of grape HDZ genes.

  1. Interleukin-6 induces keratin expression in intestinal epithelial cells: potential role of keratin-8 in interleukin-6-induced barrier function alterations.

    Science.gov (United States)

    Wang, Lixin; Srinivasan, Shanthi; Theiss, Arianne L; Merlin, Didier; Sitaraman, Shanthi V

    2007-03-16

    Keratin 8 (K8) and keratin-18 (K18) are the major intermediate filament proteins in the intestinal epithelia. The regulation and function of keratin in the intestinal epithelia is largely unknown. In this study we addressed the role and regulation of K8 and K18 expression by interleukin 6 (IL-6). Caco2-BBE cell line and IL-6 null mice were used to study the effect of IL-6 on keratin expression. Keratin expression was studied by Northern blot, Western blot, and confocal microscopy. Paracellular permeability was assessed by apical-to-basal transport of a fluorescein isothiocyanate dextran probe (FD-4). K8 was silenced using the small interfering RNA approach. IL-6 significantly up-regulated mRNA and protein levels of K8 and K18. Confocal microscopy showed a reticular pattern of intracellular keratin localized to the subapical region after IL-6 treatment. IL-6 also induced serine phosphorylation of K8. IL-6 decreased paracellular flux of FD-4 compared with vehicle-treated monolayers. K8 silencing abolished the decrease in paracellular permeability induced by IL-6. Administration of dextran sodium sulfate (DSS) significantly increased intestinal permeability in IL-6-/- mice compared with wild type mice given DSS. Collectively, our data demonstrate that IL-6 regulates the colonic expression of K8 and K18, and K8/K18 mediates barrier protection by IL-6 under conditions where intestinal barrier is compromised. Thus, our data uncover a novel function of these abundant cytoskeletal proteins, which may have implications in intestinal disorders such as inflammatory bowel disease wherein barrier dysfunction underlies the inflammatory response.

  2. An ethanolic extract of Artemisia dracunculus L. regulates gene expression of ubiquitin-proteasome system enzymes in skeletal muscle: potential role in the treatment of sarcopenic obesity.

    Science.gov (United States)

    Kirk-Ballard, Heather; Kilroy, Gail; Day, Britton C; Wang, Zhong Q; Ribnicky, David M; Cefalu, William T; Floyd, Z Elizabeth

    2014-01-01

    Obesity is linked to insulin resistance, a primary component of metabolic syndrome and type 2 diabetes. The problem of obesity-related insulin resistance is compounded when age-related skeletal muscle loss, called sarcopenia, occurs with obesity. Skeletal muscle loss results from elevated levels of protein degradation and prevention of obesity-related sarcopenic muscle loss will depend on strategies that target pathways involved in protein degradation. An extract from Artemisia dracunculus, termed PMI 5011, improves insulin signaling and increases skeletal muscle myofiber size in a rodent model of obesity-related insulin resistance. The aim of this study was to examine the effect of PMI 5011 on the ubiquitin-proteasome system, a central regulator of muscle protein degradation. Gastrocnemius and vastus lateralis skeletal muscle was obtained from KK-A(y) obese diabetic mice fed a control or 1% (w/w) PMI 5011-supplemented diet. Regulation of genes encoding enzymes of the ubiquitin-proteasome system was determined using real-time quantitative reverse transcriptase polymerase chain reaction. Although MuRF-1 ubiquitin ligase gene expression is consistently down-regulated in skeletal muscle, atrogin-1, Fbxo40, and Traf6 expression is differentially regulated by PMI 5011. Genes encoding other enzymes of the ubiquitin-proteasome system ranging from ubiquitin to ubiquitin-specific proteases are also regulated by PMI 5011. Additionally, expression of the gene encoding the microtubule-associated protein-1 light chain 3 (LC3), a ubiquitin-like protein pivotal to autophagy-mediated protein degradation, is down-regulated by PMI 5011 in the vastus lateralis. PMI 5011 alters the gene expression of ubiquitin-proteasome system enzymes that are essential regulators of skeletal muscle mass. This suggests that PMI 5011 has therapeutic potential in the treatment of obesity-linked sarcopenia by regulating ubiquitin-proteasome-mediated protein degradation. Copyright © 2014 Elsevier Inc

  3. Human health consequences of environmentally-modulated gene expression: potential roles of ELF-EMF induced epigenetic versus mutagenic mechanisms of disease.

    Science.gov (United States)

    Trosko, J E

    2000-07-01

    In order to determine if there might be biological and health consequences after exposures to extremely-low frequency electromagnetic fields (ELF-EMF), either experimentally or epidemiologically, mechanistic understanding of the potential means by which any environmental agent can affect cells in a multicellular organism has to be reviewed. The goal of this limited review is to demonstrate that, while the prevailing paradigm of the environmentally-induced acute and chronic diseases involves either cell killing (cytotoxicity) or gene/chromosome mutations (genotoxicity), alteration of the expression of genetic information at the transcriptional (turning genes "on" or "off"), translational (stabilizing or de-stabilizing the genetic message), or posttranslational (altering the gene product or protein) levels has the potential to contribute to various diseases. This latter mechanism, "epigenetic" toxicity, unlike the former two which are irreversible, is characterized by threshold-like action, multiple biochemical pathways and chronic, regular exposures to be effective. Ultimately, epigenetic toxicants affect one of four potential cell states, namely alteration of cell proliferation, cell differentiation, programmed cell death (apoptosis) or adaptive responses of differentiated cells. Copyright 2000 Wiley-Liss, Inc.

  4. Potential roles of CCR5(+ CCR6(+ dendritic cells induced by nasal ovalbumin plus Flt3 ligand expressing adenovirus for mucosal IgA responses.

    Directory of Open Access Journals (Sweden)

    Yoshiko Fukuyama

    Full Text Available We assessed the role of CCR5(+/CCR6(+/CD11b(+/CD11c(+ dendritic cells (DCs for induction of ovalbumin (OVA-specific antibody (Ab responses following mucosal immunization. Mice given nasal OVA plus an adenovirus expressing Flt3 ligand (Ad-FL showed early expansion of CCR5(+/CCR6(+/CD11b(+/CD11c(+ DCs in nasopharyngeal-associated lymphoid tissue (NALT and cervical lymph nodes (CLNs. Subsequently, this DC subset became resident in submandibular glands (SMGs and nasal passages (NPs in response to high levels of CCR-ligands produced in these tissues. CD11b(+/CD11c(+ DCs were markedly decreased in both CCR5(-/- and CCR6(-/- mice. Chimera mice reconstituted with bone marrow cells from CD11c-diphtheria toxin receptor (CD11c-DTR and CCR5(-/- or CD11c-DTR and CCR6(-/- mice given nasal OVA plus Ad-FL had elevated plasma IgG, but reduced IgA as well as low anti-OVA secretory IgA (SIgA Ab responses in saliva and nasal washes. These results suggest that CCR5(+CCR6(+ DCs play an important role in the induction of Ag-specific SIgA Ab responses.

  5. Differential expression of angiotensin II type 1 and type 2 receptors at the maternal-fetal interface: potential roles in early placental development.

    Science.gov (United States)

    Tower, C L; Lui, S; Charlesworth, N R; Smith, S D; Aplin, J D; Jones, R L

    2010-12-01

    Angiotensin II (Ang II) is locally generated in the placenta and regulates syncytial transport, vascular contractility and trophoblast invasion. It acts through two receptor subtypes, AGTR1 and AGTR2 (AT1 and AT2), which typically mediate antagonising actions. The objectives of this study are to characterise the cellular distribution of AGTR1 and AGTR2 at the maternal-fetal interface and explore the effects on cytotrophoblast turnover. Low levels of AGTR2 mRNA were detected in first trimester placental homogenates using real-time PCR. Immunohistochemistry using polyclonal antibodies against AGTR1 and AGTR2 detected the receptors in first trimester placenta, decidua basalis and villous tip outgrowths in culture. Serial staining with cytokeratin-7 was used to identify extravillous trophoblasts (EVTs). AGTR1 was found in the syncytiotrophoblast microvillous membrane, in a subpopulation of villous cytotrophoblasts, and in Hofbauer cells. AGTR1 was strongly upregulated in cytotrophoblasts in cell columns and villous tip outgrowths, but was absent in interstitial and endovascular EVTs within the decidua. AGTR2 immunostaining was present in Hofbauer cells and villous cytotrophoblasts, but was absent from syncytiotrophoblast. Faint staining was detected in cell column cytotrophoblasts and villous outgrowths, but not in EVTs within the decidua. Both receptors were detected in placental homogenates by western blotting. Ang II significantly increased proliferation of cytotrophoblasts in both villous explants and villous tip outgrowths, but did not affect apoptosis. Blockade of AGTR1 and AGTR2 together abrogated this effect. This study shows specific expression patterns for AGTR1 and AGTR2 in distinct trophoblast populations at the maternal-fetal interface and suggests that Ang II plays a role in placental development and generation of EVTs.

  6. Yersinia pestis insecticidal-like toxin complex (Tc family proteins: characterization of expression, subcellular localization, and potential role in infection of the flea vector

    Directory of Open Access Journals (Sweden)

    Spinner Justin L

    2012-12-01

    Full Text Available Abstract Background Toxin complex (Tc family proteins were first identified as insecticidal toxins in Photorhabdus luminescens and have since been found in a wide range of bacteria. The genome of Yersinia pestis, the causative agent of bubonic plague, contains a locus that encodes the Tc protein homologues YitA, YitB, YitC, and YipA and YipB. Previous microarray data indicate that the Tc genes are highly upregulated by Y. pestis while in the flea vector; however, their role in the infection of fleas and pathogenesis in the mammalian host is unclear. Results We show that the Tc proteins YitA and YipA are highly produced by Y. pestis while in the flea but not during growth in brain heart infusion (BHI broth at the same temperature. Over-production of the LysR-type regulator YitR from an exogenous plasmid increased YitA and YipA synthesis in broth culture. The increase in production of YitA and YipA correlated with the yitR copy number and was temperature-dependent. Although highly synthesized in fleas, deletion of the Tc proteins did not alter survival of Y. pestis in the flea or prevent blockage of the proventriculus. Furthermore, YipA was found to undergo post-translational processing and YipA and YitA are localized to the outer membrane of Y. pestis. YitA was also detected by immunofluorescence microscopy on the surface of Y. pestis. Both YitA and YipA are produced maximally at low temperature but persist for several hours after transfer to 37°C. Conclusions Y. pestis Tc proteins are highly expressed in the flea but are not essential for Y. pestis to stably infect or produce a transmissible infection in the flea. However, YitA and YipA localize to the outer membrane and YitA is exposed on the surface, indicating that at least YitA is present on the surface when Y. pestis is transmitted into the mammalian host from the flea.

  7. Regulation of insulin-like growth factor (IGF) I receptor expression during muscle cell differentiation. Potential autocrine role of IGF-II.

    OpenAIRE

    Rosenthal, S.M.; Brunetti, A; Brown, E J; Mamula, P W; Goldfine, I. D.

    1991-01-01

    Muscle is an important target tissue for insulin-like growth factor (IGF) action. The presence of specific, high affinity IGF receptors, as well as the expression of IGF peptides and binding proteins by muscle suggest that a significant component of IGF action in this tissue is mediated through autocrine and/or paracrine mechanisms. To explore autocrine/paracrine action of IGFs in muscle, we studied the regulation of the IGF-I receptor and the expression of IGF peptides during differentiation...

  8. Residual feed intake studies in Angus-sired cattle reveal a potential role for hypothalamic gene expression in regulating feed efficiency.

    Science.gov (United States)

    Perkins, S D; Key, C N; Garrett, C F; Foradori, C D; Bratcher, C L; Kriese-Anderson, L A; Brandebourg, T D

    2014-02-01

    Mechanisms underlying variation in residual feed intake (RFI), a heritable feed efficiency measure, are poorly understood while the relationship between RFI and meat quality is uncertain. To address these issues, 2 divergent cohorts consisting of High (HRFI) and Low (LRFI) RFI individuals were created by assessing RFI in 48 Angus-sired steers during a 70 d feeding trial to identify steers with divergent RFI. The association of RFI with indices of meat quality and expression of genes within hypothalamic and adipose tissue was then determined in LRFI and HRFI steers. While on test, feed intake was recorded daily with BW and hip heights recorded at 14 d intervals. Ultrasound measurements of rib eye area (REA) and backfat (BF) were recorded initially and before harvest. Carcass and growth data were analyzed using a mixed model with RFI level (LRFI, HRFI) as the independent variable. The least-square means (lsmeans) for RFI were -1.25 and 1.51 for the LRFI and HRFI cohorts (P intake was higher for the HRFI individuals versus the LRFI steers (P changes in gene expression within the arcuate nucleus had functional consequences. Leptin mRNA expression was 245% higher in the adipose tissue of LRFI steers consistent with lower levels of NPY and higher expression of POMC in their hypothalami. These data support the hypothesis that differences in hypothalamic neuropeptide gene expression underlie variation in feed efficiency in steers while the gonadotropin axis may also influence feed efficiency.

  9. Potential role of miR-29b in modulation of Dnmt3a and Dnmt3b expression in primordial germ cells of female mouse embryos

    NARCIS (Netherlands)

    Takada, S.; Berezikov, E.; Choi, Y.L.; Yamashita, Y.; Mano, H.

    2009-01-01

    MicroRNAs (miRNAs) are a recently discovered class of small noncoding RNAs and are implicated in an increasing number of biological processes. To examine whether miRNAs might contribute to sexual differentiation, we performed expression profiling of miRNAs in mouse embryonic gonads with the use of a

  10. Identification, expression pattern and potential role of variable lymphocyte receptor Aj-VLRA from Apostichopus japonicus in response to bacterial challenge.

    Science.gov (United States)

    Yang, Lei; Yao, Feng; Ba, Huazhong; Qin, Tong; Luan, Hong; Li, Zhengmin; Hou, Lin; Zou, Xiangyang

    2015-08-01

    The variable lymphocyte receptors (VLRs) are found in jawless vertebrates (agnathans), and specifically recognize bacteria and viruses via their leucine-rich repeats (LRRs). VLRs are believed to be adaptive immune response molecules. Echinoderms do not have adaptive immune systems; however, in the present study, a VLR cDNA named Aj-VLRA was cloned and characterized from sea cucumber, Apostichopus japonicus. The complete cDNA of Aj-VLRA was 3072 bp, including a 1995 bp open reading frame encoding 664 amino acids comprising LRR domains, a predicted transmembrane helix and an N-terminal signal peptide. As determined by quantitative real-time reverse transcription polymerase chain reaction, Aj-VLRA transcripts are ubiquitously expressed in the body wall, longitudinal muscles, intestine and respiratory tree of A. japonicus. The expression level of Aj-VLRA was upregulated after challenge with four common marine bacteria. In situ hybridization showed that the expression of Aj-VLRA was widely distributed in the four tissues, particularly in the cytoplasm of epidermal cells. Recombinantly expressed Aj-VLRA (including the LRR domains) could bind to bacteria including Micrococcus lysodeikticus (Gram+) and Vibrio anguillarum (Gram-). Collectively, the results suggested that Aj-VLRA is related to an innate immune response of A. japonicus. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. GENE EXPRESSION PROFILING OF ORBITAL ADIPOSE TISSUE FROM PATIENTS WITH GRAVES’ OPHTHALMOPATHY: A POTENTIAL ROLE FOR SOLUBLE FRIZZLED RELATED PROTEIN-1 IN ORBITAL ADIPOGENESIS

    Science.gov (United States)

    Kumar, Seema; Leontovich, Alexey; Coenen, Michael J.; Bahn, Rebecca S.

    2005-01-01

    Context: The signs and symptoms of Graves’ ophthalmopathy (GO) result from inflammation and increased volume of the orbital adipose tissues and extraocular muscles. Objective: To identify differentially regulated genes that may be involved in stimulating the orbital adipose tissue expansion seen in GO. Design: Gene expression profiling was used to compare genes expressed in orbital adipose tissues from GO patients and normal individuals. Setting: Private practice tertiary referral center. Patients: Orbital adipose tissues were collected at transantral orbital decompression surgery from 20 euthyroid patients undergoing this procedure for severe GO and at early autopsy from 8 normal individuals having no evidence of thyroid or ocular disease. Results: Of the 12,686 genes analyzed, 25 known genes were increased in expression (> 4 fold) in GO orbital tissues, while 11 genes were decreased (> 4 fold). Upregulated genes, confirmed by quantitative RT-PCR, included secreted frizzled related protein-1 (sFRP-1; 18.5 fold) and several adipocyte-related genes, including peroxisome proliferator activated receptor-γ (44.1 fold) and adiponectin (25 fold). Treatment in vitro of GO orbital preadipocytes with recombinant sFRP-1 (100 nM) significantly increased adiponectin (2.0 fold; p<.05), leptin (7 fold; p<.002), and thyrotropin receptor mRNA (13 fold; p<.003) levels, and enhanced Oil red-O staining in the cultures. Conclusions: These results support the concept that orbital adipogenesis is enhanced in GO, and suggest that elevated levels of sFRP-1 in the GO orbit may be involved in stimulating this pathogenic process. PMID:15886250

  12. Gene expression profile of high-fat diet-fed C57BL/6J mice: in search of potential role of azelaic acid.

    Science.gov (United States)

    Muthulakshmi, Shanmugam; Chakrabarti, Alok K; Mukherjee, Sanjay

    2015-03-01

    High-fat diet (HFD) elevates circulatory fatty acids and influences glucose and fat metabolism. Azelaic acid (AzA), a naturally occurring α,ω-dicarboxylic acid in wheat, rye, barley, oat seeds and sorghum, has been reported to exert antidiabetic effects in HFD-induced type 2 diabetes mellitus (T2DM) C57BL/6J mice. The present study was undertaken to identify the genes that are differentially modulated by treatment with AzA in HFD-fed mice. Mice were fed HFD for 10 weeks and subjected to intragastric administration of 80 mg/kg body weight (BW) of AzA daily along with HFD from 11 to 15 weeks. Lipid profile, adipokines and cytokines were examined in the plasma/liver of mice. Whole genome profiling was performed in the liver of mice using microarray and validated by qRT-PCR, Western blot and immunohistochemical analyses. HFD intake resulted in significantly elevated lipids (except high-density lipoproteins), resistin, tumour necrosis factor alpha and interleukin-6 with marked reduction in adiponectin. Administration of AzA to HFD-fed mice significantly restored the lipids, adipokines and cytokines to near normal. Transcript profiling revealed that HFD intake activated the genes involved in stress response, cell cycle regulation and apoptosis. Treatment with AzA caused increased expression of genes involved in reactive oxygen species (ROS) scavenging, receptor-mediated signalling, transcription, protein modification and insulin signal transduction. AzA activates insulin signal molecules leading to insulin sensitivity. The ability of AzA to modulate the expression of these genes supports the notion that AzA is a promising drug candidate for the treatment of insulin resistance associated with T2DM.

  13. Evidence and potential in vivo functions for biofluid miRNAs: From expression profiling to functional testing: Potential roles of extracellular miRNAs as indicators of physiological change and as agents of intercellular information exchange.

    Science.gov (United States)

    Iftikhar, Hina; Carney, Ginger E

    2016-04-01

    A controversial hypothesis in RNA biology is that extracellular microRNAs (miRNAs), including those in biofluids, have non-cell-autonomous activities. Several studies have characterized biofluid miRNA profiles in healthy or diseased individuals but generally have failed to identify distinct disease signatures. It remains unclear whether alterations in fluid miRNA levels are simply indicators of physiological change or whether miRNAs are taken up by new cells at concentrations sufficient to affect gene expression. There are limitations to biofluid miRNA studies performed to date: methodology for isolating and quantifying biofluid miRNAs is not standardized across studies; mechanistic details of miRNA release and uptake are incomplete; and efforts to assess non-cell-autonomous effects of extracellular miRNAs have employed predominantly in vitro strategies. We describe controversies and questions that need to be addressed to test possible in vivo roles of extracellular miRNAs and propose model organisms with rich genetic toolkits for carrying out in vivo functional analyses. © 2016 WILEY Periodicals, Inc.

  14. Divergent Expression Patterns in Two Vernicia Species Revealed the Potential Role of the Hub Gene VmAP2/ERF036 in Resistance to Fusarium oxysporum in Vernicia montana

    Directory of Open Access Journals (Sweden)

    Qiyan Zhang

    2016-12-01

    Full Text Available Tung oil tree (Vernicia fordii is a promising industrial oil crop; however, this tree is highly susceptible to Fusarium wilt disease. Conversely, Vernicia montana is resistant to the pathogen. The APETALA2/ethylene-responsive element binding factor (AP2/ERF transcription factor superfamily has been reported to play a significant role in resistance to Fusarium oxysporum. In this study, comprehensive analysis identified 75 and 81 putative Vf/VmAP2/ERF transcription factor-encoding genes in V. fordii and V. montana, respectively, which were divided into AP2, ERF, related to ABI3 and VP1 (RAV and Soloist families. After F. oxysporum infection, a majority of AP2/ERF superfamily genes showed strong patterns of repression in both V. fordii and V. montana. We then identified 53 pairs of one-to-one orthologs in V. fordii and V. montana, with most pairs of orthologous genes exhibiting similar expression in response to the pathogen. Further investigation of Vf/VmAP2/ERF gene expression in plant tissues indicated that the pairs of genes with different expression patterns in response to F. oxysporum tended to exhibit different tissue profiles in the two species. In addition, VmAP2/ERF036, showing the strongest interactions with 666 genes, was identified as a core hub gene mediating resistance. Moreover, qRT-PCR results indicated VmAP2/ERF036 showed repressed expression while its orthologous gene VfAP2/ERF036 had the opposite expression pattern during pathogen infection. Overall, comparative analysis of the Vf/VmAP2/ERF superfamily and indication of a potential hub resistance gene in resistant and susceptible Vernicia species provides valuable information for understanding the molecular basis and selection of essential functional genes for V. fordii genetic engineering to control Fusarium wilt disease.

  15. Ectopic expression of the ATP synthase β subunit on the membrane of PC-3M cells supports its potential role in prostate cancer metastasis.

    Science.gov (United States)

    Li, Wei; Li, Yulin; Li, Gaiyun; Zhou, Zilong; Chang, Xiaona; Xia, Yang; Dong, Xinjie; Liu, Zhijing; Ren, Bo; Liu, Wei; Li, Yilei

    2017-04-01

    Metastatic prostate cancer is associated with high mortality rates. Identification of metastasis-related proteins may facilitate the development of novel therapies for the treatment of metastatic disease. In the present study, we aimed to identify prostate cancer metastasis-associated membrane proteins. We developed a phage-displayed 7-mer peptide library to screen the target peptides that were specifically bound to PC-3M cells with subtractive panning from normal prostate cells and PC-3 prostate cancer cells. A novel short peptide (B04) was found to have high affinity to highly metastatic PC-3M cells. ATP synthase β subunit (ATP5B) was then identified as a binding partner of B04 on the PC-3M cell surface. ATP5B was expressed on the PC-3M cell membrane and on highly malignant human prostate cancer specimens, as shown using multiple methodologies. Furthermore, ATP5B-positive gold particles were detected on the cellular and mitochondrial membranes by immunoelectromicroscopy. These results implied the possibility that ATP5B may translocate from the inner mitochondrial membrane to the outer surface of PC-3M cells. Additional analysis showed that incubation of B04 with PC-3M cells reduced the detection of ATP5B by western blotting and flow cytometry and significantly inhibited the proliferation, invasion and metastasis of PC-3M cells. In conclusion, ATP5B, as a binding partner of a metastasis-related short peptide (B04) on prostate cancer cells, is involved in promoting prostate cancer metastasis. In conclusion, ATP5B may be a promising biomarker and therapeutic target for highly metastatic malignancies.

  16. SVA retrotransposons as potential modulators of neuropeptide gene expression.

    Science.gov (United States)

    Gianfrancesco, Olympia; Bubb, Vivien J; Quinn, John P

    2017-08-01

    Many facets of human behaviour are likely to have developed in part due to evolutionary changes in the regulation of neuropeptide and other brain-related genes. This has allowed species-specific expression patterns and unique epigenetic modulation in response to our environment, regulating response not only at the molecular level, but also contributing to differences in behaviour between individuals. As such, genetic variants or epigenetic changes that may alter neuropeptide gene expression are predicted to play a role in behavioural conditions and psychiatric illness. It is therefore of interest to identify regulatory elements that have the potential to drive differential gene expression. Retrotransposons are mobile genetic elements that are known to be drivers of genomic diversity, with the ability to alter expression of nearby genes. In particular, the SINE-VNTR-Alu (SVA) class of retrotransposons is specific to hominids, and its appearance and expansion across the genome has been associated with the evolution of numerous behavioural traits, presumably through their ability to confer unique regulatory properties at the site of their insertion. We review the evidence for SVAs as regulatory elements, exploring how polymorphic variation within these repetitive sequences can drive allele specific gene expression, which would be associated with changes in behaviour and disease risk through the alteration of molecular pathways that are central to healthy brain function. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Podoplanin expression in oral leukoplakia: tumorigenic role.

    Science.gov (United States)

    de Vicente, Juan Carlos; Rodrigo, Juan Pablo; Rodriguez-Santamarta, Tania; Lequerica-Fernández, Paloma; Allonca, Eva; García-Pedrero, Juana María

    2013-06-01

    Recent studies have identified podoplanin, a mucin-type transmembrane glycoprotein, as a biomarker for oral cancer risk in patients with oral leukoplakia (OPL). The aim of this study was to investigate the potential association between podoplanin and the risk of malignant transformation of OPL with epithelial dysplasia. In this retrospective study, podoplanin immunoexpression was analyzed in 58 patients with oral leukoplakia that showed epithelial dysplasia. Lesions with podoplanin expression in the basal and suprabasal layers of oral epithelium at one area or showing suprabasal expression at two or more areas were considered as positive. Association between podoplanin expression and oral cancer development was analyzed. Twenty-two of the 58 lesions (38%) were classified as podoplanin-positive, and the remaining 36 (62%) lesions were considered podoplanin-negative. The expression of podoplanin was correlated with the grade of dysplasia (poral cancer (poral lesions displaying positive podoplanin expression showed a significantly increased risk of developing an oral squamous cell carcinoma (hazard ratio=8.738, p=0.007). Podoplanin could be a valuable biomarker for risk assessment of malignant transformation in patients with OPL along with histological assessment. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. The Nephrology Clinical Research Nurse Role: Potential Role Conflicts.

    Science.gov (United States)

    Micklos, Lisa

    2016-01-01

    Clinical research nursing is becoming more visible to nephrology professionals. As more nephrology practices and units are participating in clinical trials, clinical research nursing is gaining interest as a career niche among nephrology nurses. This unique specialty requires that nephrology clinical nurse nurses (CRNs) reconcile the roles of nurse as caregiver and nurse as researcher, which may result in a role conflict. Nephrology nurses should be aware that they may experience this role conflict when transitioning from patient care to a position as a clinical research nurse. These nurses can rely on the American Nurses Association's Code of Ethics for Nurses and the Oncology Nursing Society's Oncology Clinical Trials Nurse Competencies to help reconcile the potential role conflict.

  19. Potential physiological role of plant glycosidase inhibitors

    DEFF Research Database (Denmark)

    Bellincampi, D.; Carmadella, L.; Delcour, J.A.

    2004-01-01

    Carbohydrate-active enzymes including glycosidases, transglycosidases, glycosyltransferases, polysaccharide lyases and carbohydrate esterases are responsible for the enzymatic processing of carbohydrates in plants. A number of carbohydrate-active enzymes are produced by microbial pathogens...... and insects responsible of severe crop losses. Plants have evolved proteinaceous inhibitors to modulate the activity of several of these enzymes. The continuing discovery of new inhibitors indicates that this research area is still unexplored and may lead to new exciting developments. To date, the role...... of the inhibitors is not completely understood. Here we review recent results obtained on the best characterised inhibitors, pointing to their possible biological role in vivo. Results recently obtained with plant transformation technology indicate that this class of inhibitors has potential biotechnological...

  20. Control of Gene Expression in Leptospira spp. by Transcription Activator-Like Effectors Demonstrates a Potential Role for LigA and LigB in Leptospira interrogans Virulence.

    Science.gov (United States)

    Pappas, Christopher J; Picardeau, Mathieu

    2015-11-01

    Leptospirosis is a zoonotic disease that affects ∼1 million people annually, with a mortality rate of >10%. Currently, there is an absence of effective genetic manipulation tools for targeted mutagenesis in pathogenic leptospires. Transcription activator-like effectors (TALEs) are a recently described group of repressors that modify transcriptional activity in prokaryotic and eukaryotic cells by directly binding to a targeted sequence within the host genome. To determine the applicability of TALEs within Leptospira spp., two TALE constructs were designed. First, a constitutively expressed TALE gene specific for the lacO-like region upstream of bgaL was trans inserted in the saprophyte Leptospira biflexa (the TALEβgal strain). Reverse transcriptase PCR (RT-PCR) analysis and enzymatic assays demonstrated that BgaL was not expressed in the TALEβgal strain. Second, to study the role of LigA and LigB in pathogenesis, a constitutively expressed TALE gene with specificity for the homologous promoter regions of ligA and ligB was cis inserted into the pathogen Leptospira interrogans (TALElig). LigA and LigB expression was studied by using three independent clones: TALElig1, TALElig2, and TALElig3. Immunoblot analysis of osmotically induced TALElig clones demonstrated 2- to 9-fold reductions in the expression levels of LigA and LigB, with the highest reductions being noted for TALElig1 and TALElig2, which were avirulent in vivo and nonrecoverable from animal tissues. This study reconfirms galactosidase activity in the saprophyte and suggests a role for LigA and LigB in pathogenesis. Collectively, this study demonstrates that TALEs are effective at reducing the expression of targeted genes within saprophytic and pathogenic strains of Leptospira spp., providing an additional genetic manipulation tool for this genus. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  1. A potential role for tetranectin in mineralization during osteogenesis

    DEFF Research Database (Denmark)

    Wewer, U M; Ibaraki, K; Schjørring, P

    1994-01-01

    cartilage or in the surrounding skeletal muscle. Using an in vitro mineralizing system, we examined osteoblastic cells at different times during their growth and differentiation. Tetranectin mRNA appeared in the cultured osteoblastic cells in parallel with mineralization, in a pattern similar...... approximately fivefold more bone material than those produced by the untransfected PC12 cell line or by the PC12 cells transfected with the expression vector with no insert (Mann Whitney rank sum test, p important direct and/or indirect role during...... osteogenesis. In conclusion, we have established a potential role for tetranectin as a bone matrix protein expressed in time and space coincident with mineralization in vivo and in vitro....

  2. Metallothioneins in human tumors and potential roles in carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Cherian, M. George; Jayasurya, A.; Bay, Boon-Huat

    2003-12-10

    Metallothioneins (MT) are a group of low-molecular weight, cysteine rich intracellular proteins, which are encoded by a family of genes containing at least 10 functional isoforms in human. The expression and induction of these proteins have been associated with protection against DNA damage, oxidative stress and apoptosis. Moreover, MT may potentially activate certain transcriptional factors by donating zinc. Although MT is a cytosolic protein in resting cells, it can be translocated transiently to the cell nucleus during cell proliferation and differentiation. A number of studies have shown an increased expression of MT in various human tumors of the breast, colon, kidney, liver, lung, nasopharynx, ovary, prostate, salivary gland, testes, thyroid and urinary bladder. However, MT is down-regulated in certain tumors such as hepatocellular carcinoma and liver adenocarcinoma. Hence, the expression of MT is not universal to all human tumors, but may depend on the differentiation status and proliferative index of tumors, along with other tissue factors and gene mutations. In certain tumors such as germ cell carcinoma, the expression of MT is closely related to the tumor grade and proliferative activity. Increased expression of MT has also been observed in less differentiated tumors. Thus, expression of MT may be a potential prognostic marker for certain tumors. There are few reports on the expression of the different isoforms of MT which have been analyzed by specific gene probes. They reveal that certain isoforms are expressed in specific cell types. The factors which can influence MT induction in human tumors are not yet understood. Down-regulation of MT synthesis in hepatic tumors may be related to hypermethylation of the MT-promoter or mutation of other genes such as the p53 tumor suppressor gene. In vitro studies using human cancer cells suggest a possible role for p53 and the estrogen-receptor on the expression and induction of MT in epithelial neoplastic cells

  3. The potential roles of EZH2 in regenerative medicine.

    Science.gov (United States)

    Chou, Ruey-Hwang; Chiu, Lian; Yu, Yung-Luen; Shyu, Woei-Cherng

    2015-01-01

    Enhancer of zeste homolog 2 (EZH2), a catalytic component of polycomb repressive complex 2, serves as a histone methyltransferase toward histone H3K27 trimethylation and also recruits DNA methyltransferases to regulate gene expression and chromatin structure. Accumulating evidence indicates the critical roles of EZH2 in stem cell maintenance and cell fate decision in differentiation into specific cell lineages. In this article, we review the updated progress in the field and the potential application of EZH2 in regenerative medicine including nervous system, muscle, pancreas, and dental pulp regeneration.

  4. Creative potential of primary school students in written expression

    National Research Council Canada - National Science Library

    Ševkušić Slavica; Maksić Slavica

    2010-01-01

    The essays of primary school students were studied as a potential source of data about their creative capacities in the field of writing and, more extensively, in the domain of linguistic expression...

  5. Lipopolysaccharide-binding protein plasma levels and liver TNF-alpha gene expression in obese patients: evidence for the potential role of endotoxin in the pathogenesis of non-alcoholic steatohepatitis.

    Science.gov (United States)

    Ruiz, Armando Guerra; Casafont, Fernando; Crespo, Javier; Cayón, Amalia; Mayorga, Marta; Estebanez, Angel; Fernadez-Escalante, José Carlos; Pons-Romero, Fernando

    2007-10-01

    Some lines of evidence suggest that endotoxin may induce non-alcoholic steatohepatitis (NASH) in a background of fatty liver. However, a clear association between increased endotoxemia and development of steatohepatitis in obese patients has not been confirmed. We aim to assess the endotoxemic state of patients with non-alcoholic fatty liver disease (NAFLD) and its relationship with the liver expression of TNF-alpha and the presence of NASH. Prospective study comprising 40 patients with morbid obesity who were diagnosed with NAFLD. Blood samples and liver biopsies were collected. Endotoxemia was assessed by the evaluation of circulating level of LPS-binding protein (LBP). Plasma levels of LBP and TNF-alpha were assessed by ELISA. The expression of TNF-alpha in liver tissue was evaluated by real-time PCR. Histological examination was performed to evaluate the presence of steatosis or NASH. Levels of LBP were increased in obese patients with NAFLD. In addition, plasma level of LBP was increased in patients with steatohepatitis (14.2 +/- 3.9 microg/mL) when compared with patients with simple steatosis (11.5 +/- 3.2 microg/mL), P=0.041. The TNF-alpha mRNA expression in liver tissue was significantly higher in patients with NASH. This increment correlated with the rise in plasma levels of LBP (r=0.412, P=0.036). NAFLD patients have elevated plasma levels of LBP and they are further increased in patients with NASH. This increase is related to a rise in TNF-alpha gene expression in the hepatic tissue which supports a role for endotoxemia in the development of steatohepatitis in obese patients.

  6. A common signaling pathway is activated in erythroid cells expressing high levels of fetal hemoglobin: a potential role for cAMP-elevating agents in β-globin disorders

    Directory of Open Access Journals (Sweden)

    Ikuta T

    2013-12-01

    Full Text Available Tohru Ikuta,1 Yuichi Kuroyanagi,1 Nadine Odo,1 Siyang Liu21Department of Anesthesiology and Perioperative Medicine, 2Department of Physiology, Medical College of Georgia, Georgia Regents University, Augusta, GA, USABackground: Although erythroid cells prepared from fetal liver, cord blood, or blood from β-thalassemia patients are known to express fetal hemoglobin at high levels, the underlying mechanisms remain elusive. We previously showed that cyclic nucleotides such as cAMP and cGMP induce fetal hemoglobin expression in primary erythroid cells. Here we report that cAMP signaling contributes to high-level fetal hemoglobin expression in erythroid cells prepared from cord blood and β-thalassemia.Methods: The status of the cAMP signaling pathway was investigated using primary erythroid cells prepared from cord blood and the mononuclear cells of patients with β-thalassemia; erythroid cells from adult bone marrow mononuclear cells served as the control.Results: We found that intracellular cAMP levels were higher in erythroid cells from cord blood and β-thalassemia than from adult bone marrow. Protein kinase A activity levels and cAMP-response element binding protein phosphorylation were higher in erythroid cells from cord blood or β-thalassemia than in adult bone marrow progenitors. Mitogen-activated protein kinase pathways, which play a role in fetal hemoglobin expression, were not consistently activated in cord blood or β-thalassemia erythroid cells. When cAMP signaling was activated in adult erythroid cells, fetal hemoglobin was induced at high levels and associated with reduced expression of BCL11A, a silencer of the β-globin gene.Conclusion: These results suggest that activated cAMP signaling may be a common mechanism among erythroid cells with high fetal hemoglobin levels, in part because of downregulation of BCL11A. Activation of the cAMP signaling pathway with cAMP-elevating agents may prove to be an important signaling mechanism to

  7. Potential role of microRNAs in mammalian female fertility.

    Science.gov (United States)

    Tesfaye, Dawit; Salilew-Wondim, Dessie; Gebremedhn, Samuel; Sohel, Md Mahmodul Hasan; Pandey, Hari Om; Hoelker, Michael; Schellander, Karl

    2016-01-01

    Since the first evidence for the involvement of microRNAs (miRNAs) in various reproductive processes through conditional knockout of DICER, several studies have been conducted to investigate the expression pattern and role of miRNAs in ovarian follicular development, oocyte maturation, embryo development, embryo-maternal communication, pregnancy establishment and various reproductive diseases. Although advances in sequencing technology have fuelled miRNA studies in mammalian species, the presence of extracellular miRNAs in various biological fluids, including follicular fluid, blood plasma, urine and milk among others, has opened a new door in miRNA research for their use as diagnostic markers. This review presents data related to the identification and expression analysis of cellular miRNA in mammalian female fertility associated with ovarian folliculogenesis, oocyte maturation, preimplantation embryo development and embryo implantation. In addition, the relevance of miRNAs to female reproductive disorders, including polycystic ovary syndrome (PCOS), endometritis and abnormal pregnancies, is discussed for various mammalian species. Most importantly, the mechanism of release and the role of extracellular miRNAs in cell-cell communication and their potential role as non-invasive markers in female fertility are discussed in detail. Understanding this layer of regulation in female reproduction processes will pave the way to understanding the genetic regulation of female fertility in mammalian species.

  8. Potential therapeutic roles for antibody mixtures.

    Science.gov (United States)

    Raju, T Shantha; Strohl, William R

    2013-10-01

    With the enormous success of recombinant monoclonal antibodies (rMAbs) as human therapeutics, there are increasing efforts underway to explore new molecular entities that mimic rMAbs to replicate this huge success. In addition to naked intact rMAbs, antibody drug conjugates (ADCs), FAb and F(ab')2 fragments and also Fc fusion proteins have been developed and/or marketed as human therapeutics to treat different human diseases, including life-threatening diseases such as cancer. Several hundreds more intact rMAbs, ADCs, FAb, F(ab')2 fragments and Fc fusion proteins are currently undergoing human clinical trials. In addition to these molecules, new type of antibody fragments such as single-chain Fvs (scFvs), VH, scFv-Fc, scFv-CH, scFAb, scFv-zipper, diabodies, bispecific antibodies and similar types of constructs are also being investigated to be developed as human monotherapeutics. Further, there are quite a few current examples of combinations of biologics being developed. For example, currently, several biopharmaceutical companies are developing combinations of antibody mixtures as human therapeutics. Accordingly, the question posed here is whether it is time to consider the possibility of developing a broader range of combinations of therapeutic biologics. Combinations of small organic molecules have been successfully used as therapeutics for many years to treat many diseases, so the context of using polypharmacology to treat human diseases is not novel. For the past several decades, intravenous immunoglobulins have successfully been used in treating various autoimmune diseases. In this context, several biotechnology companies are exploring the use of combinations of antibody mixtures as human therapeutics. This editorial discusses these current efforts and the potential future role of antibody mixtures as human therapeutics.

  9. Effects of albusin B (a bacteriocin) of Ruminococcus albus 7 expressed by yeast on growth performance and intestinal absorption of broiler chickens--its potential role as an alternative to feed antibiotics.

    Science.gov (United States)

    Wang, Han-Tsung; Yu, Chi; Hsieh, Ya-Hui; Chen, Shiau-Wei; Chen, Bao-Ji; Chen, Ching-Yi

    2011-10-01

    Bacteriocins with antimicrobial activity are considered as potential alternatives to antibiotics. The aim of this study was to investigate the effect of albusin B (bacteriocin) of Ruminococcus albus 7 expressed by yeast on the growth performance of broiler chickens. Ninety 1-day-old healthy broiler chickens were randomly divided into three groups: control, albusin B (2.5 g kg(-1)) and nosiheptide (2.5 mg kg(-1), antibiotic control). Growth performance and intestinal functions were measured at 5 weeks of age. Albusin B-supplemented broilers showed increased body weight gain compared with control broilers (54.7 ± 5.3 vs 48.5 ± 6.1 g day(-1) per bird, P alternatives to antibiotics in broiler chicken feed. Copyright © 2011 Society of Chemical Industry.

  10. Potential role of miRNAs in developmental haemostasis.

    Directory of Open Access Journals (Sweden)

    Raúl Teruel

    Full Text Available MicroRNAs (miRNAs are an abundant class of small non-coding RNAs that are negative regulators in a crescent number of physiological and pathological processes. However, their role in haemostasis, a complex physiological process involving multitude of effectors, is just beginning to be characterized. We evaluated the changes of expression of miRNAs in livers of neonates (day one after birth and adult mice by microarray and qRT-PCR trying to identify miRNAs that potentially may also be involved in the control of the dramatic change of hepatic haemostatic protein levels associated with this transition. Twenty one out of 41 miRNAs overexpressed in neonate mice have hepatic haemostatic mRNA as potential targets. Six of them identified by two in silico algorithms potentially bind the 3'UTR regions of F7, F9, F12, FXIIIB, PLG and SERPINC1 mRNA. Interestingly, miR-18a and miR-19b, overexpressed 5.4 and 8.2-fold respectively in neonates, have antithrombin, a key anti-coagulant with strong anti-angiogenic and anti-inflammatory roles, as a potential target. The levels of these two miRNAs inversely correlated with antithrombin mRNA levels during development (miR-19b: R = 0.81; p = 0.03; miR-18a: R = 0.91; p<0.001. These data suggest that miRNAs could be potential modulators of the haemostatic system involved in developmental haemostasis.

  11. The role of MicroRNAs expression in laryngeal cancer

    Science.gov (United States)

    2015-01-01

    MicroRNAs (miRs, miRs) is a class of small non-coding RNAs, which posttranscriptionally regulate gene expression. Deregulated miRs are frequently obseved in patients with laryngeal cancer. In addition, numerous studies have showed miRs play significant roles in the pathogenesis of laryngeal cancer through regulating tumor cell proliferation, metastasis, invasion and apoptosis. miR can play either an oncogenic or tumor suppressive role in laryngeal cancer. In our review, we summarize the recent researches on laryngeal cancer-associated miRs, focusing on their role in the pathogenesis of laryngeal cancer. As changes in the levels of specific miRs in tissues or serum associate with diagnosis and prognosis of patients, we will also discuss the potential use of miRs in laryngeal cancer diagnosis and prognosis. Furthermore, supplementation of oncomiRs or inhibition of tumor suppressive miRs in vivo may be future therapeutic strategy for laryngeal cancer. PMID:26079642

  12. Expression of miR-126 and its potential function in coronary artery ...

    African Journals Online (AJOL)

    shown that miRNA expression could be a valuable sig- nature for predicting the diagnosis and/or prognosis in patients of cardiovascular diseases or cancer.7,8 In cardio- vascular system, miRNAs were observed to be involved in heart and vascular development.9 Thus, it is reasonable to speculate a potential role of miRNA ...

  13. High glucose-induced oxidative stress increases transient receptor potential channel expression in human monocytes

    DEFF Research Database (Denmark)

    Wuensch, Tilo; Thilo, Florian; Krueger, Katharina

    2010-01-01

    Transient receptor potential (TRP) channel-induced cation influx activates human monocytes, which play an important role in the pathogenesis of atherosclerosis. In the present study, we investigated the effects of high glucose-induced oxidative stress on TRP channel expression in human monocytes....

  14. Dental expression and role in palliative treatment

    Directory of Open Access Journals (Sweden)

    Rajiv Saini

    2009-01-01

    Full Text Available World Health Organization defines palliative care as the active total care of patients whose disease is not responding to curative treatment. Palliative care for the terminally ill is based on a multidimensional approach to provide whole-person comfort care while maintaining optimal function; dental care plays an important role in this multidisciplinary approach. The aim of the present study is to review significance of dentist′s role to determine whether mouth care was effectively assessed and implemented in the palliative care setting. The oral problems experienced by the hospice head and neck patient clearly affect the quality of his or her remaining life. Dentist plays an essential role in palliative care by the maintenance of oral hygiene; dental examination may identify and cure opportunistic infections and dental disease like caries, periodontal disease, oral mucosal problems or prosthetic requirement. Oral care may reduce not only the microbial load of the mouth but the risk for pain and oral infection as well. This multidisciplinary approach to palliative care, including a dentist, may reduce the oral debilities that influence the patient′s ability to speak, eat or swallow. This review highlighted that without effective assessment of the mouth, the appropriate implementation of care will not be delivered. Palliative dental care has been fundamental in management of patients with active, progressive, far-advanced disease in which the oral cavity has been compromised either by the disease directly or by its treatment; the focus of care is quality of life.

  15. Global Expression for Representing Diatomic Potential-Energy Curves

    Science.gov (United States)

    Ferrante, John; Schlosser, Herbert; Smith, John R.

    1991-01-01

    A three-parameter expression that gives an accurate fit to diatomic potential curves over the entire range of separation for charge transfers between 0 and 1. It is based on a generalization of the universal binding-energy relation of Smith et al. (1989) with a modification that describes the crossover from a partially ionic state to the neutral state at large separations. The expression is tested by comparison with first-principles calculations of the potential curves ranging from covalently bonded to ionically bonded. The expression is also used to calculate spectroscopic constants form a curve fit to the first-principles curves. A comparison is made with experimental values of the spectroscopic constants.

  16. Potential Role of Atomic Force Microscopy in Systems Biology

    Science.gov (United States)

    Ramachandran, Srinivasan; Arce, Fernando Teran; Lal, Ratnesh

    2011-01-01

    Systems biology is a quantitative approach for understanding a biological system at its global level through systematic perturbation and integrated analysis of all its components. Simultaneous acquisition of information datasets pertaining to the system components (e.g., genome, proteome) is essential to implement this approach. There are limitations to such an approach in measuring gene expression levels and accounting for all proteins in the system. The success of genomic studies is critically dependent on PCR for its amplification, but PCR is very uneven in amplifying the samples, ineffective in scarce samples and unreliable in low copy number transcripts. On the other hand, lack of amplifying techniques for proteins critically limits their identification to only a small fraction of high concentration proteins. Atomic force microscopy (AFM), AFM cantilever sensors and AFM force spectroscopy in particular, could address these issues directly. In this article, we reviewed and assessed their potential role in systems biology. PMID:21766465

  17. The role of transient receptor potential channels in metabolic syndrome

    DEFF Research Database (Denmark)

    Liu, Daoyan; Zhu, Zhiming; Tepel, Martin

    2008-01-01

    Metabolic syndrome is correlated with increased cardiovascular risk and characterized by several factors, including visceral obesity, hypertension, insulin resistance, and dyslipidemia. Several members of a large family of nonselective cation entry channels, e.g., transient receptor potential (TRP......) canonical (TRPC), vanilloid (TRPV), and melastatin (TRPM) channels, have been associated with the development of cardiovascular diseases. Thus, disruption of TRP channel expression or function may account for the observed increased cardiovascular risk in metabolic syndrome patients. TRPV1 regulates...... there is no evidence that a single TRP channelopathy may be the cause of all metabolic syndrome characteristics, further studies will help to clarify the role of specific TRP channels involved in the metabolic syndrome. (Hypertens Res 2008; 31: 1989-1995)....

  18. Trigger Features for Conveying Facial Expressions: The Role of Segmentation.

    Science.gov (United States)

    Ramachandran, Vilayanur S; Chunharas, Chaipat; Smythies, Michael

    2017-01-01

    Primates are especially good at recognizing facial expression using two contrasting strategies-an individual diagnostic feature (e.g., raise eyebrows or lower mouth corner) versus a relationship between features. We report several novel experiments that demonstrate a profound role of grouping and segmentation-including stereo-on recognition of facial expressions.

  19. Sex Roles and Yielded/Expressed Self-Control.

    Science.gov (United States)

    Ganong, Lawrence H.; Coleman, Marilyn

    1987-01-01

    Results of a study of the impact of sex and sex role orientation on reported self-control behaviors showed that sex did not affect self-control or satisfaction with self-control, but sex role orientation did. Androgynous persons reported using more expressed self-control than others. (PS)

  20. Genetic aspects of pediatric asthma: potential clinical role

    African Journals Online (AJOL)

    EL-HAKIM

    There is evidence that gene-environment interactions play an especially important role in diseases, such as asthma, that have a great deal of variability in their clinical expression. Environmental factors can modify the clinical expression of genetic variability in a variety of patterns. In fact, certain genetic polymorphisms can.

  1. Daclatasvir: potential role in hepatitis C

    Science.gov (United States)

    Lee, Choongho

    2013-01-01

    Chronic hepatitis C virus (HCV) infection is responsible for the development of liver cirrhosis and hepatocellular carcinoma. It has been a tremendous burden on global health care systems. With the advent of a number of new direct-acting and host-targeting antiviral agents, current interferon-α- and ribavirin-based HCV therapy has started to move towards an interferon-sparing or even interferon-free strategy. In this regard, a recently identified NS5A inhibitor, daclatasvir, showed a great promise in clinical trials as another new class of direct-acting anti-HCV therapeutics, with a distinct mechanism of action. In this review, a variety of preclinical as well as clinical proof-of-concept studies of daclatasvir, including the studies of its discovery, mechanism of action, viral resistance, and host polymorphism profiles are reviewed. In addition, a role of daclatasvir in the future therapy for HCV patients is discussed briefly. PMID:24204123

  2. Creative potential of primary school students in written expression

    Directory of Open Access Journals (Sweden)

    Ševkušić Slavica

    2010-01-01

    Full Text Available The essays of primary school students were studied as a potential source of data about their creative capacities in the field of writing and, more extensively, in the domain of linguistic expression. Sixth and seventh grade students (N=142 wrote an essay the creativity of which was evaluated by three teachers. Based on teachers' evaluations, two extreme groups were formed, which were then mutually compared: the students who wrote creative stories (N=17 and those who did not (N=19. A mixed method approach was applied in analyzing the data about students and their essays. The quantitative research results indicate that the authors of creative stories are characterized by a considerably higher creative potential as measured by the Word Production Test and Urban-Jellen Drawing Test (TCT-DP, a better school achievement and greater knowledge in Serbian language, a wider range of interests and a more pronounced interest in language and humanities. Analysis of narratives of the two groups of stories reveals important differences between the creative and noncreative group in the format, themes and components of creative written expression. The following are perceived in the papers assessed as creative: good composition, existence of a title, a guiding idea, originality, emotional expressiveness and ethical dimension. In the concluding part the authors discuss the advantages of combining the quantitative and qualitative procedures in studying the creative potential in school context.

  3. Daclatasvir: potential role in hepatitis C

    Directory of Open Access Journals (Sweden)

    Lee C

    2013-10-01

    Full Text Available Choongho Lee College of Pharmacy, Dongguk University-Seoul, Goyang, Republic of Korea  Abstract: Chronic hepatitis C virus (HCV infection is responsible for the development of liver cirrhosis and hepatocellular carcinoma. It has been a tremendous burden on global health care systems. With the advent of a number of new direct-acting and host-targeting antiviral agents, current interferon-α- and ribavirin-based HCV therapy has started to move towards an interferon-sparing or even interferon-free strategy. In this regard, a recently identified NS5A inhibitor, daclatasvir, showed a great promise in clinical trials as another new class of direct-acting anti-HCV therapeutics, with a distinct mechanism of action. In this review, a variety of preclinical as well as clinical proof-of-concept studies of daclatasvir, including the studies of its discovery, mechanism of action, viral resistance, and host polymorphism profiles are reviewed. In addition, a role of daclatasvir in the future therapy for HCV patients is discussed briefly. Keywords: hepatitis C virus, nonstructural protein 5A, NS5A inhibitor, hepatitis C treatment

  4. Magnesium: Potential Roles in Neurovascular Disease

    Directory of Open Access Journals (Sweden)

    Jason J Chang

    2014-04-01

    Full Text Available Objective: Magnesium therapy has been studied extensively in pre-clinical and clinical trials in multiple organ systems. Cerebrovascular diseases are particularly likely to benefit from its neuroprotective properties. This review summarizes current studies of magnesium in a wide range of neurovascular diseases.Methods: We searched relevant terms in the National Library of Medicine PubMed database and selected research including basic science, translational reports, meta-analyses, and clinical studies.Results: Studies examining magnesium administration in ischemic stroke have failed to show any benefit in clinical outcome. Data on magnesium for intracerebral hemorrhage is limited. Preliminary investigations in subarachnoid hemorrhage were promising, but definitive studies did not reveal differences in clinical outcome between magnesium and placebo-treated groups. Studies examining magnesium administration in global ischemia following cardiac arrest suggest a trend toward improved clinical outcome. The strongest evidence for clinically relevant neuroprotection following magnesium administration derives from studies of pre-term infants and patients undergoing cardiac bypass and carotid endarterectomy procedures. Magnesium was found to have an excellent safety profile across all investigations.Conclusions: Magnesium is easy to administer and possesses a favorable safety profile. Its utility as a neuroprotectant in cardiac surgery, carotid enderaterectomy, and pre-term infant hypoxia remain promising. Value as a therapeutic agent in ischemic stroke, intracerebral hemorrhage and subarachnoid hemorrhage is unclear and appears to be limited by late administration. Ongoing clinical trials assessing magnesium administration in the first hours following symptom onset may help clarify the role of magnesium therapy in these disease processes.

  5. Porifera Lectins: Diversity, Physiological Roles and Biotechnological Potential

    Directory of Open Access Journals (Sweden)

    Johan Gardères

    2015-08-01

    Full Text Available An overview on the diversity of 39 lectins from the phylum Porifera is presented, including 38 lectins, which were identified from the class of demosponges, and one lectin from the class of hexactinellida. Their purification from crude extracts was mainly performed by using affinity chromatography and gel filtration techniques. Other protocols were also developed in order to collect and study sponge lectins, including screening of sponge genomes and expression in heterologous bacterial systems. The characterization of the lectins was performed by Edman degradation or mass spectrometry. Regarding their physiological roles, sponge lectins showed to be involved in morphogenesis and cell interaction, biomineralization and spiculogenesis, as well as host defense mechanisms and potentially in the association between the sponge and its microorganisms. In addition, these lectins exhibited a broad range of bioactivities, including modulation of inflammatory response, antimicrobial and cytotoxic activities, as well as anticancer and neuromodulatory activity. In view of their potential pharmacological applications, sponge lectins constitute promising molecules of biotechnological interest.

  6. The Investigation of Drug Addiction Potential among Medical Students: Role of Subjective Components of Anger

    Directory of Open Access Journals (Sweden)

    A Agha Yusefi

    2016-02-01

    Full Text Available Objective: Given that drug addiction is not merely related to a specific individual or group, and few studies have investigated the role of anger in the development of drug addiction, this study was done to investigate the role of the components of anger in predicting addiction potential. Method: A descriptive-correlation research design was used for the conduct of this study. The number of 309 medical students in Kermanshah city was selected using stratified cluster sampling and completed Spielberger's State-Trait Anger Scale (STAS and Zargar’s addiction potential questionnaire. Results: The results showed that ate anger, trait anger, anger expression-out (AXO, anger expression-in (AXI, the overall index for the expression of anger were significantly associated with addiction potential. Similarly, anger control-out (ACO, anger control-in (ACI were correlated with addiction potential. In addition, the regression analysis results indicated that the components of state anger and anger expression-in (AXI together can predict 35% of changes related to addiction potential. Conclusion: State anger and anger expression-in (AXI as subjective components of anger have a significant role in predicting addiction potential among medical students. Anger management programs for medical students, as the most important segment of the society in the field of public health, are recommended to assign more credit to these two components.

  7. Integrative analyses of gene expression and DNA methylation profiles in breast cancer cell line models of tamoxifen-resistance indicate a potential role of cells with stem-like properties

    DEFF Research Database (Denmark)

    Lin, Xue; Li, Jian; Yin, Guangliang

    2013-01-01

    Development of resistance to tamoxifen is an important clinical issue in the treatment of breast cancer. Tamoxifen resistance may be the result of acquisition of epigenetic regulation within breast cancer cells, such as DNA methylation, resulting in changed mRNA expression of genes pivotal...

  8. Potential Antidepressant Role of Neurotransmitter CART: Implications for Mental Disorders

    Directory of Open Access Journals (Sweden)

    Peizhong Mao

    2011-01-01

    Full Text Available Depression is one of the most prevalent and debilitating public health concerns. Although no single cause of depression has been identified, it appears that interaction among genetic, epigenetic, biochemical, environmental, and psychosocial factors may explain its etiology. Further, only a fraction of depressed patients show full remission while using current antidepressants. Therefore, identifying common pathways of the disorder and using that knowledge to develop more effective pharmacological treatments are two primary targets of research in this field. Brain-enriched neurotransmitter CART (cocaine- and amphetamine-regulated transcript has multiple functions related to emotions. It is a potential neurotrophic factor and is involved in the regulation of hypothalamic-pituitary-adrenal axis and stress response as well as in energy homeostasis. CART is also highly expressed in limbic system, which is considered to have an important role in regulating mood. Notably, adolescents carrying a missense mutation in the CART gene exhibit increased depression and anxiety. Hence, CART peptide may be a novel promising antidepressant agent. In this paper, we summarize recent progress in depression and CART. In particular, we emphasize a new antidepressant function for CART.

  9. Malaria diagnosis in the community: Challenges and potential role ...

    African Journals Online (AJOL)

    kemrilib

    (ACTs) by most African countries as first line treatment for malaria, an effective, but expensive treatment is available, and the case for an expanded role for rapid diagnostics in the fight against malaria is clear. Despite this perceived potential role for RDTs, some challenges hinder their introduction and scale-up in the public.

  10. Selected soil enzymes: Examples of their potential roles in the ...

    African Journals Online (AJOL)

    Soil enzymes regulate ecosystem functioning and in particular play a key role in nutrient cycling. In this review we briefly summarise potential roles of selected enzymes such as amylase, arylsulphatases, -glucosidase, cellulose, chitinase, dehydrogenase, phosphatase, protease and urease in the ecosystem. We also ...

  11. Potential roles of WRKY transcription factors in resistance to Aspergillus flavus colonization of immature maize kernels

    Science.gov (United States)

    Resistance to Aspergillus flavus by maize (Zea mays L.) is mediated by several defense proteins; however the mechanism regulating the expression of these defenses is poorly understood. This study examined the potential roles of six maize WRKY transcription factors, ZmWRKY19, ZmWRKY21, ZmWRKY53, ZmW...

  12. Xylanases of Cellulomonas flavigena: expression, biochemical characterization, and biotechnological potential.

    Science.gov (United States)

    Lisov, Alexander V; Belova, Oksana V; Lisova, Zoya A; Vinokurova, Nataliy G; Nagel, Alexey S; Andreeva-Kovalevskaya, Zhanna I; Budarina, Zhanna I; Nagornykh, Maxim O; Zakharova, Marina V; Shadrin, Andrey M; Solonin, Alexander S; Leontievsky, Alexey A

    2017-12-01

    Four xylanases of Cellulomonas flavigena were cloned, expressed in Escherichia coli and purified. Three enzymes (CFXyl1, CFXyl2, and CFXyl4) were from the GH10 family, while CFXyl3 was from the GH11 family. The enzymes possessed moderate temperature stability and a neutral pH optimum. The enzymes were more stable at alkaline pH values. CFXyl1 and CFXyl2 hydrolyzed xylan to form xylobiose, xylotriose, xylohexaose, xylopentaose, and xylose, which is typical for GH10. CFXyl3 (GH11) and CFXyl4 (GH10) formed the same xylooligosaccharides, but xylose was formed in small amounts. The xylanases made efficient saccharification of rye, wheat and oat, common components of animal feed, which indicates their high biotechnological potential.

  13. Expression of ARs in triple negative breast cancer tumors: a potential prognostic factor?

    Directory of Open Access Journals (Sweden)

    Giannos A

    2015-07-01

    Full Text Available Aris Giannos,1 Martin Filipits,2 Flora Zagouri,2,3 Anita Brandstetter,2 Alexandra Tsigginou,1 Maria Sotiropoulou,4 Irene Papaspyrou,4 Theodoros N Sergentanis,5 Theodora Psaltopoulou,5 Alexandros Rodolakis,1 Aris Antsaklis,1 Meletios-Athanasios Dimopoulos,2 Constantine Dimitrakakis1 1Department of Obstetrics and Gynaecology, Alexandra General Hospital, Medical School, University of Athens, Athens, Greece; 2Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; 3Department of Clinical Therapeutics, Alexandra General Hospital, Medical School, University of Athens, Athens, Greece; 4Department of Pathology, Alexandra General Hospital, Athens, Greece; 5Department of Hygiene, Epidemiology and Medical Statistics, Medical School, University of Athens, Athens, Greece Background/aim: In light of the controversial published literature, this study aims to examine the potential prognostic role of AR immunohistochemical expression in triple negative breast cancer (TNBC.Patients and methods: Ninety patients with TNBC were included in this study; the associations between AR expression (Allred score, clinicopathological variables (stage, grade, histological subtype, tumor size, nodal status, age at diagnosis, Ki67 expression, and p53 expression, and overall survival were evaluated.Results: AR expression was not associated with stage, grade, histological subtype, tumor size, nodal status, age at diagnosis, Ki67 expression, and p53 expression. AR immunopositivity was not associated with overall survival either at the univariate or at the multivariate Cox regression analysis (multivariate hazard ratio =0.66, 95% confidence interval: 0.26–1.70, P=0.393.Conclusion: AR expression does not seem to play a prognostic role in TNBC. Keywords: biomarkers, prognosis, AR, triple negative breast cancer

  14. Expression and distribution of transient receptor potential (TRP) channels in bladder epithelium.

    Science.gov (United States)

    Yu, Weiqun; Hill, Warren G; Apodaca, Gerard; Zeidel, Mark L

    2011-01-01

    The urothelium is proposed to be a sensory tissue that responds to mechanical stress by undergoing dynamic membrane trafficking and neurotransmitter release; however, the molecular basis of this function is poorly understood. Transient receptor potential (TRP) channels are ideal candidates to fulfill such a role as they can sense changes in temperature, osmolarity, and mechanical stimuli, and several are reported to be expressed in the bladder epithelium. However, their complete expression profile is unknown and their cellular localization is largely undefined. We analyzed expression of all 33 TRP family members in mouse bladder and urothelium by RT-PCR and found 22 specifically expressed in the urothelium. Of the latter, 10 were chosen for closer investigation based on their known mechanosensory or membrane trafficking functions in other cell types. Western blots confirmed urothelial expression of TRPC1, TRPC4, TRPV1, TRPV2, TRPV4, TRPM4, TRPM7, TRPML1, and polycystins 1 and 2 (PKD1 and PKD2) proteins. We further defined the cellular and subcellular localization of all 10 TRP channels. TRPV2 and TRPM4 were prominently localized to the umbrella cell apical membrane, while TRPC4 and TRPV4 were identified on their abluminal surfaces. TRPC1, TRPM7, and TRPML1 were localized to the cytoplasm, while PKD1 and PKD2 were expressed on the apical and basolateral membranes of umbrella cells as well as in the cytoplasm. The cellular location of TRPV1 in the bladder has been debated, but colocalization with neuronal marker calcitonin gene-related peptide indicated clearly that it is present on afferent neurons that extend into the urothelium, but may not be expressed by the urothelium itself. These findings are consistent with the hypothesis that the urothelium acts as a sentinel and by expressing multiple TRP channels it is likely it can detect and presumably respond to a diversity of external stimuli and suggest that it plays an important role in urothelial signal

  15. The Multifaceted Role of Podoplanin Expression in Hepatocellular Carcinoma

    Science.gov (United States)

    Cioca, Andreea; Ceausu, Amalia R.; Marin, Irina; Raica, Marius; Cimpean, Anca Maria

    2017-01-01

    The role of podoplanin in hepatocellular carcinoma (HCC) is not clear yet. The aim of our study was to evaluate the expression of podoplanin in HCC and to determine its role in hepatocarcinogenesis. We performed immunohistochemistry with monoclonal D2-40 antibody, on paraffin-embedded tissue sections of 72 patients diagnosed with HCC. Lymphatic vessels density (LVD) was increased in patients who had vascular invasion at the time of diagnosis (P=0.018) and in those with associated cirrhosis (P=0.006). Tumor cells showing podoplanin expression were correlated with histological grade (P=0.040). Podoplanin-expressing cancer associated fibroblasts (CAFs) were correlated with both LVD (P=0.019) and tumor cells (P=0.015). Our results sustain the dual role of podoplanin in HCC by its involvement in both HCC tumorigenesis, lymphatic neovascularization and tumor invasion invasiveness. A possible crosstalk between epithelial and stromal tumor cells in HCC tumor microenvironment may be mediated by podoplanin, but this hypothesis needs further studies to elucidate this interrelation. PMID:28348421

  16. Characteristics and potential role of M2 macrophages in COPD

    Directory of Open Access Journals (Sweden)

    He S

    2017-10-01

    Full Text Available Shengyang He, Lihua Xie, Junjuan Lu, Shenghua SunDepartment of Respiratory Medicine, The Third Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China Background: COPD is a multi-pathogenesis disease mainly caused by smoking. A further understanding of the mechanism of smoking-related COPD might contribute to preventions and treatments of this disease in the early stages. This study was designed to identify the characteristics of M2 macrophages in COPD for a better understanding about their potential role.Materials and methods: COPD models were built in the C57BL/6 mouse by cigarette smoke (CS exposure combined with intraperitoneal injection of cigarette smoke extract (CSE. The modeling efficiency was evaluated by lung function and hematoxylin and eosin (H&E staining. The number of different macrophage phenotypes was detected by immunohistochemical staining (IHS of CD206, CD86 and CD68 on the lung tissue paraffin section. The RAW264.7 cells were polarized toward the M2 phenotype by interleukin IL-4 and confirmed by a flow cytometer. The gene expression levels of TGF-βRII, Smad2, Smad3 and Smad7 in CSE-treated M2 macrophages were detected by real-time reverse transcription polymerase chain reaction (RT-PCR. The expression levels of TGF-β/Smad pathway-related makers (TGF-βRII, p-Smad2, p-Smad3, Smad7 and TGF-β in alveolar M2 macrophages were detected by two consecutive paraffin section IHS.Results: The COPD model is well established, which is confirmed by the lung function test and lung H&E staining. The whole number of macrophages and the ratio of M2/M1 phenotype are both increased (p<0.05. The level of CD206+ cells in IL-4-stimulated RAW264.7 cells is up to 93.4%, which is confirmed by a flow cytometer. The gene expression of TGF-βRII, Smad2, Smad3 and Smad7 are all enhanced (p<0.05 in CES-treated M2 macrophages, which is detected by RT-PCR. The protein levels of TGF-β/Smad pathway-related markers are

  17. PEPCK-M expression in mouse liver potentiates, not replaces, PEPCK-C mediated gluconeogenesis.

    Science.gov (United States)

    Méndez-Lucas, Andrés; Duarte, João André Gonçalves; Sunny, Nishanth E; Satapati, Santhosh; He, TianTeng; Fu, Xiaorong; Bermúdez, Jordi; Burgess, Shawn C; Perales, Jose C

    2013-07-01

    Hepatic gluconeogenesis helps maintain systemic energy homeostasis by compensating for discontinuities in nutrient supply. Liver-specific deletion of cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) abolishes gluconeogenesis from mitochondrial substrates, deregulates lipid metabolism and affects TCA cycle. While the mouse liver almost exclusively expresses PEPCK-C, humans equally present a mitochondrial isozyme (PEPCK-M). Despite clear relevance to human physiology, the role of PEPCK-M and its gluconeogenic potential remain unknown. Here, we test the significance of PEPCK-M in gluconeogenesis and TCA cycle function in liver-specific PEPCK-C knockout and WT mice. The effects of the overexpression of PEPCK-M were examined by a combination of tracer studies and molecular biology techniques. Partial PEPCK-C re-expression was used as a positive control. Metabolic fluxes were evaluated in isolated livers by NMR using (2)H and (13)C tracers. Gluconeogenic potential, together with metabolic profiling, was investigated in vivo and in primary hepatocytes. PEPCK-M expression partially rescued defects in lipid metabolism, gluconeogenesis and TCA cycle function impaired by PEPCK-C deletion, while ∼10% re-expression of PEPCK-C normalized most parameters. When PEPCK-M was expressed in the presence of PEPCK-C, the mitochondrial isozyme amplified total gluconeogenic capacity, suggesting autonomous regulation of oxaloacetate to phosphoenolpyruvate fluxes by the individual isoforms. We conclude that PEPCK-M has gluconeogenic potential per se, and cooperates with PEPCK-C to adjust gluconeogenic/TCA flux to changes in substrate or energy availability, hinting at a role in the regulation of glucose and lipid metabolism in the human liver. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  18. Distribution and Expression of Non-Neuronal Transient Receptor Potential (TRPV) Ion Channels in Rosacea

    Science.gov (United States)

    Sulk, Mathias; Seeliger, Stephan; Aubert, Jerome; Schwab, Verena D.; Cevikbas, Ferda; Rivier, Michel; Nowak, Pawel; Voegel, Johannes J.; Buddenkotte, Jörg; Steinhoff, Martin

    2011-01-01

    Rosacea is a frequent chronic inflammatory skin disease of unknown etiology. Because early rosacea reveals all characteristics of neurogenic inflammation, a central role of sensory nerves in its pathophysiology has been discussed. Neuroinflammatory mediators and their receptors involved in rosacea are poorly defined. Good candidates may be transient receptor potential (TRP) ion channels of vanilloid type (TRPV), which can be activated by many trigger factors of rosacea. Interestingly, TRPV2, TRPV3, and TRPV4 are expressed by both neuronal and non-neuronal cells. Here, we analyzed the expression and distribution of TRPV receptors in the various subtypes of rosacea on non-neuronal cells using immunohistochemistry, morphometry, double immunoflourescence, and quantitative real-time PCR (qRT-PCR) as compared with healthy skin and lupus erythematosus. Our results show that dermal immunolabeling of TRPV2 and TRPV3 and gene expression of TRPV1 is significantly increased in erythematotelangiectatic rosacea (ETR). Papulopustular rosacea (PPR) displayed an enhanced immunoreactivity for TRPV2, TRPV4, and also of TRPV2 gene expression. In phymatous rosacea (PhR)-affected skin, dermal immunostaining of TRPV3 and TRPV4 and gene expression of TRPV1 and TRPV3 was enhanced, whereas epidermal TRPV2 staining was decreased. Thus, dysregulation of TRPV channels also expressed by non-neuronal cells may be critically involved in the initiation and/or development of rosacea. TRP ion channels may be targets for the treatment of rosacea. PMID:22189789

  19. Orai1 expression pattern in tooth and craniofacial ectodermal tissues and potential functions during ameloblast differentiation.

    Science.gov (United States)

    Zheng, Li; Zinn, Vina; Lefkelidou, Anna; Taqi, Nawar; Chatzistavrou, Xanthippi; Balam, Tarek; Nervina, Jeanne; Papagerakis, Silvana; Papagerakis, Petros

    2015-10-01

    Orai1 is a plasma membrane protein that forms the pore of the calcium release activated calcium channel. Humans with mutated Orai1 present with hereditary combined immunodeficiency, congenital myopathy and anhidrotic ectodermal dysplasia. Consistent with the ectodermal dysplasia phenotype, enamel formation and mineralization is also abnormal in Orai1 deficient patients. The expression pattern and potential functions of Orai1 in enamel formation remains unclear. To contribute toward understanding the role of Orai1 in amelogenesis we characterized ORAI1 protein developmental pattern in comparison with other ectodermal organs. We also examined the effects of Orai1 down-regulation in ameloblast cell proliferation and differentiation. Our data show strong expression of ORAI1 protein during the ameloblast secretory stage, which weans at the end of the maturation stage. In salivary glands, ORAI1 is expressed mainly in acini cells. ORAI1 expression is also found in hair follicle and oral epithelium. Knockdown of Orai1 expression decreases cell proliferation and results in RNA expression levels changes of key ameloblast genes regulating enamel thickness and mineralization. This study provides insights in the anhidrotic ectodermal dysplasia phenotype due to Orai1 mutation and highlights the importance of calcium signaling in controlling ameloblast differentiation and maturation during tooth development. © 2015 Wiley Periodicals, Inc.

  20. Distribution and expression of non-neuronal transient receptor potential (TRPV) ion channels in rosacea.

    Science.gov (United States)

    Sulk, Mathias; Seeliger, Stephan; Aubert, Jerome; Schwab, Verena D; Cevikbas, Ferda; Rivier, Michel; Nowak, Pawel; Voegel, Johannes J; Buddenkotte, Jörg; Steinhoff, Martin

    2012-04-01

    Rosacea is a frequent chronic inflammatory skin disease of unknown etiology. Because early rosacea reveals all characteristics of neurogenic inflammation, a central role of sensory nerves in its pathophysiology has been discussed. Neuroinflammatory mediators and their receptors involved in rosacea are poorly defined. Good candidates may be transient receptor potential (TRP) ion channels of vanilloid type (TRPV), which can be activated by many trigger factors of rosacea. Interestingly, TRPV2, TRPV3, and TRPV4 are expressed by both neuronal and non-neuronal cells. Here, we analyzed the expression and distribution of TRPV receptors in the various subtypes of rosacea on non-neuronal cells using immunohistochemistry, morphometry, double immunoflourescence, and quantitative real-time PCR (qRT-PCR) as compared with healthy skin and lupus erythematosus. Our results show that dermal immunolabeling of TRPV2 and TRPV3 and gene expression of TRPV1 is significantly increased in erythematotelangiectatic rosacea (ETR). Papulopustular rosacea (PPR) displayed an enhanced immunoreactivity for TRPV2, TRPV4, and also of TRPV2 gene expression. In phymatous rosacea (PhR)-affected skin, dermal immunostaining of TRPV3 and TRPV4 and gene expression of TRPV1 and TRPV3 was enhanced, whereas epidermal TRPV2 staining was decreased. Thus, dysregulation of TRPV channels also expressed by non-neuronal cells may be critically involved in the initiation and/or development of rosacea. TRP ion channels may be targets for the treatment of rosacea.

  1. Malaria diagnosis in the community: Challenges and potential role ...

    African Journals Online (AJOL)

    Despite this perceived potential role for RDTs, some challenges hinder their introduction and scale-up in the public health sector. Among the requirements are significant investments in policy development, training, infrastructure, and supply chain and quality assurance systems. African Journal of Health Sciences Vol.

  2. The Potential Role of Artificial Intelligence Technology in Education.

    Science.gov (United States)

    Salem, Abdel-Badeeh M.

    The field of Artificial Intelligence (AI) and Education has traditionally a technology-based focus, looking at the ways in which AI can be used in building intelligent educational software. In addition AI can also provide an excellent methodology for learning and reasoning from the human experiences. This paper presents the potential role of AI in…

  3. Genetic aspects of pediatric asthma: potential clinical role

    African Journals Online (AJOL)

    EL-HAKIM

    Egypt J Pediatr Allergy Immunol 2008; 6(2): 45-50. 45. Genetic aspects of pediatric asthma: potential clinical role. Sarwat E. Deraz. Professor of Pediatrics, Ain Shams University, Cairo. Introduction. Bronchial asthma is a disease of continuing inflammatory disorder of the airways that causes trouble breathing1. It is a major ...

  4. Conceptualising the Potential Role of L1 in CLIL

    Science.gov (United States)

    Lin, Angel M. Y.

    2015-01-01

    Content and language integrated learning (CLIL) is a rapidly growing area of both research and practice in all parts of the world, especially in Europe and Asia. As a young discipline, CLIL has a good potential of distinguishing itself from monolingual L2 immersion education models by becoming more flexible and balanced about the role of L1 in…

  5. Original Business Modelling: Potential Roles of Creativity in Entrepreneurship Training

    DEFF Research Database (Denmark)

    Byrge, Christian; Kristiansen, Kristian Brøndum

    2017-01-01

    This extended abstract aims to design a research method for studying potential meaningful roles creativity may take in entrepreneurship training. It suggests an experimental setup using a 30 ECTS entrepreneurship course at a Danish university for conducting the experiments and the data collection...

  6. Histopathological changes in tendinopathy--potential roles of BMPs?

    Science.gov (United States)

    Lui, Pauline Po Yee

    2013-12-01

    The pathogenesis of tendinopathy remains unclear. Chondro-osteogenic BMPs such as BMP-2, BMP-4 and BMP-7 have been reported in clinical samples and animal models of tendinopathy. As chondrocyte-like cells and ossified deposits have been observed in both clinical samples and animal models of failed tendon healing tendinopathy, chondro-osteogenic BMPs might contribute to tissue metaplasia and other histopathological changes in tendinopathy. In this review I have summarized the current evidence supporting the roles of chondro-osteogenic BMPs in the histopathological changes of tendinopathy. The potential targets, effects and sources of these BMPs are discussed. I have also provided directions for future studies about the potential roles of BMPs in the pathogenesis of tendinopathy. Better understanding of the roles of these BMPs in the histopathological changes of tendinopathy could provide new options for the prevention and treatment of this disabling tendon disorder.

  7. Transient receptor potential melastatin (TRPM) 8 is expressed in freshly isolated native human odontoblasts.

    Science.gov (United States)

    Tazawa, Kento; Ikeda, Hideharu; Kawashima, Nobuyuki; Okiji, Takashi

    2017-03-01

    Cold-sensitive ion channels, such as transient receptor potential melastatin (TRPM) 8 and transient receptor potential ankyrin (TRPA) 1, may play a crucial role in the nociceptive function of odontoblasts, whereas expression of these TRP channels in human native odontoblasts remains to be elucidated. This study aimed to analyze the expression of TRPM8 and TRPA1 in freshly isolated native human odontoblasts. Odontoblasts were isolated from freshly extracted healthy human teeth (n=4); after removing the inner pulp tissues from the pulp chambers, odontoblasts remaining on the dentin surface were washed out with phosphate buffered saline and collected. Reverse transcription-polymerase chain reaction was employed to compare the expression levels of TRPM8, TRPA1, and dentin matrix acidic phosphoprotein 1 (DMP1) mRNAs between the isolated odontoblasts and the inner pulp tissues. The isolated cells were subjected to immunolocalization of TRPM8 and nestin. Paraformaldehyde-fixed, EDTA-demineralized frozen sections obtained from freshly extracted healthy human teeth (n=4) were also analyzed immunohistochemically using anti-nestin, TRPM8, and TRPA1 antibodies. Expression levels of TRPM8 and DMP1 in the isolated odontoblasts were significantly higher than those in the inner pulp tissues (podontoblastic layer of the dental pulp tissue and isolated odontoblasts, while expression of TRPA1 was not detected. TRPM8, but not TRPA1, was detected in freshly isolated native human odontoblasts at the protein and mRNA levels, suggesting that odontoblasts play an important role in detecting external cold stimulation via TRPM8 in healthy condition. Copyright © 2016. Published by Elsevier Ltd.

  8. The role of piRNA and its potential clinical implications in cancer

    Science.gov (United States)

    Assumpção, Carolina Baraúna; Calcagno, Danielle Queiroz; Araújo, Taíssa Maíra Thomaz; dos Santos, Sidney Emmanuel Batista; dos Santos, Ândrea Kely Campos Ribeiro; Riggins, Gregory Joseph; Burbano, Rommel Rodriguez; Assumpção, Paulo Pimentel

    2016-01-01

    Epigenetic mechanisms work in an orchestrated fashion to control gene expression in both homeostasis and diseases. Among small noncoding RNAs, piRNAs seem to meet the necessary requirements to be included in this epigenetic network due to their role in both transcriptional and post-transcriptional regulation. piRNAs and PIWI proteins might play important roles in cancer occurrence, prognosis and treatment as reported previously. Nevertheless, the potential clinical relevance of these molecules has yet been elucidated. A brief overview of piRNA biogenesis and their potential roles as part of an epigenetic network that is possibly involved in cancer is provided. Moreover, potential strategies based on the use of piRNAs and PIWI proteins as diagnostic and prognostic biomarkers as well as for cancer therapeutics are discussed. PMID:25929784

  9. Role of expressive behaviour for robots that learn from people

    Science.gov (United States)

    Breazeal, Cynthia

    2009-01-01

    Robotics has traditionally focused on developing intelligent machines that can manipulate and interact with objects. The promise of personal robots, however, challenges researchers to develop socially intelligent robots that can collaborate with people to do things. In the future, robots are envisioned to assist people with a wide range of activities such as domestic chores, helping elders to live independently longer, serving a therapeutic role to help children with autism, assisting people undergoing physical rehabilitation and much more. Many of these activities shall require robots to learn new tasks, skills and individual preferences while ‘on the job’ from people with little expertise in the underlying technology. This paper identifies four key challenges in developing social robots that can learn from natural interpersonal interaction. The author highlights the important role that expressive behaviour plays in this process, drawing on examples from the past 8 years of her research group, the Personal Robots Group at the MIT Media Lab. PMID:19884147

  10. The Role of Bromodomain Proteins in Regulating Gene Expression

    Directory of Open Access Journals (Sweden)

    Michael F. Duffy

    2012-05-01

    Full Text Available Histone modifications are important in regulating gene expression in eukaryotes. Of the numerous histone modifications which have been identified, acetylation is one of the best characterised and is generally associated with active genes. Histone acetylation can directly affect chromatin structure by neutralising charges on the histone tail, and can also function as a binding site for proteins which can directly or indirectly regulate transcription. Bromodomains specifically bind to acetylated lysine residues on histone tails, and bromodomain proteins play an important role in anchoring the complexes of which they are a part to acetylated chromatin. Bromodomain proteins are involved in a diverse range of functions, such as acetylating histones, remodeling chromatin, and recruiting other factors necessary for transcription. These proteins thus play a critical role in the regulation of transcription.

  11. [Expression and role of survivin in laryngeal squamous cell carcinoma and laryngeal papilloma in adults].

    Science.gov (United States)

    Xie, Hong; Zhang, Baoquan; Yin, Jinshu; Song, Faquan

    2007-05-01

    To study the expression of Survivin in laryngeal squamous cell carcinoma (LSCC) and laryngeal papilloma in adults and its significance in carcinogenesis and development of the LSCC. The expressions of Survivin protein were detected by immunohistochemistry technique in 46 cases of LSCC, 24 cases of adjacent nontumorous laryngeal epithelium, 20 cases of laryngeal papilloma and 16 cases of normal laryngeal epithelium. The positive rates of Survivin protein expression in laryngeal carcinoma, adjacent nontumorous laryngeal epithelium and laryngeal papilloma were 71.74% (33/46), 33.33% (8/24)and 40.00% (8/20) respectively. There was no expression in normal laryngeal epithelium. The positive rate of Survivin protein expression in laryngeal carcinoma was significantly higher than that in the adjacent nontumorous laryngeal epithelium, laryngeal papilloma and normal laryngeal epithelium. But there was no statistically significant correlations between Survivin protein expression and the clinicopathological characteristics of tumor site, T-stage, pathological grading, UICC-stage and lymph node metastasis (P > 0.05). Expression of Survivin protein in 3 cases in laryngeal papilloma group which turned into laryngeal carcinoma later were all positive. There was overexpression of Survivin in the laryngeal carcinoma. The expression of Survivin might play an important role in the carcinogenesis of LSCC and might be an early event during laryngeal carcinogenesis. It could be a diagnostic marker for evaluating the malignant potential of laryngeal papilloma in adults.

  12. Potential roles of optical interconnections within broadband switching modules

    Science.gov (United States)

    Lalk, Gail R.; Habiby, Sarry F.; Hartman, Davis H.; Krchnavek, Robert R.; Wilson, Donald K.; Young, Kenneth C., Jr.

    1991-04-01

    An investigation of potential physical design bottlenecks in future broadband telecommunication switches has led to the identification of several areas where optical interconnections may play a role in the practical realization of required system performance. In the model used the speed and interconnection densities as well as requirements for ease-of-access and efficient power utilization challenge conventional partitioning and packaging strategies. Potential areas where optical interconnections may relieve some of the physical design bottlenecks include fiber management at the customer interface to the switch routing and distribution of high-density interconnections within the fabric of the switch and backplane interconnections to increase system throughput.

  13. Role of the Ionic Potential in High Harmonic Generation

    CERN Document Server

    Shafir, D; Higuet, J; Soifer, H; Dagan, M; Descamps, D; Mevel, E; Petit, S; Worner, H J; Pons, B; Dudovich, N; Mairesse, Y

    2013-01-01

    Recollision processes provide direct insight into the structure and dynamics of electronic wave functions. However, the strength of the process sets its basic limitations - the interaction couples numerous degrees of freedom. In this Letter we decouple the basic steps of the process and resolve the role of the ionic potential which is at the heart of a broad range of strong field phenomena. Specifically, we measure high harmonic generation from argon atoms. By manipulating the polarization of the laser field we resolve the vectorial properties of the interaction. Our study shows that the ionic core plays a significant role in all steps of the interaction. In particular, Coulomb focusing induces an angular deflection of the electrons before recombination. A complete spatiospectral analysis reveals the influence of the potential on the spatiotemporal properties of the emitted light.

  14. Pokemon proto-oncogene in oral cancer: potential role in the early phase of tumorigenesis.

    Science.gov (United States)

    Sartini, D; Lo Muzio, L; Morganti, S; Pozzi, V; Di Ruscio, G; Rocchetti, R; Rubini, C; Santarelli, A; Emanuelli, M

    2015-05-01

    Oral squamous cell carcinoma (OSCC) represents about 90% of all oral neoplasms with a poor clinical prognosis. To improve survival of OSCC patients, it is fundamental to understand the basic molecular mechanisms characterizing oral carcinogenesis. Dysregulation of oncogenes and tumor suppressor genes seems to play a central role in tumorigenesis, including malignant transformation of the oral cavity. We analyzed the expression levels of the pro-oncogenic transcription factor Pokemon through real-time PCR, Western blot and immunohistochemistry in tumor, and normal oral tissue samples obtained from 22 patients with OSCC. The relationship between tumor characteristics and the level of Pokemon intratumor expression was also analyzed. Pokemon was significantly downregulated in OSCC. In particular, both mRNA and protein levels (tumor vs normal tissue) inversely correlated with histological grading, suggesting its potential role as a prognostic factor for OSCC. Moreover, a significant inverse correlation was found between Pokemon protein expression levels (OSCC vs normal oral mucosa) and tumor size, supporting the hypothesis that Pokemon could play an important role in the early phase of tumor expansion. This work shows that reduced expression of Pokemon is a peculiar feature of OSCC. Additional studies may establish the effective role of Pokemon in oral tumorigenesis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Original Business Modelling: Potential Roles of Creativity in Entrepreneurship Training

    DEFF Research Database (Denmark)

    Byrge, Christian; Kristiansen, Kristian Brøndum

    2017-01-01

    This extended abstract aims to design a research method for studying potential meaningful roles creativity may take in entrepreneurship training. It suggests an experimental setup using a 30 ECTS entrepreneurship course at a Danish university for conducting the experiments and the data collection...... to take place in autumn 2017. At the conferenceconference, we hope for any kind of feedback that may help us improve the quality of this forthcoming study....

  16. Aberrant expression of histone deacetylases 4 in cognitive disorders: molecular mechanisms and a potential target

    Directory of Open Access Journals (Sweden)

    Yili Wu

    2016-11-01

    Full Text Available Histone acetylation is a major mechanism of chromatin remodeling, contributing to epigenetic regulation of gene transcription. Histone deacetylases (HDACs are involved in both physiological and pathological conditions by regulating the status of histone acetylation. Although histone deacetylase 4 (HDAC4, a member of the HDAC family, may lack histone deacetylase activity, it is actively involved in regulating the transcription of genes involved in synaptic plasticity, neuronal survival and neurodevelopment by interacting with transcription factors, signal transduction molecules and HDAC3, another member of the HDAC family. HDAC4 is highly expressed in brain and its homeostasis is crucial for the maintenance of cognitive function. Accumulated evidence shows that HDAC4 expression is dysregulated in several brain disorders, including neurodegenerative diseases and mental disorders. Moreover, cognitive impairment is a characteristic feature of these diseases. It indicates that aberrant HDAC4 expression plays a pivotal role in cognitive impairment of these disorders. This review aims to describe the current understanding of HDAC4’s role in the maintenance of cognitive function and its dysregulation in neurodegenerative diseases and mental disorders, discuss underlying molecular mechanisms, and provide an outlook into targeting HDAC4 as a potential therapeutic approach to rescue cognitive impairment in these diseases.

  17. The potential roles of T-type Ca2+ channels in motor coordination

    Directory of Open Access Journals (Sweden)

    Young-Gyun ePark

    2013-10-01

    Full Text Available Specific behavioral patterns are expressed by complex combinations of muscle coordination. Tremors are simple behavioral patterns and are the focus of studies investigating motor coordination mechanisms in the brain. T-type Ca2+ channels mediate intrinsic neuronal oscillations and rhythmic burst spiking, and facilitate the generation of tremor rhythms in motor circuits. Despite substantial evidence that T-type Ca2+ channels mediate pathological tremors, their roles in physiological motor coordination and behavior remain unknown. Here, we review recent progress in understanding the roles that T-type Ca2+ channels play under pathological conditions, and discuss the potential relevance of these channels in mediating physiological motor coordination.

  18. Potential Immune Modularly Role of Glycine in Oral Gingival Inflammation

    Directory of Open Access Journals (Sweden)

    Teresa Schaumann

    2013-01-01

    Full Text Available Gingival epithelial cells (GECs represent a physical barrier against bacteria and are involved in the processes of innate immunity. Recently, an anti-inflammatory and immune-modulatory effect of the amino acid glycine has been demonstrated. However, there is only little information about the immune-modulatory effects of glycine in oral tissues. This study aimed to investigate the existence and role of the glycine receptor in gingival tissue analyzing tissues/cells from extracted human molars via immunohistochemical analysis. In vitro, GECs were challenged by inflammatory conditions with IL-1β alone or in combination with glycine and analyzed for cytokine expression of IL6/IL8 via real-time PCR. On protein level, the effect of nuclear translocalization of NFκB protein p65 was analyzed using immunofluorescence analysis. A distinct proof of the GlyR in oral gingival tissue and keratinocytes could be demonstrated. Isolated challenge of the keratinocytes with IL-1β as well as with glycine resulted in an upregulation of IL6 and IL8 mRNA expression and activation of NFκB pathway. The presence of glycine in combination with the inflammatory stimulus led to a significant decrease in inflammatory parameters. These results indicate a possible anti-inflammatory role of glycine in gingival inflammation and encourage further research on the utility of glycine in the prevention or therapy of inflammatory periodontitis.

  19. Population genetics of non-genetic traits: Evolutionary roles of stochasticity in gene expression

    KAUST Repository

    Mineta, Katsuhiko

    2015-05-01

    The role of stochasticity in evolutionary genetics has long been debated. To date, however, the potential roles of non-genetic traits in evolutionary processes have been largely neglected. In molecular biology, growing evidence suggests that stochasticity in gene expression (SGE) is common and that SGE has major impacts on phenotypes and fitness. Here, we provide a general overview of the potential effects of SGE on population genetic parameters, arguing that SGE can indeed have a profound effect on evolutionary processes. Our analyses suggest that SGE potentially alters the fate of mutations by influencing effective population size and fixation probability. In addition, a genetic control of SGE magnitude could evolve under certain conditions, if the fitness of the less-fit individual increases due to SGE and environmental fluctuation. Although empirical evidence for our arguments is yet to come, methodological developments for precisely measuring SGE in living organisms will further advance our understanding of SGE-driven evolution.

  20. Increased nuclear ?-catenin expression in oral potentially malignant lesions: A marker of epithelial dysplasia

    Science.gov (United States)

    Rojas-Alcayaga, Gonzalo; Maturana, Andrea; Aitken, Juan-Pablo; Rojas, Carolina; Ortega, Ana-Verónica

    2015-01-01

    Background Deregulation of ?-catenin is associated with malignant transformation; however, its relationship with potentially malignant and malignant oral processes is not fully understood. The aim of this study was to determine and compare the nuclear ?-catenin expression in oral dysplasia and oral squamous cell carcinoma (OSCC). Material and Methods Cross sectional study. Immunodetection of ?-catenin was performed on 72 samples, with the following distribution: 21 mild dysplasia, 12 moderate dysplasia, severe dysplasia 3, 36 OSCC including 19 well differentiated, 15 moderately differentiated and 2 poorly differentiated. Through microscopic observation the number of positive cells per 1000 epithelial cells was counted. For the statistical analysis, the Kruskal Wallis test was used. Results Nuclear expression of ?-catenin was observed in all samples with severe and moderate dysplasia, with a median of 267.5, in comparison to mild dysplasia whose median was 103.75. Only 10 samples (27.7%) with OSCC showed nuclear expression, with statistically significant differences between groups (p < 0.05). Conclusions Our results are consistent with most of the reports which show increased presence of ?-catenin in severe and moderate dysplasia compared to mild dysplasia; however the expression of nuclear ?-catenin decreased after starting the invasive neoplastic process. This suggests a role for this protein in the progression of dysplasia and early malignant transformation to OSCC. Immunodetection of ?-catenin could be a possible immune marker in the detection of oral dysplasia. Key words:Oral squamous cell carcinoma (OSCC), ?-catenin, oral dysplasia. PMID:26241451

  1. Increased nuclear β-catenin expression in oral potentially malignant lesions: A marker of epithelial dysplasia.

    Science.gov (United States)

    Reyes, Montserrat; Rojas-Alcayaga, Gonzalo; Maturana, Andrea; Aitken, Juan-Pablo; Rojas, Carolina; Ortega, Ana-Verónica

    2015-09-01

    Deregulation of β-catenin is associated with malignant transformation; however, its relationship with potentially malignant and malignant oral processes is not fully understood. The aim of this study was to determine and compare the nuclear β-catenin expression in oral dysplasia and oral squamous cell carcinoma (OSCC). Cross sectional study. Immunodetection of β-catenin was performed on 72 samples, with the following distribution: 21 mild dysplasia, 12 moderate dysplasia, severe dysplasia 3, 36 OSCC including 19 well differentiated, 15 moderately differentiated and 2 poorly differentiated. Through microscopic observation the number of positive cells per 1000 epithelial cells was counted. For the statistical analysis, the Kruskal Wallis test was used. Nuclear expression of β-catenin was observed in all samples with severe and moderate dysplasia, with a median of 267.5, in comparison to mild dysplasia whose median was 103.75. Only 10 samples (27.7%) with OSCC showed nuclear expression, with statistically significant differences between groups (p < 0.05). Our results are consistent with most of the reports which show increased presence of β-catenin in severe and moderate dysplasia compared to mild dysplasia; however the expression of nuclear β-catenin decreased after starting the invasive neoplastic process. This suggests a role for this protein in the progression of dysplasia and early malignant transformation to OSCC. Immunodetection of β-catenin could be a possible immune marker in the detection of oral dysplasia.

  2. Expression of Transient Receptor Potential Vanilloid (TRPV Channels in Different Passages of Articular Chondrocytes

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    Richard Barrett-Jolley

    2012-04-01

    Full Text Available Ion channels play important roles in chondrocyte mechanotransduction. The transient receptor potential vanilloid (TRPV subfamily of ion channels consists of six members. TRPV1-4 are temperature sensitive calcium-permeable, relatively non-selective cation channels whereas TRPV5 and TRPV6 show high selectivity for calcium over other cations. In this study we investigated the effect of time in culture and passage number on the expression of TRPV4, TRPV5 and TRPV6 in articular chondrocytes isolated from equine metacarpophalangeal joints. Polyclonal antibodies raised against TRPV4, TRPV5 and TRPV6 were used to compare the expression of these channels in lysates from first expansion chondrocytes (P0 and cells from passages 1–3 (P1, P2 and P3 by western blotting. TRPV4, TRPV5 and TRPV6 were expressed in all passages examined. Immunohistochemistry and immunofluorescence confirmed the presence of these channels in sections of formalin fixed articular cartilage and monolayer cultures of methanol fixed P2 chondrocytes. TRPV5 and TRPV6 were upregulated with time and passage in culture suggesting that a shift in the phenotype of the cells in monolayer culture alters the expression of these channels. In conclusion, several TRPV channels are likely to be involved in calcium signaling and homeostasis in chondrocytes.

  3. Role of vitamin D on the expression of glucose transporters in L6 myotubes

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    Bubblu Tamilselvan

    2013-01-01

    Full Text Available Altered expression of glucose transporters is a major characteristic of diabetes. Vitamin D has evolved widespread interest in the pathogenesis and prevention of diabetes. The present study was designed to investigate the effect of vitamin D in the overall regulation of muscle cell glucose transporter expression. L6 cells were exposed to type 1 and type 2 diabetic conditions and the effect of calcitriol (1,25, dihydroxy cholicalciferol on the expression of glucose transporters was studied by real time polymerase chain reaction (RT-PCR. There was a significant decrease in glucose transporter type 1 (GLUT1, GLUT4, vitamin D receptor (VDR, and IR expression in type 1 and 2 diabetic model compared to control group. Treatment of myoblasts with 10-7 M calcitriol for 24 h showed a significant increase in GLUT1, GLUT4, VDR, and insulin receptor (IR expression. The results indicate a potential antidiabetic function of vitamin D on GLUT1, GLUT4, VDR, and IR by improving receptor gene expression suggesting a role for vitamin D in regulation of expression of the glucose transporters in muscle cells.

  4. Global gene expression profiling reveals SPINK1 as a potential hepatocellular carcinoma marker.

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    Aileen Marshall

    Full Text Available Liver cirrhosis is the most important risk factor for hepatocellular carcinoma (HCC but the role of liver disease aetiology in cancer development remains under-explored. We investigated global gene expression profiles from HCC arising in different liver diseases to test whether HCC development is driven by expression of common or different genes, which could provide new diagnostic markers or therapeutic targets.Global gene expression profiling was performed for 4 normal (control livers as well as 8 background liver and 7 HCC from 3 patients with hereditary haemochromatosis (HH undergoing surgery. In order to investigate different disease phenotypes causing HCC, the data were compared with public microarray repositories for gene expression in normal liver, hepatitis C virus (HCV cirrhosis, HCV-related HCC (HCV-HCC, hepatitis B virus (HBV cirrhosis and HBV-related HCC (HBV-HCC. Principal component analysis and differential gene expression analysis were carried out using R Bioconductor. Liver disease-specific and shared gene lists were created and genes identified as highly expressed in hereditary haemochromatosis HCC (HH-HCC were validated using quantitative RT-PCR. Selected genes were investigated further using immunohistochemistry in 86 HCC arising in liver disorders with varied aetiology. Using a 2-fold cut-off, 9 genes were highly expressed in all HCC, 11 in HH-HCC, 270 in HBV-HCC and 9 in HCV-HCC. Six genes identified by microarray as highly expressed in HH-HCC were confirmed by RT qPCR. Serine peptidase inhibitor, Kazal type 1 (SPINK1 mRNA was very highly expressed in HH-HCC (median fold change 2291, p = 0.0072 and was detected by immunohistochemistry in 91% of HH-HCC, 0% of HH-related cirrhotic or dysplastic nodules and 79% of mixed-aetiology HCC.HCC, arising from diverse backgrounds, uniformly over-express a small set of genes. SPINK1, a secretory trypsin inhibitor, demonstrated potential as a diagnostic HCC marker and should be

  5. Gene expression changes in phosphorus deficient potato (Solanum tuberosum L. leaves and the potential for diagnostic gene expression markers.

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    John P Hammond

    Full Text Available BACKGROUND: There are compelling economic and environmental reasons to reduce our reliance on inorganic phosphate (Pi fertilisers. Better management of Pi fertiliser applications is one option to improve the efficiency of Pi fertiliser use, whilst maintaining crop yields. Application rates of Pi fertilisers are traditionally determined from analyses of soil or plant tissues. Alternatively, diagnostic genes with altered expression under Pi limiting conditions that suggest a physiological requirement for Pi fertilisation, could be used to manage Pifertiliser applications, and might be more precise than indirect measurements of soil or tissue samples. RESULTS: We grew potato (Solanum tuberosum L. plants hydroponically, under glasshouse conditions, to control their nutrient status accurately. Samples of total leaf RNA taken periodically after Pi was removed from the nutrient solution were labelled and hybridised to potato oligonucleotide arrays. A total of 1,659 genes were significantly differentially expressed following Pi withdrawal. These included genes that encode proteins involved in lipid, protein, and carbohydrate metabolism, characteristic of Pi deficient leaves and included potential novel roles for genes encoding patatin like proteins in potatoes. The array data were analysed using a support vector machine algorithm to identify groups of genes that could predict the Pi status of the crop. These groups of diagnostic genes were tested using field grown potatoes that had either been fertilised or unfertilised. A group of 200 genes could correctly predict the Pi status of field grown potatoes. CONCLUSIONS: This paper provides a proof-of-concept demonstration for using microarrays and class prediction tools to predict the Pi status of a field grown potato crop. There is potential to develop this technology for other biotic and abiotic stresses in field grown crops. Ultimately, a better understanding of crop stresses may improve our management

  6. Chromatin Insulators: A Role in Nuclear Organization and Gene Expression

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    Yang, Jingping; Corces, Victor G.

    2011-01-01

    Chromatin insulators are DNA-protein complexes with broad functions in nuclear biology. Based on the ability of insulator proteins to interact with each other, it was originally thought that insulators form loops that could constitute functional domains of co-regulated gene expression. Nevertheless, data from genome-wide localization studies indicate that insulator proteins can be present in intergenic regions as well as at the 5′, introns or 3′ of genes, suggesting a broader role in chromosome biology. Cells have developed mechanisms to control insulator activity by recruiting specialized proteins or by covalent modification of core components. Recent results suggest that insulators mediate intra- and inter-chromosomal interactions to affect transcription, imprinting and recombination. It is possible that these interactions set up cell-specific blueprints of nuclear organization that may contribute to the establishment of different patterns of gene expression during cell differentiation. As a consequence, disruption of insulator activity could result in the development of cancer or other disease states. PMID:21704228

  7. The role of p38 MAPK in neutrophil functions: single cell chemotaxis and surface marker expression.

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    Kim, Donghyuk; Haynes, Christy L

    2013-11-21

    Neutrophils act as the first line of defence in the human immune system by migrating to the site of abnormal events and performing their designated roles. One major signalling pathway that drives neutrophil action in vivo is the p38 mitogen-activated protein kinase (MAPK)-dependent pathway. Herein, a microfluidic platform is employed to explore the mechanistic role of p38 MAPK in neutrophil chemotaxis. Neutrophils, with and without p38 MAPK inhibition, were exposed to pairwise competing gradients of chemotaxis-inducing molecules. Overall, p38 MAPK inhibitor-treated neutrophils were still capable of moving toward a chemoattractant signal; however, the hierarchy of neutrophil response to various chemoattractants changed and there was more deviation from direct movement toward a chemoattractant signal in p38 MAPK-blocked cells. In a parallel fluorescence imaging study, neutrophil expression of surface receptors (CXCR1, FPR2, BLTR, CD11b and CD66b) changed when comparing untreated and p38 MAPK-blocked cells. All results demonstrate that the p38 MAPK-dependent pathway plays a critical role in neutrophil chemotaxis and this role is, in part, through the regulation of surface receptor expression. These data regarding how receptor expression and chemotaxis are influenced by the p38 MAPK pathways lend insight into neutrophil behaviour in physiological environments and the potential manipulation of p38 MAPK for therapeutic purposes.

  8. Prospective on the potential of imaging gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, Scott E; Budinger, Thomas F.

    2000-06-01

    The feasibility of the non-invasive imaging of gene expression is explored. Calculations of the possibility of the direct imaging of specific messenger RNA with radiolabeled antisense are discussed. In addition, possible mechanism for the amplification of the biological signal to enhance image detection are discussed.

  9. Glucocorticoid: A potential role in microgravity-induced bone loss

    Science.gov (United States)

    Yang, Jiancheng; Yang, Zhouqi; Li, Wenbin; Xue, Yanru; Xu, Huiyun; Li, Jingbao; Shang, Peng

    2017-11-01

    Exposure of animals and humans to conditions of microgravity, including actual spaceflight and simulated microgravity, results in numerous negative alterations to bone structure and mechanical properties. Although there are abundant researches on bone loss in microgravity, the explicit mechanism is not completely understood. At present, it is widely accepted that the absence of mechanical stimulus plays a predominant role in bone homeostasis disorders in conditions of weightlessness. However, aside from mechanical unloading, nonmechanical factors such as various hormones, cytokines, dietary nutrition, etc. are important as well in microgravity induced bone loss. The stress-induced increase in endogenous glucocorticoid (GC) levels is inevitable in microgravity environments. Moreover, it is well known that GCs have a detrimental effect to bone health at excess concentrations. Therefore, GC plays a potential role in microgravity-induced bone loss. This review summarizeds several studies and their prospective solutions to this hypothesis.

  10. Roles of Prolyl Isomerases in RNA-Mediated Gene Expression

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    Roopa Thapar

    2015-05-01

    Full Text Available The peptidyl-prolyl cis-trans isomerases (PPIases that include immunophilins (cyclophilins and FKBPs and parvulins (Pin1, Par14, Par17 participate in cell signaling, transcription, pre-mRNA processing and mRNA decay. The human genome encodes 19 cyclophilins, 18 FKBPs and three parvulins. Immunophilins are receptors for the immunosuppressive drugs cyclosporin A, FK506, and rapamycin that are used in organ transplantation. Pin1 has also been targeted in the treatment of Alzheimer’s disease, asthma, and a number of cancers. While these PPIases are characterized as molecular chaperones, they also act in a nonchaperone manner to promote protein-protein interactions using surfaces outside their active sites. The immunosuppressive drugs act by a gain-of-function mechanism by promoting protein-protein interactions in vivo. Several immunophilins have been identified as components of the spliceosome and are essential for alternative splicing. Pin1 plays roles in transcription and RNA processing by catalyzing conformational changes in the RNA Pol II C-terminal domain. Pin1 also binds several RNA binding proteins such as AUF1, KSRP, HuR, and SLBP that regulate mRNA decay by remodeling mRNP complexes. The functions of ribonucleoprotein associated PPIases are largely unknown. This review highlights PPIases that play roles in RNA-mediated gene expression, providing insight into their structures, functions and mechanisms of action in mRNP remodeling in vivo.

  11. Metallothionein Expression and Roles During Neuropathology in the CNS

    DEFF Research Database (Denmark)

    Penkowa, Milena

    2006-01-01

    /or IL-6-induced MT-I+II exert neuroprotective functions. To study MT-I+II roles in CNS, genetically modified mice with MT-I+II deficiency (MT-I+II knock-out (MT-KO) mice) or transgenic MT-I overexpression (TgMT mice) were applied along wildtype controls; as well as wildtype, and MT-KO mice receiving...... roles. Accordingly, MT-I+II reduce CNS activation of macrophages and lymphocytes including expression of proinflammatory cytokines IL-1b, IL-6, IL-12 and TNF-a. Moreover, MT-I+II are antioxidant and antiapoptotic factors counteracting reactive oxygen species (ROS)/oxidative stress, neurodegeneration...... supported by comparing various genotypes like GFAP-IL6 mice; MT-I+II deficient GFAP-IL6 (GFAP-IL6/MT-KO) mice; MT-I+II heterozygous GFAP-IL6 mice (GFAP-IL6-MT+/- mice); double-transgenic IL-6 and MT-I overexpressors (GFAP-IL6/TgMT mice); MT-KO mice; and TgMT mice. The IL-6 overexpressors are suitable...

  12. The relation of expression recognition and affective experience in facial expression processing: an event-related potential study

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    Guangheng Dong

    2010-04-01

    Full Text Available Guangheng Dong1, Shenglan Lu21Department of Psychology, 2Department of International Education, Zhejiang Normal University, Jinhua, ChinaAbstract: The present study investigates the relationship of expression recognition and affective experience during facial expression processing by event-related potentials (ERP. Facial expressions used in the present study can be divided into three categories: positive (happy, neutral (neutral, and negative (angry. Participants were asked to finish two kinds of facial recognition tasks: one was easy, and the other was difficult. In the easy task, significant main effects were found for different valence conditions, meaning that emotions were evoked effectively when participants recognized the expressions in facial expression processing. However, no difference was found in the difficult task, meaning that even if participants had identified the expressions correctly, no relevant emotion was evoked during the process. The findings suggest that emotional experience was not simultaneous with expression identification in facial expression processing, and the affective experience process could be suppressed in challenging cognitive tasks. The results indicate that we should pay attention to the level of cognitive load when using facial expressions as emotion-eliciting materials in emotion studies; otherwise, the emotion may not be evoked effectively.Keywords: affective experience, expression recognition, cognitive load, event-related potential

  13. Expressions of Critical Thinking in Role-Playing Simulations: Comparisons across Roles

    Science.gov (United States)

    Ertmer, Peggy A.; Strobel, Johannes; Cheng, Xi; Chen, Xiaojun; Kim, Hannah; Olesova, Larissa; Sadaf, Ayesha; Tomory, Annette

    2010-01-01

    The development of critical thinking is crucial in professional education to augment the capabilities of pre-professional students. One method for enhancing critical thinking is participation in role-playing simulation-based scenarios where students work together to resolve a potentially real situation. In this study, undergraduate nursing…

  14. Potential Roles of Fungal Extracellular Vesicles during Infection

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    Joffe, Luna S.; Nimrichter, Leonardo

    2016-01-01

    ABSTRACT Extracellular vesicles (EVs) are produced by virtually all cell types. Within the past few years, work in this field has revealed more information about fungal EVs. Fungal EVs have been shown to carry proteins, lipids, pigments, polysaccharides, and RNA; these components are known virulence factors, a fact which supports the hypothesis that fungal EVs concentrate pathogenic determinants. Additionally, recent studies have demonstrated that fungal EVs stimulate the host immune system. In this review, putative roles of fungal EVs are discussed, including their potential as vaccination tools and their possible contribution to pathogenesis in invasive fungal diseases. PMID:27390779

  15. The potential role of transient receptor potential type A1 as a mechanoreceptor in human periodontal ligament cells.

    Science.gov (United States)

    Tsutsumi, Takashi; Kajiya, Hiroshi; Fukawa, Teruhisa; Sasaki, Mina; Nemoto, Tetsuomi; Tsuzuki, Takashi; Takahashi, Yutaka; Fujii, Shinsuke; Maeda, Hidefumi; Okabe, Koji

    2013-12-01

    Transient receptor potential type A1 (TRPA1) is reported to be a Ca(2+) -permeable channel and is activated by cold temperatures and mechanical stimuli in the hair cells and in dorsal root ganglion. Using a DNA microarray, we found that TRPA1 was significantly up-regulated in human periodontal ligament (hPDL) cells 2 d after intermittent mechanical stimulation (iMS) loading compared with unloaded cells. Although hPDL cells are known to respond to mechanical stimulation induced by occlusal force, little is known about the expression and functional role of TRPA1 in these cells. Therefore, we investigated the effects of iMS on TRPA1 expression and its signaling pathway in hPDL cells. Intermittent mechanical stimulation loading up-regulated TRPA1 expression in hPDL cells in a time-dependent manner, but had no effect on other mechanoreceptors. Furthermore, iMS significantly increased the phosphorylation of mitogen-activated protein kinases (MAPKs), especially extracellular signal-regulated kinase 1/2 (ERK1/2) and p38, and the expression of C-C chemokine ligand 2 (CCL2). Transient receptor potential type A1 agonists also increased MAPK phosphorylation and the intracellular Ca(2+) concentration. By contrast, inhibition or silencing of TRPA1 partially suppressed iMS-induced MAPK phosphorylation. In summary, iMS during occlusion activates TRPA1 and MAPK signaling in periodontal ligament tissues, suggesting that TRPA1 regulates the mechanosensitivity of occlusal force via activation of MAPKs in hPDL cells. © 2013 Eur J Oral Sci.

  16. Potential role for peptidylarginine deiminase 2 (PAD2 in citrullination of canine mammary epithelial cell histones.

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    Brian D Cherrington

    Full Text Available Peptidylarginine Deiminases (PADs convert arginine residues on substrate proteins to citrulline. Previous reports have documented that PAD2 expression and activity varies across the estrous cycle in the rodent uterus and pituitary gland, however, the expression and function of PAD2 in mammary tissue has not been previously reported. To gain more insight into potential reproductive roles for PAD2, in this study we evaluated PAD2 expression and localization throughout the estrous cycle in canine mammary tissue and then identified possible PAD2 enzymatic targets. Immunohistochemical and immunofluorescence analysis found PAD2 expression is low in anestrus, limited to a distinct, yet sparse, subset of epithelial cells within ductal alveoli during estrus/early diestrus, and encompasses the entire epithelium of the mammary duct in late diestrus. At the subcellular level, PAD2 is expressed in the cytoplasm, and to a lesser extent, the nucleus of these epithelial cells. Surprisingly, stimulation of canine mammary tumor cells (CMT25 shows that EGF, but not estrogen or progesterone, upregulates PAD2 transcription and translation suggesting EGF regulation of PAD2 and possibly citrullination in vivo. To identify potential PAD2 targets, anti-pan citrulline western blots were performed and results showed that citrullination activity is limited to diestrus with histones appearing to represent major enzymatic targets. Use of site-specific anti-citrullinated histone antibodies found that the N-terminus of histone H3, but not H4, appears to be the primary target of PAD activity in mammary epithelium. This observation supports the hypothesis that PAD2 may play a regulatory role in the expression of lactation related genes via histone citrullination during diestrus.

  17. Expression of Potential Cancer Stem Cell Marker ABCG2 is Associated with Malignant Behaviors of Hepatocellular Carcinoma

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    Guang Zhang

    2013-01-01

    Full Text Available Background. Despite improvement in treatment, the prognosis of hepatocellular carcinoma (HCC remains disastrous. Cancer stem cells (CSCs may be responsible for cancer malignant behaviors. ATP-binding cassette, subfamily G, member 2 (ABCG2 is widely expressed in both normal and cancer stem cells and may play an important role in cancer malignant behaviors. Methods. The expression of ABCG2 in HCC tissues and SMMC-7721 cells was examined, and the relevance of ABCG2 expression with clinical characteristics was analyzed. ABCG2+ and ABCG2− cells were sorted, and the potential of tumorigenicity was determined. Expression level of ABCG2 was manipulated by RNA interference and overexpression. Malignant behaviors including proliferation, drug resistance, migration, and invasion were studied in vitro. Results. Expression of ABCG2 was found in a minor group of cells in HCC tissues and cell lines. ABCG2 expression showed tendencies of association with unfavorable prognosis factors. ABCG2 positive cells showed a superior tumorigenicity. Upregulation of ABCG2 enhanced the capacity of proliferation, doxorubicin resistance, migration, and invasion potential, while downregulation of ABCG2 significantly decreased these malignant behaviors. Conclusion. Our results indicate that ABCG2 is a potential CSC marker for HCC. Its expression level has a close relationship with tumorigenicity, proliferation, drug resistance, and metastasis ability.

  18. Enhanced A-FABP expression in visceral fat: potential contributor to the progression of NASH

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    Min Yong Yoon

    2012-09-01

    Full Text Available Background/AimsAdipose tissue is an active endocrine organ that secretes various metabolically important substances including adipokines, which represent a link between insulin resistance and nonalcoholic steatohepatitis (NASH. The factors responsible for the progression from simple steatosis to steatohepatitis remain elusive, but adipokine imbalance may play a pivotal role. We evaluated the expressions of adipokines such as visfatin, adipocyte-fatty-acid-binding protein (A-FABP, and retinol-binding protein-4 (RBP-4 in serum and tissue. The aim was to discover whether these adipokines are potential predictors of NASH.MethodsPolymerase chain reaction, quantification of mRNA, and Western blots encoding A-FABP, RBP-4, and visfatin were used to study tissue samples from the liver, and visceral and subcutaneous adipose tissue. The tissue samples were from biopsy specimens obtained from patients with proven NASH who were undergoing laparoscopic cholecystectomy due to gallbladder polyps.ResultsPatients were classified into two groups: NASH, n=10 and non-NASH, n=20 according to their nonalcoholic fatty liver disease Activity Score. Although serum A-FABP levels did not differ between the two groups, the expressions of A-FABP mRNA and protein in the visceral adipose tissue were significantly higher in NASH group than in non-NASH group (104.34 vs. 97.05, P<0.05, and 190.01 vs. 95.15, P<0.01, respectively. Furthermore, the A-FABP protein expression ratio between visceral adipose tissue and liver was higher in NASH group than in non-NASH group (4.38 vs. 1.64, P<0.05.ConclusionsNASH patients had higher levels of A-FABP expression in their visceral fat compared to non-NASH patients. This differential A-FABP expression may predispose patients to the progressive form of NASH.

  19. Fibroblast growth factor receptor-2 expression in thyroid tumor progression: potential diagnostic application.

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    Adriano Redler

    Full Text Available Fibroblast growth factor receptor-2 (FGFR-2 plays an important role in tumorigenesis. In thyroid cancer it has been observed a FGFR-2 down-modulation, but the role of this receptor has not been yet clarified. Therefore, we decided to examine the expression of both FGFR-2 isoform, FGFR-2-IIIb and FGFR-2-IIIc, in different histological thyroid variants such as hyperplasia, follicular adenoma and papillary carcinoma. Immunohistochemistry and quantitative Real-Time PCR analyses were performed on samples of hyperplasia, follicular adenoma and papillary carcinoma, compared with normal thyroid tissue. Thyroid hyperplasia did not show statistically significant reduction in FGFR-2 protein and mRNA levels. Interestingly, in both follicular adenoma and papillary carcinoma samples we observed a strongly reduced expression of both FGFR-2 isoforms. We speculate that FGFR-2 down-modulation might be an early event in thyroid carcinogenesis. Furthermore, we suggest the potential use of FGFR-2 as an early marker for thyroid cancer diagnosis.

  20. Computationally Discovered Potentiating Role of Glycans on NMDA Receptors

    Science.gov (United States)

    Sinitskiy, Anton V.; Stanley, Nathaniel H.; Hackos, David H.; Hanson, Jesse E.; Sellers, Benjamin D.; Pande, Vijay S.

    2017-04-01

    N-methyl-D-aspartate receptors (NMDARs) are glycoproteins in the brain central to learning and memory. The effects of glycosylation on the structure and dynamics of NMDARs are largely unknown. In this work, we use extensive molecular dynamics simulations of GluN1 and GluN2B ligand binding domains (LBDs) of NMDARs to investigate these effects. Our simulations predict that intra-domain interactions involving the glycan attached to residue GluN1-N440 stabilize closed-clamshell conformations of the GluN1 LBD. The glycan on GluN2B-N688 shows a similar, though weaker, effect. Based on these results, and assuming the transferability of the results of LBD simulations to the full receptor, we predict that glycans at GluN1-N440 might play a potentiator role in NMDARs. To validate this prediction, we perform electrophysiological analysis of full-length NMDARs with a glycosylation-preventing GluN1-N440Q mutation, and demonstrate an increase in the glycine EC50 value. Overall, our results suggest an intramolecular potentiating role of glycans on NMDA receptors.

  1. The Potential Roles of Bisphenol A (BPA Pathogenesis in Autoimmunity

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    Datis Kharrazian

    2014-01-01

    Full Text Available Bisphenol A (BPA is a monomer found in commonly used consumer plastic goods. Although much attention in recent years has been placed on BPA’s impact as an endocrine disruptor, it also appears to activate many immune pathways involved in both autoimmune disease development and autoimmune reactivity provocation. The current scientific literature is void of research papers linking BPA directly to human or animal onset of autoimmunity. This paper explores the impact of BPA on immune reactivity and the potential roles these mechanisms may have on the development or provocation of autoimmune diseases. Potential mechanisms by which BPA may be a contributing risk factor to autoimmune disease development and progression include its impact on hyperprolactinemia, estrogenic immune signaling, cytochrome P450 enzyme disruption, immune signal transduction pathway alteration, cytokine polarization, aryl hydrocarbon activation of Th-17 receptors, molecular mimicry, macrophage activation, lipopolysaccharide activation, and immunoglobulin pathophysiology. In this paper a review of these known autoimmune triggering mechanisms will be correlated with BPA exposure, thereby suggesting that BPA has a role in the pathogenesis of autoimmunity.

  2. Role of negative affects in pathophysiology and clinical expression of irritable bowel syndrome.

    Science.gov (United States)

    Muscatello, Maria Rosaria A; Bruno, Antonio; Scimeca, Giuseppe; Pandolfo, Gianluca; Zoccali, Rocco A

    2014-06-28

    Irritable bowel syndrome (IBS) is regarded as a multifactorial disease in which alterations in the brain-gut axis signaling play a major role. The biopsychosocial model applied to the understanding of IBS pathophysiology assumes that psychosocial factors, interacting with peripheral/central neuroendocrine and immune changes, may induce symptoms of IBS, modulate symptom severity, influence illness experience and quality of life, and affect outcome. The present review focuses on the role of negative affects, including depression, anxiety, and anger, on pathogenesis and clinical expression of IBS. The potential role of the autonomic nervous system, stress-hormone system, and immune system in the pathophysiology of both negative affects and IBS are taken into account. Psychiatric comorbidity and subclinical variations in levels of depression, anxiety, and anger are further discussed in relation to the main pathophysiological and symptomatic correlates of IBS, such as sensorimotor functions, gut microbiota, inflammation/immunity, and symptom reporting.

  3. Potential role of dopamine transporter in behavioral flexibility.

    Science.gov (United States)

    Cybulska-Klosowicz, Anita; Dabrowska, Julia; Niedzielec, Sebastian; Zakrzewska, Renata; Rozycka, Aleksandra

    2017-01-01

    Behavioral flexibility is subserved by the prefrontal cortex and the basal ganglia. Orbitofrontal cortex (OFC) and dorsomedial striatum (DMS) form a functional frontocorticostriatal circuit crucial for the mediation of flexibility during reversal learning via dopamine (DA) neurotransmission. The regulatory control in maintaining DA homeostasis and function is provided by the dopamine transporter (DAT), which therefore likely plays a significant role in controlling the influence of DA on cognitive processes. Here we used a gene knockout mouse model to investigate the role of DAT in the performance on the Attentional Set-Shifting Task (ASST) stages dependent upon the OFC and the DMS. Additionally, behavior of mice after repeated administration of selective DAT inhibitor, GBR 12909, was examined. The animals were treated with the inhibitor to elicit a compensatory DAT up-regulation following withdrawal. Learning was slower and the number of errors during reversal learning and intra-dimensional shift stages was higher in DAT+/- mutant mice than in WT mice. GBR 12909-treated mice had deficits in reversal stages of the ASST. Neuronal activation in the OFC and DMS during the ASST was examined with early growth response proteins 1 and 2 (egr-1, egr-2) immunohistochemistry. Density of egr-2 labeled cells in the OFC was lower in mutant mice than in wild-types during reversal learning and the expression of the egr-1 was lower in mutant mice in the OFC and DMS during reversal and intra-dimensional shift stages. Mice with decreased DAT levels displayed behavioral difficulties that were accompanied by a lower task-induced activation of neurons in brain regions involved in the reversal learning. Altogether, these data indicate the role of the DAT in the behavioral flexibility.

  4. Potential role of viruses in white plague coral disease.

    Science.gov (United States)

    Soffer, Nitzan; Brandt, Marilyn E; Correa, Adrienne M S; Smith, Tyler B; Thurber, Rebecca Vega

    2014-02-01

    White plague (WP)-like diseases of tropical corals are implicated in reef decline worldwide, although their etiological cause is generally unknown. Studies thus far have focused on bacterial or eukaryotic pathogens as the source of these diseases; no studies have examined the role of viruses. Using a combination of transmission electron microscopy (TEM) and 454 pyrosequencing, we compared 24 viral metagenomes generated from Montastraea annularis corals showing signs of WP-like disease and/or bleaching, control conspecific corals, and adjacent seawater. TEM was used for visual inspection of diseased coral tissue. No bacteria were visually identified within diseased coral tissues, but viral particles and sequence similarities to eukaryotic circular Rep-encoding single-stranded DNA viruses and their associated satellites (SCSDVs) were abundant in WP diseased tissues. In contrast, sequence similarities to SCSDVs were not found in any healthy coral tissues, suggesting SCSDVs might have a role in WP disease. Furthermore, Herpesviridae gene signatures dominated healthy tissues, corroborating reports that herpes-like viruses infect all corals. Nucleocytoplasmic large DNA virus (NCLDV) sequences, similar to those recently identified in cultures of Symbiodinium (the algal symbionts of corals), were most common in bleached corals. This finding further implicates that these NCLDV viruses may have a role in bleaching, as suggested in previous studies. This study determined that a specific group of viruses is associated with diseased Caribbean corals and highlights the potential for viral disease in regional coral reef decline.

  5. Trichomonas vaginalis: pathogenicity and potential role in human reproductive failure.

    Science.gov (United States)

    Mielczarek, Ewelina; Blaszkowska, Joanna

    2016-08-01

    Trichomonas vaginalis, which colonizes the genitourinary tract of men and women, is a sexually transmitted parasite causing symptomatic or asymptomatic trichomoniasis. The host-parasite relationship is very complex, and clinical symptoms cannot likely be attributed to a single pathogenic effect. Among the many factors responsible for interactions between T. vaginalis and host tissues, contact-dependent and contact-independent mechanisms are important in pathogenicity, as is the immune response. This review focuses on the potential virulence properties of T. vaginalis and its role in female and male infertility. It highlights the association between T. vaginalis infection and serious adverse health consequences experienced by women, including infertility, preterm birth and low-birth-weight infants. Long-term clinical observations and results of in vitro experimental studies indicate that in men, trichomoniasis has been also associated with infertility through inflammatory damage to the genitourinary tract or interference with sperm function. These results contribute significantly to improving our knowledge of the role of parasitic virulence factors in the development of infection and its role in human infertility.

  6. Serglycin as a potential biomarker for glioma: association of serglycin expression, extent of mast cell recruitment and glioblastoma progression

    Science.gov (United States)

    Roy, Ananya; Attarha, Sanaz; Weishaupt, Holger; Edqvist, Per-Henrik; Swartling, Fredrik J.; Bergqvist, Michael; Siebzehnrubl, Florian A.; Smits, Anja; Pontén, Fredrik; Tchougounova, Elena

    2017-01-01

    Serglycin is an intracellular proteoglycan with a unique ability to adopt highly divergent structures by glycosylation with variable types of glycosaminoglycans (GAGs) when expressed by different cell types. Serglycin is overexpressed in aggressive cancers suggesting its protumorigenic role. In this study, we explored the expression of serglycin in human glioma and its correlation with survival and immune cell infiltration. We demonstrate that serglycin is expressed in glioma and that increased expression predicts poor survival of patients. Analysis of serglycin expression in a large cohort of low- and high-grade human glioma samples reveals that its expression is grade dependent and is positively correlated with mast cell (MC) infiltration. Moreover, serglycin expression in patient-derived glioma cells is significantly increased upon MC co-culture. This is also accompanied by increased expression of CXCL12, CXCL10, as well as markers of cancer progression, including CD44, ZEB1 and vimentin. In conclusion, these findings indicate the importance of infiltrating MCs in glioma by modulating signaling cascades involving serglycin, CD44 and ZEB1. The present investigation reveals serglycin as a potential prognostic marker for glioma and demonstrates an association with the extent of MC recruitment and glioma progression, uncovering potential future therapeutic opportunities for patients. PMID:28445977

  7. Bacteriophage and their potential roles in the human oral cavity

    Directory of Open Access Journals (Sweden)

    Anna Edlund

    2015-04-01

    Full Text Available The human oral cavity provides the perfect portal of entry for viruses and bacteria in the environment to access new hosts. Hence, the oral cavity is one of the most densely populated habitats of the human body containing some 6 billion bacteria and potentially 35 times that many viruses. The role of these viral communities remains unclear; however, many are bacteriophage that may have active roles in shaping the ecology of oral bacterial communities. Other implications for the presence of such vast oral phage communities include accelerating the molecular diversity of their bacterial hosts as both host and phage mutate to gain evolutionary advantages. Additional roles include the acquisitions of new gene functions through lysogenic conversions that may provide selective advantages to host bacteria in response to antibiotics or other types of disturbances, and protection of the human host from invading pathogens by binding to and preventing pathogens from crossing oral mucosal barriers. Recent evidence suggests that phage may be more involved in periodontal diseases than were previously thought, as their compositions in the subgingival crevice in moderate to severe periodontitis are known to be significantly altered. However, it is unclear to what extent they contribute to dysbiosis or the transition of the microbial community into a state promoting oral disease. Bacteriophage communities are distinct in saliva compared to sub- and supragingival areas, suggesting that different oral biogeographic niches have unique phage ecology shaping their bacterial biota. In this review, we summarize what is known about phage communities in the oral cavity, the possible contributions of phage in shaping oral bacterial ecology, and the risks to public health oral phage may pose through their potential to spread antibiotic resistance gene functions to close contacts.

  8. Expression and distribution of three transient receptor potential vanilloid(TRPV) channel proteins in human odontoblast-like cells.

    Science.gov (United States)

    Wen, Wen; Que, Kehua; Zang, Chengcheng; Wen, Jing; Sun, Guangxu; Zhao, Zhiying; Li, Yanzhong

    2017-12-01

    Odontoblasts have been suggested to contribute to nociceptive sensation in the tooth via expression of the transient receptor potential (TRP) channels. The TRP channels as a family of nonselective cation permeable channels play an important role in sensory transduction of human. In this study, we examined the expression of transient receptor potential vanilloid-1 (TRPV1), transient receptor potential vanilloid-2 (TRPV2) and transient receptor potential vanilloid-3 (TRPV3) channels in native human odontoblasts (HODs) and long-term cultured human dental pulp cells with odontoblast phenotyoe (LHOPs) obtained from healthy wisdom teeth with the use of immunohistochemistry (IHC), immunofluorescence (IF), quantitative real-time polymerase chain reaction (qRT-PCR),western blotting (WB) and immunoelectron microscopy (IEM) assay. LHOPs samples were made into ultrathin sections, mounted on nickel grids, floated of three TRPV antibodies conjugated with 10 nm colloidal gold particles and observed under IEM at 60,000 magnifications. The relative intracellular distributions of these three channels were analyzed quantitatively on IEM images using a robust sampling, stereological estimation and statistical evaluation method. The results of IHC and IF convinced that TRPV1, TRPV2 and TRPV3 channels were expressed in native HODs and (LHOPs). The result of qRT-PCR and WB confirmed that the gene and protein expression of TRPV1, TRPV2, and TRPV3 channels and TRPV1 mRNA are more abundantly expressed than TRPV2 and TRPV3 in HODs (P distributions of these three channels are similar, and TRPV1, TRPV2 and TRPV3 proteins were preferential labeled in human odontoblast processes, mitochondria, and endoplasmic reticulum. Thus, HODs could play an important role in mediating pulp thermo-sensation due to the expression of these three TRPV channels. The difference of relative intracellular distributions of three channels suggests that special structures such as processes may have an important role

  9. Expression and roles of Slit/Robo in human ovarian cancer.

    Science.gov (United States)

    Dai, Cai Feng; Jiang, Yi Zhou; Li, Yan; Wang, Kai; Liu, Pei Shu; Patankar, Manish S; Zheng, Jing

    2011-05-01

    The Slit glycoproteins and their Roundabout (Robo) receptors regulate migration and growth of many types of cells including human cancer cells. However, little is known about the expression and roles of Slit/Robo in human ovarian cancer. Herein, we examined the expression of Slit/Robo in human normal and malignant ovarian tissues and its potential participation in regulating migration and proliferation of human ovarian cancer cells using two ovarian cancer cell lines, OVCAR-3 and SKOV-3. We demonstrated that Slit2/3 and Robo1 were immunolocalized primarily in stromal cells in human normal ovaries and in cancer cells in many histotypes of ovarian cancer tissues. Protein expression of Slit2/3 and Robo1/4 was also identified in OVCAR-3 and SKOV-3 cells. However, recombinant human Slit2 did not significantly affect SKOV-3 cell migration, and OVCAR-3 and SKOV-3 cell proliferation. Slit2 also did not induce ERK1/2 and AKT1 phosphorylation in OVCAR-3 and SKOV-3 cells. The current findings indicate that three major members (Slit2/3 and Robo1) of Slit/Robo family are widely expressed in the human normal and malignant ovarian tissues and in OVCAR-3 and SKOV-3 cells. However, Slit/Robo signaling may not play an important role in regulating human ovarian cancer cell proliferation and migration.

  10. Gene expression profiling using nanostring digital RNA counting to identify potential target antigens for melanoma immunotherapy.

    Science.gov (United States)

    Beard, Rachel E; Abate-Daga, Daniel; Rosati, Shannon F; Zheng, Zhili; Wunderlich, John R; Rosenberg, Steven A; Morgan, Richard A

    2013-09-15

    The success of immunotherapy for the treatment of metastatic cancer is contingent on the identification of appropriate target antigens. Potential targets must be expressed on tumors but show restricted expression on normal tissues. To maximize patient eligibility, ideal target antigens should be expressed on a high percentage of tumors within a histology and, potentially, in multiple different malignancies. A Nanostring probeset was designed containing 97 genes, 72 of which are considered potential candidate genes for immunotherapy. Five established melanoma cell lines, 59 resected metastatic melanoma tumors, and 31 normal tissue samples were profiled and analyzed using Nanostring technology. Of the 72 potential target genes, 33 were overexpressed in more than 20% of studied melanoma tumor samples. Twenty of those genes were identified as differentially expressed between normal tissues and tumor samples by ANOVA analysis. Analysis of normal tissue gene expression identified seven genes with limited normal tissue expression that warrant further consideration as potential immunotherapy target antigens: CSAG2, MAGEA3, MAGEC2, IL13RA2, PRAME, CSPG4, and SOX10. These genes were highly overexpressed on a large percentage of the studied tumor samples, with expression in a limited number of normal tissue samples at much lower levels. The application of Nanostring RNA counting technology was used to directly quantitate the gene expression levels of multiple potential tumor antigens. Analysis of cell lines, 59 tumors, and normal tissues identified seven potential immunotherapy targets for the treatment of melanoma that could increase the number of patients potentially eligible for adoptive immunotherapy. ©2013 AACR.

  11. Phosphatase and tensin homolog in cerebral cavernous malformation: a potential role in pathological angiogenesis.

    Science.gov (United States)

    Zhu, Yuan; Peters, Christian; Hallier-Neelsen, Monika; Miller, Dorothea; Pagenstecher, Axel; Bertalanffy, Helmut; Sure, Ulrich

    2009-03-01

    Cerebral cavernous malformations (CCMs) are the most common vascular malformation of the central nervous system and involve dysregulated angiogenesis. However, the underlying mechanism of this disease is poorly understood. Phosphatase and tensin homolog (PTEN) plays a crucial role in regulating angiogenesis. The authors attempted to determine whether PTEN is involved in the pathological angiogenesis of CCM. The authors used Western blot analysis and immunohistochemical methods to detect the expression of PTEN, PCNA, and P-Akt in the surgical specimens of CCMs and controls. The function of PTEN in cell proliferation was studied after PTEN silencing in endothelial cultures by using the short interfering RNA technique. Western blot analysis showed significant reduction of PTEN protein expression in CCMs compared with control brain tissue (p < 0.01). Immunohistochemical analysis confirmed PTEN insufficiency in 33% of vascular endothelia of CCMs, which was significantly higher than that of controls (2%, p < 0.01). Furthermore, PTEN insufficiency occurred more frequently in multiple CCMs (44%) and in small lesions (39%) than in single CCMs (28%, p < 0.05) and large lesions (30%, p < 0.05), respectively, suggesting a potential role of PTEN in the progression of the lesions. Of note, a negative correlation was observed between the expression of PTEN and PCNA in CCM endothelial cells. However, Akt was not constitutively activated in CCMs. Using cultured endothelial cells, the authors demonstrated that PTEN silencing by short interfering RNA increased Akt activation, PCNA expression, and cell proliferation (p < 0.001). Surprisingly, the PTEN silencing-mediated increase in endothelial proliferation was not reversed by the PI3K inhibitor wortmannin. In this study, the authors report for the first time a significant PTEN insufficiency in CCM vessels associated with endothelial proliferation. The in vitro study provides direct evidence for a pivotal role of PTEN in regulating

  12. Expression and prognostic role of ubiquitination factor E4B in primary hepatocellular carcinoma.

    Science.gov (United States)

    Zhang, Xiao-Fei; Pan, Qiu-Zhong; Pan, Ke; Weng, De-Sheng; Wang, Qi-Jing; Zhao, Jing-Jing; He, Jia; Liu, Qing; Wang, Dan-Dan; Jiang, Shan-Shan; Zheng, Hai-Xia; Lv, Lin; Chen, Chang-Long; Zhang, Hong-Xia; Xia, Jian-Chuan

    2016-01-01

    Ubiquitination factor E4B (UBE4B) has been speculated to have contradictory functions upon tumorigenesis as an oncogene or tumor suppressor in different types of cancers. We investigated the expression and prognostic role of UBE4B in primary hepatocellular carcinoma (HCC) using cell lines and 149 archived HCC samples. Correlation between the functions of UBE4B in HCC was also explored. We used human HCC cell lines (HepG2, Hep3B, SK-Hep1, Huh7, SMMC-7721, BEL-7402) and a normal hepatocyte cell line (LO2) along with HCC samples from patients who had undergone resection for HCC previously at our hospital. A battery of methods (real-time quantitative polymerase chain reaction; Western blotting; immunohistochjemical analyses; cell proliferation and colony formation assays; cell migration and cell invasion assays) were employed to assess various aspects of UBE4B.We found that UBE4B expression was upregulated aberrantly at mRNA and protein levels in human primary HCC tissues. Amplified expression of UBE4B was highly correlated with poor outcome. Silencing of UBE4B expression by siRNA inhibited the proliferation, colony formation, migration and invasion of HCC cells in vitro, and resulted in significant apoptosis that was associated with downregulation of expression of Bcl-2 and upregulation of expression of total p53, p-p53, Bax and Cleaved-Caspase3 in HCC cells. Our findings suggested that UBE4B might have an oncogenic role in human primary HCC, and that it could be used as a prognostic marker (as well as a potential molecular target) for the treatment of HCC. © 2015 Wiley Periodicals, Inc.

  13. Potential role of microorganisms in the pathogenesis of rosacea.

    Science.gov (United States)

    Holmes, Anna D

    2013-12-01

    Rosacea is a skin condition of abnormal inflammation and vascular dysfunction. The active contribution of a microbial agent in the development or progression of rosacea continues to be debated. Research supports the presence of commensal Demodex folliculorum mites at increased density in the skin and associates Helicobacter pylori infection of the gut with rosacea. Fewer studies implicate Staphylococcus epidermidis, Chlamydophila pneumoniae, and the Demodex-associated bacteria Bacillus oleronius. No research, however, provides a mechanism by which colonization by a microorganism translates to manifestation of the condition. Prevailing and emerging principles in the biology of the microbiome and the pathophysiology of rosacea may help to reconcile these lingering questions. Here the microorganisms implicated in rosacea are reviewed and the reaction of the microbiome to inflammation and to changes in microenvironments and macroenvironments are discussed to explain potential roles for microorganisms in rosacea pathophysiology. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  14. The potential role of microorganisms in the development of rosacea.

    Science.gov (United States)

    Lazaridou, Elizabeth; Giannopoulou, Christina; Fotiadou, Christina; Vakirlis, Eustratios; Trigoni, Anastasia; Ioannides, Demetris

    2011-01-01

    Rosacea is a chronic cutaneous disorder characterized by centrofacial persisting erythema, telangiectases, papules, pustules, edema, phymas and ocular involvement. Despite being one of the most common skin disorders, its pathogenesis remains unclear and controversial. Although the disease triggering factors are well recognized, the underlying causes of rosacea have not yet been identified. Several different postulates about its pathogenesis can be found in the medical literature. Abnormalities of the pilosebaceous unit, as well as genetic, vascular, inflammatory, environmental and microbial factors have been described. The microorganisms that have been associated include Helicobacter pylori, Demodex folliculorum, Staphylococcus epidermidis, and Chlamydia pneumonia; all the studies have been inconclusive. We review currently available scientific data on the potential pathogenetic role of microorganisms in the development of rosacea. © The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.

  15. Cytokines: Roles in atherosclerosis disease progression and potential therapeutic targets

    Science.gov (United States)

    Moss, Joe W. E.; Ramji, Dipak P.

    2017-01-01

    Atherosclerosis, the primary cause of cardiovascular disease (CVD), is a chronic inflammatory disorder in the walls of medium and large arteries. CVD is currently responsible for about one in three global deaths and this is expected to rise in the future due to an increase in the prevalence of obesity and diabetes. Current therapies for atherosclerosis mainly modulate lipid homeostasis and whilst successful at reducing the risk of a CVD-related death, they are associated with considerable residual risk and various side effects. There is therefore a need for alternative therapies aimed at regulating inflammation in order to reduce atherogenesis. This review will highlight the key role cytokines play during disease progression as well as potential therapeutic strategies to target them. PMID:27357616

  16. The role of art variables on the expression of drawing

    OpenAIRE

    Kosi, Tina

    2016-01-01

    The diploma thesis is dedicated to the art variables in conjunction with expression of drawings. In art - theoretical part of the thesis I address art on the conceptual level, which depends on each individual artist and, of course, also the viewer who is watching artwork. On the expression also affects the physical level, where the focus is primarily on the work and materials, which allow a certain type of expression. Then, I analyse the expression of drawings in terms of visual language, ...

  17. Prognostic role of syncytin expression in breast cancer

    DEFF Research Database (Denmark)

    Larsson, Lars-Inge; Holck, Susanne; Christensen, Ib Jarle

    2007-01-01

    node-negative women for syncytin expression using an immunocytochemical scoring system. Results were analyzed with the Kaplan-Meier method and with the Cox proportional hazard model. Syncytin expression was observed in 38% of the patients, and the degree of syncytin expression constituted a positive...

  18. Potential role of amino acids in pathogenesis of schizophrenia.

    Science.gov (United States)

    Saleem, Shamaila; Shaukat, Faiza; Gul, Anjuman; Arooj, Mahwish; Malik, Arif

    2017-01-01

    Schizophrenia is a syndrome of inconclusive etiopathogenesis with a prevalence of about 1% in general population. Underlying factors include genetic predisposition and defected neurodevelopment in early stages of life. The role of amino acids has been indicated in some reports. However, very few workers have detailed the effect of each amino acid in the pathophysiology of schizophrenia. Thus, in the present review, we aimed to provide an insight into the potential role of amino acids levels during schizophrenia. Any single amino acid defect cannot lead to the development of the disease. Higher concentration of glycine, serine, glutamate, homocysteine, and arginine are reported by many scientists in blood samples of patients of schizophrenia. Levels of rest of the amino acids show inconsistent results. Involvement of glutamate in pathophysiology of schizophrenia was hypothesized as early as the 1980s. It was demonstrated that dissociative anesthetics which are N-methyl-D-aspartate (NMDA) receptor antagonists can produce all negative, psychotic, cognitive, and physiological features of schizophrenia in healthy controls. This led to the development of hypothesis of NMDA receptor hypofunctioning in the pathophysiology of schizophrenia. Later on, it was also found that agents enhancing functioning of NMDA receptor at glycine modulatory site, improved symptoms in patients of schizophrenia receiving antipsychotic medications. Thus, the relationship of perturb amino acid levels with the biological basis and pathophysiology of schizophrenia is an important area to be further explored for effective management of schizophrenic patients.

  19. Potential coordination role between O-GlcNAcylation and epigenetics

    Directory of Open Access Journals (Sweden)

    Donglu Wu

    2017-05-01

    Full Text Available Abstract Dynamic changes of the post-translational O-GlcNAc modification (O-GlcNAcylation are controlled by O-linked β-N-acetylglucosamine (O-GlcNAc transferase (OGT and the glycoside hydrolase O-GlcNAcase (OGA in cells. O-GlcNAcylation often occurs on serine (Ser and threonine (Thr residues of the specific substrate proteins via the addition of O-GlcNAc group by OGT. It has been known that O-GlcNAcylation is not only involved in many fundamental cellular processes, but also plays an important role in cancer development through various mechanisms. Recently, accumulating data reveal that O-GlcNAcylation at histones or non-histone proteins can lead to the start of the subsequent biological processes, suggesting that O-GlcNAcylation as ‘protein code’ or ‘histone code’ may provide recognition platforms or executive instructions for subsequent recruitment of proteins to carry out the specific functions. In this review, we summarize the interaction of O-GlcNAcylation and epigenetic changes, introduce recent research findings that link crosstalk between O-GlcNAcylation and epigenetic changes, and speculate on the potential coordination role of O-GlcNAcylation with epigenetic changes in intracellular biological processes.

  20. The potential role of DNA methylation in abdominal aortic aneurysms.

    Science.gov (United States)

    Ryer, Evan J; Ronning, Kaitryn E; Erdman, Robert; Schworer, Charles M; Elmore, James R; Peeler, Thomas C; Nevius, Christopher D; Lillvis, John H; Garvin, Robert P; Franklin, David P; Kuivaniemi, Helena; Tromp, Gerard

    2015-05-18

    Abdominal aortic aneurysm (AAA) is a complex disorder that has a significant impact on the aging population. While both genetic and environmental risk factors have been implicated in AAA formation, the precise genetic markers involved and the factors influencing their expression remain an area of ongoing investigation. DNA methylation has been previously used to study gene silencing in other inflammatory disorders and since AAA has an extensive inflammatory component, we sought to examine the genome-wide DNA methylation profiles in mononuclear blood cells of AAA cases and matched non-AAA controls. To this end, we collected blood samples and isolated mononuclear cells for DNA and RNA extraction from four all male groups: AAA smokers (n = 11), AAA non-smokers (n = 9), control smokers (n = 10) and control non-smokers (n = 11). Methylation data were obtained using the Illumina 450k Human Methylation Bead Chip and analyzed using the R language and multiple Bioconductor packages. Principal component analysis and linear analysis of CpG island subsets identified four regions with significant differences in methylation with respect to AAA: kelch-like family member 35 (KLHL35), calponin 2 (CNN2), serpin peptidase inhibitor clade B (ovalbumin) member 9 (SERPINB9), and adenylate cyclase 10 pseudogene 1 (ADCY10P1). Follow-up studies included RT-PCR and immunostaining for CNN2 and SERPINB9. These findings are novel and suggest DNA methylation may play a role in AAA pathobiology.

  1. Decreased expression of transient receptor potential channels in cerebral vascular tissue from patients after hypertensive intracerebral hemorrhage

    DEFF Research Database (Denmark)

    Thilo, Florian; Suess, Olaf; Liu, Ying

    2011-01-01

    , TRPC5, TRPC6, TRPM4, TRPM6, and TRPM7 channels were detected in cerebral vascular tissue by quantitative real-time RT-PCR. Control cerebral vascular tissue was obtained from normotensive patients who underwent neurosurgical operation because of brain tumor. To examine a possible relation between......Recent data indicate that transient receptor potential (TRP) cation channels play an important role in hypertension. Now, we tested the hypothesis that TRP expression is altered in human cerebral vascular tissue in patients who had experienced hypertensive intracerebral hemorrhage. TRPC1, TRPC3...... the expression of TRP expression and hypoxic conditions caused by the intracerebral bleeding, we examined the expression of hypoxia inducible factor 1a (HIF1a). Transcripts of TRPC3, TRPC5, TRPM6, and HIF1a were significantly reduced in cerebral vascular tissue from patients after hypertensive intracerebral...

  2. Distinct GAGE and MAGE-A expression during early human development indicate specific roles in lineage differentiation

    DEFF Research Database (Denmark)

    Gjerstorff, Morten; Harkness, Linda; Kassem, Moustapha

    2008-01-01

    BACKGROUND: Expression of cancer/testis-associated proteins (CTAs) has traditionally been considered to be restricted to germ cells in normal tissues and to different types of malignancies. We have evaluated the potential role of CTAs in early human development. METHODS: Using immunohistochemistry...... and RT-PCR, we investigated the expression of CTAs in differentiated human embryonic stem cells (hESC) and in late embryos and early fetuses. RESULTS: We found that melanoma antigen A (MAGE-A) family members were expressed during differentiation of hESC to embryoid bodies and in teratomas, and overlapped...... with expression of the neuroectodermal markers beta-tubulin 3, Pax6 and nestin. A widespread expression of MAGE-A was also observed in neurons of the early developing central nervous system and peripheral nerves. G antigen (GAGE) expression was present in the early ectoderm of embryos, including cells...

  3. Role of chrysin on expression of insulin signaling molecules

    Directory of Open Access Journals (Sweden)

    Kottireddy Satyanarayana

    2015-01-01

    Full Text Available Background: Currently available drugs are unsuccessful for the treatment of tye-2 diabetes due to their adverseside-effects. Hence, a search for novel drugs, especially ofplant origin, continues. Chrysin (5,7-dihydroxyflavone is a flavonoid, natural component of traditional medicinal herbs, present in honey, propolis and many plant extracts that hasbeen used in traditional medicine around the world to treat numerous ailments. Objective: The present study was aimed to identify the protective role of chrysin on the expression of insulin-signaling molecules in the skeletal muscle of high fat and sucrose-induced type-2 diabetic adult male rats. Materials and Methods: The oral effective dose of chrysin (100 mg/kg body weight was given once a day until the end of the study (30 days post-induction of diabetes to high fat diet-induced diabetic rats.At the end of the experimental period, fasting blood glucose, oral glucose tolerance, serum lipid profile, lipid peroxidation (LPO and free radical generation, as well as the levels of insulin signaling molecules and tissue glycogen in the gastrocnemius muscle were assessed. Results: Diabetic rats showed impaired glucose tolerance and impairment in insulin signaling molecules (IR, IRS-1, p-IRS-1Tyr 632 , p- Akt Thr308 , glucose transporter subtype 4 [GLUT4] proteins and glycogen concentration. Serum insulin, lipid profile, LPO and free radical generation were found to be increased in diabetic control rats.The treatment with chrysin normalized the altered levels of blood glucose, serum insulin, lipid profile, LPO and insulin signaling molecules as well as GLUT4 proteins. Conclusion: Our present findings indicate that chrysin improves glycemic control through activation of insulin signal transduction in the gastrocnemius muscle of high fat and sucrose-induced type-2 diabetic male rats.

  4. Fluoxetine potentiation of methylphenidate-induced gene regulation in striatal output pathways: potential role for 5-HT1B receptor.

    Science.gov (United States)

    Van Waes, Vincent; Ehrlich, Sarah; Beverley, Joel A; Steiner, Heinz

    2015-02-01

    Drug combinations that include the psychostimulant methylphenidate plus a selective serotonin reuptake inhibitor (SSRI) such as fluoxetine are increasingly used in children and adolescents. For example, this combination is indicated in the treatment of attention-deficit/hyperactivity disorder and depression comorbidity and other mental disorders. Such co-exposure also occurs in patients on SSRIs who use methylphenidate as a cognitive enhancer. The neurobiological consequences of these drug combinations are poorly understood. Methylphenidate alone can produce gene regulation effects that mimic addiction-related gene regulation by cocaine, consistent with its moderate addiction liability. We have previously shown that combining SSRIs with methylphenidate potentiates methylphenidate-induced gene regulation in the striatum. The present study investigated which striatal output pathways are affected by the methylphenidate + fluoxetine combination, by assessing effects on pathway-specific neuropeptide markers, and which serotonin receptor subtypes may mediate these effects. Our results demonstrate that a 5-day repeated treatment with fluoxetine (5 mg/kg) potentiates methylphenidate (5 mg/kg)-induced expression of both dynorphin (direct pathway marker) and enkephalin (indirect pathway). These changes were accompanied by correlated increases in the expression of the 5-HT1B, but not 5-HT2C, serotonin receptor in the same striatal regions. A further study showed that the 5-HT1B receptor agonist CP94253 (3-10 mg/kg) mimics the fluoxetine potentiation of methylphenidate-induced gene regulation. These findings suggest a role for the 5-HT1B receptor in the fluoxetine effects on striatal gene regulation. Given that 5-HT1B receptors are known to facilitate addiction-related gene regulation and behavior, our results suggest that SSRIs may enhance the addiction liability of methylphenidate by increasing 5-HT1B receptor signaling. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Fetal Alcohol Spectrum Disorder: Potential Role of Endocannabinoids Signaling

    Directory of Open Access Journals (Sweden)

    Balapal S. Basavarajappa

    2015-10-01

    Full Text Available One of the unique features of prenatal alcohol exposure in humans is impaired cognitive and behavioral function resulting from damage to the central nervous system (CNS, which leads to a spectrum of impairments referred to as fetal alcohol spectrum disorder (FASD. Human FASD phenotypes can be reproduced in the rodent CNS following prenatal ethanol exposure. Several mechanisms are expected to contribute to the detrimental effects of prenatal alcohol exposure on the developing fetus, particularly in the developing CNS. These mechanisms may act simultaneously or consecutively and differ among a variety of cell types at specific developmental stages in particular brain regions. Studies have identified numerous potential mechanisms through which alcohol can act on the fetus. Among these mechanisms are increased oxidative stress, mitochondrial damage, interference with the activity of growth factors, glia cells, cell adhesion molecules, gene expression during CNS development and impaired function of signaling molecules involved in neuronal communication and circuit formation. These alcohol-induced deficits result in long-lasting abnormalities in neuronal plasticity and learning and memory and can explain many of the neurobehavioral abnormalities found in FASD. In this review, the author discusses the mechanisms that are associated with FASD and provides a current status on the endocannabinoid system in the development of FASD.

  6. Nutrigenomics: the role of nutrients in gene expression.

    Science.gov (United States)

    Dang, Tarana Singh; Walker, Mark; Ford, Dianne; Valentine, Ruth A

    2014-02-01

    Improved understanding of the mechanism behind periodontal tissue destruction, the potential protective role of nutrients and the advent of modern genomic measurement tools has led to an increased interest in the association between nutrition and periodontal disease. To date, evidence for a direct link between periodontal disease and nutrition has come mainly from large observational cross-sectional studies or very small double-blind randomized supplementation trials, with a large proportion finding no significant association between the nutrient being analyzed and markers of periodontal disease status. The advent of the 'genomic era' has introduced the concept of nutrigenomic studies, which aim to reveal the relationship between nutrition and the genome to provide a scientific basis for improved public health through dietary means. Used alongside relatively inexpensive high-throughput technology, this will allow the effect of diet on the etiology of periodontal disease to be studied in greater detail. As it is extremely likely that interactions between genotype and diet are important in determining the risk of the most common complex diseases, it is highly probable that these interactions will be important in determining periodontal disease risk. Numerous nutritional genetic studies where the outcome measures have been markers of disease risk, most notably cardiovascular disease and cancer, provide proof of principle, highlight the importance of understanding these interactions and illustrate where the effect of dietary modification on periodontal disease progression may have been overlooked previously by observational studies. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Expression profile of the Schistosoma japonicum degradome reveals differential protease expression patterns and potential anti-schistosomal intervention targets.

    Science.gov (United States)

    Liu, Shuai; Cai, Pengfei; Piao, Xianyu; Hou, Nan; Zhou, Xiaosu; Wu, Chuang; Wang, Heng; Chen, Qijun

    2014-10-01

    Blood fluke proteases play pivotal roles in the processes of invasion, nutrition acquisition, immune evasion, and other host-parasite interactions. Hundreds of genes encoding putative proteases have been identified in the recently published schistosome genomes. However, the expression profiles of these proteases in Schistosoma species have not yet been systematically analyzed. We retrieved and culled the redundant protease sequences of Schistosoma japonicum, Schistosoma mansoni, Echinococcus multilocularis, and Clonorchis sinensis from public databases utilizing bioinformatic approaches. The degradomes of the four parasitic organisms and Homo sapiens were then comparatively analyzed. A total of 262 S. japonicum protease sequences were obtained and the expression profiles generated using whole-genome microarray. Four main clusters of protease genes with different expression patterns were identified: proteases up-regulated in hepatic schistosomula and adult worms, egg-specific or predominantly expressed proteases, cercaria-specific or predominantly expressed proteases, and constantly expressed proteases. A subset of protease genes with different expression patterns were further validated using real-time quantitative PCR. The present study represents the most comprehensive analysis of a degradome in Schistosoma species to date. These results provide a firm foundation for future research on the specific function(s) of individual proteases and may help to refine anti-proteolytic strategies in blood flukes.

  8. Screening of Genes Specifically Expressed in Males of Fenneropenaeus chinensis and Their Potential as Sex Markers

    Directory of Open Access Journals (Sweden)

    Shihao Li

    2013-01-01

    Full Text Available The androgenic gland (AG, playing an important role in sex differentiation of male crustacean, is a target candidate to understand the mechanism of male development and to mine male-specific sex markers. An SSH library (designated as male reproduction-related tissues—SSH library, MRT-SSH library for short was constructed using cDNA from tissues located at the basal part of the 5th pereiopods, including AG and part of spermatophore sac, as tester, and the cDNA from the basal part of the 4th pereiopods of these male shrimp as driver. 402 ESTs from the SSH library were sequenced and assembled into 48 contigs and 104 singlets. Twelve contigs and 14 singlets were identified as known genes. The proteins encoded by the identified genes were categorized, according to their proposed functions, into neuropeptide hormone and hormone transporter, RNA posttranscriptional regulation, translation, cell growth and death, metabolism, genetic information processing, signal transduction/transport, or immunity-related proteins. Eleven highly expressed contigs in the SSH library were selected for validation of the MRT-SSH library and screening sex markers of shrimp. One contig, specifically expressed in male shrimp, had a potential to be developed as a transcriptomic sex marker in shrimp.

  9. Expression, Distribution and Role of Aquaporin Water Channels in Human and Animal Stomach and Intestines

    Directory of Open Access Journals (Sweden)

    Cui Zhu

    2016-08-01

    Full Text Available Stomach and intestines are involved in the secretion of gastrointestinal fluids and the absorption of nutrients and fluids, which ensure normal gut functions. Aquaporin water channels (AQPs represent a major transcellular route for water transport in the gastrointestinal tract. Until now, at least 11 AQPs (AQP1–11 have been found to be present in the stomach, small and large intestines. These AQPs are distributed in different cell types in the stomach and intestines, including gastric epithelial cells, gastric glands cells, absorptive epithelial cells (enterocytes, goblet cells and Paneth cells. AQP1 is abundantly distributed in the endothelial cells of the gastrointestinal tract. AQP3 and AQP4 are mainly distributed in the basolateral membrane of epithelial cells in the stomach and intestines. AQP7, AQP8, AQP10 and AQP11 are distributed in the apical of enterocytes in the small and large intestines. Although AQP-null mice displayed almost no phenotypes in gastrointestinal tracts, the alterations of the expression and localization of these AQPs have been shown to be associated with the pathology of gastrointestinal disorders, which suggests that AQPs play important roles serving as potential therapeutic targets. Therefore, this review provides an overview of the expression, localization and distribution of AQPs in the stomach, small and large intestine of human and animals. Furthermore, this review emphasizes the potential roles of AQPs in the physiology and pathophysiology of stomach and intestines.

  10. Expression, Distribution and Role of Aquaporin Water Channels in Human and Animal Stomach and Intestines.

    Science.gov (United States)

    Zhu, Cui; Chen, Zhuang; Jiang, Zongyong

    2016-08-29

    Stomach and intestines are involved in the secretion of gastrointestinal fluids and the absorption of nutrients and fluids, which ensure normal gut functions. Aquaporin water channels (AQPs) represent a major transcellular route for water transport in the gastrointestinal tract. Until now, at least 11 AQPs (AQP1-11) have been found to be present in the stomach, small and large intestines. These AQPs are distributed in different cell types in the stomach and intestines, including gastric epithelial cells, gastric glands cells, absorptive epithelial cells (enterocytes), goblet cells and Paneth cells. AQP1 is abundantly distributed in the endothelial cells of the gastrointestinal tract. AQP3 and AQP4 are mainly distributed in the basolateral membrane of epithelial cells in the stomach and intestines. AQP7, AQP8, AQP10 and AQP11 are distributed in the apical of enterocytes in the small and large intestines. Although AQP-null mice displayed almost no phenotypes in gastrointestinal tracts, the alterations of the expression and localization of these AQPs have been shown to be associated with the pathology of gastrointestinal disorders, which suggests that AQPs play important roles serving as potential therapeutic targets. Therefore, this review provides an overview of the expression, localization and distribution of AQPs in the stomach, small and large intestine of human and animals. Furthermore, this review emphasizes the potential roles of AQPs in the physiology and pathophysiology of stomach and intestines.

  11. Trait Expressiveness and Marital Satisfaction: The Role of Idealization Processes.

    Science.gov (United States)

    Miller, Paul J. E.; Caughlin, John P.; Huston, Ted L.

    2003-01-01

    Examines the processes that underlie the association between trait expressiveness and marital satisfaction. Analyses suggested that expressiveness promotes satisfaction by leading spouses to engage in affectionate behavior and by leading them to idealize their partner. Extends previous research by providing a plausible explanation of the…

  12. The role of MHC class I expression in developmental tumours

    NARCIS (Netherlands)

    Stern, P. L.; Rinke de Wit, T. F.

    1991-01-01

    Expression of HLA class I (-like) genes by two developmental tumour cell lines representing embryonic (Tera-2) and extra-embryonic (Jeg-3) origins is reviewed. The Tera-2 embryonal carcinoma cells are HLA negative but can be induced by gamma interferon to express HLA-A, -B, -C, and apparently -E and

  13. Potential Role of Honey in Learning and Memory

    Directory of Open Access Journals (Sweden)

    Zahiruddin Othman

    2015-04-01

    Full Text Available The composition and physicochemical properties of honey are variable depending on its floral source and often named according to the geographical location. The potential medicinal benefits of Tualang honey, a multifloral jungle honey found in Malaysia, have recently been attracting attention because of its reported beneficial effects in various diseases. This paper reviews the effects of honey, particularly Tualang honey, on learning and memory. Information regarding the effects of Tualang honey on learning and memory in human as well as animal models is gleaned to hypothesize its underlying mechanisms. These studies show that Tualang honey improves morphology of memory-related brain areas, reduces brain oxidative stress, increases brain-derived neurotrophic factor (BDNF and acetylcholine (ACh concentrations, and reduces acetylcholinesterase (AChE in the brain homogenates. Its anti-inflammatory roles in reducing inflammatory trigger and microglial activation have yet to be investigated. It is hypothesized that the improvement in learning and memory following Tualang honey supplementation is due to the significant improvement in brain morphology and enhancement of brain cholinergic system secondary to reduction in brain oxidative damage and/or upregulation of BDNF concentration. Further studies are imperative to elucidate the molecular mechanism of actions.

  14. Exploring the potential roles of biochars on land degradation mitigation

    Directory of Open Access Journals (Sweden)

    A.K. Berek

    2014-04-01

    Full Text Available Land degradation was exacerbated and its management was challenged by population growth and global climate change. The impacts of land degradation on food security, ecosystem services and biodiversity become a more serious problem particularly in developing countries. Biochar, based on the current research findings, is capable to amend degraded lands. This paper reviewed relevant biocharproperties and identified the opportunities of its using for recovering deteriorated lands.Biochar was traditionally recognized as a good absorbent, energy source, and its ash was used by farmers to recover soil fertility. Recent findings revealed that application of biochar improved soil water retention, enhanced soil aggregation, decreased soil bulk density and increased soil infiltration. It also increased soil cation exchange capacity, soil pH, mineral nutrients, reduced nutrient leaching, support microbial population and activities, and suppressed the pest. The sorption capacity of biochar to soil and water pollutants such as Pb, Cu, Ni, Cr, Cd,dioxine, atrazine, and concurrently eliminatedthe environmental problems such as hypoxia, eutrophication, and algae bloom, have also been investigated. Investigation on its role to mitigate climate change revealed that biochar is capable in reducing greenhouse gasesemissions such as CO2, N2O, and CH4. All those beneficial effects of biochars were attributed to its high porosity, large surface area and surface charge, high carbon, ash and nutrient content, and its stability to be degraded. Thus, biochar could be potential for ameliorating degraded lands

  15. Potential Role of Epigenetic Mechanism in Manganese Induced Neurotoxicity.

    Science.gov (United States)

    Tarale, Prashant; Chakrabarti, Tapan; Sivanesan, Saravanadevi; Naoghare, Pravin; Bafana, Amit; Krishnamurthi, Kannan

    2016-01-01

    Manganese is a vital nutrient and is maintained at an optimal level (2.5-5 mg/day) in human body. Chronic exposure to manganese is associated with neurotoxicity and correlated with the development of various neurological disorders such as Parkinson's disease. Oxidative stress mediated apoptotic cell death has been well established mechanism in manganese induced toxicity. Oxidative stress has a potential to alter the epigenetic mechanism of gene regulation. Epigenetic insight of manganese neurotoxicity in context of its correlation with the development of parkinsonism is poorly understood. Parkinson's disease is characterized by the α-synuclein aggregation in the form of Lewy bodies in neuronal cells. Recent findings illustrate that manganese can cause overexpression of α-synuclein. α-Synuclein acts epigenetically via interaction with histone proteins in regulating apoptosis. α-Synuclein also causes global DNA hypomethylation through sequestration of DNA methyltransferase in cytoplasm. An individual genetic difference may also have an influence on epigenetic susceptibility to manganese neurotoxicity and the development of Parkinson's disease. This review presents the current state of findings in relation to role of epigenetic mechanism in manganese induced neurotoxicity, with a special emphasis on the development of Parkinson's disease.

  16. A potential role for bat tail membranes in flight control.

    Directory of Open Access Journals (Sweden)

    James D Gardiner

    2011-03-01

    Full Text Available Wind tunnel tests conducted on a model based on the long-eared bat Plecotus auritus indicated that the positioning of the tail membrane (uropatagium can significantly influence flight control. Adjusting tail position by increasing the angle of the legs ventrally relative to the body has a two-fold effect; increasing leg-induced wing camber (i.e., locally increased camber of the inner wing surface and increasing the angle of attack of the tail membrane. We also used our model to examine the effects of flying with and without a tail membrane. For the bat model with a tail membrane increasing leg angle increased the lift, drag and pitching moment (nose-down produced. However, removing the tail membrane significantly reduced the change in pitching moment with increasing leg angle, but it had no significant effect on the level of lift produced. The drag on the model also significantly increased with the removal of the tail membrane. The tail membrane, therefore, is potentially important for controlling the level of pitching moment produced by bats and an aid to flight control, specifically improving agility and manoeuvrability. Although the tail of bats is different from that of birds, in that it is only divided from the wings by the legs, it nonetheless, may, in addition to its prey capturing function, fulfil a similar role in aiding flight control.

  17. Differential Expression of FosB Proteins and Potential Target Genes in Select Brain Regions of Addiction and Depression Patients.

    Directory of Open Access Journals (Sweden)

    Paula A Gajewski

    Full Text Available Chronic exposure to stress or drugs of abuse has been linked to altered gene expression throughout the body, and changes in gene expression in discrete brain regions are thought to underlie many psychiatric diseases, including major depressive disorder and drug addiction. Preclinical models of these disorders have provided evidence for mechanisms of this altered gene expression, including transcription factors, but evidence supporting a role for these factors in human patients has been slow to emerge. The transcription factor ΔFosB is induced in the prefrontal cortex (PFC and hippocampus (HPC of rodents in response to stress or cocaine, and its expression in these regions is thought to regulate their "top down" control of reward circuitry, including the nucleus accumbens (NAc. Here, we use biochemistry to examine the expression of the FosB family of transcription factors and their potential gene targets in PFC and HPC postmortem samples from depressed patients and cocaine addicts. We demonstrate that ΔFosB and other FosB isoforms are downregulated in the HPC but not the PFC in the brains of both depressed and addicted individuals. Further, we show that potential ΔFosB transcriptional targets, including GluA2, are also downregulated in the HPC but not PFC of cocaine addicts. Thus, we provide the first evidence of FosB gene expression in human HPC and PFC in these psychiatric disorders, and in light of recent findings demonstrating the critical role of HPC ΔFosB in rodent models of learning and memory, these data suggest that reduced ΔFosB in HPC could potentially underlie cognitive deficits accompanying chronic cocaine abuse or depression.

  18. The trafficking protein, EHD2, positively regulates cardiac sarcolemmal KATP channel surface expression: role in cardioprotection.

    Science.gov (United States)

    Yang, Hua Qian; Jana, Kundan; Rindler, Michael J; Coetzee, William A

    2017-11-13

    ATP-sensitive K+ (KATP) channels uniquely link cellular energy metabolism to membrane excitability and are expressed in diverse cell types that range from the endocrine pancreas to neurons and smooth, skeletal, and cardiac muscle. A decrease in the surface expression of KATP channels has been linked to various disorders, including dysregulated insulin secretion, abnormal blood pressure, and impaired resistance to cardiac injury. In contrast, up-regulation of KATP channel surface expression may be protective, for example, by mediating the beneficial effect of ischemic preconditioning. Molecular mechanisms that regulate KATP channel trafficking are poorly understood. Here, we used cellular assays with immunofluorescence, surface biotinylation, and patch clamping to demonstrate that Eps15 homology domain-containing protein 2 (EHD2) is a novel positive regulator of KATP channel trafficking to increase surface KATP channel density. EHD2 had no effect on cardiac Na+ channels (Nav1.5). The effect is specific to EHD2 as other members of the EHD family-EHD1, EHD3, and EHD4-had no effect on KATP channel surface expression. EHD2 did not directly affect KATP channel properties as unitary conductance and ATP sensitivity were unchanged. Instead, we observed that the mechanism by which EHD2 increases surface expression is by stabilizing KATP channel-containing caveolar structures, which results in a reduced rate of endocytosis. EHD2 also regulated KATP channel trafficking in isolated cardiomyocytes, which validated the physiologic relevance of these observations. Pathophysiologically, EHD2 may be cardioprotective as a dominant-negative EHD2 mutant sensitized cardiomyocytes to ischemic damage. Our findings highlight EHD2 as a potential pharmacologic target in the treatment of diseases with KATP channel trafficking defects.-Yang, H. Q., Jana, K., Rindler, M. J., Coetzee, W. A. The trafficking protein, EHD2, positively regulates cardiac sarcolemmal KATP channel surface expression

  19. MicroRNA-146a expression as a potential biomarker for rheumatoid ...

    African Journals Online (AJOL)

    MicroRNA-146a expression as a potential biomarker for rheumatoid arthritis in Egypt. Heba Mohamed Abdelkader Elsayed, Walaa Shawky Khater, Ayman Asaad Ibrahim, Maha Salah El-din Hamdy, Nashwa Aly Morshedy ...

  20. Potential role of estrogen receptor beta as a tumor suppressor of epithelial ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Carine Bossard

    Full Text Available Ovarian cancer is the gynecological cancer exhibiting the highest morbidity and improvement of treatments is still required. Previous studies have shown that Estrogen-receptor beta (ERβ levels decreased along with ovarian carcinogenesis. Here, we present evidence that reintroduction of ERβ in BG-1 epithelial ovarian cancer cells, which express ERα, leads in vitro to a decrease of basal and estradiol-promoted cell proliferation. ERβ reduced the frequency of cells in S phase and increased the one of cells in G2/M phase. At the molecular level, we found that ERβ downregulated total retinoblastoma (Rb, phosphorylated Rb and phospho-AKT cellular content as well as cyclins D1 and A2. In addition, ERβ had a direct effect on ERα, by strongly inhibiting its expression and activity, which could explain part of the anti-proliferative action of ERβ. By developing a novel preclinical model of ovarian cancer based on a luminescent orthotopic xenograft in athymic Nude mice, we further revealed that ERβ expression reduces tumor growth and the presence of tumor cells in sites of metastasis, hence resulting in improved survival of mice. Altogether, these findings unveil a potential tumor-suppressor role of ERβ in ovarian carcinogenesis, which could be of potential clinical relevance for the selection of the most appropriate treatment for patients.

  1. Expression of Anger in Depressed Adolescents: The Role of the Family Environment

    Science.gov (United States)

    Jackson, Jennifer; Kuppens, Peter; Sheeber, Lisa B.; Allen, Nicholas B.

    2011-01-01

    The expression of anger is considered to be abnormal in depression, yet its role is only poorly understood. In the present study we sought to clarify this role by examining the moderating influence of the family environment on overall levels of anger expression and anger reactivity in depressed and non-depressed adolescents during conflictual…

  2. Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons

    KAUST Repository

    Yang, Jiangyan

    2014-07-28

    L-lactate is a product of aerobic glycolysis that can be used by neurons as an energy substrate. Here we report that in neurons L-lactate stimulates the expression of synaptic plasticity-related genes such as Arc, c-Fos, and Zif268 through a mechanism involving NMDA receptor activity and its downstream signaling cascade Erk1/2. L-lactate potentiates NMDA receptor-mediated currents and the ensuing increase in intracellular calcium. In parallel to this, L-lactate increases intracellular levels of NADH, thereby modulating the redox state of neurons. NADH mimics all of the effects of L-lactate on NMDA signaling, pointing to NADH increase as a primary mediator of L-lactate effects. The induction of plasticity genes is observed both in mouse primary neurons in culture and in vivo in the mouse sensory-motor cortex. These results provide insights for the understanding of the molecular mechanisms underlying the critical role of astrocyte-derived L-lactate in long-term memory and long-term potentiation in vivo. This set of data reveals a previously unidentified action of L-lactate as a signaling molecule for neuronal plasticity.

  3. The Role of the Expressive Arts in Therapy.

    Science.gov (United States)

    Creadick, Theo Alcott

    1985-01-01

    Components of the expressive arts approach to therapy for disabled students are briefly described in terms of music, movement and dance, sculpture, sandplay, drawing and painting, journal writing, poetry, playwriting, puppetry, and drama. (CL)

  4. Potential roles of force cues in human stance control.

    Science.gov (United States)

    Cnyrim, Christian; Mergner, Thomas; Maurer, Christoph

    2009-04-01

    Human stance is inherently unstable. A small deviation from upright body orientation is enough to yield a gravitational component in the ankle joint torque, which tends to accelerate the body further away from upright ('gravitational torque'; magnitude is related to body-space lean angle). Therefore, to maintain a given body lean position, a corresponding compensatory torque must be generated. It is well known that subjects use kinematic sensory information on body-space lean from the vestibular system for this purpose. Less is known about kinetic cues from force/torque receptors. Previous work indicated that they are involved in compensating external contact forces such as a pull or push having impact on the body. In this study, we hypothesized that they play, in addition, a role when the vestibular estimate of the gravitational torque becomes erroneous. Reasons may be sudden changes in body mass, for instance by a load, or an impairment of the vestibular system. To test this hypothesis, we mimicked load effects on the gravitational torque in normal subjects and in patients with chronic bilateral vestibular loss (VL) with eyes closed. We added/subtracted extra torque to the gravitational torque by applying an external contact force (via cable winches and a body harness). The extra torque was referenced to body-space lean, using different proportionality factors. We investigated how it affected body-space lean responses that we evoked using sinusoidal tilts of the support surface (motion platform) with different amplitudes and frequencies (normals +/-1 degrees, +/-2 degrees, and +/-4 degrees at 0.05, 0.1, 0.2, and 0.4 Hz; patients +/-1 degrees and +/-2 degrees at 0.05 and 0.1 Hz). We found that added/subtracted extra torque scales the lean response in a systematic way, leading to increase/decrease in lean excursion. Expressing the responses in terms of gain and phase curves, we compared the experimental findings to predictions obtained from a recently published

  5. Effects of Expressive Writing on Psychological and Physical Health: The Moderating Role of Emotional Expressivity

    Science.gov (United States)

    Haltom, Kate E.; Mulvenna, Catherine M.; Lieberman, Matthew D.; Stanton, Annette L.

    2013-01-01

    The current study assessed main effects and moderators (including emotional expressiveness, emotional processing and ambivalence over emotional expression) of the effects of expressive writing in a sample of healthy adults. Young adult participants (N = 116) were randomly assigned to write for 20 minutes on four occasions about deepest thoughts and feelings regarding their most stressful/traumatic event in the past five years (expressive writing) or about a control topic (control). Dependent variables were indicators of anxiety, depression, and physical symptoms. No significant effects of writing condition were evident on anxiety, depressive symptoms, or physical symptoms. Emotional expressiveness emerged as a significant moderator of anxiety outcomes, however. Within the expressive writing group, participants high in expressiveness evidenced a significant reduction in anxiety at three-month follow-up, and participants low in expressiveness showed a significant increase in anxiety. Expressiveness did not predict change in anxiety in the control group. These findings on anxiety are consistent with the matching hypothesis, which suggests that matching a person’s naturally elected coping approach with an assigned intervention is beneficial. These findings also suggest that expressive writing about a stressful event may be contraindicated for individuals who do not typically express emotions. PMID:23742666

  6. Role of chemokine receptor CXCR2 expression in mammary tumor growth, angiogenesis and metastasis

    Directory of Open Access Journals (Sweden)

    Kalyan C Nannuru

    2011-01-01

    Full Text Available Background: Chemokines and their receptors have long been known to regulate metastasis in various cancers. Previous studies have shown that CXCR2 expression is upregulated in malignant breast cancer tissues but not in benign ductal epithelial samples. The functional role of CXCR2 in the metastatic phenotype of breast cancer still remains unclear. We hypothesize that the chemokine receptor, CXCR2, mediates tumor cell invasion and migration and promotes metastasis in breast cancer. The objective of this study is to investigate the potential role of CXCR2 in the metastatic phenotype of mouse mammary tumor cells. Materials and Methods: We evaluated the functional role of CXCR2 in breast cancer by stably downregulating the expression of CXCR2 in metastatic mammary tumor cell lines Cl66 and 4T1, using short hairpin RNA (shRNA. The effects of CXCR2 downregulation on tumor growth, invasion and metastatic potential were analyzed in vitro and in vivo. Results: We demonstrated knock down of CXCR2 in Cl66 and 4T1 cells (Cl66-shCXCR2 and 4T1-shCXCR2 cells by reverse transcriptase polymerase chain reaction (RT-PCR at the transcriptional level and by immunohistochemistry at the protein level. We did not observe a significant difference in in vitro cell proliferation between vector control and CXCR2 knock-down Cl66 or 4T1 cells. Next, we examined the invasive potential of Cl66-shCXCR2 cells by in vitro Matrigel invasion assay. We observed a significantly lower number (52 ± 5 of Cl66-shCXCR2 cells invading through Matrigel compared to control cells (Cl66-control (182 ± 3 (P < 0.05. We analyzed the in vivo metastatic potential of Cl66-shCXCR2 using a spontaneous metastasis model by orthotopically implanting cells into the mammary fat pad of female BALB/c mice. Animals were sacrificed 12 weeks post tumor implantation and tissue samples were analyzed for metastatic nodules. CXCR2 downregulation significantly inhibited tumor cell metastasis. All the mice (n = 10

  7. A composite peripheral blood gene expression measure as a potential diagnostic biomarker in bipolar disorder

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Peijs, L; Vinberg, M

    2015-01-01

    as a diagnostic and state biomarker in bipolar disorder. First, messenger RNA levels of 19 candidate genes were assessed in peripheral blood mononuclear cells of 37 rapid cycling bipolar disorder patients in different affective states (depression, mania and euthymia) during a 6-12-month period and in 40 age......Gene expression in peripheral blood has the potential to inform on pathophysiological mechanisms and has emerged as a viable avenue for the identification of biomarkers. Here, we aimed to identify gene expression candidate genes and to explore the potential for a composite gene expression measure......- and gender-matched healthy control subjects. Second, a composite gene expression measure was constructed in the first half study sample and independently validated in the second half of the sample. We found downregulation of POLG and OGG1 expression in bipolar disorder patients compared with healthy control...

  8. Social responses to expressive suppression: The role of personality judgments.

    Science.gov (United States)

    Tackman, Allison M; Srivastava, Sanjay

    2016-04-01

    Why do people who suppress their emotion-expressive behavior have difficulty forming close, supportive relationships? Previous studies have found that suppression disrupts the dynamics of social interactions and existing relationships. We evaluated a complementary hypothesis: that suppression functions as a behavioral cue leading others to form negative personality impressions of suppressors, even at zero-acquaintance. In 2 studies, participants reported personality judgments and other impressions of targets who either suppressed or expressed their emotion-expressive behavior in response to amusing or sad film clips. In findings replicated across studies, targets who suppressed either amusement or sadness were judged as less extraverted, less agreeable, and more interpersonally avoidant and anxious than targets who expressed emotions, and participants were less interested in affiliating with suppressors compared with expressers. Effects were amplified when targets suppressed amusement (compared with sadness) and when participants knew the emotional context (compared with when they did not) and, thus, could form expectations about what emotions targets should be showing. Extraversion and agreeableness judgments mediated the effect of suppression on participants' disinterest in affiliating. In Study 2, which extended Study 1 in several ways, effects were pronounced for the enthusiasm aspect of extraversion and the compassion aspect of agreeableness. We also found evidence that judgments of suppressors do not simply fall between neutral and fully expressing targets; rather, judgments of suppressors are qualitatively different. We discuss implications for understanding the social consequences of emotion regulation-in particular, how beyond disrupting relationships, suppression may prevent some relationships from even forming in the first place. (c) 2016 APA, all rights reserved).

  9. The role of expressive writing in math anxiety.

    Science.gov (United States)

    Park, Daeun; Ramirez, Gerardo; Beilock, Sian L

    2014-06-01

    Math anxiety is a negative affective reaction to situations involving math. Previous work demonstrates that math anxiety can negatively impact math problem solving by creating performance-related worries that disrupt the working memory needed for the task at hand. By leveraging knowledge about the mechanism underlying the math anxiety-performance relationship, we tested the effectiveness of a short expressive writing intervention that has been shown to reduce intrusive thoughts and improve working memory availability. Students (N = 80) varying in math anxiety were asked to sit quietly (control group) prior to completing difficulty-matched math and word problems or to write about their thoughts and feelings regarding the exam they were about to take (expressive writing group). For the control group, high math-anxious individuals (HMAs) performed significantly worse on the math problems than low math-anxious students (LMAs). In the expressive writing group, however, this difference in math performance across HMAs and LMAs was significantly reduced. Among HMAs, the use of words related to anxiety, cause, and insight in their writing was positively related to math performance. Expressive writing boosts the performance of anxious students in math-testing situations. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  10. Role of Appraisals in Expressed Anger after Trauma

    Science.gov (United States)

    Whiting, Diane; Bryant, Richard A.

    2007-01-01

    Anger is a common problem in trauma-exposed individuals. This study investigated factors that contribute to post-traumatic anger in civilian trauma survivors. Fifty-one trauma-exposed individuals were assessed for expressed anger, post-traumatic stress disorder (PTSD), daily hassles, maladaptive cognitions and blame. PTSD and non-PTSD participants…

  11. The role of facial expression in resisting enjoyable advertisements

    NARCIS (Netherlands)

    Lewiński, P.

    2015-01-01

    This dissertation on consumer resistance to enjoyable advertisements is positioned in the areas of persuasive communication and social psychology. In this thesis, it is argued that consumers can resist persuasion by controlling their facial expressions of emotion when exposed to an advertisement.

  12. Potential role of aromatase inhibitors in the treatment of endometriosis

    Directory of Open Access Journals (Sweden)

    Abu Hashim H

    2014-07-01

    Full Text Available Hatem Abu HashimDepartment of Obstetrics and Gynecology, Faculty of Medicine, Mansoura University, Mansoura, EgyptAbstract: Endometriosis is an estrogen-dependent chronic inflammatory disease affecting 5%–10% of reproductive-age women, with a prevalence of 5%–50% in infertile women and >33% of women with chronic pelvic pain. Third-generation aromatase inhibitors (AIs are approved adjuvants for the treatment of estrogen receptor-positive breast cancer. Molecular studies have revealed the presence of aromatase P450, the key enzyme in the biosynthesis of ovarian estradiol, inside the endometriotic tissue, indicating local synthesis of estradiol. Thereby, AIs represent an appealing medical option for the management of different aspects of this enigmatic disease, especially pelvic pain and infertility. Accordingly, this review aims to evaluate the potential role of AIs in the treatment of endometriosis-associated symptoms, mainly pain and infertility. Notably, several studies have demonstrated that the combination of AIs with conventional therapy as oral contraceptive pills, progestins, or gonadotropin-releasing hormone analogs can be used to control endometriosis-associated pain and pain recurrence in premenopausal women, particularly those with pain due to rectovaginal endometriosis refractory to other medical or surgical treatment. Some case reports have shown promising results in the treatment of postmenopausal endometriosis as first-line treatment, when surgery is contraindicated, or as second-line treatment in the case of postoperative recurrence. Third-generation AIs, especially letrozole, have challenged clomiphene citrate as an ovulation-induction agent in patients with polycystic ovary syndrome and in cases of unexplained infertility. However, few studies are available regarding the use of AIs to treat endometriosis-associated infertility. Therefore, larger multicenter randomized trials using AIs for the treatment of endometriosis

  13. High contextual sensitivity of metaphorical expressions and gesture blending: A video event-related potential design.

    Science.gov (United States)

    Ibáñez, Agustín; Toro, Pablo; Cornejo, Carlos; Urquina, Hugo; Hurquina, Hugo; Manes, Facundo; Weisbrod, Matthias; Schröder, Johannes

    2011-01-30

    Human communication in a natural context implies the dynamic coordination of contextual clues, paralinguistic information and literal as well as figurative language use. In the present study we constructed a paradigm with four types of video clips: literal and metaphorical expressions accompanied by congruent and incongruent gesture actions. Participants were instructed to classify the gesture accompanying the expression as congruent or incongruent by pressing two different keys while electrophysiological activity was being recorded. We compared behavioral measures and event related potential (ERP) differences triggered by the gesture stroke onset. Accuracy data showed that incongruent metaphorical expressions were more difficult to classify. Reaction times were modulated by incongruent gestures, by metaphorical expressions and by a gesture-expression interaction. No behavioral differences were found between the literal and metaphorical expressions when the gesture was congruent. N400-like and LPC-like (late positive complex) components from metaphorical expressions produced greater negativity. The N400-like modulation of metaphorical expressions showed a greater difference between congruent and incongruent categories over the left anterior region, compared with the literal expressions. More importantly, the literal congruent as well as the metaphorical congruent categories did not show any difference. Accuracy, reaction times and ERPs provide convergent support for a greater contextual sensitivity of the metaphorical expressions. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  14. CYP1B1 expression, a potential risk factor for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Goth-Goldstein, Regine; Erdmann, Christine A.; Russell, Marion

    2001-05-31

    CYP1B1 expression in non-tumor breast tissue from breast cancer patients and cancer-free individuals was determined to test the hypothesis that high CYP1B1 expression is a risk factor for breast cancer. Large interindividual variations in CYP1B1 expression were found with CYP1B1 levels notably higher in breast cancer patients than cancer-free individuals. The results indicate that CYP1B1 might play a role in breast cancer either through increased PAH activation or through metabolism of endogenous estrogen to a carcinogenic derivative.

  15. The Role of Transient Receptor Potential Channel 6 Channels in the Pulmonary Vasculature

    Directory of Open Access Journals (Sweden)

    Monika Malczyk

    2017-06-01

    Full Text Available Canonical or classical transient receptor potential channel 6 (TRPC6 is a Ca2+-permeable non-selective cation channel that is widely expressed in the heart, lung, and vascular tissues. The use of TRPC6-deficient (“knockout” mice has provided important insights into the role of TRPC6 in normal physiology and disease states of the pulmonary vasculature. Evidence indicates that TRPC6 is a key regulator of acute hypoxic pulmonary vasoconstriction. Moreover, several studies implicated TRPC6 in the pathogenesis of pulmonary hypertension. Furthermore, a unique genetic variation in the TRPC6 gene promoter has been identified, which might link the inflammatory response to the upregulation of TRPC6 expression and ultimate development of pulmonary vascular abnormalities in idiopathic pulmonary arterial hypertension. Additionally, TRPC6 is critically involved in the regulation of pulmonary vascular permeability and lung edema formation during endotoxin or ischemia/reperfusion-induced acute lung injury. In this review, we will summarize latest findings on the role of TRPC6 in the pulmonary vasculature.

  16. The Role of Transient Receptor Potential Channel 6 Channels in the Pulmonary Vasculature

    Science.gov (United States)

    Malczyk, Monika; Erb, Alexandra; Veith, Christine; Ghofrani, Hossein Ardeschir; Schermuly, Ralph T.; Gudermann, Thomas; Dietrich, Alexander; Weissmann, Norbert; Sydykov, Akylbek

    2017-01-01

    Canonical or classical transient receptor potential channel 6 (TRPC6) is a Ca2+-permeable non-selective cation channel that is widely expressed in the heart, lung, and vascular tissues. The use of TRPC6-deficient (“knockout”) mice has provided important insights into the role of TRPC6 in normal physiology and disease states of the pulmonary vasculature. Evidence indicates that TRPC6 is a key regulator of acute hypoxic pulmonary vasoconstriction. Moreover, several studies implicated TRPC6 in the pathogenesis of pulmonary hypertension. Furthermore, a unique genetic variation in the TRPC6 gene promoter has been identified, which might link the inflammatory response to the upregulation of TRPC6 expression and ultimate development of pulmonary vascular abnormalities in idiopathic pulmonary arterial hypertension. Additionally, TRPC6 is critically involved in the regulation of pulmonary vascular permeability and lung edema formation during endotoxin or ischemia/reperfusion-induced acute lung injury. In this review, we will summarize latest findings on the role of TRPC6 in the pulmonary vasculature. PMID:28670316

  17. Analysis of development-related gene expression in cloned bovine blastocysts with different developmental potential.

    Science.gov (United States)

    Li, Xiangping; Amarnath, Dasari; Kato, Yoko; Tsunoda, Yukio

    2006-01-01

    The high incidence of abnormalities in cloned calves is a most serious problem for bovine somatic cell nuclear transfer (NT) technology. Because there is little information on the differences in mRNA expression in cloned blastocysts with donor cells of different sex and origin, we compared development-related gene expression in two types of cloned bovine blastocysts with different potentials to develop into normal calves, a female adult cumulus cell line (high potential to develop into live calves) and a male fibroblast cell line (low potential to develop into live calves) to examine the correlation between the normality of cloned calves and blastocyst mRNA expression patterns. We analyzed 12 genes involved in apoptosis, growth factor signaling, metabolism, and DNA methylation in blastocysts originating from two types of donor cells and in vitro-fertilized blastocysts using quantitative real-time polymerase chain reaction. Expression of the pro-apoptotic Bax gene and anti-apoptotic Bcl-2 and Glut-1 genes in fibroblast-derived blastocysts was significantly higher than in cumulus cell-derived and in vitro-fertilized blastocysts. The high Bcl-2 and Glut-1 gene expression suggests that some embryonic cells with damaged DNA in fibroblast-derived blastocysts are not removed, and their descendants later manifest abnormal placenta or fetus formation. Transfer of pre-selected cloned blastocysts into recipients is required, however, to determine whether the expression pattern of these apoptosis-related genes reflects differences in the potential to develop into normal calves.

  18. Effects of written emotional expression: the role of positive expectancies.

    Science.gov (United States)

    Langens, Thomas A; Schüler, Julia

    2007-03-01

    Writing in an emotional way about stressful or traumatic experiences has beneficial effects on emotional well-being and physical health. Yet the mechanisms that underlie these effects still need to be explored. Integrating research on the effects of positive expectancies, the authors suggest that positive effects of written emotional expression may, in part, depend on expectancies induced by writing about emotional experiences. Two studies were conducted to test this hypothesis. In both studies, participants wrote about either an upsetting event or trivial issues. After the writing period, participants rated their expectancies that the writing intervention would improve (or impair) their emotional well-being over time. Study 1 assessed the emotional impact of an upsetting event, whereas Study 2 assessed subjective reports of physical symptoms. In both studies, outcome variables were collected both before and 6 weeks after the writing intervention. The results showed that (a) writing about upsetting experiences induced higher positive expectancies than writing about trivial issues and (b) expectancies associated with written emotional expression were related to a reduction in the emotional impact of an upsetting event (Study 1) and to a reduction in physical symptoms (Study 2). There may be 2 alternative ways to render written emotional expression effective in reducing negative emotions: (a) by rendering an emotional experience more meaningful and (b) by inducing positive affect regulation expectancies. (c) 2007 APA, all rights reserved

  19. Potential role of platelet-leukocyte aggregation in trauma-induced coagulopathy: Ex vivo findings.

    Science.gov (United States)

    Zipperle, Johannes; Altenburger, Katrin; Ponschab, Martin; Schlimp, Christoph J; Spittler, Andreas; Bahrami, Soheyl; Redl, Heinz; Schöchl, Herbert

    2017-05-01

    Platelet dysfunction has been identified as an important contributor of trauma-induced coagulopathy, but the underlying mechanism still remains to be elucidated. Trauma-associated proinflammatory stimuli strongly activate leukocytes, which in turn bind activated platelets. Therefore, we investigated the role of platelet-leukocyte aggregation (PLA) as a potential feature of trauma-induced platelet dysfunction. Whole blood from 10 healthy donors was exposed to selective and collective platelet and leukocyte agonists in order to simulate differential states of activation. PLA formation and CD11b expression as a measure of leukocyte activation were determined by flow cytometry. Platelet-mediated hemostatic function was measured by thromboelastometry (ROTEM) and impedance aggregometry (Multiplate). Activation of platelets and leukocytes was associated with diminished platelet-mediated hemostatic potential. Aggregation of platelets with monocytes rather than granulocytes resulted in a reduction of hemostatic function, as indicated by an impaired responsiveness in platelet aggregometry and a reduction of thromboelastometric maximum clot firmness. This finding was irrespective of CD11b expression and was not paralleled by a reduction of measurable platelet counts. PLA formation occurs primarily between monocytes and activated platelets and is associated with impaired platelet-mediated hemostatic function. PLA formation was not paralleled by a reduction in platelet complete blood counts.

  20. The role of local field potential coupling in epileptic synchronization.

    Science.gov (United States)

    Wu, Jiongxing; Yang, Heng; Peng, Yufeng; Fang, Liangjuan; Zheng, Wen; Song, Zhi

    2013-03-15

    (1) Neuronal synchronization underlies brain functioning, and it seems possible that blocking excessive synchronization in an epileptic neural network could reduce or even control seizures. (2) Local field potential coupling is a very common phenomenon during synchronization in networks. Removal of neurons or neuronal networks that are coupled can significantly alter the extracellular field potential. Interventions of coupling mediated by local field potentials could result in desynchronization of epileptic seizures. (3) The synchronized electrical activity generated by neurons is sensitive to changes in the size of the extracellular space, which affects the efficiency of field potential transmission and the threshold of cell excitability. (4) Manipulations of the field potential fluctuations could help block synchronization at seizure onset.

  1. The role of local field potential coupling in epileptic synchronization☆

    Science.gov (United States)

    Wu, Jiongxing; Yang, Heng; Peng, Yufeng; Fang, Liangjuan; Zheng, Wen; Song, Zhi

    2013-01-01

    This review hopes to clearly explain the following viewpoints: (1) Neuronal synchronization underlies brain functioning, and it seems possible that blocking excessive synchronization in an epileptic neural network could reduce or even control seizures. (2) Local field potential coupling is a very common phenomenon during synchronization in networks. Removal of neurons or neuronal networks that are coupled can significantly alter the extracellular field potential. Interventions of coupling mediated by local field potentials could result in desynchronization of epileptic seizures. (3) The synchronized electrical activity generated by neurons is sensitive to changes in the size of the extracellular space, which affects the efficiency of field potential transmission and the threshold of cell excitability. (4) Manipulations of the field potential fluctuations could help block synchronization at seizure onset. PMID:25206721

  2. Do cysteine residues regulate transient receptor potential canonical type 6 (TRPC6) channel protein expression?

    DEFF Research Database (Denmark)

    Thilo, Florian; Liu, Ying; Krueger, Katharina

    2012-01-01

    The regulation of calcium influx through transient receptor potential canonical type 6 channel is mandatory for the activity of human monocytes. We submit the first evidence that cysteine residues of homocysteine or acetylcysteine affect TRPC6 expression in human monocytes. We observed that patie......The regulation of calcium influx through transient receptor potential canonical type 6 channel is mandatory for the activity of human monocytes. We submit the first evidence that cysteine residues of homocysteine or acetylcysteine affect TRPC6 expression in human monocytes. We observed...... that patients with chronic renal failure had significantly elevated homocysteine levels and TRPC6 mRNA expression levels in monocytes compared to control subjects. We further observed that administration of homocysteine or acetylcysteine significantly increased TRPC6 channel protein expression compared...

  3. Potential non-B DNA regions in the human genome are associated with higher rates of nucleotide mutation and expression variation.

    Science.gov (United States)

    Du, Xiangjun; Gertz, E Michael; Wojtowicz, Damian; Zhabinskaya, Dina; Levens, David; Benham, Craig J; Schäffer, Alejandro A; Przytycka, Teresa M

    2014-11-10

    While individual non-B DNA structures have been shown to impact gene expression, their broad regulatory role remains elusive. We utilized genomic variants and expression quantitative trait loci (eQTL) data to analyze genome-wide variation propensities of potential non-B DNA regions and their relation to gene expression. Independent of genomic location, these regions were enriched in nucleotide variants. Our results are consistent with previously observed mutagenic properties of these regions and counter a previous study concluding that G-quadruplex regions have a reduced frequency of variants. While such mutagenicity might undermine functionality of these elements, we identified in potential non-B DNA regions a signature of negative selection. Yet, we found a depletion of eQTL-associated variants in potential non-B DNA regions, opposite to what might be expected from their proposed regulatory role. However, we also observed that genes downstream of potential non-B DNA regions showed higher expression variation between individuals. This coupling between mutagenicity and tolerance for expression variability of downstream genes may be a result of evolutionary adaptation, which allows reconciling mutagenicity of non-B DNA structures with their location in functionally important regions and their potential regulatory role. Published by Oxford University Press on behalf of Nucleic Acids Research 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  4. [Expression of transient receptor potential vanilloid 3 ion channel protein in human odontoblasts].

    Science.gov (United States)

    Liang, Chun-yun; Wu, Sheng; Hu, De-yu; Que, Ke-hua

    2013-11-01

    To investigate the expression of transient receptor potential vanilloid 3 (TRPV3) ion channel protein in human odontoblasts (OD). Twenty intact and healthy third molars extracted for orthodontic purpose were included. The quality of dental tissue sections was determined through HE staining, and the OD layer was further determined by dentin sialophosphoproteins (DSPP) antibody staining, and finally the expression of TRPV3 ion channel protein in human dental pulp tissue was examined by TRPV3 ion channel protein-specific antibody. The expression of TRPV3 channel proteins in human OD at different part of dental pulp was compared using Image Pro Plus (IPP) and SPSS software. TRPV3 channel protein expressed on the cell body of OD in the coronal and root pulp, and the expression in the coronal pulp was significantly higher than that in the root pulp. The TRPV3 protein also expressed at the odontoblastic process, with the higher expression in the crown (IA = 2516 ± 162) than in the root (IA = 2224 ± 150) and external root (IA = 2121 ± 92) (P 0.05). Human odonoblasts expressed TRPV3 ion channel protein and the expression level was different at different part of dental pulp OD.

  5. A novel anxiogenic role for the delta opioid receptor expressed in GABAergic forebrain neurons

    Science.gov (United States)

    Chung, Paul Chu Sin; Keyworth, Helen L.; Martin-Garcia, Elena; Charbogne, Pauline; Darcq, Emmanuel; Bailey, Alexis; Filliol, Dominique; Matifas, Audrey; Ouagazzal, Abdel-Mouttalib; Gaveriaux-Ruff, Claire; Befort, Katia; Maldonado, Rafael; Kitchen, Ian; Kieffer, Brigitte L.

    2014-01-01

    Background The delta opioid receptor (DOR) is broadly expressed throughout the nervous system and regulates chronic pain, emotional responses, motivation and memory. Neural circuits underlying DOR activities have been poorly explored by genetic approaches. Here we used conditional mouse mutagenesis to elucidate receptor function in GABAergic neurons of the forebrain. Methods We characterized DOR distribution in the brain of Dlx5/6-CreXOprd1fl/fl (Dlx-DOR) mice, and tested main central DOR functions through behavioral testing. Results DORs proteins were strongly deleted in olfactory bulb and striatum, and remained intact in cortex and basolateral amygdala. Olfactory perception, circadian activity and despair-like behaviors were unchanged. In contrast, locomotor stimulant effects of SNC80 (DOR agonist) and SKF81297 (D1 agonist) were abolished and increased, respectively. Furthermore, Dlx-DOR mice showed lower levels of anxiety in the elevated plus-maze, opposing the known high anxiety in constitutive DOR knockout animals. Also Dlx-DOR mice reached the food more rapidly in a novelty suppressed feeding (NSF) task, despite their lower motivation for food reward observed in an operant paradigm. Finally, c-fos staining after NSF was strongly reduced in amygdala, concordant with the low anxiety phenotype of Dlx-DOR mice. Conclusion Here we demonstrate that DORs expressed in the forebrain mediate the described locomotor effect of SNC80 and inhibit D1-stimulated hyperactivity. Our data also reveal an unanticipated anxiogenic role for this particular DOR subpopulation, with a potential novel adaptive role. DORs therefore exert dual anxiolytic/anxiogenic roles in emotional responses, which may both have implications in the area of anxiety disorders. PMID:25444168

  6. Role of Akt2 in regulation of metastasis suppressor 1 expression and colorectal cancer metastasis.

    Science.gov (United States)

    Agarwal, E; Robb, C M; Smith, L M; Brattain, M G; Wang, J; Black, J D; Chowdhury, S

    2017-06-01

    Survival signaling is critical for the metastatic program of cancer cells. The current study investigated the role of Akt survival proteins in colorectal cancer (CRC) metastasis and explored potential mechanisms of Akt-mediated metastasis regulation. Using an orthotopic implantation model in mice, which uniquely recapitulates the entire multistep process of CRC metastasis, combined with an inducible system of short hairpin RNA-mediated Akt isoform knockdown in human CRC cells, our studies confirm a role of Akt2 in CRC cell dissemination to distant organs in vivo. Akt2 deficiency profoundly inhibited the development of liver lesions in mice, whereas Akt1 had no effect under the experimental conditions used in the study. Array analysis of human metastatic genes identified the scaffolding protein metastasis suppressor 1 (MTSS1) as a novel Akt2-regulated gene. Inducible loss of Akt2 in CRC cells robustly upregulated MTSS1 at the messenger RNA and protein level, and the accumulated protein was functionally active as shown by its ability to engage an MTSS1-Src-cortactin inhibitory axis. MTSS1 expression led to a marked reduction in levels of functional cortacin (pcortactin Y421), an actin nucleation-promoting factor that has a crucial role in cancer cell invasion and metastasis. MTSS1 was also shown to mediate suppressive effects of Akt2 deficiency on CRC cell viability, survival, migration and actin polymerization in vitro. The relevance of these findings to human CRC is supported by analysis of The Cancer Genome Atlas (TCGA) and NCBI GEO data sets, which demonstrated inverse changes in expression of Akt2 and MTSS1 during CRC progression. Taken together, the data identify MTSS1 as a new Akt2-regulated gene, and point to suppression of MTSS1 as a key step in the metastasis-promoting effects of Akt2 in CRC cells.

  7. Gene expression signature of cigarette smoking and its role in lung adenocarcinoma development and survival.

    Directory of Open Access Journals (Sweden)

    Maria Teresa Landi

    2008-02-01

    Full Text Available Tobacco smoking is responsible for over 90% of lung cancer cases, and yet the precise molecular alterations induced by smoking in lung that develop into cancer and impact survival have remained obscure.We performed gene expression analysis using HG-U133A Affymetrix chips on 135 fresh frozen tissue samples of adenocarcinoma and paired noninvolved lung tissue from current, former and never smokers, with biochemically validated smoking information. ANOVA analysis adjusted for potential confounders, multiple testing procedure, Gene Set Enrichment Analysis, and GO-functional classification were conducted for gene selection. Results were confirmed in independent adenocarcinoma and non-tumor tissues from two studies. We identified a gene expression signature characteristic of smoking that includes cell cycle genes, particularly those involved in the mitotic spindle formation (e.g., NEK2, TTK, PRC1. Expression of these genes strongly differentiated both smokers from non-smokers in lung tumors and early stage tumor tissue from non-tumor tissue (p1.5, for each comparison, consistent with an important role for this pathway in lung carcinogenesis induced by smoking. These changes persisted many years after smoking cessation. NEK2 (p<0.001 and TTK (p = 0.002 expression in the noninvolved lung tissue was also associated with a 3-fold increased risk of mortality from lung adenocarcinoma in smokers.Our work provides insight into the smoking-related mechanisms of lung neoplasia, and shows that the very mitotic genes known to be involved in cancer development are induced by smoking and affect survival. These genes are candidate targets for chemoprevention and treatment of lung cancer in smokers.

  8. Gastrin stimulates MMP-1 expression in gastric epithelial cells: putative role in gastric epithelial cell migration.

    Science.gov (United States)

    Kumar, J Dinesh; Steele, Islay; Moore, Andrew R; Murugesan, Senthil V; Rakonczay, Zoltan; Venglovecz, Viktoria; Pritchard, D Mark; Dimaline, Rodney; Tiszlavicz, Laszlo; Varro, Andrea; Dockray, Graham J

    2015-07-15

    The pyloric antral hormone gastrin plays a role in remodeling of the gastric epithelium, but the specific targets of gastrin that mediate these effects are poorly understood. Glandular epithelial cells of the gastric corpus express matrix metalloproteinase (MMP)-1, which is a potential determinant of tissue remodeling; some of these cells express the CCK-2 receptor at which gastrin acts. We have now examined the hypothesis that gastrin stimulates expression of MMP-1 in the stomach. We determined MMP-1 transcript abundance in gastric mucosal biopsies from Helicobacter pylori negative human subjects with normal gastric mucosal histology, who had a range of serum gastrin concentrations due in part to treatment with proton pump inhibitors (PPI). The effects of gastrin were studied on gastric epithelial AGS-GR cells using Western blot and migration assays. In human subjects with increased serum gastrin due to PPI usage, MMP-1 transcript abundance was increased 2-fold; there was also increased MMP-7 transcript abundance but not MMP-3. In Western blots, gastrin increased proMMP-1 abundance, as well that of a minor band corresponding to active MMP-1, in the media of AGS-GR cells, and the response was mediated by protein kinase C and p42/44 MAP kinase. There was also increased MMP-1 enzyme activity. Gastrin-stimulated AGS-GR cell migration in both scratch wound and Boyden chamber assays was inhibited by MMP-1 immunoneutralization. We conclude that MMP-1 expression is a target of gastrin implicated in mucosal remodeling. Copyright © 2015 the American Physiological Society.

  9. The potential role of sports psychology in the obesity epidemic.

    Science.gov (United States)

    Morelli, Vincent; Davis, Carolyn

    2013-06-01

    Sports psychologists play an important role in enhancing performance among athletes. In conjunction with team physicians, they can also shed light on psychological disorders common in athletes, such as mood and eating disorders, and overtraining syndrome. Sports psychologists can also lend their expertise to assist with injury prevention and recovery and compliance issues. Sports psychology has a role in helping to reverse the growing obesity epidemic among school-aged children. These professionals, working with coaches, can increase children's levels of physical activity. Cognitive-behavioral techniques could lead to enhanced enjoyment, increased participation, improved school performance, and a reduction in obesity. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Expression of Fas ligand by human gastric adenocarcinomas: a potential mechanism of immune escape in stomach cancer.

    LENUS (Irish Health Repository)

    Bennett, M W

    2012-02-03

    BACKGROUND: Despite being immunogenic, gastric cancers overcome antitumour immune responses by mechanisms that have yet to be fully elucidated. Fas ligand (FasL) is a molecule that induces Fas receptor mediated apoptosis of activated immunocytes, thereby mediating normal immune downregulatory roles including immune response termination, tolerance acquisition, and immune privilege. Colon cancer cell lines have previously been shown to express FasL and kill lymphoid cells by Fas mediated apoptosis in vitro. Many diverse tumours have since been found to express FasL suggesting that a "Fas counterattack" against antitumour immune effector cells may contribute to tumour immune escape. AIM: To ascertain if human gastric tumours express FasL in vivo, as a potential mediator of immune escape in stomach cancer. SPECIMENS: Thirty paraffin wax embedded human gastric adenocarcinomas. METHODS: FasL protein was detected in gastric tumours using immunohistochemistry; FasL mRNA was detected in the tumours using in situ hybridisation. Cell death was detected in situ in tumour infiltrating lymphocytes using terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL). RESULTS: Prevalent expression of FasL was detected in all 30 resected gastric adenocarcinomas examined. In the tumours, FasL protein and mRNA were co-localised to neoplastic gastric epithelial cells, confirming expression by the tumour cells. FasL expression was independent of tumour stage, suggesting that it may be expressed throughout gastric cancer progression. TUNEL staining disclosed a high level of cell death among lymphocytes infiltrating FasL positive areas of tumour. CONCLUSIONS: Human gastric adenocarcinomas express the immune downregulatory molecule, FasL. The results suggest that FasL is a prevalent mediator of immune privilege in stomach cancer.

  11. CCL27: Novel Cytokine with Potential Role in Pathogenesis of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Svetlana F. Khaiboullina

    2015-01-01

    Full Text Available Multiple sclerosis (MS is an autoimmune and neurodegenerative disease of unknown etiology. Leukocyte infiltration of brain tissue and the subsequent inflammation, demyelination, axonal damage, and formation of sclerotic plaques is a hallmark of MS. Upregulation of proinflammatory cytokines has been suggested to play an essential role in regulating lymphocyte migration in MS. Here we present data on serum cytokine expression in MS cases. Increased serum levels of IL-17 and IL-23 were observed, suggesting activation of the Th17 population of immune effector cells. Additionally, increased levels of IL-22 were observed in the serum of those with acute phase MS. Unexpectedly, we observed an upregulation of the serum chemokine CCL27 in newly diagnosed and acute MS cases. CCL27 is an inflammatory chemokine associated with homing of memory T cells to sites of inflammation. Therefore, its upregulation in association with MS suggests a potential role in disease pathogenesis. Our data supports previous reports showing IL-17 and -23 upregulation in association with MS and potentially identify a previously unknown involvement for CCL27.

  12. Potential role of high mobility group box 1 in viral infectious diseases.

    Science.gov (United States)

    Wang, Haichao; Ward, Mary F; Fan, Xue-Gong; Sama, Andrew E; Li, Wei

    2006-01-01

    A nuclear protein, high mobility group box 1 (HMGB1), is released passively by necrotic cells and actively by macrophages/monocytes in response to exogenous and endogenous inflammatory stimuli. After binding to the receptor for advanced glycation end products (RAGE), or Toll-like receptor 4 (TLR4), HMGB1 activates macrophages/monocytes to express proinflammatory cytokines, chemokines, and adhesion molecules. Pharmacological suppression of its activities or release is protective against lethal endotoxemia and sepsis, establishing HMGB1 as a critical mediator of lethal systemic inflammation. In light of observations that many viruses (e.g., West Nile virus, Salmon anemia virus) can induce passive HMGB1 release, we propose a potential pathogenic role of HMGB1 in viral infectious diseases.

  13. Toxoplasma gondii Hsp90: potential roles in essential cellular processes of the parasite

    Science.gov (United States)

    Angel, Sergio O.; Figueras, Maria J.; Alomar, Maria L.; Echeverria, Pablo C.; Deng, Bin

    2014-01-01

    SUMMARY Hsp90 is a widely distributed and highly conserved molecular chaperone that is ubiquitously expressed throughout nature, being one of the most abundant proteins within non-stressed cells. This chaperone is up-regulated following stressful events and has been involved in many cellular processes. In Toxoplasma gondii, Hsp90 could be linked with many essential processes of the parasite such as host cell invasion, replication and tachyzoite-bradyzoite interconversion. A Protein-Protein Interaction (PPI) network approach of TgHsp90 has allowed inferring how these processes may be altered. In addition, data mining of T. gondii phosphoproteome and acetylome has allowed the generation of the phosphorylation and acetylation map of TgHsp90. This review focuses on the potential roles of TgHsp90 in parasite biology and the analysis of experimental data in comparison with its counterparts in yeast and humans. PMID:24560345

  14. Expressão do potencial de rendimento de cultivares de soja Yield potential expression of soybean genotypes

    Directory of Open Access Journals (Sweden)

    Hugo Motta Navarro Júnior

    2002-03-01

    Full Text Available A soja possui alto potencial de rendimento de grãos, mas em virtude da interação genótipo vs. ambiente esse potencial não é verificado em sua totalidade. Utilizando-se seis genótipos de soja de diferentes ciclos, objetivou-se estudar a expressão do potencial de rendimento de grãos e quantificá-lo durante a ontogenia. O experimento foi conduzido no ano agrícola 1996/97 na Estação Experimental Agronômica da Universidade Federal do Rio Grande do Sul, Eldorado do Sul, RS. As avaliações foram realizadas em plantas individuais e se estenderam desde o estádio de floração até o de maturação. Os resultados obtidos indicam que alto potencial de rendimento não necessariamente identifica uma planta eficiente na retenção das estruturas reprodutivas. Os potenciais de rendimento estimados na floração e no início do enchimento de grãos não se mantêm até a maturação. Genótipos com alto potencial de rendimento de grãos em R8 não apresentam os maiores potenciais de rendimento de grãos em R2 e em R5, porém, são os que apresentam as menores diferenças entre o potencial estimado em R5 e o estimado em R2.Soybean has high yield potential, which is not totally expressed due to genotype vs. environment interaction. Six soybean genotypes of different maturity groups were used with the objective of studying their yield potential expression and quantifying it during ontogeny. The experiment was conducted during the 1996/97 growing season in the Agronomic Experimental Station of the Universidade Federal do Rio Grande do Sul, Eldorado do Sul, RS, Brazil. Plants were evaluated individually from flowering until maturity. Results obtained indicate that high yield potential does not necessarily mean an efficient plant in reproductive structure retention. Yield potential estimated in the flowering and beginning of grain filling stages are not maintained until maturity. Genotypes with high yield potential in the R8 stage do not present the

  15. Potential role of lampalizumab for treatment of geographic atrophy.

    Science.gov (United States)

    Rhoades, William; Dickson, Drew; Do, Diana V

    2015-01-01

    The purpose of this article is to review the pathways underlying age-related macular degeneration and potential therapeutic targets, focusing on the complement pathway and the recent MAHALO Phase II trial of the investigational drug lampalizumab. This trial was the first to have shown positive results for the treatment of geographic atrophy in age-related macular degeneration. It has potential as a future treatment, and is currently undergoing a Phase III trial.

  16. Role of Sodium Channel on Cardiac Action Potential

    OpenAIRE

    S. H. Sabzpoushan; A. Faghani Ghodrat

    2012-01-01

    Sudden cardiac death is a major cause of death worldwide. In most cases, it's caused by abnormal action potential propagation that leads to cardiac arrhythmia. The aim of this article is to study the abnormal action potential propagation through sodium ion concentration variations. We use a new electrophysiological model that is both detailed and computationally efficient. This efficient model is based on the partial differential equation method. The central finite difference method is used f...

  17. In vivo and In vitro Identification of Endocannabinoid Signaling in Periodontal Tissues and Their Potential Role in Local Pathophysiology.

    Science.gov (United States)

    Konermann, Anna; Jäger, Andreas; Held, Stefanie A E; Brossart, P; Schmöle, Anne

    2017-03-14

    The endocannabinoid system (ECS) with its binding receptors CB1 and CB2 impacts multiple pathophysiologies not only limited to neuronal psychoactivity. CB1 is assigned to cerebral neuron action, whereas CB2 is mainly expressed in different non-neuronal tissues and associated with immunosuppressive effects. Based on these tissue-selective CB receptor roles, it was the aim of this study to analyze potential expression in periodontal tissues under physiological conditions and inflammatory states. In vivo, CB receptor expression was investigated on human periodontal biopsies with or without bacterial inflammation and on rat maxillae with or without sterile inflammation. In vitro analyses were performed on human periodontal ligament (PDL) cells at rest or under mechanical strain via qRT-PCR, Western blot, and immunocytochemistry. P periodontal tissues, both adjusted by different entities of periodontal inflammation and by mechanical stress. This indicates potential ECS function as regulatory tool in controlling of periodontal pathophysiology.

  18. Neurotrophin mRNA expression in the developing tooth suggests multiple roles in innervation and organogenesis

    National Research Council Canada - National Science Library

    Luukko, K; Arumäe, U; Karavanov, A; Moshnyakov, M; Sainio, K; Sariola, H; Saarma, M; Thesleff, I

    1997-01-01

    To analyze the roles of neurotrophins during early development of rat teeth, we studied the expression of neurotrophin mRNAs from the initiation of first molar formation to the completion of crown morphogenesis...

  19. Compositional features are potentially involved in the regulation of gene expression of tumor suppressor genes in human tissues.

    Science.gov (United States)

    Hajjari, Mohammadreza; Khoshnevisan, Atefeh; Behmanesh, Mehrdad

    2014-12-15

    Different mechanisms regulate the expression level of tissue specific genes in human. Here we report some compositional features such as codon usage bias, amino acid usage bias, codon frequency, and base composition which may be potentially related to mRNA amount of tissue specific tumor suppressor genes. Our findings support the possibility that structural elements in gene and protein may play an important role in the regulation of tumor suppressor genes, development, and tumorigenesis. The data presented here can open broad vistas in the understanding and treatment of a variety of human malignancies. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Retinoids and motor neuron disease: Potential role in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Riancho, Javier; Berciano, Maria T; Ruiz-Soto, Maria; Berciano, Jose; Landreth, Gary; Lafarga, Miguel

    2016-01-15

    Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease affecting motor neurons (MN). This fatal disease is characterized by progressive muscular atrophy and unfortunately it does not have an effective treatment. Although a small proportion of ALS cases have a familiar origin, the vast majority of them are thought to have a sporadic origin. Although the pathogenesis of ALS has not been fully elucidated, various disorders in different cellular functions such as gene expression, protein metabolism, axonal transport and glial cell disorders have been linked to MN degeneration. Among them, proteostasis is one of the best studied. Retinoids are vitamin A-derived substances that play a crucial role in embryogenesis, development, programmed cell death and other cellular functions. Retinoid agonists behave as transcription factors throughout the activation of the nuclear retinoid receptors. Several reports in the literature suggest that retinoids are involved in proteostasis regulation, by modulating its two major pathways, the ubiquitin-proteasome system and the autophagy-lysosome response. Additionally, there are some evidences for a role of retinoids themselves, in ALS pathogenesis. In this review, we discuss the importance of proteostasis disruption as a trigger for MN degeneration and the capability of retinoids to modulate it, as well as the potential therapeutic role of retinoids as a new therapy in ALS. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Antibodies and their receptors: different potential roles in mucosal defense

    NARCIS (Netherlands)

    Horton, Rachel E.; Vidarsson, Gestur

    2013-01-01

    Over recent years it has become increasingly apparent that mucosal antibodies are not only restricted to the IgM and IgA isotypes, but that also other isotypes and particularly IgG can be found in significant quantities at some mucosal surfaces, such as in the genital tract. Their role is more

  2. The potential role of flaxseed oil on lead acetateinduced kidney ...

    African Journals Online (AJOL)

    Lead (Pb+2) intoxication may initiate many disorders in humans and animals. This study investigated the role of flaxseed oil in protecting rats against Pb+2 exposures. The results showed that the administration of flaxseed oil efficiently protected albino rats against the Pb+2 caused injury, as revealed by some improvement ...

  3. The potential role of agroforestry in maintaining soil fertility on ...

    African Journals Online (AJOL)

    Despite legislation curtailing their use, they are being used for grazing, and crop and vegetable production. The soils in the cultivated dambos suffer from major phosphorus and sulphur deficiencies and have low nitrogen and organic matter content. Organic fertilizers play a significant role in maintaining soil fertility on these ...

  4. Potential protective role of hydrogen against cisplatin- induced side ...

    African Journals Online (AJOL)

    Yi Lang1. 1Department of Radiation Oncology, Sichuan Cancer Hospital, 2Department of Oncology, Chengdu First People's Hospital,. Chengdu 610041, China ... indiscriminately interact with lipids, proteins, and nucleic acids, thus leading to .... Differential roles of hydrogen peroxide and hydroxyl radical in cisplatin-induced ...

  5. Potential role for wild vegetables in household food security: a ...

    African Journals Online (AJOL)

    The value of wild edible vegetables in food security has not been given sufficient attention in South Africa. Consequently, there are no formal interventions that seek to encourage people to use traditional vegetables as sources of essential nutrients. Studies on the role of wild leafy vegetables in food security could provide ...

  6. Ectopic expression of Arabidopsis Target of Rapamycin (AtTOR) improves water-use efficiency and yield potential in rice

    Science.gov (United States)

    Bakshi, Achala; Moin, Mazahar; Kumar, M. Udaya; Reddy, Aramati Bindu Madhava; Ren, Maozhi; Datla, Raju; Siddiq, E. A.; Kirti, P. B.

    2017-02-01

    The target of Rapamycin (TOR) present in all eukaryotes is a multifunctional protein, regulating growth, development, protein translation, ribosome biogenesis, nutrient, and energy signaling. In the present study, ectopic expression of TOR gene of Arabidopsis thaliana in a widely cultivated indica rice resulted in enhanced plant growth under water-limiting conditions conferring agronomically important water-use efficiency (WUE) trait. The AtTOR high expression lines of rice exhibited profuse tillering, increased panicle length, increased plant height, high photosynthetic efficiency, chlorophyll content and low ∆13C. Δ13C, which is inversely related to high WUE, was as low as 17‰ in two AtTOR high expression lines. These lines were also insensitive to the ABA-mediated inhibition of seed germination. The significant upregulation of 15 stress-specific genes in high expression lines indicates their contribution to abiotic stress tolerance. The constitutive expression of AtTOR is also associated with significant transcriptional upregulation of putative TOR complex-1 components, OsRaptor and OsLST8. Glucose-mediated transcriptional activation of AtTOR gene enhanced lateral root formation. Taken together, our findings indicate that TOR, in addition to its multiple cellular functions, also plays an important role in response to abiotic stress and potentially enhances WUE and yield related attributes.

  7. Breast cancer associated a2 isoform vacuolar ATPase immunomodulates neutrophils: potential role in tumor progression

    Science.gov (United States)

    Ibrahim, Safaa A.; Katara, Gajendra K.; Kulshrestha, Arpita; Jaiswal, Mukesh K.; Amin, Magdy A.; Beaman, Kenneth D.

    2015-01-01

    In invasive breast cancer, tumor associated neutrophils (TAN) represent a significant portion of the tumor mass and are associated with increased angiogenesis and metastasis. Identifying the regulatory factors that control TAN behavior will help in developing ideal immunotherapies. Vacuolar ATPases (V-ATPases), multi-subunit proton pumps, are highly expressed in metastatic breast cancer cells. A cleaved peptide from a2 isoform V-ATPase (a2NTD) has immunomodulatory role in tumor microenvironment. Here, we report for the first time the role of V-ATPase in neutrophils modulation. In invasive breast cancer cells, a2NTD was detected and a2V was highly expressed on the surface. Immunohistochemical analysis of invasive breast cancer tissues revealed that increased neutrophil recruitment and blood vessel density correlated with increased a2NTD levels. In order to determine the direct regulatory role of a2NTD on neutrophils, recombinant a2NTD was used for the treatment of neutrophils isolated from the peripheral blood of healthy volunteers. Neutrophils treated with a2NTD (a2Neuɸ) showed increased secretion of IL-1RA, IL-10, CCL-2 and IL-6 that are important mediators in cancer related inflammation. Moreover, a2Neuɸ exhibited an increased production of protumorigenic factors including IL-8, matrix metaloprotinase-9 and vascular endothelial growth factor. Further, functional characterization of a2Neuɸ revealed that a2Neuɸ derived products induce in vitro angiogenesis as well as increase the invasiveness of breast cancer cells. This study establishes the modulatory effect of breast cancer associated a2V on neutrophils, by the action of a2NTD, which has a positive impact on tumor progression, supporting that a2V can be a potential selective target for breast cancer therapy. PMID:26460736

  8. Rapid Identification of Potential Drugs for Diabetic Nephropathy Using Whole-Genome Expression Profiles of Glomeruli

    Directory of Open Access Journals (Sweden)

    Jingsong Shi

    2016-01-01

    Full Text Available Objective. To investigate potential drugs for diabetic nephropathy (DN using whole-genome expression profiles and the Connectivity Map (CMAP. Methodology. Eighteen Chinese Han DN patients and six normal controls were included in this study. Whole-genome expression profiles of microdissected glomeruli were measured using the Affymetrix human U133 plus 2.0 chip. Differentially expressed genes (DEGs between late stage and early stage DN samples and the CMAP database were used to identify potential drugs for DN using bioinformatics methods. Results. (1 A total of 1065 DEGs (FDR 1.5 were found in late stage DN patients compared with early stage DN patients. (2 Piperlongumine, 15d-PGJ2 (15-delta prostaglandin J2, vorinostat, and trichostatin A were predicted to be the most promising potential drugs for DN, acting as NF-κB inhibitors, histone deacetylase inhibitors (HDACIs, PI3K pathway inhibitors, or PPARγ agonists, respectively. Conclusion. Using whole-genome expression profiles and the CMAP database, we rapidly predicted potential DN drugs, and therapeutic potential was confirmed by previously published studies. Animal experiments and clinical trials are needed to confirm both the safety and efficacy of these drugs in the treatment of DN.

  9. Role of Sodium Channel on Cardiac Action Potential

    Directory of Open Access Journals (Sweden)

    S. H. Sabzpoushan

    2012-06-01

    Full Text Available Sudden cardiac death is a major cause of death worldwide. In most cases, it's caused by abnormal action potential propagation that leads to cardiac arrhythmia. The aim of this article is to study the abnormal action potential propagation through sodium ion concentration variations. We use a new electrophysiological model that is both detailed and computationally efficient. This efficient model is based on the partial differential equation method. The central finite difference method is used for numerical solving of the two-dimensional (2D wave propagation equation. Simulations are implemented in two stages, as a single cardiac cell and as a two-dimensional grid of cells. In both stages, the normal action potential formation in case of a single cell and it's normal propagation in case of a two-dimensional grid of cells were simulated with nominal sodium ion conductance. Then, the effect of sodium ion concentration on the action potential signal was studied by reducing the sodium ion conductance. It is concluded that reducing the sodium ion conductance, decreases both passing ability and conduction velocity of the action potential wave front.

  10. CD133 and BMI1 expressions and its prognostic role in primary ...

    Indian Academy of Sciences (India)

    cancer, but the function and interaction with other major oncogenes and tumour suppressor genes is still not understood. This study aimed to analyse the expression of CD133 mRNA and its correlations with BMI1 protein expression and TP53 mutations in newly diagnosed glioblastoma patients and its role in prognosis.

  11. The Roles of Emotional Comprehension and Representational Drawing Skill in Children's Expressive Drawing

    Science.gov (United States)

    Brechet, Claire; Jolley, Richard P.

    2014-01-01

    The purpose of the present study was to investigate the roles of emotional comprehension and representational drawing skill in children's expressive drawing. Fifty 7- to 10-year-olds were asked to produce two (happy and sad) expressive drawings, two representational drawings (drawing of a man running and drawing of a house) and to answer the…

  12. Potential role of street foods as micronutrients source among low ...

    African Journals Online (AJOL)

    Although more than 40% of Nairobi's lower-income groups consume street foods, there is paucity of information available for urban policy makers and programmers on the potential contribution of street foods to micronutrient intake. A cross-sectional survey and a non-repetitive 24-hour dietary recall were employed to ...

  13. Altered muscarinic receptor expression in the cerebral cortex of epileptic rats: Restorative role of Withania somnifera.

    Science.gov (United States)

    Anju, T R; Smijin, S; Mathew, Jobin; Paulose, C S

    2017-12-07

    Temporal Lobe Epilepsy involves a sequence of events which can lead to neurotransmitter signalling alterations. Many herbal extracts are considered as alternative therapeutic method for epilepsy management. In the present study, we investigated the effect of Withania somnifera (WS) root extract and Withanolide A (WA) in the management of Temporal Lobe Epilepsy. Confocal imaging of TOPRO-3 stained cortical sections showed severe damage in epileptic brain. We also observed a reduced antioxidant potential and increased peroxide level in epileptic group. Oxidative stress resulted in the down regulation of CREB, NF-κB and TNF-α with an up regulation of the apoptotic factors Caspase 8, 3 and bax in epileptic group. Epileptic condition also resulted in an increased muscarinic receptor binding and mRNA expression in the cerebral cortex. Withania somnifera and Withanolide A significantly reversed the altered muscarinic receptor expression and reversed the oxidative stress and resultant derailment in cell signalling. Thus our studies suggest that Withania somnifera and Withanolide A play an important role in central muscarinic receptor functional balance and activation of antioxidant system in the cerebral cortex of temporal lobe epileptic condition. These findings can be of immense therapeutic significance for epileptic management.

  14. Pharmacology of Myopia and Potential Role for Intrinsic Retinal Circadian Rhythms

    Science.gov (United States)

    Stone, Richard A.; Pardue, Machelle T.; Iuvone, P. Michael; Khurana, Tejvir S.

    2013-01-01

    ; these rhythms shift in eyes developing experimental ametropia. Long-standing clinical ideas about myopia in particular have postulated a role for ambient lighting, although molecular or cellular mechanisms for these speculations have remained obscure. Experimental myopia induced by the wearing of a concave spectacle lens alters the retinal expression of a significant proportion of intrinsic circadian clock genes, as well as genes encoding a melatonin receptor and the photopigment melanopsin. Together this evidence suggests a hypothesis that the retinal clock and intrinsic retinal circadian rhythms may be fundamental to the mechanism(s) regulating refractive development, and that disruptions in circadian signals may produce refractive errors. Here we review the potential role of biological rhythms in refractive development. While much future research is needed, this hypothesis could unify many of the disparate clinical and laboratory observations addressing the pathogenesis of refractive errors. PMID:23313151

  15. HB-EGF expression as a potential biomarker of acquired middle ear cholesteatoma.

    Science.gov (United States)

    Xie, Shumin; Wang, Xiaoli; Ren, Hongmiao; Liu, Xiaoyu; Ren, Jihao; Liu, Wei

    2017-08-01

    The heparin-binding epidermal growth factor-like growth factor (HB-EGF) plays an essential role in the development and invasiveness of cholesteatoma. This study may help to realize the molecular mechanisms underlying the pathogenesis of cholesteatoma and make HB-EGF a promising target for drug intervention of cholesteatoma. To detect HB-EGF expression in human surgical specimens of acquired middle ear cholesteatoma and analyze its functional role as a regulator of epithelial keratinocytes hyperproliferation. A total of 34 patients who underwent surgical treatment for middle ear cholesteatoma were recruited in the study. The mRNA and protein expression of HB-EGF in middle ear cholesteatoma tissues and normal postauricular skin tissues was investigated by real-time quantitative reverse-transcription-polymerase chain reaction (RT-qPCR), immunohistochemical staining, and western blot. The correlation between bone resorption degree and HB-EGF expression was also analyzed. On average, compared with normal postauricular skin, expression of HB-EGF mRNA in the cholesteatoma epithelium was significantly elevated 2.41-fold by RT-qPCR, and HB-EGF protein significantly upregulated 2.32-fold by western blot. Positive HB-EGF immunostaining observed in the basal and suprabasal layers of cholesteatoma epithelium was significantly stronger than in normal postauricular skin. Meanwhile, an obviously positive correlation between HB-EGF protein expression and bone resorption degree was discovered.

  16. Expression of cytokeratin 18 and 19 in oral potentially malignant disorders: A systematic review

    Directory of Open Access Journals (Sweden)

    Sam Prasad Prabakaran

    2014-01-01

    Full Text Available The aim of this review is to evaluate the expression of cytokeratin 18 and 19 in oral potentially malignant disorders (OPMD. Systematic review was performed using Medline and PubMed. Hand searches were taken from the back references. Articles published till 15 July 2014 were included in the search. The search yielded a total of 20 articles, out of which 16 articles were eliminated, as they did not fulfill the inclusion criteria and 4 articles were included for the final analysis. The available literature showed that cytokeratin 18 and 19 were expressed in all OPMDs. The level of expression varied among different oral, potentially malignant disorders and among different studies.

  17. The potential lipolysis function of musclin and its mRNA expression ...

    African Journals Online (AJOL)

    Musclin is a newly discovered factor and its functions remain to be defined. This study investigated the tissue expression pattern of musclin gene and its potential effect on lipid metabolism. Musclin mRNA levels in adipose, muscle tissues and primary adipocytes were examined by quantitative PCR. The musclin gene ...

  18. Pulsatile atheroprone shear stress affects the expression of transient receptor potential channels in human endothelial cells

    DEFF Research Database (Denmark)

    Thilo, Florian; Vorderwülbecke, Bernd J; Marki, Alex

    2012-01-01

    The goal of the study was to assess whether pulsatile atheroprone shear stress modulates the expression of transient receptor potential (TRP) channels, TRPC3, TRPC6, TRPM7, and TRPV1 mRNA, in human umbilical vascular endothelial cells. Exposure of cultured vascular endothelial cells to defined...

  19. Expression of miR-126 and its potential function in coronary artery ...

    African Journals Online (AJOL)

    Expression of miR-126 and its potential function in coronary artery disease. Xiaoyan Wang1, Yajun Lian2, Xin Wen3, Jing Guo2, Zhiping Wang2,. Sheng Jiang2, Yaodong Hu2. 1. Department of Ultrasound, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi, China. 2. Department of Cardiology ...

  20. Anteroposterior Patterning of Gene Expression in the Human Infant Sclera: Chondrogenic Potential and Wnt Signaling.

    Science.gov (United States)

    Seko, Yuko; Azuma, Noriyuki; Yokoi, Tadashi; Kami, Daisuke; Ishii, Ryuga; Nishina, Sachiko; Toyoda, Masashi; Shimokawa, Hitoyata; Umezawa, Akihiro

    2017-01-01

    Purpose/Aim: We sought to identify the anteroposterior spatial gene expression hierarchy in the human sclera to develop a hypothesis for axial elongation and deformity of the eyeball. We analyzed the global gene expression of human scleral cells derived from distinct parts of the human infant sclera obtained from surgically enucleated eyes with retinoblastoma, using Affymetrix GeneChip oligonucleotide arrays, and compared, in particular, gene expression levels between the anterior and posterior parts of the sclera. The ages of three donors were 10M, 4M, and 1Y9M. K-means clustering analysis of gene expression revealed that expression levels of cartilage-associated genes such as COLXIA and ACAN increased from the anterior to the posterior part of the sclera. Microarray analyses and RT-PCR data showed that the expression levels of MGP, COLXIA, BMP4, and RARB were significantly higher in the posterior than in the anterior sclera of two independent infant eyes. Conversely, expression levels of WNT2, DKK2, GREM1, and HOXB2 were significantly higher in the anterior sclera. Among several Wnt-family genes examined, WNT2B was found to be expressed at a significantly higher level in the posterior sclera, and the reverse order was observed for WNT2. The results of luciferase reporter assays suggested that a GSK-3β inhibitor stimulated Wnt/β-catenin signaling particularly strongly in the posterior sclera. The expression pattern of RARB, a myopia-related gene, was similar in three independent eyes. Chondrogenic potential was higher and Wnt/β-catenin signaling was more potently activated by a GSK-3β inhibitor in the posterior than in the anterior part of the human infant sclera. Although the differences in the gene expression profiles between the anterior and posterior sclera might be involved only in normal growth processes, this anteroposterior hierarchy in the sclera might contribute to disorders involving abnormal elongation and deformity of the eyeball, including myopia.

  1. Potential role of remote sensing in disaster relief management

    Science.gov (United States)

    Rush, M.; Holguin, A.; Vernon, S.

    1976-01-01

    Baseline or predisaster data which would be useful to decision making in the immediate postdisaster period were suggested for the six areas of public health concern along with guidelines for organizing these data. Potential sources of these data are identified. In order to fully assess the impact of a disaster on an area, information about its predisaster status must be known. Aerial photography is one way of acquiring and recording such data.

  2. The potential role of nintedanib in treating colorectal cancer.

    Science.gov (United States)

    Rossi, Antonio; Latiano, Tiziana Pia; Parente, Paola; Chiarazzo, Cinzia; Limosani, Filomena; Di Maggio, Gabriele; Maiello, Evaristo

    2017-08-01

    Angiogenesis leads to the growth, progression, and metastases of a variety of solid tumors, including metastatic colorectal cancer (mCRC), involving particularly the family of vascular endothelial growth factors (VEGF) and their receptors (VEGFR). Several anti-angiogenic inhibitors are already registered for mCRC therapy: bevacizumab, aflibercept, ramucirumab, regorafenib. Nintedanib is a new triple angiokinase oral inhibitor that potently blocks the proangiogenic pathways mediated by VEGFR, platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR). Areas covered: The current state-of-the-art of anti-angiogenic inhibitors employed in the treatment mCRC patients, and in particular the role of nintedanib in this setting, is reviewed and discussed here. A structured search of bibliographic databases for peer-reviewed research literature and of main meetings using a focused review question was undertaken. Expert opinion: In first-line therapy, a phase II randomized trial showed that nintedanib plus chemotherapy was not inferior to the bevacizumab-based regimen. In heavily pretreated mCRC patients nintedanib improved some outcomes. During the natural history of mCRC resistances to anti-angiogenic therapies can set in and in this context, nintedanib, due to its triple inhibition, might play a role in compensatory angiogenesis overcoming the resistance developed due to VEGF directed therapy.

  3. The potential role of Neutral Beam Injection in EU DEMO

    Science.gov (United States)

    Vincenzi, Pietro; Artaud, Jean-Francois; Bolzonella, Tommaso; Giruzzi, Gerardo

    2016-10-01

    EU DEMO studies for pulsed (DEMO1) and steady-state (DEMO2) concepts are currently in the pre-conceptual phase. Present DEMO1 design is based on ITER baseline H-mode scenario, while DEMO2 is based on advanced scenarios with moderate reversed q profile sustained by non-inductive currents. One of the possible flattop heating power systems currently considered is Neutral Beam Injection (NBI). In this work the role of NBI in DEMO1 and DEMO2 is investigated by means of integrated simulations of DEMO scenarios using METIS fast tokamak modelling tool. Limitations, requirements and benefits of the use of a NBI system are discussed. For DEMO1 pulsed concept, the role of NBI is mainly central plasma heating for scenario stability (high fusion power H-mode). As a by-product of the tangential injection, NBI is capable of current drive, which is favorable in order to extend the discharge duration. Regarding a steady-state DEMO2 concept, in addition to plasma heating, NBI becomes a direct actuator for the advanced scenario by driving a considerable part of the plasma current. This requires more than 100MW with off-axis injection. The effect of an increase of the injection energy on the driven current density profile is also presented for DEMO2.

  4. Dietary emulsifiers directly alter human microbiota composition and gene expression ex vivo potentiating intestinal inflammation.

    Science.gov (United States)

    Chassaing, Benoit; Van de Wiele, Tom; De Bodt, Jana; Marzorati, Massimo; Gewirtz, Andrew T

    2017-08-01

    The intestinal microbiota plays a central role in the development of many chronic inflammatory diseases including IBD and metabolic syndrome. Administration of substances that alter microbiota composition, including the synthetic dietary emulsifiers polysorbate 80 (P80) and carboxymethylcellulose (CMC), can promote such inflammatory disorders. However, that inflammation itself impacts microbiota composition has obfuscated defining the extent to which these compounds or other substances act directly upon the microbiota versus acting on host parameters that promote inflammation, which subsequently reshapes the microbiota. We examined the direct impact of CMC and P80 on the microbiota using the mucosal simulator of the human intestinal microbial ecosystem (M-SHIME) model that maintains a complex stable human microbiota in the absence of a live host. This approach revealed that both P80 and CMC acted directly upon human microbiota to increase its proinflammatory potential, as revealed by increased levels of bioactive flagellin. The CMC-induced increase in flagellin was rapid (1 day) and driven by altered microbiota gene expression. In contrast, the P80-induced flagellin increase occurred more slowly and was closely associated with altered species composition. Transfer of both emulsifier-treated M-SHIME microbiotas to germ-free recipient mice recapitulated many of the host and microbial alterations observed in mice directly treated with emulsifiers. These results demonstrate a novel paradigm of deconstructing host-microbiota interactions and indicate that the microbiota can be directly impacted by these commonly used food additives, in a manner that subsequently drives intestinal inflammation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  5. Comprehensive expression analysis suggests overlapping and specific roles of rice glutathione S-transferase genes during development and stress responses

    Directory of Open Access Journals (Sweden)

    Bhattacharjee Annapurna

    2010-01-01

    Full Text Available Abstract Background Glutathione S-transferases (GSTs are the ubiquitous enzymes that play a key role in cellular detoxification. Although several GSTs have been identified and characterized in various plant species, the knowledge about their role in developmental processes and response to various stimuli is still very limited. In this study, we report genome-wide identification, characterization and comprehensive expression analysis of members of GST gene family in crop plant rice, to reveal their function(s. Results A systematic analysis revealed the presence of at least 79 GST genes in the rice genome. Phylogenetic analysis grouped GST proteins into seven classes. Sequence analysis together with the organization of putative motifs indicated the potential diverse functions of GST gene family members in rice. The tandem gene duplications have contributed a major role in expansion of this gene family. Microarray data analysis revealed tissue-/organ- and developmental stage-specific expression patterns of several rice GST genes. At least 31 GST genes showed response to plant hormones auxin and cytokinin. Furthermore, expression analysis showed the differential expression of quite a large number of GST genes during various abiotic stress (20, arsenate stress (32 and biotic stress (48 conditions. Many of the GST genes were commonly regulated by developmental processes, hormones, abiotic and biotic stresses. Conclusion The transcript profiling suggests overlapping and specific role(s of GSTs during various stages of development in rice. Further, the study provides evidence for the role of GSTs in mediating crosstalk between various stress and hormone response pathways and represents a very useful resource for functional analysis of selected members of this family in rice.

  6. Antibodies and their receptors: different potential roles in mucosal defence

    Directory of Open Access Journals (Sweden)

    Rachel eHorton

    2013-07-01

    Full Text Available Over recent years it has become increasingly apparent that mucosal antibodies are not only restricted to the IgM and IgA isotypes, but that also other isotypes and particularly IgG can be found in significant quantities at some mucosal surfaces, such as in the genital tract. Their role is more complex than traditionally believed with, among other things, the discovery of novel function of mucosal immunoglobulin receptors. A thorough knowledge in the source and function and mucosal immunoglobulins is particularly important in development of vaccines providing mucosal immunity, and also in the current climate of microbicide development, to combat major world health issues such as HIV. We present here a comprehensive review of human antibody mediated mucosal immunity.

  7. Potential Role of Probiotics in Mechanism of Intestinal Immunity

    Directory of Open Access Journals (Sweden)

    Imran Rashid Rajput and Wei Fen Li*

    2012-06-01

    Full Text Available Probiotics are nonpathogenic bacteria exert a constructive influence on health or physiology of the host. Effect of probiotics in the intestinal defense against variety of diseases is well known. The probiotics are involved in the mechanism of intestinal defense, support as antagonist against pathogens, improve intestinal epithelial layer and boost the innate as well as adaptive immunity. However these responses are also exerted by intestinal components. The intestinal components as well as probiotics play a reciprocal role to enhance the immune response of the individual. The possibilities of mechanism of action include the stimulation of epithelial cells, activation of dendritic cells via toll-like receptors (TLRs, conversely produce cytokines. These observations reviewed together advocate that specific immunomodulatory properties of probiotic bacteria should be focusing on mechanism of action via antigen presenting cells (APC.

  8. Fluid Intelligence and Automatic Neural Processes in Facial Expression Perception: An Event-Related Potential Study.

    Science.gov (United States)

    Liu, Tongran; Xiao, Tong; Li, Xiaoyan; Shi, Jiannong

    2015-01-01

    The relationship between human fluid intelligence and social-emotional abilities has been a topic of considerable interest. The current study investigated whether adolescents with different intellectual levels had different automatic neural processing of facial expressions. Two groups of adolescent males were enrolled: a high IQ group and an average IQ group. Age and parental socioeconomic status were matched between the two groups. Participants counted the numbers of the central cross changes while paired facial expressions were presented bilaterally in an oddball paradigm. There were two experimental conditions: a happy condition, in which neutral expressions were standard stimuli (p = 0.8) and happy expressions were deviant stimuli (p = 0.2), and a fearful condition, in which neutral expressions were standard stimuli (p = 0.8) and fearful expressions were deviant stimuli (p = 0.2). Participants were required to concentrate on the primary task of counting the central cross changes and to ignore the expressions to ensure that facial expression processing was automatic. Event-related potentials (ERPs) were obtained during the tasks. The visual mismatch negativity (vMMN) components were analyzed to index the automatic neural processing of facial expressions. For the early vMMN (50-130 ms), the high IQ group showed more negative vMMN amplitudes than the average IQ group in the happy condition. For the late vMMN (320-450 ms), the high IQ group had greater vMMN responses than the average IQ group over frontal and occipito-temporal areas in the fearful condition, and the average IQ group evoked larger vMMN amplitudes than the high IQ group over occipito-temporal areas in the happy condition. The present study elucidated the close relationships between fluid intelligence and pre-attentive change detection on social-emotional information.

  9. Fluid Intelligence and Automatic Neural Processes in Facial Expression Perception: An Event-Related Potential Study.

    Directory of Open Access Journals (Sweden)

    Tongran Liu

    Full Text Available The relationship between human fluid intelligence and social-emotional abilities has been a topic of considerable interest. The current study investigated whether adolescents with different intellectual levels had different automatic neural processing of facial expressions. Two groups of adolescent males were enrolled: a high IQ group and an average IQ group. Age and parental socioeconomic status were matched between the two groups. Participants counted the numbers of the central cross changes while paired facial expressions were presented bilaterally in an oddball paradigm. There were two experimental conditions: a happy condition, in which neutral expressions were standard stimuli (p = 0.8 and happy expressions were deviant stimuli (p = 0.2, and a fearful condition, in which neutral expressions were standard stimuli (p = 0.8 and fearful expressions were deviant stimuli (p = 0.2. Participants were required to concentrate on the primary task of counting the central cross changes and to ignore the expressions to ensure that facial expression processing was automatic. Event-related potentials (ERPs were obtained during the tasks. The visual mismatch negativity (vMMN components were analyzed to index the automatic neural processing of facial expressions. For the early vMMN (50-130 ms, the high IQ group showed more negative vMMN amplitudes than the average IQ group in the happy condition. For the late vMMN (320-450 ms, the high IQ group had greater vMMN responses than the average IQ group over frontal and occipito-temporal areas in the fearful condition, and the average IQ group evoked larger vMMN amplitudes than the high IQ group over occipito-temporal areas in the happy condition. The present study elucidated the close relationships between fluid intelligence and pre-attentive change detection on social-emotional information.

  10. Potential roles for prions and protein-only inheritance in cancer

    Science.gov (United States)

    Antony, H; Wiegmans, AP; Wei, MQ; Chernoff, YO; Khanna, KK; Munn, AL

    2011-01-01

    Inherited mutations are known to cause familial cancers. However, the cause of sporadic cancers, which likely represent the majority of cancers, is yet to be elucidated. Sporadic cancers contain somatic mutations (including oncogenic mutations), however, the origin of these mutations is unclear. An intriguing possibility is that a stable alteration occurs in somatic cells prior to oncogenic mutations and promotes the subsequent accumulation of oncogenic mutations. This review explores the possible role of prions and protein-only inheritance in cancer. Genetic studies using lower eukaryotes, primarily yeast, have identified a large number of proteins as prions that confer dominant phenotypes with cytoplasmic (non-Mendelian) inheritance. Many of these have mammalian functional homologs. The human prion protein (PrP) is known to cause neurodegenerative diseases and has now been found to be up-regulated in multiple cancers. PrP expression in cancer cells contributes to cancer progression and resistance to various cancer therapies. Epigenetic changes in gene expression and hyper-activation of MAP kinase (MAPK) signalling, processes that in lower eukaryotes are affected by prions, play important roles in oncogenesis in humans. Prion phenomena in yeast appear to be influenced by stresses and there is considerable evidence for association of some amyloids with biologically positive functions. This suggests that if protein-only somatic inheritance exists in mammalian cells, it might contribute to cancer phenotypes. Here we highlight evidence in the literature for an involvement of prion or prion-like mechanisms in cancer and how they may in the future be viewed as diagnostic markers and potential therapeutic targets. PMID:22138778

  11. Potential Role of Dipeptidyl Peptidase IV in the Pathophysiology of Heart Failure

    Directory of Open Access Journals (Sweden)

    Thiago A. Salles

    2015-02-01

    Full Text Available Dipeptidyl peptidase IV (DPPIV is a widely expressed multifunctional serine peptidase that exists as a membrane-anchored cell surface protein or in a soluble form in the plasma and other body fluids. Numerous substrates are cleaved at the penultimate amino acid by DPPIV, including glucagon-like peptide-1 (GLP-1, brain natriuretic peptide (BNP and stromal cell-derived factor-1 (SDF-α, all of which play important roles in the cardiovascular system. In this regard, recent reports have documented that circulating DPPIV activity correlates with poorer cardiovascular outcomes in human and experimental heart failure (HF. Moreover, emerging evidence indicates that DPPIV inhibitors exert cardioprotective and renoprotective actions in a variety of experimental models of cardiac dysfunction. On the other hand, conflicting results have been found when translating these promising findings from preclinical animal models to clinical therapy. In this review, we discuss how DPPIV might be involved in the cardio-renal axis in HF. In addition, the potential role for DPPIV inhibitors in ameliorating heart disease is revised, focusing on the effects of the main DPPIV substrates on cardiac remodeling and renal handling of salt and water.

  12. Role of regenerating gene IA expression on local invasion and survival in nasopharyngeal carcinoma.

    Science.gov (United States)

    Xing, Haijie; Chen, Xiangdong; Han, Yaofeng

    2017-11-21

    Regenerating gene IA (REGIA) plays an important role in tissue regeneration and tumors prognosis of epithelium origin. However, the role of REGIA in nasopharyngeal carcinoma (NPC) is unclear. This study aims to investigate the expression and function of REG1A in NPC. We have found that there was 63 patients with REGIA positive expression of 155 patients in this study (40.65%). The positive expression rate of REGIA was 30.50, 44.44 and 47.83% in stage T2, T3 and T4 patients, respectively. The REGIA expression was significantly difference in T2 and T4 stage tumors or T2 and T3-T4 stage. The positive expression rate of REGIA was found to be higher in patients with cervical lymph node persistence than those with cervical lymph node complete regression. Patients with negative REGIA expression had a better overall survival and free survival than those with REGIA positive expression. In addition, according to the univariate and multivariate analysis, the REGIA expression was an independent adverse prognostic factor for NPC patients. REGIA expression was a useful biomarker in NPC patients for assessing T stage and survival.

  13. On the potential role of glutamate transport in mental fatigue

    Directory of Open Access Journals (Sweden)

    Hansson Elisabeth

    2004-11-01

    Full Text Available Abstract Mental fatigue, with decreased concentration capacity, is common in neuroinflammatory and neurodegenerative diseases, often appearing prior to other major mental or physical neurological symptoms. Mental fatigue also makes rehabilitation more difficult after a stroke, brain trauma, meningitis or encephalitis. As increased levels of proinflammatory cytokines are reported in these disorders, we wanted to explore whether or not proinflammatory cytokines could induce mental fatigue, and if so, by what mechanisms. It is well known that proinflammatory cytokines are increased in major depression, "sickness behavior" and sleep deprivation, which are all disorders associated with mental fatigue. Furthermore, an influence by specific proinflammatory cytokines, such as interleukin (IL-1, on learning and memory capacities has been observed in several experimental systems. As glutamate signaling is crucial for information intake and processing within the brain, and due to the pivotal role for glutamate in brain metabolism, dynamic alterations in glutamate transmission could be of pathophysiological importance in mental fatigue. Based on this literature and observations from our own laboratory and others on the role of astroglial cells in the fine-tuning of glutamate neurotransmission we present the hypothesis that the proinflammatory cytokines tumor necrosis factor-α, IL-1β and IL-6 could be involved in the pathophysiology of mental fatigue through their ability to attenuate the astroglial clearance of extracellular glutamate, their disintegration of the blood brain barrier, and effects on astroglial metabolism and metabolic supply for the neurons, thereby attenuating glutamate transmission. To test whether our hypothesis is valid or not, brain imaging techniques should be applied with the ability to register, over time and with increasing cognitive loading, the extracellular concentrations of glutamate and potassium (K+ in humans suffering from

  14. On the potential role of glutamate transport in mental fatigue.

    Science.gov (United States)

    Rönnbäck, Lars; Hansson, Elisabeth

    2004-11-04

    Mental fatigue, with decreased concentration capacity, is common in neuroinflammatory and neurodegenerative diseases, often appearing prior to other major mental or physical neurological symptoms. Mental fatigue also makes rehabilitation more difficult after a stroke, brain trauma, meningitis or encephalitis. As increased levels of proinflammatory cytokines are reported in these disorders, we wanted to explore whether or not proinflammatory cytokines could induce mental fatigue, and if so, by what mechanisms.It is well known that proinflammatory cytokines are increased in major depression, "sickness behavior" and sleep deprivation, which are all disorders associated with mental fatigue. Furthermore, an influence by specific proinflammatory cytokines, such as interleukin (IL)-1, on learning and memory capacities has been observed in several experimental systems. As glutamate signaling is crucial for information intake and processing within the brain, and due to the pivotal role for glutamate in brain metabolism, dynamic alterations in glutamate transmission could be of pathophysiological importance in mental fatigue. Based on this literature and observations from our own laboratory and others on the role of astroglial cells in the fine-tuning of glutamate neurotransmission we present the hypothesis that the proinflammatory cytokines tumor necrosis factor-alpha, IL-1beta and IL-6 could be involved in the pathophysiology of mental fatigue through their ability to attenuate the astroglial clearance of extracellular glutamate, their disintegration of the blood brain barrier, and effects on astroglial metabolism and metabolic supply for the neurons, thereby attenuating glutamate transmission. To test whether our hypothesis is valid or not, brain imaging techniques should be applied with the ability to register, over time and with increasing cognitive loading, the extracellular concentrations of glutamate and potassium (K+) in humans suffering from mental fatigue. At

  15. Expression profiling of the RPE in zebrafish smarca4 mutant revealed altered signals that potentially affect RPE and retinal differentiation

    Science.gov (United States)

    Ma, Ping; Collery, Ross; Trowbridge, Sara; Zhong, Wenxuan; Leung, Yuk Fai

    2014-01-01

    retina and the RPE of zebrafish mutants in which both of these tissues are affected by the underlying mutation. Specifically, we have used the method to identify a group of 39 genes that can potentially explain the melanogenesis defect in the smarca4 RPE. In addition, several genes in this group are secreted signaling molecules. Thus, this observation further implicates that the smarca4 RPE might play a role in the retinal dystrophic phenotype in smarca4. PMID:24426776

  16. Cannabinoids: is there a potential treatment role in epilepsy?

    Science.gov (United States)

    Blair, Robert E; Deshpande, Laxmikant S; DeLorenzo, Robert J

    2015-01-01

    Cannabinoids have been used medicinally for centuries, and in the last decade, attention has focused on their broad therapeutic potential particularly in seizure management. While some cannabinoids have demonstrated anticonvulsant activity in experimental studies, their efficacy for managing clinical seizures has not been fully established. This commentary will touch on our understanding of the brain endocannabinoid system's regulation of synaptic transmission in both physiological and pathophysiological conditions, and review the findings from both experimental and clinical studies on the effectiveness of cannabinoids to suppress epileptic seizures. At present, there is preliminary evidence that non-psychoactive cannabinoids may be useful as anticonvulsants, but additional clinical trials are needed to fully evaluate the efficacy and safety of these compounds for the treatment of epilepsy.

  17. The potential roles of nanobiomaterials in distraction osteogenesis.

    Science.gov (United States)

    Makhdom, Asim M; Nayef, Lamees; Tabrizian, Maryam; Hamdy, Reggie C

    2015-01-01

    Distraction osteogenesis (DO) technique is used worldwide to treat many orthopedic conditions. Although successful, one limitation of this technique is the extended period of fixators until the bone is consolidated. The application of growth factors (GFs) is one promising approach to accelerate bone regeneration during DO. Despite promising in vivo results, its use is still limited in the clinic. This is secondary to inherent limitations of these GFs. Therefore, a development of delivery systems that allow sustained sequential release is necessary. Nanoparticles and nanocomposites have prevailing properties that can overcome the limitations of the current delivery systems. In addition, their use can overcome the current challenges associated with the insufficient mechanical properties of scaffolds and suboptimal osteogenic differentiation of transplanted cells in the distraction gap. We discuss the clinical implications, and potential early applications of the nanoparticles and nanocomposites for developing new treatments to accelerate bone regeneration in DO. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. The role of local voltage potentials in outflow tract ectopy

    DEFF Research Database (Denmark)

    Thomsen, P.E.B.; Johannessen, A.; Jons, C.

    2010-01-01

    Discrete, fragmented, local voltage potentials (LVPs) have been observed in electrograms recorded at the ablation site in patients undergoing radiofrequency ablation for arrhythmias originating in both the right and left ventricular outflow tract; however, the incidence and the significance...... of the LVP with respect to arrhythmogenesis is uncertain. We studied 25 patients with outflow tract arrhythmias referred for radiofrequency catheter ablation and recorded high-amplified intracardiac electrograms close to the site of origin of the arrhythmia. Ten patients undergoing ablation...... in the ventricular premature beats. In 10 patients, ventricular parasystole was suggested by varying coupling intervals > 100 ms, and fusion beats allowing for the estimation of the least common denominator of R-R intervals. In 23 of the 25 patients, the 12-lead electrocardiogram (ECG) and intracardiac contact...

  19. Role of Site-Specific N-Glycans Expressed on GluA2 in the Regulation of Cell Surface Expression of AMPA-Type Glutamate Receptors.

    Directory of Open Access Journals (Sweden)

    Yusuke Takeuchi

    Full Text Available The AMPA-type glutamate receptor (AMPAR, which is a tetrameric complex composed of four subunits (GluA1-4 with several combinations, mediates the majority of rapid excitatory synaptic transmissions in the nervous system. Cell surface expression levels of AMPAR modulate synaptic plasticity, which is considered one of the molecular bases for learning and memory formation. To date, a unique trisaccharide (HSO3-3GlcAβ1-3Galβ1-4GlcNAc, human natural killer-1 (HNK-1 carbohydrate, was found expressed specifically on N-linked glycans of GluA2 and regulated the cell surface expression of AMPAR and the spine maturation process. However, evidence that the HNK-1 epitope on N-glycans of GluA2 directly affects these phenomena is lacking. Moreover, it is thought that other N-glycans on GluA2 also have potential roles in the regulation of AMPAR functions. In the present study, using a series of mutants lacking potential N-glycosylation sites (N256, N370, N406, and N413 within GluA2, we demonstrated that the mutant lacking the N-glycan at N370 strongly suppressed the intracellular trafficking of GluA2 from the endoplasmic reticulum (ER in HEK293 cells. Cell surface expression of GluA1, which is a major subunit of AMPAR in neurons, was also suppressed by co-expression of the GluA2 N370S mutant. The N370S mutant and wild-type GluA2 were co-immunoprecipitated with GluA1, suggesting that N370S was properly associated with GluA1. Moreover, we found that N413 was the main potential site of the HNK-1 epitope that promoted the interaction of GluA2 with N-cadherin, resulting in enhanced cell surface expression of GluA2. The HNK-1 epitope on N-glycan at the N413 of GluA2 was also involved in the cell surface expression of GluA1. Thus, our data suggested that site-specific N-glycans on GluA2 regulate the intracellular trafficking and cell surface expression of AMPAR.

  20. The potential role of dopamine D₃ receptor neurotransmission in cognition.

    Science.gov (United States)

    Nakajima, Shinichiro; Gerretsen, Philip; Takeuchi, Hiroyoshi; Caravaggio, Fernando; Chow, Tiffany; Le Foll, Bernard; Mulsant, Benoit; Pollock, Bruce; Graff-Guerrero, Ariel

    2013-08-01

    Currently available treatments have limited pro-cognitive effects for neuropsychiatric disorders, such as schizophrenia, Parkinson's disease and Alzheimer's disease. The primary objective of this work is to review the literature on the role of dopamine D₃ receptors in cognition, and propose dopamine D₃ receptor antagonists as possible cognitive enhancers for neuropsychiatric disorders. A literature search was performed to identify animal and human studies on D₃ receptors and cognition using PubMed, MEDLINE and EMBASE. The search terms included "dopamine D₃ receptor" and "cognition". The literature search identified 164 articles. The results revealed: (1) D₃ receptors are associated with cognitive functioning in both healthy individuals and those with neuropsychiatric disorders; (2) D₃ receptor blockade appears to enhance while D₃ receptor agonism seems to impair cognitive function, including memory, attention, learning, processing speed, social recognition and executive function independent of age; and (3) D₃ receptor antagonists may exert their pro-cognitive effect by enhancing the release of acetylcholine in the prefrontal cortex, disinhibiting the activity of dopamine neurons projecting to the nucleus accumbens or prefrontal cortex, or activating CREB signaling in the hippocampus. These findings suggest that D₃ receptor blockade may enhance cognitive performance in healthy individuals and treat cognitive dysfunction in individuals with a neuropsychiatric disorder. Clinical trials are needed to confirm these effects. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

  1. SLE and pregnancy: the potential role for regulatory T cells.

    Science.gov (United States)

    Tower, Clare; Crocker, Ian; Chirico, Debora; Baker, Philip; Bruce, Ian

    2011-02-01

    Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder that disproportionally affects women, especially in their reproductive years. SLE is associated with considerable pregnancy-related morbidity--including fetal loss, preterm birth, fetal growth restriction and pre-eclampsia. CD4+CD25+ regulatory T (T(REG)) cells have a potent immunosuppressive function and contribute to immunological self-tolerance. These cells might be essential for successful placental development by ensuring fetal tolerance. The numbers of T(REG) cells are augmented during normal pregnancy and, conversely, diminished numbers are associated with pregnancy loss and pre-eclampsia. Several studies have shown that patients with SLE have decreased numbers of T(REG) cells that might be functionally defective. This defective T(REG) cell functioning could predispose women with SLE to pregnancy complications. This article provides an overview of current knowledge of the role and function of T(REG) cells in SLE and pregnancy and how these cells might contribute to improving pregnancy-related outcomes in patients with SLE in the future.

  2. The Potential Role of Satellites in Detecting and Tracking Tsunamis

    Science.gov (United States)

    Allan, T.

    2007-12-01

    Until the morning of December 26 2004 it was not entirely clear if a radar altimeter in polar-orbit around the Earth could detect a low amplitude tsunami wave travelling at high speed across the ocean surface. The answer came when by chance the satellite Jason flew over the Indian Ocean on that fateful morning and recorded a double- peaked wave with peak-to-trough amplitude of 80 cm. A constellation of fit-for-purpose microsatellites, equipped with radar altimeters, had already been proposed as a means of delivering continuous global observations on sea state to ships, platforms and forecasting centres. It will be demonstrated through a computer animation how such a system, working in conjunction with the global network of ground stations for detecting undersea earthquakes, could be instantly switched to pick up and track the progress of a tsunami. Furthermore, all studies carried out to date on the role of ocean currents and eddies in determining the global transport of heat, and its effect on future climate, have concluded that finer spatial resolution is required than that achieved today. It will be shown how this requirement could also be met by a constellation of altimeters. Various schemes for operating such a system will be discussed.

  3. Peripheral artery disease: potential role of ACE-inhibitor therapy

    Directory of Open Access Journals (Sweden)

    Giuseppe Coppola

    2008-12-01

    Full Text Available Giuseppe Coppola, Giuseppe Romano, Egle Corrado, Rosa Maria Grisanti, Salvatore NovoDepartment of Internal Medicine, Cardiovascular and Nephro-Urological Diseases, Chair of Cardiovascular Disease, University of Palermo, Palermo, ItalyAbstract: Subjects with peripheral arterial disease (PAD of the lower limbs are at high risk for cardiovascular and cerebrovascular events and the prevalence of coronary artery disease in such patients is elevated. Recent studies have shown that regular use of cardiovascular medications, such as therapeutic and preventive agents for PAD patients, seems to be promising in reducing long-term mortality and morbidity. The angiotensin-converting-enzyme (ACE system plays an important role in the pathogenesis and progression of atherosclerosis, and ACE-inhibitors (ACE-I seem to have vasculoprotective and antiproliferative effects as well as a direct antiatherogenic effect. ACE-I also promote the degradation of bradykinin and the release of nitric oxide, a potent vasodilator; further, thay have shown important implications for vascular oxidative stress. Other studies have suggested that ACE-I may also improve endothelial dysfunction. ACE-I are useful for reducing the risk of cardiovascular events in clinical and subclinical PAD. Particularly, one agent of the class (ie, ramipril has shown in many studies to able to significantly reduce cardiovascular morbidity and mortality in patients with PAD.Keywords: atherosclerosis, peripheral arterial disease, endothelial dysfunction, ACE-inhibitors

  4. [Potential role of the angiogenic factor "EG-VEGF" in gestational trophoblastic diseases].

    Science.gov (United States)

    Boufettal, H; Feige, J-J; Benharouga, M; Aboussaouira, T; Nadifi, S; Mahdaoui, S; Samouh, N; Alfaidy, N

    2013-10-01

    Gestational trophoblastic disease (MGT) includes a wide spectrum of pathologies of the placenta, ranging from benign precancerous lesions, with gestational trophoblastic tumors. Metastases are the leading causes of death as a result of this tumor. They represent a major problem for obstetrics and for the public health system. To date, there is no predictor of the progression of molar pregnancies to gestational trophoblastic tumor (GTT). Only an unfavorable plasma hCG monitoring after evacuation of hydatidiform mole is used to diagnose a TTG. The causes of the development of this cancer are still poorly understood. Increasing data in the literature suggests a close association between the development of this tumor and poor placental vascularization during the first trimester of pregnancy. The development of the human placenta depends on a coordination between the trophoblast and endothelial cells. A disruption in the expression of angiogenic factors could contribute to uterine or extra-uterine tissue invasion by extravillous trophoblast, contributing to the development of TTG. This review sheds lights on the phenomenon of angiogenesis during normal and abnormal placentation, especially during the MGT and reports preliminary finding concerning, the variability of expression of "Endocrine Gland-Derived Vascular Endothelial Growth Factor" (EG-VEGF), a specific placental angiogenic factor, in normal and molar placentas, and the potential role of differentiated expressions of the main placental angiogenic factors in the scalability of hydatidiform moles towards a recovery or towards the development of gestational trophoblastic tumor. Deciphering the mechanisms by which the angiogenic factor influences these processes will help understand the pathophysiology of MGT and to create opportunities for early diagnosis and treatment of the latter. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  5. Potential role of rivaroxaban in patients with acute coronary syndrome

    Directory of Open Access Journals (Sweden)

    Fitchett DH

    2012-11-01

    Full Text Available David H FitchettDivision of Cardiology, Department of Medicine, St Michael's Hospital, University of Toronto, Toronto, Ontario, CanadaAbstract: Patients with acute coronary syndrome (ACS continue to be at risk for recurrent ischemic events, despite an early invasive strategy and the use of dual antiplatelet therapy. The anticoagulant pathway remains activated for a prolonged period after ACS and, consequently, has been a target for treatment. Early studies with warfarin indicated its benefit, but the risk of bleeding and the complexities of warfarin anticoagulation resulted in little use of this strategy. Rivaroxaban, apixaban, and dabigatran are new specific inhibitors of anticoagulant factors (Xa or IIa currently available for the prevention of thrombosis and/or thromboembolism. Thus far, studies with dabigatran and apixaban in ACS have shown no clinical benefit and bleeding has been increased. The ATLAS ACS 2-TIMI 51 trial observed the impact of rivaroxaban 2.5 mg and 5 mg twice daily in patients with recent ACS receiving current management (both early invasive strategy and dual antiplatelet therapy with aspirin and clopidogrel over a follow-up period of over 1 year. Rivaroxaban 2.5 mg twice daily reduced cardiovascular death, myocardial infarction, or stroke by 16%, and both cardiovascular and all-cause mortality by approximately 20%. Although major bleeding increased from 0.6% to 2.1% and intracranial hemorrhage from 0.2% to 0.6%, there was no increase in fatal bleeding. The role of rivaroxaban in the management of ACS is discussed in this review. The reduction in mortality is the main finding that could lead to the use of rivaroxaban in the management of ACS in high-risk individuals with a low bleeding risk.Keywords: cardiovascular death, myocardial infarction, stroke, anticoagulation, bleeding risk

  6. Review: MicroRNAs in assisted reproduction and their potential role in IVF failure.

    Science.gov (United States)

    Siristatidis, Charalampos; Vogiatzi, Paraskevi; Brachnis, Nikos; Liassidou, Aspasia; Iliodromiti, Zoe; Bettocchi, Stefano; Chrelias, Charalampos

    2015-01-01

    MicroRNAs (miRNAs) have recently emerged as important regulators of gene expression stability. In the endometrium, miRNAs are involved in the dynamic changes associated with the menstrual cycle, implicated in implantation and in reproductive disorders. We performed a review in an attempt to assess the potential biological pathways linking altered miRNAs profiles with in vitro fertilisation (IVF) failure. Crucially, as miRNAs appear to have a significant role in the course of reproduction, they are excellent research candidates with the potential to enable a better understanding over the underlying molecular activities that prevent implantation and further progression of the embryo. Further steps include in-depth pathway mapping of the implantation process and the characterization of the respective miRNAs and associated links. The efficiency of any intervention should determine whether miRNA profiling could possibly be adopted in routine practice to substantially improve the diagnostic accuracy and, in parallel, the directed treatment of the next-generation IVF. Copyright © 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  7. Extracellular Vesicles from Adipose Tissue—A Potential Role in Obesity and Type 2 Diabetes?

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    Xuan Gao

    2017-08-01

    Full Text Available Adipose tissue plays a key role in the development of insulin resistance and its pathological sequelae, such as type 2 diabetes and non-alcoholic fatty liver disease. Dysfunction in the adipose tissue response to storing excess fatty acids as triglyceride can lead to adipose tissue inflammation and spillover of fatty acids from this tissue and accumulation of fatty acids as lipid droplets in ectopic sites, such as liver and muscle. Extracellular vesicles (EVs are released from adipocytes and have been proposed to be involved in adipocyte/macrophage cross talk and to affect insulin signaling and transforming growth factor β expression in liver cells leading to metabolic disease. Furthermore EV produced by adipose tissue-derived mesenchymal stem cells (ADSC can promote angiogenesis and cancer cell migration and have neuroprotective and neuroregenerative properties. ADSC EVs have therapeutic potential in vascular and neurodegenerative disease and may also be used to target specific functional miRNAs to cells. Obesity is associated with an increase in adipose-derived EV which may be related to the metabolic complications of obesity. In this review, we discuss our current knowledge of EV produced by adipose tissue and the potential impact of adipose tissue-derived EV on metabolic diseases associated with obesity.

  8. Evapotranspiration Cycles in a High Latitude Agroecosystem: Potential Warming Role

    Science.gov (United States)

    Ruairuen, Watcharee

    2015-01-01

    As the acreages of agricultural lands increase, changes in surface energetics and evapotranspiration (ET) rates may arise consequently affecting regional climate regimes. The objective of this study was to evaluate summertime ET dynamics and surface energy processes in a subarctic agricultural farm in Interior Alaska. The study includes micrometeorological and hydrological data. Results covering the period from June to September 2012 and 2013 indicated consistent energy fractions: LE/Rnet (67%), G/Rnet (6%), H/Rnet (27%) where LE is latent heat flux, Rnet is the surface net radiation, G is ground heat flux and H is the sensible heat flux. Additionally actual surface evapotranspiration from potential evaporation was found to be in the range of 59 to 66%. After comparing these rates with those of most prominent high latitude ecosystems it is argued here that if agroecosystem in high latitudes become an emerging feature in the land-use, the regional surface energy balance will significantly shift in comparison to existing Arctic natural ecosystems. PMID:26368123

  9. Somatic growth of lean children: the potential role of sleep.

    Science.gov (United States)

    Jiang, Yan-Rui; Spruyt, Karen; Chen, Wen-Juan; Shen, Xiao-Ming; Jiang, Fan

    2014-08-01

    Despite the current obesity pandemic, childhood malnutrition remains an urgent, public health concern. Similar to the obesity pandemic, childhood malnutrition is influenced by genetic and a number of social, environmental and biological factors. In this study, we investigated the association between sleep duration and somatic growth in lean children. A stratified, randomly clustered sampling design was used to select fifth grade students from 10 primary schools in Shanghai. Based on a body mass index below the 15th percentile a subsample of 143 lean children aged 10-11 years old was defined. Sleep duration and other potential confounders were surveyed through parental or self-report questionnaires. Body measurements were collected and used to calculate the Z score of weight, height, body mass index as well as body fat percentage. Compared with children who slept gained more weight after adjusting for confounding factors. When children slept 9-10 hours, they had significantly higher Z score of weight and body mass index. Prolonged sleep not only benefits weight gain but also improves height in lean children. Our findings might provide important public health advice such that prolonged sleep may be an effective modifier of nutritional problems in childhood.

  10. Salmonella-mediated cancer therapy: Roles and potential

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Vu Hong [Dept. of Experimental TherapeuticsBeckman Research Institute of City of Hope, Duarte (United States); Min, Jung Joon [Dept. of Nuclear MedicineChonnam National University Medical School, Gwangju (Korea, Republic of)

    2017-06-15

    The use of bacteria for cancer therapy, which was proposed many years ago, was not recognized as a potential therapeutic strategy until recently. Technological advances and updated knowledge have enabled the genetic engineering of bacteria for their safe and effective application in the treatment of cancer. The efficacy of radiotherapy depends mainly on tissue oxygen levels, and low oxygen concentrations in necrotic and hypoxic regions are a common cause of treatment failure. In addition, the distribution of a drug is important for the therapeutic effect of chemotherapy, and the poor vasculature in tumors impairs drug delivery, limiting the efficacy of a drug, especially in necrotic and hypoxic regions. Bacteria-mediated cancer therapy (BMCT) relies on facultative anaerobes that can survive in well or poorly oxygenated regions, and it therefore improves the therapeutic efficacy drug distribution throughout the tumor mass. Since the mid-1990s, the number of published bacterial therapy papers has increased rapidly, with a doubling time of 2.5 years in which the use of Salmonella increased significantly. BMCT is being reevaluated to overcome some of the drawbacks of conventional therapies. This review focuses on Salmonella-mediated cancer therapy as the most widely used type of BMCT.{sub 2}.

  11. Potential role of punicalagin against oxidative stress induced testicular damage

    Directory of Open Access Journals (Sweden)

    Faiza Rao

    2016-01-01

    Full Text Available Punicalagin is isolated from pomegranate and widely used for the treatment of different diseases in Chinese traditional medicine. This study aimed to evaluate the effect of Punicalagin (purity ≥98% on oxidative stress induced testicular damage and its effect on fertility. We detected the antioxidant potential of punicalagin in lipopolysaccharide (LPS induced oxidative stress damage in testes, also tried to uncover the boosting fertility effect of Punicalagin (PU against oxidative stress-induced infertility. Results demonstrated that 9 mg kg−1 for 7 days treatment significantly decreases LPS induced oxidative damage in testes and nitric oxide production. The administration of oxidative stress resulted in a significant reduction in testes antioxidants GSH, T-SOD, and CAT raised LPO, but treatment with punicalagin for 7 days increased antioxidant defense GSH, T-SOD, and CAT by the end of the experiment and reduced LPO level as well. PU also significantly activates Nrf2, which is involved in regulation of antioxidant defense systems. Hence, the present research categorically elucidates the protective effect of punicalagin against LPS induced oxidative stress induced perturbation in the process of spermatogenesis and significantly increased sperm health and number. Moreover, fertility success significantly decreased in LPS-injected mice compared to controls. Mice injected with LPS had fertility indices of 12.5%, while others treated with a combination of PU + LPS exhibited 75% indices. By promoting fertility and eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of infertility.

  12. Potential role of punicalagin against oxidative stress induced testicular damage.

    Science.gov (United States)

    Rao, Faiza; Tian, Hui; Li, Wenqing; Hung, Helong; Sun, Fei

    2016-01-01

    Punicalagin is isolated from pomegranate and widely used for the treatment of different diseases in Chinese traditional medicine. This study aimed to evaluate the effect of Punicalagin (purity ≥98%) on oxidative stress induced testicular damage and its effect on fertility. We detected the antioxidant potential of punicalagin in lipopolysaccharide (LPS) induced oxidative stress damage in testes, also tried to uncover the boosting fertility effect of Punicalagin (PU) against oxidative stress-induced infertility. Results demonstrated that 9 mg kg-1 for 7 days treatment significantly decreases LPS induced oxidative damage in testes and nitric oxide production. The administration of oxidative stress resulted in a significant reduction in testes antioxidants GSH, T-SOD, and CAT raised LPO, but treatment with punicalagin for 7 days increased antioxidant defense GSH, T-SOD, and CAT by the end of the experiment and reduced LPO level as well. PU also significantly activates Nrf2, which is involved in regulation of antioxidant defense systems. Hence, the present research categorically elucidates the protective effect of punicalagin against LPS induced oxidative stress induced perturbation in the process of spermatogenesis and significantly increased sperm health and number. Moreover, fertility success significantly decreased in LPS-injected mice compared to controls. Mice injected with LPS had fertility indices of 12.5%, while others treated with a combination of PU + LPS exhibited 75% indices. By promoting fertility and eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of infertility.

  13. The potential role of exercise in neuro-oncology

    Directory of Open Access Journals (Sweden)

    Prue eCormie

    2015-04-01

    Full Text Available Patients with brain and other central nervous system cancers experience debilitating physical, cognitive and emotional effects that significantly compromise quality of life. Few efficacious pharmacological strategies or supportive care interventions exist to ameliorate these sequelae and patients report high levels of unmet needs in these areas. There is strong theoretical rationale to suggest exercise may be an effective intervention to aid in the management of neuro-oncological disorders. Clinical research has established the efficacy of appropriate exercise in counteracting physical impairments such as fatigue and functional decline, cognitive impairment as well as psychological effects including depression and anxiety. While there is promise for exercise to enhance physical and psychosocial wellbeing of patients diagnosed with neurologic malignancies, these patients have unique needs and research is urgently required to explore optimal exercise prescription specific to these patients to maximise safety and efficacy. This perspective article is a discussion of potential rehabilitative effects of targeted exercise programs for patients with brain and other central nervous system cancers and highlights future research directions.

  14. Expression of antizyme inhibitor 2 in mast cells and role of polyamines as selective regulators of serotonin secretion.

    Science.gov (United States)

    Kanerva, Kristiina; Lappalainen, Jani; Mäkitie, Laura T; Virolainen, Susanna; Kovanen, Petri T; Andersson, Leif C

    2009-08-31

    Upon IgE-mediated activation, mast cells (MC) exocytose their cytoplasmic secretory granules and release a variety of bioactive substances that trigger inflammatory responses. Polyamines mediate numerous cellular and physiological functions. We report here that MCs express antizyme inhibitor 2 (AZIN2), an activator of polyamine biosynthesis, previously reported to be exclusively expressed in the brain and testis. We have investigated the intracellular localization of AZIN2 both in resting and activated MCs. In addition, we have examined the functional role of polyamines, downstream effectors of AZIN2, as potential regulators of MC activity. Immunostainings show that AZIN2 is expressed in primary and neoplastic human and rodent MCs. We demonstrate that AZIN2 localizes in the Vamp-8 positive, serotonin-containing subset of MC granules, but not in tryptase-containing granules, as revealed by double immunofluorescence stainings. Furthermore, activation of MCs induces rapid upregulation of AZIN2 expression and its redistribution, suggesting a role for AZIN2 in secretory granule exocytosis. We also demonstrate that release of serotonin from activated MCs is polyamine-dependent whereas release of histamine and beta-hexosaminidase is not, indicating a granule subtype-specific function for polyamines. The study reports for the first time the expression of AZIN2 outside the brain and testis, and demonstrates the intracellular localization of endogenous AZIN2 in MCs. The granule subtype-specific expression and its induction after MC activation suggest a role for AZIN2 as a local, in situ regulator of polyamine biosynthesis in association with serotonin-containing granules of MCs. Furthermore, our data indicates a novel function for polyamines as selective regulators of serotonin release from MCs.

  15. Expression of antizyme inhibitor 2 in mast cells and role of polyamines as selective regulators of serotonin secretion.

    Directory of Open Access Journals (Sweden)

    Kristiina Kanerva

    Full Text Available BACKGROUND: Upon IgE-mediated activation, mast cells (MC exocytose their cytoplasmic secretory granules and release a variety of bioactive substances that trigger inflammatory responses. Polyamines mediate numerous cellular and physiological functions. We report here that MCs express antizyme inhibitor 2 (AZIN2, an activator of polyamine biosynthesis, previously reported to be exclusively expressed in the brain and testis. We have investigated the intracellular localization of AZIN2 both in resting and activated MCs. In addition, we have examined the functional role of polyamines, downstream effectors of AZIN2, as potential regulators of MC activity. METHODOLOGY/PRINCIPAL FINDINGS: Immunostainings show that AZIN2 is expressed in primary and neoplastic human and rodent MCs. We demonstrate that AZIN2 localizes in the Vamp-8 positive, serotonin-containing subset of MC granules, but not in tryptase-containing granules, as revealed by double immunofluorescence stainings. Furthermore, activation of MCs induces rapid upregulation of AZIN2 expression and its redistribution, suggesting a role for AZIN2 in secretory granule exocytosis. We also demonstrate that release of serotonin from activated MCs is polyamine-dependent whereas release of histamine and beta-hexosaminidase is not, indicating a granule subtype-specific function for polyamines. CONCLUSIONS/SIGNIFICANCE: The study reports for the first time the expression of AZIN2 outside the brain and testis, and demonstrates the intracellular localization of endogenous AZIN2 in MCs. The granule subtype-specific expression and its induction after MC activation suggest a role for AZIN2 as a local, in situ regulator of polyamine biosynthesis in association with serotonin-containing granules of MCs. Furthermore, our data indicates a novel function for polyamines as selective regulators of serotonin release from MCs.

  16. A novel transposon construct expressing PhoA with potential for studying protein expression and translocation in Mycoplasma gallisepticum

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    Panicker Indu S

    2012-07-01

    Full Text Available Abstract Background Mycoplasma gallisepticum is a major poultry pathogen and causes severe economic loss to the poultry industry. In mycoplasmas lipoproteins are abundant on the membrane surface and play a critical role in interactions with the host, but tools for exploring their molecular biology are limited. Results In this study we examined whether the alkaline phosphatase gene (phoA from Escherichia coli could be used as a reporter in mycoplasmas. The promoter region from the gene for elongation factor Tu (ltuf and the signal and acylation sequences from the vlhA 1.1 gene, both from Mycoplasma gallisepticum , together with the coding region of phoA , were assembled in the transposon-containing plasmid pISM2062.2 (pTAP to enable expression of alkaline phosphatase (AP as a recombinant lipoprotein. The transposon was used to transform M. gallisepticum strain S6. As a control, a plasmid containing a similar construct, but lacking the signal and acylation sequences, was also produced (pTP and also introduced into M. gallisepticum . Using a colorimetric substrate for detection of alkaline phosphatase activity, it was possible to detect transformed M. gallisepticum . The level of transcription of phoA in organisms transformed with pTP was lower than in those transformed with pTAP, and alkaline phosphatase was not detected by immunoblotting or enzymatic assays in pTP transformants, eventhough alkaline phosphatase expression could be readily detected by both assays in pTAP transformants. Alkaline phosphatase was shown to be located in the hydrophobic fraction of transformed mycoplasmas following Triton X-114 partitioning and in the membrane fraction after differential fractionation. Trypsin proteolysis confirmed its surface exposure. The inclusion of the VlhA lipoprotein signal sequence in pTAP enabled translocation of PhoA and acylation of the amino terminal cysteine moiety, as confirmed by the effect of treatment with globomycin and radiolabelling

  17. The potential role of neuropathic mechanisms in dry eye syndromes.

    Science.gov (United States)

    Mcmonnies, Charles W

    Dry eye syndromes can involve both nociceptive and neuropathic symptoms. Nociceptive symptoms are the normal physiological responses to noxious stimuli. Neuropathic symptoms are caused by a lesion or disease of the somatosensory nervous system and can be the result of hypersensitisation of peripheral or central corneal and conjunctival somatosensory nerves. For example, inflammation could induce neuroplastic peripheral sensitisation of the ocular surface or lid wiper and exacerbate nociceptive symptoms. Neuropathic symptoms may explain the incommensurate relation between signs and symptoms in some dry eye syndromes although absence of signs of a dry eye syndrome may also be a consequence of inappropriate methods used when examining for them. Involvement of neuropathic mechanisms may also help explain dry eye symptoms which occur in association with reduced corneal sensitivity. This review includes a discussion of the potential for ocular symptoms involving neuropathic mechanisms to contribute to psychosocial problems such as depression, stress, anxiety and sleep disorders as well as for these types of psychosocial problems to contribute to neuropathic mechanisms and dry eye syndromes. Failure to consider the possibility that neuropathic mechanisms can contribute to dry eye syndromes may reduce accuracy of diagnosis and the suitability of treatment provided. Dry eye symptoms in the absence of commensurate evidence of tear dysfunction, and unsatisfactory response to tear dysfunction therapies should prompt consideration of neuropathic mechanisms being involved. Symptoms which persist after local anaesthetic instillation are more likely to be neuropathic in origin. Reducing inflammation may help limit any associated neuroplastic hypersensitivity. Copyright © 2016 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.

  18. Potential renovascular hypertension, space missions, and the role of magnesium

    Directory of Open Access Journals (Sweden)

    William J Rowe

    2009-11-01

    Full Text Available William J RoweFormer Assistant Clinical Professor of Medicine, Medical University of Ohio at Toledo, Keswick, VA, USAAbstract: Space flight (SF and dust inhalation in habitats cause hypertension whereas in SF (alone there is no consistent hypertension but reduced diurnal blood pressure (BP variation instead. Current pharmaceutical subcutaneous delivery systems are inadequate and there is impairment in the absorption, metabolism, excretion, and deterioration of some pharmaceuticals. Data obtained from the National Aeronautics and Space Administration through the Freedom of Information Act shows that Irwin returned from his 12-day Apollo 15 mission in 1971 and was administered a bicycle stress test. With just three minutes of exercise, his BP was >275/125 mm Hg (heart rate of only 130 beats per minute. There was no acute renal insult. Irwin’s apparent spontaneous remission is suggested to be related to the increase of a protective vasodilator, and his atrial natriuretic peptide (ANP reduced with SF because of reduced plasma volume. With invariable malabsorption and loss of bone/muscle storage sites, there are significant (P < 0.0001 reductions of magnesium (Mg required for ANP synthesis and release. Reductions of Mg and ANP can trigger pronounced angiotensin (200%, endothelin, and catecholamine elevations (clearly shown in recent years and vicious cycles between the latter and Mg deficits. There is proteinuria, elevated creatinine, and reduced renal concentrating ability with the potential for progressive inflammatory and oxidative stress-induced renal disease and hypertension with vicious cycles. After SF, animals show myocardial endothelial injuries and increased vascular resistance of extremities in humans. Even without dust, hypertension might eventually develop from renovascular hypertension during very long missions. Without sufficient endothelial protection from pharmaceuticals, a comprehensive gene research program should begin now

  19. Beyond Gender Stereotypes in Language Comprehension: Self Sex-Role Descriptions Affect the Brain's Potentials Associated with Agreement Processing.

    Science.gov (United States)

    Canal, Paolo; Garnham, Alan; Oakhill, Jane

    2015-01-01

    We recorded Event-Related Potentials to investigate differences in the use of gender information during the processing of reflexive pronouns. Pronouns either matched the gender provided by role nouns (such as "king" or "engineer") or did not. We compared two types of gender information, definitional information, which is semantic in nature (a mother is female), or stereotypical (a nurse is likely to be female). When they followed definitional role-nouns, gender-mismatching pronouns elicited a P600 effect reflecting a failure in the agreement process. When instead the gender violation occurred after stereotypical role-nouns the Event Related Potential response was biphasic, being positive in parietal electrodes and negative in anterior left electrodes. The use of a correlational approach showed that those participants with more "feminine" or "expressive" self sex-role descriptions showed a P600 response for stereotype violations, suggesting that they experienced the mismatch as an agreement violation; whereas less "expressive" participants showed an Nref effect, indicating more effort spent in linking the pronouns with the possible, although less likely, counter-stereotypical referent.

  20. Smoker Identity and Its Potential Role in Young Adults’ Smoking Behavior: A Meta-Ethnography

    Science.gov (United States)

    2015-01-01

    Objective: Identity is an important influence on behavior. To identify potential targets for smoking cessation interventions in young adults, we synthesized findings from qualitative studies on smoker identity and potential influences on smoking and smoking cessation. Methods: A systematic search of 4 electronic databases up to September 19, 2013, was conducted to identify qualitative studies on smoker identity in smokers and ex-smokers aged 16–34. Key concepts were extracted from individual studies and synthesized into higher-order interpretations by following the principles of meta-ethnography. Results: Seventeen relevant papers were identified. At the highest level of interpretation, we identified 4 types of findings: (a) contributory factors to identity, (b) identity in relation to smoking, (c) contextual and temporal patterning, and (d) behavior in relation to smoking. Contributory factors included the desire to establish aspirational individual and social identities, enact a smoker identity appropriate to the momentary social context, and alter personal nonsmoking rules when consuming alcohol. Smoker identity was multifaceted and incorporated individuals’ defensive rationalizations, and both positive and negative feelings attached to it. Smoker identities took time to develop, were subject to change, and were context dependent. Identity was found to play a role in quit attempts. Conclusions: Qualitative research into the identity of young adult smokers has established it as a multifaceted phenomenon serving important functions but also involving conflict and defensive rationalizations. It develops over time and contextual factors influence its expression. The nature of a smoker’s identity can play an important role in smoking cessation. PMID:25622078

  1. Smoker identity and its potential role in young adults' smoking behavior: A meta-ethnography.

    Science.gov (United States)

    Tombor, Ildiko; Shahab, Lion; Herbec, Aleksandra; Neale, Joanne; Michie, Susan; West, Robert

    2015-10-01

    Identity is an important influence on behavior. To identify potential targets for smoking cessation interventions in young adults, we synthesized findings from qualitative studies on smoker identity and potential influences on smoking and smoking cessation. A systematic search of 4 electronic databases up to September 19, 2013, was conducted to identify qualitative studies on smoker identity in smokers and ex-smokers aged 16-34. Key concepts were extracted from individual studies and synthesized into higher-order interpretations by following the principles of meta-ethnography. Seventeen relevant papers were identified. At the highest level of interpretation, we identified 4 types of findings: (a) contributory factors to identity, (b) identity in relation to smoking, (c) contextual and temporal patterning, and (d) behavior in relation to smoking. Contributory factors included the desire to establish aspirational individual and social identities, enact a smoker identity appropriate to the momentary social context, and alter personal nonsmoking rules when consuming alcohol. Smoker identity was multifaceted and incorporated individuals' defensive rationalizations, and both positive and negative feelings attached to it. Smoker identities took time to develop, were subject to change, and were context dependent. Identity was found to play a role in quit attempts. Qualitative research into the identity of young adult smokers has established it as a multifaceted phenomenon serving important functions but also involving conflict and defensive rationalizations. It develops over time and contextual factors influence its expression. The nature of a smoker's identity can play an important role in smoking cessation. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

  2. Spatial heterogeneity of myocardial perfusion predicts local potassium channel expression and action potential duration.

    Science.gov (United States)

    Stoll, Marion; Quentin, Michael; Molojavyi, Andrej; Thämer, Volker; Decking, Ulrich K M

    2008-02-01

    In the heart, there is not only a transmural gradient of left ventricular perfusion and action potential duration (APD), but also spatial heterogeneity within each myocardial layer, where local blood flow and energy turnover vary more than three-fold between individual regions. We analysed at high spatial resolution whether a corresponding heterogeneity also extends to ion channel gene expression and APD. In the open-chest beagle dog, left ventricular 300 microL samples of very low or high flow were identified by radioactive microspheres and expression levels determined by quantitative PCR. The distribution of epicardial APD was assessed by mapping local activation repolarization intervals (ARIs) and QT interval (QT). ERG, the potassium channel mediating IKr, and KChIP2, the interacting protein modulating Ito, were increased in Low flow (3.3- and 2.5-fold, P channel expression and APD. Whenever this newly recognized intramural dispersion of APD increases, it may contribute to arrhythmogenesis.

  3. Clinicopathological significance and prognostic role of EZH2 expression in non-small cell lung cancer.

    Science.gov (United States)

    Kim, Nae Yu; Pyo, Jung-Soo

    2017-07-01

    The aim of this study was to investigate the clinicopathological characteristics and prognostic role of enhancer of zeste homologue 2 (EZH2) expression in non-small cell lung cancer (NSCLC). The correlation between EZH2 expression and the clinicopathological characteristics, including sex, smoking history, tumor differentiation, histologic type, tumor stage, and lymph node metastasis, was evaluated through a meta-analysis. In addition, the prognostic value of EZH2 expression was elucidated. This study included 1,932 patients with NSCLC from 11 eligible studies. The overall rate of EZH2 expression was 0.548 [95% confidence interval (CI) 0.491-0.604]. There were significant correlations between EZH2 expression and male sex and smoking history. The expression rate of EZH2 was significantly lower in adenocarcinoma than in other histologic types. Furthermore, EZH2 expression rates were higher in NSCLC with moderately and poorly differentiation and nodal disease than in well-differentiated NSCLC without nodal disease. There was a significant correlation between EZH2 expression and worse overall and disease-free survival [hazard ratio (HR) 1.938, 95% CI 1.617-2.323 and HR 1.713, 95% CI 1.366-2.149, respectively]. Subgroup analysis revealed no significant difference for the prognostic effect of EZH2 expression between histologic types or detection methods. Our data collectively suggest that EZH2 expression is significantly correlated with aggressive tumor behavior and poor prognosis in NSCLC. Copyright © 2017 Elsevier GmbH. All rights reserved.

  4. The potential role of vitamin D in the link between obesity and asthma severity/control in children.

    Science.gov (United States)

    Vo, Phuong; Bair-Merritt, Megan; Camargo, Carlos A

    2015-06-01

    Childhood obesity and asthma are major public health problems. Obesity is not only associated with increased risk of incident asthma, but it may worsen asthma severity/control. Although the mechanisms linking obesity with asthma expression have not been completely elucidated, evidence suggests that increased frequency of acute respiratory infection (ARI) and decreased corticosteroid responsiveness may help to explain how obesity worsens asthma expression. In addition, obese individuals have low vitamin D status, and emerging evidence suggests vitamin D affects risk of ARI and corticosteroid responsiveness in individuals with asthma. In this review, we summarize the association between obesity and asthma severity/control in children and discuss ARI and corticosteroid responsiveness as potential mediators in the obesity-asthma pathway. We also discuss the potential role of vitamin D, including a brief summary of recent randomized controlled trials of vitamin D supplementation.

  5. Radiation Therapy Overcomes Adverse Prognostic Role of Cyclooxygenase-2 Expression on Reed-Sternberg Cells in Early Hodgkin Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Mestre, Francisco [Service of Radiation Therapy, University Hospital Son Espases, Instituto de Investigación Sanitaria de Palma, Palma de Mallorca (Spain); Gutiérrez, Antonio, E-mail: antoniom.gutierrez@ssib.es [Service of Hematology, University Hospital Son Espases, Instituto de Investigación Sanitaria de Palma, Palma de Mallorca (Spain); Rodriguez, Jose [MD Anderson Cancer Center, Madrid (Spain); Ramos, Rafael [Service of Pathology, University Hospital Son Espases, Instituto de Investigación Sanitaria de Palma, Palma de Mallorca (Spain); Garcia, Juan Fernando [Spanish National Cancer Research Centre, Madrid (Spain); Martinez-Serra, Jordi [Service of Hematology, University Hospital Son Espases, Instituto de Investigación Sanitaria de Palma, Palma de Mallorca (Spain); Casasus, Marta; Nicolau, Cristina [Service of Radiation Therapy, Policlinica Miramar, Palma de Mallorca (Spain); Bento, Leyre; Herraez, Ines [Service of Hematology, University Hospital Son Espases, Instituto de Investigación Sanitaria de Palma, Palma de Mallorca (Spain); Lopez-Perezagua, Paloma [Service of Radiology, IDISPA, Palma de Mallorca (Spain); Daumal, Jaime [Service of Nuclear Medicine, IDISPA, Palma de Mallorca (Spain); Besalduch, Joan [Service of Hematology, University Hospital Son Espases, Instituto de Investigación Sanitaria de Palma, Palma de Mallorca (Spain)

    2015-05-01

    Purpose: To analyze the role of radiation therapy (RT) on the adverse prognostic influence of cyclooxygenase-2 (COX-2) expression on Reed-Sternberg (RS) cells, in the setting of early Hodgkin lymphoma (HL) treated with ABVD (adriamycin, vinblastine, bleomycin, dacarbazine). Methods and Materials: In the present study we retrospectively investigated the prognostic value of COX-2 expression in a large (n=143), uniformly treated early HL population from the Spanish Network of HL using tissue microarrays. Univariate and multivariate analyses were done, including the most recognized clinical variables and the potential role of administration of adjuvant RT. Results: Median age was 31 years; the expression of COX-2 defined a subgroup with significantly worse prognosis. Considering COX-2{sup +} patients, those who received RT had significantly better 5-year progression-free survival (PFS) (80% vs 54% if no RT; P=.008). In contrast, COX-2{sup −} patients only had a modest, nonsignificant benefit from RT in terms of 5-year PFS (90% vs 79%; P=.13). When we compared the outcome of patients receiving RT considering the expression of COX-2 on RS cells, we found a nonsignificant 10% difference in terms of PFS between COX-2{sup +} and COX-2{sup −} patients (P=.09), whereas the difference between the 2 groups was important (25%) in patients not receiving RT (P=.04). Conclusions: Cyclooxygenase-2 RS cell expression is an adverse independent prognostic factor in early HL. Radiation therapy overcomes the worse prognosis associated with COX-2 expression on RS cells, acting in a chemotherapy-independent way. Cyclooxygenase-2 RS cell expression may be useful for determining patient candidates with early HL to receive consolidation with RT.

  6. Heterogeneity in SDF-1 expression defines the vasculogenic potential of adult cardiac progenitor cells.

    Directory of Open Access Journals (Sweden)

    Claudia O Rodrigues

    Full Text Available The adult myocardium has been reported to harbor several classes of multipotent progenitor cells (CPCs with tri-lineage differentiation potential. It is not clear whether c-kit+CPCs represent a uniform precursor population or a more complex mixture of cell types.To characterize and understand vasculogenic heterogeneity within c-kit+presumptive cardiac progenitor cell populations.c-kit+, sca-1+ CPCs obtained from adult mouse left ventricle expressed stem cell-associated genes, including Oct-4 and Myc, and were self-renewing, pluripotent and clonogenic. Detailed single cell clonal analysis of 17 clones revealed that most (14/17 exhibited trilineage differentiation potential. However, striking morphological differences were observed among clones that were heritable and stable in long-term culture. 3 major groups were identified: round (7/17, flat or spindle-shaped (5/17 and stellate (5/17. Stellate morphology was predictive of vasculogenic differentiation in Matrigel. Genome-wide expression studies and bioinformatic analysis revealed clonally stable, heritable differences in stromal cell-derived factor-1 (SDF-1 expression that correlated strongly with stellate morphology and vasculogenic capacity. Endogenous SDF-1 production contributed directly to vasculogenic differentiation: both shRNA-mediated knockdown of SDF-1 and AMD3100, an antagonist of the SDF-1 receptor CXC chemokine Receptor-4 (CXCR4, reduced tube-forming capacity, while exogenous SDF-1 induced tube formation by 2 non-vasculogenic clones. CPCs producing SDF-1 were able to vascularize Matrigel dermal implants in vivo, while CPCs with low SDF-1 production were not.Clonogenic c-kit+, sca-1+ CPCs are heterogeneous in morphology, gene expression patterns and differentiation potential. Clone-specific levels of SDF-1 expression both predict and promote development of a vasculogenic phenotype via a previously unreported autocrine mechanism.

  7. Analyzing Members' Motivations to Participate in Role-Playing and Self-Expression Based Virtual Communities

    Science.gov (United States)

    Lee, Young Eun; Saharia, Aditya

    With the rapid growth of computer mediated communication technologies in the last two decades, various types of virtual communities have emerged. Some communities provide a role playing arena, enabled by avatars, while others provide an arena for expressing and promoting detailed personal profiles to enhance their offline social networks. Due to different focus of these virtual communities, different factors motivate members to participate in these communities. In this study, we examine differences in members’ motivations to participate in role-playing versus self-expression based virtual communities. To achieve this goal, we apply the Wang and Fesenmaier (2004) framework, which explains members’ participation in terms of their functional, social, psychological, and hedonic needs. The primary contributions of this study are two folds: First, it demonstrates differences between role-playing and self-expression based communities. Second, it provides a comprehensive framework describing members’ motivation to participate in virtual communities.

  8. GENE AND PROTEIN EXPRESSION PROFILING OF PANCREATIC TUMOURS REVEAL DYSREGULATED PATHWAYS AND NOVEL POTENTIAL BIOMARKER.

    Science.gov (United States)

    Nweke, E N; Ntwasa, M N; Brand, M B; Devar, J D; Smith, M D; Candy, G P

    2017-06-01

    Pancreatic cancer (PDAC) is a deadly type of cancer with almost an equal amount of new cases and deaths observed yearly. It accounts for about 7% of cancer-related deaths worldwide. In many multi-racial societies including South Africa, the black population has the highest incidence rate. Less than 5% of PDAC patients live up to 5 years. The lack of specific and sensitive diagnostic PDAC biomarkers is strongly responsible for this poor statistic. The discovery of differentially expressed genes and proteins associated with PDAC is crucial to elucidating this condition and may lead to biomarker finding and further understanding of the disease. Tissue samples were obtained from Black South African PDAC patients during the Whipple procedure. Using focused arrays and RNA Sequencing, we have shown differentially expressed genes and proteins between tumour and normal tissue samples of PDAC patients in the quest for potential biomarker discovery. Furthermore, we utilised multiple bioinformatics tools to identify pathways and biological processes enriched by differentially expressed genes/proteins, and to discover novel variants and novel potential PDAC biomarkers. Real-time PCR and ELISA were also employed to validate our novel potential PDAC biomarker. We have identified novel 1) potential transcriptomic and 2) proteomic biomarkers of pancreatic cancer. Our identified transcriptomic biomarker has a sensitivity and specificity of 100% and 80% respectively. Furthermore, we observed novel genetic variants and dysregulated pathways occurring during pancreatic carcinogenesis. This study has identified novel potential biomarkers which can help in the diagnosis of PDAC. Information obtained from enriched signalling pathways help in further understanding the biology of PDAC. Going forward, the identified novel potential biomarkers need to be further validated in a larger sample number using easily accessible samples like blood.

  9. Prostate-specific membrane antigen expression is a potential prognostic marker in endometrial adenocarcinoma.

    Science.gov (United States)

    Mhawech-Fauceglia, Paulette; Smiraglia, Dominic J; Bshara, Wiam; Andrews, Christopher; Schwaller, Juerg; South, Stacey; Higgs, Donald; Lele, Shashikant; Herrmann, Francois; Odunsi, Kunle

    2008-03-01

    The aim of this study was to determine the role of prostate-specific membrane antigen (PSMA) as a prognostic marker in endometrial adenocarcinoma (EAC) and to explore whether its down-regulation could be due to epigenetic mechanism. First, we examined the expression and the prognostic value of PSMA by semiquantitative reverse transcription-PCR and immunohistochemistry in EAC tissue samples. Second, to explore the role of CpG methylation in down-regulation PSMA in EAC, we evaluated PSMA CpG island methylation using methylation-specific PCR in cells lines and in a subset of patients' samples. Furthermore, association of the status of tumor methylation to the clinical and histologic variables was also evaluated. Higher PSMA mRNA levels were associated with stage I (P = 0.046) and PSMA protein intensity by immunohistochemistry (P = 0.032). In multivariate analysis, loss of PSMA expression was associated with a worse disease-free survival (P = 0.02). PSMA was methylated in prostate cell lines (DU145 and PC3) and endometrial cell lines. In addition, PSMA was methylated in 5 of 18 samples (all 5 had low PSMA mRNA value). There was a significant association between PSMA methylation and loss of protein expression by immunohistochemistry and PSMA-RNA level with P value of 0.036 and 0.011, respectively. In addition, there was an association between PSMA methylation and tumor size (P = 0.025). In summary, (a) PSMA is underexpressed in advanced stage EAC, (b) loss of PSMA expression can be considered as a prognostic marker in patients with EAC, and (c) loss of PSMA expression in a subset of EAC cases could be due to epigenetic silencing.

  10. Accurate analytical expression of the electrostatic potential close to a grid placed between two plates

    Science.gov (United States)

    Orjubin, G.

    2017-10-01

    The potential distribution between a grid and two plates is an electrostatic problem already solved for MultiWire detectors used in Nuclear Physics, where theoretical expressions are obtained assuming linear charge distributions. In this paper, the accuracy of the line model is investigated close to the wires, using both analytical and numerical approaches. In the symmetric case where the grid is at equal distances between two grounded plates, it is shown that the error can be modeled using a quadrupole charge. After solving the electrostatic problem for the asymmetric case, a larger discrepancy is found, and is interpreted as a consequence of a dipole charge on the electrode. Two different models of this dipole are then implemented, leading to an accurate theoretical expression of the potential.

  11. Role of sodium tungstate as a potential antiplatelet agent

    Directory of Open Access Journals (Sweden)

    Fernández-Ruiz R

    2015-05-01

    slightly this response. In human blood, a dose-dependent effect was observed. At 200 µM, closure times in the PFA-100 were prolonged. On denuded vessels, %SC and thrombi formation (%T decreased with Na2O4W. Neither the aggregating response nor the viscoelastic clot properties were affected.Conclusion: Na2O4W decreases consistently the hemostatic capacity of platelets, inhibiting their adhesive and cohesive properties under flow conditions in mice and in human blood, resulting in smaller thrombi. Although Na2O4W may be acting on platelet PTP1B, other potential targets should not be disregarded. Keywords: sodium tungstate, protein tyrosine phosphatase 1B, platelet adhesion, antiplatelet agents

  12. On the role of deformed Coulomb potential in fusion using energy ...

    Indian Academy of Sciences (India)

    any important role at higher incident energies, are dominating factors at below barrier energies. At low incident energies, many potentials are available to calculate the nuclear part of the interaction potential such as proximity-based potential models [4]. Among the various proximity-based models, the Skyrme energy density ...

  13. Expression, Localization of SUMO-1, and Analyses of Potential SUMOylated Proteins in Bubalus bubalis Spermatozoa

    OpenAIRE

    Rahim Dad Brohi; Li Wang; Najla Ben Hassine; Jing Cao; Hira Sajjad Talpur; Di Wu; Chun-Jie Huang; Zia-Ur Rehman; Dinesh Bhattarai; Li-Jun Huo

    2017-01-01

    Mature spermatozoa have highly condensed DNA that is essentially silent both transcriptionally and translationally. Therefore, post translational modifications are very important for regulating sperm motility, morphology, and for male fertility in general. Protein sumoylation was recently demonstrated in human and rodent spermatozoa, with potential consequences for sperm motility and DNA integrity. We examined the expression and localization of small ubiquitin-related modifier-1 (SUMO-1) in t...

  14. Expression, Localization of SUMO-1, and Analyses of Potential SUMOylated Proteins in Bubalus bubalis Spermatozoa

    Directory of Open Access Journals (Sweden)

    Rahim Dad Brohi

    2017-06-01

    Full Text Available Mature spermatozoa have highly condensed DNA that is essentially silent both transcriptionally and translationally. Therefore, post translational modifications are very important for regulating sperm motility, morphology, and for male fertility in general. Protein sumoylation was recently demonstrated in human and rodent spermatozoa, with potential consequences for sperm motility and DNA integrity. We examined the expression and localization of small ubiquitin-related modifier-1 (SUMO-1 in the sperm of water buffalo (Bubalus bubalis using immunofluorescence analysis. We confirmed the expression of SUMO-1 in the acrosome. We further found that SUMO-1 was lost if the acrosome reaction was induced by calcium ionophore A23187. Proteins modified or conjugated by SUMO-1 in water buffalo sperm were pulled down and analyzed by mass spectrometry. Sixty proteins were identified, including proteins important for sperm morphology and motility, such as relaxin receptors and cytoskeletal proteins, including tubulin chains, actins, and dyneins. Forty-six proteins were predicted as potential sumoylation targets. The expression of SUMO-1 in the acrosome region of water buffalo sperm and the identification of potentially SUMOylated proteins important for sperm function implicates sumoylation as a crucial PTM related to sperm function.

  15. Expression, Localization of SUMO-1, and Analyses of Potential SUMOylated Proteins in Bubalus bubalis Spermatozoa.

    Science.gov (United States)

    Brohi, Rahim Dad; Wang, Li; Hassine, Najla Ben; Cao, Jing; Talpur, Hira Sajjad; Wu, Di; Huang, Chun-Jie; Rehman, Zia-Ur; Bhattarai, Dinesh; Huo, Li-Jun

    2017-01-01

    Mature spermatozoa have highly condensed DNA that is essentially silent both transcriptionally and translationally. Therefore, post translational modifications are very important for regulating sperm motility, morphology, and for male fertility in general. Protein sumoylation was recently demonstrated in human and rodent spermatozoa, with potential consequences for sperm motility and DNA integrity. We examined the expression and localization of small ubiquitin-related modifier-1 (SUMO-1) in the sperm of water buffalo (Bubalus bubalis) using immunofluorescence analysis. We confirmed the expression of SUMO-1 in the acrosome. We further found that SUMO-1 was lost if the acrosome reaction was induced by calcium ionophore A23187. Proteins modified or conjugated by SUMO-1 in water buffalo sperm were pulled down and analyzed by mass spectrometry. Sixty proteins were identified, including proteins important for sperm morphology and motility, such as relaxin receptors and cytoskeletal proteins, including tubulin chains, actins, and dyneins. Forty-six proteins were predicted as potential sumoylation targets. The expression of SUMO-1 in the acrosome region of water buffalo sperm and the identification of potentially SUMOylated proteins important for sperm function implicates sumoylation as a crucial PTM related to sperm function.

  16. Regulation of CCN2 gene expression and possible roles in developing tooth germs.

    Science.gov (United States)

    Kanyama, Manabu; Shimo, Tsuyoshi; Sugito, Hiroki; Nagayama, Motohiko; Kuboki, Takuo; Pacifici, Maurizio; Koyama, Eiki

    2013-11-01

    CCN proteins are extracellular and cell-associated molecules involved in several developmental processes, but their expression patterns and regulation in tooth development remain unclear. Here we first determined the expression patterns of CCN genes in mouse tooth germs. We found that at early stages CCN2 was detected in dental lamina, dental mesenchyme, and primary enamel knot, while other CCN family members were expressed broadly. By the bell stage, all members were expressed in differentiating odontoblasts and ameloblasts, but CCN1 and CCN2 transcripts were conspicuous in differentiating osteoblasts in dental follicle. Next, we asked what signalling molecules regulate CCN2 expression and what roles CCN2 may have. We found that upon surgical removal of dental epithelium CCN2 was not longer expressed in dental mesenchyme in cultured bud stage germs. Implantation of beads pre-coated with BMPs and FGFs onto E12-13 mandibular explants induced CCN2 expression in dental mesenchyme. There was a dose-dependent effect of BMP-4 on CCN2 induction; a concentration of 100 ng/μl was able to induce strong CCN2 expression while a minimum concentration of 25 ng/μl was needed to elicit appreciable expression. Importantly, Noggin treatment inhibited endogenous and BMP-induced CCN2 expression, verifying that CCN2 expression in developing tooth germs requires BMP signalling. Lastly, we found that rCCN2 stimulated proliferation in dental mesenchyme in a dose-dependent manner. Together, the data indicate that expression of CCN genes is spatio-temporally regulated in developing tooth germs. CCN2 expression appears to depend on epithelial and mesenchymal-derived signalling factors, and CCN2 can elicit strong proliferation in dental mesenchyme. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Increased expression of Nlp, a potential oncogene in ovarian cancer, and its implication in carcinogenesis.

    Science.gov (United States)

    Qu, Danni; Qu, Hongyan; Fu, Ming; Zhao, Xuelian; Liu, Rong; Sui, Lihua; Zhan, Qimin

    2008-08-01

    Nlp (Ninein-like protein), a novel centrosome protein involved in microtubule nucleation, has been studied extensively in our laboratory, and its overexpression has been found in some human tumors. To understand the role of Nlp in human ovarian cancer development, we studied the correlation of Nlp expression with clinicopathological parameters and survival in epithelial ovarian cancer, and the impact of Nlp overexpression on ovarian cancer cells. Nlp expression in normal, borderline, benign and malignant epithelial ovarian tissues was examined by immunohistochemistry. The correlation between Nlp expression and tumor grade, FIGO stage and histological type was also evaluated. Survival was calculated using Kaplan-Meier estimates. Cell proliferation and apoptosis were assayed after stable transfection of pEGFP-C3-Nlp or empty vector in human ovarian cancer cell line SKOV3. Nlp was positive in 1 of 10 (10%) normal ovarian tissues, 5 of 34 (14.7%) benign tumors, 9 of 26 (34.6%) borderline tumors and 73 of 131 (56.0%) ovarian tumors. Nlp immunoreactivity intensity significantly correlated with tumor grade, but not with FIGO stage or histological type. Kaplan-Meier curves showed that Nlp overexpression was marginally associated with decreased overall survival. Overexpression of Nlp enhanced proliferation and inhibited apoptosis induced by paclitaxel in the SKOV3 cell line. Overexpression of Nlp in ovarian tumors raises the possibility that Nlp may play a role in ovarian carcinogenesis.

  18. Expression Atlas of the Deubiquitinating Enzymes in the Adult Mouse Retina, Their Evolutionary Diversification and Phenotypic Roles.

    Directory of Open Access Journals (Sweden)

    Mariona Esquerdo

    Full Text Available Ubiquitination is a relevant cell regulatory mechanism to determine protein fate and function. Most data has focused on the role of ubiquitin as a tag molecule to target substrates to proteasome degradation, and on its impact in the control of cell cycle, protein homeostasis and cancer. Only recently, systematic assays have pointed to the relevance of the ubiquitin pathway in the development and differentiation of tissues and organs, and its implication in hereditary diseases. Moreover, although the activity and composition of ubiquitin ligases has been largely addressed, the role of the deubiquitinating enzymes (DUBs in specific tissues, such as the retina, remains mainly unknown. In this work, we undertook a systematic analysis of the transcriptional levels of DUB genes in the adult mouse retina by RT-qPCR and analyzed the expression pattern by in situ hybridization and fluorescent immunohistochemistry, thus providing a unique spatial reference map of retinal DUB expression. We also performed a systematic phylogenetic analysis to understand the origin and the presence/absence of DUB genes in the genomes of diverse animal taxa that represent most of the known animal diversity. The expression landscape obtained supports the potential subfunctionalization of paralogs in those families that expanded in vertebrates. Overall, our results constitute a reference framework for further characterization of the DUB roles in the retina and suggest new candidates for inherited retinal disorders.

  19. Role of the transient receptor potential vanilloid 1 in inflammation and sepsis

    Directory of Open Access Journals (Sweden)

    Devesa I

    2011-05-01

    Full Text Available Isabel Devesa1, Rosa Planells-Cases2, Gregorio Fernández-Ballester1, José Manuel González-Ros1, Antonio Ferrer-Montiel1, Asia Fernández-Carvajal11Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, Alicante; 2Centro de Investigación Príncipe Felipe, Valencia, SpainAbstract: The transient receptor potential vanilloid 1 (TRPV1 is a thermoreceptor that responds to noxious temperatures, as well as to chemical agonists, such as vanilloids and protons. In addition, its channel activity is notably potentiated by proinflammatory mediators released upon tissue damage. The TRPV1 contribution to sensory neuron sensitization by proalgesic agents has signaled this receptor as a prime target for analgesic and anti-inflammatory drug intervention. However, TRPV1 antagonists have notably failed in clinical and preclinical studies because of their unwanted side effects. Recent reports have unveiled previously unrecognized anti-inflammatory and protective functions of TRPV1 in several diseases. For instance, this channel has been suggested to play an anti-inflammatory role in sepsis. Therefore, the use of potent TRPV1 antagonists as a general strategy to treat inflammation must be cautiously considered, given the deleterious effects that may arise from inhibiting the population of channels that have a protective function. The use of TRPV1 antagonists may be limited to treating those pathologies where enhanced receptor activity contributes to the inflamed state. Alternatively, therapeutic paradigms, such as reduction of inflammatory-mediated increase of receptor expression in the cell surface, may be a better strategy to prevent abrogation of the TRPV1 subpopulation involved in anti-inflammatory and protective processes.Keywords: transient receptor potential, nociceptor, capsaicin, pain, ion channel, analgesia

  20. Nitrate transporters in leaves and their potential roles in foliar uptake of nitrogen dioxide

    Directory of Open Access Journals (Sweden)

    Yanbo eHu

    2014-07-01

    Full Text Available While plant roots are specialized organs for the uptake and transport of water and nutrients, the absorption of gaseous or liquid mineral elements by aerial plant parts has been recognized since more than one century. Nitrogen (N is an essential macronutrient which generally absorbed either as nitrate (NO3- or ammonium (NH4+ by plant roots. Gaseous nitrogen pollutants like N dioxide (NO2 can also be absorbed by plant surfaces and assimilated via the NO3– assimilation pathway. The subsequent NO3– flux may induce or repress the expression of various NO3–-responsive genes encoding for instance, the transmembrane transporters, NO3–/NO2– (nitrite reductase, or assimilatory enzymes involved in N metabolism. Based on the existing information, the aim of this review was to theoretically analyze the potential link between foliar NO2 absorption and N transport and metabolism. For such purpose, an overview of the state of knowledge on the NO3– transporter genes identified in leaves or shoots of various species and their roles for NO3– transport across the tonoplast and plasma membrane, in addition to the process of phloem loading is briefly provided. It is assumed that a NO2-induced ac-cumulation of NO3–/NO2– may alter the expression of such genes, hence linking transmembrane NO3– transporters and foliar uptake of NO2. It is likely that NRT1/NRT2 gene expression and spe-cies-dependent apoplastic buffer capacity may be also related to the species-specific foliar NO2 uptake process. It is concluded that further work focusing on the expression of NRT1 (NRT1.1, NRT1.7, NRT1.11 and NRT1.12, NRT2 (NRT2.1, NRT2.4 and NRT2.5 and chloride channel family genes (CLCa and CLCd may help us elucidate the physiological and metabolic response of plants fumigated with NO2.

  1. PYGOPUS2 expression in prostatic adenocarcinoma is a potential risk stratification marker for PSA progression following radical prostatectomy.

    Science.gov (United States)

    Kao, Kenneth R; Popadiuk, Paul; Thoms, John; Aoki, Satoko; Anwar, Shahgul; Fitzgerald, Emily; Andrews, Phillip; Voisey, Kim; Gai, Luis; Challa, Satya; He, Zhijian; Gonzales-Aguirre, Paola; Simmonds, Andrea; Popadiuk, Catherine

    2017-09-18

    Prostate cancer (PrCa) is the most frequently diagnosed non-cutaneous cancer in men. Without clear pathological indicators of disease trajectory at diagnosis, management of PrCa is challenging, given its wide-ranging manifestation from indolent to highly aggressive disease. This study examines the role in PrCa of the Pygopus (PYGO)2 chromatin effector protein as a risk stratification marker in PrCa. RNA expression was performed in PrCa cell lines using Northern and RT-PCR analyses. Protein levels were assessed using immunoblot and immunofluorescence. Immunohistochemistry was performed on tissue microarrays constructed from radical prostatectomies with 5-year patient follow-up data including Gleason score tumour staging, margin and lymph node involvement and prostate serum antigen (PSA) levels. Biochemical recurrence (BR) was defined as a postoperative PSA level of >0.2 nL. Univariate and multivariate analyses were performed using SAS and Kaplan-Meier curves using graphPad (Prism). In vitro depletion of PYGO2 by RNAi in both androgen receptor positive and negative PrCa cell lines attenuated growth and reduced Ki67 and 47S rRNA expression, while PYGO2 protein was localised to the nuclei of tumours as determined by immunohistochemistry. High expression levels of PYGO2 in tumours (n=156) were correlated with BR identified as PSA progression, after 7-year follow-up independent of other traditional risk factors. Most importantly, high PYGO2 levels in intermediate grade tumours suggested increased risk of recurrence over those with negative or weak expression. Our data suggest that elevated PYGO2 expression in primary prostate adenocarcinoma is a potential risk factor for BR. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. Upregulated expression of NKG2D and its ligands give potential therapeutic targets for patients with thymoma.

    Science.gov (United States)

    Xuan, X Y; Zhang, J F; Hu, G M; Li, Q R; Liu, P P; Du, Y

    2015-07-01

    The activating receptor NKG2D (natural killer group 2, member D) of natural killer (NK) cells promotes tumor immune surveillance by targeting ligands selectively induced on cancer cells, and thus having an important role in antitumor immune response. Because these ligands are not widely expressed on healthy adult tissue, NKG2D ligands may present as useful target for immunotherapeutic approaches in cancer. In this study, to elucidate the role of NKG2D-NKG2D ligand interaction in thymoma tissues and to evaluate the potential role of NKG2D ligands as therapeutic target for thymoma, we examined the expression of NKG2D and its specific ligands: MICA (major histocompatibility complex class I chain-related protein A), MICB (major histocompatibility complex class I chain-related protein B) and ULBP (UL16-binding protein) in 36 thymomas (6 subtype A, 6 subtype AB, 8 subtype B1, 5 subtype B2, 6 subtype B3 and 5 subtype C), 15 thymic atrophy and 8 thymic hyperplasia by immunohistochemistry and reverse transcription-real-time-PCR methods. We demonstrated that both mRNA and protein levels of NKG2D, MICA, MICB and ULBP were upregulated in six types of thymomas compared with those in atrophic thymus or proliferating thymus. Furthermore, the NKG2D ligands were found to be frequently coexpressed on thymoma cells. Furthermore, the expression of MICA, MICB and ULBP in subtype C was higher compared with those in subtype A, AB, B1, B2 and B3. Thus, we concluded that high expressions of NKG2D, MICA, MICB and ULBP1 were shown in patients with thymoma, and this may enhance the recognition function of NK cells to eliminate tumor cells. MICA, MICB and ULBP presented an attractive target for thymoma therapy. The abnormal expression of NKG2D, MICA, MICB and ULBP1 can provide us with evidence of the occurrence of thymoma and could also be used as a target in the treatment of thymoma.

  3. Recognition and Suppression of Transfected Plasmids by Protein ZNF511-PRAP1, a Potential Molecular Barrier to Transgene Expression

    Science.gov (United States)

    Qiu, Guo-Hua; Leung, Carol Ho-Wing; Yun, Tong; Xie, Xiaojin; Laban, Mirtha; Hooi, Shing Chuan

    2011-01-01

    Nonviral vectors present considerable advantages over viral counterparts in gene transfer. However, the poor expression efficiency of the transfected genes poses a challenge for their use in gene therapy, primarily due to the inability of these vectors to overcome various barriers, including the biological barriers. Here, we report that ZNF511-PRAP1 may be involved in the recognition and inactivation of transfected plasmids. ZNF511-PRAP1 is induced by transfection of plasmid DNA and suppresses the transcription of transfected plasmids. It binds directly to the p21 promoter in transfected plasmids but not the endogenous counterpart. Similarly, ZNF511-PRAP1 suppresses the expression of the green fluorescent protein reporter gene on transiently transfected plasmids but not an integrated red fluorescence reporter gene with the same cytomegalovirus (CMV) promoter. Therefore, ZNF511-PRAP1 is able to differentiate between exogenous/nonintegrated and endogenous/integrated DNA. The suppression by ZNF511-PRAP1 is independent of DNA methylation and can be abolished by trichostatin A (TSA) treatment and knockdown of HDAC2 and/or ZNF511-PRAP1. Furthermore, ZNF511-PRAP1 interacts directly with HDAC2. Our results revealed that transfected plasmids are recognized by ZNF511-PRAP1 and suppressed by a repressor complex comprising ZNF511-PRAP1 and HDAC2 and suggest that ZNF511-PRAP1 could play a role as a potential molecular barrier in nonviral transgene expression. PMID:21540836

  4. Molecular Characterization, Tissue Distribution and Expression, and Potential Antiviral Effects of TRIM32 in the Common Carp (Cyprinus carpio).

    Science.gov (United States)

    Wang, Yeda; Li, Zeming; Lu, Yuanan; Hu, Guangfu; Lin, Li; Zeng, Lingbing; Zhou, Yong; Liu, Xueqin

    2016-10-09

    Tripartite motif-containing protein 32 (TRIM32) belongs to the tripartite motif (TRIM) family, which consists of a large number of proteins containing a RING (Really Interesting New Gene) domain, one or two B-box domains, and coiled coil motif followed by different C-terminal domains. The TRIM family is known to be implicated in multiple cellular functions, including antiviral activity. However, it is presently unknown whether TRIM32 of common carp ( Cyprinus carpio ) has the antiviral effect. In this study, the sequence, expression, and antiviral function of TRIM32 homolog from common carp were analyzed. The full-length coding sequence region of trim32 was cloned from common carp. The results showed that the expression of TRIM32 (mRNA) was highest in the brain, remained stably expressed during embryonic development, and significantly increased following spring viraemia of carp virus (SVCV) infection. Transient overexpression of TRIM32 in affected Epithelioma papulosum cyprinid cells led to significant decrease of SVCV production as compared to the control group. These results suggested a potentially important role of common carp TRIM32 in enhancing host immune response during SVCV infection both in vivo and in vitro.

  5. Expression profiling and functional analysis of Populus WRKY23 reveals a regulatory role in defense.

    Science.gov (United States)

    Levée, Valérie; Major, Ian; Levasseur, Caroline; Tremblay, Laurence; MacKay, John; Séguin, Armand

    2009-01-01

    WRKY transcription factors are key regulators that activate and fine-tune stress responses, including defense responses against pathogens. We isolated a poplar (Populus tremulaxPopulus alba) cDNA sequence, PtWRKY23, that encodes the ortholog of Arabidopsis WRKY23 and present the functional analysis of WRKY23, with emphasis on its potential role in resistance to rust infection. To investigate the function of PtWRKY23, we examined PtWRKY23 expression after stress treatments by qRT-PCR and generated PtWRKY23-misexpressing plants. Transgenic plants were assessed for resistance to Melampsora rust and were analyzed using the poplar Affymetrix GeneChip and histological techniques to study the consequences of PtWRKY23 misexpression. PtWRKY23 is rapidly induced by Melampsora infection and elicitor treatments and poplars overexpressing and underexpressing PtWRKY23 were both more susceptible to Melampsora infection than wild type. Transcriptome analysis of PtWRKY23 overexpressors revealed a significant overlap with the Melampsora-infection response. Transcriptome analysis also suggests that PtWRKY23 affects redox homeostasis and cell wall-related metabolism, which was confirmed by analyses that showed that PtWRKY23-misexpressing plants have altered peroxidase activity, apparent H(2)O(2) accumulation and lignin deposition. Our results show that PtWRKY23 affects resistance to Melampsora infection and that this may be caused by deregulation of genes that disrupt redox homeostasis and cell wall metabolism.

  6. Molecular Expression Profile Reveals Potential Biomarkers and Therapeutic Targets in Canine Endometrial Lesions.

    Directory of Open Access Journals (Sweden)

    Fabiana Azevedo Voorwald

    Full Text Available Cystic endometrial hyperplasia (CEH, mucometra, and pyometra are common uterine diseases in intact dogs, with pyometra being a life threatening disease. This study aimed to determine the gene expression profile of these lesions and potential biomarkers for closed-cervix pyometra, the most severe condition. Total RNA was extracted from 69 fresh endometrium samples collected from 21 healthy female dogs during diestrus, 16 CEH, 15 mucometra and 17 pyometra (eight open and nine closed-cervixes. Global gene expression was detected using the Affymetrix Canine Gene 1.0 ST Array. Unsupervised analysis revealed two clusters, one mainly composed of diestrus and CEH samples and the other by 12/15 mucometra and all pyometra samples. When comparing pyometra with other groups, 189 differentially expressed genes were detected. SLPI, PTGS2/COX2, MMP1, S100A8, S100A9 and IL8 were among the top up-regulated genes detected in pyometra, further confirmed by external expression data. Notably, a particular molecular profile in pyometra from animals previously treated with exogenous progesterone compounds was observed in comparison with pyometra from untreated dogs as well as with other groups irrespective of exogenous hormone treatment status. In addition to S100A8 and S100A9 genes, overexpression of the inflammatory cytokines IL1B, TNF and IL6 as well as LTF were detected in the pyometra from treated animals. Interestingly, closed pyometra was more frequently detected in treated dogs (64% versus 33%, with IL1B, TNF, LBP and CXCL10 among the most relevant overexpressed genes. This molecular signature associated with potential biomarkers and therapeutic targets, such as CXCL10 and COX2, should guide future clinical studies. Based on the gene expression profile we suggested that pyometra from progesterone treated dogs is a distinct molecular entity.

  7. Molecular Expression Profile Reveals Potential Biomarkers and Therapeutic Targets in Canine Endometrial Lesions

    Science.gov (United States)

    Voorwald, Fabiana Azevedo; Marchi, Fabio Albuquerque; Villacis, Rolando Andre Rios; Alves, Carlos Eduardo Fonseca; Toniollo, Gilson Hélio; Amorim, Renee Laufer

    2015-01-01

    Cystic endometrial hyperplasia (CEH), mucometra, and pyometra are common uterine diseases in intact dogs, with pyometra being a life threatening disease. This study aimed to determine the gene expression profile of these lesions and potential biomarkers for closed-cervix pyometra, the most severe condition. Total RNA was extracted from 69 fresh endometrium samples collected from 21 healthy female dogs during diestrus, 16 CEH, 15 mucometra and 17 pyometra (eight open and nine closed-cervixes). Global gene expression was detected using the Affymetrix Canine Gene 1.0 ST Array. Unsupervised analysis revealed two clusters, one mainly composed of diestrus and CEH samples and the other by 12/15 mucometra and all pyometra samples. When comparing pyometra with other groups, 189 differentially expressed genes were detected. SLPI, PTGS2/COX2, MMP1, S100A8, S100A9 and IL8 were among the top up-regulated genes detected in pyometra, further confirmed by external expression data. Notably, a particular molecular profile in pyometra from animals previously treated with exogenous progesterone compounds was observed in comparison with pyometra from untreated dogs as well as with other groups irrespective of exogenous hormone treatment status. In addition to S100A8 and S100A9 genes, overexpression of the inflammatory cytokines IL1B, TNF and IL6 as well as LTF were detected in the pyometra from treated animals. Interestingly, closed pyometra was more frequently detected in treated dogs (64% versus 33%), with IL1B, TNF, LBP and CXCL10 among the most relevant overexpressed genes. This molecular signature associated with potential biomarkers and therapeutic targets, such as CXCL10 and COX2, should guide future clinical studies. Based on the gene expression profile we suggested that pyometra from progesterone treated dogs is a distinct molecular entity. PMID:26222498

  8. Exploration of Potential Roles of a New LOXL2 Splicing Variant Using Network Knowledge in Esophageal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Bing-Li Wu

    2014-01-01

    Full Text Available LOXL2 (lysyl oxidase-like 2, an enzyme that catalyzes oxidative deamination of lysine residue, is upregulated in esophageal squamous cell carcinoma (ESCC. A LOXL2 splice variant LOXL2-e13 and its wild type were overexpressed in ESCC cells followed by microarray analyses. In this study, we explored the potential role and molecular mechanism of LOXL2-e13 based on known protein-protein interactions (PPIs, following microarray analysis of KYSE150 ESCC cells overexpressing a LOXL2 splice variant, denoted by LOXL2-e13, or its wild-type counterpart. The differentially expressed genes (DEGs of LOXL2-WT and LOXL2-e13 were applied to generate individual PPI subnetworks in which hundreds of DEGs interacted with thousands of other proteins. These two DEG groups were annotated by Functional Annotation Chart analysis in the DAVID bioinformatics database and compared. These results found many specific annotations indicating the potential specific role or mechanism for LOXL2-e13. The DEGs of LOXL2-e13, comparing to its wild type, were prioritized by the Random Walk with Restart algorithm. Several tumor-related genes such as ERO1L, ITGA3, and MAPK8 were found closest to LOXL2-e13. These results provide helpful information for subsequent experimental identification of the specific biological roles and molecular mechanisms of LOXL2-e13. Our study also provides a work flow to identify potential roles of splice variants with large scale data.

  9. Expression of HIV-1 antigens in plants as potential subunit vaccines

    Directory of Open Access Journals (Sweden)

    Tanzer Fiona L

    2008-06-01

    Full Text Available Abstract Background Human immunodeficiency virus type 1 (HIV-1 has infected more than 40 million people worldwide, mainly in sub-Saharan Africa. The high prevalence of HIV-1 subtype C in southern Africa necessitates the development of cheap, effective vaccines. One means of production is the use of plants, for which a number of different techniques have been successfully developed. HIV-1 Pr55Gag is a promising HIV-1 vaccine candidate: we compared the expression of this and a truncated Gag (p17/p24 and the p24 capsid subunit in Nicotiana spp. using transgenic plants and transient expression via Agrobacterium tumefaciens and recombinant tobamovirus vectors. We also investigated the influence of subcellular localisation of recombinant protein to the chloroplast and the endoplasmic reticulum (ER on protein yield. We partially purified a selected vaccine candidate and tested its stimulation of a humoral and cellular immune response in mice. Results Both transient and transgenic expression of the HIV antigens were successful, although expression of Pr55Gag was low in all systems; however, the Agrobacterium-mediated transient expression of p24 and p17/p24 yielded best, to more than 1 mg p24/kg fresh weight. Chloroplast targeted protein levels were highest in transient and transgenic expression of p24 and p17/p24. The transiently-expressed p17/p24 was not immunogenic in mice as a homologous vaccine, but it significantly boosted a humoral and T cell immune response primed by a gag DNA vaccine, pTHGagC. Conclusion Transient agroinfiltration was best for expression of all of the recombinant proteins tested, and p24 and p17/p24 were expressed at much higher levels than Pr55Gag. Our results highlight the usefulness of plastid signal peptides in enhancing the production of recombinant proteins meant for use as vaccines. The p17/p24 protein effectively boosted T cell and humoral responses in mice primed by the DNA vaccine pTHGagC, showing that this plant

  10. Triphenyl phosphate-induced developmental toxicity in zebrafish: potential role of the retinoic acid receptor.

    Science.gov (United States)

    Isales, Gregory M; Hipszer, Rachel A; Raftery, Tara D; Chen, Albert; Stapleton, Heather M; Volz, David C

    2015-04-01

    Using zebrafish as a model, we previously reported that developmental exposure to triphenyl phosphate (TPP) - a high-production volume organophosphate-based flame retardant - results in dioxin-like cardiac looping impairments that are independent of the aryl hydrocarbon receptor. Using a pharmacologic approach, the objective of this study was to investigate the potential role of retinoic acid receptor (RAR) - a nuclear receptor that regulates vertebrate heart morphogenesis - in mediating TPP-induced developmental toxicity in zebrafish. We first revealed that static exposure of zebrafish from 5-72h post-fertilization (hpf) to TPP in the presence of non-toxic concentrations of an RAR antagonist (BMS493) significantly enhanced TPP-induced toxicity (relative to TPP alone), even though identical non-toxic BMS493 concentrations mitigated retinoic acid (RA)-induced toxicity. BMS493-mediated enhancement of TPP toxicity was not a result of differential TPP uptake or metabolism, as internal embryonic doses of TPP and diphenyl phosphate (DPP) - a primary TPP metabolite - were not different in the presence or absence of BMS493. Using real-time PCR, we then quantified the relative change in expression of cytochrome P450 26a1 (cyp26a1) - a major target gene for RA-induced RAR activation in zebrafish - and found that RA and TPP exposure resulted in a ∼5-fold increase and decrease in cyp26a1 expression, respectively, relative to vehicle-exposed embryos. To address whether TPP may interact with human RARs, we then exposed Chinese hamster ovary cells stably transfected with chimeric human RARα-, RARβ-, or RARγ to TPP in the presence of RA, and found that TPP significantly inhibited RA-induced luciferase activity in a concentration-dependent manner. Overall, our findings suggest that zebrafish RARs may be involved in mediating TPP-induced developmental toxicity, a mechanism of action that may have relevance to humans. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Prognostic role of hypoxia-inducible factor-1 alpha expression in osteosarcoma: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Ren HY

    2016-03-01

    Full Text Available Hai-Yong Ren,1 Yin-Hua Zhang,1,2 Heng-Yuan Li,1 Tao Xie,1 Ling-Ling Sun,1 Ting Zhu,1 Sheng-Dong Wang,1 Zhao-Ming Ye1 1Department of Orthopaedics, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 2The First Department of Orthopaedics, Hospital of Zhejiang General Corps of Armed Police Forces, Jiaxing, People’s Republic of China Background: Hypoxia-inducible factor-1α (HIF-1α plays an important role in tumor progression and metastasis. A number of studies have investigated the association of HIF-1α with prognosis and clinicopathological characteristics of osteosarcoma but yielded inconsistent results.  Method: Systematic computerized searches were performed in PubMed, Embase, and Web of Science databases for relevant original articles. The pooled hazard ratios (HRs and odds ratios (ORs with corresponding confidence intervals (CIs were calculated to assess the prognostic value of HIF-1α expression. The standard mean difference was used to analyze the continuous variable.  Results: Finally, nine studies comprising 486 patients were subjected to final analysis. Protein expression level of HIF-1α was found to be significantly related to overall survival (HR =3.0; 95% CI: 1.46–6.15, disease-free survival (HR =2.23; 95% CI: 1.26–3.92, pathologic grade (OR =21.33; 95% CI: 4.60–98.88, tumor stage (OR =10.29; 95% CI: 3.55–29.82, chemotherapy response (OR =9.68; 95% CI: 1.87–50.18, metastasis (OR =5.06; 95% CI: 2.87–8.92, and microvessel density (standard mean difference =2.83; 95% CI: 2.28–3.39.  Conclusion: This meta-analysis revealed that overexpression of HIF-1α is a predictive factor of poor outcomes for osteosarcoma. HIF-1α appeared to play an important role in prognostic evaluation and may be a potential target in antitumoral therapy. Keywords: HIF-1α, osteosarcoma, prognosis, meta-analysis

  12. Potential Role of Concentrating Solar Power in Enabling High Renewables Scenarios in the United States

    Energy Technology Data Exchange (ETDEWEB)

    Denholm, P.; Hand, M.; Mai, T.; Margolis, R.; Brinkman, G.; Drury, E.; Mowers, M.; Turchi, C.

    2012-10-01

    This work describes the analysis of concentrating solar power (CSP) in two studies -- The SunShot Vision Study and the Renewable Electricity Futures Study -- and the potential role of CSP in a future energy mix.

  13. The potential role of perceived support for reduction of special education teachers’ burnout

    National Research Council Canada - National Science Library

    Viviana Langher; Andrea Caputo; Maria Elisabetta Ricci

    2017-01-01

    .... This study explored the potential role of perceived support for reduction of burnout in a sample of 276 special education teachers working in lower (n=130) and higher (n=146) secondary schools...

  14. Expression and Function of Transmembrane-4 Superfamily (Tetraspanin Proteins in Osteoclasts: Reciprocal Roles of Tspan-5 and NET-6 during Osteoclastogenesis

    Directory of Open Access Journals (Sweden)

    Kaori Iwai

    2007-01-01

    Conclusions: These data indicate that a diversity of tetraspanins is expressed in osteoclast precursors, and that cell fusion during osteoclastogenesis is regulated by cooperation of distinct tetraspanin family proteins such as Tspan-5 and NET-6. This study indicates that functional alterations of tetraspanin family proteins may have therapeutic potential in diseases where osteoclasts play a major role, such as rheumatoid arthritis and osteoporosis.

  15. The potential use of expression profiling: implications for predicting treatment response in rheumatoid arthritis.

    Science.gov (United States)

    Smith, Samantha Louise; Plant, Darren; Eyre, Stephen; Barton, Anne

    2013-07-01

    Whole genome expression profiling, or transcriptomics, is a high throughput technology with the potential for major impacts in both clinical settings and drug discovery and diagnostics. In particular, there is much interest in this technique as a mechanism for predicting treatment response. Gene expression profiling entails the quantitative measurement of messenger RNA levels for thousands of genes simultaneously with the inherent possibility of identifying biomarkers of response to a particular therapy or by singling out those at risk of serious adverse events. This technology should contribute to the era of stratified medicine, in which patient specific populations are matched to potentially beneficial drugs via clinical tests. Indeed, in the oncology field, gene expression testing is already recommended to allow rational use of therapies to treat breast cancer. However, there are still many issues surrounding the use of the various testing platforms available and the statistical analysis associated with the interpretation of results generated. This review will discuss the implications this promising technology has in predicting treatment response and outline the various advantages and pitfalls associated with its use.

  16. Expression of matrix metalloproteinase-9 in oral potentially malignant disorders: A systematic review.

    Science.gov (United States)

    Venugopal, Archana; Uma Maheswari, T N

    2016-01-01

    Matrix metalloproteinase-9 (MMP-9) is an inducible enzyme. Oral potentially malignant disorders (OPMDs) are considered as the early tissue changes that happen due to various habits such as smoking tobacco, chewing tobacco or stress. This alteration in the tissues alters the expression of MMP-9. The rationale of the review is to know the expression of MMP-9 in OPMDs. Hand searching and electronic databases such as PubMed and ScienceDirect were done for mesh terms such as OPMDs and MMP-9. Eight articles were obtained, after applying inclusion and exclusion criteria. These articles were assessed with QUADAS and data were extracted and evaluated. The included eight studies were done in 182 oral squamous cell carcinoma cases, 430 OPMDs (146 oral lichen planus, 264 leukoplakia and 20 oral submucous fibrosis) and 352 healthy controls evaluated for MMP-9. MMP-9 expression was found to be elevated in tissue, serum and saliva samples of OPMDs than in healthy controls. There is only one study in each serum and saliva samples to evaluate MMP-9. Saliva being noninvasive and serum being minimally invasive, more studies need to be done in both serum and saliva to establish MMP-9 as an early diagnostic marker in OPMDs to know its potential in malignant transformation.

  17. Role of Catechin Quinones in the Induction of EpRE-Mediated Gene Expression

    NARCIS (Netherlands)

    Muzolf-Panek, M.; Gliszczynska-Swiglo, A.; Haan, de L.H.J.; Aarts, J.M.M.J.G.; Szymusiak, H.; Vervoort, J.J.M.; Tyrakowska, B.; Rietjens, I.M.C.M.

    2008-01-01

    In the present study, the ability of green tea catechins to induce electrophile-responsive element (EpRE)-mediated gene expression and the role of their quinones in the mechanism of this induction were investigated. To this end, Hepa1c1c7 mouse hepatoma cells were used, stably transfected with a

  18. Metallothionein I+II expression and their role in experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Penkowa, M; Hidalgo, J

    2000-01-01

    We examined the expression and roles of neuroprotective metallothionein-I+II (MT-I+II) in the rat CNS in experimental autoimmune encephalomyelitis (EAE), an animal model for the human autoimmune disease, multiple sclerosis (MS). EAE caused significant macrophage activation, T-lymphocyte infiltrat...

  19. The role of redox status on chemokine expression in acute pancreatitis

    OpenAIRE

    Yubero, S.; Ramudo, L.; Manso, M.A.; De Dios, I.

    2009-01-01

    The role of redox status on chemokine expression in acute pancreatitis correspondance: Corresponding author. Departamento Fisiologia y Farmacologia. Edificio Departamental Campus Miguel de Unamuno 37007 Salamanca Spain. Fax: +34 923 294673. (De Dios, I.) (De Dios, I.) Department of Physiology and Pharmacology. University of Salamanca. 37007 Salamanca. Spain--> - (Yubero, S.) Department of Physiology and Pharmacology. ...

  20. Expression and role of PAK6 after spinal cord injury in adult rat

    Directory of Open Access Journals (Sweden)

    CHEN Xiang-dong

    2012-02-01

    Full Text Available 【Abstract】Objective: To observe p21-activated kinase 6 (PAK6 expression and its possible role after spinal cord injury (SCI in adult rat. Methods: Sprague-Dawley rats were subjected to spinal cord injury. To explore the pathological and physiological significance of PAK6, the expression patterns and distribution of PAK6 were observed by Western blot, immunohistochemistry and immunofluorescence. Results: Western blot analysis showed PAK6 protein level was significantly up-regulated on day 2 and day 4, then reduced and had no up-regulation till day 14. Immunohistochemistry analysis showed that the expression of PAK6 was significantly increased on day 4 compared with the control group. Besides, double immunofluorescence staining showed PAK6 was primarily expressed in the neurons and astrocytes in the control group. While after injury, the expression of PAK6 was increased significantly in the astrocytes and neurons, and the astrocytes were largely proliferated. We also examined the expression of proliferating cell nuclear antigen (PCNA and found its change was correlated with the expression of PAK6. Importantly, double immunofluorescence staining revealed that cell proliferation evaluated by PCNA appeared in many PAK6-expressing cells on day 4 after injury. Conclusion: The up-regulation of PAK6 in the injured spinal cord may be associated with glial proliferation. Key words: PAK6 protein, human; p21-activated kinases; Spinal cord injury; Astrocytes

  1. Potential role of odontoblasts in the innate immune response of the dental pulp

    Directory of Open Access Journals (Sweden)

    Tetiana Haniastuti

    2008-09-01

    Full Text Available Background: Odontoblasts are the cells lining of tooth’s hard structure at the dentin-pulp border, which become the first cells encountered oral microorganisms entering dentin. However, they do not only form a physical barrier by producing dentin, but also provide an innate immune barrier for the tooth. Purpose: The aim of this review was to discuss the potential role of odontoblasts in the innate immune response of the dental pulp. Reviews: Recent studies have proven that odontoblasts express toll-like receptors, and capable of producing chemokines (i.e. IL-8, CCL2, CXCL2, and CXCL10, and cytokines (IL-1β and TNF-α following lipopolysacharide exposure. Thereby odontoblasts are actively participating in the recruitment of immune cells in response to caries–derived bacterial products. Furthermore, odontoblasts also produce antimicrobial peptides (hBD-1, hBD-2, and hBD-3, and transform growth factor β that induce antimicrobial and anti-inflammatory activities. Conclusion: The presence of those innate immune molecules indicates that the nonspecific, natural, and rapidly acting defense may also be an important function of odontoblasts.

  2. A potential role for Helicobacter pylori heat shock protein 60 in gastric tumorigenesis

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chen-Si [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China); School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan (China); He, Pei-Juin [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China); Tsai, Nu-Man [School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan (China); Li, Chi-Han; Yang, Shang-Chih; Hsu, Wei-Tung [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China); Wu, Ming-Shiang [Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Wu, Chang-Jer [Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan (China); Cheng, Tain-Lu [Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Liao, Kuang-Wen, E-mail: kitchhen@yahoo.com.tw [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China)

    2010-02-05

    Helicobacter pylori has been found to promote the malignant process leading to gastric cancer. Heat shock protein 60 of H. pylori (HpHSP60) was previously been identified as a potent immunogene. This study investigates the role of HpHSP60 in gastric cancer carcinogenesis. The effect of HpHSP60 on cell proliferation, anti-death activity, angiogenesis and cell migration were explored. The results showed that HpHSP60 enhanced migration by gastric cancer cells and promoted tube formation by umbilical vein endothelial cells (HUVECs); however, HpHSP60 did not increase cell proliferation nor was this protein able to rescue gastric cancer cells from death. Moreover, the results also indicated HpHSP60 had different effects on AGS gastric cancer cells or THP-1 monocytic cells in terms of their expression of pro-inflammatory cytokines, which are known to be important to cancer development. We propose that HpHSP60 may trigger the initiation of carcinogenesis by inducing pro-inflammatory cytokine release and by promoting angiogenesis and metastasis. Thus, this extracellular pathogen-derived HSP60 is potentially a vigorous virulence factor that can act as a carcinogen during gastric tumorigenesis.

  3. [Transposon expression and potential effects on gene regulation of Brassica rapa and B. oleracea genomes].

    Science.gov (United States)

    Zhao, Mei-Xia; Zhang, Biao; Liu, Sheng-Yi; Ma, Jian-Xin

    2013-08-01

    Transposons or transposable elements (TEs) are ubiquitous and most abundant DNA components in higher eukaryotes. Recent sequencing of the Brassica rapa and B. oleracea genomes revealed that the amplification of TEs is one of the main factors inducing the difference in genome size. However, the expressions of TEs and the TE effects on gene regulation and functions of these two Brassica diploid species were unclear. Here, we analyzed the RNA sequencing data of leaves, roots, and stems from B. rapa and B. oleracea. Our data showed that overall TEs in either genome expressed at very low levels, and the expression levels of different TE categories and families varied among different organs. Moreover, even for the same TE category or family, the expression activities were distinct between the two Brassica diploids. Forty-one and nine LTR retrotransposons with the transcripts that read into their adjacent sequences have the distances shorter than 2 kb and 100 bp compared to the downstream genes. These LTR retrotransposon readout transcriptions may produce sense or antisense transcripts of nearby genes, with the effects on activating or silencing corresponding genes. Meanwhile, intact LTRs were detected at stronger readout activities than solo LTRs. Of the TEs inserted into genes, the frequencies were ob-served at a higher level in B. rapa than in B. oleracea. In addition, DNA transposons were prone to insert or retain in the intronic regions of genes in either Brassica genomes. These results revealed that the TEs may have potential effects on regulating protein coding genes.

  4. Hepatocyte growth factor (HGF) receptor expression and role of HGF during embryonic mouse testis development.

    Science.gov (United States)

    Ricci, G; Catizone, A; Innocenzi, A; Galdieri, M

    1999-12-01

    The hepatocyte growth factor (HGF) receptor, c-met, transduces the HGF multiple biological activities. During embryonic development the system HGF/c-met regulates the morphogenesis of different organs and tissues. In this study we examined c-met gene expression during mouse testis development and, by means of Northern blot and in situ hybridization, we report the receptor expression pattern. C-met expression is not detectable in male genital ridges isolated from embryos at 11.5 days postcoitum (dpc). In testes isolated from 12.5 and 13.5 dpc, c-met expression is detectable and essentially localized in the developing cords. Male genital ducts do not express c-met at the reported ages, whereas female ducts appear c-met positive. Moreover, we report that HGF is able to induce testicular morphogenesis in vitro. Male genital ridges isolated from embryos at 11.5 dpc are morphologically nonorganized. Culturing 11.5 dpc urogenital ridges in the presence of HGF we obtained testis organization and testicular cord formation. Our data demonstrate that c-met is expressed during the beginning period of testis differentiation and that HGF is able to support testicular differentiation in vitro. All these data indicate that this growth factor, besides its role as mitogenic factor, plays a fundamental role during testicular cord formation probably inducing cell migration and/or cell differentiation. Copyright 1999 Academic Press.

  5. Role of the mar-sox-rob regulon in regulating outer membrane porin expression.

    Science.gov (United States)

    Chubiz, Lon M; Rao, Christopher V

    2011-05-01

    Multiple factors control the expression of the outer membrane porins OmpF and OmpC in Escherichia coli. In this work, we investigated the role of the mar-sox-rob regulon in regulating outer membrane porin expression in response to salicylate. We provide both genetic and physiological evidence that MarA and Rob can independently activate micF transcription in response to salicylate, leading to reduced OmpF expression. MarA was also found to repress OmpF expression through a MicF-independent pathway. In the case of OmpC, we found that its transcription was moderately increased in response to salicylate. However, this increase was independent of MarA and Rob. Finally, we found that the reduction in OmpF expression in a tolC mutant is due primarily to Rob. Collectively, this work further clarifies the coordinated role of MarA and Rob in regulating the expression of the outer membrane porins.

  6. Parvovirus Expresses a Small Noncoding RNA That Plays an Essential Role in Virus Replication.

    Science.gov (United States)

    Wang, Zekun; Shen, Weiran; Cheng, Fang; Deng, Xuefeng; Engelhardt, John F; Yan, Ziying; Qiu, Jianming

    2017-04-15

    -associated (VA) RNAs and Epstein-Barr virus-encoded small RNAs (EBERs) with respect to RNA sequence, representing a third species of this kind of Pol III-dependent viral noncoding RNA and the first noncoding RNA identified in autonomous parvoviruses. Unlike the VA RNAs, BocaSR localizes to the viral DNA replication centers of the nucleus and is essential for expression of viral nonstructural proteins independent of RNA-activated protein kinase R and replication of HBoV1 genomes. The identification of BocaSR and its role in virus DNA replication reveals potential avenues for developing antiviral therapies. Copyright © 2017 American Society for Microbiology.

  7. Media Impact on Fright Reactions and Belief in UFOs: The Potential Role of Mental Imagery.

    Science.gov (United States)

    Sparks, Glenn G.; And Others

    1995-01-01

    Explores the potential role of mental imagery for media effects in emotional responses to frightening mass media, and in the effects of the media on beliefs in UFOs. Finds that individual differences in vividness of mental imagery may play a crucial role in moderating both types of media impact. (SR)

  8. The potential role of hydrogen energy in India and Western Europe

    NARCIS (Netherlands)

    van Ruijven, B.J.|info:eu-repo/dai/nl/304834521; Lakshmikanth, H.D.; van Vuuren, D.P.; de Vries, B.|info:eu-repo/dai/nl/068361599

    2008-01-01

    We used the TIMER energy model to explore the potential role of hydrogen in the energy systems of India and Western Europe, looking at the impacts on its main incentives: climate policy, energy security and urban air pollution. We found that hydrogen will not play a major role in both regions

  9. Beyond gender stereotypes in language comprehension: self sex-role descriptions affect the brain's potentials associated with agreement processing

    Directory of Open Access Journals (Sweden)

    Paolo eCanal

    2015-12-01

    Full Text Available We recorded Event-Related Potentials to investigate differences in the use of gender information during the processing of reflexive pronouns. Pronouns either matched the gender provided by role nouns (such as king or engineer or did not. We compared two types of gender information, definitional information, which is semantic in nature (a mother is female, or stereotypical (a nurse is likely to be female. When they followed definitional role-nouns, gender-mismatching pronouns elicited a P600 effect reflecting a failure in the agreement process. When instead the gender violation occurred after stereotypical role-nouns the ERP response was biphasic, being positive in parietal electrodes and negative in anterior left electrodes. The use of a correlational approach showed that those participants with more feminine or expressive self sex-role descriptions showed a P600 response for stereotype violations, suggesting that they experienced the mismatch as an agreement violation; whereas less expressive participants showed an Nref effect, indicating more effort spent in linking the pronouns with the possible, although less likely, counter-stereotypical referent.

  10. The role of vitamin D in multiple sclerosis: biology & biochemistry, epidemiology and potential roles in treatment.

    Science.gov (United States)

    Simpson, Steve; der Mei, Ingrid van; Taylor, Bruce

    2017-09-21

    Multiple sclerosis (MS) is a progressive, demyelinating condition of the central nervous system, manifesting in loss or alterations in function of sensory, motor and cognitive function. Of the various environmental and behavioural risk factors identified as playing a role in MS onset and progression, perhaps none has been as consistent as vitamin D. In this review, we will endeavour to present a general background on the role of vitamin D in human health and particularly in MS, as well as the substantial epidemiological evidence in support of vitamin D's role in MS. Identified initially indirectly via the oft-noted latitudinal gradient in MS prevalence and incidence, vitamin D has since been demonstrated to have a strong and consistent inverse association with MS risk and clinical course. Cases have much lower levels of the diagnostic metabolite of vitamin D, 25-hydroxyvitamin D (25(OH)D) compared to healthy controls, while those with more active disease have lower levels of 25(OH)D than other cases with less active disease. These case-control and cross-sectional study results led the way to cohort studies which indicated significant inverse associations between serum 25(OH)D and clinical activity in MS. The combined weight of indirect and direct observational evidence have been the impetus for completed and ongoing randomised trials of vitamin D supplementation, alone or in addition to standard immunomodulatory medications, as an intervention in MS onset and clinical course. Moreover, in addition to being a distinct factor in MS aetiology, vitamin D has been demonstrated to interact with a variety of other risk factors, from genetic predictors like HLA-DR1 genotype to behavioural factors like smoking. There is an abundance of epidemiological evidence, both direct and indirect, as well as significant biological plausibility substantiating a role for vitamin D in the onset & progression of multiple sclerosis. Copyright© Bentham Science Publishers; For any queries

  11. Intratubular germ cell neoplasia of the human testis: heterogeneous protein expression and relation to invasive potential

    Science.gov (United States)

    Mitchell, Rod T; Camacho-Moll, Maria; Macdonald, Joni; Anderson, Richard A; Kelnar, Christopher JH; O’Donnell, Marie; Sharpe, Richard M; Smith, Lee B; Grigor, Ken M; Wallace, W Hamish B; Stoop, Hans; Wolffenbuttel, Katja P; Donat, Roland

    2014-01-01

    Testicular germ cell cancer develops from pre-malignant intratubular germ cell neoplasia, unclassified cells that are believed to arise from failure of normal maturation of fetal germ cells from gonocytes (OCT4+/ MAGEA4−) into pre-spermatogonia (OCT4−/MAGEA4+). Intratubular germ cell neoplasia cell subpopulations based on stage of germ cell differentiation have been described, however the importance of these subpopulations in terms of invasive potential has not been reported. We hypothesised that cells expressing an immature (OCT4+/MAGEA4−) germ cell profile would exhibit an increased proliferation rate compared to those with a mature profile (OCT4+/ MAGEA4+). Therefore, we performed triple immunofluorescence and stereology to quantify the different intratubular germ cell neoplasia cell subpopulations, based on expression of germ cell (OCT4, PLAP, AP2γ, MAGEA4, VASA) and proliferation (Ki67) markers, in testis sections from patients with pre-invasive disease, seminoma and non-seminoma. We compared these subpopulations with normal human fetal testis and with seminoma cells. Heterogeneity of protein expression was demonstrated in intratubular germ cell neoplasia cells with respect to gonocyte and spermatogonial markers. It included an embryonic/fetal germ cell subpopulation lacking expression of the definitive intratubular germ cell neoplasia marker OCT4, that did not correspond to a physiological (fetal) germ cell subpopulation. OCT4+/MAGEA4- cells showed a significantly increased rate of proliferation compared with the OCT4+/MAGEA4+ population (12.8 v 3.4%, pneoplasia, which appears to be an important factor in determining invasive potential of intratubular germ cell neoplasia to seminomas. PMID:24457464

  12. Functional role of acetylcholine and the expression of cholinergic receptors and components in osteoblasts.

    Science.gov (United States)

    Sato, Tsuyoshi; Abe, Takahiro; Chida, Dai; Nakamoto, Norimichi; Hori, Naoko; Kokabu, Shoichiro; Sakata, Yasuaki; Tomaru, Yasuhisa; Iwata, Takanori; Usui, Michihiko; Aiko, Katsuya; Yoda, Tetsuya

    2010-02-19

    Recent studies have indicated that acetylcholine (ACh) plays a vital role in various tissues, while the role of ACh in bone metabolism remains unclear. Here we demonstrated that ACh induced cell proliferation and reduced alkaline phosphatase (ALP) activity via nicotinic (nAChRs) and muscarinic acetylcholine receptors (mAChRs) in osteoblasts. We detected mRNA expression of several nAChRs and mAChRs. Furthermore, we showed that cholinergic components were up-regulated and subunits/subtypes of acetylcholine receptors altered during osteoblast differentiation. To our knowledge, this is the first report demonstrating that osteoblasts express specific acetylcholine receptors and cholinergic components and that ACh plays a possible role in regulating the proliferation and differentiation of osteoblasts. Crown Copyright 2010. Published by Elsevier B.V. All rights reserved.

  13. Identification of metalloprotease/disintegrins in Xenopus laevis testis with a potential role in fertilization.

    Science.gov (United States)

    Shilling, F M; Krätzschmar, J; Cai, H; Weskamp, G; Gayko, U; Leibow, J; Myles, D G; Nuccitelli, R; Blobel, C P

    1997-06-15

    Proteins containing a membrane-anchored metalloprotease domain, a disintegrin domain, and a cysteine-rich region (MDC proteins) are thought to play an important role in mammalian fertilization, as well as in somatic cell-cell interactions. We have identified PCR sequence tags encoding the disintegrin domain of five distinct MDC proteins from Xenopus laevis testis cDNA. Four of these sequence tags (xMDC9, xMDC11.1, xMDC11.2, and xMDC13) showed strong similarity to known mammalian MDC proteins, whereas the fifth (xMDC16) apparently represents a novel family member. Northern blot analysis revealed that the mRNA for xMDC16 was only expressed in testis, and not in heart, muscle, liver, ovaries, or eggs, whereas the mRNAs corresponding to the four other PCR products were expressed in testis and in some or all somatic tissues tested. The xMDC16 protein sequence, as predicted from the full-length cDNA, contains a metalloprotease domain with the active-site sequence HEXXH, a disintegrin domain, a cysteine-rich region, an EGF repeat, a transmembrane domain, and a short cytoplasmic tail. To study a potential role for these xMDC proteins in fertilization, peptides corresponding to the predicted integrin-binding domain of each protein were tested for their ability to inhibit X. laevis fertilization. Cyclic and linear xMDC16 peptides inhibited fertilization in a concentration-dependent manner, whereas xMDC16 peptides that were scrambled or had certain amino acid replacements in the predicted integrin-binding domain did not affect fertilization. Cyclic and linear xMDC9 peptides and linear xMDC13 peptides also inhibited fertilization similarly to xMDC16 peptides, whereas peptides corresponding to the predicted integrin-binding site of xMDC11.1 and xMDC11.2 did not. These results are discussed in the context of a model in which multiple MDC protein-receptor interactions are necessary for fertilization to occur.

  14. Identification of potential biomarkers and drugs for papillary thyroid cancer based on gene expression profile analysis.

    Science.gov (United States)

    Qu, Ting; Li, Yan-Ping; Li, Xiao-Hong; Chen, Yan

    2016-12-01

    The present study aimed to systematically examine the molecular mechanisms of papillary thyroid cancer (PTC), and identify potential biomarkers and drugs for the treatment of PTC. Two microarray data sets (GSE3467 and GSE3678), containing 16 PTC samples and 16 paired normal samples, were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified using the Linear Models for Microarray Analysis package. Subsequently, the common DEGs were screened for functional and pathway enrichment analysis using the Database for Annotation Visualization and Integrated Discovery. The representative interaction subnetwork was further derived using Molecular Complex Detection software. In addition, the potential drugs for the hub DEGs in the subnetwork were screened from DrugBank and the potential drug‑like ligands, which interacted with genes, were selected using MTiOpenScreen. A total of 167 common DEGs, including 77 upregulated and 90 downregulated DEGs, were screened. The common DEGs were associated with the functions of plasma membrane, extracellular matrix, response to steroid hormone stimulus and cell adhesion, and the pathways of tyrosine metabolism and cell adhesion molecules were significantly enriched. A total of eight common DEGs (MET, SERPINA1, LGALS3, FN1, TNFRSF11B, LAMB3 and COL13A1) were involved in the subnetwork. The two drugs, lanoteplase and ocriplasmin, and four drugs, β‑mercaptoethanol, recombinant α 1‑antitrypsin, PPL‑100 and API, were found for FN1 and SERPINA1, respectively. The common DEGs identified may be potential biomarkers for PCT. FN1 and SERPINA1 may be involved in PTC by regulating epithelial‑to‑mesenchymal transition and responding to steroid hormone stimuli, respectively. Ocriplasmin, β‑mercaptoethanol and recombinant α 1‑antitrypsin may be potential drugs for the treatment of PTC.

  15. Proteome profiling of neuroblastoma-derived exosomes reveal the expression of proteins potentially involved in tumor progression.

    Directory of Open Access Journals (Sweden)

    Danilo Marimpietri

    Full Text Available Neuroblastoma (NB is the most common extracranial solid tumor in childhood, with grim prognosis in a half of patients. Exosomes are nanometer-sized membrane vesicles derived from the multivesicular bodies (MVBs of the endocytic pathway and released by normal and neoplastic cells. Tumor-derived exosomes have been shown in different model systems to carry molecules that promote cancer growth and dissemination. In this respect, we have here performed the first characterization and proteomic analysis of exosomes isolated from human NB cell lines by filtration and ultracentrifugation. Electron microscopy demonstrated that NB-derived exosomes exhibited the characteristic cup-shaped morphology. Dynamic light scattering studies showed a bell-shaped curve and a polydispersity factor consistent with those of exosomes. Zeta potential values suggested a good nanoparticle stability. We performed proteomic analysis of NB-derived exosomes by two dimension liquid chromatography separation and mass spectrometry analyses using the multidimensional protein identification technology strategy. We found that the large majority of the proteins identified in NB derived exosomes are present in Exocarta database including tetraspanins, fibronectin, heat shock proteins, MVB proteins, cytoskeleton-related proteins, prominin-1 (CD133, basigin (CD147 and B7-H3 (CD276. Expression of the CD9, CD63 and CD81 tetraspanins, fibronectin, CD133, CD147 and CD276 was validated by flow cytometry. Noteworthy, flow cytometric analysis showed that NB-derived exosomes expressed the GD2 disialoganglioside, the most specific marker of NB. In conclusion, this study shows that NB-derived exosomes express a discrete set of molecules involved in defense response, cell differentiation, cell proliferation and regulation of other important biological process. Thus, NB-derived exosomes may play an important role in the modulation of tumor microenvironment and represent potential tumor biomarkers.

  16. Triphenyl phosphate-induced developmental toxicity in zebrafish: Potential role of the retinoic acid receptor

    Energy Technology Data Exchange (ETDEWEB)

    Isales, Gregory M.; Hipszer, Rachel A.; Raftery, Tara D. [Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC (United States); Chen, Albert; Stapleton, Heather M. [Division of Environmental Sciences and Policy, Nicholas School of the Environment, Duke University, Durham, NC (United States); Volz, David C., E-mail: volz@mailbox.sc.edu [Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC (United States)

    2015-04-15

    Highlights: • Triphenyl phosphate-induced toxicity in zebrafish embryos is enhanced in the presence of a retinoic acid receptor antagonist. • Triphenyl phosphate uptake or metabolism within zebrafish embryos is not altered in the presence of a retinoic acid receptor antagonist. • Triphenyl phosphate decreases expression of cytochrome P450 26a1 in zebrafish embryos. • Triphenyl phosphate inhibits retinoic acid-induced activation of human retinoic acid receptors. - Abstract: Using zebrafish as a model, we previously reported that developmental exposure to triphenyl phosphate (TPP) – a high-production volume organophosphate-based flame retardant – results in dioxin-like cardiac looping impairments that are independent of the aryl hydrocarbon receptor. Using a pharmacologic approach, the objective of this study was to investigate the potential role of retinoic acid receptor (RAR) – a nuclear receptor that regulates vertebrate heart morphogenesis – in mediating TPP-induced developmental toxicity in zebrafish. We first revealed that static exposure of zebrafish from 5–72 h post-fertilization (hpf) to TPP in the presence of non-toxic concentrations of an RAR antagonist (BMS493) significantly enhanced TPP-induced toxicity (relative to TPP alone), even though identical non-toxic BMS493 concentrations mitigated retinoic acid (RA)-induced toxicity. BMS493-mediated enhancement of TPP toxicity was not a result of differential TPP uptake or metabolism, as internal embryonic doses of TPP and diphenyl phosphate (DPP) – a primary TPP metabolite – were not different in the presence or absence of BMS493. Using real-time PCR, we then quantified the relative change in expression of cytochrome P450 26a1 (cyp26a1) – a major target gene for RA-induced RAR activation in zebrafish – and found that RA and TPP exposure resulted in a ∼5-fold increase and decrease in cyp26a1 expression, respectively, relative to vehicle-exposed embryos. To address whether TPP may

  17. Differential effect of CLK SR Kinases on HIV-1 gene expression: potential novel targets for therapy

    Directory of Open Access Journals (Sweden)

    Dobson Wendy

    2011-06-01

    Full Text Available Abstract Background RNA processing plays a critical role in the replication of HIV-1, regulated in part through the action of host SR proteins. To explore the impact of modulating SR protein activity on virus replication, the effect of increasing or inhibiting the activity of the Cdc2-like kinase (CLK family of SR protein kinases on HIV-1 expression and RNA processing was examined. Results Despite their high homology, increasing individual CLK expression had distinct effects on HIV-1, CLK1 enhancing Gag production while CLK2 inhibited the virus. Parallel studies on the anti-HIV-1 activity of CLK inhibitors revealed a similar discrepant effect on HIV-1 expression. TG003, an inhibitor of CLK1, 2 and 4, had no effect on viral Gag synthesis while chlorhexidine, a CLK2, 3 and 4 inhibitor, blocked virus production. Chlorhexidine treatment altered viral RNA processing, decreasing levels of unspliced and single spliced viral RNAs, and reduced Rev accumulation. Subsequent experiments in the context of HIV-1 replication in PBMCs confirmed the capacity of chlorhexidine to suppress virus replication. Conclusions Together, these findings establish that HIV-1 RNA processing can be targeted to suppress virus replication as demonstrated by manipulating individual CLK function and identified chlorhexidine as a lead compound in the development of novel anti-viral therapies.

  18. Gene expression analysis after receptor tyrosine kinase activation reveals new potential melanoma proteins

    Directory of Open Access Journals (Sweden)

    Krause Michael

    2010-07-01

    Full Text Available Abstract Background Melanoma is an aggressive tumor with increasing incidence. To develop accurate prognostic markers and targeted therapies, changes leading to malignant transformation of melanocytes need to be understood. In the Xiphophorus melanoma model system, a mutated version of the EGF receptor Xmrk (Xiphophorus melanoma receptor kinase triggers melanomagenesis. Cellular events downstream of Xmrk, such as the activation of Akt, Ras, B-Raf or Stat5, were also shown to play a role in human melanomagenesis. This makes the elucidation of Xmrk downstream targets a useful method for identifying processes involved in melanoma formation. Methods Here, we analyzed Xmrk-induced gene expression using a microarray approach. Several highly expressed genes were confirmed by realtime PCR, and pathways responsible for their induction were revealed using small molecule inhibitors. The expression of these genes was also monitored in human melanoma cell lines, and the target gene FOSL1 was knocked down by siRNA. Proliferation and migration of siRNA-treated melanoma cell lines were then investigated. Results Genes with the strongest upregulation after receptor activation were FOS-like antigen 1 (Fosl1, early growth response 1 (Egr1, osteopontin (Opn, insulin-like growth factor binding protein 3 (Igfbp3, dual-specificity phosphatase 4 (Dusp4, and tumor-associated antigen L6 (Taal6. Interestingly, most genes were blocked in presence of a SRC kinase inhibitor. Importantly, we found that FOSL1, OPN, IGFBP3, DUSP4, and TAAL6 also exhibited increased expression levels in human melanoma cell lines compared to human melanocytes. Knockdown of FOSL1 in human melanoma cell lines reduced their proliferation and migration. Conclusion Altogether, the data show that the receptor tyrosine kinase Xmrk is a useful tool in the identification of target genes that are commonly expressed in Xmrk-transgenic melanocytes and melanoma cell lines. The identified molecules constitute

  19. Gene expression analysis after receptor tyrosine kinase activation reveals new potential melanoma proteins.

    Science.gov (United States)

    Teutschbein, Janka; Haydn, Johannes M; Samans, Birgit; Krause, Michael; Eilers, Martin; Schartl, Manfred; Meierjohann, Svenja

    2010-07-21

    Melanoma is an aggressive tumor with increasing incidence. To develop accurate prognostic markers and targeted therapies, changes leading to malignant transformation of melanocytes need to be understood. In the Xiphophorus melanoma model system, a mutated version of the EGF receptor Xmrk (Xiphophorus melanoma receptor kinase) triggers melanomagenesis. Cellular events downstream of Xmrk, such as the activation of Akt, Ras, B-Raf or Stat5, were also shown to play a role in human melanomagenesis. This makes the elucidation of Xmrk downstream targets a useful method for identifying processes involved in melanoma formation. Here, we analyzed Xmrk-induced gene expression using a microarray approach. Several highly expressed genes were confirmed by realtime PCR, and pathways responsible for their induction were revealed using small molecule inhibitors. The expression of these genes was also monitored in human melanoma cell lines, and the target gene FOSL1 was knocked down by siRNA. Proliferation and migration of siRNA-treated melanoma cell lines were then investigated. Genes with the strongest upregulation after receptor activation were FOS-like antigen 1 (Fosl1), early growth response 1 (Egr1), osteopontin (Opn), insulin-like growth factor binding protein 3 (Igfbp3), dual-specificity phosphatase 4 (Dusp4), and tumor-associated antigen L6 (Taal6). Interestingly, most genes were blocked in presence of a SRC kinase inhibitor. Importantly, we found that FOSL1, OPN, IGFBP3, DUSP4, and TAAL6 also exhibited increased expression levels in human melanoma cell lines compared to human melanocytes. Knockdown of FOSL1 in human melanoma cell lines reduced their proliferation and migration. Altogether, the data show that the receptor tyrosine kinase Xmrk is a useful tool in the identification of target genes that are commonly expressed in Xmrk-transgenic melanocytes and melanoma cell lines. The identified molecules constitute new possible molecular players in melanoma development

  20. Expression and distribution of the transient receptor potential cationic channel ankyrin 1 (TRPA1) in the human vagina.

    Science.gov (United States)

    Ückert, S; Sonnenberg, J E; Albrecht, K; Kuczyk, M A; Hedlund, P

    2015-01-01

    The transient receptor potential cationic channel type A1 (TRPA1), belonging to a superfamily of cationic membrane channels, has been suggested to act as mechano- and pain sensor and, thus, to play a role in neurotransmission in the human body, including the urogenital tract. While the expression of TRPA1 has been investigated in a variety of tissues, up until today, no study has addressed the expression and distribution in the female genital tract. The present study aimed to investigate the expression and distribution of TRPA1 protein in human vaginal tissue. Reverse transcriptase PCR (RT-PCR) was applied in order to identify messenger ribonuleic acid specifically encoding for TRPA/A1. The distribution of TRPA1 in relation to the neuronal nitric oxide synthase (nNOS) and the signaling peptide calcitonin gene-related peptide (CGRP) was examined by means of immunohistochemical methods (double-antibody technique, laser fluorescence microscopy). RT-PCR analysis revealed the expression of mRNA encoding sequences specific for TRPA in the vaginal wall and epithelium. Immunostaining related to TRPA1 was observed in the basal epithelium and in slender varicose nerve fibers transversing the subepithelial and stromal space of the vaginal sections. In addition, these fibers presented immunoreactivity specific for nNOS or CGRP. The smooth musculature of the vaginal wall and small vessels interspersing the tissue did not present signals related to TRPA1. The findings indicate that TRPA1 might be involved in afferent neurotransmission in the vagina and work synergistically together with the nitric oxide/cyclic guanosine monophosphate pathway.

  1. Intestinal lactic acid bacteria from Muscovy duck as potential probiotics that alter adhesion factor gene expression.

    Science.gov (United States)

    Xie, Z L; Bai, D P; Xie, L N; Zhang, W N; Huang, X H; Huang, Y F

    2015-10-09

    The purpose of this study was to assess the suitability of lactic acid bacteria (LABs) isolated from Muscovy duck as a potential probiotic. Isolates were identified by targeted polymerase chain reaction and assessed in vitro for probiotic characteristics such as autoaggregation; surface-charge; hydrophobicity; tolerance to acidic pH, bile salts and protease; and expression of genes involved in Caco-2 cell adhesion. The LAB isolates exhibited strong resistance to high bile concentration and acidic pH, produced lactic acid, and bacteriostatic (P probiotic bacteria and can facilitate the establishment of criteria to select probiotic strains for the prevention of diarrhea.

  2. Increased transient receptor potential vanilloid type 1 (TRPV1) channel expression in hypertrophic heart

    DEFF Research Database (Denmark)

    Thilo, Florian; Liu, Ying; Schulz, Nico

    2010-01-01

    The aim of this study was to compare the expression of transient receptor potential vanilloid type 1 (TRPV1) channels in hypertrophic hearts from transgenic mice showing overexpression of the catalytic subunit alpha of protein phosphatase 2A alpha (PP2Ac alpha) with wild-type mice and with TRPV1......-/- mice. Transcripts of TRPV1, matrix metalloproteinase 9 (MMP9), discoidin domain receptor family, member 2 (DDR-2), atrial natriuretic peptide (ANP), GATA 4, and regulatory microRNA (miR-21) were analyzed using quantitative real-time PCR. Ventricle-to-body-weight-ratio was significantly higher in PP2Ac...

  3. Extracellular Vesicles: Role in Inflammatory Responses and Potential Uses in Vaccination in Cancer and Infectious Diseases

    Science.gov (United States)

    Campos, João Henrique; Soares, Rodrigo Pedro; Ribeiro, Kleber; Cronemberger Andrade, André; Batista, Wagner Luiz; Torrecilhas, Ana Claudia

    2015-01-01

    Almost all cells and organisms release membrane structures containing proteins, lipids, and nucleic acids called extracellular vesicles (EVs), which have a wide range of functions concerning intercellular communication and signaling events. Recently, the characterization and understanding of their biological role have become a main research area due to their potential role in vaccination, as biomarkers antigens, early diagnostic tools, and therapeutic applications. Here, we will overview the recent advances and studies of Evs shed by tumor cells, bacteria, parasites, and fungi, focusing on their inflammatory role and their potential use in vaccination and diagnostic of cancer and infectious diseases. PMID:26380326

  4. HLA-G expression and role in advanced-stage classical Hodgkin lymphoma

    Directory of Open Access Journals (Sweden)

    G. Caocci

    2016-04-01

    Full Text Available Non-classical human leucocyte antigen (HLA-G class I molecules have an important role in tumor immune escape mechanisms. We investigated HLA-G expression in lymphonode biopsies taken from 8 controls and 20 patients with advanced-stage classical Hodgkin lymphoma (cHL, in relationship to clinical outcomes and the HLA-G 14-basepair (14-bp deletion-insertion (del-ins polymorphism. Lymphnode tissue sections were stained using a specific murine monoclonal HLA-G antibody. HLA-G protein expression was higher in cHL patients than controls. In the group of PET-2 positive (positron emission tomography carried out after 2 cycles of standard chemotherapy patients with a 2-year progression-free survival rate (PFS of 40%, we observed high HLA-G protein expression within the tumor microenvironment with low expression on Hodgkin and Reed-Sternberg (HRS cells. Conversely, PET-2 negative patients with a PFS of 86% had higher HLA-G protein expression levels on HRS cells compared to the microenvironment. Lower expression on HRS cells was significantly associated with the HLA-G 14-bp ins/ins genotype. These preliminary data suggest that the immunohistochemical pattern of HLA-G protein expression may represent a useful tool for a tailored therapy in patients with cHL, based on the modulation of HLA-G expression in relation to achievement of negative PET-2.These preliminary data suggest that the immunohistochemical pattern of HLA-G protein expression may represent a useful tool for a tailored therapy in patients with cHL, based on the modulation of HLA-G expression in relation to achievement of negative PET-2.

  5. Exploring Expressive Vocabulary Variability in Two-Year-Olds: The Role of Working Memory.

    Science.gov (United States)

    Newbury, Jayne; Klee, Thomas; Stokes, Stephanie F; Moran, Catherine

    2015-12-01

    This study explored whether measures of working memory ability contribute to the wide variation in 2-year-olds' expressive vocabulary skills. Seventy-nine children (aged 24-30 months) were assessed by using standardized tests of vocabulary and visual cognition, a processing speed measure, and behavioral measures of verbal working memory and phonological short-term memory. Strong correlations were observed between phonological short-term memory, verbal working memory, and expressive vocabulary. Speed of spoken word recognition showed a moderate significant correlation with expressive vocabulary. In a multivariate regression model for expressive vocabulary, the most powerful predictor was a measure of phonological short-term memory (accounting for 66% unique variance), followed by verbal working memory (6%), sex (2%), and age (1%). Processing speed did not add significant unique variance. These findings confirm previous research positing a strong role for phonological short-term memory in early expressive vocabulary acquisition. They also extend previous research in two ways. First, a unique association between verbal working memory and expressive vocabulary in 2-year-olds was observed. Second, processing speed was not a unique predictor of variance in expressive vocabulary when included alongside measures of working memory.

  6. Neural differentiation potential of human bone marrow-derived mesenchymal stromal cells: misleading marker gene expression

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    Montzka Katrin

    2009-03-01

    Full Text Available Abstract Background In contrast to pluripotent embryonic stem cells, adult stem cells have been considered to be multipotent, being somewhat more restricted in their differentiation capacity and only giving rise to cell types related to their tissue of origin. Several studies, however, have reported that bone marrow-derived mesenchymal stromal cells (MSCs are capable of transdifferentiating to neural cell types, effectively crossing normal lineage restriction boundaries. Such reports have been based on the detection of neural-related proteins by the differentiated MSCs. In order to assess the potential of human adult MSCs to undergo true differentiation to a neural lineage and to determine the degree of homogeneity between donor samples, we have used RT-PCR and immunocytochemistry to investigate the basal expression of a range of neural related mRNAs and proteins in populations of non-differentiated MSCs obtained from 4 donors. Results The expression analysis revealed that several of the commonly used marker genes from other studies like nestin, Enolase2 and microtubule associated protein 1b (MAP1b are already expressed by undifferentiated human MSCs. Furthermore, mRNA for some of the neural-related transcription factors, e.g. Engrailed-1 and Nurr1 were also strongly expressed. However, several other neural-related mRNAs (e.g. DRD2, enolase2, NFL and MBP could be identified, but not in all donor samples. Similarly, synaptic vesicle-related mRNA, STX1A could only be detected in 2 of the 4 undifferentiated donor hMSC samples. More significantly, each donor sample revealed a unique expression pattern, demonstrating a significant variation of marker expression. Conclusion The present study highlights the existence of an inter-donor variability of expression of neural-related markers in human MSC samples that has not previously been described. This donor-related heterogeneity might influence the reproducibility of transdifferentiation protocols as

  7. Event-related potentials to task-irrelevant changes in facial expressions

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    Astikainen Piia

    2009-07-01

    Full Text Available Abstract Background Numerous previous experiments have used oddball paradigm to study change detection. This paradigm is applied here to study change detection of facial expressions in a context which demands abstraction of the emotional expression-related facial features among other changing facial features. Methods Event-related potentials (ERPs were recorded in adult humans engaged in a demanding auditory task. In an oddball paradigm, repeated pictures of faces with a neutral expression ('standard', p = .9 were rarely replaced by pictures with a fearful ('fearful deviant', p = .05 or happy ('happy deviant', p = .05 expression. Importantly, facial identities changed from picture to picture. Thus, change detection required abstraction of facial expression from changes in several low-level visual features. Results ERPs to both types of deviants differed from those to standards. At occipital electrode sites, ERPs to deviants were more negative than ERPs to standards at 150–180 ms and 280–320 ms post-stimulus. A positive shift to deviants at fronto-central electrode sites in the analysis window of 130–170 ms post-stimulus was also found. Waveform analysis computed as point-wise comparisons between the amplitudes elicited by standards and deviants revealed that the occipital negativity emerged earlier to happy deviants than to fearful deviants (after 140 ms versus 160 ms post-stimulus, respectively. In turn, the anterior positivity was earlier to fearful deviants than to happy deviants (110 ms versus 120 ms post-stimulus, respectively. Conclusion ERP amplitude differences between emotional and neutral expressions indicated pre-attentive change detection of facial expressions among neutral faces. The posterior negative difference at 150–180 ms latency resembled visual mismatch negativity (vMMN – an index of pre-attentive change detection previously studied only to changes in low-level features in vision. The positive anterior difference in

  8. A new role for GABAergic transmission in the control of male rat sexual behavior expression.

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    Rodríguez-Manzo, Gabriela; Canseco-Alba, Ana

    2017-03-01

    GABAergic transmission in the ventral tegmental area (VTA) exerts a tonic inhibitory influence on mesolimbic dopaminergic neurons' activity. Blockade of VTA GABAA receptors increases dopamine release in the nucleus accumbens (NAcc). Increases in NAcc dopamine levels typically accompany sexual behavior display. Copulation to satiety is characterized by the instatement of a long lasting (72h) sexual behavior inhibition and the mesolimbic system appears to be involved in this phenomenon. GABAergic transmission in the VTA might play a role in the maintenance of this long lasting sexual inhibitory state. To test this hypothesis, in the present work we investigated the effect of GABAA receptor blockade in sexually exhausted males 24h after copulation to satiety, once the sexual inhibitory state is established, and compared it with its effect in sexually experienced rats. Results showed that low doses of systemically administered bicuculline induced sexual behavior expression in sexually exhausted rats, but lacked an effect on copulation of sexually experienced animals. Intra-VTA bilateral infusion of bicuculline did not modify sexual behavior of sexually experienced rats, but induced sexual behavior expression in all the sexually exhausted males. Hence, GABA plays a role in the control of sexual behavior expression at the VTA. The role played by GABAergic transmission in male sexual behavior expression of animals with distinct sexual behavior conditions is discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Isolation and gene expression analysis of single potential human spermatogonial stem cells.

    Science.gov (United States)

    von Kopylow, K; Schulze, W; Salzbrunn, A; Spiess, A-N

    2016-04-01

    It is possible to isolate pure populations of single potential human spermatogonial stem cells without somatic contamination for down-stream applications, for example cell culture and gene expression analysis. We isolated pure populations of single potential human spermatogonial stem cells (hSSC) without contaminating somatic cells and analyzed gene expression of these cells via single-cell real-time RT-PCR. The isolation of a pure hSSC fraction could enable clinical applications such as fertility preservation for prepubertal boys and in vitro-spermatogenesis. By utilizing largely nonspecific markers for the isolation of spermatogonia (SPG) and hSSC, previously published cell selection methods are not able to deliver pure target cell populations without contamination by testicular somatic cells. However, uniform cell populations free of somatic cells are necessary to guarantee defined growth conditions in cell culture experiments and to prevent unintended stem cell differentiation. Fibroblast growth factor receptor 3 (FGFR3) is a cell surface protein of human undifferentiated A-type SPG and a promising candidate marker for hSSC. It is exclusively expressed in small, non-proliferating subgroups of this spermatogonial cell type together with the pluripotency-associated protein and spermatogonial nuclear marker undifferentiated embryonic cell transcription factor 1 (UTF1). We specifically selected the FGFR3-positive spermatogonial subpopulation from two 30 mg biopsies per patient from a total of 37 patients with full spermatogenesis and three patients with meiotic arrest. We then employed cell selection with magnetic beads in combination with a fluorescence-activated cell sorter antibody directed against human FGFR3 to tag and visually identify human FGFR3-positive spermatogonia. Positively selected and bead-labeled cells were subsequently picked with a micromanipulator. Analysis of the isolated cells was carried out by single-cell real-time RT-PCR, real-time RT

  10. Ciliary neurotrophic factor role in myelin oligodendrocyte glycoprotein expression in Cuprizone-induced multiple sclerosis mice.

    Science.gov (United States)

    Salehi, Zivar; Hadiyan, Sara Pishgah; Navidi, Reza

    2013-05-01

    Multiple sclerosis (MS) is an inflammatory disease of the central nervous system that leads to loss of myelin and oligodendrocytes and damage to axons. Myelin oligodendrocyte glycoprotein (MOG) is a minor component of the myelin sheath, but is an important autoantigen linked to the pathogenesis of MS. Ciliary neurotrophic factor (CNTF) has been shown to enhance the generation, maturation, and survival of oligodendrocytes in culture medium. The aim of this study was to demonstrate the role of CNTF on MOG expression in the cerebral cortex of Cuprizone-induced MS mice. The mice were treated by Cuprizone for five weeks in order to induce MS. The mice were then divided into 3 groups. The first group was injected subcutaneously (SC) by CNTF in the amount of 250 μg/kg BW per day. The second group (SHAM) was injected SC by normal saline and the third group was left without injection as the control group. After four weeks the mice were killed and the cerebral cortex was harvested and the expression of MOG was studied by Western blotting. The data from this study show that the MOG expression was significantly increased in the CNTF-injected group as compared to the other groups. It is concluded that CNTF increases the MOG expression and may be important in the pathophysiology of MS. It is also concluded that CNTF may play a role in the process of remyelination by inducing the MOG expression.

  11. Redundant phenazine operons in Pseudomonas aeruginosa exhibit environment-dependent expression and differential roles in pathogenicity.

    Science.gov (United States)

    Recinos, David A; Sekedat, Matthew D; Hernandez, Adriana; Cohen, Taylor Sitarik; Sakhtah, Hassan; Prince, Alice S; Price-Whelan, Alexa; Dietrich, Lars E P

    2012-11-20

    Evolutionary biologists have postulated that several fitness advantages may be conferred by the maintenance of duplicate genes, including environmental adaptation resulting from differential regulation. We examined the expression and physiological contributions of two redundant operons in the adaptable bacterium Pseudomonas aeruginosa PA14. These operons, phzA1-G1 (phz1) and phzA2-G2 (phz2), encode nearly identical sets of proteins that catalyze the synthesis of phenazine-1-carboxylic acid, the precursor for several phenazine derivatives. Phenazines perform diverse roles in P. aeruginosa physiology and act as virulence factors during opportunistic infections of plant and animal hosts. Although reports have indicated that phz1 is regulated by the Pseudomonas quinolone signal, factors controlling phz2 expression have not been identified, and the relative contributions of these redundant operons to phenazine biosynthesis have not been evaluated. We found that in liquid cultures, phz1 was expressed at higher levels than phz2, although phz2 showed a greater contribution to phenazine production. In colony biofilms, phz2 was expressed at high levels, whereas phz1 expression was not detectable, and phz2 was responsible for virtually all phenazine production. Analysis of mutants defective in quinolone signal synthesis revealed a critical role for 4-hydroxy-2-heptylquinoline in phz2 induction. Finally, deletion of phz2, but not of phz1, decreased lung colonization in a murine model of infection. These results suggest that differential regulation of the redundant phz operons allows P. aeruginosa to adapt to diverse environments.

  12. The role of palmitoylation in functional expression of nicotinic alpha7 receptors.

    Science.gov (United States)

    Drisdel, Renaldo C; Manzana, Ehrine; Green, William N

    2004-11-17

    Neuronal alpha-bungarotoxin receptors (BgtRs) are nicotinic receptors that require as yet unidentified post-translational modifications to achieve functional expression. In this study, we examined the role of protein palmitoylation in BgtR expression. BgtR alpha7 subunits are highly palmitoylated in neurons from brain and other cells capable of BgtR expression, such as pheochromocytoma 12 (PC12) cells. In PC12 cells, alpha7 subunits are palmitoylated with a stoichiometry of approximately one palmitate per subunit, and inhibition of palmitoylation blocks BgtR expression. In cells incapable of BgtR expression, such as human embryonic kidney cells, alpha7 subunits are not significantly palmitoylated. However, in these same cells, chimeric subunits with the N-terminal half of alpha7 fused to the C-terminal half of serotonin-3A receptor (alpha7/5-HT3A) subunits form functional BgtRs that are palmitoylated to an extent similar to that of BgtRalpha7 subunits in PC12 cells. Palmitoylation of PC12 and alpha7/5-HT3A BgtRs occurred during assembly in the endoplasmic reticulum (ER). In conclusion, our data indicate a function for protein palmitoylation in which palmitoylation of assembling alpha7 subunits in the ER has a role in the formation of functional BgtRs.

  13. Characterisation of the potential function of SVA retrotransposons to modulate gene expression patterns.

    Science.gov (United States)

    Savage, Abigail L; Bubb, Vivien J; Breen, Gerome; Quinn, John P

    2013-05-21

    Retrotransposons are a major component of the human genome constituting as much as 45%. The hominid specific SINE-VNTR-Alus are the youngest of these elements constituting 0.13% of the genome; they are therefore a practical and amenable group for analysis of both their global integration, polymorphic variation and their potential contribution to modulation of genome regulation. Consistent with insertion into active chromatin we have determined that SVAs are more prevalent in genic regions compared to gene deserts. The consequence of which, is that their integration has greater potential to have affects on gene regulation. The sequences of SVAs show potential for the formation of secondary structure including G-quadruplex DNA. We have shown that the human specific SVA subtypes (E-F1) show the greatest potential for forming G-quadruplexes within the central tandem repeat component in addition to the 5' 'CCCTCT' hexamer. We undertook a detailed analysis of the PARK7 SVA D, located in the promoter of the PARK7 gene (also termed DJ-1), in a HapMap cohort where we identified 2 variable number tandem repeat domains and 1 tandem repeat within this SVA with the 5' CCCTCT element being one of the variable regions. Functionally we were able to demonstrate that this SVA contains multiple regulatory elements that support reporter gene expression in vitro and further show these elements exhibit orientation dependency. Our data supports the hypothesis that SVAs integrate preferentially in to open chromatin where they could modify the existing transcriptional regulatory domains or alter expression patterns by a variety of mechanisms.

  14. Gene expression profiles resulting from stable loss of p53 mirrors its role in tissue differentiation.

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    Oliver Couture

    Full Text Available The tumor suppressor gene p53 is involved in a variety of cellular activities such as cellular stress responses, cell cycle regulation and differentiation. In our previous studies we have shown p53's transcription activating role to be important in osteoblast differentiation. There is still a debate in the literature as to whether p53 inhibits or promotes differentiation. We have found p53 heterozygous mice to show a p53 dependency on some bone marker gene expression that is absent in knockout mice. Mice heterozygous for p53 also show a higher incidence of osteosarcomas than p53 knockout mice. This suggests that p53 is able to modify the environment within osteoblasts. In this study we compare changes in gene expression resulting after either a transient or stable reduction in p53. Accordingly we reduced p53 levels transiently and stably in C2C12 cells, which are capable of both myoblast and osteoblast differentiation, and compared the changes in gene expression of candidate genes regulated by the p53 pathway. Using a PCR array to assay for p53 target genes, we have found different expression profiles when comparing stable versus transient knockdown of p53. As expected, several genes with profound changes after transient p53 loss were related to apoptosis and cell cycle regulation. In contrast, stable p53 loss produced a greater change in MyoD and other transcription factors with tissue specific roles, suggesting that long term loss of p53 affects tissue homeostasis to a greater degree than changes resulting from acute loss of p53. These differences in gene expression were validated by measuring promoter activity of different pathway specific genes involved in differentiation. These studies suggest that an important role for p53 is context dependent, with a stable reduction in p53 expression affecting normal tissue physiology more than acute loss of p53.

  15. In the Intestinal Mucosa of Children With Potential Celiac Disease IL-21 and IL-17A are Less Expressed than in the Active Disease.

    Science.gov (United States)

    Borrelli, Melissa; Gianfrani, Carmen; Lania, Giuliana; Aitoro, Rosita; Ferrara, Katia; Nanayakkara, Merlin; Ponticelli, Domenico; Zanzi, Delia; Discepolo, Valentina; Vitale, Serena; Barone, Maria Vittoria; Troncone, Riccardo; Auricchio, Renata; Maglio, Mariantonia

    2016-01-01

    Potential celiac disease (CD) patients are at an increased risk to developing CD as indicated by positive CD-associated serology. We investigated in duodenal mucosa of such patients the presence of both IL-21 and IL-17A and the role of gliadin peptides and IL-15 in their expression. Duodenal biopsies from 76 active CD, 90 potential CD, and 58 control patients were analyzed for IL-21 and/or IL-17A production by quantitative real-time PCR, immunohistochemistry, flow cytometry, and ELISA. The presence of IL-21 receptor was investigated by western blot. Potential CD duodenal fragments were cultured with gliadin peptides (PTG) and/or IL-15 and the expression/production of IL-21 and IL-17A assessed by quantitative real-time PCR and by immunohistochemistry. In potential CD, IL-21 was lower than in active CD, in terms of RNA expression (P<0.01), density of lamina propria (LP) IL-21(+) cells (P<0.05), and protein secretion (P<0.05). Also, IL-21R was weakly detectable in potential CD. Several LP cell types produced IL-21 in CD. In potential CD, CD4(+)IL-21(+) cells increased after PMA-ionomycin stimulation and co-produced IFN-γ but not IL-17A. After 24 hours of culture stimulation with PTG, IL-21-producing cells increased but not the ones producing IL-17A. This increase was further enhanced by the addition of IL-15 to culture medium. In potential CD, IL-21 is less expressed than in active CD; however, IL-21-producing cells are present and prone to respond after specific stimuli. This suggests a key role of IL-21 in the progression of mucosal damage in CD.

  16. AKT isoforms have distinct hippocampal expression and roles in synaptic plasticity.

    Science.gov (United States)

    Levenga, Josien; Wong, Helen; Milstead, Ryan A; Keller, Bailey N; LaPlante, Lauren E; Hoeffer, Charles A

    2017-11-27

    AKT is a kinase regulating numerous cellular processes in the brain, and mutations in AKT are known to affect brain function. AKT is indirectly implicated in synaptic plasticity, but its direct role has not been studied. Moreover, three highly related AKT isoforms are expressed in the brain, but their individual roles are poorly understood. We find in Mus musculus , each AKT isoform has a unique expression pattern in the hippocampus, with AKT1 and AKT3 primarily in neurons but displaying local differences, while AKT2 is in astrocytes. We also find isoform-specific roles for AKT in multiple paradigms of hippocampal synaptic plasticity in area CA1. AKT1, but not AKT2 or AKT3, is required for L-LTP through regulating activity-induced protein synthesis. Interestingly, AKT activity inhibits mGluR-LTD, with overlapping functions for AKT1 and AKT3. In summary, our studies identify distinct expression patterns and roles in synaptic plasticity for AKT isoforms in the hippocampus.

  17. Expression of CCL19 from Oncolytic Vaccinia Enhances Immunotherapeutic Potential while Maintaining Oncolytic Activity

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    Jun Li

    2012-12-01

    Full Text Available Promising phase II clinical results have been reported recently for several oncolytic viral therapeutics, including strains based on vaccinia virus. One reason for this has been an increased appreciation of the critical therapeutic importance of the immune response raised by these viruses. However, the most commonly used approaches to enhance these immunotherapeutic effects in oncolytic viruses, typically though expression of cytokine transgenes, often also result in a reduction in oncolytic activity and premature clearance of the virotherapy from the tumor. Approaches that enhance the immunotherapeutic effects while maintaining oncolytic activity would therefore be beneficial. Here, it is demonstrated that the expression of the chemokine CCL19 (ELC from an oncolytic vaccinia virus (vvCCL19 results in increased antitumor effects in syngeneic mouse tumor models. This corresponded with increased t cell and dendritic cell infiltration into the tumor. However, vvCCL19 persisted in the tumor at equivalent levels to a control virus without CCL19, demonstrating that oncolytic activity was not curtailed. Instead, vvCCL19 was cleared rapidly and selectively from normal tissues and organs, indicating a potentially increased safety profile. The therapeutic activity of vvCCL19 could be further significantly increased through combination with adoptive transfer of therapeutic immune cells expressing CCR7, the receptor for CCL19. This approach therefore represents a means to increase the safety and therapeutic benefit of oncolytic viruses, used alone or in combination with immune cell therapies.

  18. Invasion potential and N-acetylgalactosamine expression in a human melanoma model.

    Science.gov (United States)

    Rye, P D; Fodstad, O; Emilsen, E; Bryne, M

    1998-02-09

    Reactivity of the N-acetylgalactosamine-binding Helix pomatia agglutinin (HPA) in tumours has been associated with poor prognosis and metastasis development. In our LOX/FEMX-I human melanoma model, the binding of HPA correlates with experimental lung metastasis formation in athymic nude mice. In the present study, the metastatic potential of 2 human melanoma cell lines (LOX and FEMX-I) was assessed in relation to carbohydrate and invasive phenotype. Immunocytological and invasion assays highlighted significant differences between these 2 cell lines. Immuno-cytochemical analysis confirmed the widespread expression of HPA-binding glycoconjugates on LOX but not FEMX-I cells. One of these HPA-binding glycoconjugates, the Tn antigen, was expressed highly on the surface of LOX cells but only weakly in the cytoplasm of FEMX-I cells. The sialyl Tn antigen was expressed in FEMX-I but not in LOX cells. There was no difference between the cell lines in adhesion/rate of trapping in athymic nude mouse lung tissues. In Matrigel invasion assays, LOX cells demonstrated an invasion potential more than 6 times greater than that observed with FEMX-I cells. Matrigel invasion of LOX cells was inhibited after incubation with HPA (89%) compared to controls with HPA and GalNAc blocking sugar or without HPA (p < 0.0005 at 5 df). In contrast, there was no inhibitory effect with the anti-Tn antibody IE3. Invasion of FEMX-I cells was not affected by the lectin and the IE3 antibody. Immuno-cytochemical analysis revealed expression of the terminal galactose- and polylactosamine-binding lectin galectin 3 (Mac-2) in these melanoma cell lines. Expression of both the lectin and its receptor may be a contributory feature in the pulmonary invasion of LOX melanoma cells. Overall, our findings suggest that HPA-binding glycoconjugates other than the alphaGalNAc-O-Ser/Thr of the Tn antigen may be important in the extracellular matrix invasion of LOX melanoma cells.

  19. Decorin over-expression by decidual cells in preeclampsia: a potential blood biomarker.

    Science.gov (United States)

    Siddiqui, Mohammad F; Nandi, Pinki; Girish, Gannareddy V; Nygard, Karen; Eastabrook, Genevieve; de Vrijer, Barbra; Han, Victor K M; Lala, Peeyush K

    2016-09-01

    difference between the 2 subject groups was noted in villus mesenchymal cells. Similarly decorin messenger RNA expression at the tissue level in chorionic villi (primarily resulting from fetally derived mesenchymal cells) did not differ significantly between control and preeclampsia placentas. These findings were validated with immunostaining for decorin protein. Second, knocking down decorin gene in a decorin over-expressing endometrial cell line (used as an in vitro surrogate of decorin over-expressing decidual cells) in cocultures with extravillous trophoblast cells abrogated its invasion-restraining actions on trophoblast cells, which indicated paracrine contribution of decorin over-expressing decidua to the poor trophoblast invasiveness in situ. Finally, retrospective measurement of plasma decorin levels during the second trimester in 28 body mass index-matched pairs of control subjects and subjects with preeclampsia revealed elevated plasma decorin levels in all subjects with preeclampsia in all body mass index groups. A receiver operating characteristic curve analysis revealed strong diagnostic performance of plasma decorin in the prediction of preeclampsia status. Although there was no significant gestational age-related change in decorin levels during the second trimester in control or subjects with preeclampsia, we found that plasma decorin had a significant inverse relationship with body mass index or bodyweight. We conclude that decorin over-expression by basal decidual cells is associated with hypoinvasive phenotype and poor endovascular differentiation of trophoblast cells in preeclampsia and that elevated plasma decorin concentration is a potential predictive biomarker for preeclampsia before the onset of clinical signs. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Protective role of amantadine in mitochondrial dysfunction and oxidative stress mediated by hepatitis C virus protein expression.

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    Quarato, Giovanni; Scrima, Rosella; Ripoli, Maria; Agriesti, Francesca; Moradpour, Darius; Capitanio, Nazzareno; Piccoli, Claudia

    2014-06-15

    Amantadine is an antiviral and antiparkinsonian drug that has been evaluated in combination therapies against hepatitis C virus (HCV) infection. Controversial results have been reported concerning its efficacy, and its mechanism of action remains unclear. Data obtained in vitro suggested a role of amantadine in inhibiting HCV p7-mediated cation conductance. In keeping with the fact that mitochondria are responsible to ionic fluxes and that HCV infection impairs mitochondrial function, we investigated a potential role of amantadine in modulating mitochondrial function. Using a well-characterized inducible cell line expressing the full-length HCV polyprotein, we found that amantadine not only prevented but also rescued HCV protein-mediated mitochondrial dysfunction. Specifically, amantadine corrected (i) overload of mitochondrial Ca²⁺; (ii) inhibition of respiratory chain activity and oxidative phosphorylation; (iii) reduction of membrane potential; and (iv) overproduction of reactive oxygen species. The effects of amantadine were observed within 15 min following drug administration and confirmed in Huh-7.5 cells transfected with an infectious HCV genome. These effects were also observed in cells expressing subgenomic HCV constructs, indicating that they are not mediated or only in part mediated by p7. Single organelle analyzes carried out on isolated mouse liver mitochondria demonstrated that amantadine induces hyperpolarization of the membrane potential. Moreover, amantadine treatment increased the calcium threshold required to trigger mitochondrial permeability transition opening. In conclusion, these results support a role of amantadine in preserving cellular bioenergetics and redox homeostasis in HCV-infected cells and unveil an effect of the drug which might be exploited for a broader therapeutic utilization. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Potential mechanisms underlying estrogen-induced expression of the molluscan estrogen receptor (ER) gene

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    Tran, Thi Kim Anh [School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308 (Australia); Department of Agriculture, Forestry and Fisheries, Vinh University, 182 Le Duan St., Vinh City, Nghe An (Viet Nam); MacFarlane, Geoff R. [School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308 (Australia); Kong, Richard Yuen Chong [Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong Special Administrative Region (China); O’Connor, Wayne A. [New South Wales Department of Primary Industries, Port Stephens Fisheries Institute, Taylors Beach, NSW 2316 (Australia); Yu, Richard Man Kit, E-mail: Richard.Yu@newcastle.edu.au [School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308 (Australia)

    2016-10-15

    Highlights: • This is the first report on the putative promoter sequence of a molluscan ER gene. • The gene promoter contains putative binding sites for direct and indirect interaction with ER. • E2 upregulates ER gene expression in the ovary in vitro and in vivo. • E2-induced gene expression may require a novel ligand-dependent receptor. • The ER proximal promoter is hypomethylated regardless of gene expression levels. - Abstract: In vertebrates, estrogens and estrogen mimicking chemicals modulate gene expression mainly through a genomic pathway mediated by the estrogen receptors (ERs). Although the existence of an ER orthologue in the mollusc genome has been known for some time, its role in estrogen signalling has yet to be deciphered. This is largely due to its constitutive (ligand-independent) activation and a limited mechanistic understanding of its regulation. To fill this knowledge gap, we cloned and characterised an ER cDNA (sgER) and the 5′-flanking region of the gene from the Sydney rock oyster Saccostrea glomerata. The sgER cDNA is predicted to encode a 477-amino acid protein that contains a DNA-binding domain (DBD) and a ligand-binding domain (LBD) typically conserved among both vertebrate and invertebrate ERs. A comparison of the sgER LBD sequence with those of other ligand-dependent ERs revealed that the sgER LBD is variable at several conserved residues known to be critical for ligand binding and receptor activation. Ligand binding assays using fluorescent-labelled E2 and purified sgER protein confirmed that sgER is devoid of estrogen binding. In silico analysis of the sgER 5′-flanking sequence indicated the presence of three putative estrogen responsive element (ERE) half-sites and several putative sites for ER-interacting transcription factors, suggesting that the sgER promoter may be autoregulated by its own gene product. sgER mRNA is ubiquitously expressed in adult oyster tissues, with the highest expression found in the ovary

  2. Role and species–specific expression of colon T cell homing receptor GPR15 in colitis

    Science.gov (United States)

    Nguyen, Linh P.; Pan, Junliang; Dinh, Theresa Thanh; Hadeiba, Husein; O’Hara, Edward; Ebtikar, Ahmad; Hertweck, Arnulf; Gökmen, M. Refik; Lord, Graham M.; Jenner, Richard G.

    2014-01-01

    Lymphocyte recruitment maintains intestinal immune homeostasis but also contributes to inflammation. The orphan chemoattractant receptor GPR15 mediates regulatory T cell homing and immunosuppression in the mouse colon. We show that GPR15 is also expressed by mouse TH17 and TH1 effector cells, and is required for colitis in a model that depends on their trafficking to the colon. In humans GPR15 is expressed by effector cells including pathogenic TH2 cells in ulcerative colitis, but is not expressed by regulatory T (Treg) cells. The TH2 transcriptional activator GATA-3 and the Treg–associated transcriptional repressor FOXP3 robustly bind human, but not mouse, GPR15 enhancer sequences, correlating with expression. Our results highlight species differences in GPR15 regulation, and suggest it as a potential therapeutic target for colitis. PMID:25531831

  3. Challenges in testing genetically modified crops for potential increases in endogenous allergen expression for safety.

    Science.gov (United States)

    Panda, R; Ariyarathna, H; Amnuaycheewa, P; Tetteh, A; Pramod, S N; Taylor, S L; Ballmer-Weber, B K; Goodman, R E

    2013-02-01

    Premarket, genetically modified (GM) plants are assessed for potential risks of food allergy. The major risk would be transfer of a gene encoding an allergen or protein nearly identical to an allergen into a different food source, which can be assessed by specific serum testing. The potential that a newly expressed protein might become an allergen is evaluated based on resistance to digestion in pepsin and abundance in food fractions. If the modified plant is a common allergenic source (e.g. soybean), regulatory guidelines suggest testing for increases in the expression of endogenous allergens. Some regulators request evaluating endogenous allergens for rarely allergenic plants (e.g. maize and rice). Since allergic individuals must avoid foods containing their allergen (e.g. peanut, soybean, maize, or rice), the relevance of the tests is unclear. Furthermore, no acceptance criteria are established and little is known about the natural variation in allergen concentrations in these crops. Our results demonstrate a 15-fold difference in the major maize allergen, lipid transfer protein between nine varieties, and complex variation in IgE binding to various soybean varieties. We question the value of evaluating endogenous allergens in GM plants unless the intent of the modification was production of a hypoallergenic crop. © 2012 John Wiley & Sons A/S.

  4. The Na, K-ATPase β-Subunit Isoforms Expression in Glioblastoma Multiforme: Moonlighting Roles

    Science.gov (United States)

    Rotoli, Deborah; Cejas, Mariana-Mayela; Maeso, María-del-Carmen; Pérez-Rodríguez, Natalia-Dolores; Morales, Manuel; Ávila, Julio

    2017-01-01

    Glioblastoma multiforme (GBM) is the most common form of malignant glioma. Recent studies point out that gliomas exploit ion channels and transporters, including Na, K-ATPase, to sustain their singular growth and invasion as they invade the brain parenchyma. Moreover, the different isoforms of the β-subunit of Na, K-ATPase have been implicated in regulating cellular dynamics, particularly during cancer progression. The aim of this study was to determine the Na, K-ATPase β subunit isoform subcellular expression patterns in all cell types responsible for microenvironment heterogeneity of GBM using immunohistochemical analysis. All three isoforms, β1, β2/AMOG (Adhesion Molecule On Glia) and β3, were found to be expressed in GBM samples. Generally, β1 isoform was not expressed by astrocytes, in both primary and secondary GBM, although other cell types (endothelial cells, pericytes, telocytes, macrophages) did express this isoform. β2/AMOG and β3 positive expression was observed in the cytoplasm, membrane and nuclear envelope of astrocytes and GFAP (Glial Fibrillary Acidic Protein) negative cells. Interestingly, differences in isoforms expression have been observed between primary and secondary GBM: in secondary GBM, β2 isoform expression in astrocytes was lower than that observed in primary GBM, while the expression of the β3 subunit was more intense. These changes in β subunit isoforms expression in GBM could be related to a different ionic handling, to a different relationship between astrocyte and neuron (β2/AMOG) and to changes in the moonlighting roles of Na, K-ATPase β subunits as adaptor proteins and transcription factors. PMID:29117147

  5. Beauveria bassiana Lipase A expressed in Komagataella (Pichia pastoris with potential for biodiesel catalysis

    Directory of Open Access Journals (Sweden)

    Ana Claudia Vici

    2015-10-01

    Full Text Available Lipases (EC 3.1.1.3 comprise a biotechnologically important group of enzymes because they are able to catalyze both hydrolysis and synthesis reactions, depending on the amount of water in the system. One of the most interesting application of lipase is in the biofuel industry for biodiesel production by oil and ethanol (or methanol transesterification. Entomopathogenic fungi, which are potential source of lipases, are still poorly explored in biotechnological processes. The present work reports the heterologous expression and biochemical characterization of a novel Beauveria bassiana lipase with potential for biodiesel production. The His-tagged B. bassiana lipase A (BbLA was produced in Komagataella pastoris in Buffered Methanol Medium (BMM induced with 1% methanol at 30 °C. Purified BbLA was activated with 0.05% Triton X-100 and presented optimum activity at pH 6.0 and 50°C. N-glycosylation of the recombinant BbLA accounts for 31.5% of its molecular weight. Circular dichroism and molecular modeling confirmed a structure composed of α-helix and β-sheet, similar to α/β hydrolases. Immobilized BbLA was able to promote transesterification reactions in fish oil, demonstrating potential for biodiesel production. BbLA was successfully produced in Komagataella pastoris and shows potential use for biodiesel production by the ethanolysis reaction.

  6. Perception of threat from emotions and its role in poor emotional expression within eating pathology.

    Science.gov (United States)

    Ioannou, Korina; Fox, John R E

    2009-01-01

    Recent research has documented links between eating disorder (ED) symptomatology and emotional expression deficits. Relevant theoretical models have alluded to the functional role of disordered eating in alleviating affect that is felt to be otherwise unmanageable and threatening. Nevertheless, research examining ED individuals' perceptions of emotional states has been sparse, while empirical studies have predominantly focused on global conceptualizations of emotion, failing to address discrete affect states. The current study had three aims: (a) to determine the relation between ED symptomatology and emotional expression, in a sample of women with ED, in an attempt to confirm previous findings of an inverse relation; (b) to test the hypothesis that women with ED inhibit the expression of emotions perceived as threatening, by examining the relation between emotional expression and perceptions of threat from emotion, while partialling out the effects of depression; and (c) to determine whether, amongst women with ED, perceptions of threat from anger are uniquely associated with emotional inhibition, when the effects of depression and body dissatisfaction are controlled for. Results demonstrated that (a) emotional expression was negatively related with the three Eating Disorders Inventory-3 subscales (drive for thinness, bulimia and body dissatisfaction); (b) perceived threat from emotion, particularly anger, was negatively correlated with emotional expression, when depression was partialled out in the analysis; and (c) perceived threat from anger significantly and uniquely predicted emotional inhibition, over and above the effects of body dissatisfaction and depression, in a sample of women with ED symptomatology. It is suggested that anger may be perceived as particularly threatening amongst women with ED, and play a significant role in the emotional expression difficulties that this population experiences. The implications of the current findings are discussed in

  7. The role of Alg13 N-acetylglucosaminyl transferase in the expression of pathogenic features of Candida albicans.

    Science.gov (United States)

    Niewiadomska, Monika; Janik, Anna; Perlińska-Lenart, Urszula; Piłsyk, Sebastian; Palamarczyk, Grażyna; Kruszewska, Joanna S

    2017-04-01

    The pathogenic potential of Candida albicans depends on adhesion to the host cells mediated by highly glycosylated adhesins, hyphae formation and growth of biofilm. These factors require effective N-glycosylation of proteins. Here, we present consequences of up- and down-regulation of the newly identified ALG13 gene encoding N-acetylglucosaminyl transferase, a potential member of the Alg7p/Alg13p/Alg14p complex catalyzing the first two initial reactions in the N-glycosylation process. We constructed C. albicans strain alg13∆::hisG/TRp-ALG13 with one allele of ALG13 disrupted and the other under the control of a regulatable promoter, TRp. Gene expression and enzyme activity were measured using RT-qPCR and radioactive substrate. Cell wall composition was estimated by HPLC DIONEX. Protein glycosylation status was analyzed by electrophoresis of HexNAcase, a model N-glycosylated protein in C. albicans. Both decreased and elevated expression of ALG13 changed expression of all members of the complex and resulted in a decreased activity of Alg7p and Alg13p and under-glycosylation of HexNAcase. The alg13 strain was also defective in hyphae formation and growth of biofilm. These defects could result from altered expression of genes encoding adhesins and from changes in the carbohydrate content of the cell wall of the mutant. This work confirms the important role of protein N-glycosylation in the pathogenic potential of C. albicans. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Role of matrix metalloproteinase 13 gene expression in the evaluation of radiation response in oral squamous cell carcinoma

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    Shankar Sharan Singh

    2017-01-01

    Full Text Available BACKGROUND: Matrix Metalloproteinase 13 (MMP13 is a member of collagenase family and it is involved in the degradation of extracellular matrix and basement membrane protein. It is thought to be associated with tumor invasion and metastasis. Elevated MMP13 expression has been found in carcinoma of the breast, urinary bladder, head and neck and others. It is observed that MMP13 gene is also correlated with radiation response in OSCC (Oral squamous cell carcinoma cell line based study. The present study correlates the MMP13 expressions with clinicopathological parameters and radiation response in OSCC patients. MATERIALS AND METHODS: The MMP13 mRNA levels were determined by employing qRT-PCR (real-time quantitative reverse transcriptase-polymerase chain reaction. RESULTS: We observed high expression of MMP13 mRNA in OSCC patients when compared with matched controls. Statistically significant up regulation of MMP13 mRNA expression was found in tobacco chewers, advanced T-stage (p < 0.001 and lymph node metastasis (p < 0.01. MMP13 mRNA levels were also elevated in non responders as compared to responders to radiation treatment. CONCLUSIONS: To the best of our knowledge, this is the first report that indicates role of MMP13 in radiation response in OSCC patients and could be used as potential bio-marker for radiotherapy treatment in OSCC patients.

  9. Erythropoietin receptor expression is a potential prognostic factor in human lung adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Anita Rózsás

    Full Text Available Recombinant human erythropoietins (rHuEPOs are used to treat cancer-related anemia. Recent preclinical studies and clinical trials, however, have raised concerns about the potential tumor-promoting effects of these drugs. Because the clinical significance of erythropoietin receptor (EPOR signaling in human non-small cell lung cancer (NSCLC also remains controversial, our aim was to study whether EPO treatment modifies tumor growth and if EPOR expression has an impact on the clinical behavior of this malignancy. A total of 43 patients with stage III-IV adenocarcinoma (ADC and complete clinicopathological data were included. EPOR expression in human ADC samples and cell lines was measured by quantitative real-time polymerase chain reaction. Effects of exogenous rHuEPOα were studied on human lung ADC cell lines in vitro. In vivo growth of human ADC xenografts treated with rHuEPOα with or without chemotherapy was also assessed. In vivo tumor and endothelial cell (EC proliferation was determined by 5-bromo-2'-deoxy-uridine (BrdU incorporation and immunofluorescent labeling. Although EPOR mRNA was expressed in all of the three investigated ADC cell lines, rHuEPOα treatment (either alone or in combination with gemcitabine did not alter ADC cell proliferation in vitro. However, rHuEPOα significantly decreased tumor cell proliferation and growth of human H1975 lung ADC xenografts. At the same time, rHuEPOα treatment of H1975 tumors resulted in accelerated tumor endothelial cell proliferation. Moreover, in patients with advanced stage lung ADC, high intratumoral EPOR mRNA levels were associated with significantly increased overall survival. This study reveals high EPOR level as a potential novel positive prognostic marker in human lung ADC.

  10. The associated expression of Maspin and Bax proteins as a potential prognostic factor in intrahepatic cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Borghetti Angelo F

    2006-10-01

    Full Text Available Abstract Background Maspin, a member of the serpin family, is a suppressor of tumor growth, an inhibitor of angiogenesis and an inducer of apoptosis. Maspin induces apoptosis by increasing Bax, a member of the Bcl-2 family of apoptosis-regulating proteins. In this exploratory study, we investigated the associated expression of Maspin and Bax proteins as a potential prognostic factor in intrahepatic cholangiocarcinoma (IHCCA. Methods Twenty-two paraffin-embedded samples were analyzed by immunohistochemical methods using Maspin, Bax and CD34 antibodies. Maspin was scored semiquantitatively (HSCORE. Apoptosis was assessed using an antibody against cleaved caspase-3. Results The strong relationship observed between the expression of Maspin and Bax, indicates that Bax is likely to be the key effector of Maspin-mediated induction of apoptosis as indicated by the activation of cleaved caspase-3. We categorized Maspin HSCORE by calculating the optimal cutpoint. A Maspin HSCORE above the cutpoint was inversely related with tumor dimension, depth of tumor and vascular invasion. Uni/multivariate analysis suggests that a Maspin HSCORE below the cutpoint significantly worsens the patients' prognosis. Tumors with Maspin HSCORE below the cutpoint had a shorter survival (11+/-5 months than did patients with Maspin HSCORE above the cutpoint (27+/-4 months, whereas Kaplan-Meier analysis and logrank test showed no significant difference in overall survival between the patients. Conclusion The associated expression of Maspin and Bax might delay tumor progression in IHCCA. Maspin above the cutpoint might counteract tumor development by increasing cell apoptosis, and by decreasing tumor mass and cell invasion. The combined expression of Maspin and Bax appears to influence the susceptibility of tumor cholangiocytes to apoptosis and thus may be involved in delaying IHCCA progression.

  11. [The role of experience in the neurology of facial expression of emotions].

    Science.gov (United States)

    Gordillo, Fernando; Pérez, Miguel A; Arana, José M; Mestas, Lilia; López, Rafael M

    2015-04-01

    Facial expression of emotion has an important social function that facilitates interaction between people. This process has a neurological basis, which is not isolated from the context, or the experience of the interaction between people in that context. Yet, to date, the impact that experience has on the perception of emotions is not completely understood. To discuss the role of experience in the recognition of facial expression of emotions and to analyze the biases towards emotional perception. The maturation of the structures that support the ability to recognize emotion goes through a sensitive period during adolescence, where experience may have greater impact on emotional recognition. Experiences of abuse, neglect, war, and stress generate a bias towards expressions of anger and sadness. Similarly, positive experiences generate a bias towards the expression of happiness. Only when people are able to use the facial expression of emotions as a channel for understanding an expression, will they be able to interact appropriately with their environment. This environment, in turn, will lead to experiences that modulate this capacity. Therefore, it is a self-regulatory process that can be directed through the implementation of intervention programs on emotional aspects.

  12. Role of the oxytocin receptor expressed in the rostral medullary raphe in thermoregulation during cold conditions

    Directory of Open Access Journals (Sweden)

    Yoshiyuki eKasahara

    2015-11-01

    Full Text Available Recent papers have reported that oxytocin (Oxt and the oxytocin receptor (Oxtr may be involved in the regulation of food intake in mammals. We therefore suspected the Oxt/Oxtr system to be involved in energy homeostasis. In previous studies, we found a tendency toward obesity in Oxtr-deficient mice, as well as impaired thermoregulation when these mice were exposed to cold conditions. In the present study, we observed the expression of Oxtr in the rostral medullary raphe (RMR, the brain region known to control thermogenesis in brown adipose tissue. Through immunohistochemistry, we detected neurons expressing Oxtr and c-Fos in the RMR of mice exposed to cold conditions. Up to 40% of Oxtr-positive neurons in RMR were classified as glutamatergic neurons, as shown by immunostaining using anti-VGLUT3 antibody. In addition, mice with exclusive expression of Oxtr in the RMR were generated by injecting an AAV-Oxtr vector into the RMR region of Oxtr-deficient mice. We confirmed the recovery of thermoregulatory ability in the manipulated mice during exposure to cold conditions. Moreover, mice with RMR-specific expression of Oxtr lost the typical morphological change in brown adipose tissue observed in Oxtr-deficient mice. Additionally, increased expression of the β3-adrenergic receptor gene, Adrb3 was observed in brown adipose tissue. These results are the first to show the critical role of RMR Oxtr expression in thermoregulation during cold conditions.

  13. Linking child maltreatment history with child abuse potential: Relative roles of maltreatment types

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    Mitkovic-Voncina Marija

    2014-01-01

    Full Text Available The independent roles of each childhood maltreatment type on child abuse potential in adults have been insufficiently explored and are inconsistent, with dissociation as one of the possible suggested mediators of intergenerational child abuse. We investigated these effects among 164 non-clinical adult parents, who filled in general questionnaires: Childhood Trauma Questionnaire (CTQ, Child Abuse Potential Inventory (CAPI and Dissociative Experience Scale (DES. Among all maltreatment types (emotional, physical and sexual abuse, emotional and physical neglect, emotional abuse was the only independent predictor in the regression model of child abuse potential. The relationship between emotional abuse history and child abuse potential was partially mediated by dissociation. The findings could speak in favor of the potentially unique detrimental role of emotional abuse in intergenerational maltreatment, with dissociation as one of the possible mechanisms.

  14. Gene co-expression networks and profiles reveal potential biomarkers of boar taint in pigs

    DEFF Research Database (Denmark)

    Drag, Markus; Skinkyté-Juskiené, R.; Do, D. N.

    and enrichment analysis and semantic filtering revealed the GO terms “catalytic activity” and “transferase activity” to be overrepresented (p steroid hormones. Extraction of hub...... active tissue. GOseq was used to find enriched gene ontology (GO) terms and REVIGO was used to filter semantic similarities. In both liver and testis, a GO termed “oxidoreductase activity” was enriched (p steroid metabolism, including androstenone...... synthesis. In testis, >80 DE genes were functionally classified by the PANTHER tool to “Gonadotropin releasing hormone receptor” and “Wnt signaling” pathways which play a role in reproductive maturation and proliferation of spermatogonia, respectively. WGCNA was used to build co-expression modules...

  15. [The role of light in the developement of RPE degeneration in AMD and potential cytoprotection of minocycline].

    Science.gov (United States)

    Kernt, M; Thiele, S; Hirneiss, C; Neubauer, A S; Lackerbauer, C-A; Ulbig, M W; Kampik, A

    2011-10-01

    Light-induced oxidative stress is an suggested reason for retinal pigment epithelium (RPE) degeneration in age-related macular degeneration (AMD). This study investigates the influence of light on intracellular reactive oxygen species (ROS) and apoptosis in the human RPE and potential cytoprotective effects of the tetracycline antibiotic minocycline. Primary human RPE cells were either pre- or post-incubated with minocycline and then exposed to white light or oxidative stress (600 µM, H(2)O(2)). Then viability, induction of intracellular reactive oxygen species (ROS), apoptosis and cell death was determined. Expression of apoptotic BAX and anti-apoptotic Bcl-2 protein and their mRNA were determined by RT-PCR and Western blot analysis. Both light exposure and oxidative stress decreased RPE cell viability and Bcl-2 expression and increased intracellular ROS, apoptotic cell death, and BAX expression. Minocycline reduced these effects under certain conditions. This study demonstrates that minocycline effectively protects human RPE cells against oxidative damage. However, in the light of minocycline's photosensitising properties its potential role in AMD treatment needs further evaluation. © Georg Thieme Verlag KG Stuttgart · New York.

  16. Characterization of MicroRNA Expression Profiles and Identification of Potential Biomarkers in Leprosy.

    Science.gov (United States)

    Jorge, Karina T O S; Souza, Renan P; Assis, Marieta T A; Araújo, Marcelo G; Locati, Massimo; Jesus, Amélia M R; Dias Baptista, Ida M F; Lima, Cristiano X; Teixeira, Antônio L; Teixeira, Mauro M; Soriani, Frederico M

    2017-05-01

    Leprosy is an important cause of disability in the developing world. Early diagnosis is essential to allow for cure and to interrupt transmission of this infection. MicroRNAs (miRNAs) are important factors for host-pathogen interaction and they have been identified as biomarkers for various infectious diseases. The expression profile of 377 microRNAs were analyzed by TaqMan low-density array (TLDA) in skin lesions of tuberculoid and lepromatous leprosy patients as well as skin specimens from healthy controls. In a second step, 16 microRNAs were selected for validation experiments with reverse transcription-quantitative PCR (qRT-PCR) in skin samples from new individuals. Principal-component analysis followed by logistic regression model and receiver operating characteristic (ROC) curve analyses were performed to evaluate the diagnostic potential of selected miRNAs. Four patterns of differential expression were identified in the TLDA experiment, suggesting a diagnostic potential of miRNAs in leprosy. After validation experiments, a combination of four miRNAs (miR-101, miR-196b, miR-27b, and miR-29c) was revealed as able to discriminate between healthy control and leprosy patients with 80% sensitivity and 91% specificity. This set of miRNAs was also able to discriminate between lepromatous and tuberculoid patients with a sensitivity of 83% and 80% specificity. In this work, it was possible to identify a set of miRNAs with good diagnostic potential for leprosy. Copyright © 2017 American Society for Microbiology.

  17. Zirconium-89 labeled panitumumab: a potential immuno-PET probe for HER1-expressing carcinomas.

    Science.gov (United States)

    Bhattacharyya, Sibaprasad; Kurdziel, Karen; Wei, Ling; Riffle, Lisa; Kaur, Gurmeet; Hill, G Craig; Jacobs, Paula M; Tatum, James L; Doroshow, James H; Kalen, Joseph D

    2013-05-01

    Anti-HER1 monoclonal antibody (mAb), panitumumab (Vectibix) is a fully human mAb approved by the FDA for the treatment of epidermal growth factor receptor (EGFR, HER1)-expressing colorectal cancers. By combining the targeted specificity of panitumumab with the quantitative in vivo imaging capabilities of PET, we evaluated the potential of (89)Zr-DFO-panitumumab PET/CT imaging and performed non-invasive, in vivo imaging of HER1 expression and estimated human dosimetry. Panitumumab was radiolabeled with (89)Zr using a derivative of desferrioxamine (DFO-Bz-NCS) and with (111)In using CHX-A" DTPA as bifunctional chelators. Comparative biodistribution/dosimetry of both radiotracers was performed in non-tumor bearing athymic nude mice (n=2 females and n=2 males) over 1-week following i.v. injection of either using (89)Zr-DFO-panitumumab or (111)In-CHX-A"-DTPA-panitumumab. Micro-PET/CT imaging of female athymic nude mice bearing human breast cancer tumors (n=5 per tumor group) with variable HER1-expression very low (BT-474), moderate (MDA-MB-231), and very high (MDA-MB-468) was performed at over 1 week following i.v. injection of (89)Zr-DFO-panitumumab. Radiochemical yield and purity of (89)Zr-Panitumumab was >70% and >98% respectively with specific activity 150 ± 10 MBq/mg of panitumumab in a ~4 hr synthesis time. Biodistribution of (111)In-CHX-A" DTPA -panitumumab and (89)Zr-DFO-panitumumab in athymic non-tumor bearing nude mice displayed similar percent injected dose per gram of tissue with prominent accumulation of both tracers in the lymph nodes, a known clearance mechanism of panitumumab. Also exhibited was prolonged blood pool with no evidence of targeted accumulation in any organ. Human radiation dose estimates showed similar biodistributions with estimated human effective doses of 0.578 and 0.183 mSv/MBq for (89)Zr-DFO-panitumumab and (111)In-CHX-A"-DTPA-panitumumab, respectively. Given the potential quantitative and image quality advantages of PET, imaging of

  18. Advances in transient receptor potential vanilloid-2 channel expression and function in tumor growth and progression.

    Science.gov (United States)

    Liberati, Sonia; Morelli, Maria B; Amantini, Consuelo; Santoni, Matteo; Nabissi, Massimo; Cardinali, Claudio; Santoni, Giorgio

    2014-01-01

    Aim of this review is to study the role of the TRPV2 channel, a member of the TRPV subfamily of TRP channels, in tumor progression. Physiologically, the triggering of TRPV2 by agonists/activators (e.g., growth factors, hormones and cannabinoids), by inducing TRPV2 translocation from the endosome to the plasmatic membrane, inhibit cell proliferation and induce necrosis and/or apoptosis. Thus, loss or alterations of TRPV2 proliferative and apoptotic signals, results in uncontrolled proliferation and augmented resistance to apoptotic stimuli. For example in prostate cancer cells, the TRPV2 activation following lysophospholipid or adrenomedullin stimulation enhances the invasiveness of cancer cells; furthermore, the increased malignancy of castration-resistant prostate cancer cells was associated with enhanced TRPV2 expression, mainly in metastatic prostate cancer cells. In addition, the TRPV2 cellular functions may also to be related to the presence of TRPV2 variants, able to interfere with the physiological functions of normal TRPV2 channels. In this regard, bladder cancer tumors show loss or reduction of a short TRPV2 variant during cancer progression, with increased malignancy and invasiveness. High expression of TRPV2 was also observed more frequently in esophageal squamous cell carcinoma patients with advanced pT stage, lymph node metastasis and advanced pathological stage.

  19. The Role of Antimicrobial Peptides in Influenza Virus Infection and Their Potential as Antiviral and Immunomodulatory Therapy

    Directory of Open Access Journals (Sweden)

    I-Ni Hsieh

    2016-09-01

    Full Text Available Influenza A virus (IAV remains a major threat that can cause severe morbidity and mortality due to rapid genomic variation. Resistance of IAVs to current anti-IAV drugs has been emerging, and antimicrobial peptides (AMPs have been considered to be potential candidates for novel treatment against IAV infection. AMPs are endogenous proteins playing important roles in host defense through direct antimicrobial and antiviral activities and through immunomodulatory effects. In this review, we will discuss the anti-IAV and immunomodulatory effects of classical AMPs (defensins and cathelicidins, and proteins more recently discovered to have AMP-like activity (histones and Alzheimer’s associated β-amyloid. We will discuss the interactions between AMPs and other host defense proteins. Major emphasis will be placed on novel synthetic AMPs derived from modification of natural proteins, and on potential methods of increasing expression of endogenous AMPs, since these approaches may lead to novel antiviral therapeutics.

  20. Role of promoter element in c-mpl gene expression induced by TPO.

    Science.gov (United States)

    Sunohara, Masataka; Morikawa, Shigeru; Fuse, Akira; Sato, Iwao

    2013-01-01

    Thrombopoietin (TPO) and its receptor, c-Mpl, play the crucial role for the development of megakaryocyte and considered to regulate megakaryocytopoiesis. Previously we reported that TPO increased the c-mpl promoter activity determined by a transient expression system using a vector containing the luciferase gene as a reporter and the expression of the c-mpl gene is modulated by transcription through a protein kinase C (PKC)-dependent pathway in the megakaryoblastic cells. In this research, to elucidate the required elements in c-mpl promoter, the promoter activity of the deletion constructs and site-directed mutagenesis were measured by a transient transfection assay system. Destruction of -77GATA in c-mpl promoter decreased the activity by 22.8%. Our study elucidated that -77GATA involved in TPO-induced c-mpl gene expression in a human megakaryoblastic cell line, CMK.

  1. Role of extrathyroidal TSHR expression in adipocyte differentiation and its association with obesity

    Directory of Open Access Journals (Sweden)

    Lu Sumei

    2012-01-01

    Full Text Available Abstract Background Obesity is known to be associated with higher risks of cardiovascular disease, metabolic syndrome, and diabetes mellitus. Thyroid-stimulating hormone (TSHR is the receptor for thyroid-stimulating hormone (TSH, or thyrotropin, the key regulator of thyroid functions. The expression of TSHR, once considered to be limited to thyrocytes, has been so far detected in many extrathyroidal tissues including liver and fat. Previous studies have shown that TSHR expression is upregulated when preadipocytes differentiate into mature adipocytes, suggestive of a possible role of TSHR in adipogenesis. However, it remains unclear whether TSHR expression in adipocytes is implicated in the pathogenesis of obesity. Methods In the present study, TSHR expression in adipose tissues from both mice and human was analyzed, and its association with obesity was evaluated. Results We here showed that TSHR expression was increased at both mRNA and protein levels when 3T3-L1 preadipocytes were induced to differentiate. Knockdown of TSHR blocked the adipocyte differentiation of 3T3-L1 preadipocytes as evaluated by Oil-red-O staining for lipid accumulation and by RT-PCR analyses of PPAR-γ and ALBP mRNA expression. We generated obesity mice (C57/BL6 by high-fat diet feeding and found that the TSHR protein expression in visceral adipose tissues from obesity mice was significantly higher in comparison with the non-obesity control mice (P Conclusion Taken together, these results suggested that TSHR is an important regulator of adipocyte differentiation. Dysregulated expression of TSHR in adipose tissues is associated with obesity, which may involve a mechanism of excess adipogenesis.

  2. Role of sphingosine 1-phosphate receptor expression in eosinophils of patients with allergic rhinitis, and effect of topical nasal steroid treatment on this receptor expression.

    LENUS (Irish Health Repository)

    Mackle, T

    2008-12-01

    Recent research has indicated that sphingosine 1-phosphate plays a role in allergy. This study examined the effect of allergen challenge on the expression of sphingosine 1-phosphate receptors on the eosinophils of allergic rhinitis patients, and the effect of steroid treatment on this expression.

  3. Biological roles and therapeutic potential of hydroxy-carboxylic acid receptors

    Directory of Open Access Journals (Sweden)

    Kashan eAhmed

    2011-10-01

    Full Text Available In the recent past, deorphanization studies have described intermediates of energy metabolism to activate G protein-coupled receptors (GPCRs and to thereby regulate metabolic functions. GPR81, GPR109A and GPR109B, formerly known as the nicotinic acid receptor family, are encoded by clustered genes and share a high degree of sequence homology. Recently, hydroxy-carboxylic acids were identified as endogenous ligands of GPR81, GPR109A and GPR109B, and therefore these receptors have been placed into a novel receptor family of hydroxy-carboxylic acid (HCA receptors. The HCA1 receptor (GPR81 is activated by the glycolytic metabolite 2-hydroxy-propionic acid (lactate, the HCA2 receptor is activated by the ketone body 3-hydroxy-butyric acid and the HCA3 receptor (GPR109B is a receptor for the β-oxidation intermediate 3-hydroxy-octanoic acid. While HCA1 and HCA2 receptors are present in most mammalian species, the HCA3 receptor is exclusively found in humans and higher primates. HCA receptors are expressed in adipose tissue and mediate anti-lipolytic effects in adipocytes through Gi-type G-protein-dependent inhibition of adenylyl cyclase. HCA2 and HCA3 inhibit lipolysis during conditions of increased β-oxidation such as prolonged fasting, whereas HCA1 mediates the anti-lipolytic effects of insulin in the fed state. As HCA2 is a receptor for the established anti-dyslipidemic drug nicotinic acid, HCA1 and HCA3 also represent promising drug targets and several synthetic ligands for HCA receptors have been developed. In this article, we will summarize the deorphanization and pharmacological characterization of HCA receptors. Moreover, we will discuss recent progress in elucidating the physiological and pathophysiological role to further evaluate the therapeutic potential of the HCA receptor family for the treatment of metabolic disease.

  4. The potential role for use of mitochondrial DNA copy number as predictive biomarker in presbycusis.

    Science.gov (United States)

    Falah, Masoumeh; Houshmand, Massoud; Najafi, Mohammad; Balali, Maryam; Mahmoudian, Saeid; Asghari, Alimohamad; Emamdjomeh, Hessamaldin; Farhadi, Mohammad

    2016-01-01

    Age-related hearing impairment, or presbycusis, is the most common communication disorder and neurodegenerative disease in the elderly. Its prevalence is expected to increase, due to the trend of growth of the elderly population. The current diagnostic test for detection of presbycusis is implemented after there has been a change in hearing sensitivity. Identification of a pre-diagnostic biomarker would raise the possibility of preserving hearing sensitivity before damage occurs. Mitochondrial dysfunction, including the production of reactive oxygen species and induction of expression of apoptotic genes, participates in the progression of presbycusis. Mitochondrial DNA sequence variation has a critical role in presbycusis. However, the nature of the relationship between mitochondrial DNA copy number, an important biomarker in many other diseases, and presbycusis is undetermined. Fifty-four subjects with presbycusis and 29 healthy controls were selected after ear, nose, throat examination and pure-tone audiometry. DNA was extracted from peripheral blood samples. The copy number of mitochondrial DNA relative to the nuclear genome was measured by quantitative real-time polymerase chain reaction. Subjects with presbycusis had a lower median mitochondrial DNA copy number than healthy subjects and the difference was statistically significant ( P =0.007). Mitochondrial DNA copy number was also significantly associated with degree of hearing impairment ( P =0.025) and audiogram configuration ( P =0.022). The findings of this study suggest that lower mitochondrial DNA copy number is responsible for presbycusis through alteration of mitochondrial function. Moreover, the significant association of mitochondrial DNA copy number in peripheral blood samples with the degree of hearing impairment and audiogram configuration has potential for use as a standard test for presbycusis, providing the possibility of the development of an easy-to-use biomarker for the early detection of

  5. PPARγ Expression and Function in Mycobacterial Infection: Roles in Lipid Metabolism, Immunity, and Bacterial Killing

    Directory of Open Access Journals (Sweden)

    Patricia E. Almeida

    2012-01-01

    Full Text Available Tuberculosis continues to be a global health threat, with drug resistance and HIV coinfection presenting challenges for its control. Mycobacterium tuberculosis, the etiological agent of tuberculosis, is a highly adapted pathogen that has evolved different strategies to subvert the immune and metabolic responses of host cells. Although the significance of peroxisome proliferator-activated receptor gamma (PPARγ activation by mycobacteria is not fully understood, recent findings are beginning to uncover a critical role for PPARγ during mycobacterial infection. Here, we will review the molecular mechanisms that regulate PPARγ expression and function during mycobacterial infection. Current evidence indicates that mycobacterial infection causes a time-dependent increase in PPARγ expression through mechanisms that involve pattern recognition receptor activation. Mycobacterial triggered increased PPARγ expression and activation lead to increased lipid droplet formation and downmodulation of macrophage response, suggesting that PPARγ expression might aid the mycobacteria in circumventing the host response acting as an escape mechanism. Indeed, inhibition of PPARγ enhances mycobacterial killing capacity of macrophages, suggesting a role of PPARγ in favoring the establishment of chronic infection. Collectively, PPARγ is emerging as a regulator of tuberculosis pathogenesis and an attractive target for the development of adjunctive tuberculosis therapies.

  6. Expression and Role of GPR87 in Urothelial Carcinoma of the Bladder

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    Yoshiyuki Kakehi

    2013-06-01

    Full Text Available The orphan GPR87 has recently been matched with its ligand LPA, which is a lipid mediator with multiple physiological functions, including cancer cell proliferation. This study aimed to clarify the role of GPR87 in urothelial carcinoma of the bladder. GPR87 expression was assessed in seven human bladder cancer cell lines. A replication-deficient recombinant adenoviral vector expressing shRNA targeting GPR87 (Ad-shGPR87, was constructed. Gene silencing was carried out using Ad-shGPR87. Immunohistochemical analysis was performed for transurethral resection of bladder tumor samples from 71 patients with non-muscle-invasive bladder cancer. We observed GPR87 expression in five of the seven cell lines, and silencing GPR87 gene expression significantly reduced cell viability. GPR87 expression was positive in 38 (54% of 71 tumors. Ki-67 index was associated with positive GPR87 staining status (p < 0.0001. Patients with GPR87-positive tumors had shorter intravesical recurrence-free survival than those with GPR87-negative tumors (p = 0.010. Multivariate analysis revealed that GPR87 staining status was an independent prognostic parameter for intravesical recurrence (p = 0.041. Progression from non-muscle-invasive to muscle-invasive tumor was more frequently observed in patients with GPR87-positive tumors, although this trend did not reach statistical significance (p = 0.056. These results warrant further prospective studies to clarify the role of GPR87 expression in intravesical recurrence and progression in bladder cancer.

  7. Synthesis and evaluation of radioiodinated cyclooxygenase-2 inhibitors as potential SPECT tracers for cyclooxygenase-2 expression

    Energy Technology Data Exchange (ETDEWEB)

    Kuge, Yuji [Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan)]. E-mail: kuge@pharm.kyoto-u.ac.jp; Katada, Yumiko [Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Shimonaka, Sayaka [Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Temma, Takashi [Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Kimura, Hiroyuki [Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Kiyono, Yasushi [Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Yokota, Chiaki [Cerebrovascular Laboratory, National Cardiovascular Center Research Institute, Osaka 565-8565 (Japan); Minematsu, Kazuo [Cerebrovascular Division, Department of Medicine, National Cardiovascular Center Research Institute, Osaka 565-8565 (Japan); Seki, Koh-ichi [Central Institute of Isotope Science, Hokkaido University, Hokkaido 060-8638 (Japan); Tamaki, Nagara [Department of Nuclear Medicine, Graduate School of Medicine, Hokkaido University, Hokkaido 060-8638 (Japan); Ohkura, Kazue [Department of Radiopharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Hokkaido 061-0293 (Japan); Saji, Hideo [Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan)

    2006-01-15

    Although several COX-2 inhibitors have recently been radiolabeled, their potential for imaging COX-2 expression remains unclear. In particular, the sulfonamide moiety of COX-2 inhibitors may cause slow blood clearance of the radiotracer, due to its affinity for carbonic anhydrase (Canada) in erythrocytes. Thus, we designed a methyl sulfone-type analogue, 5-(4-iodophenyl)-1-[4-(methylsulfonyl)phenyl]-3-trifluoromethyl-1H-pyrazole (IMTP). In this study, the potential of radioiodinated IMTP was assessed in comparison with a {sup 125}I-labeled celecoxib analogue with a sulfonamide moiety ({sup 125}I-IATP). Methods: The COX inhibitory potency was assessed by measuring COX-catalyzed oxidation by hydrogen peroxide. The biodistribution of {sup 125}I-IMTP and {sup 125}I-IATP was determined by the ex vivo tissue counting method in rats. Distribution of the labeled compounds to rat blood cells was measured. Results: The COX-2 inhibitory potency of IMTP (IC{sub 5}=5.16 {mu}M) and IATP (IC{sub 5}=8.20 {mu}M) was higher than that of meloxicam (IC{sub 5}=29.0 {mu}M) and comparable to that of SC-58125 (IC{sub 5}=1.36 {mu}M). The IC{sub 5} ratios (COX-1/COX-2) indicated the high isoform selectivity of IMTP and IATP for COX-2. Significant levels of {sup 125}I-IMTP and {sup 125}I-IATP were observed in the kidneys and the brain (organs known to express COX-2). The blood clearance of {sup 125}I-IMTP was much faster than that of {sup 125}I-IATP. Distribution of {sup 125}I-IATP to blood cells (88.0%) was markedly higher than that of {sup 125}I-IMTP (18.1%), which was decreased by CA inhibitors. Conclusions: Our results showed a high inhibitory potency and selectivity of IMTP for COX-2. The substitution of a sulfonamide moiety to a methyl sulfone moiety effectively improved the blood clearance of the compound, indicating the loss of the cross reactivity with CA in {sup 125}I-IMTP. {sup 123}I-IMTP may be a potential SPECT radiopharmaceutical for COX-2 expression.

  8. Expression profiles of SnoN in normal and cancerous human tissues support its tumor suppressor role in human cancer.

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    Nadine S Jahchan

    Full Text Available SnoN is a negative regulator of TGF-β signaling and also an activator of the tumor suppressor p53 in response to cellular stress. Its role in human cancer is complex and controversial with both pro-oncogenic and anti-oncogenic activities reported. To clarify its role in human cancer and provide clinical relevance to its signaling activities, we examined SnoN expression in normal and cancerous human esophageal, ovarian, pancreatic and breast tissues. In normal tissues, SnoN is expressed in both the epithelium and the surrounding stroma at a moderate level and is predominantly cytoplasmic. SnoN levels in all tumor epithelia examined are lower than or similar to that in the matched normal samples, consistent with its anti-tumorigenic activity in epithelial cells. In contrast, SnoN expression in the stroma is highly upregulated in the infiltrating inflammatory cells in high-grade esophageal and ovarian tumor samples, suggesting that SnoN may potentially promote malignant progression through modulating the tumor microenvironment in these tumor types. The overall levels of SnoN expression in these cancer tissues do not correlate with the p53 status. However, in human cancer cell lines with amplification of the snoN gene, a strong correlation between increased SnoN copy number and inactivation of p53 was detected, suggesting that the tumor suppressor SnoN-p53 pathway must be inactivated, either through downregulation of SnoN or inactivation of p53, in order to allow cancer cell to proliferate and survive. These data strongly suggest that SnoN can function as a tumor suppressor at early stages of tumorigenesis in human cancer tissues.

  9. Altered virulence potential of Salmonella Enteritidis cultured in different foods: A cumulative effect of differential gene expression and immunomodulation.

    Science.gov (United States)

    Jaiswal, Sangeeta; Sahoo, Prakash Kumar; Ryan, Daniel; Das, Jugal Kishore; Chakraborty, Eesha; Mohakud, Nirmal Kumar; Suar, Mrutyunjay

    2016-08-02

    Salmonella enterica serovars Enteritidis (S. Enteritidis) is one of the most common causes of food borne illness. Bacterial growth environment plays an important role in regulating gene expression thereby affecting the virulence profile of the bacteria. Different foods present diverse growth conditions which may affect the pathogenic potential of the bacteria. In the present study, the effect of food environments on the pathogenic potential of S. Enteritidis has been evaluated. S. Enteritidis was grown in different foods e.g. egg white, peanut butter and milk, and virulent phenotypes were compared to those grown in Luria Bertani broth. In-vivo experiments in C57BL/6 mice revealed S. Enteritidis grown in egg white did not induce significant (panalysis revealed SPI-1 effectors were downregulated in bacteria grown in egg white. Interestingly, bacteria grown in egg white showed reversal of phenotype upon change in growth media to LB. Additionally, bacteria grown in milk and peanut butter showed different degrees of virulence in mice as compared to those grown in LB media. Thus, the present study demonstrates that, S. Enteritidis grown in egg white colonizes systemic sites without causing colitis in a mouse model, while bacteria grown in milk and peanut butter show different pathogenicity profiles suggesting that food environments significantly affect the pathogenicity of S. Enteritidis. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Avian WNT4 in the female reproductive tracts: potential role of oviduct development and ovarian carcinogenesis.

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    Chul-Hong Lim

    Full Text Available The wingless-type MMTV integration site family of proteins (WNTs is highly conserved secreted lipid-modified signaling molecules that play a variety of pivotal roles in developmental events such as embryogenesis, tissue homeostasis and cell polarity. Although, of these proteins, WNT4 is known to be involved in genital development in fetuses of mammalian species, its role is unknown in avian species. Therefore, in this study, we investigated expression profiles, as well as hormonal and post-transcriptional regulation of WNT4 expression in the reproductive tract of female chickens. Results of this study demonstrated that WNT4 is most abundant in the stromal and luminal epithelial cells of the isthmus and shell gland of the oviduct, respectively. WNT4 is also most abundant in the glandular epithelium of the shell gland of the oviduct of laying hens at 3 h post-ovulation during the laying cycle. In addition, treatment of young chicks with diethylstilbestrol (DES, a synthetic estrogen agonist stimulated WNT4 only in the glandular epithelial cells of the isthmus and shell gland of the oviduct. Moreover, results of our study demonstrated that miR-1786 influences WNT4 expression via specific binding sites in its 3'-UTR. On the other hand, our results also indicate that WNT4 is expressed predominantly in the glandular epithelium of cancerous ovaries, but not in normal ovaries of hens. Collectively, these results indicate cell-specific expression of WNT4 in the reproductive tract of chickens and that it likely has crucial roles in development and function of oviduct as well as initiation of ovarian carcinogenesis in laying hens.

  11. Ancestry as a potential modifier of gene expression in breast tumors from Colombian women.

    Directory of Open Access Journals (Sweden)

    Silvia J Serrano-Gómez

    Full Text Available Hispanic/Latino populations are a genetically admixed and heterogeneous group, with variable fractions of European, Indigenous American and African ancestries. The molecular profile of breast cancer has been widely described in non-Hispanic Whites but equivalent knowledge is lacking in Hispanic/Latinas. We have previously reported that the most prevalent breast cancer intrinsic subtype in Colombian women was Luminal B as defined by St. Gallen 2013 criteria. In this study we explored ancestry-associated differences in molecular profiles of Luminal B tumors among these highly admixed women.We performed whole-transcriptome RNA-seq analysis in 42 Luminal tumors (21 Luminal A and 21 Luminal B from Colombian women. Genetic ancestry was estimated from a panel of 80 ancestry-informative markers (AIM. We categorized patients according to Luminal subtype and to the proportion of European and Indigenous American ancestry and performed differential expression analysis comparing Luminal B against Luminal A tumors according to the assigned ancestry groups.We found 5 genes potentially modulated by genetic ancestry: ERBB2 (log2FC = 2.367, padj<0.01, GRB7 (log2FC = 2.327, padj<0.01, GSDMB (log2FC = 1.723, padj<0.01, MIEN1 (log2FC = 2.195, padj<0.01 and ONECUT2 (log2FC = 2.204, padj<0.01. In the replication set we found a statistical significant association between ERBB2 expression with Indigenous American ancestry (p = 0.02, B = 3.11. This association was not biased by the distribution of HER2+ tumors among the groups analyzed.Our results suggest that genetic ancestry in Hispanic/Latina women might modify ERBB2 gene expression in Luminal tumors. Further analyses are needed to confirm these findings and explore their prognostic value.

  12. When dispositional and role power fit: implications for self-expression and self-other congruence.

    Science.gov (United States)

    Chen, Serena; Langner, Carrie A; Mendoza-Denton, Rodolfo

    2009-03-01

    Integrating and extending the literatures on social power and person-environment fit, 4 studies tested the hypothesis that when people's dispositional beliefs about their capacity to influence others fit their assigned role power, they are more likely to engage in self-expression-that is, behave in line with their states and traits-thereby increasing their likelihood of being perceived by others in a manner congruent with their own self-judgments (i.e., self-other congruence). In Studies 1-3, dispositionally high- and low-power participants were randomly assigned to play a high- or low-power role in an interaction with a confederate. When participants' dispositional and role power fit (vs. conflicted), they reported greater self-expression (Study 1). Furthermore, under dispositional-role power fit conditions, the confederate's ratings of participants' emotional experiences (Study 2) and personality traits (Study 3) were more congruent with participants' self-reported emotions and traits. Study 4's results replicated Study 3's results using an implicit manipulation of power and outside observers' (rather than a confederate's) ratings of participants. Implications for research on power and person perception are discussed.

  13. Plant expressed coccidial antigens as potential vaccine candidates in protecting chicken against coccidiosis.

    Science.gov (United States)

    Sathish, Kota; Sriraman, Rajan; Subramanian, B Mohana; Rao, N Hanumantha; Kasa, Balaji; Donikeni, Jagan; Narasu, M Lakshmi; Srinivasan, V A

    2012-06-22

    Coccidiosis is a disease caused by intracellular parasites belonging to the genus Eimeria. In the present study, we transiently expressed two coccidial antigens EtMIC1 and EtMIC2 as poly histidine-tagged fusion proteins in tobacco. We have evaluated the protective efficacy of plant expressed EtMIC1 as monovalent and as well as bi-valent formulation where EtMIC1 and EtMIC2 were used in combination. The protective efficacy of these formulations was evaluated using homologous challenge in chickens. We observed better serum antibody response, weight gain and reduced oocyst shedding in birds immunized with EtMIC1 and EtMIC2 as bivalent formulation compared to monovalent formulation. However, IFN-γ response was not significant in birds immunized with EtMIC1 compared to the birds immunized with EtMIC2. Our results indicate the potential use of these antigens as vaccine candidates. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Potentiation of anthrax vaccines using protective antigen-expressing viral replicon vectors.

    Science.gov (United States)

    Wang, Hai-Chao; An, Huai-Jie; Yu, Yun-Zhou; Xu, Qing

    2015-02-01

    DNA vaccines require improvement for human use because they are generally weak stimulators of the immune system in humans. The efficacy of DNA vaccines can be improved using a viral replicon as vector to administer antigen of pathogen. In this study, we comprehensively evaluated the conventional non-viral DNA, viral replicon DNA or viral replicon particles (VRP) vaccines encoding different forms of anthrax protective antigen (PA) for specific immunity and protective potency against anthrax. Our current results clearly suggested that these viral replicon DNA or VRP vaccines derived from Semliki Forest virus (SFV) induced stronger PA-specific immune responses than the conventional non-viral DNA vaccines when encoding the same antigen forms, which resulted in potent protection against challenge with the Bacillus anthracis strain A16R. Additionally, the naked PA-expressing SFV replicon DNA or VRP vaccines without the need for high doses or demanding particular delivery regimens elicited robust immune responses and afforded completely protective potencies, which indicated the potential of the SFV replicon as vector of anthrax vaccines for use in clinical application. Therefore, our results suggest that these PA-expressing SFV replicon DNA or VRP vaccines may be suitable as candidate vaccines against anthrax. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. In silico identification of coffee genome expressed sequences potentially associated with resistance to diseases.

    Science.gov (United States)

    Alvarenga, Samuel Mazzinghy; Caixeta, Eveline Teixeira; Hufnagel, Bárbara; Thiebaut, Flávia; Maciel-Zambolim, Eunize; Zambolim, Laércio; Sakiyama, Ney Sussumu

    2010-10-01

    Sequences potentially associated with coffee resistance to diseases were identified by in silico analyses using the database of the Brazilian Coffee Genome Project (BCGP). Keywords corresponding to plant resistance mechanisms to pathogens identified in the literature were used as baits for data mining. Expressed sequence tags (ESTs) related to each of these keywords were identified with tools available in the BCGP bioinformatics platform. A total of 11,300 ESTs were mined. These ESTs were clustered and formed 979 EST-contigs with similarities to chitinases, kinases, cytochrome P450 and nucleotide binding site-leucine rich repeat (NBS-LRR) proteins, as well as with proteins related to disease resistance, pathogenesis, hypersensitivity response (HR) and plant defense responses to diseases. The 140 EST-contigs identified through the keyword NBS-LRR were classified according to function. This classification allowed association of the predicted products of EST-contigs with biological processes, including host defense and apoptosis, and with molecular functions such as nucleotide binding and signal transducer activity. Fisher's exact test was used to examine the significance of differences in contig expression between libraries representing the responses to biotic stress challenges and other libraries from the BCGP. This analysis revealed seven contigs highly similar to catalase, chitinase, protein with a BURP domain and unknown proteins. The involvement of these coffee proteins in plant responses to disease is discussed.

  16. In silico identification of coffee genome expressed sequences potentially associated with resistance to diseases

    Directory of Open Access Journals (Sweden)

    Samuel Mazzinghy Alvarenga

    2010-01-01

    Full Text Available Sequences potentially associated with coffee resistance to diseases were identified by in silico analyses using the database of the Brazilian Coffee Genome Project (BCGP. Keywords corresponding to plant resistance mechanisms to pathogens identified in the literature were used as baits for data mining. Expressed sequence tags (ESTs related to each of these keywords were identified with tools available in the BCGP bioinformatics platform. A total of 11,300 ESTs were mined. These ESTs were clustered and formed 979 EST-contigs with similarities to chitinases, kinases, cytochrome P450 and nucleotide binding site-leucine rich repeat (NBS-LRR proteins, as well as with proteins related to disease resistance, pathogenesis, hypersensitivity response (HR and plant defense responses to diseases. The 140 EST-contigs identified through the keyword NBS-LRR were classified according to function. This classification allowed association of the predicted products of EST-contigs with biological processes, including host defense and apoptosis, and with molecular functions such as nucleotide binding and signal transducer activity. Fisher's exact test was used to examine the significance of differences in contig expression between libraries representing the responses to biotic stress challenges and other libraries from the BCGP. This analysis revealed seven contigs highly similar to catalase, chitinase, protein with a BURP domain and unknown proteins. The involvement of these coffee proteins in plant responses to disease is discussed.

  17. Ancestry as a potential modifier of gene expression in breast tumors from Colombian women.

    Science.gov (United States)

    Serrano-Gómez, Silvia J; Sanabria-Salas, María Carolina; Garay, Jone; Baddoo, Melody C; Hernández-Suarez, Gustavo; Mejía, Juan Carlos; García, Oscar; Miele, Lucio; Fejerman, Laura; Zabaleta, Jovanny

    2017-01-01

    Hispanic/Latino populations are a genetically admixed and heterogeneous group, with variable fractions of European, Indigenous American and African ancestries. The molecular profile of breast cancer has been widely described in non-Hispanic Whites but equivalent knowledge is lacking in Hispanic/Latinas. We have previously reported that the most prevalent breast cancer intrinsic subtype in Colombian women was Luminal B as defined by St. Gallen 2013 criteria. In this study we explored ancestry-associated differences in molecular profiles of Luminal B tumors among these highly admixed women. We performed whole-transcriptome RNA-seq analysis in 42 Luminal tumors (21 Luminal A and 21 Luminal B) from Colombian women. Genetic ancestry was estimated from a panel of 80 ancestry-informative markers (AIM). We categorized patients according to Luminal subtype and to the proportion of European and Indigenous American ancestry and performed differential expression analysis comparing Luminal B against Luminal A tumors according to the assigned ancestry groups. We found 5 genes potentially modulated by genetic ancestry: ERBB2 (log2FC = 2.367, padjancestry (p = 0.02, B = 3.11). This association was not biased by the distribution of HER2+ tumors among the groups analyzed. Our results suggest that genetic ancestry in Hispanic/Latina women might modify ERBB2 gene expression in Luminal tumors. Further analyses are needed to confirm these findings and explore their prognostic value.

  18. Transient receptor potential V2 expressed in sensory neurons is activated by probenecid.

    Science.gov (United States)

    Bang, Sangsu; Kim, Kyung Yoon; Yoo, Sungjae; Lee, Sang-Heon; Hwang, Sun Wook

    2007-09-25

    Temperature-activated transient receptor potential ion channels (thermoTRPs) are known to function as ambient temperature sensors and are also involved in peripheral pain sensation. The thermoTRPs are activated by a variety of chemicals, of which specific activators have been utilized to explore the physiology of particular channels and sensory nerve subtypes. The use of capsaicin for TRPV1 is an exemplary case for nociceptor studies. In contrast, specific agents for another vanilloid subtype channel, TRPV2 have been lacking. Here, we show that probenecid is able to activate TRPV2 using electrophysiological and calcium imaging techniques with TRPV2-expressing HEK293T cells. Five other sensory thermoTRPs-TRPV1, TRPV3, TRPV4, TRPM8 and TRPA1-failed to show a response to this drug in the same heterologous expression system, suggesting that probenecid is a specific activator for TRPV2. Probenecid-evoked responses were also reproduced in a distinct subset of cultured trigeminal neurons that were responsive to 2-aminoethoxydiphenyl borate, a TRPV1-3 activator. The probenecid-sensitive neurons were mainly distributed in a medium to large-diameter population, in agreement with previous observations with TRPV2 immunolocalization. Under inflammation, probenecid elicited nociceptive behaviors in in vivo assays. These results suggest that TRPV2 is specifically activated by probenecid and that this chemical might be useful for investigation of pain-related TRPV2 function.

  19. The Predicting Role of Difficulties in Emotion Regulation and Distress Tolerance in Students’ Addiction Potential

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    M Esmaeilinasab

    2014-11-01

    Full Text Available Objective: This study aimed to determine the predicting role of difficulties in emotion regulation and distress tolerance in addiction potential in university students. Method: The sample included 180 students of Allameh Tabatabaei University (82 males and 88 females who were selected randomly. For this correlational study, the Addiction Potential Scale, Difficulties in Emotion Regulation Scale, and Distress Tolerance Scale (Simons & Gaher, 2005 were administered among selected sample. Results: The results showed that difficulties in emotion regulation could predict 37.5 percent of addiction potential and between its subscales, lack of emotional clarity, had the most important role. Also, distress tolerance was not significantly related to addiction potential. Conclusion: By considering of results, it can be said students’ training in improving of emotion regulation is useful in preventing of addiction.

  20. Role of feedback and network architecture in controlling virulence gene expression in Bordetella.

    Science.gov (United States)

    Prajapat, Mahendra Kumar; Saini, Supreet

    2013-11-01

    Bordetella is a Gram-negative bacterium responsible for causing whooping cough in a broad range of host organisms. For successful infection, Bordetella controls expression of four distinct classes of genes (referred to as class 1, 2, 3, and 4 genes) at distinct times in the infection cycle. This control is executed by a single two-component system, BvgAS. Interestingly, the transmembrane component of the two-component system, BvgS, consists of three phospho-transfer domains leading to phosphorylation of the response regulator, BvgA. Phosphorylated BvgA then controls expression of virulence genes and also controls bvgAS transcription. In this work, we perform simulations to characterize the role of the network architecture in governing gene expression in Bordetella. Our results show that the wild-type network is locally optimal for controlling the timing of expression of the different classes of genes involved in infection. In addition, the interplay between environmental signals and positive feedback aids the bacterium identify precise conditions for and control expression of virulence genes.

  1. Role of WNT10A-expressing kidney fibroblasts in acute interstitial nephritis.

    Directory of Open Access Journals (Sweden)

    Akihiro Kuma

    Full Text Available WNT signaling mediates various physiological and pathological processes. We previously showed that WNT10A is a novel angio/stromagenic factor involved in such processes as tumor growth, wound healing and tissue fibrosis. In this study, we investigated the role of WNT10A in promoting the fibrosis that is central to the pathology of acute interstitial nephritis (AIN. We initially asked whether there is an association between kidney function (estimated glomerular filtration rate; eGFR and WNT10A expression using kidney biopsies from 20 patients with AIN. Interestingly, patients with WNT10A expression had significantly lower eGFR than WNT10A-negative patients. However, changes in kidney function were not related to the level of expression of other WNT family members. Furthermore, there was positive correlation between WNT10A and α-SMA expression. We next investigated the involvement of WNT10A in kidney fibrosis processes using COS1 cells, a kidney fibroblast cell line. WNT10A overexpression increased the level of expression of fibronectin and peroxiredoxin 5. Furthermore, WNT10A overexpression renders cells resistant to apoptosis induced by hydrogen peroxide and high glucose. Collectively, WNT10A may induce kidney fibrosis and associate with kidney dysfunction in AIN.

  2. Roles of histamine on the expression of aldehyde dehydrogenase 1 in endometrioid adenocarcinoma cell line

    Science.gov (United States)

    Wang, Yi; Jiang, Yang; Ikeda, Jun-ichiro; Tian, Tian; Sato, Atsushi; Ohtsu, Hiroshi; Morii, Eiichi

    2014-01-01

    Cancer-initiating cells (CICs) are a limited number of cells that are essential for maintenance, recurrence, and metastasis of tumors. Aldehyde dehydrogenase 1 (ALDH1) has been recognized as a marker of CICs. We previously reported that ALDH1-high cases of uterine endometrioid adenocarcinoma showed poor prognosis, and that ALDH1 high population was more tumorigenic, invasive, and resistant to apoptosis than ALDH1 low population. Histamine plays a critical role in cancer cell proliferation, migration, and invasion. Here, we examined the effect of histamine on ALDH1 expression in endometrioid adenocarcinoma cell line. The addition of histamine increased ALDH1 high population, which was consistent with the result that histamine enhanced the invasive ability and the resistance to anticancer drug. Among 4 types of histamine receptors, histamine H1 and H2 receptor (H1R and H2R) were expressed in endometrioid adenocarcinoma cell line. The addition of H1R agonist but not H2R agonist increased ALDH1. The antagonist H1R but not H2R inhibited the effect of histamine on ALDH1 expression. These results indicated that histamine increased the expression of ALDH1 via H1R but not H2R. These findings may provide the evidence for exploring a new strategy to suppress CICs by inhibiting ALDH1 expression with histamine. PMID:25045085

  3. P73 expression in neuroblastoma: a role in the biology of advanced tumors?

    Science.gov (United States)

    Matos, P; Isidro, G; Vieira, E; Lacerda, A F; Martins, A G; Boavida, M G

    2001-01-01

    p73, a recently identified gene showing high homology to p53 and mapping to 1p36.33, was presented as a candidate gene for neuroblastoma. In this study the authors evaluate the levels and allelic nature of p73 expression in primary neuroblastomas using reverse transcription-polymerase chain reaction-restriction fragment length polymorphism strategies based on intragenic polymorphisms. From 32 neuroblastoma patients, 11 were heterozygous for the p73 polymorphisms analyzed. p73 expression was found to be low in the correspondent tumors and while all 6 stages 1 and 2 tumors presented biallelic expression, 4 out of the 5 stage 4 tumors showed only one active p73 allele. Analysis of blood samples from 8 healthy donors and 4 neuroblastoma patients revealed much higher levels of p73 expression, and exclusively of biallelic nature. These results are supportive of a role for p73 in the biology of neuroblastoma, particularly in some advanced tumors. Nevertheless, the G81A/C91T polymorphism, previously implicated in regulating the expression of p73, did not show any significant association with neuroblastoma development.

  4. Cytokine expression in mice exposed to diesel exhaust particles by inhalation. Role of tumor necrosis factor

    Directory of Open Access Journals (Sweden)

    Loft Steffen

    2006-02-01

    Full Text Available Abstract Background Particulate air pollution has been associated with lung and cardiovascular disease, for which lung inflammation may be a driving mechanism. The pro-inflammatory cytokine, tumor necrosis factor (TNF has been suggested to have a key-role in particle-induced inflammation. We studied the time course of gene expression of inflammatory markers in the lungs of wild type mice and Tnf-/- mice after exposure to diesel exhaust particles (DEPs. Mice were exposed to either a single or multiple doses of DEP by inhalation. We measured the mRNA level of the cytokines Tnf and interleukin-6 (Il-6 and the chemokines, monocyte chemoattractant protein (Mcp-1, macrophage inflammatory protein-2 (Mip-2 and keratinocyte derived chemokine (Kc in the lung tissue at different time points after exposure. Results Tnf mRNA expression levels increased late after DEP-inhalation, whereas the expression levels of Il-6, Mcp-1 and Kc increased early. The expression of Mip-2 was independent of TNF if the dose was above a certain level. The expression levels of the cytokines Kc, Mcp-1 and Il-6, were increased in the absence of TNF. Conclusion Our data demonstrate that Tnf is not important in early DEP induced inflammation and rather exerts negative influence on Mcp-1 and Kc mRNA levels. This suggests that other signalling pathways are important, a candidate being one involving Mcp-1.

  5. Role of NeuroD1 on the negative regulation of Pomc expression by glucocorticoid.

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    Rehana Parvin

    Full Text Available The mechanism of the negative regulation of proopiomelanocortin gene (Pomc by glucocorticoids (Gcs is still unclear in many points. Here, we demonstrated the involvement of neurogenic differentiation factor 1 (NeuroD1 in the Gc-mediated negative regulation of Pomc. Murine pituitary adrenocorticotropic hormone (ACTH producing corticotroph tumor-derived AtT20 cells were treated with dexamethasone (DEX (1-100 nM and cultured for 24 hrs. Thereafter, Pomc mRNA expression was studied by quantitative real-time PCR and rat Pomc promoter (-703/+58 activity was examined by luciferase assay. Both Pomc mRNA expression and Pomc promoter activity were inhibited by DEX in a dose-dependent manner. Deletion and point mutant analyses of Pomc promoter suggested that the DEX-mediated transcriptional repression was mediated via E-box that exists at -376/-371 in the promoter. Since NeuroD1 is known to bind to and activate E-box of the Pomc promoter, we next examined the effect of DEX on NeuroD1 expression. Interestingly, DEX dose-dependently inhibited NeuroD1 mRNA expression, mouse NeuroD1 promoter (-2.2-kb activity, and NeuroD1 protein expression in AtT20 cells. In addition, we confirmed the inhibitory effect of DEX on the interaction of NeuroD1 and E-box on Pomc promoter by chromatin immunoprecipitation (ChIP assay. Finally, overexpression of mouse NeuroD1 could rescue the DEX-mediated inhibition of Pomc mRNA expression and Pomc promoter activity. Taken together, it is suggested that the suppression of NeuroD1 expression and the inhibition of NeuroD1/E-box interaction may play an important role in the Gc-mediated negative regulation of Pomc.

  6. The Role of Academic Burnout, Resilience, and Perceived Stress in Predicting Students\\\\\\' Addiction Potential

    OpenAIRE

    mojtaba salmabadi; Hossein Salimi Bajestani; hamze Khayami Abiz; Reza javan

    2015-01-01

    Objective: This study aimed at determining the role of academic burnout, resilience, and perceived stress in predicting students' addiction potential. Method: In this correlational study, the number of 200 high school students in of South Khorasan province was selected as the participants through random cluster sampling and they responded to the three pertinent questionnaires, namely resilience scale, academic burnout scale, perceived stress scale, and addiction potential scale. Results: The ...

  7. A potential role for intragenic miRNAs on their hosts' interactome

    Directory of Open Access Journals (Sweden)

    Kuo Winston P

    2010-10-01

    Full Text Available Abstract Background miRNAs are small, non-coding RNA molecules that mainly act as negative regulators of target gene messages. Due to their regulatory functions, they have lately been implicated in several diseases, including malignancies. Roughly half of known miRNA genes are located within previously annotated protein-coding regions ("intragenic miRNAs". Although a role of intragenic miRNAs as negative feedback regulators has been speculated, to the best of our knowledge there have been no conclusive large-scale studies investigating the relationship between intragenic miRNAs and host genes and their pathways. Results miRNA-containing host genes were three times longer, contained more introns and had longer 5' introns compared to a randomly sampled gene cohort. These results are consistent with the observation that more than 60% of intronic miRNAs are found within the first five 5' introns. Host gene 3'-untranslated regions (3'-UTRs were 40% longer and contained significantly more adenylate/uridylate-rich elements (AREs compared to a randomly sampled gene cohort. Coincidentally, recent literature suggests that several components of the miRNA biogenesis pathway are required for the rapid decay of mRNAs containing AREs. A high-confidence set of predicted mRNA targets of intragenic miRNAs also shared many of these features with the host genes. Approximately 20% of intragenic miRNAs were predicted to target their host mRNA transcript. Further, KEGG pathway analysis demonstrated that 22 of the 74 pathways in which host genes were associated showed significant overrepresentation of proteins encoded by the mRNA targets of associated intragenic miRNAs. Conclusions Our findings suggest that both host genes and intragenic miRNA targets may potentially be subject to multiple layers of regulation. Tight regulatory control of these genes is likely critical for cellular homeostasis and absence of disease. To this end, we examined the potential for negative

  8. Transient receptor potential channel superfamily: Role in lower urinary tract function.

    Science.gov (United States)

    Ogawa, Teruyuki; Imamura, Tetsuya; Nakazawa, Masaki; Hiragata, Shiro; Nagai, Takashi; Minagawa, Tomonori; Yokoyama, Hitoshi; Ishikawa, Masakuni; Domen, Takahisa; Ishizuka, Osamu

    2015-11-01

    Lower urinary tract symptoms associated with neurogenic bladder and overactive bladder syndrome are mediated in part by members of the transient receptor potential channel superfamily. The best studied member of this superfamily is the vanilloid receptor. Other transient receptor potential channels, such as the melastatin receptor and the ankyrin receptor, are also active in the pathogenesis of lower urinary tract dysfunction. However, the detailed mechanisms by which the transient receptor potential channels contribute to lower urinary tract symptoms are still not clear, and the therapeutic benefits of modulating transient receptor potential channel activity have not been proved in the clinical setting. In the present review, to better understand the pathophysiology and therapeutic potential for lower urinary tract symptoms, we summarize the presence and role of different members of the transient receptor potential channel superfamily in the lower urinary tract. © 2015 The Japanese Urological Association.

  9. Understanding the role of keratins 8 and 18 in neoplastic potential of breast cancer derived cell lines.

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    Sapna V Iyer

    Full Text Available BACKGROUND: Breast cancer is a complex disease which cannot be defined merely by clinical parameters like lymph node involvement and histological grade, or by routinely used biomarkers like estrogen receptor (ER, progesterone receptor (PGR and epidermal growth factor receptor 2 (HER2 in diagnosis and prognosis. Breast cancer originates from the epithelial cells. Keratins (K are cytoplasmic intermediate filament proteins of epithelial cells and changes in the expression pattern of keratins have been seen during malignant transformation in the breast. Expression of the K8/18 pair is seen in the luminal cells of the breast epithelium, and its role in prognostication of breast cancer is not well understood. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we have modulated K8 expression to understand the role of the K8/18 pair in three different breast epithelium derived cell lines: non-transformed MCF10A, transformed but poorly invasive MDA MB 468 and highly invasive MDA MB 435. The up-regulation of K8 in the invasive MDA MB 435 cell line resulted in a significant decrease in proliferation, motility, in-vitro invasion, tumor volume and lung metastasis. The down-regulation of K8 in MDA MB 468 resulted in a significant increase in transformation potential, motility and invasion in-vitro, while MCF10A did not show any changes in cell transformation assays. CONCLUSIONS/SIGNIFICANCE: These results indicate the role of K8/18 in modulating invasion in breast cancer -its presence correlating with less invasive phenotype and absence correlating with highly invasive, dedifferentiated phenotype. These data may have important implications for prognostication of breast cancer.

  10. The EGFR pathway regulates BCRP expression in NSCLC cells: role of erlotinib.

    Science.gov (United States)

    Porcelli, Letizia; Giovannetti, Elisa; Assaraf, Yehuda G; Jansen, Gerrit; Scheffer, George L; Kathman, Ietje; Azzariti, Amalia; Paradiso, Angelo; Peters, Godefridus J

    2014-01-01

    While multidrug resistance (MDR) in cancer is well established, little is known about the cellular pathways regulating the expression and trafficking of the MDR efflux transporter like BCRP (ABCG2). Here we evaluated the role of signalling downstream of EGFR on BCRP expression and sub-cellular localization using lung cancer cells harboring BCRP but expressing various EGFR and Ras activating mutations; A549 (K-Ras-G12S), H292 wild-type EGFR and Ras, and H1650 (EGFR-DelE747-A750). Immunocytochemistry and immunofluorescence studies demonstrated that BCRP was predominantly intracellular but its expression was found also on the plasma membrane in A549 and H1650 cells with activated Ras and EGFR. Remarkably, EGFR inhibition by erlotinib at IC₅₀ concentrations induced a differential timedependent alteration in BCRP gene and protein expression. In H1650 cells, erlotinib enhanced both the total and plasma membrane degradation of BCRP by ubiquitination within 6-24 hours, whereas BCRP expression regained the original basal levels after 48 hours. In erlotinib treated H292 cells, BCRP levels decreased at 24 hours until 72 hours, whereas in A549 cells erlotinib initially reduced BCRP expression but then induced its accumulation on the plasma membrane at 72 hours. We further found that the PI3K/Akt inhibitor LY294002 down-regulated BCRP expression, hence showing that the Akt pathway is involved in the regulation of BCRP expression but not in its localization in these lung cancer cell lines. Finally, the selective BCRP transport inhibitor Ko143 did not increase erlotinib sensitivity, but did decrease the transport activity of BCRP in A549 and H1650 cells as it induced the accumulation of its transport substrate topotecan. In conclusion, our results suggest that the EGFR and Akt pathways are involved in regulation of BCRP expression, trafficking and drug transport activity. These findings warrant future studies on the pharmacologic modulation of these pathways to enhance the

  11. An Epigenetic Role for Disrupted Paternal Gene Expression in Postzygotic Seed Abortion in Arabidopsis Interspecific Hybrids.

    Science.gov (United States)

    Kirkbride, Ryan C; Yu, Helen Hong; Nah, Gyoungju; Zhang, Changqing; Shi, Xiaoli; Chen, Z Jeffrey

    2015-12-07

    Interspecific hybrids often increase the levels of heterozygosity and hybrid vigor, but some interspecific hybrid seeds are aborted shortly after fertilization. The mechanism behind this postzygotic seed abortion is poorly understood. Here, we report genome-wide analysis of allelic expression changes in developing siliques and seeds in three F1 interspecific crosses between Arabidopsis thaliana (Col, Ler, or C24) and Arabidopsis arenosa. The majority of maternally expressed genes (MEGs) were shared among all three F1 interspecific crosses, whereas ∼90% of 272 paternally expressed genes (PEGs) were found only in one or two F1 crosses, suggesting a role for disrupted paternal gene expression in seed abortion that varies in different crosses. Consistent with this notion, 12 PEGs in the infertile interspecific hybrids matched MEGs in fertile intraspecific hybrids. This disruption of PEGs in the interspecific hybrids was consistent with the upregulation of the genes in the paternal-excess interploidy cross (2X6) between a diploid mother and a hexaploid father, leading to the seed abortion. Moreover, a subset of PEGs in the interspecific crosses were also upregulated in the intraspecific hybrid met1XWT or meaXWT, in which the mutant of MET1 (DNA METHYLTRANSFERASE1) or MEDEA, a Polycomb Repressive Complex2 gene, was used as the maternal parent. These data suggest that maternal epigenetic factors and paternal gene expression play important roles in the postzygotic seed abortion in interspecific hybrids or neo-allopolyploids. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

  12. The role of Nanog expression in tamoxifen-resistant breast cancer cells

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    Arif K

    2015-06-01

    Full Text Available Khalid Arif,1 Issam Hussain,1 Carol Rea,1 Mohamed El-Sheemy2 1School of Life Sciences, University of Lincoln, Brayford Pool, 2Lincoln County Hospital, Greetwell Road, Lincoln, Lincolnshire, UK Abstract: There is an accumulation of evidence that shows a significant role of cancer stem cells in tumor initiation, proliferation, relapse, and metastasis. Nanog is the most important core transcription marker of stem cells, known by its role in maintaining pluripotency, proliferation, and differentiation. Therefore, this study aimed to examine the role of Nanog in breast cancer cell tamoxifen resistance and its implications in breast cancer treatment. In this study, the expression of the three core transcription markers Nanog, Oct3/4, and Sox2 were quantitatively evaluated using flow cytometry. Then, small interfering RNA (siRNA against human Nanog was transfected into tamoxifen-resistant breast cancer cells via Lipofectamine 2000. Nanog gene expression in the cells was detected using reverse transcription polymerase chain reaction (RT-PCR. The change in cell proliferation was evaluated using the tetrazolium bromide method. An enzyme-linked immunosorbent assay was used to detect apoptosis of the transfected cells alone and in combination with 4-hydroxytamoxifen. The results showed a high level expression of Nanog, Oct3/4, and Sox2 in MDA-MB-231 and MCF7/tamoxifen resistant cells compared with MCF7/wild-type. siRNA-mediated Nanog gene silencing can efficiently inhibit cell proliferation and induce apoptosis of tamoxifen-resistant breast cancer cells. This study provides a basis for further study of the role of Nanog in developing resistance to tamoxifen, its implication in breast cancer management, and as a new strategy to enhance response to endocrine therapy. Keywords: breast cancer, cancer stem cell, Nanog, tamoxifen, estrogen receptor

  13. Role of NKG2D-Expressing NK Cells and sMICA in Immune Surveillance of Advanced Lung Cancer

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    Jing LIANG

    2009-01-01

    Full Text Available Background and objective NKG2D-expressing NK cells and soluble major histocompatibility complex class Ⅰ-related chain A (sMICA is one of aroused general interests in tumor research area recently. The aimof the study is to investigate the levels of NKG2D-expressing NK cells and sMICA in peripheral blood of advanced lung cancer which are remarkably related to clinical significance and analyse the role of NKG2D-expressing NK cells and sMICA in immune surveillance. Methods Flow cytometry was used to determine the percentage of NKG2D-expressing NK cells, T cell subsets, NK cells, and ELISA was used to mesure the levels of sMICA in peripheral blood of 115 advanced lung cancer patients and 50 healthy controls. Results Compared with control group, the levels of sMICA、CD8+T cells, NK cells increased, while the levels of NKG2D-expressing NK cells, CD3+ T cells, CD4+ T cells, CD4+ T/CD8+ T in experimental group decreased. NKG2D-expressing NK cells had a perfect negative correlation with sMICA (r =-0.319, P <0.05. NKG2D-expressing NK cells had positive correlation with CD4+ T cells, CD4+ T/CD8+ T and negative correlationwith CD8+ T cells (P <0.05, sMICA had negative correlation with CD4+ T cells, CD4+ T/CD8+ T and positive correlation with CD8+ T cells (P <0.05, they had no significant correlation with CD3+ T cells, NK cells respectively (P <0.05. Conclusion Accumulation of sMICA in serum may lead to the down-modulation of NKG2D-expressing NK which has been proposed to be a novel mechanism used by cancer cells to evade the tumor immunosurveillance. They may be potential indicators investigating immune functions and helpful in the evaluation of their happening and proceeding.

  14. The Role of Infrastructure Potential of the Financial Market in Ensuring its Flexibility and Security

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    Chunitska Iryna I.

    2017-03-01

    Full Text Available The article is dedicated to determining the role of infrastructure potential of the financial market in ensuring its security and flexibility. The aim of the article is to assess the role of infrastructure potential of the financial market in ensuring its flexibility and security. Threats to the financial market security are systematized by sources of formation, scale, duration and nature of influence. The essence of security and flexibility of the financial market is defined. There systematized indicators of security and flexibility of the financial market in interrelation with the components of infrastructure potential of the financial market. The methodology for determining the level of economic safety and flexibility of the financial market is substantiated, the corresponding calculations are made. Also the methodology for calculating the normalized index of the infrastructure potential of the financial market is developed. The correlation-regression analysis of the connection between development of the infrastructure potential of the financial market, its security and flexibility is carried out. The results of the calculations showed that the degree of implementation of the financial market infrastructure potential at the current stage of development of the Ukrainian economy is insufficient. It does not contribute to achieving the necessary level of flexibility and security of the financial market. Each of the components of infrastructure potential requires changing approaches to regulation aimed at ensuring the systematic development of the financial market. Most of the identified problems are mainly related to dysfunctionality of the technological and information components of the infrastructural potential of the financial market. This is manifested in the low level of confidence in it from the part of the household sector as well as in the poor efficiency of regulation of certain segments of the financial market. That is why the

  15. Potential role of cathepsin B in the embryonic and larval development of clam Meretrix meretrix.

    Science.gov (United States)

    Wang, Xiaomei; Liu, Baozhong; Tang, Baojun; Xiang, Jianhai

    2011-06-15

    This study was designed to investigate the possible role of Meretrix meretrix cathepsin B (MmeCB) in embryonic and larval development. MmeCB mRNA expression profile was revealed by semi-quantitative RT-PCR. The level of MmeCB mRNA expression was low in trochophore stage but high in pedveliger stage. MmeCB protein expression was detected in the digestive gland, velum, and epidermis along the edges of the shell in D-larvae and pedveligers by immunocytochemistry. In post larvae, MmeCB protein expression was noticed abundant in the digestive gland, whereas a modest expression was identified in the gill filament. The average shell length of larvae hatched from embryos treated with 0.01, 1, and 10 µmol/L Ca074Me (a cathepsin B inhibitor) was significantly shorter than that of control groups. The metamorphosis rates of larvae treated with 0.01 and 1 µmol/L Ca074Me were significantly lower than that of control groups in 4-day larvae, but not in 5-day larvae. Taken together, these results indicated that MmeCB may have stimulatory effects on embryonic development, metamorphosis, and larval growth during M. meretrix larval development. Copyright © 2011 Wiley-Liss, Inc., A Wiley Company.

  16. Minimizing the unpredictability of transgene expression in plants: the role of genetic insulators.

    Science.gov (United States)

    Singer, Stacy D; Liu, Zongrang; Cox, Kerik D

    2012-01-01

    The genetic transformation of plants has become a necessary tool for fundamental plant biology research, as well as the generation of engineered plants exhibiting improved agronomic and industrial traits. However, this technology is significantly hindered by the fact that transgene expression is often highly variable amongst independent transgenic lines. Two of the major contributing factors to this type of inconsistency are inappropriate enhancer-promoter interactions and chromosomal position effects, which frequently result in mis-expression or silencing of the transgene, respectively. Since the precise, often tissue-specific, expression of the transgene(s) of interest is often a necessity for the successful generation of transgenic plants, these undesirable side effects have the potential to pose a major challenge for the genetic engineering of these organisms. In this review, we discuss strategies for improving foreign gene expression in plants via the inclusion of enhancer-blocking insulators, which function to impede enhancer-promoter communication, and barrier insulators, which block the spread of heterochromatin, in transgenic constructs. While a complete understanding of these elements remains elusive, recent studies regarding their use in genetically engineered plants indicate that they hold great promise for the improvement of transgene expression, and thus the future of plant biotechnology.

  17. Potential role of biotechnology tools for genetic improvement of “lost ...

    African Journals Online (AJOL)

    The paper considers the potential role of biotechnology applications like DNA markers in understanding the evolution, origin, distribution and diversity of fonio in Africa; somaclonal variation in generating genetic variability in fonio; and genetic transformation in circumventing fonio breeding barriers to introduce alien genes ...

  18. The Potential Role of Perceived Support for Reduction of Special Education Teachers' Burnout

    Science.gov (United States)

    Langher, Viviana; Caputo, Andrea; Ricci, Maria Elisabetta

    2017-01-01

    Teacher burnout is conceived as a general concern in special education because of the emotionally demanding work context. This study explored the potential role of perceived support for reduction of burnout in a sample of 276 special education teachers working in lower (n=130) and higher (n=146) secondary schools. Participants completed the…

  19. Developing Effective Earthquake Risk Reduction Strategies: The Potential Role of Academic Institutions in Lebanon

    Science.gov (United States)

    Baytiyeh, Hoda

    2015-01-01

    Lebanon faces the risk of powerful earthquakes with potentially devastating effects. However, the Lebanese people in general have not yet recognized this risk, as current educational programs and government officials have failed to inform them about it. This article discusses the essential role that Lebanese institutions of higher education should…

  20. The potential role of honey and its polyphenols in preventing heart ...

    African Journals Online (AJOL)

    Honey is rich in phenolic compounds, which act as natural antioxidants and are becoming increasingly popular because of their potential role in contributing to human health. A wide range of phenolic constituents is present in honey like quercetin, caffeic acid phenethyl ester (CAPE), acacetin, kaempferol, galangin which ...

  1. Potential role of biotechnology tools for genetic improvement of “lost ...

    African Journals Online (AJOL)

    Admin

    Potential role of biotechnology tools for genetic improvement of “lost crops of Africa”: the case of fonio. (Digitaria exilis and Digitaria iburua). Danladi Dada KUTA1*, Emmanuel KWON-NDUNG2, Stephen DACHI2, Mark UKWUNGWU2 and. Emmanuel Dada IMOLEHIN2. 1National Biotechnology Advanced Laboratory, Sheda ...

  2. Endosialin and Associated Protein Expression in Soft Tissue Sarcomas: A Potential Target for Anti-Endosialin Therapeutic Strategies

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    Daniel J. O’Shannessy

    2016-01-01

    Full Text Available Endosialin (CD248, TEM-1 is expressed in pericytes, tumor vasculature, tumor fibroblasts, and some tumor cells, including sarcomas, with limited normal tissue expression, and appears to play a key role in tumor-stromal interactions, including angiogenesis. Monoclonal antibodies targeting endosialin have entered clinical trials, including soft tissue sarcomas. We evaluated a cohort of 94 soft tissue sarcoma samples to assess the correlation between gene expression and protein expression by immunohistochemistry for endosialin and PDGFR-β, a reported interacting protein, across available diagnoses. Correlations between the expression of endosialin and 13 other genes of interest were also examined. Within cohorts of soft tissue diagnoses assembled by tissue type (liposarcoma, leiomyosarcoma, undifferentiated sarcoma, and other, endosialin expression was significantly correlated with a better outcome. Endosialin expression was highest in liposarcomas and lowest in leiomyosarcomas. A robust correlation between protein and gene expression data for both endosialin and PDGFR-β was observed. Endosialin expression positively correlated with PDGFR-β and heparin sulphate proteoglycan 2 and negatively correlated with carbonic anhydrase IX. Endosialin likely interacts with a network of extracellular and hypoxia activated proteins in sarcomas and other tumor types. Since expression does vary across histologic groups, endosialin may represent a selective target in soft tissue sarcomas.

  3. Potential protective role of bariatric surgery against breast cancer in postmenopausal women

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    Irina Balescu

    2017-05-01

    Full Text Available Obesity is a major public health problem worldwide especially due to the metabolic disorders which seem to be induced by an excessive amount of adipose tissue. Therefore attention was focused on evaluating the role of bariatric surgery in order to offer a better control of the comorbidities such as diabetes mellitus, arterial hypertension or dyslipidemia which are widely accepted as causes of increased morbidity and mortality among obese patients. Once these benefits have been widely demonstrated, attention was focused on studying the potential protective role of bariatric surgery against development of various malignancies such a breast, endometrial, pancreatic or even colorectal cancer. This is a literature review regarding the potential protective role of bariatric surgery against breast cancer among obese women worldwide.

  4. RECORDED-ROLE PLAY IN EFL CLASSROOM: A WAY OF MAXIMIZING STUDENTS‟ POTENTIAL IN SPEAKING

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    Krismiyati Krismiyati

    2017-04-01

    Full Text Available Teaching English for non English Department students will be quite a challenge as the students have various background and interest. Handling those students in a big number in a class that requires them to speak is another impending challenge. This is an action research on role-play in English classroom for Information Technology students. This study tries to see whether recorded-role play could maximize students‘ potential in speaking. This study involved 30 students taking English course in Information Technology Faculty. The students were given a situation in which they had to act the role play. They drafted the role -play before they recorded it. The result shows that students felt less tense in acting the role. They also got more time to practice their pronunciation before recording. It even gave students who felt reluctant and shy in the class to actively participate. In addition, students could play around with the supporting background sound to show their creativity. Surprisingly, most students do their best to show their effort in their speaking as the end-product would be played in the classroom, even the most quiet students performed really well. Finally, this recorded-role play proved to be an effective way to maximize students‘ potential in speaking.

  5. Expression of five cathepsins in murine melanomas of varying metastatic potential and normal tissues.

    Science.gov (United States)

    Qian, F; Bajkowski, A S; Steiner, D F; Chan, S J; Frankfater, A

    1989-09-01

    The relative levels of mRNAs for cathepsins B, D, H, L, and S in eight normal murine tissues and three murine melanoma variants, B16-F1, B16-F10, and B16a, have been analyzed by RNA dot blot and densitometry. A direct correlation was observed between the levels of cathepsin B mRNA and the metastatic potentials of these three melanoma variants. The relative amount of cathepsin B mRNA in B16a, which is the melanoma variant with the highest metastatic potential, was at least 3 times greater than that found in any of the normal murine tissues surveyed. Similar results were obtained in analyses of either solid tumors or of cultures of tumor cells, confirming that the tumor cells themselves were the source for the elevated expression of cathepsin B mRNA. Northern blot analysis revealed the presence of three cathepsin B transcripts of 5.0, 4.0, and 2.2 kilobases in the melanoma variants, while only the 2.2-kilobase transcript was seen in the normal murine tissues. Concurrently with the mRNA analysis, enzyme assays for cathepsin B activity were also performed using synthetic peptide substrates. The assays revealed increased cathepsin B activities in the melanoma variants, corresponding well with the increased cathepsin B mRNA levels, and in addition demonstrated that all three of the melanoma variants secreted a latent form of cathepsin B into conditioned medium, which could be activated by limited proteolysis with pepsin. The levels of the latent enzyme released by the murine melanoma variants correlated well with the levels of cathepsin B mRNA and with the metastatic potentials as determined by spontaneous metastasis form a s.c. site.

  6. A role for gene duplication and natural variation of gene expression in the evolution of metabolism.

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    Daniel J Kliebenstein

    Full Text Available BACKGROUND: Most eukaryotic genomes have undergone whole genome duplications during their evolutionary history. Recent studies have shown that the function of these duplicated genes can diverge from the ancestral gene via neo- or sub-functionalization within single genotypes. An additional possibility is that gene duplicates may also undergo partitioning of function among different genotypes of a species leading to genetic differentiation. Finally, the ability of gene duplicates to diverge may be limited by their biological function. METHODOLOGY/PRINCIPAL FINDINGS: To test these hypotheses, I estimated the impact of gene duplication and metabolic function upon intraspecific gene expression variation of segmental and tandem duplicated genes within Arabidopsis thaliana. In all instances, the younger tandem duplicated genes showed higher intraspecific gene expression variation than the average Arabidopsis gene. Surprisingly, the older segmental duplicates also showed evidence of elevated intraspecific gene expression variation albeit typically lower than for the tandem duplicates. The specific biological function of the gene as defined by metabolic pathway also modulated the level of intraspecific gene expression variation. The major energy metabolism and biosynthetic pathways showed decreased variation, suggesting that they are constrained in their ability to accumulate gene expression variation. In contrast, a major herbivory defense pathway showed significantly elevated intraspecific variation suggesting that it may be under pressure to maintain and/or generate diversity in response to fluctuating insect herbivory pressures. CONCLUSION: These data show that intraspecific variation in gene expression is facilitated by an interaction of gene duplication and biological activity. Further, this plays a role in controlling diversity of plant metabolism.

  7. The roles of Tenascin C and Fibronectin 1 in adhesive capsulitis: a pilot gene expression study

    Directory of Open Access Journals (Sweden)

    Carina Cohen

    Full Text Available OBJECTIVES: We evaluated mRNA expression levels of genes that encode TGF-β1; the TGF-β1 receptor; the collagen-modifying enzymes LOX, PLOD1, and PLOD2; and the extracellular matrix proteins COMP, FN1, TNC and TNXB in synovial/capsule specimens from patients with idiopathic adhesive capsulitis. Possible associations between the measured mRNA levels and clinical parameters were also investigated. METHODS: We obtained glenohumeral joint synovium/capsule specimens from 9 patients with idiopathic adhesive capsulitis who had not shown improvement in symptoms after 5 months of physiotherapy. Adhesive capsulitis was confirmed in all patients by magnetic resonance imaging. We also obtained specimens from 8 control patients who had underwent surgery for acute acromioclavicular joint dislocation and who had radiological indication of glenohumeral capsule alteration based on arthroscopic evaluation. mRNA expression in the synovium/capsule specimens was analyzed by quantitative reverse transcription PCR. The B2M and HPRT1 genes were used as references to normalize target gene expression in the shoulder tissue samples. RESULTS: The synovium/capsule samples from the patients with adhesive capsulitis had significantly higher TNC and FN1 expression than those from the controls. Additionally, symptom duration directly correlated with expression of TGFβ1 receptor I. CONCLUSION: Elevated levels of TNC and FN1 expression may be a marker of capsule injury. Upregulation of TGFβ1 receptor I seems to be dependent on symptom duration; therefore, TGFβ signaling may be involved in adhesive capsulitis. As such, TNC, FN1 and TGFβ1 receptor I may also play roles in adhesive capsulitis by contributing to capsule inflammation and fibrosis.

  8. The role of Hsp70 in oxi-inflamm-aging and its use as a potential biomarker of lifespan.

    Science.gov (United States)

    Martínez de Toda, I; De la Fuente, M

    2015-12-01

    The heat-shock protein 70 (HSPA1A or Hsp70) acts as a cellular defense mechanism its expression being induced under stressful conditions. Aging has been related to an impairment in this induction. However, an extended longevity has been associated with its increased expression. According to the oxidation-inflammation theory of aging, chronic oxidative stress and inflammatory stress situations (with higher levels of oxidant and inflammatory compounds and lower antioxidant and anti-inflammatory defenses) are the basis of the age-related alterations of body cells. Since oxidation and inflammation are interlinked processes, and Hsp70 has been shown to confer protection against the harmful effects of oxidative stress as well as modulating the inflammatory status, it could play a role as a regulator of the rate of aging. This role may be different in mitotic and post-mitotic tissues due to the differences in their age-related mechanisms of response, such as apoptosis. Mechanisms affected by Hsp70 that can interfere with the deleterious effects of excessive oxidative stress and chronic low-grade inflammation and that are closely related to the aging process have been detailed. In addition, the potential use of the basal levels (with their differences in post-mitotic and mitotic tissues), the inducible levels, as well as the extracellular levels of Hsp70 as possible biomarkers of the rate of aging and lifespan, have also been discussed.

  9. Functional Roles of microRNAs in Agronomically Important Plants—Potential as Targets for Crop Improvement and Protection

    Science.gov (United States)

    Djami-Tchatchou, Arnaud T.; Sanan-Mishra, Neeti; Ntushelo, Khayalethu; Dubery, Ian A.

    2017-01-01

    MicroRNAs (miRNAs) are a class of small non-coding RNAs that have recently emerged as important regulators of gene expression, mainly through cleavage and/or translation inhibition of the target mRNAs during or after transcription. miRNAs play important roles by regulating a multitude of biological processes in plants which include maintenance of genome integrity, development, metabolism, and adaptive responses toward environmental stresses. The increasing population of the world and their food demands requires focused efforts for the improvement of crop plants to ensure sustainable food production. Manipulation of mRNA transcript abundance via miRNA control provides a unique strategy for modulating differential plant gene expression and miRNAs are thus emerging as the next generation targets for genetic engineering for improvement of the agronomic properties of crops. However, a deeper understanding of its potential and the mechanisms involved will facilitate the design of suitable strategies to obtain the desirable traits with minimum trade-offs in the modified crops. In this regard, this review highlights the diverse roles of conserved and newly identified miRNAs in various food and industrial crops and recent advances made in the uses of miRNAs to improve plants of agronomically importance so as to significantly enhance crop yields and increase tolerance to various environmental stress agents of biotic—or abiotic origin. PMID:28382044

  10. Functional Roles of microRNAs in Agronomically Important Plants-Potential as Targets for Crop Improvement and Protection.

    Science.gov (United States)

    Djami-Tchatchou, Arnaud T; Sanan-Mishra, Neeti; Ntushelo, Khayalethu; Dubery, Ian A

    2017-01-01

    MicroRNAs (miRNAs) are a class of small non-coding RNAs that have recently emerged as important regulators of gene expression, mainly through cleavage and/or translation inhibition of the target mRNAs during or after transcription. miRNAs play important roles by regulating a multitude of biological processes in plants which include maintenance of genome integrity, development, metabolism, and adaptive responses toward environmental stresses. The increasing population of the world and their food demands requires focused efforts for the improvement of crop plants to ensure sustainable food production. Manipulation of mRNA transcript abundance via miRNA control provides a unique strategy for modulating differential plant gene expression and miRNAs are thus emerging as the next generation targets for genetic engineering for improvement of the agronomic properties of crops. However, a deeper understanding of its potential and the mechanisms involved will facilitate the design of suitable strategies to obtain the desirable traits with minimum trade-offs in the modified crops. In this regard, this review highlights the diverse roles of conserved and newly identified miRNAs in various food and industrial crops and recent advances made in the uses of miRNAs to improve plants of agronomically importance so as to significantly enhance crop yields and increase tolerance to various environmental stress agents of biotic-or abiotic origin.

  11. Role of Adrenal Glucocorticoid Signaling in Prefrontal Cortex Gene Expression and Acute Behavioral Responses to Ethanol

    Science.gov (United States)

    Costin, Blair N.; Wolen, Aaron R.; Fitting, Sylvia; Shelton, Keith L.; Miles, Michael F.

    2012-01-01

    Background Glucocorticoid hormones modulate acute and chronic behavioral and molecular responses to drugs of abuse including psychostimulants and opioids. There is growing evidence that glucocorticoids might also modulate behavioral responses to ethanol. Acute ethanol activates the HPA axis, causing release of adrenal glucocorticoid hormones. Our prior genomic studies suggest glucocorticoids play a role in regulating gene expression in the prefrontal cortex (PFC) of DBA2/J (D2) mice following acute ethanol administration. However, few studies have analyzed the role of glucocorticoid signaling in behavioral responses to acute ethanol. Such work could be significant, given the predictive value for level of response to acute ethanol in the risk for alcoholism. Methods We studied whether the glucocorticoid receptor (GR) antagonist, RU-486, or adrenalectomy (ADX) altered male D2 mouse behavioral responses to acute (locomotor activation, anxiolysis or loss-of-righting reflex (LORR)) or repeated (sensitization) ethanol treatment. Whole genome microarray analysis and bioinformatics approaches were used to identify PFC candidate genes possibly responsible for altered behavioral responses to ethanol following ADX. Results ADX and RU-486 both impaired acute ethanol (2 g/kg) induced locomotor activation in D2 mice without affecting basal locomotor activity. However, neither ADX nor RU-486 altered initiation of ethanol sensitization (locomotor activation or jump counts), ethanol-induced anxiolysis or LORR. ADX mice showed microarray gene expression changes in PFC that significantly overlapped with acute ethanol-responsive gene sets derived by our prior microarray studies. Q-rtPCR analysis verified that ADX decreased PFC expression of Fkbp5 while significantly increasing Gpr6 expression. In addition, high dose RU-486 pre-treatment blunted ethanol-induced Fkbp5 expression. Conclusions Our studies suggest that ethanol’s activation of adrenal glucocorticoid release and subsequent

  12. Cadmium-induced malignant transformation in rat liver cells: role of aberrant oncogene expression and minimal role of oxidative stress.

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    Qu, Wei; Diwan, Bhalchandra A; Reece, Jeffrey M; Bortner, Carl D; Pi, Jingbo; Liu, Jie; Waalkes, Michael P

    2005-04-10

    Our study examined the role of oxidative stress and aberrant gene expression in malignant transformation induced by chronic, low-level cadmium exposure in non-tumorigenic rat liver epithelial cell line, TRL 1215. Cells were cultured in 1.0 microM cadmium (as CdCl(2)) for up to 28 weeks and compared to passage-matched control cells. The level of cadmium used for transformation produced no evidence of increased superoxide (O(2) (-*.)) or hydrogen peroxide (H(2)O(2)) levels in the early stages of exposure (hr). The chronic cadmium exposed liver epithelial cells (CCE-LE) were hyperproliferative with a growth rate about 3-fold higher than control cells. CCE-LE cells produced highly aggressive tumors upon inoculation into mice confirming malignant transformation. Analysis of cellular reactive oxygen species (ROS) showed that CCE-LE cells possessed markedly lower basal levels of intracellular O(2) (-*.)and H(2)O(2) and were very tolerant to high-dose (50 microM) cadmium-induced ROS. Time course studies showed the production of ROS by high-dose cadmium was abolished well in advance of malignant transformation. In contrast, marked overexpression of the oncogenes c-myc and c-jun occurred in transformed CCE-LE cells as evidenced by up to 10-fold increases in both transcript and protein. A significant increase in DNA-binding activity of the transcription factors AP-1 and NF-kappaB occurred in CCE-LE cells. Increases in oncogene expression and transcription factor activity occurred concurrently with malignant transformation. Thus, cadmium-induced ROS occurs as an early, high-dose event but is abolished well in advance of malignant transformation. Low-level chronic cadmium triggers oncogene overexpression possibly by altering critical transcription factor activity. Such changes in cellular gene expression likely culminate in the loss of growth control and cadmium-induced neoplastic transformation in CCE-LE cells, whereas generation of ROS by cadmium seemed to play a minimal role

  13. Expression and role of GLUT-1, MCT-1, and MCT-4 in malignant pleural mesothelioma.

    Science.gov (United States)

    Mogi, Ai; Koga, Kaori; Aoki, Mikiko; Hamasaki, Makoto; Uesugi, Noriko; Iwasaki, Akinori; Shirakusa, Takayuki; Tamura, Kazuo; Nabeshima, Kazuki

    2013-01-01

    Malignant cells supply their energy needs through increased glucose consumption, producing large quantities of lactic acid via glycolysis. Glucose transporters (GLUTs) and monocarboxylate transporters (MCTs) are therefore commonly up-regulated in human malignancies to mediate glucose influx and lactic acid efflux, respectively. However, their roles in malignant pleural mesothelioma (MPM) have not been fully elucidated. Here, we evaluated GLUT-1, MCT-1, and MCT-4 expression in human MPM and reactive mesothelial hyperplasia (RMH) and elucidated their biological role in vitro. GLUT-1, MCT-1, and MCT-4 expression was determined in human MPM (n = 35) and RMH (n = 20) specimens by immunohistochemistry and in frozen tissue, and MPM cell lines, by real-time reverse transcription-polymerase chain reaction and western blot analysis. GLUT-1, MCT-1, and MCT-4 functions in MPM were evaluated by transfection with small interfering RNA. Immunohistochemical analysis revealed higher levels of GLUT-1, MCT-1, and MCT-4 in MPM than in RMH. Additionally, GLUT-1, MCT-1, and MCT-4 mRNA levels were higher in MPM than in non-neoplastic mesothelial cell lines. The siRNA-mediated knockdown of GLUT-1 or MCT-1 significantly suppressed tumor cell proliferation, and MCT-1 silencing inhibited invasion and induced apoptosis. Taken together, these results indicate that combined application of GLUT-1, MCT-1, and MCT-4 immunohistochemistry might be useful in differentiating MPM from RMH and suggest that MCT-1plays an important biological role.

  14. Lisinopril Protects Against the Adriamycin Nephropathy and Reverses the Renalase Reduction: Potential Role of Renalase in Adriamycin Nephropathy

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    Pengxun Han

    2013-09-01

    Full Text Available Aims: To investigate the potential role of renalase in adriamycin nephropathy and the effect of lisinopril on the regulation of renalase. Methods: Adriamycin nephropathy was induced in male Wistar rats (n=12 by a single injection of adriamycin at 2 mg/kg body weight. Rats were then randomly assigned to a model group or a treatment group, to which were administered distilled water or the angiotensin converting enzyme inhibitor lisinopril, respectively, for 12 weeks. Six normal rats served as controls. At the end of study, physiological parameters and systolic blood pressure were measured. Glomerulosclerosis and tubulointerstitial injury were assessed by histopathology Renalase protein expression in kidney was quantified by immunohistochemistry and immunoblotting. The serum concentration and urinary excretion of renalase were determined by enzyme-linked immunosorbent assay. Results: In model group rats, proteinuria and systolic blood pressure were elevated. Increased serum renalase concentration was observed; however, renalase protein expression in the kidney was significantly decreased. Compared with the model group, decreased proteinuria, lower systolic blood pressure, and fewer morphologic lesions were detected in the treatment group. Although levels of serum renalase were similar, accumulation of renalase in urine and kidney tissue increased notably in the treatment group compared with the model group. Conclusions: This study suggests that renalase may be involved in the process of adriamycin-induced renal injuries. Lisinopril may attenuate adriamycin-induced kidney injury by controlling blood pressure, which may be partially attributed to the renalase expression and secretion.

  15. Carbohydrates in plant immunity and plant protection: roles and potential application as foliar sprays

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    Sophie eTrouvelot

    2014-11-01

    Full Text Available Increasing interest is devoted to carbohydrates for their roles in plant immunity. Some of them are elicitors of plant defenses whereas other ones act as signaling molecules in a manner similar to phytohormones. This review first describes the main classes of carbohydrates associated to plant immunity, their role and mode of action. More precisely, the state of the art about perception of PAMP, MAMP and DAMP type oligosaccharides is presented and examples of induced defense events are provided. A particular attention is paid to the structure / activity relationships of these compounds. The role of sugars as signaling molecules, especially in plant microbe interactions, is also presented. Secondly, the potentialities and limits of foliar sprays of carbohydrates to stimulate plant immunity for crop protection against diseases are discussed, with focus on the roles of the leaf cuticle and phyllosphere microflora.

  16. The Opioid System in Temporal Lobe Epilepsy: Functional Role and Therapeutic Potential

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    Johannes Burtscher

    2017-08-01

    Full Text Available Temporal lobe epilepsy is considered to be one of the most common and severe forms of focal epilepsies. Patients often develop cognitive deficits and emotional blunting along the progression of the disease. The high incidence of resistance to antiepileptic drugs and a frequent lack of admissibility to surgery poses an unmet medical challenge. In the urgent quest of novel treatment strategies, neuropeptides are interesting candidates, however, their therapeutic potential has not yet been exploited. This review focuses on the functional role of the endogenous opioid system with respect to temporal lobe epilepsy, specifically in the hippocampus. The role of dynorphins and kappa opioid receptors (KOPr as modulators of neuronal excitability is well understood: both the reduced release of glutamate as well of postsynaptic hyperpolarization were shown in glutamatergic neurons. In line with this, low levels of dynorphin in humans and mice increase the risk of epilepsy development. The role of enkephalins is not understood so well. On one hand, some agonists of the delta opioid receptors (DOPr display pro-convulsant properties probably through inhibition of GABAergic interneurons. On the other hand, enkephalins play a neuro-protective role under hypoxic or anoxic conditions, most probably through positive effects on mitochondrial function. Despite the supposed absence of endorphins in the hippocampus, exogenous activation of the mu opioid receptors (MOPr induces pro-convulsant effects. Recently-expanded knowledge of the complex ways opioid receptors ligands elicit their effects (including biased agonism, mixed binding, and opioid receptor heteromers, opens up exciting new therapeutic potentials with regards to seizures and epilepsy. Potential adverse side effects of KOPr agonists may be minimized through functional selectivity. Preclinical data suggest a high potential of such compounds to control seizures, with a strong predictive validity toward human

  17. Adolescents self-esteem and its role in the anger expression

    OpenAIRE

    Agnieszka Kruczek; Izabela Grzankowska

    2017-01-01

    Purpose of the study: Main purposes of conducted studies were to assess adolescents self-esteem and to recognise the selfesteem role in the expression of anger. Material and method: The study involved 221 people (including 95 girls and 126 boys) aged 15–18 years. There have been applied a Polish adaptation of Coopersmith Self-Esteem Inventory (CSEI) by Z. Juczyński and N. Ogińska-Bulik and Z. Juczyński Anger Expression Scale (SEG) and our own survey. Results: The analysis has reveale...

  18. The role of F3 in the vocal expression of emotions.

    Science.gov (United States)

    Waaramaa, Teija; Alku, Paavo; Laukkanen, Anne-Maria

    2006-01-01

    The present study investigates the role of F3 in the perception of valence of emotional expressions by using a vowel [a:] with different F3 values: the original, one with F3 either lowered or raised by 30% in frequency, and one with F3 removed. The vowel [a:] was extracted from the simulated emotions, inverse filtered and manipulated. The resulting 12 synthesized samples were randomized and presented to 30 listeners who evaluated the valence (positiveness/negativeness) of the expressions. The vowel with raised F3 was perceived more often as positive than the sample with original (p = 0.063), lowered (p = 0.006) or removed F3 (p = 0.066). F3 may affect perception of valence if the signal has sufficient energy in high frequency range.

  19. Calpain-1 Expression in Triple-Negative Breast Cancer: A Potential Prognostic Factor Independent of the Proliferative/Apoptotic Index

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    Shadia M. Al-Bahlani

    2017-01-01

    Full Text Available Triple-negative breast cancer (TNBC is an aggressive type of breast cancer in which calpain system plays an important role in its cellular processes including apoptosis and proliferation. Although such roles have been assessed in tumor pathogenesis, the correlation of its expression to the proliferating/apoptotic index has not been studied yet. Immunohistochemical staining of calpain-1 was performed on paraffin-embedded tissues to correlate its expression with clinicopathological variables and outcome. The proliferation activity was determined by calculating the percentage of cells expressing the Ki-67 antigen. The apoptotic index was assessed morphologically and biochemically using Haematoxylin & Eosin method and Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, respectively. Calpain-1 was significantly expressed in TNBC tissues varying from low to high with a significant correlation to lymph node status but not with the other clinicopathological variables, suggesting its role as a prognostic factor. In addition, a positive correlation was found between both apoptotic counts assays (P<0.001, r=0.547 as well as with proliferation (P=0.045. Calpain-1 expression had no significant correlation with either proliferation (P=0.29 or apoptotic indices (P=0.071 and P=0.100. Determining calpain-1 expression may provide relevant prognostic value for TNBC cancer patients.

  20. Gene expression profile analysis of colorectal cancer to investigate potential mechanisms using bioinformatics

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    Kou YB

    2015-04-01

    Full Text Available Yubin Kou,1,2* Suya Zhang,3* Xiaoping Chen,2 Sanyuan Hu1 1Department of General Surgery, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 2Department of General Surgery, 3Department of Neurology, Shuguang Hospital Baoshan Branch, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: This study aimed to explore the underlying molecular mechanisms of colorectal cancer (CRC using bioinformatics analysis. Using GSE4107 datasets downloaded from the Gene Expression Omnibus, the differentially expressed genes (DEGs were screened by comparing the RNA expression from the colonic mucosa between 12 CRC patients and ten healthy controls using a paired t-test. The Gene Ontology (GO functional and pathway enrichment analyses of DEGs were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID software followed by the construction of a protein–protein interaction (PPI network. In addition, hub gene identification and GO functional and pathway enrichment analyses of the modules were performed. A total of 612 up- and 639 downregulated genes were identified. The upregulated DEGs were mainly involved in the regulation of cell growth, migration, and the MAPK signaling pathway. The downregulated DEGs were significantly associated with oxidative phosphorylation, Alzheimer’s disease, and Parkinson’s disease. Moreover, FOS, FN1, PPP1CC, and CYP2B6 were selected as hub genes in the PPI networks. Two modules (up-A and up-B in the upregulated PPI network and three modules (d-A, d-B, and d-C in the downregulated PPI were identified with the threshold of Molecular Complex Detection (MCODE Molecular Complex Detection (MCODE score ≥4 and nodes ≥6. The genes in module up-A were significantly enriched in neuroactive ligand–receptor interactions and the calcium signaling pathway. The genes in module d-A were enriched in four pathways, including oxidative

  1. The Role of Protamine 2 Gene Expression and Caspase 9 Activity in Male Infertility.

    Science.gov (United States)

    Zalata, Adel A; Mokhtar, Naglaa; Atwa, Amany; Khaled, Mohamed; Shaker, Olfat G

    2016-03-01

    Approximately 15% of couples are affected by infertility with the man responsible in almost half of the cases. PRMs (protamines) confer a higher order of DNA packaging in sperm than that in somatic cells. Because of the critical roles of PRMs in spermatid differentiation, aberrations in PRM expression or changes in protein structure could be causes of certain types of idiopathic human male infertility. The aim of this study was to give insight into the role of PRM2 gene expression and caspase 9 activity in the pathogenesis of male infertility. The current study included 70 men with idiopathic infertility and 64 fertile men who attended the andrology outpatient clinic at Mansoura University Hospital. Semen sample analyses were done according to WHO recommendations. The acrosome reaction of spermatozoa recovered from each sample was assessed. Samples were separated using discontinuous gradient separation. From each semen sample mature sperm were separated from immature sperm. The resulting samples were divided into 2 parts, including one to determine caspase 9 activity and the other for RNA extraction and reverse transcriptase-polymerase chain reaction of PRM2 gene expression. The polymerase chain reaction product was electrophoresed on 2% agarose gel. PRM2 gene expression was significantly decreased in immature sperm extracted from the fertile and infertile groups. Caspase 9 activity was significantly increased in immature sperm extracted from both groups. Low levels of PRM2 may be associated with morphological abnormalities, initiation of the apoptotic pathway and decreasing sperm motility. PRM2 may be an important marker to better understand the key regulatory pathway of spermatogenesis and it may act as a crucial part of fertilization. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  2. An investigation into vocal expressions of emotions: the roles of valence, culture, and acoustic factors

    Science.gov (United States)

    Sauter, Disa

    This PhD is an investigation of vocal expressions of emotions, mainly focusing on non-verbal sounds such as laughter, cries and sighs. The research examines the roles of categorical and dimensional factors, the contributions of a number of acoustic cues, and the influence of culture. A series of studies established that naive listeners can reliably identify non-verbal vocalisations of positive and negative emotions in forced-choice and rating tasks. Some evidence for underlying dimensions of arousal and valence is found, although each emotion had a discrete expression. The role of acoustic characteristics of the sounds is investigated experimentally and analytically. This work shows that the cues used to identify different emotions vary, although pitch and pitch variation play a central role. The cues used to identify emotions in non-verbal vocalisations differ from the cues used when comprehending speech. An additional set of studies using stimuli consisting of emotional speech demonstrates that these sounds can also be reliably identified, and rely on similar acoustic cues. A series of studies with a pre-literate Namibian tribe shows that non-verbal vocalisations can be recognized across cultures. An fMRI study carried out to investigate the neural processing of non-verbal vocalisations of emotions is presented. The results show activation in pre-motor regions arising from passive listening to non-verbal emotional vocalisations, suggesting neural auditory-motor interactions in the perception of these sounds. In sum, this thesis demonstrates that non-verbal vocalisations of emotions are reliably identifiable tokens of information that belong to discrete categories. These vocalisations are recognisable across vastly different cultures and thus seem to, like facial expressions of emotions, comprise human universals. Listeners rely mainly on pitch and pitch variation to identify emotions in non verbal vocalisations, which differs with the cues used to comprehend

  3. Binding of galectin-1 to integrin β1 potentiates drug resistance by promoting survivin expression in breast cancer cells

    Science.gov (United States)

    Nam, KeeSoo; Son, Seog-ho; Oh, Sunhwa; Jeon, Donghwan; Kim, Hyungjoo; Noh, Dong-Young; Kim, Sangmin; Shin, Incheol

    2017-01-01

    Galectin-1 is a β-galactoside binding protein secreted by many types of aggressive cancer cells. Although many studies have focused on the role of galectin-1 in cancer progression, relatively little attention has been paid to galectin-1 as an extracellular therapeutic target. To elucidate the molecular mechanisms underlying galectin-1-mediated cancer progression, we established galectin-1 knock-down cells via retroviral delivery of short hairpin RNA (shRNA) against galectin-1 in two triple-negative breast cancer (TNBC) cell lines, MDA-MB-231 and Hs578T. Ablation of galectin-1 expression decreased cell proliferation, migration, invasion, and doxorubicin resistance. We found that these effects were caused by decreased galectin-1-integrin β1 interactions and suppression of the downstream focal adhesion kinase (FAK)/c-Src pathway. We also found that silencing of galectin-1 inhibited extracellular signal-regulated kinase (ERK)/signal transducer and activator of transcription 3 (STAT3) signaling, thereby down-regulating survivin expression. This finding implicates STAT3 as a transcription factor for survivin. Finally, rescue of endogenous galectin-1 knock-down and recombinant galectin-1 treatment both recovered signaling through the FAK/c-Src/ERK/STAT3/survivin pathway. Taken together, these results suggest that extracellular galectin-1 contributes to cancer progression and doxorubicin resistance in TNBC cells. These effects appear to be mediated by galectin-1-induced up-regulation of the integrin β1/FAK/c-Src/ERK/STAT3/survivin pathway. Our results imply that extracellular galectin-1 has potential as a therapeutic target for triple-negative breast cancer. PMID:28415760

  4. Adipose Expression of Tumor Necrosis Factor-α: Direct Role in Obesity-Linked Insulin Resistance

    Science.gov (United States)

    Hotamisligil, Gokhan S.; Shargill, Narinder S.; Spiegelman, Bruce M.

    1993-01-01

    Tumor necrosis factor-α (TNF-α) has been shown to have certain catabolic effects on fat cells and whole animals. An induction of TNF-α messenger RNA expression was observed in adipose tissue from four different rodent models of obesity and diabetes. TNF-α protein was also elevated locally and systemically. Neutralization of TNF-α in obese fa/fa rats caused a significant increase in the peripheral uptake of glucose in response to insulin. These results indicate a role for TNF-α in obesity and particularly in the insulin resistance and diabetes that often accompany obesity.

  5. Connecting biodiversity and potential functional role in modern euxinic environments by microbial metagenomics.

    Science.gov (United States)

    Llorens-Marès, Tomàs; Yooseph, Shibu; Goll, Johannes; Hoffman, Jeff; Vila-Costa, Maria; Borrego, Carles M; Dupont, Chris L; Casamayor, Emilio O

    2015-07-01

    Stratified sulfurous lakes are appropriate environments for studying the links between composition and functionality in microbial communities and are potentially modern analogs of anoxic conditions prevailing in the ancient ocean. We explored these aspects in the Lake Banyoles karstic area (NE Spain) through metagenomics and in silico reconstruction of carbon, nitrogen and sulfur metabolic pathways that were tightly coupled through a few bacterial groups. The potential for nitrogen fixation and denitrification was detected in both autotrophs and heterotrophs, with a major role for nitrogen and carbon fixations in Chlorobiaceae. Campylobacterales accounted for a large percentage of denitrification genes, while Gallionellales were putatively involved in denitrification, iron oxidation and carbon fixation and may have a major role in the biogeochemistry of the iron cycle. Bacteroidales were also abundant and showed potential for dissimilatory nitrate reduction to ammonium. The very low abundance of genes for nitrification, the minor presence of anammox genes, the high potential for nitrogen fixation and mineralization and the potential for chemotrophic CO2 fixation and CO oxidation all provide potential clues on the anoxic zones functioning. We observed higher gene abundance of ammonia-oxidizing bacteria than ammonia-oxidizing archaea that may have a geochemical and evolutionary link related to the dominance of Fe in these environments. Overall, these results offer a more detailed perspective on the microbial ecology of anoxic environments and may help to develop new geochemical proxies to infer biology and chemistry interactions in ancient ecosystems.

  6. Randomized controlled trial of expressive writing for psychological and physical health: the moderating role of emotional expressivity.

    Science.gov (United States)

    Niles, Andrea N; Haltom, Kate E Byrne; Mulvenna, Catherine M; Lieberman, Matthew D; Stanton, Annette L

    2014-01-01

    The current study assessed main effects and moderators (including emotional expressiveness, emotional processing, and ambivalence over emotional expression) of the effects of expressive writing in a sample of healthy adults. Young adult participants (N=116) were randomly assigned to write for 20 minutes on four occasions about deepest thoughts and feelings regarding their most stressful/traumatic event in the past five years (expressive writing) or about a control topic (control). Dependent variables were indicators of anxiety, depression, and physical symptoms. No significant effects of writing condition were evident on anxiety, depressive symptoms, or physical symptoms. Emotional expressiveness emerged as a significant moderator of anxiety outcomes, however. Within the expressive writing group, participants high in expressiveness evidenced a significant reduction in anxiety at three-month follow-up, and participants low in expressiveness showed a significant increase in anxiety. Expressiveness did not predict change in anxiety in the control group. These findings on anxiety are consistent with the matching hypothesis, which suggests that matching a person's naturally elected coping approach with an assigned intervention is beneficial. These findings also suggest that expressive writing about a stressful event may be contraindicated for individuals who do not typically express emotions.

  7. [The expression of oncogene c-myc and its role on human laryngeal cancer].

    Science.gov (United States)

    Long, Xiaobo; Hu, Shuang; Cao, Pingping; Liu, Zheng; Zhen, Hongtao; Cui, Yonghua

    2009-12-01

    To detect the expression of oncogene c-myc and explore its role on human laryngeal cancer. The mRNA and of oncogene c-myc levels were detected in human laryngeal cancer tissues and laryngeal normal tissues by the means of real-time PCR and immunohistochemistry, respectively. Compared with normal laryngeal tissues, the mRNA and protein levels of oncogene c-myc were both upregulated in laryngeal cancer tissues of all differentiation degree (P<0.05). Moreover, the level of c-myc was inverse correlated with the differentiation degree in human laryngeal cancer tissues. The oncogene c-myc is overexpressed in human laryngeal cancer tissues, and c-myc may play an important role in carcinogenesis and progression of human laryngeal cancer tissues. It may provide a new target for gene therapy of human laryngeal cancer.

  8. The potential role for use of mitochondrial DNA copy number as predictive biomarker in presbycusis

    Directory of Open Access Journals (Sweden)

    Falah M

    2016-10-01

    Full Text Available Masoumeh Falah,1,2 Massoud Houshmand,3 Mohammad Najafi,2 Maryam Balali,1 Saeid Mahmoudian,1 Alimohamad Asghari,4 Hessamaldin Emamdjomeh,1 Mohammad Farhadi1 1ENT and Head & Neck Research Center and Department, Iran University of Medical Sciences, Tehran, Iran; 2Cellular and Molecular Research Center, Biochemistry Department, Iran University of Medical Sciences, Tehran, Iran; 3Department of Medical Genetics, National Institute for Genetic Engineering and Biotechnology, Tehran, Iran; 4Skull base research center, Iran University of Medical Sciences, Tehran, Iran Objectives: Age-related hearing impairment, or presbycusis, is the most common communication disorder and neurodegenerative disease in the elderly. Its prevalence is expected to increase, due to the trend of growth of the elderly population. The current diagnostic test for detection of presbycusis is implemented after there has been a change in hearing sensitivity. Identification of a pre-diagnostic biomarker would raise the possibility of preserving hearing sensitivity before damage occurs. Mitochondrial dysfunction, including the production of reactive oxygen species and induction of expression of apoptotic genes, participates in the progression of presbycusis. Mitochondrial DNA sequence variation has a critical role in presbycusis. However, the nature of the relationship between mitochondrial DNA copy number, an important biomarker in many other diseases, and presbycusis is undetermined.Methods: Fifty-four subjects with presbycusis and 29 healthy controls were selected after ear, nose, throat examination and pure-tone audiometry. DNA was extracted from peripheral blood samples. The copy number of mitochondrial DNA relative to the nuclear genome was measured by quantitative real-time polymerase chain reaction.Results: Subjects with presbycusis had a lower median mitochondrial DNA copy number than healthy subjects and the difference was statistically significant (P=0.007. Mitochondrial DNA

  9. Reverse engineering model structures for soil and ecosystem respiration: the potential of gene expression programming

    Directory of Open Access Journals (Sweden)

    I. Ilie

    2017-09-01

    Full Text Available Accurate model representation of land–atmosphere carbon fluxes is essential for climate projections. However, the exact responses of carbon cycle processes to climatic drivers often remain uncertain. Presently, knowledge derived from experiments, complemented by a steadily evolving body of mechanistic theory, provides the main basis for developing such models. The strongly increasing availability of measurements may facilitate new ways of identifying suitable model structures using machine learning. Here, we explore the potential of gene expression programming (GEP to derive relevant model formulations based solely on the signals present in data by automatically applying various mathematical transformations to potential predictors and repeatedly evolving the resulting model structures. In contrast to most other machine learning regression techniques, the GEP approach generates readable models that allow for prediction and possibly for interpretation. Our study is based on two cases: artificially generated data and real observations. Simulations based on artificial data show that GEP is successful in identifying prescribed functions, with the prediction capacity of the models comparable to four state-of-the-art machine learning methods (random forests, support vector machines, artificial neural networks, and kernel ridge regressions. Based on real observations we explore the responses of the different components of terrestrial respiration at an oak forest in south-eastern England. We find that the GEP-retrieved models are often better in prediction than some established respiration models. Based on their structures, we find previously unconsidered exponential dependencies of respiration on seasonal ecosystem carbon assimilation and water dynamics. We noticed that the GEP models are only partly portable across respiration components, the identification of a general terrestrial respiration model possibly prevented by equifinality issues. Overall

  10. Reverse engineering model structures for soil and ecosystem respiration: the potential of gene expression programming

    Science.gov (United States)

    Ilie, Iulia; Dittrich, Peter; Carvalhais, Nuno; Jung, Martin; Heinemeyer, Andreas; Migliavacca, Mirco; Morison, James I. L.; Sippel, Sebastian; Subke, Jens-Arne; Wilkinson, Matthew; Mahecha, Miguel D.

    2017-09-01

    Accurate model representation of land-atmosphere carbon fluxes is essential for climate projections. However, the exact responses of carbon cycle processes to climatic drivers often remain uncertain. Presently, knowledge derived from experiments, complemented by a steadily evolving body of mechanistic theory, provides the main basis for developing such models. The strongly increasing availability of measurements may facilitate new ways of identifying suitable model structures using machine learning. Here, we explore the potential of gene expression programming (GEP) to derive relevant model formulations based solely on the signals present in data by automatically applying various mathematical transformations to potential predictors and repeatedly evolving the resulting model structures. In contrast to most other machine learning regression techniques, the GEP approach generates readable models that allow for prediction and possibly for interpretation. Our study is based on two cases: artificially generated data and real observations. Simulations based on artificial data show that GEP is successful in identifying prescribed functions, with the prediction capacity of the models comparable to four state-of-the-art machine learning methods (random forests, support vector machines, artificial neural networks, and kernel ridge regressions). Based on real observations we explore the responses of the different components of terrestrial respiration at an oak forest in south-eastern England. We find that the GEP-retrieved models are often better in prediction than some established respiration models. Based on their structures, we find previously unconsidered exponential dependencies of respiration on seasonal ecosystem carbon assimilation and water dynamics. We noticed that the GEP models are only partly portable across respiration components, the identification of a general terrestrial respiration model possibly prevented by equifinality issues. Overall, GEP is a promising

  11. The dual role of cyclin C connects stress regulated gene expression to mitochondrial dynamics

    Directory of Open Access Journals (Sweden)

    Randy Strich

    2014-09-01

    Full Text Available Following exposure to cytotoxic agents, cellular damage is first recognized by a variety of sensor mechanisms. Thenceforth, the damage signal is transduced to the nucleus to install the correct gene expression program including the induction of genes whose products either detoxify destructive compounds or repair the damage they cause. Next, the stress signal is disseminated throughout the cell to effect the appropriate changes at organelles including the mitochondria. The mitochondria represent an important signaling platform for the stress response. An initial stress response of the mitochondria is extensive fragmentation. If the damage is prodigious, the mitochondria fragment (fission and lose their outer membrane integrity leading to the release of pro-apoptotic factors necessary for programmed cell death (PCD execution. As this complex biological process contains many moving parts, it must be exquisitely coordinated as the ultimate decision is life or death. The conserved C-type cyclin plays an important role in executing this molecular Rubicon by coupling changes in gene expression to mitochondrial fission and PCD. Cyclin C, along with its cyclin dependent kinase partner Cdk8, associates with the RNA polymerase holoenzyme to regulate transcription. In particular, cyclin C-Cdk8 repress many stress responsive genes. To relieve this repression, cyclin C is destroyed in cells exposed to pro-oxidants and other stressors. However, prior to its destruction, cyclin C, but not Cdk8, is released from its nuclear anchor (Med13, translocates from the nucleus to the cytoplasm where it interacts with the fission machinery and is both necessary and sufficient to induce extensive mitochondria fragmentation. Furthermore, cytoplasmic cyclin C promotes PCD indicating that it mediates both mitochondrial fission and cell death pathways. This review will summarize the role cyclin C plays in regulating stress-responsive transcription. In addition, we will detail

  12. Role of nitric oxide in long-term potentiation of the rat medial vestibular nuclei.

    Science.gov (United States)

    Grassi, S; Pettorossi, V E

    2000-01-01

    In rat brainstem slices, we investigated the role of nitric oxide in long-term potentiation induced in the ventral portion of the medial vestibular nuclei by high-frequency stimulation of the primary vestibular afferents. The nitric oxide scavenger [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide ] and the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester were administered before and after induction of potentiation. Both drugs completely prevented long-term potentiation, whereas they did not impede the potentiation build-up, or affect the already established potentiation. These results demonstrate that the induction, but not the maintenance of vestibular long-term potentiation, depends on the synthesis and release into the extracellular medium of nitric oxide. In addition, we analysed the effect of the nitric oxide donor sodium nitroprusside on vestibular responses. Sodium nitroprusside induced long-term potentiation, as evidenced through the field potential enhancement and unit peak latency decrease. This potentiation was impeded by D, L-2-amino-5-phosphonopentanoic acid, and was reduced under blockade of synaptosomal platelet-activating factor receptors by ginkgolide B and group I metabotropic glutamate receptors by (R,S)-1-aminoindan-1, 5-dicarboxylic acid. When reduced, potentiation fully developed following the washout of antagonist, demonstrating an involvement of platelet-activating factor and group I metabotropic glutamate receptors in its full development. Potentiation induced by sodium nitroprusside was also associated with a decrease in the paired-pulse facilitation ratio, which persisted under ginkgolide B, indicating that nitric oxide increases glutamate release independently of platelet-activating factor-mediated presynaptic events. We suggest that nitric oxide, released after the activation of N-methyl-D-aspartate receptors, acts as a retrograde messenger leading to an enhancement of glutamate release to a

  13. Bone marrow-derived macrophages exclusively expressed caveolin-2: The role of inflammatory activators and hypoxia.

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    Maceckova, Michaela; Martiskova, Hana; Koudelka, Adolf; Kubala, Lukas; Lojek, Antonin; Pekarova, Michaela

    2015-11-01

    Caveolins are specific proteins involved in regulation of signal transduction to intracellular space. Still, their contribution to immune functions has not been completely clarified. Thus, we decided to characterize the expression of caveolins in bone marrow-derived macrophages (BMDMs) under resting and inflammatory conditions. The effect of classical activators (lipopolysaccharide, LPS; interferon-gamma, IFN-γ) was further potentiated with hypoxic (5% O2) conditions. The activation of p44/42-extracellular signal-regulated kinases 1 and 2 (ERK1/2) and expression of caveolin-1, -2, and -3, hypoxia inducible factor-1 alpha (HIF-1α), as well as inducible nitric oxide synthase (iNOS) was monitored using the Western blot technique. The production of nitric oxide (NO) and tumor necrosis factor-alpha (TNFα) was analyzed by Griess method or ELISA, respectively. BMDMs were also transfected with siRNA against caveolin-2. Importantly, our study showed for the first time that BMDMs expressed only caveolin-2, and its level decreased after activation of macrophages with LPS, IFN-γ, and/or hypoxia. The expression of caveolin-2 negatively correlates with the iNOS and HIF-1α protein levels, as well as with the LPS/IFN-γ- and hypoxia-induced activation of ERK1/2. We concluded that caveolin-2 is most probably involved in regulation of pro-inflammatory responses of BMDMs, triggered via activation of ERK1/2. Copyright © 2015 Elsevier GmbH. All rights reserved.

  14. The Role of Co-occurring Emotions and Personality Traits in Anger Expression

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    Mill, Aire; Kööts-Ausmees, Liisi; Allik, Jüri; Realo, Anu

    2018-01-01

    The main aim of the current study was to examine the role of co-occurring emotions and their interactive effects with the Big Five personality traits in anger expression. Everyday anger expression (“anger-in” and “anger-out” behavior) was studied with the experience-sampling method in a group of 110 participants for 14 consecutive days on 7 random occasions per day. Our results showed that the simultaneously co-occurring emotions that buffer against anger expression are sadness, surprise, disgust, disappointment, and irritation for anger-in behavior, and fear, sadness and disappointment for anger-out reactions. While previous studies have shown that differentiating one's current affect into discrete emotion categories buffers against anger expression (Pond et al., 2012), our study further demonstrated the existence of specific interactive effects between the experience of momentary emotions and personality traits that lead to higher levels of either suppression or expression of anger behavior (or both). For example, the interaction between the trait Openness and co-occurring surprise, in predicting anger-in behavior, indicates that less open people hold their anger back more, and more open people use less anger-in behavior. Co-occurring disgust increases anger-out reactions in people low in Conscientiousness, but decreases anger-out reactions in people high in Conscientiousness. People high in Neuroticism are less likely to engage in anger-in behavior when experiencing disgust, surprise, or irritation alongside anger, but show more anger out in the case of co-occurring contempt. The results of the current study help to further clarify the interactions between the basic personality traits and the experience of momentary co-occurring emotions in determining anger behavior. PMID:29479333

  15. Role of Dicer1-Dependent Factors in the Paracrine Regulation of Epididymal Gene Expression.

    Directory of Open Access Journals (Sweden)

    Olivia Jerczynski

    Full Text Available Dicer1 is an endoribonuclease involved in the biogenesis of functional molecules such as microRNAs (miRNAs and endogenous small interfering RNAs (endo-siRNAs. These small non-coding RNAs are important regulators of post-transcriptional gene expression and participate in the control of male fertility. With the knowledge that 1 Dicer1-dependent factors are required for proper sperm maturation in the epididymis, and that 2 miRNAs are potent mediators of intercellular communication in most biological systems, we investigated the role of Dicer1-dependent factors produced by the proximal epididymis (initial segment/caput- including miRNAs- on the regulation of epididymal gene expression in the distal epididymis regions (i.e. corpus and cauda. To this end, we performed comparative microarray and ANOVA analyses on control vs. Defb41iCre/wt;Dicer1fl/fl mice in which functional Dicer1 is absent from the principal cells of the proximal epididymis. We identified 35 and 33 transcripts that displayed significant expression level changes in the corpus and cauda regions (Fold change > 2 or 2 or < -2; p < 0.01. These miRNAs are secreted via extracellular vesicles (EVs derived from the DC2 epididymal principal cell line, and their expression correlates with target transcripts involved in distinct biological pathways, as evidenced by in silico analysis. Albeit correlative and based on in silico approach, our study proposes that Dicer1-dependent factors trigger- directly or not-significant genes expression changes in distinct regions of this organ. The paracrine control of functions important to post-testicular sperm maturation by Dicer1-dependent factors may open new avenues for the identification of molecular targets important to male fertility control.

  16. Role of plant expression systems in antibody production for passive immunization.

    Science.gov (United States)

    Virdi, Vikram; Depicker, Ann

    2013-01-01

    Passive immunization is a method to achieve immediate protection against infectious agents by administering pathogen-specific antibodies. It has proven to be lifesaving for many acute infections, and it is now also used for cancer treatment. Passive immunization therapies, however, are extremely expensive because they require large amounts of specific antibodies that are produced predominantly in mammalian expression systems. The cost for manufacturing plant-made antibodies is estimated to be comparatively low since plant production systems require relatively less capital investments. In addition, they are not prone to mammalian pathogens, which also eases downstream processing along with making it a safe expression system. Moreover, some of the recent developments in transient expression have enabled rapid, cGMP (current Good Manufacturing Practices) compliant manufacturing of antibodies. Whether lower production costs will be reflected in a lower market price for purified antibodies will be known when more plant-produced antibodies come to the market. Promisingly, the current molecular techniques in the field of in planta expression have enabled high-level production of a variety of antibodies in different plant organs, like roots/tubers/fruits, leaves and seeds, of a variety of plants, like potato, tobacco, maize, rice, tomato and pea, providing a very wide range of possible plant-based passive immunization therapies. For instance, the production of antibodies in edible tissues would allow for a unique, convenient, needle-less, oral passive immunization at the gastric mucosal surface. The technological advances, together with the innate capacity of plant tissues to assemble complex antibodies, will enable carving a niche in the antibody market. This non-exhaustive review aims to shed light on the role of plants as a flexible expression system for passive immunotherapy, which we envisage to progress alongside the conventional production platforms to manufacture

  17. Adaptable interaction between aquaporin-1 and band 3 reveals a potential role of water channel in blood CO2transport.

    Science.gov (United States)

    Hsu, Kate; Lee, Ting-Ying; Periasamy, Ammasi; Kao, Fu-Jen; Li, Li-Tzu; Lin, Chuang-Yu; Lin, Hui-Ju; Lin, Marie

    2017-10-01

    Human CO 2 respiration requires rapid conversion between CO 2 and HCO 3 - Carbonic anhydrase II facilitates this reversible reaction inside red blood cells, and band 3 [anion exchanger 1 (AE1)] provides a passage for HCO 3 - flux across the cell membrane. These 2 proteins are core components of the CO 2 transport metabolon. Intracellular H 2 O is necessary for CO 2 /HCO 3 - conversion. However, abundantly expressed aquaporin 1 (AQP1) in erythrocytes is thought not to be part of band 3 complexes or the CO 2 transport metabolon. To solve this conundrum, we used Förster resonance energy transfer (FRET) measured by fluorescence lifetime imaging (FLIM-FRET) and identified interaction between aquaporin-1 and band 3 at a distance of 8 nm, within the range of dipole-dipole interaction. Notably, their interaction was adaptable to membrane tonicity changes. This suggests that the function of AQP1 in tonicity response could be coupled or correlated to its function in band 3-mediated CO 2 /HCO 3 - exchange. By demonstrating AQP1 as a mobile component of the CO 2 transport metabolon, our results uncover a potential role of water channel in blood CO 2 transport and respiration.-Hsu, K., Lee, T.-Y., Periasamy, A., Kao, F.-J., Li, L.-T., Lin, C.-Y., Lin, H.-J., Lin, M. Adaptable interaction between aquaporin-1 and band 3 reveals a potential role of water channel in blood CO 2 transport. © FASEB.

  18. The potential role of exercise in chronic stress-related changes in AMPA receptor phenotype underlying synaptic plasticity.

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    Leem, Yea-Hyun

    2017-12-31

    Chronic stress can cause disturbances in synaptic plasticity, such as longterm potentiation, along with behavioral defects including memory deficits. One major mechanism sustaining synaptic plasticity involves the dynamics and contents of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) in the central nervous system. In particular, chronic stress-induced disruption of AMPARs includes it abnormal expression, trafficking, and calcium conductance at glutamatergic synapses, which contributes to synaptic plasticity at excitatory synapses. Exercise has the effect of promoting synaptic plasticity in neurons. However, the contribution of exercise to AMPAR behavior under chronic stressful maladaptation remains unclear. The present article reviews the information about the chronic stress-related synaptic plasticity and the role of exercise from the previous-published articles. AMPAR-mediated synaptic transmission is an important for chronic stress-related changes of synaptic plasticity, and exercise may at least partly contribute to these episodes. The present article discusses the relationship between AMPARs and synaptic plasticity in chronic stress, as well as the potential role of exercise.

  19. REDEFINING THE POTENTIAL ROLE OF CHARISMATIC LANGUAGE TEACHERS IN CREATING SUPPORTIVE ACADEMIC ATMOSPHERE THROUGH STUDENTS’ MOTIVATIONAL AROUSAL

    Directory of Open Access Journals (Sweden)

    Adi Suryani

    2016-06-01

    Full Text Available Charismatic language teachers have considerable potentials to nurture motivations in their students. They have personal magnetism which frequently they exhibit through their characters, communication, and how they develop relationship with their students. Charismatic teachers tend to be energetic, emphatic, warm, express confidence, love challenge, communicate vision, develop warm communication, put concern, trust, be inspiring and motivational. These characters allow them to be role model and inspire their motivation to their students. Their trusting behaviour also can lead to the creation of supportive classroom climate since supportive learning situation needs sense of autonomy. By having this sense of autonomy, students can voice their perspectives, beliefs and finally develop their autonomy self-regulation. By using their personal aura, charismatic language teachers can stimulate their students’ inner motivation.

  20. Perilipin Expression Reveals Adipogenic Potential of hADSCs inside Superporous Polymeric Cellular Delivery Systems